Directory of Open Access Journals (Sweden)
Reshef Tal
2012-01-01
Full Text Available Background. Assisted reproductive technology has been linked to the increased incidence of monozygotic twinning. It is of clinical importance due to the increased risk of complications in multiple pregnancies in general and in monozygotic twins in particular. Case. A 29-year-old female, nulligravida underwent her first IVF cycle. Three poor-quality cleavage stage embryos were transferred resulting in monochorionic triamniotic triplets and dichorionic diamniotic twins. Selective embryo reduction was performed at 12 weeks leaving dichorionic twins. The patient underwent emergency cesarean section due to preterm labor and nonreassuring fetal heart tracing at 30 weeks of gestation. Conclusion. Our case emphasizes that even embryos with significant morphological abnormalities should be considered viable and the possibility of simultaneous spontaneous embryo splitting must be factored into determining number of embryos to transfer.
Dienone-phenol Rearrangement of C-9 Oxygenated Decalinic Dienone and Analogs through B-Ring Cleavage
Institute of Scientific and Technical Information of China (English)
无
2003-01-01
Dehydrogenation of 9-hydroxy decalinic enones and analogs with DDQ resulted in a formal dienone-phenol type rearrangement via B-ring cleavage, while the corresponding dienone acetates underwent base-catalyzed formal dienone-phenol type rearrangement analogously.
Spontaneous tension haemopneumothorax.
Patterson, Benjamin Oliver; Itam, Sarah; Probst, Fey
2008-10-31
We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported.Aetiology and current approach to spontaneous haemothorax are discussed briefly.
Spontaneous tension haemopneumothorax
Directory of Open Access Journals (Sweden)
Itam Sarah
2008-10-01
Full Text Available Abstract We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported. Aetiology and current approach to spontaneous haemothorax are discussed briefly.
Video-assisted thoracoscopy treatment of spontaneous pneumothorax
International Nuclear Information System (INIS)
Chen Haitao; Ren Jian; Che Jiaming; Hang Junbiao; Qiu Weicheng; Chen Zhongyuan
2002-01-01
Objective: To propose a treatment protocol by video thoracoscopy in spontaneous pneumothorax. Methods: One hundred and three patients underwent Video-assisted thoracoscopy (VATS) treatment of spontaneous pneumothorax and hemothorax. Indications included recurrent pneumothorax, persistent air leakage following conservative therapy, complicated hemothorax and CT scan identified bullae formation. Results: No operative deaths occurred, conversion rate was 2.91%, recurrence rate was 0.97%, complication rate was 3.81% and mean postoperative hospital stay was 5.6 days. Conclusions: VATS treatment of spontaneous pneumothorax is better than open chest surgery and also superior than conservative therapy
Thoracoscopic modified pleural tent for spontaneous pneumothorax.
Kawachi, Riken; Matsuwaki, Rie; Tachibana, Keisei; Karita, Shin; Nakazato, Yoko; Tanaka, Ryota; Nagashima, Yasushi; Takei, Hidefumi; Kondo, Haruhiko
2016-08-01
We developed a modified pleural tent (m-tent) procedure and used it in our hospital in almost 30 consecutive patients with spontaneous pneumothorax. The objective of this study was to clarify the feasibility and effectiveness of a thoracoscopic m-tent for the treatment of spontaneous pneumothorax. From July 2013 to November 2014, 107 patients with spontaneous pneumothorax were treated in our institution. Eighty-nine of these patients were analysed retrospectively. The inclusion criteria for thoracoscopic m-tent for spontaneous pneumothorax were multiple and widespread bullae, postoperative relapse and secondary spontaneous pneumothorax. The surgical procedures were usually performed through three ports. After bullectomy, an m-tent is made to strip the parietal pleura off the chest wall from about the level of the fourth or fifth rib to the apex, and two or three ligations are then applied to fix the pleural tent and lung parenchyma. Patients in whom an m-tent was not indicated underwent bullectomy plus coverage using absorbable materials. Twenty-seven patients underwent bullectomy plus m-tent (m-tent group) and 62 underwent bullectomy plus coverage over a staple line using an absorbable material such as a polyglycolic acid sheet or nitrocellulose sheet (coverage group). No severe postoperative complications were observed in either group. The m-tent and coverage groups showed significant differences in operation time (129 vs 86 min, mean), haemorrhage (12.8 vs 7.2 ml), postoperative hospital stay (3.7 vs 2.9 days) and postoperative painkiller intake (8.6 vs 6.8 days). Recurrence was observed in 1 (3.7%) and 2 patients (3.2%), respectively. The thoracoscopic m-tent procedure requires a longer operation, a longer hospital stay and greater painkiller intake. However, these differences are acceptable, and an m-tent should be considered as an option for pleural reinforcement in spontaneous pneumothorax, especially in patients who are complicated with severe pulmonary
Spontaneous tension haemopneumothorax
Patterson, Benjamin Oliver; Itam, Sarah; Probst, Fey
2008-01-01
Abstract We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such c...
Vertebrate Embryonic Cleavage Pattern Determination.
Hasley, Andrew; Chavez, Shawn; Danilchik, Michael; Wühr, Martin; Pelegri, Francisco
2017-01-01
The pattern of the earliest cell divisions in a vertebrate embryo lays the groundwork for later developmental events such as gastrulation, organogenesis, and overall body plan establishment. Understanding these early cleavage patterns and the mechanisms that create them is thus crucial for the study of vertebrate development. This chapter describes the early cleavage stages for species representing ray-finned fish, amphibians, birds, reptiles, mammals, and proto-vertebrate ascidians and summarizes current understanding of the mechanisms that govern these patterns. The nearly universal influence of cell shape on orientation and positioning of spindles and cleavage furrows and the mechanisms that mediate this influence are discussed. We discuss in particular models of aster and spindle centering and orientation in large embryonic blastomeres that rely on asymmetric internal pulling forces generated by the cleavage furrow for the previous cell cycle. Also explored are mechanisms that integrate cell division given the limited supply of cellular building blocks in the egg and several-fold changes of cell size during early development, as well as cytoskeletal specializations specific to early blastomeres including processes leading to blastomere cohesion. Finally, we discuss evolutionary conclusions beginning to emerge from the contemporary analysis of the phylogenetic distributions of cleavage patterns. In sum, this chapter seeks to summarize our current understanding of vertebrate early embryonic cleavage patterns and their control and evolution.
Cleavage and creep fracture of rock salt
International Nuclear Information System (INIS)
Chan, K.S.; Munson, D.E.; Bodner, S.R.
1996-01-01
The dominant failure mechanism in rock salt at ambient temperature is either cleavage or creep fracture. Since the transition of creep fracture to cleavage in a compressive stress field is not well understood, failure of rock salt by cleavage and creep fracture is analyzed in this paper to elucidate the effect of stress state on the competition between these two fracture mechanisms. For cleavage fracture, a shear crack is assumed to cause the formation and growth of a symmetric pair of wing cracks in a predominantly compressive stress field. The conditions for wing-crack instability are derived and presented as the cleavage fracture boundary in the fracture mechanism map. Using an existing creep fracture model, stress conditions for the onset of creep fracture and isochronous failure curves of specified times-to-rupture are calculated and incorporated into the fracture mechanism map. The regimes of dominance by cleavage and creep fracture are established and compared with experimental data. The result indicates that unstable propagation of cleavage cracks occurs only in the presence of tensile stress. The onset of creep fracture is promoted by a tensile stress, but can be totally suppressed by a high confining pressure. Transition of creep fracture to cleavage occurs when critical conditions of stress difference and tensile stress for crack instability are exceeded
International Nuclear Information System (INIS)
Craft, Willie Warren; Dutch, Rebecca Ellis
2005-01-01
The Hendra virus fusion (HeV F) protein is synthesized as a precursor, F 0 , and proteolytically cleaved into the mature F 1 and F 2 heterodimer, following an HDLVDGVK 109 motif. This cleavage event is required for fusogenic activity. To determine the amino acid requirements for processing of the HeV F protein, we constructed multiple mutants. Individual and simultaneous alanine substitutions of the eight residues immediately upstream of the cleavage site did not eliminate processing. A chimeric SV5 F protein in which the furin site was substituted for the VDGVK 109 motif of the HeV F protein was not processed but was expressed on the cell surface. Another chimeric SV5 F protein containing the HDLVDGVK 109 motif of the HeV F protein underwent partial cleavage. These data indicate that the upstream region can play a role in protease recognition, but is neither absolutely required nor sufficient for efficient processing of the HeV F protein
Radiologic findings of acute spontaneous subdural hematomas
Energy Technology Data Exchange (ETDEWEB)
Kim, Hyun Jung; Bae, Won Kyong; Gyu, Cha Jang; Kim, Gun Woo; Cho, Won Su; Kim, Il Young; Lee, Kyung Suk [Soonchunhyang University, Chonan (Korea, Republic of). Chonan Hospital
1998-03-01
To evaluate the characteristic CT and cerebral angiographic findings in patients with acute spontaneous subdural hematomas and correlate these imaging findings with causes of bleeding and clinical outcome. Twenty-one patients with nontraumatic acute spontaneous subdural hematoma presenting during the last five years underwent CT scanning and cerebral angiography was performed in twelve. To determine the cause of bleedings, CT and angiographic findings were retrospectively analysed. Clinical history, laboratory and operative findings, and final clinical outcome were reviewed. Acute spontaneous subdural hematoma is a rare condition, and the mortality rate is high. In patients with acute spontaneous subdural hematoma, as seen on CT, associated subarachnoid or intracerebral hemorrhage is strongly indicative of intracerebral vascular abnormalities such as aneurysm and arteriovenous malformation, and cerebral angiography is necessary. To ensure proper treatment and thus markedly reduce mortality, the causes of bleedings should be prompty determined by means of cerebral angiography. (author). 20 refs., 1 tab., 4 figs.
The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single-Molecule FRET.
Yang, Mengyi; Peng, Sijia; Sun, Ruirui; Lin, Jingdi; Wang, Nan; Chen, Chunlai
2018-01-09
Off-target binding and cleavage by Cas9 pose major challenges in its application. How the conformational dynamics of Cas9 govern its nuclease activity under on- and off-target conditions remains largely unknown. Here, using intra-molecular single-molecule fluorescence resonance energy transfer measurements, we revealed that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits among three major conformational states, mainly reflecting significant conformational mobility of the catalytic HNH domain. We also uncovered surprising long-range allosteric communication between the HNH domain and the RNA/DNA heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic site, which demonstrated that a unique proofreading mechanism served as the last checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the allosteric communication and proofreading step. Modulating interactions between Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these sites provides an alternative route to improve and optimize the CRISPR/Cas9 toolbox. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Spontaneous coronary artery dissection associated with apical hypertrophic cardiomyopathy
International Nuclear Information System (INIS)
Tuncer, M.; Gumrukcuoglu, H.A.; Ekim, H.; Gunes, Y.; Simsek, H.
2010-01-01
Apical hypertrophic cardiomyopathy (HCM) is a relatively uncommon inherited disease. Spontaneous coronary artery dissection (SCAD) is also uncommonly observed, which often occurs in pregnant or post partum women but is rare in men. This report describes a 38 years old man with apical hypertrophic cardiomyopathy who developed SCAD leading to acute inferior myocardial infarction. After emergent appendectomy operation at another hospital, he was immediately transferred to the Cardiology Department of our hospital due to acute myocardial infarction. He emergently underwent coronary angiography which showed a long dissection involving the right coronary. He underwent an emergent CABG with cardiopulmonary bypass. Postoperative recovery was uneventful and he was discharged. According to our knowledge, no case of spontaneous coronary artery dissection associated with apical hypertrophic cardiomyopathy unrelated to postpartum period or oral contraceptive use has been reported so far. (author)
Embryo apoptosis identification: Oocyte grade or cleavage stage?
Bakri, Noraina Mohd; Ibrahim, Siti Fatimah; Osman, Nurul Atikah; Hasan, Nurhaslina; Jaffar, Farah Hanan Fathihah; Rahman, Zulaiha Abdul; Osman, Khairul
2015-01-01
Apoptosis is a programed cell death that is vital for tissue homeostasis. However, embryo apoptosis had been known to be related to embryo fragmentation which should be avoided in in vitro fertilization (IVF). The purpose of this study was to evaluate the relationship of embryo apoptosis with the grade of immature oocytes and cleavage stage of in vitro produced (IVP) cattle embryos. This study consisted of 345 oocytes collected through ovary slicing. Immature oocytes were graded as A, B and C. This grading was based on cumulus cell thickness and compactness. All oocytes then underwent an in vitro maturation (IVM) procedure. An IVF was done 24 h after IVM culture. Prior to staining, stage of cleaved embryos was determined and classified as either 2, 4, 8 or >8-cell embryo stage. Apoptosis status of cleaved IVP embryos was determined by using annexin V-FITC staining technique at 48 and 72 h post insemination (hpi). Apoptosis status for each embryo was classified as either early or late. The result showed that there was no significant difference (p > 0.05) of apoptosis status among grade A, B and C embryos. All grades of oocytes showed embryo apoptosis where 1.5% late apoptosis for grade A, 4.5% and 10.4% of early and late apoptosis for grade B and grade C. Early apoptosis was not seen in grade A embryo. We also noted no significant difference (p > 0.05) of apoptosis status between 2, 4, 8 and >8-cell embryo stage. Early apoptosis was also not seen in >8-cell stage. Even though there were no differences in apoptosis expression between the three classes, the cleavage rate of grade A oocytes was significantly higher (p < 0.01) than grade B and grade C. In conclusion, the apoptosis expression in the embryo can occur regardless of the oocyte quality and the cleavage stage of the embryo produced. PMID:26858565
Microstructure and cleavage in lath martensitic steels
International Nuclear Information System (INIS)
Morris, John W Jr; Kinney, Chris; Pytlewski, Ken; Adachi, Y
2013-01-01
In this paper we discuss the microstructure of lath martensitic steels and the mechanisms by which it controls cleavage fracture. The specific experimental example is a 9Ni (9 wt% Ni) steel annealed to have a large prior austenite grain size, then examined and tested in the as-quenched condition to produce a relatively coarse lath martensite. The microstructure is shown to approximate the recently identified ‘classic’ lath martensite structure: prior austenite grains are divided into packets, packets are subdivided into blocks, and blocks contain interleaved laths whose variants are the two Kurjumov–Sachs relations that share the same Bain axis of the transformation. When the steel is fractured in brittle cleavage, the laths in the block share {100} cleavage planes and cleave as a unit. However, cleavage cracks deflect or blunt at the boundaries between blocks with different Bain axes. It follows that, as predicted, the block size governs the effective grain size for cleavage. (paper)
Recurrence rate after thoracoscopic surgery for primary spontaneous pneumothorax.
Dagnegård, Hanna H; Rosén, Alice; Sartipy, Ulrik; Bergman, Per
2017-08-01
There is an on-going discussion regarding the recurrence rate after surgery for primary spontaneous pneumothorax by video assisted thoracic surgery (VATS) or by thoracotomy access. This study aimed to describe the recurrence rate, and to identify a possible learning curve, following surgery for primary spontaneous pneumothorax by VATS. All patients who underwent surgery for primary spontaneous pneumothorax by VATS at Karolinska University Hospital 2004-2013 were reviewed. Preoperative and operative characteristics were obtained from medical records. Patients were followed-up through telephone interviews or questionnaires and by review of medical records. The primary outcome of interest was time to recurrence of pneumothorax requiring intervention. Outcomes were compared between patients operated during 2004-June 2010 and July 2010-2013. 219 patients who underwent 234 consecutive procedures were included. The mean follow-up times were 6.3 and 2.9 years in the early and late period, respectively. The postoperative recurrence rate in the early period was 16% (11%-25%), 18% (12%-27%), and 18% (12%-27%), at 1, 3 and 5 years, compared to 1.7% (0.4%-6.8%), 7.6% (3.7%-15%), and 9.8% (4.8%-19%) at 1, 3 and 5 years, in the late period (p = 0.016). We found that the recurrence rate after thoracoscopic surgery for primary spontaneous pneumothorax decreased significantly during the study period. Our results strongly suggest that thoracoscopic surgery for pneumothorax involve a substantial learning curve.
Modeling and inferring cleavage patterns in proliferating epithelia.
Directory of Open Access Journals (Sweden)
Ankit B Patel
2009-06-01
Full Text Available The regulation of cleavage plane orientation is one of the key mechanisms driving epithelial morphogenesis. Still, many aspects of the relationship between local cleavage patterns and tissue-level properties remain poorly understood. Here we develop a topological model that simulates the dynamics of a 2D proliferating epithelium from generation to generation, enabling the exploration of a wide variety of biologically plausible cleavage patterns. We investigate a spectrum of models that incorporate the spatial impact of neighboring cells and the temporal influence of parent cells on the choice of cleavage plane. Our findings show that cleavage patterns generate "signature" equilibrium distributions of polygonal cell shapes. These signatures enable the inference of local cleavage parameters such as neighbor impact, maternal influence, and division symmetry from global observations of the distribution of cell shape. Applying these insights to the proliferating epithelia of five diverse organisms, we find that strong division symmetry and moderate neighbor/maternal influence are required to reproduce the predominance of hexagonal cells and low variability in cell shape seen empirically. Furthermore, we present two distinct cleavage pattern models, one stochastic and one deterministic, that can reproduce the empirical distribution of cell shapes. Although the proliferating epithelia of the five diverse organisms show a highly conserved cell shape distribution, there are multiple plausible cleavage patterns that can generate this distribution, and experimental evidence suggests that indeed plants and fruitflies use distinct division mechanisms.
Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm
International Nuclear Information System (INIS)
Gonzalez Valverde, F.M.; Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.
2007-01-01
Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture
Live births after polar body biopsy and frozen-thawed cleavage stage embryo transfer: case report.
Guimarães, Fernando; Roque, Matheus; Valle, Marcello; Kostolias, Alessandra; Azevedo, Rodrigo A de; Martinhago, Ciro D; Sampaio, Marcos; Geber, Selmo
2016-12-01
Pre-implantation genetic diagnosis (PGD) or screening (PGS) technology, has emerged and developed in the past few years, benefiting couples as it allows the selection and transfer of healthy embryos during IVF treatments. These techniques can be performed in oocytes (polar-body biopsy) or embryos (blastomere or trophectoderm biopsy). In this case report, we describe the first two live births to be published in Brazil after a polar-body (PB) biopsy. In case 1, a 42-year-old was submitted to PB biopsy with PGS due to advanced maternal age and poor ovarian reserve. Five MII oocytes underwent first and second polar body biopsy and four cleavage embryos were cryopreserved. The PGS analysis resulted in two euploid embryos (next generation sequence). A frozen-thawed embryo transfer (FET) was performed after endometrial priming and a healthy baby was delivered after a cesarean section (37 weeks, female, 3390g, 47.5 cm). In case 2, a 40-year old patient with balanced translocation and poor ovarian response was submitted to PB biopsy. Two MII oocytes underwent first and second polar body biopsy and two embryos were cryopreserved in cleavage stage. The analysis resulted in one euploid embryo that was transferred after endometrial priming. A preterm healthy baby (34 weeks, female, 2100g, 40 cm) was delivered via cesarean section. In conclusion, although the blastocyst biopsy is the norm when performing PGS/PGD during IVF treatments, other alternatives (as PB biopsy) should be considered in some specific situations.
Intermolecular cleavage by UmuD-like mutagenesis proteins
McDonald, John P.; Frank, Ekaterina G.; Levine, Arthur S.; Woodgate, Roger
1998-01-01
The activity of a number of proteins is regulated by self-processing reactions. Elegant examples are the cleavage of the prokaryotic LexA and λCI transcriptional repressors and the UmuD-like mutagenesis proteins. Various studies support the hypothesis that LexA and λCI cleavage reactions are predominantly intramolecular in nature. The recently described crystal structure of the Escherichia coli UmuD′ protein (the posttranslational cleavage product of the UmuD protein) suggests, however, that the region of the protein corresponding to the cleavage site is at least 50 Å away from the catalytic active site. We considered the possibility, therefore, that the UmuD-like proteins might undergo self-processing that, in contrast to LexA and λCI, occurs via an intermolecular rather than intramolecular reaction. To test this hypothesis, we introduced into E. coli compatible plasmids with mutations at either the cleavage or the catalytic site of three UmuD-like proteins. Cleavage of these proteins only occurs in the presence of both plasmids, indicating that the reaction is indeed intermolecular in nature. Furthermore, this intermolecular reaction is completely dependent upon the multifunctional RecA protein and leads to the restoration of cellular mutagenesis in nonmutable E. coli strains. Intermolecular cleavage of a biotinylated UmuD active site mutant was also observed in vitro in the presence of the wild-type UmuD′ protein, indicating that in addition to the intact UmuD protein, the normal cleavage product (UmuD′) can also act as a classical enzyme. PMID:9465040
Spontaneous coronary artery dissection: complete angiographic resolution without stenting
Directory of Open Access Journals (Sweden)
Alexandre Abizaid
2007-09-01
Full Text Available A case of spontaneous coronary artery dissection in a 49-year-oldwoman is presented. She did not present the classical cardiovascular riskfactors. Etiology and treatment are discussed. She underwent primarypercutaneous coronary intervention of the left anterior descendingartery with no stenting and had complete angiographic resolution.
Regioselectivity in the Reductive Bond Cleavage of Diarylalkylsulfonium Salts
DEFF Research Database (Denmark)
Kampmeier, Jack; Mansurul Hoque, AKM; D. Saeva, Franklin
2009-01-01
products vary from regiospecific alkyl cleavage to predominant aryl cleavage as a function of the potential of the reducing agent. We conclude that differences between the reductive cleavages of mono- and diarylsulfonium salts are direct consequences of the structures of the sulfuranyl radical......- tolylethylsulfonium and di-4-tolyl-2-phenylethylsulfonium salts by a variety of one-electron reducing agents ranging in potential from -0.77 to +2.5 eV (vs SCE) and including thermal reductants, indirect electrolyses mediated by a series of cyanoaromatics, and excited singlet states. We report that the cleavage...... intermediates and the bond dissociation energies of the alkyl and aryl bonds. Competitions between the rates of cleavage and oxidation of the intermediate sulfuranyl radicals and between concerted and stepwise mechanisms are discussed to explain the variations in bond cleavage products as a function...
Spontaneous Splenic Rupture in Melanoma
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Hadi Mirfazaelian
2014-01-01
Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.
Time Course of Early Postadmission Hematoma Expansion in Spontaneous Intracerebral Hemorrhage
DEFF Research Database (Denmark)
Ovesen, Christian; Christensen, Anders Fogh; Krieger, Derk W
2014-01-01
spontaneous intracerebral hematoma within 4.5 hours. On admission, patients underwent noncontrast computed tomography (CT) and CT angiography. Serial hematoma volume estimations by transcranial B-mode ultrasound were effected through the contralateral transtemporal bone window by obtaining sagittal...
Secondary isotope effects on alpha-cleavage reactions
International Nuclear Information System (INIS)
Ingemann, S.; Hammerum, S.
1980-01-01
Kinetic deuterium isotope effects on mass spectral reactions have in several instances been utilized to provide structural information and to answer mechanistic questions. Typically, the influence of the deuterium label on the rate of one of a number of competing reactions has been studied. Secondary isotope effects have usually been assumed to be relatively insignificant in comparison with the observed kinetic effects, even though various workers have shown that secondary isotope effects may indeed exert a considerable influence on the rates of competing simple cleavages. Recent studies have provided quantitative data to show that the mere presence of deuterium atoms up to six bonds away may influence the rate of a simple cleavage reaction. In relation to an investigation of rearrangements accompanying simple cleavage reactions, a semi-quantitative measure was needed of the variation of the secondary isotope effect with the number of bonds between the deuterium label and the point of rupture. The influence has therefore been examined of the presence of remote deuterium atoms on a typical simple cleavage reaction, the α-cleavage of aliphatic amines. As a model compound, N-methyldipentylamine was chosen, systematically labelled with deuterium. (author)
International Nuclear Information System (INIS)
Gillilan, R.E.; Pohl, T.M.; Whalen, D.L.
1982-01-01
Data are reported that indicate that 6-methoxy-1,2,3-tetrahydronaphthalene oxide undergoes a spontaneous reaction to yield mostly 6-methyoxy-2-tetralone. Hydrogen-migration is reported to be the rate determining step in the reaction. Reaction mechanisms involving a one-step reaction with a concurrent C-O bond cleavage and hydrogen migration or reversible C-O bond cleavage followed by the rate-limiting hydrogen migration are proposed, but no clear distinction between the schemes is made
Surgical treatment versus conventional chest tube drainage in primary spontaneous pneumothorax
DEFF Research Database (Denmark)
Olesen, Winnie Hedevang; Katballe, Niels; Sindby, Jesper Eske
2018-01-01
OBJECTIVES: Primary spontaneous pneumothorax frequently recurs after chest tube management. Evidence is lacking whether patients may benefit from surgery following their first episode. METHODS: We performed a multicentre, randomized trial and enrolled young, otherwise healthy patients admitted...... with their first episode of primary spontaneous pneumothorax and treated using conventional chest tube drainage. Patients underwent high-resolution computed tomography on fully expanded lungs, and using web-based randomization, we assigned patients to continued conservative chest tube treatment or chest tube...... treatment to prevent recurrence in patients with their first presentation of primary spontaneous pneumothorax and should be the standard of care when high-resolution computed tomography demonstrates bullae ≥2 cm. Clinical trial registration: ClinicalTrial.gov: NCT 02866305....
Directory of Open Access Journals (Sweden)
Michael Kinori
2012-01-01
Full Text Available We report a patient with gyrate atrophy, a rare metabolic disease, who had bilateral late spontaneous posterior dislocation of in-the-bag posterior chamber intraocular lens (PCIOL. He underwent pars plana vitrectomy, PCIOL retrieval and anterior chamber intraocular lens implantation in both eyes. This report may imply that patients with gyrate atrophy are at risk for spontaneous dislocation of intraocular lenses.
Quantification of DNA cleavage specificity in Hi-C experiments.
Meluzzi, Dario; Arya, Gaurav
2016-01-08
Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to deduce genomewide interactions between arbitrary loci. A key step in these experiments is the cleavage of cross-linked chromatin with a restriction endonuclease. Although this cleavage should happen specifically at the enzyme's recognition sequence, an unknown proportion of cleavage events may involve other sequences, owing to the enzyme's star activity or to random DNA breakage. A quantitative estimation of these non-specific cleavages may enable simulating realistic Hi-C read pairs for validation of downstream analyses, monitoring the reproducibility of experimental conditions and investigating biophysical properties that correlate with DNA cleavage patterns. Here we describe a computational method for analyzing Hi-C read pairs to estimate the fractions of cleavages at different possible targets. The method relies on expressing an observed local target distribution downstream of aligned reads as a linear combination of known conditional local target distributions. We validated this method using Hi-C read pairs obtained by computer simulation. Application of the method to experimental Hi-C datasets from murine cells revealed interesting similarities and differences in patterns of cleavage across the various experiments considered. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
Dataset of cocoa aspartic protease cleavage sites
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Katharina Janek
2016-09-01
Full Text Available The data provide information in support of the research article, “The cleavage specificity of the aspartic protease of cocoa beans involved in the generation of the cocoa-specific aroma precursors” (Janek et al., 2016 [1]. Three different protein substrates were partially digested with the aspartic protease isolated from cocoa beans and commercial pepsin, respectively. The obtained peptide fragments were analyzed by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS/MS and identified using the MASCOT server. The N- and C-terminal ends of the peptide fragments were used to identify the corresponding in-vitro cleavage sites by comparison with the amino acid sequences of the substrate proteins. The same procedure was applied to identify the cleavage sites used by the cocoa aspartic protease during cocoa fermentation starting from the published amino acid sequences of oligopeptides isolated from fermented cocoa beans. Keywords: Aspartic protease, Cleavage sites, Cocoa, In-vitro proteolysis, Mass spectrometry, Peptides
Cleavage events and sperm dynamics in chick intrauterine embryos.
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Hyung Chul Lee
Full Text Available This study was undertaken to elucidate detailed event of early embryogenesis in chicken embryos using a noninvasive egg retrieval technique before oviposition. White Leghorn intrauterine eggs were retrieved from 95 cyclic hens aged up to 54-56 weeks and morphogenetic observation was made under both bright field and fluorescent image in a time course manner. Differing from mammals, asymmetric cleavage to yield preblastodermal cells was observed throughout early embryogenesis. The first two divisions occurred synchronously and four polarized preblastodermal cells resulted after cruciform cleavage. Then, asynchronous cleavage continued in a radial manner and overall cell size in the initial cleavage region was smaller than that in the distal area. Numerous sperms were visible, regardless of zygotic nuclei formation. Condensed sperm heads were present mainly in the perivitelline space and cytoplasm, and rarely in the yolk region, while decondensed sperm heads were only visible in the yolk. In conclusion, apparent differences in sperm dynamics and early cleavage events compared with mammalian embryos were detected in chick embryo development, which demonstrated polarized cleavage with penetrating supernumerary sperm into multiple regions.
Heo, Jinsol; Kim, Se Hyeuk
2013-01-01
Carotenoid cleavage dioxygenases (CCDs) are enzymes that catalyze the oxidative cleavage of carotenoids at a specific double bond to generate apocarotenoids. In this study, we investigated the activity and substrate preferences of NSC3, a CCD of Nostoc sp. strain PCC 7120, in vivo and in vitro using natural and nonnatural carotenoid structures. NSC3 cleaved β-apo-8′-carotenal at 3 positions, C-13C-14, C-15C-15′, and C-13′C-14′, revealing a unique cleavage pattern. NSC3 cleaves the natural structure of carotenoids 4,4′-diaponeurosporene, 4,4′-diaponeurosporen-4′-al, 4,4′-diaponeurosporen-4′-oic acid, 4,4′-diapotorulene, and 4,4′-diapotorulen-4′-al to generate novel cleavage products (apo-14′-diaponeurosporenal, apo-13′-diaponeurosporenal, apo-10′-diaponeurosporenal, apo-14′-diapotorulenal, and apo-10′-diapotorulenal, respectively). The study of carotenoids with natural or nonnatural structures produced by using synthetic modules could provide information valuable for understanding the cleavage reactions or substrate preferences of other CCDs in vivo and in vitro. PMID:23524669
In vivo analysis of the Notch receptor S1 cleavage.
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Robert J Lake
2009-08-01
Full Text Available A ligand-independent cleavage (S1 in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control.
Vliet, T. van; Schaik, F. van; Schreurs, W.H.P.; Berg, H. van den
1996-01-01
In view of controversies about assessment of the β-carotene cleavage activity, methodological aspects and problems of the dioxygenase assay are described. Using rat and hamster intestinal preparations the method was optimized on retinal formation, the only cleavage product we could demonstrate. It
Pripper: prediction of caspase cleavage sites from whole proteomes
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Salmi Jussi
2010-06-01
Full Text Available Abstract Background Caspases are a family of proteases that have central functions in programmed cell death (apoptosis and inflammation. Caspases mediate their effects through aspartate-specific cleavage of their target proteins, and at present almost 400 caspase substrates are known. There are several methods developed to predict caspase cleavage sites from individual proteins, but currently none of them can be used to predict caspase cleavage sites from multiple proteins or entire proteomes, or to use several classifiers in combination. The possibility to create a database from predicted caspase cleavage products for the whole genome could significantly aid in identifying novel caspase targets from tandem mass spectrometry based proteomic experiments. Results Three different pattern recognition classifiers were developed for predicting caspase cleavage sites from protein sequences. Evaluation of the classifiers with quality measures indicated that all of the three classifiers performed well in predicting caspase cleavage sites, and when combining different classifiers the accuracy increased further. A new tool, Pripper, was developed to utilize the classifiers and predict the caspase cut sites from an arbitrary number of input sequences. A database was constructed with the developed tool, and it was used to identify caspase target proteins from tandem mass spectrometry data from two different proteomic experiments. Both known caspase cleavage products as well as novel cleavage products were identified using the database demonstrating the usefulness of the tool. Pripper is not restricted to predicting only caspase cut sites, but it gives the possibility to scan protein sequences for any given motif(s and predict cut sites once a suitable cut site prediction model for any other protease has been developed. Pripper is freely available and can be downloaded from http://users.utu.fi/mijopi/Pripper. Conclusions We have developed Pripper, a tool for
Energy Technology Data Exchange (ETDEWEB)
Horikoshi, Toru; Naganuma, Hirofumi; Fukasawa, Isao; Uchida, Mikito; Nukui, Hideaki [Yamanashi Medical Univ., Tamaho (Japan)
1998-09-01
The clinical and radiological characteristics of self-resolving hematoma were assessed retrospectively in a series of patients with chronic subdural hematomas (SDHs) treated over a recent 6-year period in a local hospital. Spontaneous resolution was observed in five of 27 hematomas occurring in four of 23 patients. Clinical and radiological findings of the four cases were compared to those of the remaining 19 cases. All spontaneously resolving SDHs were asymptomatic or only caused mild transient headache, and disappeared within 4 to 9 months after head injury. All spontaneously resolving SDHs were located in the frontal region, and maximum thickness and midline displacement were less than those in the other 19 patients who were symptomatic and underwent surgery. Computed tomography demonstrated a low density line between the hematoma and the cerebral cortex, indicative of remaining cerebrospinal fluid space in four of five hematomas. Spontaneously resolving SDH is more frequent than formerly expected. Asymptomatic SDHs localized in the frontal region with small mass signs can be expected to disappear spontaneously without deterioration. (author)
International Nuclear Information System (INIS)
Merson, E.; Kudrya, A.V.; Trachenko, V.A.; Merson, D.; Danilov, V.; Vinogradov, A.
2016-01-01
“True” cleavage (TC) and quasi-cleavage (QC) fracture surfaces of low-carbon steel specimens tested in liquid nitrogen and after hydrogen charging respectively were investigated by quantitative confocal laser scanning microscopy (CLSM) and conventional scanning electron microscopy (SEM) with electron-backscattered diffraction (EBSD). Topological and crystallographic features of the TC fracture surface are found in good agreement with the generally accepted cleavage mechanism: TC facets diameters correspond to those of grains; the crack path strictly follows the crystallographic orientation of grains and the most of the cleavage cracks are parallel to {100} planes. On the 2D SEM images, the QC facets appeared resembling the TC ones in terms of river line patterns, shapes and sizes. However, the substantial differences between the topography of these two kinds of fracture surfaces were revealed by 3D CLSM: the average misorientation angle between QC facets and the roughness of the QC fracture surface were much lower than those measured for TC. It is demonstrated that all these features are attributed to the specific fracture mechanism operating during hydrogen-assisted cracking.
Energy Technology Data Exchange (ETDEWEB)
Merson, E. [Institute of Advanced Technologies, Togliatti State University, 445667 (Russian Federation); Kudrya, A.V.; Trachenko, V.A. [Department of Physical Metallurgy and the Physics of Strength, NUST MISiS, Moscow 119490 (Russian Federation); Merson, D. [Institute of Advanced Technologies, Togliatti State University, 445667 (Russian Federation); Laboratory for Advanced Materials, Kazan Federal University, Naberezhnye Chelny 423812, Republic of Tatarstan (Russian Federation); Danilov, V. [Institute of Advanced Technologies, Togliatti State University, 445667 (Russian Federation); Vinogradov, A. [Institute of Advanced Technologies, Togliatti State University, 445667 (Russian Federation); Department of Engineering Design and Materials, Norwegian University of Science and Technology – NTNU, N-7491 Trondheim (Norway)
2016-05-17
“True” cleavage (TC) and quasi-cleavage (QC) fracture surfaces of low-carbon steel specimens tested in liquid nitrogen and after hydrogen charging respectively were investigated by quantitative confocal laser scanning microscopy (CLSM) and conventional scanning electron microscopy (SEM) with electron-backscattered diffraction (EBSD). Topological and crystallographic features of the TC fracture surface are found in good agreement with the generally accepted cleavage mechanism: TC facets diameters correspond to those of grains; the crack path strictly follows the crystallographic orientation of grains and the most of the cleavage cracks are parallel to {100} planes. On the 2D SEM images, the QC facets appeared resembling the TC ones in terms of river line patterns, shapes and sizes. However, the substantial differences between the topography of these two kinds of fracture surfaces were revealed by 3D CLSM: the average misorientation angle between QC facets and the roughness of the QC fracture surface were much lower than those measured for TC. It is demonstrated that all these features are attributed to the specific fracture mechanism operating during hydrogen-assisted cracking.
Lizardo, Radhames E; Langness, Simone; Davenport, Katherine P; Kling, Karen; Fairbanks, Timothy; Bickler, Stephen W; Grabowski, Julia
2015-12-01
Antiinflammatory medications are thought to reduce the effectiveness of pleurodesis performed for the treatment of spontaneous pneumothorax. We reviewed our experience with children undergoing video-assisted thorascopic surgery (VATS) with pleurodesis for pneumothorax to determine if ketorolac administration influences patient outcomes. A retrospective review of patients who underwent VATS pleurodesis for spontaneous pneumothorax from 2009 to 2013 at a pediatric hospital was performed. Length of stay, radiographic pneumothorax resolution prior to discharge, and ipsilateral recurrence rates were compared in patients who did and did not receive perioperative ketorolac. Over a 50-month period, 51 patients underwent VATS with mechanical pleurodesis for spontaneous pneumothorax. The average age was 15.5years, and 76% were male. Ketorolac was administered to 26/51 patients. There were no differences in average length of stay (11.3 vs 10.9days, p=0.36), incidence of residual pneumothorax at discharge (22/41 vs 19/41, p=0.48), or ipsilateral recurrence (5/10 vs 5/10, p=1). Despite the intrinsic antiinflammatory properties of ketorolac, our data suggests that its use for patients undergoing pleurodesis for spontaneous pneumothorax does not detrimentally influence the outcomes of surgery. Therefore, we conclude that ketorolac can be used for pain control in this population. Large-scale studies are warranted to validate these findings. Published by Elsevier Inc.
Urosepsis complicated by a spontaneous bladder perforation.
Lutwak, Nancy; Dill, Curt
2011-11-08
The authors present a case of a 72-year-old diabetic male s/p pelvic irradiation for prostate carcinoma who arrived in the emergency department with complaints of shaking chills. After admission for urosepsis, he developed severe abdominal pain and examination revealed a diffusely tender abdomen. The patient was diagnosed with spontaneous urinary bladder perforation and underwent surgery. After several weeks of intravenous antibiotics, he was discharged with multiple drains in place and bilateral nephrostomy tubes.
Functional analysis of coordinated cleavage in V(D)J recombination.
Kim, D R; Oettinger, M A
1998-08-01
V(D)J recombination in vivo requires a pair of signals with distinct spacer elements of 12 and 23 bp that separate conserved heptamer and nonamer motifs. Cleavage in vitro by the RAG1 and RAG2 proteins can occur at individual signals when the reaction buffer contains Mn2+, but cleavage is restricted to substrates containing two signals when Mg2+ is the divalent cation. By using a novel V(D)J cleavage substrate, we show that while the RAG proteins alone establish a moderate preference for a 12/23 pair versus a 12/12 pair, a much stricter dependence of cleavage on the 12/23 signal pair is produced by the inclusion of HMG1 and competitor double-stranded DNA. The competitor DNA serves to inhibit the cleavage of substrates carrying a 12/12 or 23/23 pair, as well as the cutting at individual signals in 12/23 substrates. We show that a 23/33 pair is more efficiently recombined than a 12/33 pair, suggesting that the 12/23 rule can be generalized to a requirement for spacers that differ from each other by a single helical turn. Furthermore, we suggest that a fixed spatial orientation of signals is required for cleavage. In general, the same signal variants that can be cleaved singly can function under conditions in which a signal pair is required. However, a chemically modified substrate with one noncleavable signal enables us to show that formation of a functional cleavage complex is mechanistically separable from the cleavage reaction itself and that although cleavage requires a pair of signals, cutting does not have to occur simultaneously at both. The implications of these results are discussed with respect to the mechanism of V(D)J recombination and the generation of chromosomal translocations.
Spontaneous group synchronization of movements and respiratory rhythms.
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Erwan Codrons
Full Text Available We tested whether pre-assigned arm movements performed in a group setting spontaneously synchronized and whether synchronization extended to heart and respiratory rhythms. We monitored arm movements, respiration and electrocardiogram at rest and during spontaneous, music and metronome-associated arm-swinging. No directions were given on whether or how the arm swinging were to be synchronized between participants or with the external cues. Synchronization within 3 groups of 10 participants studied collectively was compared with pseudo-synchronization of 3 groups of 10 participants that underwent an identical protocol but in an individual setting. Motor synchronization was found to be higher in the collective groups than in the individuals for the metronome-associated condition. On a repetition of the protocol on the following day, motor synchronization in the collective groups extended to the spontaneous, un-cued condition. Breathing was also more synchronized in the collective groups than in the individuals, particularly at rest and in the music-associated condition. Group synchronization occurs without explicit instructions, and involves both movements and respiratory control rhythms.
Spontaneous resorption of sub-retinal cortical lens material
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Salil S Gadkari
2014-01-01
Full Text Available We report a rare case of retained sub-retinal cortical material, which underwent spontaneous resorption. Patient presented with a left eye traumatic retinal detachment with a large retinal tear and posteriorly dislocated cataractous lens. Vitrectomy, lensectomy, silicone oil injection, and endolaser were performed. A good visual result was achieved. The report draws attention to this condition and highlights possible technique for minimizing risk of this complication in similar cases.
A deep azygoesophageal recess may increase the risk of secondary spontaneous pneumothorax.
Takahashi, Tsuyoshi; Kawashima, Mitsuaki; Kuwano, Hideki; Nagayama, Kazuhiro; Nitadori, Jyunichi; Anraku, Masaki; Sato, Masaaki; Murakawa, Tomohiro; Nakajima, Jun
2017-09-01
The azygoesophageal recess (AER) is known as a possible cause of bulla formation in patients with spontaneous pneumothorax. However, there has been little focus on the depth of the AER. We evaluated the relationship between the depth of the AER and pneumothorax development. We conducted a retrospective study of 80 spontaneous pneumothorax patients who underwent surgery at our institution. We evaluated the depth of the AER on preoperative computed tomography scans. Ruptured bullae at the AER were found in 12 patients (52.2%) with secondary spontaneous pneumothorax (SSP) and 8 patients (14.0%) with primary spontaneous pneumothorax (PSP) (p < 0.001). In patients with ruptured bullae at the AER, 10 SSP patients (83.3%) had a deep AER while only 2 PSP patients (25%) had a deep AER (p = 0.015). A deep AER was more frequently associated with SSP than with PSP. A deep AER may contributes to bulla formation and rupture in SSP patients.
Cleavage sites within the poliovirus capsid protein precursors
International Nuclear Information System (INIS)
Larsen, G.R.; Anderson, C.W.; Dorner, A.J.; Semler, B.L.; Wimmer, E.
1982-01-01
Partial amino-terminal sequence analysis was performed on radiolabeled poliovirus capsid proteins VP1, VP2, and VP3. A computer-assisted comparison of the amino acid sequences obtained with that predicted by the nucleotide sequence of the poliovirus genome allows assignment of the amino terminus of each capsid protein to a unique position within the virus polyprotein. Sequence analysis of trypsin-digested VP4, which has a blocked amino terminus, demonstrates that VP4 is encoded at or very near to the amino terminus of the polyprotein. The gene order of the capsid proteins is VP4-VP2-VP3-VP1. Cleavage of VP0 to VP4 and VP2 is shown to occur between asparagine and serine, whereas the cleavages that separate VP2/VP3 and VP3/VP1 occur between glutamine and glycine residues. This finding supports the hypothesis that the cleavage of VP0, which occurs during virion morphogenesis, is distinct from the cleavages that separate functional regions of the polyprotein
A new cultural cleavage in post-modern society
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Jan-Erik Lane
2007-09-01
Full Text Available The attitudes towards gender and homosexuality tend to be linked at the micro level (individuals, which explains the political saliency of this newly emerging cleavage. At the macro level (country, the main finding is that the value orientations towards gender and homosexuality are strongly embedded in the basic cultural or civilisation differences among countries. As developing countries modernise and enter post-modernity, they will also experience the gender cleavage, especially when they adhere to an individualistic culture. Cultural cleavages in the post-modern society, whether in rich or developing countries, can only be properly researched by the survey method. It opens up a large area for both micro and macro analyses in the social sciences.
Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations.
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José B Oliveira-Martins
Full Text Available The cellular form of the prion protein, PrP(C, undergoes extensive proteolysis at the alpha site (109K [see text]H110. Expression of non-cleavable PrP(C mutants in transgenic mice correlates with neurotoxicity, suggesting that alpha-cleavage is important for PrP(C physiology. To gain insights into the mechanisms of alpha-cleavage, we generated a library of PrP(C mutants with mutations in the region neighbouring the alpha-cleavage site. The prevalence of C1, the carboxy adduct of alpha-cleavage, was determined for each mutant. In cell lines of disparate origin, C1 prevalence was unaffected by variations in charge and hydrophobicity of the region neighbouring the alpha-cleavage site, and by substitutions of the residues in the palindrome that flanks this site. Instead, alpha-cleavage was size-dependently impaired by deletions within the domain 106-119. Almost no cleavage was observed upon full deletion of this domain. These results suggest that alpha-cleavage is executed by an alpha-PrPase whose activity, despite surprisingly limited sequence specificity, is dependent on the size of the central region of PrP(C.
Spontaneous Hypoglycemia After Islet Autotransplantation for Chronic Pancreatitis.
Lin, Yu Kuei; Faiman, Charles; Johnston, Philip C; Walsh, R Matthew; Stevens, Tyler; Bottino, Rita; Hatipoglu, Betul A
2016-10-01
Spontaneous hypoglycemia has been reported in patients after total pancreatectomy (TP) and islet autotransplantation (IAT) with maintained insulin independence. Details surrounding these events have not been well described. The objective of the study was to determine the frequency and characteristics of spontaneous hypoglycemia in patients undergoing TP-IAT and/or to ascertain predictive or protective factors of its development. This was an observational cohort study in 40 patients who underwent TP-IAT from August 2008 to May 2014, with a median follow-up of 34 months. The study was conducted at a single institution (Cleveland Clinic). Patients included recipients of TP-IAT. The intervention included small, frequent meals in those patients who developed spontaneous hypoglycemia. Incidence of spontaneous hypoglycemia development, characteristics of the patients developing hypoglycemia, and their response to small, frequent meals were measured. Six of 12 patients, who maintained insulin independence, developed spontaneous hypoglycemia. The episodes could be fasting, postprandial, and/or exercise associated, with the frequency ranging from two to three times daily to once every 1-2 weeks. All patients experienced at least one episode that required external assistance, glucagon administration, and/or emergent medical attention. Patients who developed hypoglycemia had a lower median age and tended to have a lower median islet equivalent/kg body weight but a higher median total islet equivalent, body mass index, and homeostatic model assessment for insulin resistance score. All patients who received small, frequent meal intervention had improvement in severity and/or frequency of the hypoglycemic episodes. Spontaneous hypoglycemia is prevalent after TP-IAT. Although the underlying pathophysiology responsible for these hypoglycemia events remains to be elucidated, small, frequent meal intervention is helpful in ameliorating this condition.
Comparative and phylogenetic perspectives of the cleavage process in tailed amphibians.
Desnitskiy, Alexey G; Litvinchuk, Spartak N
2015-10-01
The order Caudata includes about 660 species and displays a variety of important developmental traits such as cleavage pattern and egg size. However, the cleavage process of tailed amphibians has never been analyzed within a phylogenetic framework. We use published data on the embryos of 36 species concerning the character of the third cleavage furrow (latitudinal, longitudinal or variable) and the magnitude of synchronous cleavage period (up to 3-4 synchronous cell divisions in the animal hemisphere or a considerably longer series of synchronous divisions followed by midblastula transition). Several species from basal caudate families Cryptobranchidae (Andrias davidianus and Cryptobranchus alleganiensis) and Hynobiidae (Onychodactylus japonicus) as well as several representatives from derived families Plethodontidae (Desmognathus fuscus and Ensatina eschscholtzii) and Proteidae (Necturus maculosus) are characterized by longitudinal furrows of the third cleavage and the loss of synchrony as early as the 8-cell stage. By contrast, many representatives of derived families Ambystomatidae and Salamandridae have latitudinal furrows of the third cleavage and extensive period of synchronous divisions. Our analysis of these ontogenetic characters mapped onto a phylogenetic tree shows that the cleavage pattern of large, yolky eggs with short series of synchronous divisions is an ancestral trait for the tailed amphibians, while the data on the orientation of third cleavage furrows seem to be ambiguous with respect to phylogeny. Nevertheless, the midblastula transition, which is characteristic of the model species Ambystoma mexicanum (Caudata) and Xenopus laevis (Anura), might have evolved convergently in these two amphibian orders.
Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions.
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Rémi Baroso
Full Text Available Angioedema without wheals (AE is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh, but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases.We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker.We retrospectively investigated high molecular weight kininogen (HK cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis.Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98-175μg/mL, n = 51 and in healthy women (90-176μg/mL, n = 74, while HK cleavage was lower (p14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13 or two weeks after AE attack (n = 2, HK cleavage was not fully restored, suggesting its use as a post-attack assay.As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management.
Chemical cleavage reactions of DNA on solid support: application in mutation detection
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Cotton Richard GH
2003-05-01
Full Text Available Abstract Background The conventional solution-phase Chemical Cleavage of Mismatch (CCM method is time-consuming, as the protocol requires purification of DNA after each reaction step. This paper describes a new version of CCM to overcome this problem by immobilizing DNA on silica solid supports. Results DNA test samples were loaded on to silica beads and the DNA bound to the solid supports underwent chemical modification reactions with KMnO4 (potassium permanganate and hydroxylamine in 3M TEAC (tetraethylammonium chloride solution. The resulting modified DNA was then simultaneously cleaved by piperidine and removed from the solid supports to afford DNA fragments without the requirement of DNA purification between reaction steps. Conclusions The new solid-phase version of CCM is a fast, cost-effective and sensitive method for detection of mismatches and mutations.
Detection of nucleic acid sequences by invader-directed cleavage
Brow, Mary Ann D.; Hall, Jeff Steven Grotelueschen; Lyamichev, Victor; Olive, David Michael; Prudent, James Robert
1999-01-01
The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The 5' nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof. The present invention further relates to methods and devices for the separation of nucleic acid molecules based by charge.
Controllable laser thermal cleavage of sapphire wafers
Xu, Jiayu; Hu, Hong; Zhuang, Changhui; Ma, Guodong; Han, Junlong; Lei, Yulin
2018-03-01
Laser processing of substrates for light-emitting diodes (LEDs) offers advantages over other processing techniques and is therefore an active research area in both industrial and academic sectors. The processing of sapphire wafers is problematic because sapphire is a hard and brittle material. Semiconductor laser scribing processing suffers certain disadvantages that have yet to be overcome, thereby necessitating further investigation. In this work, a platform for controllable laser thermal cleavage was constructed. A sapphire LED wafer was modeled using the finite element method to simulate the thermal and stress distributions under different conditions. A guide groove cut by laser ablation before the cleavage process was observed to guide the crack extension and avoid deviation. The surface and cross section of sapphire wafers processed using controllable laser thermal cleavage were characterized by scanning electron microscopy and optical microscopy, and their morphology was compared to that of wafers processed using stealth dicing. The differences in luminous efficiency between substrates prepared using these two processing methods are explained.
Chirality-controlled spontaneous twisting of crystals due to thermal topochemical reaction.
Rai, Rishika; Krishnan, Baiju P; Sureshan, Kana M
2018-03-20
Crystals that show mechanical response against various stimuli are of great interest. These stimuli induce polymorphic transitions, isomerizations, or chemical reactions in the crystal and the strain generated between the daughter and parent domains is transcribed into mechanical response. We observed that the crystals of modified dipeptide LL (N 3 -l-Ala-l-Val-NHCH 2 C≡CH) undergo spontaneous twisting to form right-handed twisted crystals not only at room temperature but also at 0 °C over time. Using various spectroscopic techniques, we have established that the twisting is due to the spontaneous topochemical azide-alkyne cycloaddition (TAAC) reaction at room temperature or lower temperatures. The rate of twisting can be increased by heating, exploiting the faster kinetics of the TAAC reaction at higher temperatures. To address the role of molecular chirality in the direction of twisting the enantiomer of dipeptide LL, N 3 -d-Ala-d-Val-NHCH 2 C≡CH (DD), was synthesized and topochemical reactivity and mechanoresponse of its crystals were studied. We have found that dipeptide DD not only underwent TAAC reaction, giving 1,4-triazole-linked pseudopolypeptides of d-amino acids, but also underwent twisting with opposite handedness (left-handed twisting), establishing the role of molecular chirality in controlling the direction of mechanoresponse. This paper reports ( i ) a mechanical response due to a thermal reaction and ( ii ) a spontaneous mechanical response in crystals and ( iii ) explains the role of molecular chirality in the handedness of the macroscopic mechanical response.
The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single-Molecule FRET
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Mengyi Yang
2018-01-01
Full Text Available Summary: Off-target binding and cleavage by Cas9 pose major challenges in its application. How the conformational dynamics of Cas9 govern its nuclease activity under on- and off-target conditions remains largely unknown. Here, using intra-molecular single-molecule fluorescence resonance energy transfer measurements, we revealed that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits among three major conformational states, mainly reflecting significant conformational mobility of the catalytic HNH domain. We also uncovered surprising long-range allosteric communication between the HNH domain and the RNA/DNA heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic site, which demonstrated that a unique proofreading mechanism served as the last checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the allosteric communication and proofreading step. Modulating interactions between Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these sites provides an alternative route to improve and optimize the CRISPR/Cas9 toolbox. : Yang et al. revealed significant conformational dynamics of Cas9 at global and local scales using single-molecule FRET. They uncovered surprising long-range allosteric communication between the HNH nuclease domain and the RNA/DNA heteroduplex at the PAM-distal end that serves as a proofreading checkpoint to govern the nuclease activity and specificity of Cas9. Keywords: CRISPR, Cas9, single-molecule, FRET, conformational dynamics, proofreading, off-target, allosteric communication, genome editing
Full Length Research Paper Curcumin induces cleavage of -catenin ...
African Journals Online (AJOL)
β-Catenin/Tcf-4 signaling pathway plays important roles in colorectal tumorigenesis. RT-PCR, western blotting and immunoprecipitation were used to study the effects of curcumin on β-catenin/Tcf-4 signaling pathway in HT-29 cells. Treatment of curcumin could induce cleavage of β-catenin and the cleavage could be ...
Spontaneous evolution of an unusual cortical malformation in SOX2 anophthalmia syndrome
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Jay Desai
2013-01-01
Full Text Available Brain malformations such as agenesis and dysgenesis of corpus callosum, pituitary hypoplasia, hypothalamic hamartoma, mesial temporal periventricular heterotopia, and abnormally oriented and misshapen hippocampi have been described with SOX2 gene mutations. A neocortical malformation is presented here in association with SOX2 deletion that over time underwent spontaneous evolution and decrease in size.
Spontaneous and traumatic hepatic rupture: imaging findings and minimally invasive treatment
International Nuclear Information System (INIS)
Palacio, Glaucia Andrade e Silva; D'Ippolito, Giuseppe
2003-01-01
Spontaneous hepatic bleeding is a rare condition. Our aim was to describe the imaging findings and minimally invasive treatment using transcatheter arterial embolization in patients with spontaneous and traumatic hepatic rupture. Three patients presented acute hemoperitoneum dur to hepatic rupture caused by spontaneous rupture of hepatocellular carcinoma, HELLP syndrome and a blunt hepatic trauma. The patients were submitted to ultrasound and computed tomography of the abdomen and subsequently treated by transcatheter arterial embolization. All patients underwent helical computed tomography before and after treatments. Computed tomography played an important role in the evaluation and follow-up in the therapeutic intervention. Different types of liver injuries were identified. Transcatheter arterial embolization blocked arterial hemorrhage in the patients who were hemodynamically unstable. The conclusion was: transcatheter arterial embolization is an effective and well-tolerated treatment method for the management of hepatic rupture and computed tomography is an excellent method for the diagnosis and follow-up of these patients. (author)
Outcomes of the Tower Crane Technique with a 15-mm Trocar in Primary Spontaneous Pneumothorax
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Yooyoung Chong
2016-04-01
Full Text Available Background: Video-assisted thoracoscopic surgery (VATS pulmonary wedge resection has emerged as the standard treatment for primary spontaneous pneumothorax. Recently, single-port VATS has been introduced and is now widely performed. This study aimed to evaluate the outcomes of the Tower crane technique as novel technique using a 15-mm trocar and anchoring suture in primary spontaneous pneumothorax. Methods: Patients who underwent single- port VATS wedge resection in Chungnam National University Hospital from April 2012 to March 2014 were enrolled. The medical records of the enrolled patients were reviewed retrospectively. Results: A total of 1,251 patients were diagnosed with pneumothorax during this period, 270 of whom underwent VATS wedge resection. Fifty-two of those operations were single-port VATS wedge resections for primary spontaneous pneumothorax performed by a single surgeon. The median age of the patients was 19.3±11.5 years old, and 43 of the patients were male. The median duration of chest tube drainage following the operation was 2.3±1.3 days, and mean postoperative hospital stay was 3.2±1.3 days. Prolonged air leakage for more than three days following the operation was observed in one patient. The mean duration of follow-up was 18.7±6.1 months, with a recurrence rate of 3.8%. Conclusion: The tower crane technique with a 15-mm trocar may be a promising treatment modality for patients presenting with primary spontaneous pneumothorax.
DEFF Research Database (Denmark)
Joergensen, Mette Warming; Agerholm, Inge; Hindkjaer, Johnny
2014-01-01
PURPOSE: To analyze the cleavage patterns in dipronuclear (2PN) and tripronuclear (3PN) embryos in relation to fertilization method. METHOD: Time-lapse analysis. RESULTS: Compared to 2PN, more 3PN IVF embryos displayed early cleavage into 3 cells (p ... stage (p embryos, the 2nd and 3rd cleavage cycles were completed within the expected time frame. However, timing of the cell divisions within the cleavage cycles differed between the two groups. In contrast......, the completion of the 1st, 2nd, and 3rd cleavage cycle was delayed, but with a similar division pattern for 3PN ICSI compared with the 2PN ICSI embryos. 3PN, more often than 2PN ICSI embryos, displayed early cleavage into 3 cells (p = 0.03) and arrested development from the compaction stage and onwards (p = 0...
RecA-mediated cleavage reaction of Lambda repressor and DNA ...
African Journals Online (AJOL)
PRECIOUS
2010-01-11
Jan 11, 2010 ... hydrolyze ATP at all, but fulfills RecA functions such as cleavage of Lambda repressor and strand .... DNA binding properties of RecA and may result in an in- .... AMP-PNP there is no cleavage of Lambda repressor (Figure.
International Nuclear Information System (INIS)
Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik; Whittaker, Gary R.
2012-01-01
A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.
Energy Technology Data Exchange (ETDEWEB)
Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States); Whittaker, Gary R., E-mail: grw7@cornell.edu [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States)
2012-12-05
A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.
Outcomes after endoscopic port surgery for spontaneous intracerebral hematomas.
Ochalski, Pawel; Chivukula, Srinivas; Shin, Samuel; Prevedello, Daniel; Engh, Johnathan
2014-05-01
Spontaneous intracerebral hemorrhages (ICHs) cause significant morbidity and mortality. Traditional open surgical management strategies offer limited benefit except for the most superficial hemorrhages in select patients. Recent reports suggest that endoscopic approaches may improve outcomes, particularly for deep subcortical hemorrhages. However, the management of these patients remains controversial. We reviewed our experience using endoscopic port surgery to identify characteristics that may predict acceptable outcomes. We completed a retrospective chart and imaging review of patients who underwent endoscopic port surgery for evacuation of spontaneous ICH at a single center. Data were gathered regarding patient demographics, hemorrhage locations, operative findings, and clinical outcomes. From 2007 to 2011, 18 patients underwent evacuation of spontaneous intracerebral hematomas using an endoscopic port. The mean age in years was 62 years (range, 43-84 years). Six of 18 patients (33%) died before discharge, and 2 others (11%) died after at least 1 month of survival. Of 12 initial survivors, all were discharged to a rehabilitation or nursing facility. Complete hematoma evacuation was achieved in 7 of 18 patients, with the remaining 11 having a partial evacuation. The patients who died (n = 6) before discharge were statistically more likely to have a left-sided hemorrhage, partial evacuation, or older age than the survivors; death at least 1 month after evacuation was additionally associated with greater preoperative hematoma volumes. Our series demonstrates that endoscopic port surgery for acute intracerebral hematoma evacuation has the ability to achieve significant decompression of large and deep-seated hematomas. Patient age, extent of evacuation, laterality, and preoperative hematoma volume appear to influence patient outcome. Most overall outcomes remain poor. Future studies are necessary to determine if surgical evacuation is in fact superior to best
Short RNA guides cleavage by eukaryotic RNase III.
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Bruno Lamontagne
Full Text Available In eukaryotes, short RNAs guide a variety of enzymatic activities that range from RNA editing to translation repression. It is hypothesized that pre-existing proteins evolved to bind and use guide RNA during evolution. However, the capacity of modern proteins to adopt new RNA guides has never been demonstrated. Here we show that Rnt1p, the yeast orthologue of the bacterial dsRNA-specific RNase III, can bind short RNA transcripts and use them as guides for sequence-specific cleavage. Target cleavage occurred at a constant distance from the Rnt1p binding site, leaving the guide RNA intact for subsequent cleavage. Our results indicate that RNase III may trigger sequence-specific RNA degradation independent of the RNAi machinery, and they open the road for a new generation of precise RNA silencing tools that do not trigger a dsRNA-mediated immune response.
Radionuclide cisternographic findings in patients with spontaneous intracranial hypotension
International Nuclear Information System (INIS)
Jung, Dong Jin; Kim, Jae Seung; Ryu, Jin Sook; Shin, Jung Woo; Im, Joo Hyuk; Lee, Myoung Chong; Jung, Sung Joo; Moon, Dae Hyuk; Lee, Hee Kyung
1998-01-01
Radionuclide cisternography may be helpful in understanding pathophysiology of postural headache and low CSF pressure in patients with spontaneous intracranial hypotension. The purpose of this study was to characterize radionuclide cisternogrpahic findings of spontaneous intracranial hypotension. The study population consists of 15 patients with spontaneous intracranial hypotension. Diagnosis was based on their clinical symptoms and results of lumbar puncture. All patients underwent radionuclide cisternography following injection of 111 to 222 MBq of Tc-99m DTPA into the lumbar subarachnoid space. Sequential images were obtained between 1/2 hour and 24 hour after the injection of Tc-99m DTPA. Radioactivity of the bladder, soft tissue uptake, migration of radionuclide in the subarachnoid space, and extradural leakage of radionuclide were evaluated according to the scan time. Radionuclide cisternogram showed delayed migration of radionuclide into the cerebral convexity (14/15), increased soft tissue uptake (11/15), and early visualization of bladder activity at 30 min (6/10) and 2 hr (13/13). Cisternography also demonstrated leakage site of CSF in 4 cases and 2 of these were depicted at 30min. Epidural blood patch was done in 11 patients and headache was improved in all cases. The characteristics findings of spontaneous intracranial hypotension were delayed migration of radionuclide and early visualization of the soft tissue and bladder activity. These scintigraphic findings suggest that CSF leakage rather than increased CSF absorption or decreased production may be the main pathophysiology of spontaneous intracranial hypotension. Early and multiple imaging including the bladder and soft tissue is required to observe the entire dynamics of radionuclide migration
Spontaneous Thrombosis of a Bicuspid Aortic valve due to Primary Antiphospholipid Syndrome
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Sarah Farrell
2010-08-01
Full Text Available We present the case of a 51-year-old man who was admitted as an emergency with spontaneous thrombosis of the aortic valve and ascending aorta. At operation he was found to have a congenitally bicuspid aortic valve and subsequent investigation revealed primary antiphospholipid syndrome. He underwent successful removal of the thrombus combined with mechanical replacement of the aortic valve.
Spontaneous bleeding from liver after open heart surgery.
Mir, Najeeb H; Shah, Mian T; Obeid, Mahmoud Ali; Gallo, Ricardo; Aliter, Hashem
2013-01-01
Intra-abdominal hemorrhage after open heart surgery is very uncommon in routine clinical practice. There are case reports of having bleeding from spleen or liver after starting low molecular weight heparin (LMWH) postoperatively. Our patient is a 58-year-old man with mitral valve regurgitation, who underwent mitral valve repair and developed intra-abdominal hemorrhage 8h after open heart surgery. The exploratory laparotomy revealed the source of bleeding from ruptured sub-capsular liver hematoma and oozing from raw areas of the liver surface. Liver packing was done to control the bleeding. The gastrointestinal complications after open heart surgery are rare and spontaneous bleeding from spleen has been reported. This is the first case from our hospital to have intra-abdominal hemorrhage after open heart surgery. Spontaneous bleeding from liver is a possible complication after open heart surgery. We submit the case for the academic interest and to discuss the possible cause of hemorrhage. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Spontaneous subarachnoid haemorrhage and outcome--results from Tan Tock Seng Hospital, Singapore.
Wong, S H; Yeo, T T; Seow, W T; Tan, K K; Ong, P L
1999-07-01
To ascertain the number of cases of spontaneous (aneurysmal) subarachnoid haemorrhage presenting to Tan Tock Seng Hospital, Singapore, over a one year period, the demographics of the patients involved, their treatment and their eventual outcome. A retrospective study from June 1995 to June 1996. There were 62 patients admitted over this period with an average of 5 patients per month. Their ages ranged from 9 to 85 years with a mean of 54 years. All 62 patients underwent 4-vessel cerebral angiograms. Forty-three patients (69%) underwent clipping of their aneurysms. Twelve patients (19%) had negative angiograms. Four patients (6%) underwent coiling of their aneurysms via interventional neuroradiology techniques. Patients with subarachnoid haemorrhage of Grades 1 to 3 on the WFNS (World Federation of Neurological Surgeons) grading had a favourable outcome (Glasgow Outcome Score of 4 and 5) in 85% of the cases. The overall mortality rate for the operated group (all grades) was 11%. However for the group with good WFNS grading, namely the Grade 1 to 2 groups, there were no deaths. Twenty-four percent of patients developed clinically symptomatic vasospasm. Eighteen percent of patients required ventriculo-peritoneal shunting for hydrocephalus secondary to the subarachnoid haemorrhage. The overall management mortality (operated and non-operated cases) was 14% for proven aneurysmal and angiographically-negative spontaneous subarachnoid haemorrhage. These results are comparable to that of other reputable centers reported in the literature.
Johnson, D J; Pemberton, S; Acquila, M; Mori, P G; Tuddenham, E G; O'Brien, D P
1994-04-01
A novel CRM+ mutation, factor VIII position 373 serine to leucine substitution (FVIII 373-Leu) was identified during a survey of Factor VIII (FVIII) mutations. We have purified the variant protein from the patient's plasma in order to allow further characterisation of the molecule. The CRM+ plasma contained 120% Factor VIII antigen (FVIII:Ag) and 6% Factor VIII coagulant activity (FVIII:C). After purification the mutant FVIII was subjected to thrombin proteolysis, and was thereby activated 5.6-fold compared with 7-fold for wild type molecule. Subsequently, spontaneous inactivation of the mutant was much slower than noted for wild type FVIII. Western blot analysis using monoclonal antibodies demonstrated that thrombin cleavage of FVIII 373-Leu at positions 740 and 1689 were normal but that cleavage at position 372 was completely absent. Crystallographic coordinates of the active site of thrombin complexed to fibrinopeptide A were used to explore possible mechanistic reasons for the failure of thrombin to cleave the mutant FVIII at position 372. Steric hindrance between the mutant side chain and the side chain of the P1 residue was apparent. We conclude that the functional defect of FVIII 373-Leu results from the inability of thrombin to cleave the mutant at position 372-373, and propose that this is due to steric hindrance by the side chain of leucine 373, preventing correct formation of the enzyme substrate complex.
Spontaneous intracranial hypotension
International Nuclear Information System (INIS)
Cardwell, C.; Cox, I.; Baldey, A.
2002-01-01
Full text: A 49-year old female presented with severe postural headache with no history of trauma. A Computed Tomography (CT) study of the brain demonstrated abnormal meningeal enhancement raising the possibility of leptomeningeal metastases. The patient was then referred to Magnetic Resonance Imaging (MRI) which demonstrated diffuse smooth dural enhancement with ancillary findings characteristic of spontaneous intracranial hypotension. The patient was then referred to Nuclear Medicine to confirm the diagnosis and localise the presumed leak 400MBq of 99mTc DTPA was injected via lumbar puncture into the L3-L4 subarachnoid space Posterior images of the spine were taken with a GE XRT single head gamma camera at 1 and 4 hours post administration of radionuclide. Images demonstrated abnormal early arrival of radionuclide in the kidneys and bladder at 1 hour and abnormal leak of tracer was demonstrate at the level of the first thoracic vertebra on the right side at 4 hours. This confirmed CSF leak at this level. Consequently the patient underwent a blood patch and her symptoms resolved. Spontaneous Intracranial Hypotension is a syndrome often unrecognised presenting with symptoms including severe postural headache neck stiffness nausea vomiting tinnitus and vertigo. The diagnosis is frequently suspected from findings on MRI, but Nuclear Medicine CSF imaging provides a readily available and cost effective method for confirming the diagnosis, and for making the diagnosis in patients who are unsuitable for or do not have access to MRI. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc
Spontaneous intracranial hypotension
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Cardwell, C; Cox, I; Baldey, A [St. F.X. Cabrini Hospital, VIC (Australia). Departments of Nuclear Medicine and Magnetic Resonance Imaging
2002-07-01
Full text: A 49-year old female presented with severe postural headache with no history of trauma. A Computed Tomography (CT) study of the brain demonstrated abnormal meningeal enhancement raising the possibility of leptomeningeal metastases. The patient was then referred to Magnetic Resonance Imaging (MRI) which demonstrated diffuse smooth dural enhancement with ancillary findings characteristic of spontaneous intracranial hypotension. The patient was then referred to Nuclear Medicine to confirm the diagnosis and localise the presumed leak 400MBq of 99mTc DTPA was injected via lumbar puncture into the L3-L4 subarachnoid space Posterior images of the spine were taken with a GE XRT single head gamma camera at 1 and 4 hours post administration of radionuclide. Images demonstrated abnormal early arrival of radionuclide in the kidneys and bladder at 1 hour and abnormal leak of tracer was demonstrate at the level of the first thoracic vertebra on the right side at 4 hours. This confirmed CSF leak at this level. Consequently the patient underwent a blood patch and her symptoms resolved. Spontaneous Intracranial Hypotension is a syndrome often unrecognised presenting with symptoms including severe postural headache neck stiffness nausea vomiting tinnitus and vertigo. The diagnosis is frequently suspected from findings on MRI, but Nuclear Medicine CSF imaging provides a readily available and cost effective method for confirming the diagnosis, and for making the diagnosis in patients who are unsuitable for or do not have access to MRI. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc.
Effect of microstructure on the cleavage fracture strength of low carbon Mn-Ni-Mo bainitic steels
International Nuclear Information System (INIS)
Im, Young-Roc; Lee, Byeong-Joo; Oh, Yong Jun; Hong, Jun Hwa; Lee, Hu-Chul
2004-01-01
The effects of the microstructure on the cleavage fracture strength of low carbon Mn-Ni-Mo bainitic steels were examined. A four-point bend test and double-notched bend specimens were used to measure the cleavage fracture strength of the alloys and identify the cleavage initiating micro-cracks, respectively. The cleavage fracture strength and DBTT of Mn-Ni-Mo bainitic steels were strongly affected by the alloy carbon content. The decrease in the alloy carbon content resulted in a decrease in the inter-lath cementite-crowded layers and higher cleavage fracture strength. Micro-cracks that formed across the inter-lath cementite-crowded layers were observed to initiate cleavage fracture. The width of these inter-lath cementite-crowded layers was accepted as a cleavage initiating micro-crack size in the micro-mechanical modeling of the cleavage fracture, and the measured cleavage strength values of the bainitic Mn-Ni-Mo steels were well represented by the modified Griffith relationship
Directory of Open Access Journals (Sweden)
Jack Xie
2010-08-01
Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.
Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia virus
International Nuclear Information System (INIS)
D'Costa, Susan M.; Antczak, James B.; Pickup, David J.; Condit, Richard C.
2004-01-01
Most vaccinia virus intermediate and late mRNAs possess 3' ends that are extremely heterogeneous in sequence. However, late mRNAs encoding the cowpox A-type inclusion protein (ATI), the second largest subunit of the RNA polymerase, and the late telomeric transcripts possess homogeneous 3' ends. In the case of the ATI mRNA, it has been shown that the homogeneous 3' end is generated by a post-transcriptional endoribonucleolytic cleavage event. We have determined that the F17R gene also produces homogeneous transcripts generated by a post-transcriptional cleavage event. Mapping of in vivo mRNA shows that the major 3' end of the F17R transcript maps 1262 nt downstream of the F17R translational start site. In vitro transcripts spanning the in vivo 3' end are cleaved in an in vitro reaction using extracts from virus infected cells, and the site of cleavage is the same both in vivo and in vitro. Cleavage is not observed using extract from cells infected in the presence of hydroxyurea; therefore, the cleavage factor is either virus-coded or virus-induced during the post-replicative phase of virus replication. The cis-acting sequence responsible for cleavage is orientation specific and the factor responsible for cleavage activity has biochemical properties similar to the factor required for cleavage of ATI transcripts. Partially purified cleavage factor generates cleavage products of expected size when either the ATI or F17R substrates are used in vitro, strongly suggesting that cleavage of both transcripts is mediated by the same factor
Spontaneous regression in an ulcerated CK7 positive Merkel cell carcinoma
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Anza Khader
2015-01-01
Full Text Available Merkel cell carcinoma is an aggressive and frequently lethal tumor of the elderly, associated with sun exposure and immunosuppression which is less common in the dark-skinned. We report the case of a 40-year-old woman who presented with multiple slowly progressive, mildly itchy ulcerated plaques of size ranging from 2 × 3 cm to 5 × 7 cm on the left knee of 1 year duration. Skin biopsy showed diffuse dermal infiltration by small round cells with molding of cells and lymphocyte infiltration. The cells stained positive for cytokeratin (CK 20, CK7, neuron-specific enolase, and chromogranin. The skin lesions underwent spontaneous regression within 1 month of skin biopsy and have not recurred during the past 2 years. The immune mechanisms triggered by biopsy possibly explain the spontaneous regression.
Radiologic assessment of spinal CSF leakage in spontaneous intracranial hypotension
International Nuclear Information System (INIS)
Han, Chang Jin; Kim, Ji Hyung; Kim, Jang Sung; Kim, Sun Yong; Suh, Jung Ho
1999-01-01
To assess the usefulness of imaging modalities in the detection of spinal CSF leakage in spontaneous intracranial hypotension. Fifteen patients who complained of postural headache without any preceding cause showed typical brain MR findings of intracranial hypotension, including radiologically confirmed CSF leakage. All fifteen underwent brain MRI and radionuclide cisternography. CT myelography was performed in eight patients and spinal MRI in six. Medical records, imaging findings and the incidence of spinal CSF leakage during each modality were retrospectively reviewed. CSF leakage was most common at the cervicothoracic junction, where in seven of 15 cases it was seen on radionuclide cisternography as increased focal paraspinal activity. Leakage was noted at the mid-tho-racic level in three patients, at the upper thoracic level in two, and at the cervical and lumbar levels in the remaining two. In two patients multiple CSF leaks were noted, and in all, early radioactive accumulation in the bladder was visualized. CT myelography revealed extrathecal and paraspinal contrast leakage in three of eight patients, and among those who underwent spinal MRI, dural enhancement was observed at the site of CSF leakage in all six, abnormal CSF signal in the neural foramen in one, and epidural CSF collection in one. Radionuclide cisternography is a useful method for the detection of CSF leakage in spontaneous intracranial hypotension. CT myelography and spinal MRI help determine the precise location of leakage
Coronavirus 3CLpro proteinase cleavage sites: Possible relevance to SARS virus pathology
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Blom Nikolaj
2004-06-01
Full Text Available Abstract Background Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS, efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. Results We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR, transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. Conclusions Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website: http://www.cbs.dtu.dk/services/NetCorona/.
Prediction of proteasome cleavage motifs by neural networks
DEFF Research Database (Denmark)
Kesimir, C.; Nussbaum, A.K.; Schild, H.
2002-01-01
physiological conditions. Our algorithm has been trained not only on in vitro data, but also on MHC Class I ligand data, which reflect a combination of immunoproteasome and constitutive proteasome specificity. This feature, together with the use of neural networks, a non-linear classification technique, make...... the prediction of MHC Class I ligand boundaries more accurate: 65% of the cleavage sites and 85% of the non-cleavage sites are correctly determined. Moreover, we show that the neural networks trained on the constitutive proteasome data learns a specificity that differs from that of the networks trained on MHC...
International Nuclear Information System (INIS)
Yanagisawa, Y.; Nakagome, H.; Takematsu, T.; Takao, T.; Sato, N.; Takahashi, M.; Maeda, H.
2011-01-01
Cleavage strength for YBCO-coated conductor is extremely low, typically 0.5 MPa. The remarkable weakness is due to cracks on the slit edge of the conductor. The cleavage stress appears on YBCO double pancake coils impregnated with epoxy. The cleavage stress should be avoided in the coil winding. Cleavage strength for an YBCO-coated conductor at 77 K was investigated with a model experiment. The nominal cleavage strength for an YBCO-coated conductor is extremely low, typically 0.5 MPa. This low nominal cleavage strength is due to stress concentration on a small part of the YBCO-coated conductor in cleavage fracture. Debonding by the cleavage stress occurs at the interface between the buffer layer and the Hastelloy substrate. The nominal cleavage strength for a slit edge of the conductor is 2.5-times lower than that for the original edge of the conductor; cracks and micro-peel existing over the slit edge reduce the cleavage strength for the slit edge. Cleavage stress and peel stress should be avoided in coil winding, as they easily delaminate the YBCO-coated conductor, resulting in substantial degradation of coil performance. These problems are especially important for epoxy impregnated YBCO-coated conductor coils. It appears that effect of cleavage stress and peel stress are mostly negligible for paraffin impregnated YBCO-coated conductor coils or dry wound YBCO-coated conductor coils.
Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA
International Nuclear Information System (INIS)
Hastings, P.J.; Quah, S.-K.; Borstel, R.C. von
1976-01-01
It is stated that strains of yeast carrying mutations in many of the steps in pathways repairing radiation-induced damage to DNA have enhanced spontaneous mutation rates. Most strains isolated because they have enhanced spontaneous mutation carry mutations in DNA repair systems. This suggests that much spontaneous mutation arises by mutagenic repair of spontaneous lesions. (author)
Schievink, Wouter I; Schwartz, Marc S; Maya, M Marcel; Moser, Franklin G; Rozen, Todd D
2012-04-01
Spontaneous intracranial hypotension is an important cause of headaches and an underlying spinal CSF leak can be demonstrated in most patients. Whether CSF leaks at the level of the skull base can cause spontaneous intracranial hypotension remains a matter of controversy. The authors' aim was to examine the frequency of skull base CSF leaks as the cause of spontaneous intracranial hypotension. Demographic, clinical, and radiological data were collected from a consecutive group of patients evaluated for spontaneous intracranial hypotension during a 9-year period. Among 273 patients who met the diagnostic criteria for spontaneous intracranial hypotension and 42 who did not, not a single instance of CSF leak at the skull base was encountered. Clear nasal drainage was reported by 41 patients, but a diagnosis of CSF rhinorrhea could not be established. Four patients underwent exploratory surgery for presumed CSF rhinorrhea. In addition, the authors treated 3 patients who had a postoperative CSF leak at the skull base following the resection of a cerebellopontine angle tumor and developed orthostatic headaches; spinal imaging, however, demonstrated the presence of a spinal source of CSF leakage in all 3 patients. There is no evidence for an association between spontaneous intracranial hypotension and CSF leaks at the level of the skull base. Moreover, the authors' study suggests that a spinal source for CSF leakage should even be suspected in patients with orthostatic headaches who have a documented skull base CSF leak.
Flanking signal and mature peptide residues influence signal peptide cleavage
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Ranganathan Shoba
2008-12-01
Full Text Available Abstract Background Signal peptides (SPs mediate the targeting of secretory precursor proteins to the correct subcellular compartments in prokaryotes and eukaryotes. Identifying these transient peptides is crucial to the medical, food and beverage and biotechnology industries yet our understanding of these peptides remains limited. This paper examines the most common type of signal peptides cleavable by the endoprotease signal peptidase I (SPase I, and the residues flanking the cleavage sites of three groups of signal peptide sequences, namely (i eukaryotes (Euk (ii Gram-positive (Gram+ bacteria, and (iii Gram-negative (Gram- bacteria. Results In this study, 2352 secretory peptide sequences from a variety of organisms with amino-terminal SPs are extracted from the manually curated SPdb database for analysis based on physicochemical properties such as pI, aliphatic index, GRAVY score, hydrophobicity, net charge and position-specific residue preferences. Our findings show that the three groups share several similarities in general, but they display distinctive features upon examination in terms of their amino acid compositions and frequencies, and various physico-chemical properties. Thus, analysis or prediction of their sequences should be separated and treated as distinct groups. Conclusion We conclude that the peptide segment recognized by SPase I extends to the start of the mature protein to a limited extent, upon our survey of the amino acid residues surrounding the cleavage processing site. These flanking residues possibly influence the cleavage processing and contribute to non-canonical cleavage sites. Our findings are applicable in defining more accurate prediction tools for recognition and identification of cleavage site of SPs.
Staggering in the cleavage pattern of E. coli ABC-excinuclease
International Nuclear Information System (INIS)
Myles, G.M.; Van Houten, B.; Sancar, A.
1986-01-01
E. coli ABC excinuclease is a complex of three proteins encoded by the uvrA, uvrB, and uvrC genes. The enzyme repairs DNA mono and diadducts by the single strand cleavage of DNA eight phosphodiester bond 5' and four or five phosphodiester bonds 3' to a DNA lesion and facilitates the removal of the resulting twelve or thirteen nucleotide fragment. In this study, the authors have investigated the excision pattern for ultraviolet (UV) induced diadducts, i.e. cyclobutane pyrimidine dimers and pyrimidine-pyrimidone (6-4) photoproducts. Terminally (5' or 3') labeled DNA was irradiated with 254nm UV and treated with ABC excinuclease before and after photoreactivation of cyclobutane dimers by E. coli DNA photolyase. In this way, the authors were able to differentiate between the cleavage pattern of pyrimidine dimers and of (6-4) photoproducts. Their results show that certain TT cyclobutane dimers and rare TT (6-4) photoproducts are excised by cleavage seven and, less frequently, six phosphodiester bonds to the 5' side of the DNA lesion in addition to the primary cutting site at the eight 5' phosphodiester bond. The 3' cleavage sites are maintained at the fourth and fifth phosphodiester bonds for the these UV induced lesions. These data indicate that the cleavage pattern of the ABC excinuclease may be dependent upon both the type of DNA lesion as well as it surrounding nucleotide sequence. In addition, the authors analysis shows that (6-4) photoproducts are much better substrates for ABC excinuclease than are pyrimidine dimers
Spontaneous Rotation of a Toric Implantable Collamer Lens
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Alejandro Navas
2010-11-01
Full Text Available We present a case of toric implantable collamer lens (TICL spontaneous rotation in a patient with myopic astigmatism. A 23-year-old female underwent TICL implantation. Preoperative uncorrected visual acuity (UCVA was 20/800 and 20/1200, respectively, with –7.75 –4.25 × 0° and –8.25 –5.25 × 180°. The left eye achieved an UCVA of 20/30. After 3 months of successful implantation of TICL in the left eye, the patient presented with a sudden decrease in visual acuity in the left eye. UCVA was 20/100 with a refraction of +2.50 –4.50 × 165°. We observed the toric marks with a 30° rotation from the original position and decided to reposition the TICL, obtaining a final UCVA of 20/25, which remained stable at 6 months’ follow-up. TICL can present a considerable rotation that compromises visual acuity. The relocation of TICL is a safe and effective procedure to recover visual acuity due to significant spontaneous TICL rotation.
Downstream element determines RNase Y cleavage of the saePQRS operon in Staphylococcus aureus.
Marincola, Gabriella; Wolz, Christiane
2017-06-02
In gram-positive bacteria, RNase J1, RNase J2 and RNase Y are thought to be major contributors to mRNA degradation and maturation. In Staphylococcus aureus, RNase Y activity is restricted to regulating the mRNA decay of only certain transcripts. Here the saePQRS operon was used as a model to analyze RNase Y specificity in living cells. A RNase Y cleavage site is located in an intergenic region between saeP and saeQ. This cleavage resulted in rapid degradation of the upstream fragment and stabilization of the downstream fragment. Thereby, the expression ratio of the different components of the operon was shifted towards saeRS, emphasizing the regulatory role of RNase Y activity. To assess cleavage specificity different regions surrounding the sae CS were cloned upstream of truncated gfp, and processing was analyzed in vivo using probes up- and downstream of CS. RNase Y cleavage was not determined by the cleavage site sequence. Instead a 24-bp double-stranded recognition structure was identified that was required to initiate cleavage 6 nt upstream. The results indicate that RNase Y activity is determined by secondary structure recognition determinants, which guide cleavage from a distance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Protein cleavage strategies for an improved analysis of the membrane proteome
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Poetsch Ansgar
2006-03-01
Full Text Available Abstract Background Membrane proteins still remain elusive in proteomic studies. This is in part due to the distribution of the amino acids lysine and arginine, which are less frequent in integral membrane proteins and almost absent in transmembrane helices. As these amino acids are cleavage targets for the commonly used protease trypsin, alternative cleavage conditions, which should improve membrane protein analysis, were tested by in silico digestion for the three organisms Saccharomyces cerevisiae, Halobacterium sp. NRC-1, and Corynebacterium glutamicum as hallmarks for eukaryotes, archea and eubacteria. Results For the membrane proteomes from all three analyzed organisms, we identified cleavage conditions that achieve better sequence and proteome coverage than trypsin. Greater improvement was obtained for bacteria than for yeast, which was attributed to differences in protein size and GRAVY. It was demonstrated for bacteriorhodopsin that the in silico predictions agree well with the experimental observations. Conclusion For all three examined organisms, it was found that a combination of chymotrypsin and staphylococcal peptidase I gave significantly better results than trypsin. As some of the improved cleavage conditions are not more elaborate than trypsin digestion and have been proven useful in practice, we suppose that the cleavage at both hydrophilic and hydrophobic amino acids should facilitate in general the analysis of membrane proteins for all organisms.
Cleavage and Cell Adhesion Properties of Human Epithelial Cell Adhesion Molecule (HEPCAM)*
Tsaktanis, Thanos; Kremling, Heidi; Pavšič, Miha; von Stackelberg, Ricarda; Mack, Brigitte; Fukumori, Akio; Steiner, Harald; Vielmuth, Franziska; Spindler, Volker; Huang, Zhe; Jakubowski, Jasmine; Stoecklein, Nikolas H.; Luxenburger, Elke; Lauber, Kirsten; Lenarčič, Brigita; Gires, Olivier
2015-01-01
Human epithelial cell adhesion molecule (HEPCAM) is a tumor-associated antigen frequently expressed in carcinomas, which promotes proliferation after regulated intramembrane proteolysis. Here, we describe extracellular shedding of HEPCAM at two α-sites through a disintegrin and metalloprotease (ADAM) and at one β-site through BACE1. Transmembrane cleavage by γ-secretase occurs at three γ-sites to generate extracellular Aβ-like fragments and at two ϵ-sites to release human EPCAM intracellular domain HEPICD, which is efficiently degraded by the proteasome. Mapping of cleavage sites onto three-dimensional structures of HEPEX cis-dimer predicted conditional availability of α- and β-sites. Endocytosis of HEPCAM warrants acidification in cytoplasmic vesicles to dissociate protein cis-dimers required for cleavage by BACE1 at low pH values. Intramembrane cleavage sites are accessible and not part of the structurally important transmembrane helix dimer crossing region. Surprisingly, neither chemical inhibition of cleavage nor cellular knock-out of HEPCAM using CRISPR-Cas9 technology impacted the adhesion of carcinoma cell lines. Hence, a direct function of HEPCAM as an adhesion molecule in carcinoma cells is not supported and appears to be questionable. PMID:26292218
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Ting Wei
Full Text Available The NTB-VPg polyprotein from tomato ringspot virus is an integral membrane replication protein associated with endoplasmic reticulum membranes. A signal peptidase (SPase cleavage was previously detected in the C-terminal region of NTB-VPg downstream of a 14 amino acid (aa-long hydrophobic region (termed TM2. However, the exact location of the cleavage site was not determined. Using in vitro translation assays, we show that the SPase cleavage site is conserved in the NTB-VPg protein from various ToRSV isolates, although the rate of cleavage varies from one isolate to another. Systematic site-directed mutagenesis of the NTB-VPg SPase cleavage sites of two ToRSV isolates allowed the identification of sequences that affect cleavage efficiency. We also present evidence that SPase cleavage in the ToRSV-Rasp2 isolate occurs within a GAAGG sequence likely after the AAG (GAAG/G. Mutation of a downstream MAAV sequence to AAAV resulted in SPase cleavage at both the natural GAAG/G and the mutated AAA/V sequences. Given that there is a distance of seven aa between the two cleavage sites, this indicates that there is flexibility in the positioning of the cleavage sites relative to the inner surface of the membrane and the SPase active site. SPase cleavage sites are typically located 3-7 aa downstream of the hydrophobic region. However, the NTB-VPg GAAG/G cleavage site is located 17 aa downstream of the TM2 hydrophobic region, highlighting unusual features of the NTB-VPg SPase cleavage site. A putative 11 aa-long amphipathic helix was identified immediately downstream of the TM2 region and five aa upstream of the GAAG/G cleavage site. Based on these results, we present an updated topology model in which the hydrophobic and amphipathic domains form a long tilted helix or a bent helix in the membrane lipid bilayer, with the downstream cleavage site(s oriented parallel to the membrane inner surface.
Successful medical management of a neonate with spontaneous splenic rupture and severe hemophilia A.
Badawy, Sherif M; Rossoff, Jenna; Yallapragada, Sushmita; Liem, Robert I; Sharathkumar, Anjali A
2017-03-01
Splenic rupture in neonates is a rare event, usually occurring in the setting of underlying predisposing conditions. Here, we present the case of a term neonate who presented with worsening anemia in the setting of known hemolytic disease during the newborn period and was later found to have a spontaneous splenic rupture. He was subsequently diagnosed with severe hemophilia A, and was managed medically with recombinant factor VIII replacement therapy without any surgical intervention. This is the first reported case of a neonate who had spontaneous splenic rupture and severe hemophilia A, and underwent successful medical treatment without any surgical intervention. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.
Calicivirus 3C-like proteinase inhibits cellular translation by cleavage of poly(A)-binding protein.
Kuyumcu-Martinez, Muge; Belliot, Gaël; Sosnovtsev, Stanislav V; Chang, Kyeong-Ok; Green, Kim Y; Lloyd, Richard E
2004-08-01
Caliciviruses are single-stranded RNA viruses that cause a wide range of diseases in both humans and animals, but little is known about the regulation of cellular translation during infection. We used two distinct calicivirus strains, MD145-12 (genus Norovirus) and feline calicivirus (FCV) (genus Vesivirus), to investigate potential strategies used by the caliciviruses to inhibit cellular translation. Recombinant 3C-like proteinases (r3CL(pro)) from norovirus and FCV were found to cleave poly(A)-binding protein (PABP) in the absence of other viral proteins. The norovirus r3CL(pro) PABP cleavage products were indistinguishable from those generated by poliovirus (PV) 3C(pro) cleavage, while the FCV r3CL(pro) products differed due to cleavage at an alternate cleavage site 24 amino acids downstream of one of the PV 3C(pro) cleavage sites. All cleavages by calicivirus or PV proteases separated the C-terminal domain of PABP that binds translation factors eIF4B and eRF3 from the N-terminal RNA-binding domain of PABP. The effect of PABP cleavage by the norovirus r3CL(pro) was analyzed in HeLa cell translation extracts, and the presence of r3CL(pro) inhibited translation of both endogenous and exogenous mRNAs. Translation inhibition was poly(A) dependent, and replenishment of the extracts with PABP restored translation. Analysis of FCV-infected feline kidney cells showed that the levels of de novo cellular protein synthesis decreased over time as virus-specific proteins accumulated, and cleavage of PABP occurred in virus-infected cells. Our data indicate that the calicivirus 3CL(pro), like PV 3C(pro), mediates the cleavage of PABP as part of its strategy to inhibit cellular translation. PABP cleavage may be a common mechanism among certain virus families to manipulate cellular translation.
Bruno, Mark
2015-04-01
Down-regulation of the potato carotenoid cleavage dioxygenase 4 (StCCD4) transcript level led to tubers with altered morphology and sprouting activity, which also accumulated higher levels of violaxanthin and lutein leading to elevated carotenoid amounts. This phenotype indicates a role of this enzyme in tuber development, which may be exerted by a cleavage product. In this work, we investigated the enzymatic activity of StCCD4, by expressing the corresponding cDNA in carotenoid accumulating Escherichia coli strains and by performing in vitro assays with heterologously expressed enzyme. StCCD4 catalyzed the cleavage of all-. trans-β-carotene at the C9\\'-C10\\' double bond, leading to β-ionone and all-. trans-β-apo-10\\'-carotenal, both in vivo and in vitro. The enzyme also cleaved β,β-cryptoxanthin, zeaxanthin and lutein either at the C9\\'-C10\\' or the C9-C10 double bond in vitro. In contrast, we did not observe any conversion of violaxanthin and only traces of activity with 9-. cis-β-carotene, which led to 9-. cis-β-apo-10\\'-carotenal. Our data indicate that all-. trans-β-carotene is the likely substrate of StCCD4 in planta, and that this carotene may be precursor of an unknown compound involved in tuber development.
[Recent knowledge about intestinal absorption and cleavage of carotenoids].
Borel, P; Drai, J; Faure, H; Fayol, V; Galabert, C; Laromiguière, M; Le Moël, G
2005-01-01
Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the
Endocytic down-regulation of ErbB2 is stimulated by cleavage of its C-terminus
DEFF Research Database (Denmark)
Lerdrup, Mads; Bruun, Silas; Grandal, Michael Vibo
2007-01-01
inhibition of HSP90 with geldanamycin this cleavage is accompanied by proteasome-dependent endocytosis of ErbB2. However, it is unknown whether C-terminal cleavage is linked to endocytosis. To study ErbB2 cleavage and endocytic trafficking, we fused yellow fluorescent protein (YFP) and cyan fluorescent...
Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease
Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S
2013-01-01
Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism. PMID:23365169
Effects of Cysteamine on Sheep Embryo Cleavage Rates
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Sinem Ö. ENGİNLER
2015-01-01
Full Text Available Oxidative stress during in vitro culture leads to defects in development of gametes and embryos. Several antioxidants such as cysteamine, L-ascorbic acid, beta mercaptoethanol, cysteine, glutathione, proteins, vitamins have been used to supplement culture media to counter the oxidative stress. This study was conducted to detect the effect of adding cysteamine to the maturation medium to subsequent cleavage rates of sheep embryos. Totally 604 ovaries were obtained by ten replica and 2060 oocytes were collected. The cumulus oocyte complexes were recovered by the slicing method. A total of 1818 selected oocytes were divided into two groups and used for maturation (88.25%. The first group was created as supplemented with cysteamine (Group A and second group (Group B, control without cysteamine in TCM-199. The two groups were incubated for 24 h at 38.8 °C in an atmosphere of 5% CO2 in humidified air for in vitro maturation (IVM. After IVM, oocytes were fertilized with 50 x 107 / mL fresh ram semen in BSOF medium for 18 h. After fertilization, maturation groups were divided into two subgroups with different culture media: Group AI-SOF (Synthetic Oviduct Fluid medium, Group AII-CR1aa (Charles Rosencrans medium, Group BI-SOF and Group BII-CR1aa were achieved. Cleavage rates were evaluated at day 2. post insemination. The rates of cleavage were detected as 59.54% (184/309, 55.44% (173/312, 65.34% (215/329, 59.34% (200/337 respectively, with showing no statistically significant difference between the groups at the level of P>0.05. In conclusion, supplementing cysteamine to maturation media in TCM-199 did not affect the cleavage rates of sheep embryos in SOF and CR1aa culture media.
Variable context Markov chains for HIV protease cleavage site prediction.
Oğul, Hasan
2009-06-01
Deciphering the knowledge of HIV protease specificity and developing computational tools for detecting its cleavage sites in protein polypeptide chain are very desirable for designing efficient and specific chemical inhibitors to prevent acquired immunodeficiency syndrome. In this study, we developed a generative model based on a generalization of variable order Markov chains (VOMC) for peptide sequences and adapted the model for prediction of their cleavability by certain proteases. The new method, called variable context Markov chains (VCMC), attempts to identify the context equivalence based on the evolutionary similarities between individual amino acids. It was applied for HIV-1 protease cleavage site prediction problem and shown to outperform existing methods in terms of prediction accuracy on a common dataset. In general, the method is a promising tool for prediction of cleavage sites of all proteases and encouraged to be used for any kind of peptide classification problem as well.
Chang, Chia-Wei; Lee, Wei-Ju; Liao, Yi-Chu; Chang, Ming-Hong
2013-11-01
We investigate electrodiagnostic markers to determine which parameters are the best predictors of spontaneous electromyographic (EMG) activity in carpal tunnel syndrome (CTS). We enrolled 229 patients with clinically proven and nerve conduction study (NCS)-proven CTS, as well as 100 normal control subjects. All subjects were evaluated using electrodiagnostic techniques, including median distal sensory latencies (DSLs), sensory nerve action potentials (SNAPs), distal motor latencies (DMLs), compound muscle action potentials (CMAPs), forearm median nerve conduction velocities (FMCVs) and wrist-palm motor conduction velocities (W-P MCVs). All CTS patients underwent EMG examination of the abductor pollicis brevis (APB) muscle, and the presence or absence of spontaneous EMG activities was recorded. Normal limits were determined by calculating the means ± 2 standard deviations from the control data. Associations between parameters from the NCS and EMG findings were investigated. In patients with clinically diagnosed CTS, abnormal median CMAP amplitudes were the best predictors of spontaneous activity during EMG examination (p95% (positive predictive rate >95%). If the median CMAP amplitude was higher than the normal limit (>4.9 mV), the rate of no spontaneous EMG activity was >94% (negative predictive rate >94%). An abnormal SNAP amplitude was the second best predictor of spontaneous EMG activity (p<0.001; OR 4.13; 95% CI 2.16-7.90), and an abnormal FMCV was the third best predictor (p=0.01; OR 2.10; 95% CI 1.20-3.67). No other nerve conduction parameters had significant power to predict spontaneous activity upon EMG examination. The CMAP amplitudes of the APB are the most powerful predictors of the occurrence of spontaneous EMG activity. Low CMAP amplitudes are strongly associated with spontaneous activity, whereas high CMAP amplitude are less associated with spontaneous activity, implying that needle EMG examination should be recommended for the detection of
Changes in Contact Area in Meniscus Horizontal Cleavage Tears Subjected to Repair and Resection.
Beamer, Brandon S; Walley, Kempland C; Okajima, Stephen; Manoukian, Ohan S; Perez-Viloria, Miguel; DeAngelis, Joseph P; Ramappa, Arun J; Nazarian, Ara
2017-03-01
To assess the changes in tibiofemoral contact pressure and contact area in human knees with a horizontal cleavage tear before and after treatment. Ten human cadaveric knees were tested. Pressure sensors were placed under the medial meniscus and the knees were loaded at twice the body weight for 20 cycles at 0°, 10°, and 20° of flexion. Contact area and pressure were recorded for the intact meniscus, the meniscus with a horizontal cleavage tear, after meniscal repair, after partial meniscectomy (single leaflet), and after subtotal meniscectomy (double leaflet). The presence of a horizontal cleavage tear significantly increased average peak contact pressure and reduced effective average tibiofemoral contact area at all flexion angles tested compared with the intact state (P contact pressure after creation of the horizontal cleavage tear. Repairing the horizontal cleavage tear restored peak contact pressures and areas to within 15% of baseline, statistically similar to the intact state at all angles tested (P contact pressure and reduced average contact area at all degrees of flexion compared with the intact state (P contact area and a significant elevation in contact pressure. These changes may accelerate joint degeneration. A suture-based repair of these horizontal cleavage tears returns the contact area and contact pressure to nearly normal, whereas both partial and subtotal meniscectomy lead to significant reductions in contact area and significant elevations in contact pressure within the knee. Repairing horizontal cleavage tears may lead to improved clinical outcomes by preserving meniscal tissue and the meniscal function. Understanding contact area and peak contact pressure resulting from differing strategies for treating horizontal cleavage tears will allow the surgeon to evaluate the best strategy for treating his or her patients who present with this meniscal pathology. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier
Oxidative cleavage of erucic acid for the synthesis of brassylic acid
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Mohammed J. Nasrullah; Pooja Thapliyal; Erica N. Pfarr; Nicholas S. Dusek; Kristofer L. Schiele; James A. Bahr
2010-10-29
The main focus of this work is to synthesize Brassylic Acid (BA) using oxidative cleavage of Erucic Acid (EA). Crambe (Crambe abyssinica) is an industrial oilseed grown in North Dakota. Crambe has potential as an industrial fatty acid feedstock as a source of Erucic acid (EA). It has approximately 50-60 % of EA, a C{sub 22} monounsaturated fatty acid. Oxidative cleavage of unsaturated fatty acids derived from oilseeds produces long chain (9, 11, and 13 carbon atoms) dibasic and monobasic acids. These acids are known commercial feedstocks for the preparation of nylons, polyesters, waxes, surfactants, and perfumes. Other sources of EA are Rapeseed seed oil which 50-60 % of EA. Rapeseed is grown outside USA. The oxidative cleavage of EA was done using a high throughput parallel pressure reactor system. Kinetics of the reaction shows that BA yields reach a saturation at 12 hours. H{sub 2}WO{sub 4} was found to be the best catalyst for the oxidative cleavage of EA. High yields of BA were obtained at 80 C with bubbling of O{sub 2} or 10 bar of O{sub 2} for 12 hours.
Caspase-Dependent Apoptosis Induced by Telomere Cleavage and TRF2 Loss
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Asha S. Multani
2000-07-01
Full Text Available Chromosomal abnormalities involving telomeric associations (TAs often precede replicative senescence and abnormal chromosome configurations. We report here that telomere cleavage following exposure to proapoptotic agents is an early event in apoptosis. Exposure of human and murine cancer cells to a variety of pro-apoptotic stimuli (staurosporine, thapsigargin, anti-Fas antibody, cancer chemotherapeutic agents resulted in telomere cleavage and aggregation, finally their extrusion from the nuclei. Telomere loss was associated with arrest of cells in G2/M phase and preceded DNA fragmentation. Telomere erosion and subsequent large-scale chromatin cleavage were inhibited by overexpression of the anti -apoptotic protein, bcl-2, two peptide caspase inhibitors (BACMK and zVADfmk, indicating that both events are regulated by caspase activation. The results demonstrate that telomere cleavage is an early chromatin alteration detected in various cancer cell lines leading to drug-induced apoptosis, suggest that this event contributes to mitotic catastrophe and induction of cell death. Results also suggest that the decrease of telomeric-repeat binding factor 2 (TRF2 may be the earliest event in the ara-C-induced telomere shortening, induction of endoreduplication and chromosomal fragmentation leading to cell death.
Bruno, Mark; Beyer, Peter; Al-Babili, Salim
2015-04-15
Down-regulation of the potato carotenoid cleavage dioxygenase 4 (StCCD4) transcript level led to tubers with altered morphology and sprouting activity, which also accumulated higher levels of violaxanthin and lutein leading to elevated carotenoid amounts. This phenotype indicates a role of this enzyme in tuber development, which may be exerted by a cleavage product. In this work, we investigated the enzymatic activity of StCCD4, by expressing the corresponding cDNA in carotenoid accumulating Escherichia coli strains and by performing in vitro assays with heterologously expressed enzyme. StCCD4 catalyzed the cleavage of all-trans-β-carotene at the C9'-C10' double bond, leading to β-ionone and all-trans-β-apo-10'-carotenal, both in vivo and in vitro. The enzyme also cleaved β,β-cryptoxanthin, zeaxanthin and lutein either at the C9'-C10' or the C9-C10 double bond in vitro. In contrast, we did not observe any conversion of violaxanthin and only traces of activity with 9-cis-β-carotene, which led to 9-cis-β-apo-10'-carotenal. Our data indicate that all-trans-β-carotene is the likely substrate of StCCD4 in planta, and that this carotene may be precursor of an unknown compound involved in tuber development. Copyright © 2015 Elsevier Inc. All rights reserved.
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Paul M. Graham, DO
2018-05-01
Full Text Available We report a case of histologically confirmed primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT that subsequently underwent spontaneous regression in the absence of systemic treatment. The case showed an atypical lymphoid infiltrate that was CD20+ and MUM-1+ and CD10–. A subsequent biopsy of the spontaneously regressed lesion showed fibrosis associated with a lymphocytic infiltrate comprising reactive T cells. PCDLBCL-LT is a cutaneous B-cell lymphoma with a poor prognosis, which is usually treated with chemotherapy. We describe a case of clinical and histologic spontaneous regression in a patient with PCDLBCL-LT who had a negative systemic workup but a recurrence over a year after his initial presentation. Key words: B cell, lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, regression
Pressure modulates the self-cleavage step of the hairpin ribozyme
Schuabb, Caroline; Kumar, Narendra; Pataraia, Salome; Marx, Dominik; Winter, Roland
2017-03-01
The ability of certain RNAs, denoted as ribozymes, to not only store genetic information but also catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth. This, however, might have evolved under extreme environmental conditions, including the deep sea with pressures in the kbar regime. Here we study pressure-induced effects on the self-cleavage of hairpin ribozyme by following structural changes in real-time. Our results suggest that compression of the ribozyme leads to an accelerated transesterification reaction, being the self-cleavage step, although the overall process is retarded in the high-pressure regime. The results reveal that favourable interactions between the reaction site and neighbouring nucleobases are strengthened under pressure, resulting therefore in an accelerated self-cleavage step upon compression. These results suggest that properly engineered ribozymes may also act as piezophilic biocatalysts in addition to their hitherto known properties.
Pleurectomy versus pleural abrasion for primary spontaneous pneumothorax in children.
Joharifard, Shahrzad; Coakley, Brian A; Butterworth, Sonia A
2017-05-01
Primary spontaneous pneumothorax (PSP) represents a common indication for urgent surgical intervention in children. First episodes are often managed with thoracostomy tube, whereas recurrent episodes typically prompt surgery involving apical bleb resection and pleurodesis, either via pleurectomy or pleural abrasion. The purpose of this study was to assess whether pleurectomy or pleural abrasion was associated with lower postoperative recurrence. The records of patients undergoing surgery for PSP between February 2005 and December 2015 were retrospectively reviewed. Recurrence was defined as an ipsilateral pneumothorax requiring surgical intervention. Bivariate logistic regressions were used to identify factors associated with recurrence. Fifty-two patients underwent 64 index operations for PSP (12 patients had surgery for contralateral pneumothorax, and each instance was analyzed separately). The mean age was 15.7±1.2years, and 79.7% (n=51) of patients were male. In addition to apical wedge resection, 53.1% (n=34) of patients underwent pleurectomy, 39.1% (n=25) underwent pleural abrasion, and 7.8% (n=5) had no pleural treatment. The overall recurrence rate was 23.4% (n=15). Recurrence was significantly lower in patients who underwent pleurectomy rather than pleural abrasion (8.8% vs. 40%, p<0.01). In patients who underwent pleural abrasion without pleurectomy, the relative risk of recurrence was 2.36 [1.41-3.92, p<0.01]. Recurrence of PSP is significantly reduced in patients undergoing pleurectomy compared to pleural abrasion. Level III, retrospective comparative therapeutic study. Copyright © 2017 Elsevier Inc. All rights reserved.
Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte
2017-10-01
We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.
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Lafuente Esther M
2010-09-01
Full Text Available Abstract Background Proteasomes play a central role in the major histocompatibility class I (MHCI antigen processing pathway. They conduct the proteolytic degradation of proteins in the cytosol, generating the C-terminus of CD8 T cell epitopes and MHCI-peptide ligands (P1 residue of cleavage site. There are two types of proteasomes, the constitutive form, expressed in most cell types, and the immunoproteasome, which is constitutively expressed in mature dendritic cells. Protective CD8 T cell epitopes are likely generated by the immunoproteasome and the constitutive proteasome, and here we have modeled and analyzed the cleavage by these two proteases. Results We have modeled the immunoproteasome and proteasome cleavage sites upon two non-overlapping sets of peptides consisting of 553 CD8 T cell epitopes, naturally processed and restricted by human MHCI molecules, and 382 peptides eluted from human MHCI molecules, respectively, using N-grams. Cleavage models were generated considering different epitope and MHCI-eluted fragment lengths and the same number of C-terminal flanking residues. Models were evaluated in 5-fold cross-validation. Judging by the Mathew's Correlation Coefficient (MCC, optimal cleavage models for the proteasome (MCC = 0.43 ± 0.07 and the immunoproteasome (MCC = 0.36 ± 0.06 were obtained from 12-residue peptide fragments. Using an independent dataset consisting of 137 HIV1-specific CD8 T cell epitopes, the immunoproteasome and proteasome cleavage models achieved MCC values of 0.30 and 0.18, respectively, comparatively better than those achieved by related methods. Using ROC analyses, we have also shown that, combined with MHCI-peptide binding predictions, cleavage predictions by the immunoproteasome and proteasome models significantly increase the discovery rate of CD8 T cell epitopes restricted by different MHCI molecules, including A*0201, A*0301, A*2402, B*0702, B*2705. Conclusions We have developed models that are specific
Qian, Guian; Lei, Wei-Sheng; Niffenegger, M.; González-Albuixech, V. F.
2018-04-01
The work relates to the effect of temperature on the model parameters in local approaches (LAs) to cleavage fracture. According to a recently developed LA model, the physical consensus of plastic deformation being a prerequisite to cleavage fracture enforces any LA model of cleavage fracture to observe initial yielding of a volume element as its threshold stress state to incur cleavage fracture in addition to the conventional practice of confining the fracture process zone within the plastic deformation zone. The physical consistency of the new LA model to the basic LA methodology and the differences between the new LA model and other existing models are interpreted. Then this new LA model is adopted to investigate the temperature dependence of LA model parameters using circumferentially notched round tensile specimens. With the published strength data as input, finite element (FE) calculation is conducted for elastic-perfectly plastic deformation and the realistic elastic-plastic hardening, respectively, to provide stress distributions for model calibration. The calibration results in temperature independent model parameters. This leads to the establishment of a 'master curve' characteristic to synchronise the correlation between the nominal strength and the corresponding cleavage fracture probability at different temperatures. This 'master curve' behaviour is verified by strength data from three different steels, providing a new path to calculate cleavage fracture probability with significantly reduced FE efforts.
International Nuclear Information System (INIS)
Rosenfield, A.R.; Shetty, D.K.; Skidmore, A.J.
1983-01-01
This note reports the results of a fractographic study conducted on a group of 1T compact fracture toughness specimens of a heavy-section A508 steel denoted TSE6 tested in the ductile-brittle transition region (22 and 82 0 C). The fatigue-precracked specimens were loaded at a rapid rate (760 or 550 mm per second) to promote cleavage-crack growth and lower-bound toughness behavior. All specimens experienced unstable cleavage fracture prior to reaching a maximum in the load displacement curve. Some ductile crack growth occurred in half of the specimens. The objective of fractographic examinations was to understand the observed statistical variations in cleavage initiation by (a) locating the origins of unstable cleavage fracture in the vicinity of the fatigue-precrack or ductilerupture crack fronts, (b) identifying microstructural features associated with the triggering of cleavage, and (c) documenting characteristic fracture surface dimensions such as the extent of stable-crack growth prior to unstable cleavage (Δα) and the distance of the cleavage origin from the ductilerupture front, /chi/ (or fatigue-crack front when Δα = 0)
Lu, Yu Yu; Wang, Hsin Yi; Lin, Ying; Lin, Wan Yu
2012-09-01
Radionuclide Cisternography (RNC) is of potential value in pointing out the sites of cerebrospinal fluid (CSF) leakage in patients with spontaneous intracranial hypotension (SIH). In the current report, we present two patients who underwent RNC for suspected CSF leakage. Both patients underwent magnetic resonance imaging (MRI) and RNC for evaluation. We describe a simple method to increase the detection ability of RNC for CSF leakage in patients with SIH.
Sensitive and fast mutation detection by solid phase chemical cleavage
DEFF Research Database (Denmark)
Hansen, Lise Lotte; Justesen, Just; Kruse, Torben A
1996-01-01
We have developed a solid phase chemical cleavage method (SpCCM) for screening large DNA fragments for mutations. All reactions can be carried out in microtiterwells from the first amplification of the patient (or test) DNA through the search for mutations. The reaction time is significantly...... reduced compared to the conventional chemical cleavage method (CCM), and even by using a uniformly labelled probe, the exact position and nature of the mutation can be revealed. The SpCCM is suitable for automatization using a workstation to carry out the reactions and a fluorescent detection-based DNA...
On the formation and nature of quasi-cleavage fracture surfaces in hydrogen embrittled steels
Energy Technology Data Exchange (ETDEWEB)
Martin, May L.; Fenske, Jamey A.; Liu, Grace S.; Sofronis, Petros [University of Illinois, Dept. of Materials Science and Engineering, 1304 W. Green St., Urbana, IL 61801 (United States); Robertson, Ian M., E-mail: ianr@illinois.edu [University of Illinois, Dept. of Materials Science and Engineering, 1304 W. Green St., Urbana, IL 61801 (United States)
2011-02-15
Quasi-cleavage, a common feature of hydrogen-induced fracture surfaces, is generally taken as being cleavage-like but not along a known cleavage plane. Despite the frequency with which this surface is observed, the relationship to the underlying microstructure remains unknown. Through a combination of topographical reconstruction of secondary electron microscope fractographs and a transmission electron microscopy study of the microstructure from site-specific locations, it will be shown that the features on quasi-cleavage surfaces are ridges that can be correlated with sub-surface intense and highly localized deformation bands. It will be demonstrated that the fracture surface arises from the growth and coalescence of voids that initiate at and extend along slip band intersections. This mechanism and process is fully consistent with hydrogen enhancing and localizing plastic processes.
MR imaging and clinical findings of spontaneous spinal epidural hematoma
Energy Technology Data Exchange (ETDEWEB)
Kim, Sam Soo [Seoul City Boramae Hospital, Seoul (Korea, Republic of); Han, Moon Hee; Kim, Hyun Beom [College of Medicine, Seoul National University, Seoul (Korea, Republic of)] [and others
2000-01-01
To describe the MR imaging and clinical findings of spontaneous spinal epidural hematoma. The MR and clinical findings in six patients (M:F=3D4:2;adult:child=3D3:3) with spontaneous spinal epidural hematoma were reviewed. Five patients without any predisposing factor which might cause the condition and one with acute myelogenous leukemia were included. Emergency surgery was performed in two patients, and the other four were managed conservatively. The epidural lesion involved between three and seven vertebrae (mean:4.5), and relative to the spinal cord was located in the posterior-lateral (n=3D4), anterior (n=3D1), or right lateral (n=3D1) area. The hematoma was isointense (n=3D1) or hyperintense (n=3D5) with spinal cord on T1-weighted images, and hypointense (n=3D2) or hyperintense (n=3D4) on T2-weighted images. It was completely absorbed in four of five patients who underwent follow-up MR imaging, but not changed in one. The clinical outcome of these patients was complete recovery (n=3D4), spastic cerebral palsy (n=3D1), or unknown (n=3D1). Because of the lesion's characteristic signal intensity; MR imaging is very useful in the diagnosis and evaluation of spontaneous spinal epidural hematoma. (author)
Bruno, Mark; Beyer, Peter D.; Al-Babili, Salim
2015-01-01
amounts. This phenotype indicates a role of this enzyme in tuber development, which may be exerted by a cleavage product. In this work, we investigated the enzymatic activity of StCCD4, by expressing the corresponding cDNA in carotenoid accumulating
Numerical modeling of ductile tearing effects on cleavage fracture toughness
International Nuclear Information System (INIS)
Dodds, R.H. Jr.; Tang, M.; Anderson, T.L.
1994-05-01
Experimental studies demonstrate a significant effect of specimen size, a/W ratio and prior ductile tearing on cleavage fracture toughness values (J c ) measured in the ductile-to-brittle transition region of ferritic materials. In the lower-transition region, cleavage fracture often occurs under conditions of large-scale yielding but without prior ductile crack extension. The increased toughness develops when plastic zones formed at the crack tip interact with nearby specimen surfaces which relaxes crack-tip constraint (stress triaxiality). In the mid-to-upper transition region, small amounts of ductile crack extension (often c -values. Previous work by the authors described a micromechanics fracture model to correct measured J c -values for the mechanistic effects of large-scale yielding. This new work extends the model to also include the influence of ductile crack extension prior to cleavage. The paper explores development of the new model, provides necessary graphs and procedures for its application and demonstrates the effects of the model on fracture data sets for two pressure vessel steels (A533B and A515)
Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein.
Welch, Brett D; Liu, Yuanyuan; Kors, Christopher A; Leser, George P; Jardetzky, Theodore S; Lamb, Robert A
2012-10-09
The paramyxovirus parainfluenza virus 5 (PIV5) enters cells by fusion of the viral envelope with the plasma membrane through the concerted action of the fusion (F) protein and the receptor binding protein hemagglutinin-neuraminidase. The F protein folds initially to form a trimeric metastable prefusion form that is triggered to undergo large-scale irreversible conformational changes to form the trimeric postfusion conformation. It is thought that F refolding couples the energy released with membrane fusion. The F protein is synthesized as a precursor (F0) that must be cleaved by a host protease to form a biologically active molecule, F1,F2. Cleavage of F protein is a prerequisite for fusion and virus infectivity. Cleavage creates a new N terminus on F1 that contains a hydrophobic region, known as the FP, which intercalates target membranes during F protein refolding. The crystal structure of the soluble ectodomain of the uncleaved form of PIV5 F is known; here we report the crystal structure of the cleavage-activated prefusion form of PIV5 F. The structure shows minimal movement of the residues adjacent to the protease cleavage site. Most of the hydrophobic FP residues are buried in the uncleaved F protein, and only F103 at the newly created N terminus becomes more solvent-accessible after cleavage. The conformational freedom of the charged arginine residues that compose the protease recognition site increases on cleavage of F protein.
Critical cleavage fracture stress characterization of A508 nuclear pressure vessel steels
International Nuclear Information System (INIS)
Wu, Sujun; Jin, Huijin; Sun, Yanbin; Cao, Luowei
2014-01-01
The critical cleavage fracture stress of SA508 Gr.4N and SA508 Gr.3 low alloy reactor pressure vessel (RPV) steels was studied through the combination of experiments and finite element method (FEM) analysis. The results showed that the value of the local cleavage fracture stress, σ F , of SA508 Gr.4N steel was significantly higher than that of SA508 Gr.3 steel. Detailed microstructural analysis was carried out using FEGSEM which revealed much smaller grains, finer and more homogenous carbide particles formed in SA508 Gr.4N steel. Compared with the SA508 Gr.3 steel currently used in the nuclear industry, the SA508 Gr.4N steel possesses higher strength and notch toughness as well as improved cleavage fracture behavior, and is considered a better candidate RPV steel for the next generation nuclear reactors. - Highlights: • Critical cleavage fracture stress was calculated through experiments and FEM. • Effects of both grain and carbide particle sizes on σ F were discussed. • The SA508 Gr.4N steel is a better candidate for the next generation nuclear reactors
A set of simple cell processes is sufficient to model spiral cleavage.
Brun-Usan, Miguel; Marín-Riera, Miquel; Grande, Cristina; Truchado-Garcia, Marta; Salazar-Ciudad, Isaac
2017-01-01
During cleavage, different cellular processes cause the zygote to become partitioned into a set of cells with a specific spatial arrangement. These processes include the orientation of cell division according to: an animal-vegetal gradient; the main axis (Hertwig's rule) of the cell; and the contact areas between cells or the perpendicularity between consecutive cell divisions (Sachs' rule). Cell adhesion and cortical rotation have also been proposed to be involved in spiral cleavage. We use a computational model of cell and tissue biomechanics to account for the different existing hypotheses about how the specific spatial arrangement of cells in spiral cleavage arises during development. Cell polarization by an animal-vegetal gradient, a bias to perpendicularity between consecutive cell divisions (Sachs' rule), cortical rotation and cell adhesion, when combined, reproduce the spiral cleavage, whereas other combinations of processes cannot. Specifically, cortical rotation is necessary at the 8-cell stage to direct all micromeres in the same direction. By varying the relative strength of these processes, we reproduce the spatial arrangement of cells in the blastulae of seven different invertebrate species. © 2017. Published by The Company of Biologists Ltd.
Spontaneous regression of residual low-grade cerebellar pilocytic astrocytomas in children
International Nuclear Information System (INIS)
Gunny, Roxana S.; Saunders, Dawn E.; Hayward, Richard D.; Phipps, Kim P.; Harding, Brian N.
2005-01-01
Cerebellar low-grade astrocytomas (CLGAs) of childhood are benign tumours and are usually curable by surgical resection alone or combined with adjuvant radiotherapy. To undertake a retrospective study of our children with CLGA to determine the optimum schedule for surveillance imaging following initial surgery. In this report we describe the phenomenon of spontaneous regression of residual tumour and discuss its prognostic significance regarding future imaging. A retrospective review was conducted of children treated for histologically proven CLGA at Great Ormond Street Hospital from 1988 to 1998. Of 83 children with CLGA identified, 13 (15.7%) had incomplete resections. Two children with large residual tumours associated with persistent symptoms underwent additional treatment. Eleven children were followed by surveillance imaging alone for a mean of 6.83 years (range 2-13.25 years). Spontaneous tumour regression was seen in 5 (45.5%) of the 11 children. There were no differences in age, gender, symptomatology, histological grade or Ki-67 fractions between those with spontaneous tumour regression and those with progression. There was a non-significant trend that larger volume residual tumours progressed. Residual tumour followed by surveillance imaging may either regress or progress. For children with residual disease we recommend surveillance imaging every 6 months for the first 2 years, every year for years 3, 4 and 5, then every second year if residual tumour is still present 5 years after initial surgery. This would detect not only progressive or recurrent disease, but also spontaneous regression which can occur later than disease progression. (orig.)
Boron-doped diamond electrodes for the electrochemical oxidation and cleavage of peptides.
Roeser, Julien; Alting, Niels F A; Permentier, Hjalmar P; Bruins, Andries P; Bischoff, Rainer
2013-07-16
Electrochemical oxidation of peptides and proteins is traditionally performed on carbon-based electrodes. Adsorption caused by the affinity of hydrophobic and aromatic amino acids toward these surfaces leads to electrode fouling. We compared the performance of boron-doped diamond (BDD) and glassy carbon (GC) electrodes for the electrochemical oxidation and cleavage of peptides. An optimal working potential of 2000 mV was chosen to ensure oxidation of peptides on BDD by electron transfer processes only. Oxidation by electrogenerated OH radicals took place above 2500 mV on BDD, which is undesirable if cleavage of a peptide is to be achieved. BDD showed improved cleavage yield and reduced adsorption for a set of small peptides, some of which had been previously shown to undergo electrochemical cleavage C-terminal to tyrosine (Tyr) and tryptophan (Trp) on porous carbon electrodes. Repeated oxidation with BDD electrodes resulted in progressively lower conversion yields due to a change in surface termination. Cathodic pretreatment of BDD at a negative potential in an acidic environment successfully regenerated the electrode surface and allowed for repeatable reactions over extended periods of time. BDD electrodes are a promising alternative to GC electrodes in terms of reduced adsorption and fouling and the possibility to regenerate them for consistent high-yield electrochemical cleavage of peptides. The fact that OH-radicals can be produced by anodic oxidation of water at elevated positive potentials is an additional advantage as they allow another set of oxidative reactions in analogy to the Fenton reaction, thus widening the scope of electrochemistry in protein and peptide chemistry and analytics.
Postoperative recurrence after VATS for spontaneous pneumothorax
International Nuclear Information System (INIS)
Katsuno, Gotaro; Tsumura, Makoto; Kokudo, Yasutaka; Muraoka, Atsushi; Tsuruno, Masaki
2003-01-01
A total of 88 cases of 81 patients with spontaneous pneumothorax treated at the hospital from March 1992 to August 2001 were subjected to a study of examining preoperative chest CT and thoracographic findings from the standpoint of postoperative recurrence. Preoperative chest CT and thoracography were conducted in 82 cases and 41 cases (including 25 cases with continuous air leakage), respectively. Eight (9.1%) patients developed recurrence of pneumothorax, and three patients of them underwent reoperation. Considering the intraoperative findings, newly formed bullae appeared to be a cause of recurrence. Resulting from these examinations, we conclude that it is difficult to predict the risk factor for postoperative recurrence at this time, in addition, it is important that the area of air leakage can be confirmed by thoracoscopic findings. (author)
Cleavage mechanoluminescence in elemental and III-V semiconductors
International Nuclear Information System (INIS)
Chandra, B.P.; Patel, R.P.; Gour, Anubha S.; Chandra, V.K.; Gupta, R.K.
2003-01-01
The present paper reports the theory of mechanoluminescence (ML) produced during cleavage of elemental and III-V semiconductors. It seems that the formation of crack-induced localized states is responsible for the ML excitation produced during the cleavage of elemental and III-V semiconductors. According to this mechanism, as the atoms are drawn away from each other in an advancing crack tip, the decreasing wave function overlap across the crack may result in localized states which is associated with increasing electron energy. If the energy of these localized states approach that of the conduction band, transition to the conduction band via tunnelling would be possible, creating minority carriers, and consequently the electron-hole recombination may give rise to mechanoluminescence. When an elemental or III-V semiconductor is cleaved, initially the ML intensity increases with time, attains a peak value I m at the time t m corresponding to completion of the cleavage of the semiconductor, and then it decreases following power law decay. Expressions are derived for the ML intensity I m corresponding to the peak of the ML intensity versus time curve and for the total ML intensity I T . It is shown that both I m and I T should increase directly with the area of the newly created surfaces of the crystals. From the measurements of the ML intensity, the velocity of crack propagation in material can be determined by using the relation v=H/t m
Implementation of a combinatorial cleavage and deprotection scheme
DEFF Research Database (Denmark)
Nielsen, John; Rasmussen, Palle H.
1996-01-01
Phthalhydrazide libraries are synthesized in solution from substituted hydrazines and phthalimides in several different library formats including single compounds, indexed sub-libraries and a full library. When carried out during solid-phase synthesis, this combinatorial cleavage and deprotection...
Spontaneous splenic rupture and Anisakis appendicitis presenting as abdominal pain: a case report
Directory of Open Access Journals (Sweden)
Valle Joaquín
2012-04-01
Full Text Available Abstract Introduction Anisakidosis, human infection with nematodes of the family Anisakidae, is caused most commonly by Anisakis simplex. Acquired by the consumption of raw or undercooked marine fish or squid, anisakidosis occurs where such dietary customs are practiced, including Japan, the coastal regions of Europe and the United States. Rupture of the spleen is a relatively common complication of trauma and many systemic disorders affecting the reticuloendothelial system, including infections and neoplasias. A rare subtype of rupture occurring spontaneously and arising from a normal spleen has been recognized as a distinct clinicopathologic entity. Herein we discuss the case of a woman who presented to our institution with appendicitis secondary to Anisakis and spontaneous spleen rupture. Case presentation We report the case of a 53-year-old Caucasian woman who presented with hemorrhagic shock and abdominal pain and was subsequently found to have spontaneous spleen rupture and appendicitis secondary to Anisakis simplex. She underwent open surgical resection of the splenic rupture and the appendicitis without any significant postoperative complications. Histopathologic examination revealed appendicitis secondary to Anisakis simplex and splenic rupture of undetermined etiology. Conclusions To the best of our knowledge, this report is the first of a woman with the diagnosis of spontaneous spleen rupture and appendicitis secondary to Anisakis simplex. Digestive anisakiasis may present as an acute abdomen. Emergency physicians should know and consider this diagnosis in patients with ileitis or colitis, especially if an antecedent of raw or undercooked fish ingestion is present. Spontaneous rupture of the spleen is an extremely rare event. Increased awareness of this condition will enhance early diagnosis and effective treatment. Further research is required to identify the possible risk factors associated with spontaneous rupture of the spleen.
Xu, Jia-Qi; Choy, Jacky C P; Tang, Jennifer Y M; Liu, Tian-Yin; Luo, Hao; Lou, Vivian W Q; Lum, Terry Y S; Wong, Gloria H Y
2017-09-01
To investigate the predictive value of symptoms of dementia that the person or an informant noticed spontaneously in determining the clinical severity of dementia. Cross-sectional. Community-based open-referral dementia assessment service in Hong Kong between 2005 and 2013. Help-seekers for dementia assessment service and their informants (N = 965 dyads). Participants underwent a clinical dementia interview based on the Clinical Dementia Rating. Spontaneous complaints that the person and the informant made that had prompted their help-seeking of groups with interview results suggestive of no impairment, mild cognitive impairment, and dementia were compared. Logistic regression was used to evaluate the predictive value of spontaneous complaints for clinical severity. Independent raters blinded to clinical results coded spontaneously reported symptoms into theoretical themes: memory, executive function, language, time and place orientation, neuropsychiatric, mood, and avolition. Memory problems were the most frequently reported complaints for participants (87.7%) and their informants (95.5%), followed by self-reported language (33.0%) and informant-reported orientation (33.0%) difficulties. Informant-reported but not self-reported symptoms predicted clinical severity. Compared with the persons themselves, informants reported more pervasive symptoms corresponding to clinical severity. Persons with dementia self-reported fewer types of symptoms than their healthy or mildly impaired counterparts. Spontaneously reported language and orientation symptoms by the informant distinguished persons with mild or worse dementia (P < .001, Nagelkerke coefficient of determination = 29.7%, percentage correct 85.6%). The type and pervasiveness of symptoms spontaneously that informants reported predicted clinical severity. This may provide a quick reference for triage. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.
Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus
Licitra, Beth N.; Millet, Jean K.; Regan, Andrew D.; Hamilton, Brian S.; Rinaldi, Vera D.; Duhamel, Gerald E.
2013-01-01
Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses. PMID:23763835
Trichomonas vaginalis Metalloproteinase Induces mTOR Cleavage of SiHa Cells
Quan, Juan-Hua; Choi, In-Wook; Yang, Jung-Bo; Zhou, Wei; Cha, Guang-Ho; Zhou, Yu; Ryu, Jae-Sook
2014-01-01
Trichomonas vaginalis secretes a number of proteases which are suspected to be the cause of pathogenesis; however, little is understood how they manipulate host cells. The mammalian target of rapamycin (mTOR) regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. We detected various types of metalloproteinases including GP63 protein from T. vaginalis trophozoites, and T. vaginalis GP63 metalloproteinase was confirmed by sequencing and western blot. When SiHa cells were stimulated with live T. vaginalis, T. vaginalis excretory-secretory products (ESP) or T. vaginalis lysate, live T. vaginalis and T. vaginalis ESP induced the mTOR cleavage in both time- and parasite load-dependent manner, but T. vaginalis lysate did not. Pretreatment of T. vaginalis with a metalloproteinase inhibitor, 1,10-phenanthroline, completely disappeared the mTOR cleavage in SiHa cells. Collectively, T. vaginalis metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite. PMID:25548410
Condensed tannins: A novel rearrangement of procyanidins and prodelphinidins in thiolytic cleavage
G. Wayne McGraw; Jan P. Steynberg; Richard W. Hemingway
1993-01-01
Conditions commonly used for the thiolytic cleavage of interflavanoid bonds of condensed tannins also result in cleavage of the C4 to C10 bond of flavan units. Subsequenet lectrophilic attack of the C4 carbocation on the C2' or C6' of the B-ring, and loss of phloroglucinol (the A-ring), result in the formation of a mixture of 1,3-dithiobenzyl-2,4,s,6-...
Spontaneous massive hemopneumothorax: Double trouble with a twist
Directory of Open Access Journals (Sweden)
Milta Kuriakose
2017-01-01
Full Text Available Spontaneous hemopneumothorax (SHP is observed in 3%–7% cases of spontaneous pneumothorax where the tear of an adhesion can lead to bleeding with associated hemothorax. This condition has been reported in patients with hemophilia, sarcoidosis, congenital cystic adenomatoid malformation, systemic lupus erythematosus, etc., Here, we describe an unusual case of acute massive SHP in a 62-year-old male who underwent a percutaneous transluminal coronary angioplasty (PTCA and presented with worsening dyspnea over the next 3 days. On evaluation, he had a massive hemopneumothorax which was considered to be secondary to the use of anticoagulants during the PTCA procedure. Pleural fluid analysis revealed frank blood and was consistent with the diagnosis of hemothorax. Surprisingly, the pleural fluid cytology revealed malignant cells. As the patient had a normal chest X-ray 3 days ago, thoracoscopic pleural biopsy was taken which confirmed the diagnosis of an epithelioid mesothelioma. Although post-PTCA or mesothelioma-associated hemothorax has been rarely reported, these two conditions have not been associated with SHP. Since the patient had no prior clinicoradiological features of mesothelioma, the procedure, and the anticoagulants probably contributed to the massive and rapid accumulation of blood. The presence of small amount of air added further confusion to the dual etiology and has not been described earlier.
Yeast ribonuclease III uses a network of multiple hydrogen bonds for RNA binding and cleavage.
Lavoie, Mathieu; Abou Elela, Sherif
2008-08-19
Members of the bacterial RNase III family recognize a variety of short structured RNAs with few common features. It is not clear how this group of enzymes supports high cleavage fidelity while maintaining a broad base of substrates. Here we show that the yeast orthologue of RNase III (Rnt1p) uses a network of 2'-OH-dependent interactions to recognize substrates with different structures. We designed a series of bipartite substrates permitting the distinction between binding and cleavage defects. Each substrate was engineered to carry a single or multiple 2'- O-methyl or 2'-fluoro ribonucleotide substitutions to prevent the formation of hydrogen bonds with a specific nucleotide or group of nucleotides. Interestingly, introduction of 2'- O-methyl ribonucleotides near the cleavage site increased the rate of catalysis, indicating that 2'-OH are not required for cleavage. Substitution of nucleotides in known Rnt1p binding site with 2'- O-methyl ribonucleotides inhibited cleavage while single 2'-fluoro ribonucleotide substitutions did not. This indicates that while no single 2'-OH is essential for Rnt1p cleavage, small changes in the substrate structure are not tolerated. Strikingly, several nucleotide substitutions greatly increased the substrate dissociation constant with little or no effect on the Michaelis-Menten constant or rate of catalysis. Together, the results indicate that Rnt1p uses a network of nucleotide interactions to identify its substrate and support two distinct modes of binding. One mode is primarily mediated by the dsRNA binding domain and leads to the formation of stable RNA/protein complex, while the other requires the presence of the nuclease and N-terminal domains and leads to RNA cleavage.
Polycystin-1 C-terminal Cleavage Is Modulated by Polycystin-2 Expression*
Bertuccio, Claudia A.; Chapin, Hannah C.; Cai, Yiqiang; Mistry, Kavita; Chauvet, Veronique; Somlo, Stefan; Caplan, Michael J.
2009-01-01
Autosomal dominant polycystic kidney disease is caused by mutations in the genes encoding polycystin-1 (PC-1) and polycystin-2 (PC-2). PC-1 cleavage releases its cytoplasmic C-terminal tail (CTT), which enters the nucleus. To determine whether PC-1 CTT cleavage is influenced by PC-2, a quantitative cleavage assay was utilized, in which the DNA binding and activation domains of Gal4 and VP16, respectively, were appended to PC-1 downstream of its CTT domain (PKDgalvp). Cells cotransfected with the resultant PKDgalvp fusion protein and PC-2 showed an increase in luciferase activity and in CTT expression, indicating that the C-terminal tail of PC-1 is cleaved and enters the nucleus. To assess whether CTT cleavage depends upon Ca2+ signaling, cells transfected with PKDgalvp alone or together with PC-2 were incubated with several agents that alter intracellular Ca2+ concentrations. PC-2 enhancement of luciferase activity was not altered by any of these treatments. Using a series of PC-2 C-terminal truncated mutations, we identified a portion of the PC-2 protein that is required to stimulate PC-1 CTT accumulation. These data demonstrate that release of the CTT from PC-1 is influenced and stabilized by PC-2. This effect is independent of Ca2+ but is regulated by sequences contained within the PC-2 C-terminal tail, suggesting a mechanism through which PC-1 and PC-2 may modulate a novel signaling pathway. PMID:19491093
Restriction enzyme cleavage of ultraviolet-damaged Simian virus 40 and pBR322 DNA
International Nuclear Information System (INIS)
Cleaver, J.E.
1983-01-01
Cleavage of specific DNA sequences by the restriction enzymes EcoRI, HindIII and TaqI was prevented when the DNA was irradiated with ultraviolet light. Most of the effects were attributed to cyclobutane pyrimidine dimers in the recognition sequences; the effectiveness of irradiation was directly proportional to the number of potential dimer sites in the DNA. Combining EcoRI with dimer-specific endonuclease digestion revealed that pyrimidine dimers blocked cleavage within one base-pair on the strand opposite to the dimer but did not block cleavage three to four base-pairs away on the same strand. These are the probable limits for the range of influence of pyrimidine dimers along the DNA, at least for this enzyme. The effect of irradiation on cleavage by TaqI seemed far greater than expected for the cyclobutane dimer yield, possibly because of effects from photoproducts flanking the tetranucleotide recognition sequence and the effect of non-cyclobutane (6-4)pyrimidine photoproducts involving adjacent T and C bases. (author)
Control of extracellular cleavage of ProBDNF by high frequency neuronal activity
Nagappan, Guhan; Zaitsev, Eugene; Senatorov, Vladimir V.; Yang, Jianmin; Hempstead, Barbara L.; Lu, Bai
2009-01-01
Pro- and mature neurotrophins often elicit opposing biological effects. For example, mature brain-derived neurotrophic factor (mBDNF) is critical for long-term potentiation induced by high-frequency stimulation, whereas proBDNF facilitate long-term depression induced by low-frequency stimulation. Because mBDNF is derived from proBDNF by endoproteolytic cleavage, mechanisms regulating the cleavage of proBDNF may control the direction of BDNF regulation. Using methods that selectively detect pr...
Payer, Michael; Agosti, Reto
2010-11-01
Spontaneous idiopathic acute spinal subdural hematomas are highly exceptional. Neurological symptoms are usually severe, and rapid diagnosis with MRI is mandatory. Surgical evacuation has frequently been used therapeutically; however, spontaneous recovery in mild cases has also been reported. We present a case of spontaneous recovery from severe paraparesis after spontaneous acute SSDH, and review the English-speaking literature.
Stimulation of NADH-dependent microsomal DNA strand cleavage by rifamycin SV.
Kukiełka, E; Cederbaum, A I
1995-04-15
Rifamycin SV is an antibiotic anti-bacterial agent used in the treatment of tuberculosis. This drug can autoxidize, especially in the presence of metals, and generate reactive oxygen species. A previous study indicated that rifamycin SV can increase NADH-dependent microsomal production of reactive oxygen species. The current study evaluated the ability of rifamycin SV to interact with iron and increase microsomal production of hydroxyl radical, as detected by conversion of supercoiled plasmid DNA into the relaxed open circular state. The plasmid used was pBluescript II KS(-), and the forms of DNA were separated by agarose-gel electrophoresis. Incubation of rat liver microsomes with plasmid plus NADH plus ferric-ATP caused DNA strand cleavage. The addition of rifamycin SV produced a time- and concentration-dependent increase in DNA-strand cleavage. No stimulation by rifamycin SV occurred in the absence of microsomes, NADH or ferric-ATP. Stimulation occurred with other ferric complexes besides ferric-ATP, e.g. ferric-histidine, ferric-citrate, ferric-EDTA, and ferric-(NH4)2SO4. Rifamycin SV did not significantly increase the high rates of DNA strand cleavage found with NADPH as the microsomal reductant. The stimulation of NADH-dependent microsomal DNA strand cleavage was completely blocked by catalase, superoxide dismutase, GSH and a variety of hydroxyl-radical-scavenging agents, but not by anti-oxidants that prevent microsomal lipid peroxidation. Redox cycling agents, such as menadione and paraquat, in contrast with rifamycin SV, stimulated the NADPH-dependent reaction; menadione and rifamycin SV were superior to paraquat in stimulating the NADH-dependent reaction. These results indicate that rifamycin SV can, in the presence of an iron catalyst, increase microsomal production of reactive oxygen species which can cause DNA-strand cleavage. In contrast with other redox cycling agents, the stimulation by rifamycin SV is more pronounced with NADH than with NADPH as the
Adam Smith, R; Sewell, Sarah L; Giorgio, Todd D
2008-01-01
The development and in vitro performance of a modular nanoscale system capable of specific structural modification by enzymatic activity is described in this work. Due to its small physical size and adaptable characteristics, this system has the potential for utilization in targeted delivery systems and biosensing. Nanoparticle probes were synthesized containing two distinct fluorescent species including a quantum dot base particle and fluorescently labeled cleavable peptide substrate. Activity of these probes was monitored by gel electrophoresis with quantitative cleavage measurements made by fluorometric analysis. The model proximity-activated nanoparticles studied here exhibit significant susceptibility to cleavage by matrix metalloprotease-7 (MMP-7) at physiologically relevant concentrations, with nearly complete cleavage of available substrate molecules after 24 hours. This response is specific to MMP-7 enzyme activity, as cleavage is completely inhibited with the addition of EDTA. Utilization of enzyme-specific modification is a sensitive approach with broad applications for targeted therapeutics and biosensing. The versatility of this nanoparticle system is highlighted in its modular design, as it has the capability to integrate characteristics for detection, biosensing, targeting, and payload delivery into a single, multifunctional nanoparticle structure. PMID:18488420
Delpy, Jean-Philippe; Pagès, Pierre-Benoit; Mordant, Pierre; Falcoz, Pierre-Emmanuel; Thomas, Pascal; Le Pimpec-Barthes, Francoise; Dahan, Marcel; Bernard, Alain
2016-03-01
There are no guidelines regarding the surgical approach for spontaneous pneumothorax. It has been reported, however, that the risk of recurrence following video-assisted thoracic surgery is higher than that following open thoracotomy (OT). The objective of this study was to determine whether this higher risk of recurrence following video-assisted thoracic surgery could be attributable to differences in intraoperative parenchymal resection and the pleurodesis technique. Data for 7647 patients operated on for primary or secondary spontaneous pneumothorax between 1 January 2005 and 31 December 2012 were extracted from Epithor®, the French national database. The type of pleurodesis and parenchymal resection was collected. Outcomes were (i) bleeding, defined as postoperative pleural bleeding; (ii) pulmonary and pleural complications, defined as atelectasis, pneumonia, empyema, prolonged ventilation, acute respiratory distress syndrome and prolonged air leaks; (iii) in-hospital length of stay and (iv) recurrence, defined as chest drainage or surgery for a second pneumothorax. Of note, 6643 patients underwent videothoracoscopy and 1004 patients underwent OT. When compared with the thoracotomy group, the videothoracoscopy group was associated with more parenchymal resections (62.4 vs 80%, P = 0.01), fewer mechanical pleurodesis procedures (93 vs 77.5%, P pneumothorax, videothoracoscopy is associated with a higher rate of recurrence than OT. This difference might be attributable to differences in the pleurodesis technique rather than differences in the parenchymal resection. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
PROSPER: an integrated feature-based tool for predicting protease substrate cleavage sites.
Directory of Open Access Journals (Sweden)
Jiangning Song
Full Text Available The ability to catalytically cleave protein substrates after synthesis is fundamental for all forms of life. Accordingly, site-specific proteolysis is one of the most important post-translational modifications. The key to understanding the physiological role of a protease is to identify its natural substrate(s. Knowledge of the substrate specificity of a protease can dramatically improve our ability to predict its target protein substrates, but this information must be utilized in an effective manner in order to efficiently identify protein substrates by in silico approaches. To address this problem, we present PROSPER, an integrated feature-based server for in silico identification of protease substrates and their cleavage sites for twenty-four different proteases. PROSPER utilizes established specificity information for these proteases (derived from the MEROPS database with a machine learning approach to predict protease cleavage sites by using different, but complementary sequence and structure characteristics. Features used by PROSPER include local amino acid sequence profile, predicted secondary structure, solvent accessibility and predicted native disorder. Thus, for proteases with known amino acid specificity, PROSPER provides a convenient, pre-prepared tool for use in identifying protein substrates for the enzymes. Systematic prediction analysis for the twenty-four proteases thus far included in the database revealed that the features we have included in the tool strongly improve performance in terms of cleavage site prediction, as evidenced by their contribution to performance improvement in terms of identifying known cleavage sites in substrates for these enzymes. In comparison with two state-of-the-art prediction tools, PoPS and SitePrediction, PROSPER achieves greater accuracy and coverage. To our knowledge, PROSPER is the first comprehensive server capable of predicting cleavage sites of multiple proteases within a single substrate
Fe-Catalyzed Oxidative Cleavage of Unsaturated Fatty Acids
Spannring, P.
2013-01-01
The oxidative cleavage of unsaturated fatty acids into aldehydes or carboxylic acids gives access to valuable products. The products can be used as chemical building blocks, as emulsifiers or in the paint or polymer industry. Ozonolysis is applied industrially to cleave the fatty acid oleic acid
Signal peptide discrimination and cleavage site identification using SVM and NN.
Kazemian, H B; Yusuf, S A; White, K
2014-02-01
About 15% of all proteins in a genome contain a signal peptide (SP) sequence, at the N-terminus, that targets the protein to intracellular secretory pathways. Once the protein is targeted correctly in the cell, the SP is cleaved, releasing the mature protein. Accurate prediction of the presence of these short amino-acid SP chains is crucial for modelling the topology of membrane proteins, since SP sequences can be confused with transmembrane domains due to similar composition of hydrophobic amino acids. This paper presents a cascaded Support Vector Machine (SVM)-Neural Network (NN) classification methodology for SP discrimination and cleavage site identification. The proposed method utilises a dual phase classification approach using SVM as a primary classifier to discriminate SP sequences from Non-SP. The methodology further employs NNs to predict the most suitable cleavage site candidates. In phase one, a SVM classification utilises hydrophobic propensities as a primary feature vector extraction using symmetric sliding window amino-acid sequence analysis for discrimination of SP and Non-SP. In phase two, a NN classification uses asymmetric sliding window sequence analysis for prediction of cleavage site identification. The proposed SVM-NN method was tested using Uni-Prot non-redundant datasets of eukaryotic and prokaryotic proteins with SP and Non-SP N-termini. Computer simulation results demonstrate an overall accuracy of 0.90 for SP and Non-SP discrimination based on Matthews Correlation Coefficient (MCC) tests using SVM. For SP cleavage site prediction, the overall accuracy is 91.5% based on cross-validation tests using the novel SVM-NN model. © 2013 Published by Elsevier Ltd.
Spontaneous Perforation of Common Bile Duct: A Rare Presentation of Gall Stones Disease
Directory of Open Access Journals (Sweden)
Duminda Subasinghe
2016-01-01
Full Text Available Background. Spontaneous perforation of the extrahepatic biliary system is a rare presentation of gall stones. Very few cases of bile duct perforation have been reported in adults. It is rarely suspected or correctly diagnosed preoperatively. Case Presentation. A 66-year-old female presented at the surgical emergency with 3 days’ history of severe upper abdominal pain with distension and repeated episodes of vomiting, as she had evidence of generalized peritonitis and underwent an exploratory laparotomy. A single 0.5 cm × 0.5 cm free perforation was present on the anterolateral surface of the common bile duct at the junction of cystic duct. A cholecystectomy and the CBD exploration were performed. Conclusion. Spontaneous perforation of the extrahepatic bile duct is a rare but important presentation of gall stones in adults. Therefore, awareness of the clinical presentation, expert ultrasound examination, and surgery are important aspects in the management.
Sequence specificity of DNA cleavage by Micrococcus luteus γ endonuclease
International Nuclear Information System (INIS)
Hentosh, P.; Henner, W.D.; Reynolds, R.J.
1985-01-01
DNA fragments of defined sequence have been used to determine the sites of cleavage by γ-endonuclease activity in extracts prepared from Micrococcus luteus. End-labeled DNA restriction fragments of pBR322 DNA that had been irradiated under nitrogen in the presence of potassium iodide or t-butanol were treated with M. luteus γ endonuclease and analyzed on irradiated DNA preferentially at the positions of cytosines and thymines. DNA cleavage occurred immediately to the 3' side of pyrimidines in irradiated DNA and resulted in fragments that terminate in a 5'-phosphoryl group. These studies indicate that both altered cytosines and thymines may be important DNA lesions requiring repair after exposure to γ radiation
DNA Cleavage Activity of Diazonium Salts: Chemical Nucleases
KIZIL, Murat
2014-01-01
4-Fenoldiazonium tetrafluoroborate and 4-benzoicaciddiazonium tetrafluoroborate was prepared and was shown to be an effective DNA cleavage agent in the presence of the 1-electron donor copper(II) chloride. Its mechanism involves the generation of the aryl radical cleaving DNA by hydrogen atom abstraction from deoxyribose sugar.
Németh, Balázs Csaba; Wartmann, Thomas; Halangk, Walter; Sahin-Tóth, Miklós
2013-08-16
Chymotrypsin C (CTRC) is a proteolytic regulator of trypsinogen autoactivation in humans. CTRC cleavage of the trypsinogen activation peptide stimulates autoactivation, whereas cleavage of the calcium binding loop promotes trypsinogen degradation. Trypsinogen mutations that alter these regulatory cleavages lead to increased intrapancreatic trypsinogen activation and cause hereditary pancreatitis. The aim of this study was to characterize the regulation of autoactivation of mouse trypsinogens by mouse Ctrc. We found that the mouse pancreas expresses four trypsinogen isoforms to high levels, T7, T8, T9, and T20. Only the T7 activation peptide was cleaved by mouse Ctrc, causing negligible stimulation of autoactivation. Surprisingly, mouse Ctrc poorly cleaved the calcium binding loop in all mouse trypsinogens. In contrast, mouse Ctrc readily cleaved the Phe-150-Gly-151 peptide bond in the autolysis loop of T8 and T9 and inhibited autoactivation. Mouse chymotrypsin B also cleaved the same peptide bond but was 7-fold slower. T7 was less sensitive to chymotryptic regulation, which involved slow cleavage of the Leu-149-Ser-150 peptide bond in the autolysis loop. Modeling indicated steric proximity of the autolysis loop and the activation peptide in trypsinogen, suggesting the cleaved autolysis loop may directly interfere with activation. We conclude that autoactivation of mouse trypsinogens is under the control of mouse Ctrc with some notable differences from the human situation. Thus, cleavage of the trypsinogen activation peptide or the calcium binding loop by Ctrc is unimportant. Instead, inhibition of autoactivation via cleavage of the autolysis loop is the dominant mechanism that can mitigate intrapancreatic trypsinogen activation.
Vodonik, S A; Gray, G R
1988-04-01
The fate of 4-linked D-glucopyranosyluronic residues under reductive-cleavage conditions was investigated by using the Klebsiella aerogenes type 54 strain A3 capsular polysaccharide. Treatment of the fully methylated polysaccharide with triethylsilane and trimethylsilyl trifluoromethanesulfonate in dichloromethane, followed by in situ acetylation, yielded 1,5-anhydro-2,3,4,6-tetra-O-methyl-D-glucitol, 3,4-di-O-acetyl-1,5-anhydro-2,6-di-O-methyl-D-glucitol, and 3-O-acetyl-1,5-anhydro-2,4-di-O-methyl-L-fucitol, as expected, but the expected product of reductive cleavage of the 4-linked D-glucopyranosyluronic residue, namely, methyl 3-O-acetyl-2,6-anhydro-4,5-di-O-methyl-L-gulonate, was not observed. Instead, methyl 2-O-acetyl-3,6-anhydro-4,5-di-O-methyl-L-gulonate (6) was identified as the sole product of reductive cleavage of the 4-linked D-glucopyranosyluronic residue. That compound 6 arose as a result of rearrangement during reductive cleavage rather than by reductive cleavage of a 5-linked D-glucofuranosyluronic residue, was established by reductive cleavage of the fully methylated polysaccharide following reduction of its ester groups with either lithium aluminum hydride or lithium aluminum deuteride. The products of the latter reductive cleavage were the same as before, except for the absence of 6 and the presence of 4,6-di-O-acetyl-1,5-anhydro-2,3-di-O-methyl-D-glucitol, or its 6,6-dideuterio isomer. Although the reductive-cleavage technique is suitable for the direct analysis of polysaccharides containing 4-linked D-glucopyranosyluronic residues, it does not establish whether the uronic residue is a 4-linked pyranoside or a 5-linked furanoside. The expected product is, however, derived from the 4-linked D-glucopyranosyluronic residue after sequential methylation, reduction of its ester group and reductive cleavage.
Bekisz, Marek; Shendye, Ninad; Raciborska, Ida; Wróbel, Andrzej; Waleszczyk, Wioletta J.
2017-08-01
The process of learning induces plastic changes in neuronal network of the brain. Our earlier studies on mice showed that classical conditioning in which monocular visual stimulation was paired with an electric shock to the tail enhanced GABA immunoreactivity within layer 4 of the monocular part of the primary visual cortex (V1), contralaterally to the stimulated eye. In the present experiment we investigated whether the same classical conditioning paradigm induces changes of neuronal excitability in this cortical area. Two experimental groups were used: mice that underwent 7-day visual classical conditioning and controls. Patch-clamp whole-cell recordings were performed from ex vivo slices of mouse V1. The slices were perfused with the modified artificial cerebrospinal fluid, the composition of which better mimics the brain interstitial fluid in situ and induces spontaneous activity. The neuronal excitability was characterized by measuring the frequency of spontaneous action potentials. We found that layer 4 star pyramidal cells located in the monocular representation of the "trained" eye in V1 had lower frequency of spontaneous activity in comparison with neurons from the same cortical region of control animals. Weaker spontaneous firing indicates decreased general excitability of star pyramidal neurons within layer 4 of the monocular representation of the "trained" eye in V1. Such effect could result from enhanced inhibitory processes accompanying learning in this cortical area.
Programmable RNA recognition and cleavage by CRISPR/Cas9.
O'Connell, Mitchell R; Oakes, Benjamin L; Sternberg, Samuel H; East-Seletsky, Alexandra; Kaplan, Matias; Doudna, Jennifer A
2014-12-11
The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA-DNA complementarity to identify target sites for sequence-specific double-stranded DNA (dsDNA) cleavage. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, known as the protospacer adjacent motif (PAM), next to and on the strand opposite the twenty-nucleotide target site in dsDNA. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in a large range of prokaryotic and eukaryotic cell types, and in whole organisms, but it has been thought to be incapable of targeting RNA. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalysed DNA cleavage. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous messenger RNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable transcript recognition without the need for tags.
International Nuclear Information System (INIS)
Pearson, Margot N.; Rohrmann, George F.
2004-01-01
The predicted Env protein of insect retroviruses (errantiviruses) is related to the envelope fusion protein of a major division of the Baculoviridae. The highest degree of homology is found in a region that contains a furin cleavage site in the baculovirus proteins and an adjacent sequence that has the properties of a fusion peptide. In this investigation, the homologous region in the Env protein of the gypsy retrovirus of Drosophila melanogaster (DmegypV) was investigated. Alteration of the predicted DmegypV Env proteinase cleavage site from RIAR to AIAR significantly reduced cleavage of Env in both Spodoptera frugiperda (Sf-9) and D. melanogaster (S2) cell lines. When the predicted DmegypV Env cleavage site RIAR was substituted for the cleavage sequence RRKR in the Lymantria dispar nucleopolyhedrovirus fusion protein (LD130) sequence, cleavage of the hybrid LD130 molecules still occurred, although at a reduced level. The conserved 21-amino acid sequence just downstream of the cleavage site, which is thought to be the fusion peptide in LD130, was also characterized. When this sequence from DmegypV Env was substituted for the homologous sequence in LD130, cleavage still occurred, but no fusion was observed in either cell type. In addition, although a DmegypV-Env-green fluorescent protein construct localized to cell membranes, no cell fusion was observed
Spontaneous rapid reduction of a large acute subdural hematoma.
Lee, Chul-Hee; Kang, Dong Ho; Hwang, Soo Hyun; Park, In Sung; Jung, Jin-Myung; Han, Jong Woo
2009-12-01
The majority of acute post-traumatic subdural hematomas (ASDH) require urgent surgical evacuation. Spontaneous resolution of ASDH has been reported in some cases. We report here on a case of a patient with a large amount of ASDH that was rapidly reduced. A 61-yr-old man was found unconscious following a high speed motor vehicle accident. On initial examination, his Glasgow Coma Score scale was 4/15. His pupils were fully dilated and non-reactive to bright light. Brain computed tomography (CT) showed a massive right-sided ASDH. The decision was made to treat him conservatively because of his poor clinical condition. Another brain CT approximately 14 hr after the initial scan demonstrated a remarkable reduction of the previous ASDH and there was the new appearance of high density in the subdural space adjacent to the falx and the tentorium. Thirty days after his admission, brain CT revealed chronic SDH and the patient underwent surgery. The patient is currently able to obey simple commands. In conclusion, spontaneous rapid resolution/reduction of ASDH may occur in some patients. The mechanisms are most likely the result of dilution by cerebrospinal fluid and the redistribution of hematoma especially in patients with brain atrophy.
Surgical treatment for elderly patients with secondary spontaneous pneumothorax.
Igai, Hitoshi; Kamiyoshihara, Mitsuhiro; Ibe, Takashi; Kawatani, Natsuko; Shimizu, Kimihiro
2016-05-01
Our objective was to evaluate the validity of surgery for secondary spontaneous pneumothorax (SSP) by comparison with other treatments or with perioperative results for primary spontaneous pneumothorax (PSP). Between January 2009 and March 2015, 144 patients with SSP, aged 60 years or over, were treated in our institution. We reviewed the patients' characteristics, perioperative results, and relapse rate. Treatment to arrest air-leakage included surgery (n = 79), drainage only (n = 30), and pleurodesis (n = 35), and the pneumothorax relapse rate or mortality before discharge was compared for each. Additionally, we compared the perioperative results or relapse rate between SSP (n = 70) and PSP (n = 70) in patients who underwent 3-port thoracoscopic surgery. There was a significant difference in the relapse rate between the surgery and non-surgery groups (5.3 vs. 27.4 %, p = 0.0006). However, no significant difference in mortality before discharge was determined (p = 0.66). Significant differences were identified between the SSP and PSP groups for operation time, duration of chest drainage, and the length of postoperative hospitalization, and the postoperative morbidity were greater in the SSP group (p pneumothorax relapse, compared with drainage or pleurodesis, and is feasible if the appropriate perioperative management is performed.
Drosha regulates gene expression independently of RNA cleavage function
DEFF Research Database (Denmark)
Gromak, Natalia; Dienstbier, Martin; Macias, Sara
2013-01-01
Drosha is the main RNase III-like enzyme involved in the process of microRNA (miRNA) biogenesis in the nucleus. Using whole-genome ChIP-on-chip analysis, we demonstrate that, in addition to miRNA sequences, Drosha specifically binds promoter-proximal regions of many human genes in a transcription......-dependent manner. This binding is not associated with miRNA production or RNA cleavage. Drosha knockdown in HeLa cells downregulated nascent gene transcription, resulting in a reduction of polyadenylated mRNA produced from these gene regions. Furthermore, we show that this function of Drosha is dependent on its N......-terminal protein-interaction domain, which associates with the RNA-binding protein CBP80 and RNA Polymerase II. Consequently, we uncover a previously unsuspected RNA cleavage-independent function of Drosha in the regulation of human gene expression....
Polycystin-1 Cleavage and the Regulation of Transcriptional Pathways
Merrick, David; Bertuccio, Claudia A.; Chapin, Hannah C.; Lal, Mark; Chauvet, Veronique; Caplan, Michael J.
2013-01-01
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end stage renal disease, affecting ~1 in 1,000 people. The disease is characterized by the development of numerous large fluid filled renal cysts over the course of decades. These cysts compress the surrounding renal parenchyma and impair its function. Mutations in two genes are responsible for ADPKD. The protein products of both of these genes, polycystin-1 and polycystin-2, localize to the primary cilium and participate in a wide variety of signaling pathways. Polycystin-1 undergoes several proteolytic cleavages that produce fragments that manifest biological activities. Recent results suggest that the production of polycystin-1 cleavage fragments is necessary and sufficient to account for at least some, although certainly not all, of the physiological functions of the parent protein. PMID:23824180
Cell-surface acceleration of urokinase-catalyzed receptor cleavage
DEFF Research Database (Denmark)
Høyer-Hansen, G; Ploug, M; Behrendt, N
1997-01-01
by a prior incubation of the cells with uPA inactivated by diisopropyl fluorophosphate, demonstrating a requirement for specific receptor binding of the active uPA to obtain the high-efficiency cleavage of cell-bound uPAR. Furthermore, amino-terminal sequence analysis revealed that uPAR(2+3), purified from U...
Fetal hemoglobin is much less prone to DNA cleavage compared to the adult protein
Directory of Open Access Journals (Sweden)
Sandeep Chakane
2017-08-01
Full Text Available Hemoglobin (Hb is well protected inside the red blood cells (RBCs. Upon hemolysis and when free in circulation, Hb can be involved in a range of radical generating reactions and may thereby attack several different biomolecules. In this study, we have examined the potential damaging effects of cell-free Hb on plasmid DNA (pDNA. Hb induced cleavage of supercoiled pDNA (sc pDNA which was proportional to the concentration of Hb applied. Almost 70% of sc pDNA was converted to open circular or linear DNA using 10 µM of Hb in 12 h. Hb can be present in several different forms. The oxy (HbO2 and met forms are most reactive, while the carboxy-protein shows only low hydrolytic activity. Hemoglobin A (HbA could easily induce complete pDNA cleavage while fetal hemoglobin (HbF was three-fold less reactive. By inserting, a redox active cysteine residue on the surface of the alpha chain of HbF by site-directed mutagenesis, the DNA cleavage reaction was enhanced by 82%. Reactive oxygen species were not directly involved in the reaction since addition of superoxide dismutase and catalase did not prevent pDNA cleavage. The reactivity of Hb with pDNA can rather be associated with the formation of protein based radicals. Keywords: Adult hemoglobin, Fetal hemoglobin, Supercoiled plasmid DNA, DNA cleavage, Cysteine, Protein radicals
A Case Report of Ruptured Spontaneous Heterotopic Pregnancy
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F Seidoshohadaei
2008-04-01
Full Text Available ABSTRACT: Introduction & Objective: Heterotopic pregnancy refers to the simultaneous occurrence of pregnancy intrauterine and outside of uterine corpus. It is most often manifested in women who have undergone artificial reproductive technology (ART but rarely occurs spontaneously. Heterotopic pregnancy still remains as a diagnostic and therapeutic challenge to practitioners. In this situation physicians should have high suspicion for diagnosis and intrauterine pregnancy protection. This study reported a case of ruptured spontaneous heterotopic pregnancy. Case: A 32 year-old woman with abdominal pain, nausea, vomiting and hypovolumic shock in 1386 referred to emergency department in Sanandaj hospital. She reported one previous cesarean section. On examination, the patient's abdomen was distended. She had generalized tenderness and rebound tenderness in abdomen. The ultrasonographic examination revealed large amount of fluid in pelvic and abdominal cavity with a large hematoma in right adnex but there was intrauterine pregnancy at 7 weeks with normal fetal heart activity. She underwent laparotomy for heterotopic pregnancy and ruptured tube with tubal pregnancy removed. Intrauterine pregnancy continued without problem and led to birth of a healthy female neonate. Conclusion: Physicians should be quite cautious of heterotopic pregnancy in woman at reproductive age. Any abnormality on physical examination or ultrasonography of a patient with intrauterine pregnancy and abdominal pain should heighten the clinician's suspicion for heterotopic pregnancy
Abyssal fiction: common shares, colonial cleavages
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Alexandre Montaury
2016-12-01
Full Text Available The paper aims to develop a reflection on the interaction between the legacies of colonialism and traditional symbolic and cultural practices in African Portuguese-speaking spaces. From a preliminary analysis of fictional texts of wide circulation in Brazil, aims to examine the cleavages, or “abyssal lines” that constitute experiences printed in the daily life of the former Portuguese colony of Cape Verde, Mozambique and Angola.---DOI: http://dx.doi.org/10.21881/abriluff.2016n17a378
When Is the Optimal Timing of the Surgical Treatment for Secondary Spontaneous Pneumothorax?
Jeon, Hyun Woo; Kim, Young-Du; Choi, Si Young; Park, Jae Kil
2017-01-01
Objectives The definition of spontaneous pneumothorax is accumulation of air in the pleural space, resulting in dyspnea or chest pain. Unlike primary spontaneous pneumothorax, secondary pneumothorax can be a life-threatening condition and spontaneous healing rate is uncommon. Although surgery is the most effective treatment modality for pneumothorax, surgical management and timing is difficult where there is underlying lung disease and/or medical comorbidities. Prolonged air leakage increases the morbidity and mortality in thoracic surgery. We hypothesized that duration of air leakage before operation may lead to increase in complications. Methods This study is a retrospective review of 155 consecutive patients with air leakage who underwent bullectomy for secondary spontaneous pneumothorax from January 2005 to July 2013. The patients were divided according to the duration of preoperative air leakage. The patients were followed-up until the time of last visit or death. Postoperative morbidity and mortality were assessed and the risk factors for complications were analyzed. Results The median age was 65 years (range, 52-88) with male predominance (96.13%). The median duration of preoperative air leakage was 6 days (range, 1-30). The median surgery time was 90 minutes (range, 25-300) and median hospital stay after operation was 7 days (range, 3-75). Postoperative complications occurred in 38 patients (24.52%) and postoperative recurrence was shown to have occurred in 8 patients (5.16%). With multivariate analysis, risk factors for postoperative complications were: underlying interstitial lung disease and air leakage > 5 days before operation. Conclusion Persistent air leakage was a major surgical indication for pneumothorax. Early surgical treatment reduced postoperative complications for secondary spontaneous pneumothorax. Georg Thieme Verlag KG Stuttgart · New York.
Wang, Chao; Shen, Zhujing; Huang, Peiyu; Qian, Wei; Yu, Xinfeng; Sun, Jianzhong; Yu, Hualiang; Yang, Yihong; Zhang, Minming
2017-06-01
Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain function. However, little is known about the associations between the local spontaneous brain activity and smoking cessation treatment outcomes. In the present analysis, we aimed to evaluate whether the local features of spontaneous brain activity prior to the target quit date was associated with the smoking cessation outcomes. All the participants underwent magnetic resonance imaging scans and smoking-related behavioral assessments. After a 12-week treatment with varenicline, 23 smokers succeeded in quitting smoking and 32 failed. Smokers underwent functional magnetic resonance imaging (fMRI) scanning prior to an open label smoking cessation treatment trial. Regional homogeneity (ReHo) was used to measure spontaneous brain activity, and whole-brain voxel-wise comparisons of ReHo were performed to detect brain regions with altered spontaneous brain activity between relapser and quitter groups. After controlling for potentially confounding factors including years of education, years smoked, cigarettes smoked per day and FTND score as covariates, compared to quitters, relapsers displayed significantly decreased ReHo in bilateral posterior cingulate cortex (PCC), as well as increased ReHo in left superior temporal gyrus (STG). These preliminary results suggest that regional brain function variables may be promising predictors of smoking relapse. This study provided novel insights into the neurobiological mechanisms underlying smoking relapse. A deeper understanding of the neurobiological mechanisms associated with relapse may result in novel pharmacological and behavioral interventions.
Directory of Open Access Journals (Sweden)
Chenyu Zhang
2009-05-01
Full Text Available Bacterial pathogens employ a variety of survival strategies when they invade eukaryotic cells. The amoeba Dictyostelium discoideum is used as a model host to study the pathogenic mechanisms that Legionella pneumophila, the causative agent of Legionnaire's disease, uses to kill eukaryotic cells. Here we show that the infection of D. discoideum by L. pneumophila results in a decrease in mitochondrial messenger RNAs, beginning more than 8 hours prior to detectable host cell death. These changes can be mimicked by hydrogen peroxide treatment, but not by other cytotoxic agents. The mitochondrial large subunit ribosomal RNA (LSU rRNA is also cleaved at three specific sites during the course of infection. Two LSU rRNA fragments appear first, followed by smaller fragments produced by additional cleavage events. The initial LSU rRNA cleavage site is predicted to be on the surface of the large subunit of the mitochondrial ribosome, while two secondary sites map to the predicted interface with the small subunit. No LSU rRNA cleavage was observed after exposure of D. discoideum to hydrogen peroxide, or other cytotoxic chemicals that kill cells in a variety of ways. Functional L. pneumophila type II and type IV secretion systems are required for the cleavage, establishing a correlation between the pathogenesis of L. pneumophila and D. discoideum LSU rRNA destruction. LSU rRNA cleavage was not observed in L. pneumophila infections of Acanthamoeba castellanii or human U937 cells, suggesting that L. pneumophila uses distinct mechanisms to interrupt metabolism in different hosts. Thus, L. pneumophila infection of D. discoideum results in dramatic decrease of mitochondrial RNAs, and in the specific cleavage of mitochondrial rRNA. The predicted location of the cleavage sites on the mitochondrial ribosome suggests that rRNA destruction is initiated by a specific sequence of events. These findings suggest that L. pneumophila specifically disrupts mitochondrial
Ford, M.; Ferguson, C.C.
1985-01-01
In south-west Ireland, hydrothermally formed arsenopyrite crystals in a Devonian mudstone have responded to Variscan deformation by brittle extension fracture and fragment separation. The interfragment gaps and terminal extension zones of each crystal are infilled with fibrous quartz. Stretches within the cleavage plane have been calculated by the various methods available, most of which can be modified to incorporate terminal extension zones. The Strain Reversal Method is the most accurate currently available but still gives a minimum estimate of the overall strain. The more direct Hossain method, which gives only slightly lower estimates with this data, is more practical for field use. A strain ellipse can be estimated from each crystal rosette composed of three laths (assuming the original interlimb angles were all 60??) and, because actual rather than relative stretches are estimated, this provides a lower bound to the area increase in the plane of cleavage. Based on the average of our calculated strain ellipses this area increase is at least 114% and implies an average shortening across the cleavage of at least 53%. However, several lines of evidence suggest that the cleavage deformation was more intense and more oblate than that calculated, and we argue that a 300% area increase in the cleavage plane and 75% shortening across the cleavage are more realistic estimates of the true strain. Furthermore, the along-strike elongation indicated is at least 80%, which may be regionally significant. Estimates of orogenic contraction derived from balanced section construction should therefore take into account the possibility of a substantial strike elongation, and tectonic models that can accommodate such elongations need to be developed. ?? 1985.
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Olivier Barré
Full Text Available Type II transmembrane serine proteases (TTSPs are a family of cell membrane tethered serine proteases with unclear roles as their cleavage site specificities and substrate degradomes have not been fully elucidated. Indeed just 52 cleavage sites are annotated in MEROPS, the database of proteases, their substrates and inhibitors.To profile the active site specificities of the TTSPs, we applied Proteomic Identification of protease Cleavage Sites (PICS. Human proteome-derived database searchable peptide libraries were assayed with six human TTSPs (matriptase, matriptase-2, matriptase-3, HAT, DESC and hepsin to simultaneously determine sequence preferences on the N-terminal non-prime (P and C-terminal prime (P' sides of the scissile bond. Prime-side cleavage products were isolated following biotinylation and identified by tandem mass spectrometry. The corresponding non-prime side sequences were derived from human proteome databases using bioinformatics. Sequencing of 2,405 individual cleaved peptides allowed for the development of the family consensus protease cleavage site specificity revealing a strong specificity for arginine in the P1 position and surprisingly a lysine in P1' position. TTSP cleavage between R↓K was confirmed using synthetic peptides. By parsing through known substrates and known structures of TTSP catalytic domains, and by modeling the remainder, structural explanations for this strong specificity were derived.Degradomics analysis of 2,405 cleavage sites revealed a similar and characteristic TTSP family specificity at the P1 and P1' positions for arginine and lysine in unfolded peptides. The prime side is important for cleavage specificity, thus making these proteases unusual within the tryptic-enzyme class that generally has overriding non-prime side specificity.
Change in radiosensitivity of sea-urchin eggs during early cleavage stages
International Nuclear Information System (INIS)
Nakamura, I.
1977-01-01
When sea-urchin eggs were irradiated with 137 Cs γ-rays, their radiosensitivity, expressed by the percentage which formed pluteus larvae, fluctuated during the early cleavage cycle. Split-dose irradiations were made both in the sensitive and resistant phases. For eggs in the sensitive phase, the effect of the first exposure of 500 rad was not diminished during the interval before the second exposure. Eggs irradiated in the resistant phase were only slightly damaged. Results implied that fluctuations in radiosensitivity of sea-urchin eggs were caused mainly by different degrees of non-repairable damage in each phase of cleavage rather than by different recovery abilities. (author)
Leroy, Catherine; Belkina, Natalya V.; Long, Thavy; Deruy, Emeric; Dissous, Colette; Shaw, Stephen; Tulasne, David
2016-01-01
The lymphocyte-oriented kinase (LOK), also called serine threonine kinase 10 (STK10), is synthesized mainly in lymphocytes. It is involved in lymphocyte migration and polarization and can phosphorylate ezrin, radixin, and moesin (the ERM proteins). In a T lymphocyte cell line and in purified human lymphocytes, we found LOK to be cleaved by caspases during apoptosis. The first cleavage occurs at aspartic residue 332, located between the kinase domain and the coiled-coil regulation domain. This cleavage generates an N-terminal fragment, p50 N-LOK, containing the kinase domain and a C-terminal fragment, which is further cleaved during apoptosis. Although these cleavages preserve the entire kinase domain, p50 N-LOK displays no kinase activity. In apoptotic lymphocytes, caspase cleavages of LOK are concomitant with a decrease in ERM phosphorylation. When non-apoptotic lymphocytes from mice with homozygous and heterozygous LOK knockout were compared, the latter showed a higher level of ERM phosphorylation, but when apoptosis was induced, LOK−/− and LOK+/− lymphocytes showed the same low level, confirming in vivo that LOK-induced ERM phosphorylation is prevented during lymphocyte apoptosis. Our results demonstrate that cleavage of LOK during apoptosis abolishes its kinase activity, causing a decrease in ERM phosphorylation, crucial to the role of the ERM proteins in linking the plasma membrane to actin filaments. PMID:26945071
Leroy, Catherine; Belkina, Natalya V; Long, Thavy; Deruy, Emeric; Dissous, Colette; Shaw, Stephen; Tulasne, David
2016-05-06
The lymphocyte-oriented kinase (LOK), also called serine threonine kinase 10 (STK10), is synthesized mainly in lymphocytes. It is involved in lymphocyte migration and polarization and can phosphorylate ezrin, radixin, and moesin (the ERM proteins). In a T lymphocyte cell line and in purified human lymphocytes, we found LOK to be cleaved by caspases during apoptosis. The first cleavage occurs at aspartic residue 332, located between the kinase domain and the coiled-coil regulation domain. This cleavage generates an N-terminal fragment, p50 N-LOK, containing the kinase domain and a C-terminal fragment, which is further cleaved during apoptosis. Although these cleavages preserve the entire kinase domain, p50 N-LOK displays no kinase activity. In apoptotic lymphocytes, caspase cleavages of LOK are concomitant with a decrease in ERM phosphorylation. When non-apoptotic lymphocytes from mice with homozygous and heterozygous LOK knockout were compared, the latter showed a higher level of ERM phosphorylation, but when apoptosis was induced, LOK(-/-) and LOK(+/-) lymphocytes showed the same low level, confirming in vivo that LOK-induced ERM phosphorylation is prevented during lymphocyte apoptosis. Our results demonstrate that cleavage of LOK during apoptosis abolishes its kinase activity, causing a decrease in ERM phosphorylation, crucial to the role of the ERM proteins in linking the plasma membrane to actin filaments. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Spontaneous external gallbladder perforation
International Nuclear Information System (INIS)
Noeldge, G.; Wimmer, B.; Kirchner, R.
1981-01-01
Spontaneous perforation of the gallbladder is one complication of cholelithiasis. There is a greater occurence of free perforation in the peritoneal cavity with bilary pertonitis, followed by the perforation into the stomach, small intestine and colon. A single case of the nowadays rare spontaneous perforation in and through the abdominal wall will be reported. Spontaneous gallbladder perforation appears nearly asymptomatic in its clinical course because of absent biliary peritonitis. (orig.) [de
Caspase-2 cleavage of tau reversibly impairs memory.
Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H
2016-11-01
In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.
Kobayashi, Maki; Aida, Masatoshi; Nagaoka, Hitoshi; Begum, Nasim A; Kitawaki, Yoko; Nakata, Mikiyo; Stanlie, Andre; Doi, Tomomitsu; Kato, Lucia; Okazaki, Il-mi; Shinkura, Reiko; Muramatsu, Masamichi; Kinoshita, Kazuo; Honjo, Tasuku
2009-12-29
To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5' to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) controls the supercoiling of DNA by nicking, rotating, and religating one strand of DNA. Curiously, Top1 reduction or AID overexpression causes the genomic instability. Here, we report that the inactivation of Top1 by its specific inhibitor camptothecin drastically blocked both the S region cleavage and CSR, indicating that Top1 is responsible for the S region cleavage in CSR. Surprisingly, AID expression suppressed Top1 mRNA translation and reduced its protein level. In addition, the decrease in the Top1 protein by RNA-mediated knockdown augmented the AID-dependent S region cleavage, as well as CSR. Furthermore, Top1 reduction altered DNA structure of the Smu region. Taken together, AID-induced Top1 reduction alters S region DNA structure probably to non-B form, on which Top1 can introduce nicks but cannot religate, resulting in S region cleavage.
Carotenoid-cleavage activities of crude enzymes from Pandanous amryllifolius.
Ningrum, Andriati; Schreiner, Matthias
2014-11-01
Carotenoid degradation products, known as norisoprenoids, are aroma-impact compounds in several plants. Pandan wangi is a common name of the shrub Pandanus amaryllifolius. The genus name 'Pandanus' is derived from the Indonesian name of the tree, pandan. In Indonesia, the leaves from the plant are used for several purposes, e.g., as natural colorants and flavor, and as traditional treatments. The aim of this study was to determine the cleavage of β-carotene and β-apo-8'-carotenal by carotenoid-cleavage enzymes isolated from pandan leaves, to investigate dependencies of the enzymatic activities on temperature and pH, to determine the enzymatic reaction products by using Headspace Solid Phase Microextraction Gas Chromatography/Mass Spectrophotometry (HS-SPME GC/MS), and to investigate the influence of heat treatment and addition of crude enzyme on formation of norisoprenoids. Crude enzymes from pandan leaves showed higher activity against β-carotene than β-apo-8'-carotenal. The optimum temperature of crude enzymes was 70°, while the optimum pH value was 6. We identified β-ionone as the major volatile reaction product from the incubations of two different carotenoid substrates, β-carotene and β-apo-8'-carotenal. Several treatments, e.g., heat treatment and addition of crude enzymes in pandan leaves contributed to the norisoprenoid content. Our findings revealed that the crude enzymes from pandan leaves with carotenoid-cleavage activity might provide a potential application, especially for biocatalysis, in natural-flavor industry. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.
Tesco, Giuseppina; Koh, Young Ho; Tanzi, Rudolph E
2003-11-14
The amyloid precursor protein (APP) undergoes "alternative" proteolysis mediated by caspases. Three major caspase recognition sites have been identified in the APP, i.e. one at the C terminus (Asp720) and two at the N terminus (Asp197 and Asp219). Caspase cleavage at Asp720 has been suggested as leading to increased production of Abeta. Thus, we set out to determine which putative caspase sites in APP, if any, are cleaved in Chinese hamster ovary cell lines concurrently with the increased Abeta production that occurs during apoptosis. We found that cleavage at Asp720 occurred concurrently with caspase 3 activation and the increased production of total secreted Abeta and Abeta1-42 in association with staurosporine- and etoposide-induced apoptosis. To investigate the contribution of caspase cleavage of APP to Abeta generation, we expressed an APP mutant truncated at Asp720 that mimics APP caspase cleavage at the C-terminal site. This did not increase Abeta generation but, in contrast, dramatically decreased Abeta production in Chinese hamster ovary cells. Furthermore, the ablation of caspase-dependent cleavage at Asp720, Asp197, and Asp219 (by site-directed mutagenesis) did not prevent enhanced Abeta production following etoposide-induced apoptosis. These findings indicate that the enhanced Abeta generation associated with apoptosis does not require cleavage of APP at its C-terminal (Asp720) and/or N-terminal caspase sites.
Hyperbaric oxygen therapy in spontaneous brain abscess patients
DEFF Research Database (Denmark)
Bartek, Jiri; Jakola, Asgeir S; Skyrman, Simon
2016-01-01
BACKGROUND: There is a need to improve outcome in patients with brain abscesses and hyperbaric oxygen therapy (HBOT) is a promising treatment modality. The objective of this study was to evaluate HBOT in the treatment of intracranial abscesses. METHOD: This population-based, comparative cohort...... study included 40 consecutive adult patients with spontaneous brain abscess treated surgically between January 2003 and May 2014 at our institution. Twenty patients received standard therapy with surgery and antibiotics (non-HBOT group), while the remaining 20 patients also received adjuvant HBOT (HBOT...... group). RESULTS: Resolution of brain abscesses and infection was seen in all patients. Two patients had reoperations after HBOT initiation (10 %), while nine patients (45 %) in the non-HBOT group underwent reoperations (p = 0.03). Of the 26 patients who did not receive HBOT after the first surgery, 15...
Risk factors for cesarean delivery in primigravida during spontaneous labor
International Nuclear Information System (INIS)
Hc, C.; Yahya, M.S.; Mooi, C.S.
2015-01-01
Objective: To identify the risk factors for cesarean delivery among primigravida at Hospital Serdang. Methodology: This was a case control study which involved total 260 of 130 primigravida patients that underwent cesarean section (cases) and 130 primigravida patients that underwent vaginal delivery (control) at obstetrics and gynaecology department of Hospital Serdang, Malaysia from January until June 2013. A standardized proforma was used to collect the data of each primigravida patient presenting in spontaneous labour at term with singleton pregnancy with either caesarean or vaginal delivery. Results: Majority of the cases were Malaysian (86.9%) and mostly were from Malay ethnic group (75.4%). In multivariate logistic regression analysis, presence of hypertension status (odds ratio (OR) 5.7, 95% CI; 1.56-20.84) and gestational age less than 40 weeks (OR 2.60, 95% CI 1.34-5.02), fetal weight more than 3000 gm (OR 1.8, 95% CI 1.1-2.95), were associated with higher odds of cesarean delivery. Conclusion: Primigravida with presence of hypertension, having gestational age less than 40 weeks and heavier fetus were associated with higher odds of cesarean delivery. (author)
Definition of spontaneous reconnection
International Nuclear Information System (INIS)
Schindler, K.
1984-01-01
The author discusses his view of driven versus spontaneous. There is a close link between ''spontaneous'' and ''instability.'' One of the prominent examples for instability is the thermal convection instability. Just to remind you, if you heat a fluid layer from below, it takes a certain Rayleigh number to make it unstable. Beyond the onset point you find qualitatively new features. That is called ''spontaneous,'' and this is a bit more than semantics. It's a new qualitative property that appears and it is spontaneous although we have an energy flux through the system. It's a misconception, to call this ''driven'' pointing at the energy flux through it. Of course, the convection would not exist without this energy flux. But what makes it ''spontaneous'' is that without any particular external signal, a new qualitative feature appears. And this is what is called an ''instability'' and ''spontaneous.'' From these considerations the author got a little reassured of what distinction should be made in the field of the magnetosphere. If we have a smooth energy transport into the magnetosphere and suddenly we have this qualitatively new feature (change of B-topology) coming up; then, using this terminology we don't have a choice other than calling this spontaneous or unstable, if you like. If we ''tell'' the system where it should make its neutral line and where it should make its plasmoids, then, it is driven. And this provides a very clear-cut observational distinction. The author emphasizes the difference he sees is a qualitative difference, not only a quantitative one
SOCIAL CLEAVAGES IN THE AMERICAN SOCIETY AS A FACTOR OF 2016 PRESIDENTIAL CAMPAIGN
Directory of Open Access Journals (Sweden)
P. S. Kanevskiy
2017-01-01
Full Text Available Current article is dedicated to analysis of social cleavages in the American elections and the ways they influenced on presidential election in 2016. Originally developed by S. Rokkan and S.M. Lipset, social cleavages became a classic theme for contemporary political sociology. However, despite the fact that the theory has been developing primarily by Americans, it has been rarely used to analyze electoral system in the USA. Traditionally it’s been aimed at European and developing countries where electoral fragmentation is seen more clearly. But recent changes in the American society and the political system demonstrate the emergence of social cleavages that had not been inherent before. The article shows how American electoral space transformed since the 1980s and how it became more fragmented under the influence of social, economic and ideological factors. Elections in 2016 became a watershed for social cleavages that accumulated through time and aggravated even more considering internal crises in the Democratic and more so in the Republican parties. Donald Trump’s victory is an impersonation of the American party system crisis and of the mainstream politicians’ inability to find proper explanation of the changing electorate. Author shows that American society today is polarized even more than many European countries while group identification determines vectors of political change.
Electrostatic instability of some jellium model lattices of high symmetry to their plane cleavage
International Nuclear Information System (INIS)
Kholopov, Eugene V; Kalashnikova, Vita V
2007-01-01
Jellium model structures composed of regular lattices of equal point charges immersed in a neutralizing uniform background are considered. The symmetric description eliminating the effect of potentials without transverse structural modulation is extended to the events specified by alternating distances between point-charge planes. Based on modulated potentials typical of plane-wise lattice summation, the energy of interaction between two semi-infinite hemi-crystals divided by a plane is obtained for cubic and hexagonal crystals, where all the characteristic orientations of the cleavage plane are taken into account. We found that simple cubic and hexagonal lattices, as well as cubic and hexagonal diamond structures, turn out to be unstable for certain cleavage planes. The most favourable cleavage planes for the bcc, fcc and hcp structures are also emphasized
Spontaneous haemorrhage and rupture of third ventricular colloid cyst.
LENUS (Irish Health Repository)
Ogbodo, Elisha
2012-01-01
Acute bleeding within a colloid cyst of the third ventricle represents a rare event causing sudden increase in the cyst volume that may lead to acute hydrocephalus and rapid neurological deterioration. We report a case of spontaneous rupture of haemorrhagic third ventricular colloid cyst and its management. A 77-year-old ex-smoker presented with unsteady gait, incontinence and gradually worsening confusion over a 3-week period. Brain CT scan findings were highly suggestive of a third ventricular colloid cyst with intraventricular rupture. He underwent cyst excision and histopathology, which confirmed the radiological diagnosis with evidence of haemorrhage within the cyst. A ventriculo peritoneal shunt was performed for delayed hydrocephalus. Surgical management of these patients must include emergency ventriculostomy followed by prompt surgical removal of the haemorrhagic cyst.
International Nuclear Information System (INIS)
Sorensen, B.S.; Jensen, P.S.; Andersen, A.H.; Christiansen, K.; Alsner, J.; Thomsen, B.; Westergaard, O.
1990-01-01
The effect of the 2-nitroimidazole Ro 15-0216 upon the interaction between purified topoisomerase II and its DNA substrate was investigated. The cleavage reaction in the presence of this DNA-nonintercalative drug took place with the hallmarks of a regular topoisomerase II mediated cleavage reaction, including covalent linkage of the enzyme to the cleaved DNA. In the presence of Ro 15-0216, topoisomerase II mediated cleavage was extensively stimulated at major cleavage sites of which only one existed in the 4363 base pair pBR322 molecule. The sites stimulated by Ro 15-0216 shared a pronounced sequence homology, indicating that a specific nucleotide sequence is crucial for the action of this drug. The effect of Ro 15-0216 thus differs from that of the clinically important topoisomerase II targeted agents such as mAMSA, VM26, and VP16, which enhance enzyme-mediated cleavage at a multiple number of sites. In contrast to the previous described drugs, Ro 15-0216 did not exert any inhibitory effect on the enzyme's catalytic activity. This observation might be ascribed to the low stability of the cleavage complexes formed in the presence of Ro 15-0216 as compared to the stability of the ones formed in the presence of traditional topoisomerase II targeted drugs
Kinetics of phycocyanobilin cleavage from C-phycocyanin by methanolysis
DEFF Research Database (Denmark)
Malwade, Chandrakant Ramkrishna; Roda Serrat, Maria Cinta; Christensen, Knud Villy
2016-01-01
Phycocyanobilin (PCB) is an important linear tetrapyrrolic molecule for food as well as pharmaceutical industry. It is obtained from blue-green algae, where it is attached covalently to phycobiliproteins (C-PC and APC) present in the light harvesting complexes. In this work, cleavage of PCB from...
Hilbert, Brendan J.; Hayes, Janelle A.; Stone, Nicholas P.; Xu, Rui-Gang
2017-01-01
Abstract Many viruses use a powerful terminase motor to pump their genome inside an empty procapsid shell during virus maturation. The large terminase (TerL) protein contains both enzymatic activities necessary for packaging in such viruses: the adenosine triphosphatase (ATPase) that powers DNA translocation and an endonuclease that cleaves the concatemeric genome at both initiation and completion of genome packaging. However, how TerL binds DNA during translocation and cleavage remains mysterious. Here we investigate DNA binding and cleavage using TerL from the thermophilic phage P74-26. We report the structure of the P74-26 TerL nuclease domain, which allows us to model DNA binding in the nuclease active site. We screened a large panel of TerL variants for defects in binding and DNA cleavage, revealing that the ATPase domain is the primary site for DNA binding, and is required for nuclease activity. The nuclease domain is dispensable for DNA binding but residues lining the active site guide DNA for cleavage. Kinetic analysis of DNA cleavage suggests flexible tethering of the nuclease domains during DNA cleavage. We propose that interactions with the procapsid during DNA translocation conformationally restrict the nuclease domain, inhibiting cleavage; TerL release from the capsid upon completion of packaging unlocks the nuclease domains to cleave DNA. PMID:28082398
Baron, Alice; Verdié, Pascal; Martinez, Jean; Lamaty, Frédéric
2011-02-04
A new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclization-cleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process.
Directory of Open Access Journals (Sweden)
Susannah L. Hewitt
2017-10-01
Full Text Available Many DNA lesions associated with lymphoid malignancies are linked to off-target cleavage by the RAG1/2 recombinase. However, off-target cleavage has mostly been analyzed in the context of DNA repair defects, confounding any mechanistic understanding of cleavage deregulation. We identified a conserved SQ phosphorylation site on RAG2 365 to 366 that is involved in feedback control of RAG cleavage. Mutation of serine 365 to a non-phosphorylatable alanine permits bi-allelic and bi-locus RAG-mediated breaks in the same cell, leading to reciprocal translocations. This phenomenon is analogous to the phenotype we described for ATM kinase inactivation. Here, we establish deregulated cleavage itself as a driver of chromosomal instability without the associated repair defect. Intriguingly, a RAG2-S365E phosphomimetic rescues the deregulated cleavage of ATM inactivation, reducing the incidence of reciprocal translocations. These data support a model in which feedback control of cleavage and maintenance of genome stability involves ATM-mediated phosphorylation of RAG2.
International Nuclear Information System (INIS)
Del Prete, G.F.; Vercelli, D.; Tiri, A.; Maggi, E.; Rossi, O.; Romagnani, S.; Ricci, M.
1987-01-01
The in vitro effects of radiation, diterpine forskolin (FK), and hydrocortisone (HC) on the in vitro spontaneous IgE synthesis by peripheral blood B-lymphocytes from atopic patients were investigated. Without affecting cell viability, in vitro irradiation inhibited in a dose-dependent fashion de novo IgE synthesis in vitro by B cells from all patients examined with a mean 40% reduction of in vitro IgE product after treatment with 100 rads. In contrast, the in vitro IgE production by the U266 myeloma cell line was unaffected, even by irradiation with 1600 rads. The addition to B cell cultures from atopic patients of FK consistently resulted in a dose-dependent inhibition of the spontaneous IgE production in vitro. The addition to cultures of 10(-5) and 10(-6) molar concentrations of HC was also usually inhibitory, whereas lower HC concentrations were uneffective or even enhanced the spontaneous in vitro IgE synthesis. When 10(-6) molar concentrations of both HC and FK were combined in culture, a summation inhibitory effect on the spontaneous IgE synthesis was observed. In contrast, neither FK nor HC had inhibitory effect on the in vitro spontaneous IgE synthesis by the U266 myeloma cell line. The spontaneous in vitro IgE synthesis by B cells from patients with Hodgkin's disease, demonstrating high levels of serum IgE, was strongly reduced or virtually abolished after patients underwent total nodal irradiation to prevent the spread of the disease. In addition, the in vitro spontaneous IgE synthesis by B cells from atopic patients was markedly decreased or abolished by in vivo administration of betamethasone
Glioblastoma Multiforme Presenting as Spontaneous Intracerebral Hemorrhage
Directory of Open Access Journals (Sweden)
Cagatay Ozdol
2014-06-01
Full Text Available Brain tumors with concomitant intracerebral hemorrhage are rarely encountered. Hemorrhage as the initial presentation of a brain tumour may pose some diagnostic problems, especially if the tumour is small or the hemorrhage is abundant. We present a 47-year-old man who admitted to the emergency department with sudden onset headache, right blurred vision and gait disturbance. A non-contrast cranial computerized tomography scan performed immediately after his admission revealed a well circumscribed right occipitoparietal haematoma with intense peripheral edema causing compression of the ipsilateral ventricles. On 6th hour of his admission the patient%u2019s neurological status deteriorated and he subsequently underwent emergent craniotomy and microsurgical evacuation of the haematoma. The histopathological examination of the mass was consistent with a glioblastoma multiforme. Neoplasms may be hidden behind each case of spontaneous intracerebral hemorrhage. Histological sampling and investigation is mandatory in the presence of preoperative radiological features suggesting a neoplasm.
Pigment dispersion syndrome associated with spontaneous subluxation of crystalline lens
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Vikas Veerwal
2017-01-01
Full Text Available Pigment dispersion syndrome (PDS is an ocular condition characterized by a dispersion of iris pigment throughout the eye. This pigment is deposited in a characteristic manner on the corneal endothelium as Krukenberg's spindle, anterior surface of the iris, in the trabecular meshwork, on the lens and zonule and occasionally on the anterior hyaloid face. Even with deposition of pigment on zonular fibers, no zonular weakness, or zonular dehiscence has been reported in these cases. We report a unique case of PDS with bilateral spontaneous subluxation of crystalline lens. With characteristic findings of pigment distribution in both his eyes, the patient had concave iris configuration with heavily pigmented trabecular meshwork confirming the diagnosis of PDS. The patient had bilateral 180° temporal subluxation of crystalline lens in both his eyes. The usual cause of lens subluxation such as Marfan's Syndrome and Ehler's Danlos Syndrome was ruled out. The patient underwent right eye followed by left eye intracapsular cataract extraction with ab-interno technique with postoperative best-corrected visual acuity (BCVA of 6/9 in both eyes. Spontaneous subluxation of crystalline lens in isolated PDS is not known to occur and has been reported by means of this case. We recommend a thorough assessment of zonular status in all cases of PDS.
Pigment dispersion syndrome associated with spontaneous subluxation of crystalline lens.
Veerwal, Vikas; Goyal, Jawahar Lal; Jain, Parul; Arora, Ritu
2017-01-01
Pigment dispersion syndrome (PDS) is an ocular condition characterized by a dispersion of iris pigment throughout the eye. This pigment is deposited in a characteristic manner on the corneal endothelium as Krukenberg's spindle, anterior surface of the iris, in the trabecular meshwork, on the lens and zonule and occasionally on the anterior hyaloid face. Even with deposition of pigment on zonular fibers, no zonular weakness, or zonular dehiscence has been reported in these cases. We report a unique case of PDS with bilateral spontaneous subluxation of crystalline lens. With characteristic findings of pigment distribution in both his eyes, the patient had concave iris configuration with heavily pigmented trabecular meshwork confirming the diagnosis of PDS. The patient had bilateral 180° temporal subluxation of crystalline lens in both his eyes. The usual cause of lens subluxation such as Marfan's Syndrome and Ehler's Danlos Syndrome was ruled out. The patient underwent right eye followed by left eye intracapsular cataract extraction with ab-interno technique with postoperative best-corrected visual acuity (BCVA) of 6/9 in both eyes. Spontaneous subluxation of crystalline lens in isolated PDS is not known to occur and has been reported by means of this case. We recommend a thorough assessment of zonular status in all cases of PDS.
Wolf, Myles; White, Kenneth E
2014-07-01
High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.
Wang, Jianhao; Fan, Jie; Liu, Li; Ding, Shumin; Liu, Xiaoqian; Wang, Jianpeng; Gao, Liqian; Chattopadhaya, Souvik; Miao, Peng; Xia, Jiang; Qiu, Lin; Jiang, Pengju
2017-10-01
Herein, a novel assay has been developed for monitoring PreScission protease (His-PSP) mediated enzyme cleavage of ATTO 590 labeled peptide substrate (ATTO-LEV). This novel method is based on combining the use of capillary electrophoresis and fluorescence detection (CE-FL) to dynamically monitor the enzyme cleavage activity. A multivalent peptide substrate was first constructed by immobilizing His-tagged ATTO 590 labeled peptide substrate (ATTO-LEVH6) onto the surface of CdSe/ZnS quantum dots (QDs). Once successfully immobilized, the novel multivalent peptide substrate resulted in the Förster resonance energy transfer (FRET) from QDs to ATTO 590. The ATTO-LEVH6-QD assembly was then incubated with His-PSP to study the proteolytic cleavage of surface bound ATTO-LEVH6 by CE-FL. Our data suggests that PreScission-mediated proteolytic cleavage is enzyme concentration- and incubation time-dependent. By combining capillary electrophoresis, QDs and FRET, our study herein not only provides a new method for the detection and dynamically monitoring of PSP enzyme cleavage activity, but also can be extended to the detection of many other enzymes and proteases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Metabolic Engineering to Develop a Pathway for the Selective Cleavage of Carbon-Nitrogen Bonds
Energy Technology Data Exchange (ETDEWEB)
John J. Kilbane II
2005-10-01
The objective of the project is to develop a biochemical pathway for the selective cleavage of C-N bonds in molecules found in petroleum. Specifically a novel biochemical pathway will be developed for the selective cleavage of C-N bonds in carbazole. The cleavage of the first C-N bond in carbazole is accomplished by the enzyme carbazole dioxygenase, that catalyzes the conversion of carbazole to 2-aminobiphenyl-2,3-diol. The genes encoding carbazole dioxygenase were cloned from Sphingomonas sp. GTIN11 and from Pseudomonas resinovorans CA10. The selective cleavage of the second C-N bond has been challenging, and efforts to overcome that challenge have been the focus of recent research in this project. Enrichment culture experiments succeeded in isolating bacterial cultures that can metabolize 2-aminobiphenyl, but no enzyme capable of selectively cleaving the C-N bond in 2-aminobiphenyl has been identified. Aniline is very similar to the structure of 2-aminobiphenyl and aniline dioxygenase catalyzes the conversion of aniline to catechol and ammonia. For the remainder of the project the emphasis of research will be to simultaneously express the genes for carbazole dioxygenase and for aniline dioxygenase in the same bacterial host and then to select for derivative cultures capable of using carbazole as the sole source of nitrogen.
Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous Speech.
Furlanis, Giovanni; Ridolfi, Mariana; Polverino, Paola; Menichelli, Alina; Caruso, Paola; Naccarato, Marcello; Sartori, Arianna; Torelli, Lucio; Pesavento, Valentina; Manganotti, Paolo
2018-07-01
Aphasia is one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute stroke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening test. Our study is a single-center prospective observational study conducted at the Stroke Unit of the University Medical Hospital of Trieste (January-December 2016). Patients treated with thrombolysis and nontreated patients underwent 3 aphasia assessments through our rapid screening test (at baseline, 24 hours, and 72 hours). The screening test assesses spontaneous speech, oral comprehension of words, reading aloud and comprehension of written words, oral comprehension of sentences, naming, repetition of words and a sentence, and writing words. The study included 40 patients: 18 patients treated with thrombolysis and 22 nontreated patients. Both groups improved over time. Among all language parameters, spontaneous speech was statistically significant between 24 and 72 hours (P value = .012), and between baseline and 72 hours (P value = .017). Our study demonstrates that patients treated with thrombolysis experience greater improvement in language than the nontreated patients. The difference between the 2 groups is increasingly evident over time. Moreover, spontaneous speech is the parameter marked by the greatest improvement. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Spontaneous intracranial hypotension.
LENUS (Irish Health Repository)
Fullam, L
2012-01-31
INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.
Directory of Open Access Journals (Sweden)
Haddiya I
2016-03-01
Full Text Available Intissar Haddiya,1 Hakim Hamzaoui,1 Zitouna Alhamany,2 Fatime-zohra Berkchi,1 Hakima Rhou,1 Loubna Benamar,1 Naima Ouzeddoun,1 Rabea Bayahia1 1Department of Nephrology-Dialysis-Renal Transplantation, Ibn Sina University Hospital, Rabat, Morocco; 2Department of Pathology, Rabat Children's Hospital, Ibn Sina University Hospital, Rabat, Morocco Background: Spontaneous rupture of the kidney is uncommon and is mainly caused by renal tumors. Only a few cases are caused by vasculitis. We report here the first case of spontaneous rupture of kidney resulting from mixed cryoglobulinemia. Case presentation: A 44-year-old man presented with sudden onset of fever, acute pulmonary edema, left flank abdominal pain unassociated with trauma, and rapidly progressive renal failure requiring dialysis. Computed tomography of the abdomen revealed a large perirenal hematoma of the left kidney. During conservative surgery, the patient underwent renal biopsy that showed renal vasculitis and membranoproliferative glomerulonephritis with intracapillary microthrombi. Tests were positive for mixed cryoglobulinemia caused by Sjögren's syndrome. The patient was better after immunosuppressive therapy, with the disappearance of clinical symptoms and the recovery of baseline renal function. Conclusion: We report on this case and discuss a possible link between spontaneous rupture of kidney and mixed cryoglobulinemia-associated Sjögren's syndrome. Keywords: mixed cryoglobulinemia, Sjögren's syndrome, spontaneous rupture of kidney, renal hematoma, Wünderlich syndrome
Wang, Anthony C; Gemmete, Joseph J; Keegan, Catherine E; Witt, Cordelie E; Muraszko, Karin M; Than, Khoi D; Maher, Cormac O
2011-11-01
Roberts/SC phocomelia syndrome (RBS) is a rare but distinct genetic disorder with an autosomal recessive inheritance pattern. It has been associated with microcephaly, craniofacial malformation, cavernous hemangioma, encephalocele, and hydrocephalus. There are no previously reported cases of RBS with intracranial aneurysms. The authors report on a patient with a history of RBS who presented with a spontaneous posterior fossa hemorrhage. Multiple small intracranial aneurysms were noted on a preoperative CT angiogram. The patient underwent emergency craniotomy for evacuation of the hemorrhage. A postoperative angiogram confirmed the presence of multiple, distal small intracranial aneurysms.
Directory of Open Access Journals (Sweden)
Shamsa Ali
2010-01-01
Full Text Available Varicocele is still an enigma. Its effects on semen analysis, fertility and, more re-cently, early ejaculation and spontaneous abortion in spouses are not yet fully understood. In this retrospective study, we evaluated these four parameters (semen analysis, fertility, early ejacu-lation and spontaneous abortion among spouses in relation to varicocele and varicocelectomy during a 13-year period. A total of 1,711 patients with varicocele underwent varicocelectomy by high inguinal method (251 cases, subinguinal method (1,375 cases, scrotal method (34 cases, and subinguinal method with local anesthesia (38 cases. Our complication rate was acceptable. Sperm count, motility and morphology increased three months post operation in 55, 51, and 46%, respectively (P value 0.000, 0.000, and 0.015, respectively. Paternity was 56% after one year of post varicocelectomy follow-up. Only 7 out of 82 azoospermic men had sperm in their semen after varicocelectomy and only one of them with mild spermatogenic hypoplasia became a father. The spontaneous abortion rate in the spouses of respondents was 59%. Early ejaculation improved in 75% of the respondents. In conclusion, varicocelectomy does not improve sperm parameters in all men, but it improves pregnancy rate, early ejaculation, and scrotal pain.
Influence of the austenitizing temperature in the cleavage facet size of Niocor 2
International Nuclear Information System (INIS)
Darwish, F.A.I.; Teixeira, J.C.G.; Fernandes, R.A.; Juer, S.
1983-01-01
Convetional Charpy specimens of Niocor 2 steel cooled in air from various austenitizing temperatures were fractured at -196 0 C so as to insure failure by cleavage. The cleavage facet size distribution was determined and then correlated with the grain size and other aspects of the microstructure. The results that the average facet size can be increased through a coarsening of the microstructure. For the case where the γ→α transformation products are predominantely acicular, the facet size is shown to depend on substructural aspects primarily the lath packet size. (Author) [pt
[Cleavage of DNA fragments induced by UV nanosecond laser excitation at 193 nm].
Vtiurina, N N; Grokhovskiĭ, S L; Filimonov, I V; Medvedkov, O I; Nechipurenko, D Iu; Vasil'ev, S A; Nechipurenko, Iu D
2011-01-01
The cleavage of dsDNA fragments in aqueous solution after irradiation with UV laser pulses at 193 nm has been studied. Samples were investigated using polyacrylamide gel electrophoresis. The intensity of damage of particular phosphodiester bond after hot alkali treatment was shown to depend on the base pair sequence. It was established that the probability of cleavage is twice higher for sites of DNA containing two or more successively running guanine residues. A possible mechanism of damage to the DNA molecule connected with the migration of holes along the helix is discussed.
[Spontaneous bacterial peritonitis].
Velkey, Bálint; Vitális, Eszter; Vitális, Zsuzsanna
2017-01-01
Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.
International Nuclear Information System (INIS)
De Lutio di Castelguidone, Elisabetta; Pinto, Antonio; Merola, Stefanella; Stavolo, Ciro; Romano, Luigia
2005-01-01
Purpose: To assess the role of CT in the evaluation of traumatic and spontaneous oesophageal perforation. Materials and methods: From March 2001 to May 2003, we studied 12 patients (7 males and 5 females; age range: 25-66 years, mean age: 43.5 years) with suspected oesophageal perforation due to motor-vehicle accidents (4 cases), stab wound (one case), post-intubation (2 cases), foreign body ingestion (2 cases) and spontaneous (3 cases). Five patients underwent standard chest and cervical radiography; two patients with suspected foreign body ingestion also underwent a gastrografin swallow study; all of the 12 patients underwent CT of the neck, chest and abdomen before and after intravenous, and in four cases oral, administration of contrast material. Results: In 5 patients with cervical, thoracic and abdominal trauma, the CT examination showed the presence of pleuroparenchymal injury (pneumothorax, pleural effusion and subcutaneous emphysema) as well as findings suggestive of oesophageal perforation: peri-oesophageal air (5 cases), peri-oesophageal fluid (4 cases), oesophageal wall thickening (3 cases), oesophageal wall laceration (2 cases) with abnormal course of the nasogastric tube in one of them and extraluminal extravasation of oral contrast material (2 cases). In two patients with post-intubation complications, CT showed the presence of a small peri-oesophageal fluid collection containing small gas bubbles in one case, and a gross peri-oesophageal abscess-like collection in the second case. In the 2 patients with foreign body ingestion, the plain radiography associated with CT showed the presence of a thin metal object in the cervical region (fragment of a dental plate) and a small extraluminal extravasation of gastrografin in one case, whereas in the other case CT showed the presence of a foreign body (chicken bone) in the hypopharynx with oesophageal wall thickening and peri-oesophageal oedema. In the remaining three patients with suspected spontaneous
Affect of Presenilin Mutations on APP Cleavage; Insights into the Pathogenesis of FAD
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Nuomin eLi
2016-03-01
Full Text Available Alzheimer disease (AD is characterized by progressive memory loss, reduction in cognitive functions, and damage to the brain. The β-amyloid precursor protein can be sequentially cleaved by β- secretase and γ-secretase. Mutations in the presenilin1(PS1) are the most common cause of Familial Alzheimer’s disease ( FAD. PS1 mutations can alter the activity of γ-secretase on the cleavage of the β-amyloid precursor protein, causing increased Aβ production. Previous studies show that the βAPP-C-terminal fragment is first cleaved by β-scretase, primarily generating long fragments of Aβ48 and Aβ49, followed by the stepwise cleavage of every three amino acid residues at the C terminus, resulting in Aβ48-, 45-, 42 line and Aβ49-, 46-, 43-, 40 line. Here, we used LC-MS/MS to analyze unique peptides IAT, VVIA, ITL,TVI,IVI through sequential cleavage, combined with ELISA to test the level of Aβ42 and Aβ40 for validation. The results show that most FAD mutant PS1 can alter the level of Aβ42 and Aβ40 monitored by the Aβ42/Aβ40 ratio. Among them, 6 mutants (I143T, H163P, S170F, Q223R, M233V and G384A affect the Aβ42/40 ratio through both Aβ49-40 and Aβ48-38 lines; L166P through decreasing the Aβ49-40 line, 6 mutants (I143V, M146V, G217A, E280A, L381V and L392V through increasing the Aβ48-42 line. More importantly, we found some mutations can affect the γ-secretase cleavage preference of α-CTF and β-CTF. In conclusion, we found that the FAD PS1 mutations mainly increase the generation of Aβ42 by decreasing the cleavage of Aβ42-Aβ38 and Aβ43-Aβ40.
Genetics Home Reference: primary spontaneous pneumothorax
... Home Health Conditions Primary spontaneous pneumothorax Primary spontaneous pneumothorax Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Primary spontaneous pneumothorax is an abnormal accumulation of air in the ...
High-resolution characterization of sequence signatures due to non-random cleavage of cell-free DNA.
Chandrananda, Dineika; Thorne, Natalie P; Bahlo, Melanie
2015-06-17
High-throughput sequencing of cell-free DNA fragments found in human plasma has been used to non-invasively detect fetal aneuploidy, monitor organ transplants and investigate tumor DNA. However, many biological properties of this extracellular genetic material remain unknown. Research that further characterizes circulating DNA could substantially increase its diagnostic value by allowing the application of more sophisticated bioinformatics tools that lead to an improved signal to noise ratio in the sequencing data. In this study, we investigate various features of cell-free DNA in plasma using deep-sequencing data from two pregnant women (>70X, >50X) and compare them with matched cellular DNA. We utilize a descriptive approach to examine how the biological cleavage of cell-free DNA affects different sequence signatures such as fragment lengths, sequence motifs at fragment ends and the distribution of cleavage sites along the genome. We show that the size distributions of these cell-free DNA molecules are dependent on their autosomal and mitochondrial origin as well as the genomic location within chromosomes. DNA mapping to particular microsatellites and alpha repeat elements display unique size signatures. We show how cell-free fragments occur in clusters along the genome, localizing to nucleosomal arrays and are preferentially cleaved at linker regions by correlating the mapping locations of these fragments with ENCODE annotation of chromatin organization. Our work further demonstrates that cell-free autosomal DNA cleavage is sequence dependent. The region spanning up to 10 positions on either side of the DNA cleavage site show a consistent pattern of preference for specific nucleotides. This sequence motif is present in cleavage sites localized to nucleosomal cores and linker regions but is absent in nucleosome-free mitochondrial DNA. These background signals in cell-free DNA sequencing data stem from the non-random biological cleavage of these fragments. This
A Rare Case of Spontaneous Pneumocephalus Associated with Nontraumatic Cerebrospinal Fluid Leak
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Murad Baba
2016-01-01
Full Text Available Introduction. Spontaneous nontraumatic pneumocephalus (PNC and cerebrospinal fluid (CSF leaks are both very uncommon conditions. We report a rare case of spontaneous pneumocephalus associated with CSF leak secondary to right sphenoid sinus bony defect without history of trauma. Case Description. 51-year-old Hispanic female with past medical history of hypertension and idiopathic intracranial hypertension (Pseudotumor Cerebri presented to the emergency room complaining of headache and clear discharge from the right nostril. Physical examination was significant for right frontal sinus tenderness and clear discharge from right nostril. Computed Tomography (CT scan of the brain showed moderate amount of extra-axial air within the right cerebral hemisphere indicative of pneumocephalus. CT scan of facial bones showed bony defect along the right sphenoid sinus with abnormal CSF collection. The patient was started on intravenous antibiotics for meningitis prophylaxis and subsequently underwent transsphenoidal repair of cerebrospinal fluid leak with abdominal fat graft. CSF rhinorrhea stopped completely after the surgery with near complete resolution of pneumocephalus before discharge. Conclusions. Early identification of pneumocephalus and surgical intervention can help decrease the morbidity and avoid possible complications. Idiopathic intracranial hypertension, although rare, can lead to CSF leak and pneumocepahlus.
Dual CRISPR-Cas9 Cleavage Mediated Gene Excision and Targeted Integration in Yarrowia lipolytica.
Gao, Difeng; Smith, Spencer; Spagnuolo, Michael; Rodriguez, Gabriel; Blenner, Mark
2018-05-29
CRISPR-Cas9 technology has been successfully applied in Yarrowia lipolytica for targeted genomic editing including gene disruption and integration; however, disruptions by existing methods typically result from small frameshift mutations caused by indels within the coding region, which usually resulted in unnatural protein. In this study, a dual cleavage strategy directed by paired sgRNAs is developed for gene knockout. This method allows fast and robust gene excision, demonstrated on six genes of interest. The targeted regions for excision vary in length from 0.3 kb up to 3.5 kb and contain both non-coding and coding regions. The majority of the gene excisions are repaired by perfect nonhomologous end-joining without indel. Based on this dual cleavage system, two targeted markerless integration methods are developed by providing repair templates. While both strategies are effective, homology mediated end joining (HMEJ) based method are twice as efficient as homology recombination (HR) based method. In both cases, dual cleavage leads to similar or improved gene integration efficiencies compared to gene excision without integration. This dual cleavage strategy will be useful for not only generating more predictable and robust gene knockout, but also for efficient targeted markerless integration, and simultaneous knockout and integration in Y. lipolytica. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO.
Zhu, Xinyu; Fang, Liurong; Wang, Dang; Yang, Yuting; Chen, Jiyao; Ye, Xu; Foda, Mohamed Frahat; Xiao, Shaobo
2017-02-01
Porcine deltacoronavirus (PDCoV) causes acute enteric disease and mortality in seronegative neonatal piglets. Previously we have demonstrated that PDCoV infection suppresses the production of interferon-beta (IFN-β), while the detailed mechanisms are poorly understood. Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV. The PDCoV nsp5 cleavage site in the NEMO protein was identified as glutamine 231, and was identical to the porcine epidemic diarrhea virus nsp5 cleavage site, revealing the likelihood of a common target in NEMO for coronaviruses. Furthermore, this cleavage impaired the ability of NEMO to activate the IFN response and downstream signaling. Taken together, our findings reveal PDCoV nsp5 to be a newly identified IFN antagonist and enhance the understanding of immune evasion by deltacoronaviruses. Copyright © 2016 Elsevier Inc. All rights reserved.
Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations
Zuo, Zhicheng; Liu, Jin
2016-11-01
The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (spCas9) along with a single guide RNA (sgRNA) has emerged as a versatile toolbox for genome editing. Despite recent advances in the mechanism studies on spCas9-sgRNA-mediated double-stranded DNA (dsDNA) recognition and cleavage, it is still unclear how the catalytic Mg2+ ions induce the conformation changes toward the catalytic active state. It also remains controversial whether Cas9 generates blunt-ended or staggered-ended breaks with overhangs in the DNA. To investigate these issues, here we performed the first all-atom molecular dynamics simulations of the spCas9-sgRNA-dsDNA system with and without Mg2+ bound. The simulation results showed that binding of two Mg2+ ions at the RuvC domain active site could lead to structurally and energetically favorable coordination ready for the non-target DNA strand cleavage. Importantly, we demonstrated with our simulations that Cas9-catalyzed DNA cleavage produces 1-bp staggered ends rather than generally assumed blunt ends.
Mizrahi, Daniel J; Kaushik, Chhavi; Adamo, Robert
2017-03-01
Hemoperitoneum with hypovolemic shock from avulsion of a pedunculated leiomyoma is a rare but highly fatal condition that can occur spontaneously or as a result of trauma. We report a case of hemoperitoneum and hypovolemic shock secondary to a bleeding leiomyoma detected via computed tomography (CT) scan in a 39 year old premenopausal, gravida 0 female that presented with abdominal pain and became hemodynamically unstable in the emergency department. A preoperative bimanual exam revealed a mass consistent with a 20 week gestational uterus. Following fluid resuscitation, the patient underwent emergent myomectomy and ligation of the right uterine artery and was discharged home in good condition.
Ziprasidone-induced spontaneous orgasm.
Boora, K; Chiappone, K; Dubovsky, S; Xu, J
2010-06-01
Neuroleptic treatment in schizophrenic patients has been associated with sexual dysfunction, including impotence and decreased libido. Spontaneous ejaculation without sexual arousal during typical antipsychotic treatment is a rare condition that has been described with zuclopentixol, trifluoperazine, and thiothixene. Here, we are reporting a case of spontaneous orgasm with ziprasidone in a bipolar patient. This patient began to repeatedly experience spontaneous sexual arousal and orgasm, which she had never experienced in the past. Ziprasidone might be causing an increase in sexual orgasm by 5-HT2 receptor antagonism, which preclinical evidence suggests that it facilitates dopamine release in the cortex.
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Joshua T Schiffer
Full Text Available Most chronic viral infections are managed with small molecule therapies that inhibit replication but are not curative because non-replicating viral forms can persist despite decades of suppressive treatment. There are therefore numerous strategies in development to eradicate all non-replicating viruses from the body. We are currently engineering DNA cleavage enzymes that specifically target hepatitis B virus covalently closed circular DNA (HBV cccDNA, the episomal form of the virus that persists despite potent antiviral therapies. DNA cleavage enzymes, including homing endonucleases or meganucleases, zinc-finger nucleases (ZFNs, TAL effector nucleases (TALENs, and CRISPR-associated system 9 (Cas9 proteins, can disrupt specific regions of viral DNA. Because DNA repair is error prone, the virus can be neutralized after repeated cleavage events when a target sequence becomes mutated. DNA cleavage enzymes will be delivered as genes within viral vectors that enter hepatocytes. Here we develop mathematical models that describe the delivery and intracellular activity of DNA cleavage enzymes. Model simulations predict that high vector to target cell ratio, limited removal of delivery vectors by humoral immunity, and avid binding between enzyme and its DNA target will promote the highest level of cccDNA disruption. Development of de novo resistance to cleavage enzymes may occur if DNA cleavage and error prone repair does not render the viral episome replication incompetent: our model predicts that concurrent delivery of multiple enzymes which target different vital cccDNA regions, or sequential delivery of different enzymes, are both potentially useful strategies for avoiding multi-enzyme resistance. The underlying dynamics of cccDNA persistence are unlikely to impact the probability of cure provided that antiviral therapy is given concurrently during eradication trials. We conclude by describing experiments that can be used to validate the model, which
Active site mutations change the cleavage specificity of neprilysin.
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Travis Sexton
Full Text Available Neprilysin (NEP, a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe(563 and Ser(546. Among the mutants studied in detail we observed changes in their activity towards leucine(5-enkephalin, insulin B chain, and amyloid β(1-40. For example, NEP(F563I displayed an increase in preference towards cleaving leucine(5-enkephalin relative to insulin B chain, while mutant NEP(S546E was less discriminating than neprilysin. Mutants NEP(F563L and NEP(S546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid ß(1-40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential.
Cleavage of thymine N3-H bonds by low-energy electrons attached to base π* orbitals
International Nuclear Information System (INIS)
Theodore, Magali; Sobczyk, Monika; Simons, Jack
2006-01-01
In this work, we extend our earlier studies on single strand break (SSB) formation in DNA to consider the possibility of cleaving a thymine N 3 -H bond to generate a nitrogen-centered anion and a hydrogen radical which might proceed to induce further bond cleavages. In earlier studies, we considered SSBs induced by low-energy electrons that attach to DNA bases' π* orbitals or to phosphate P=O π* orbitals to cleave sugar-phosphate C-O bonds or base-sugar N 1 -C bonds. We also studied the effects of base π-stacking on the rates of such bond cleavages. To date, our results suggest that sugar-phosphate C-O bonds have the lowest barriers to cleavage, that attachment of electrons with energies below 2 eV most likely occurs at the base π* orbitals, that electrons with energy above 2 eV can also attach to phosphate P=O π* orbitals, and that base π stacking has a modest but slowing effect on the rates of SSB formation. However, we had not yet examined the possibility that base N 3 -H bonds could rupture subsequent to base π* orbital capture. In the present work, the latter possibility is considered and it is found that the barrier to cleavage of the N 3 -H bond in thymine is considerably higher than for cleaving sugar-phosphate C-O bonds, so our prediction that SSB formation is dominated by C-O bond cleavage remains intact
Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases
2016-01-01
Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. On the basis of previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10–100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons. (1) The activity of the metabolites was abrogated by a reducing agent. (2) Compounds inhibited topoisomerase II activity when they were incubated with the enzyme prior to the addition of DNA. (3) Compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption. PMID:26132160
Foreman, David J.; Dziekonski, Eric T.; McLuckey, Scott A.
2018-04-01
A new approach for the identification of intact proteins has been developed that relies on the generation of relatively few abundant products from specific cleavage sites. This strategy is intended to complement standard approaches that seek to generate many fragments relatively non-selectively. Specifically, this strategy seeks to maximize selective cleavage at aspartic acid and proline residues via collisional activation of precursor ions formed via electrospray ionization (ESI) under denaturing conditions. A statistical analysis of the SWISS-PROT database was used to predict the number of arginine residues for a given intact protein mass and predict a m/z range where the protein carries a similar charge to the number of arginine residues thereby enhancing cleavage at aspartic acid residues by limiting proton mobility. Cleavage at aspartic acid residues is predicted to be most favorable in the m/z range of 1500-2500, a range higher than that normally generated by ESI at low pH. Gas-phase proton transfer ion/ion reactions are therefore used for precursor ion concentration from relatively high charge states followed by ion isolation and subsequent generation of precursor ions within the optimal m/z range via a second proton transfer reaction step. It is shown that the majority of product ion abundance is concentrated into cleavages C-terminal to aspartic acid residues and N-terminal to proline residues for ions generated by this process. Implementation of a scoring system that weights both ion fragment type and ion fragment area demonstrated identification of standard proteins, ranging in mass from 8.5 to 29.0 kDa. [Figure not available: see fulltext.
Peng, Zhou; Bu, Jiexun; McLuckey, Scott A.
2017-09-01
We examine a gas-phase approach for converting a subset of amino acid residues in polypeptide cations to dehydroalanine (Dha). Subsequent activation of the modified polypeptide ions gives rise to specific cleavage N-terminal to the Dha residue. This process allows for the incorporation of selective cleavages in the structural characterization of polypeptide ions. An ion/ion reaction within the mass spectrometer between a multiply protonated polypeptide and the sulfate radical anion introduces a radical site into the multiply protonated polypeptide reactant. Subsequent collisional activation of the polypeptide radical cation gives rise to radical side chain loss from one of several particular amino acid side chains (e.g., leucine, asparagine, lysine, glutamine, and glutamic acid) to yield a Dha residue. The Dha residues facilitate preferential backbone cleavages to produce signature c- and z-ions, demonstrated with cations derived from melittin, mechano growth factor (MGF), and ubiquitin. The efficiencies for radical side chain loss and for subsequent generation of specific c- and z-ions have been examined as functions of precursor ion charge state and activation conditions using cations of ubiquitin as a model for a small protein. It is noted that these efficiencies are not strongly dependent on ion trap collisional activation conditions but are sensitive to precursor ion charge state. Moderate to low charge states show the greatest overall yields for the specific Dha cleavages, whereas small molecule losses (e.g., water/ammonia) dominate at the lowest charge states and proton catalyzed amide bond cleavages that give rise to b- and y-ions tend to dominate at high charge states. [Figure not available: see fulltext.
ATP-Dependent C–F Bond Cleavage Allows the Complete Degradation of 4-Fluoroaromatics without Oxygen
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Oliver Tiedt
2016-08-01
Full Text Available Complete biodegradation of the abundant and persistent fluoroaromatics requires enzymatic cleavage of an arylic C–F bond, probably the most stable single bond of a biodegradable organic molecule. While in aerobic microorganisms defluorination of fluoroaromatics is initiated by oxygenases, arylic C–F bond cleavage has never been observed in the absence of oxygen. Here, an oxygen-independent enzymatic aryl fluoride bond cleavage is described during the complete degradation of 4-fluorobenzoate or 4-fluorotoluene to CO2 and HF in the denitrifying Thauera aromatica: the ATP-dependent defluorination of 4-fluorobenzoyl-coenzyme A (4-F-BzCoA to benzoyl-coenzyme A (BzCoA and HF, catalyzed by class I BzCoA reductase (BCR. Adaptation to growth with the fluoroaromatics was accomplished by the downregulation of a promiscuous benzoate-CoA ligase and the concomitant upregulation of 4-F-BzCoA-defluorinating/dearomatizing BCR on the transcriptional level. We propose an unprecedented mechanism for reductive arylic C–F bond cleavage via a Birch reduction-like mechanism resulting in a formal nucleophilic aromatic substitution. In the proposed anionic 4-fluorodienoyl-CoA transition state, fluoride elimination to BzCoA is favored over protonation to a fluorinated cyclic dienoyl-CoA.
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Bin Gao
Full Text Available Delusions of schizophrenia have been found to be associated with alterations of some brain regions in structure and task-induced activation. However, the relationship between spontaneously occurring symptoms and spontaneous brain activity remains unclear. In the current study, 14 schizophrenic patients with delusions and 14 healthy controls underwent a resting-state functional magnetic resonance imaging (RS-fMRI scan. Patients with delusions of schizophrenia patients were rated with Positive and Negative Syndrome Scale (PANSS and Characteristics of Delusional Rating Scale (CDRS. Regional homogeneity (ReHo was calculated to measure the local synchronization of the spontaneous activity in a voxel-wise way. A two-sample t-test showed that ReHo of the right anterior cingulate gyrus and left medial superior frontal gyrus were higher in patients, and ReHo of the left superior occipital gyrus was lower, compared to healthy controls. Further, among patients, correlation analysis showed a significant difference between delusion scores of CRDS and ReHo of brain regions. ReHo of the left medial superior frontal gyrus was negatively correlated with patients' CDRS scores but not with delusional PANSS scores. These results suggested that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of delusion in schizophrenia.
Gao, Bin; Wang, Yiquan; Liu, Weibo; Chen, Zhiyu; Zhou, Heshan; Yang, Jinyu; Cohen, Zachary; Zhu, Yihong; Zang, Yufeng
2015-01-01
Delusions of schizophrenia have been found to be associated with alterations of some brain regions in structure and task-induced activation. However, the relationship between spontaneously occurring symptoms and spontaneous brain activity remains unclear. In the current study, 14 schizophrenic patients with delusions and 14 healthy controls underwent a resting-state functional magnetic resonance imaging (RS-fMRI) scan. Patients with delusions of schizophrenia patients were rated with Positive and Negative Syndrome Scale (PANSS) and Characteristics of Delusional Rating Scale (CDRS). Regional homogeneity (ReHo) was calculated to measure the local synchronization of the spontaneous activity in a voxel-wise way. A two-sample t-test showed that ReHo of the right anterior cingulate gyrus and left medial superior frontal gyrus were higher in patients, and ReHo of the left superior occipital gyrus was lower, compared to healthy controls. Further, among patients, correlation analysis showed a significant difference between delusion scores of CRDS and ReHo of brain regions. ReHo of the left medial superior frontal gyrus was negatively correlated with patients' CDRS scores but not with delusional PANSS scores. These results suggested that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of delusion in schizophrenia.
International Nuclear Information System (INIS)
Kunz, Stefan; Edelmann, Kurt H.; Torre, Juan-Carlos de la; Gorney, Robert; Oldstone, Michael B.A.
2003-01-01
The glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) serves as virus attachment protein to its receptor on host cells and is a key determinant for cell tropism, pathogenesis, and epidemiology of the virus. The GP of LCMV is posttranslationally cleaved by the subtilase SKI-1/S1P into two subunits, the peripheral GP1, which is implicated in receptor binding, and the transmembrane GP2 that is structurally similar to the fusion active membrane proximal portions of the glycoproteins of other enveloped viruses. The present study shows that cleavage by SKI-1/S1P is not required for cell surface expression of LCMVGP on infected cells but is essential for its incorporation into virions and for the production of infectious virus particles. In absence of SKI-1/S1P cleavage, cell-to-cell propagation of the virus was markedly reduced. Further, proteolytic processing of LCMVGP depends on the presence of a cluster of basic amino acids at the C-terminus of the cytoplasmic domain of GP2, a structural motif that is conserved in Old World arenaviruses. The effect of the truncation of the cytoplasmic tail on cleavage suggests a structural interdependence between the cytoplasmic domain and the ectodomains of LCMVGP
Sequence specific inhibition of DNA restriction enzyme cleavage by PNA
DEFF Research Database (Denmark)
Nielsen, P.E.; Egholm, M.; Berg, R.H.
1993-01-01
Plasmids containing double-stranded 10-mer PNA (peptide nucleic acid chimera) targets proximally flanked by two restriction enzyme sites were challenged with the complementary PNA or PNAs having one or two mismatches, and the effect on the restriction enzyme cleavage of the flanking sites was ass...
Cleavage of desmin by cysteine proteases: Calpains and cathepsin B
DEFF Research Database (Denmark)
Baron, Caroline; Jacobsen, S.; Purslow, P.P.
2004-01-01
The intermediate filament protein, desmin, was purified from pork longissimus dorsi and incubated with either P-calpain, m-calpain or cathepsin B. Proteolysis of desmin was followed using SDS-PAGE and Western blotting. After incubation of desmin with the proteases, cleavage sites on the desmin mo...
Cerebral Vasospasm with Ischemia following a Spontaneous Spinal Subarachnoid Hemorrhage
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Sophia F. Shakur
2013-01-01
Full Text Available Cerebral vasospasm is a well-known consequence of aneurysmal subarachnoid hemorrhage (SAH triggered by blood breakdown products. Here, we present the first case of cerebral vasospasm with ischemia following a spontaneous spinal SAH. A 67-year-old woman, who was on Coumadin for atrial fibrillation, presented with chest pain radiating to the back accompanied by headache and leg paresthesias. The international normalized ratio (INR was 4.5. Ten hours after presentation, she developed loss of movement in both legs and lack of sensation below the umbilicus. Spine MRI showed intradural hemorrhage. Her coagulopathy was reversed, and she underwent T2 to T12 laminectomies. A large subarachnoid hematoma was evacuated. Given her complaint of headache preoperatively and the intraoperative finding of spinal SAH, a head CT was done postoperatively that displayed SAH in peripheral sulci. On postoperative day 5, she became obtunded. Brain MRI demonstrated focal restricted diffusion in the left frontoparietal area. Formal angiography revealed vasospasm in anterior cerebral arteries bilaterally and right middle cerebral artery. Vasospasm was treated, and she returned to baseline within 48 hours. Spontaneous spinal SAH can result in the same sequelae typically associated with aneurysmal SAH, and the clinician must have a degree of suspicion in such patients. The pathophysiological mechanisms underlying cerebral vasospasm may explain this unique case.
Pettit, Steven C; Gulnik, Sergei; Everitt, Lori; Kaplan, Andrew H
2003-01-01
Activation of the human immunodeficiency virus type 1 (HIV-1) protease is an essential step in viral replication. As is the case for all retroviral proteases, enzyme activation requires the formation of protease homodimers. However, little is known about the mechanisms by which retroviral proteases become active within their precursors. Using an in vitro expression system, we have examined the determinants of activation efficiency and the order of cleavage site processing for the protease of HIV-1 within the full-length GagPol precursor. Following activation, initial cleavage occurs between the viral p2 and nucleocapsid proteins. This is followed by cleavage of a novel site located in the transframe domain. Mutational analysis of the dimer interface of the protease produced differential effects on activation and specificity. A subset of mutations produced enhanced cleavage at the amino terminus of the protease, suggesting that, in the wild-type precursor, cleavages that liberate the protease are a relatively late event. Replacement of the proline residue at position 1 of the protease dimer interface resulted in altered cleavage of distal sites and suggests that this residue functions as a cis-directed specificity determinant. In summary, our studies indicate that interactions within the protease dimer interface help determine the order of precursor cleavage and contribute to the formation of extended-protease intermediates. Assembly domains within GagPol outside the protease domain also influence enzyme activation.
Can laccases catalyze bond cleavage in lignin?
DEFF Research Database (Denmark)
Munk, Line; Sitarz, Anna Katarzyna; Kalyani, Dayanand
2015-01-01
illustrations of the putative laccase catalyzed reactions, including the possible reactions of the reactive radical intermediates taking place after the initial oxidation of the phenol-hydroxyl groups, we show that i) Laccase activity is able to catalyze bond cleavage in low molecular weight phenolic lignin......-substituted phenols, benzenethiols, polyphenols, and polyamines, which may be oxidized. In addition, the currently available analytical methods that can be used to detect enzyme catalyzed changes in lignin are summarized, and an improved nomenclature for unequivocal interpretation of the action of laccases on lignin...
Energy Technology Data Exchange (ETDEWEB)
Palacio, Glaucia Andrade e Silva; D' Ippolito, Giuseppe [Hospital Sao Luis, Sao Paulo, SP (Brazil). Setor de Disgnostico por Imagem]. E-mail: gl.palacio@bol.com.br; Farias, Andre P. [Hospital Sao Luis, Sao Paulo, SP (Brazil). Setor de Tomografia Computadorizada e Ressonancia Magnetica; Carnevale, Francisco Cesar [Hospital Sao Luis, Sao Paulo, SP (Brazil). Setor de Radiologia Intervencionista; Salem, Marcelo Zindel [Hospital Sao Luis, Sao Paulo, SP (Brazil). Setor de Gastroenterologia Cirurgica; Ricca, Artur Berti [Hospital Sao Luis, Sao Paulo, SP (Brazil)
2003-12-01
Spontaneous hepatic bleeding is a rare condition. Our aim was to describe the imaging findings and minimally invasive treatment using transcatheter arterial embolization in patients with spontaneous and traumatic hepatic rupture. Three patients presented acute hemoperitoneum dur to hepatic rupture caused by spontaneous rupture of hepatocellular carcinoma, HELLP syndrome and a blunt hepatic trauma. The patients were submitted to ultrasound and computed tomography of the abdomen and subsequently treated by transcatheter arterial embolization. All patients underwent helical computed tomography before and after treatments. Computed tomography played an important role in the evaluation and follow-up in the therapeutic intervention. Different types of liver injuries were identified. Transcatheter arterial embolization blocked arterial hemorrhage in the patients who were hemodynamically unstable. The conclusion was: transcatheter arterial embolization is an effective and well-tolerated treatment method for the management of hepatic rupture and computed tomography is an excellent method for the diagnosis and follow-up of these patients. (author)
Rebel, J.M.J.; Leendertse, C.H.; Dekker, A.; Moormann, R.J.M.
2003-01-01
We studied VP0 cleavage of Swine vesicular disease virus (SVDV), a member of the Picornaviridae using a full-length cDNA copy of the Dutch SVDV isolate. The influences of mutations, introduced at the cleavage site of SVDV, on VP0 cleavage, RNA encapsidation and viral infection were studied. Double
Katrancioglu, Ozgur; Akkas, Yucel; Arslan, Sulhattin; Sahin, Ekber
2015-07-01
Other than trauma, rib fracture can occur spontaneously due to a severe cough or sneeze. In this study, patients with spontaneous rib fractures were analyzed according to age, sex, underlying pathology, treatment, and complications. Twelve patients who presented between February 2009 and February 2011 with spontaneous rib fracture were reviewed retrospectively. The patients' data were evaluated according to anamnesis, physical examination, and chest radiographs. The ages of the patients ranged from 34 to 77 years (mean 55.91 ± 12.20 years), and 7 (58.4%) were male. All patients had severe cough and chest pain. The fractures were most frequently between 4th and 9th ribs; multiple rib fractures were detected in 5 (41.7%) patients. Eight (66.7%) patients had chronic obstructive pulmonary disease, 2 (16.7%) had bronchial asthma, and 2 (16.7%) had osteoporosis. Bone densitometry revealed a high risk of bone fracture in all patients. Patients with chronic obstructive pulmonary disease or bronchial asthma had been treated with high-dose steroids for over a year. Spontaneous rib fracture due to severe cough may occur in patients with osteoporosis, chronic obstructive pulmonary disease, or bronchial asthma, receiving long-term steroid therapy. If these patients have severe chest pain, chest radiography should be performed to check for bone lesions. © The Author(s) 2015.
Senger, Moritz; Stripp, Sven T; Soboh, Basem
2017-07-14
Metalloenzymes catalyze complex and essential processes, such as photosynthesis, respiration, and nitrogen fixation. For example, bacteria and archaea use [NiFe]-hydrogenases to catalyze the uptake and release of molecular hydrogen (H 2 ). [NiFe]-hydrogenases are redox enzymes composed of a large subunit that harbors a NiFe(CN) 2 CO metallo-center and a small subunit with three iron-sulfur clusters. The large subunit is synthesized with a C-terminal extension, cleaved off by a specific endopeptidase during maturation. The exact role of the C-terminal extension has remained elusive; however, cleavage takes place exclusively after assembly of the [NiFe]-cofactor and before large and small subunits form the catalytically active heterodimer. To unravel the functional role of the C-terminal extension, we used an enzymatic in vitro maturation assay that allows synthesizing functional [NiFe]-hydrogenase-2 of Escherichia coli from purified components. The maturation process included formation and insertion of the NiFe(CN) 2 CO cofactor into the large subunit, endoproteolytic cleavage of the C-terminal extension, and dimerization with the small subunit. Biochemical and spectroscopic analysis indicated that the C-terminal extension of the large subunit is essential for recognition by the maturation machinery. Only upon completion of cofactor insertion was removal of the C-terminal extension observed. Our results indicate that endoproteolytic cleavage is a central checkpoint in the maturation process. Here, cleavage temporally orchestrates cofactor insertion and protein assembly and ensures that only cofactor-containing protein can continue along the assembly line toward functional [NiFe]-hydrogenase. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
On the mechanism of action of ribonucleases: dinucleotide cleavage catalyzed by imidazole and Zn2+.
Breslow, R; Huang, D L; Anslyn, E
1989-01-01
Cyclization/cleavage of the 2-(p-nitrophenyl) phosphate ester of propylene glycol is catalyzed by imidazole and, much more effectively, by Zn2+ with imidazole. In the latter case, the mechanism involves simultaneous Lewis acid/base catalysis. Similar Zn2+ and imidazole catalysis of cyclization/cleavage is seen with the dinucleotide 3',5'-UpU (uridylyluridine). Again, the zinc system is much more effective than is catalysis by imidazole alone, and in this case simultaneous Lewis acid/base cata...
Saxena, Mayur; Changede, Rishita; Hone, James; Wolfenson, Haguy; Sheetz, Michael P
2017-12-13
Cell growth depends upon formation of cell-matrix adhesions, but mechanisms detailing the transmission of signals from adhesions to control proliferation are still lacking. Here, we find that the scaffold protein talin undergoes force-induced cleavage in early adhesions to produce the talin rod fragment that is needed for cell cycle progression. Expression of noncleavable talin blocks cell growth, adhesion maturation, proper mechanosensing, and the related property of EGF activation of motility. Further, the expression of talin rod in the presence of noncleavable full-length talin rescues cell growth and other functions. The cleavage of talin is found in early adhesions where there is also rapid turnover of talin that depends upon calpain and TRPM4 activity as well as the generation of force on talin. Thus, we suggest that an important function of talin is its control over cell cycle progression through its cleavage in early adhesions.
Directory of Open Access Journals (Sweden)
Siniša Urban
2014-09-01
Full Text Available Rhomboid proteases are integral membrane enzymes that regulate cell signaling, adhesion, and organelle homeostasis pathways, making substrate specificity a key feature of their function. Interestingly, we found that perturbing the membrane pharmacologically in living cells had little effect on substrate processing but induced inappropriate cleavage of nonsubstrates by rhomboid proteases. A subclass of drugs known to modulate γ-secretase activity acted on the membrane directly and induced nonsubstrate cleavage by rhomboid proteases but left true substrate cleavage sites unaltered. These observations highlight an active role for the membrane in guiding rhomboid selectivity and caution that membrane-targeted drugs should be evaluated for cross-activity against membrane-resident enzymes that are otherwise unrelated to the intended drug target. Furthermore, some γ-secretase-modulating activity or toxicity could partly result from global membrane effects.
Energy Technology Data Exchange (ETDEWEB)
Weber, Nicholas D., E-mail: nweber@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Aubert, Martine, E-mail: maubert@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Dang, Chung H., E-mail: cdang@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Stone, Daniel, E-mail: dstone2@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Jerome, Keith R., E-mail: kjerome@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Department of Microbiology, University of Washington, Seattle, WA 98195 (United States)
2014-04-15
Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.
Directory of Open Access Journals (Sweden)
Shoba Subramanian
Full Text Available The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P(1 - P(4 amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P(2 position. Second, with overlapping peptides spanning alpha and beta globin and proteolysis-dependent (18O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P(2 Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents.
Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.
Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika
2016-03-04
Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.
International Nuclear Information System (INIS)
Shioyama, Yasukazu; Matsueda, Kiyoshi; Horihata, Koushi; Kimura, Masashi; Nishida, Norifumi; Kishi, Kazushi; Terada, Masaki; Sato, Morio; Yamada, Ryusaku
1996-01-01
A 51-year-old man with posthepatitis cirrhosis underwent a transjugular intrahepatic portosystemic shunt (TIPS) for bleeding of recurrent esophageal varices. The patient had a coexisting, spontaneous, splenorenal shunt. He subsequently developed hepatic encephalopathy, presumably due to excessive portosystemic shunting. Since medical management resulted in no significant improvement, the splenorenal shunt was embolized from the jugular vein approach via renal vein access during temporary balloon occlusion. Within a few days, the patient's hepatic encephalopathy resolved. Twelve months later the patient showed no recurrence of encephalopathy and had maintained a patent TIPS
Kim, Kyung Soo
2017-05-15
Simultaneous bilateral primary spontaneous pneumothorax (SBPSP) is rare, but requires surgery on both sides, in patients with definite bilateral bullae to prevent life-threatening conditions. Recently, uniportal video-assisted thoracoscopic surgery (VATS) has been widely accepted as a less invasive technique for the treatment of pneumothorax. Thus, we introduced single-staged uniportal VATS technique in the supine position, for the management of two cases of SBPSP. A 17-year-old boy presented with bilateral spontaneous pneumothorax and he underwent single-staged uniportal VATS in the supine position. Single wide draping in consecutive bilateral approaches removes the needs of changing patients' position. Whole thoracoscopic procedure for wedge resection of bullae lesions was conducted without difficulty. The total operation time took 65 min and the patient discharged 3 days after the operation. The patient was followed for 24 months without recurrence of both sides. Another 18-year-old boy was admitted with bilateral spontaneous pneumothorax and single-staged uniportal VATS was also performed in the supine position. The total operation time took 79 min and the patient discharged on postoperative day 4. He was followed for 19 months without recurrence of both sides. Single-staged uniportal VATS approach yielded satisfactory results from simplicity that not requires position change compared to conventional multi-ports VATS in the lateral position, and with better cosmetics. This technique is thought to be a feasible procedure in selective patients with SBPSP or with contralateral bullae for preventive role.
Directory of Open Access Journals (Sweden)
Marie Trudel
2016-01-01
Full Text Available Polycystin-1 (PC1 plays an essential role in renal tubular morphogenesis, and PC1 dysfunction causes human autosomal dominant polycystic kidney disease. A fundamental characteristic of PC1 is post-translational modification via cleavage at the juxtamembrane GPCR proteolysis site (GPS motif that is part of the larger GAIN domain. Given the considerable biochemical complexity of PC1 molecules generated in vivo by this process, GPS cleavage has several profound implications on the intracellular trafficking and localization in association with their particular function. The critical nature of GPS cleavage is further emphasized by the increasing numbers of PKD1 mutations that significantly affect this cleavage process. The GAIN domain with the GPS motif therefore represents the key structural element with fundamental importance for PC1 and might be polycystic kidney disease’s (PKD Achilles’ heel in a large spectrum of PKD1 missense mutations. We highlight the central roles of PC1 cleavage for the regulation of its biogenesis, intracellular trafficking and function, as well as its significance in polycystic kidney disease.
Changes in spontaneous brain activity in early Parkinson's disease.
Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue
2013-08-09
Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of pbrain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0.69). These results indicate that the abnormal resting state spontaneous brain activity associated with patients with early PD can be revealed by Reho analysis. Copyright
Cell elongation is an adaptive response for clearing long chromatid arms from the cleavage plane
Kotadia, Shaila; Montembault, Emilie; Sullivan, William
2012-01-01
Chromosome segregation must be coordinated with cell cleavage to ensure correct transmission of the genome to daughter cells. Here we identify a novel mechanism by which Drosophila melanogaster neuronal stem cells coordinate sister chromatid segregation with cleavage furrow ingression. Cells adapted to a dramatic increase in chromatid arm length by transiently elongating during anaphase/telophase. The degree of cell elongation correlated with the length of the trailing chromatid arms and was concomitant with a slight increase in spindle length and an enlargement of the zone of cortical myosin distribution. Rho guanine-nucleotide exchange factor (Pebble)–depleted cells failed to elongate during segregation of long chromatids. As a result, Pebble-depleted adult flies exhibited morphological defects likely caused by cell death during development. These studies reveal a novel pathway linking trailing chromatid arms and cortical myosin that ensures the clearance of chromatids from the cleavage plane at the appropriate time during cytokinesis, thus preserving genome integrity. PMID:23185030
Metabolic cleavage of cell-penetrating peptides in contact with epithelial models
DEFF Research Database (Denmark)
Tréhin, Rachel; Nielsen, Hanne Mørck; Jahnke, Heinz-Georg
2004-01-01
We assessed the metabolic degradation kinetics and cleavage patterns of some selected CPP (cell-penetrating peptides) after incubation with confluent epithelial models. Synthesis of N-terminal CF [5(6)-carboxyfluorescein]-labelled CPP, namely hCT (human calcitonin)-derived sequences, Tat(47-57) a...
Carotenoid Cleavage Oxygenases from Microbes and Photosynthetic Organisms: Features and Functions
Directory of Open Access Journals (Sweden)
Oussama Ahrazem
2016-10-01
Full Text Available Apocarotenoids are carotenoid-derived compounds widespread in all major taxonomic groups, where they play important roles in different physiological processes. In addition, apocarotenoids include compounds with high economic value in food and cosmetics industries. Apocarotenoid biosynthesis starts with the action of carotenoid cleavage dioxygenases (CCDs, a family of non-heme iron enzymes that catalyze the oxidative cleavage of carbon–carbon double bonds in carotenoid backbones through a similar molecular mechanism, generating aldehyde or ketone groups in the cleaving ends. From the identification of the first CCD enzyme in plants, an increasing number of CCDs have been identified in many other species, including microorganisms, proving to be a ubiquitously distributed and evolutionarily conserved enzymatic family. This review focuses on CCDs from plants, algae, fungi, and bacteria, describing recent progress in their functions and regulatory mechanisms in relation to the different roles played by the apocarotenoids in these organisms.
Kim, Kyungsub; Sim, Se-Hoon; Jeon, Che Ok; Lee, Younghoon; Lee, Kangseok
2011-02-01
RNase III, a double-stranded RNA-specific endoribonuclease, degrades bdm mRNA via cleavage at specific sites. To better understand the mechanism of cleavage site selection by RNase III, we performed a genetic screen for sequences containing mutations at the bdm RNA cleavage sites that resulted in altered mRNA stability using a transcriptional bdm'-'cat fusion construct. While most of the isolated mutants showed the increased bdm'-'cat mRNA stability that resulted from the inability of RNase III to cleave the mutated sequences, one mutant sequence (wt-L) displayed in vivo RNA stability similar to that of the wild-type sequence. In vivo and in vitro analyses of the wt-L RNA substrate showed that it was cut only once on the RNA strand to the 5'-terminus by RNase III, while the binding constant of RNase III to this mutant substrate was moderately increased. A base substitution at the uncleaved RNase III cleavage site in wt-L mutant RNA found in another mutant lowered the RNA-binding affinity by 11-fold and abolished the hydrolysis of scissile bonds by RNase III. Our results show that base substitutions at sites forming the scissile bonds are sufficient to alter RNA cleavage as well as the binding activity of RNase III. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Snake venom serine proteinases specificity mapping by proteomic identification of cleavage sites.
Zelanis, André; Huesgen, Pitter F; Oliveira, Ana Karina; Tashima, Alexandre K; Serrano, Solange M T; Overall, Christopher M
2015-01-15
Many snake venom toxins are serine proteases but their specific in vivo targets are mostly unknown. Various act on components of the coagulation cascade, and fibrinolytic and kallikrein-kinin systems to trigger various pathological effects observed in the envenomation. Despite showing high similarity in terms of primary structure snake venom serine proteinases (SVSPs) show exquisite specificity towards macromolecular substrates. Therefore, the characterization of their peptide bond specificity is important for understanding the active site preference associated with effective proteolysis as well as for the design of peptide substrates and inhibitors. Bothrops jararaca contains various SVSPs among which Bothrops protease A is a specific fibrinogenolytic agent and PA-BJ is a platelet-activating enzyme. In this study we used proteome derived peptide libraries in the Proteomic Identification of protease Cleavage Sites (PICS) approach to explore the peptide bond specificity of Bothrops protease A and PA-BJ in order to determine their individual peptide cleavage sequences. A total of 371 cleavage sites (208 for Bothrops protease A and 163 for PA-BJ) were detected and both proteinases displayed a clear preference for arginine at the P1 position. Moreover, the analysis of the specificity profiles of Bothrops protease A and PA-BJ revealed subtle differences in the preferences along P6-P6', despite a common yet unusual preference for Pro at P2. Taken together, these results map the subsite specificity of both SVSPs and shed light in the functional differences between these proteinases. Proteolysis is key to various pathological effects observed upon envenomation by viperid snakes. The use of the Proteomic Identification of protease Cleavage Sites (PICS) approach for the easy mapping of proteinase subsite preferences at both the prime- and non-prime sides concurrently gives rise to a fresh understanding of the interaction of the snake venom serine proteinases with peptide and
Zhu, Yuanyuan; Liang, Xinle; Zhang, Hong; Feng, Wei; Liu, Ye; Zhang, Fuming; Linhardt, Robert J
2017-05-02
Aspergillus oryzae koji plays a crucial role in fermented food products due to the hydrolytic activities of secreted enzymes. In the present study, we performed a comparative secretome analysis of the industrial strain of Aspergillus oryzae 3.042 and its spontaneous mutantZJGS-LZ-21. One hundred and fifty two (152) differential protein spots were excised (p<0.05), and 25 proteins were identified. Of the identified proteins, 91.3% belonged to hydrolytic enzymes acting on carbohydrates or proteins. Consistent with their enzyme activities, the expression of 14 proteins involved in the degradation of cellulose, hemicellulose, starch and proteins, increased in the ZJGS-LZ-21isolate. In particular, increased levels of acid protease (Pep) may favor the degradation of soy proteins in acidic environments and promote the cleavage of allergenic soybean proteins in fermentation, resulting in improvements of product safety and quality. The ZJGS-LZ-21 isolate showed higher protein secretion and increased hydrolytic activities than did strain 3.042, indicating its promising application in soybean paste fermentation. Copyright © 2017 Elsevier B.V. All rights reserved.
Unconjugated Bilirubin Inhibits Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Protease
Lu, Rui-Nan; Yang, Shangbin; Wu, Haifeng M.; Zheng, X. Long
2015-01-01
Summary Background Bilirubin is a yellow breakdown product of heme catabolism. Increased serum levels of unconjugated bilirubin are conditions commonly seen in premature neonates and adults with acute hemolysis including thrombotic microangiopathy. Previous studies have shown that unconjugated bilirubin lowers plasma ADAMTS13 activity, but the mechanism is not fully understood. Objectives The study is to determine whether unconjugated bilirubin directly inhibits the cleavage of von Willebrand factor (VWF) and its analogs by ADAMTS13. Methods Fluorogenic, SELDI-TOF mass spectrometric assay, and Western blotting analyses were employed to address this question. Results Unconjugated bilirubin inhibits the cleavage of F485-rVWF73-H, D633-rVWF73-H, and GST-rVWF71-11K by ADAMTS13 in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of ~13 μM, ~70 μM, and ~17 μM, respectively. Unconjugated bilirubin also dose-dependently inhibits the cleavage of multimeric VWF by ADAMTS13 under denaturing conditions. The inhibitory activity of bilirubin on the cleavage of D633-rVWF73-H and multimeric VWF, but not F485-rVWF73-H, was eliminated after incubation with bilirubin oxidase that converts bilirubin to biliverdin. Furthermore, plasma ADAMTS13 activity in patients with hyperbilirubinemia is lower prior to than after treatment with bilirubin oxidase. Conclusions unconjugated bilirubin directly inhibits ADAMTS13’s ability to cleave both peptidyl and native VWF substrates in addition to its interference with certain fluorogenic assays. Our findings may help proper interpretation of ADAMTS13 results under pathological conditions. Whether elevated serum unconjugated bilirubin has an adverse effect in vivo remains to be determined in our future study. PMID:25782102
Spontaneous compactification to homogeneous spaces
International Nuclear Information System (INIS)
Mourao, J.M.
1988-01-01
The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations
Lewis, John G; Elder, Peter A
2017-07-01
Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation and is a non-functional member of the family of serine protease inhibitors (serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL can be cleaved by human neutrophil elastase, released from activated neutrophils, and can also be cleaved at nearby site(s) by elastase released by Pseudomonas aeruginosa, and at two further sites, also within the RCL, by bovine chymotrypsin. Cleavage of the RCL results in a conformational change accompanied by a marked decrease in affinity for cortisol and hence its release at the site of proteolysis. These cleavages are irreversible and the similar half-lives of cleaved and intact CBG could mean that there may be some advantage in slowing the rate of CBG cleavage in acute inflammation thereby increasing the proportion of intact CBG in circulation. Here we show, for the first time, that pre-incubation of tethered human CBG with two monoclonal antibodies to the RCL of CBG protects against cleavage by all three enzymes. Furthermore, in plasma, pre-incubation with both RCL monoclonal antibodies delays neutrophil elastase cleavage of the RCL and one of these RCL monoclonal antibodies also delays bovine chymotrypsin cleavage of the RCL. These findings may provide a basis and rationale for the concept of the use of RCL antibodies as therapeutic agents to effectively increase the proportion of intact CBG in circulation which may be of benefit in acute inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Photoenhanced Oxidative DNA Cleavage with Non-Heme Iron(II) Complexes
Li, Qian; Browne, Wesley R.; Roelfes, Gerard
2010-01-01
The DNA cleavage activity of iron(II) complexes of a series of monotopic pentadentate N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine (N4Py)-derived ligands (1-5) was investigated under laser irradiation at 473, 400.8, and 355 nm in the absence of a reducing agent and compared to that under
Directory of Open Access Journals (Sweden)
Zakia Khanam
2015-10-01
Full Text Available In developing countries, the increasing gap between population growth and food supply has created renewed interest in finding reliable and cheap natural resources of nutraceutical value and health promoting properties. Therefore, the present study deals with the phytochemical analyses and DNA cleavage activity of Averrhoa carambola L. fruit (starfruit extracts. The phytochemical studies involve colour tests and quantification of phenolics and flavonoids of the prepared ethanolic and aqueous extracts. Identification of phenolic acids and flavonoids present in the extracts were conducted by high performance liquid chromatography (HPLC equipped with diode array detector (DAD. DNA cleavage activity of the extracts was evaluated through gel electrophoresis against plasmid Escherichia coli DNA at different concentrations (0.125–0.60 μg/μl. The results of the study exhibited that the starfruit is a rich source of polyphenols and all the extracts exhibited a dose dependent DNA cleavage activity, whereas ethanolic extract induced more cleavage as compared to the aqueous extract. In conclusion, the present study provides preliminary evidence with regard to nutraceutical value of the fruit. So, further extensive study is a prerequisite to exploit DNA cleaving properties of the fruit extracts for therapeutic application.
Directory of Open Access Journals (Sweden)
Yujie Dai
2017-12-01
Full Text Available The data presented in this article are related to the research article entitled âThe mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl free radicalâ (Dai et al., 2017 [1]. This article includes the structures of three kinds of disaccharides such as maltose, fructose and cellobiose, the diagrammatic sketch of the hydrogen abstraction reaction of the disaccharides by hydroxyl radical, the structure of the transition states for pyran ring opening of moiety A and cleavage of α(1â2 glycosidic bond starting from the hydrogen abstraction of C6âH in moiety A of sucrose, the transition state structure for cleavage of α(1â2 glycosidic bond starting from the hydrogen abstraction of C1â²-H in moiety B of sucrose, the transition state structure, sketch for the reaction process and relative energy change of the reaction pathway for direct cleavage of α(1â4 glycosidic bond starting from hydrogen abstraction of C6â²âH of moiety B of maltose.
Single-stranded DNA cleavage by divergent CRISPR-Cas9 enzymes
Ma, Enbo; Harrington, Lucas B.; O’Connell, Mitchell R.; Zhou, Kaihong; Doudna, Jennifer A.
2015-01-01
Summary Double-stranded DNA (dsDNA) cleavage by Cas9 is a hallmark of type II CRISPR-Cas immune systems. Cas9–guide RNA complexes recognize 20-base-pair sequences in DNA and generate a site-specific double-strand break, a robust activity harnessed for genome editing. DNA recognition by all studied Cas9 enzymes requires a protospacer adjacent motif (PAM) next to the target site. We show that Cas9 enzymes from evolutionarily divergent bacteria can recognize and cleave single-stranded DNA (ssDNA) by an RNA-guided, PAM-independent recognition mechanism. Comparative analysis shows that in contrast to the type II-A S. pyogenes Cas9 that is widely used for genome engineering, the smaller type II-C Cas9 proteins have limited dsDNA binding and unwinding activity and promiscuous guide-RNA specificity. These results indicate that inefficiency of type II-C Cas9 enzymes for genome editing results from a limited ability to cleave dsDNA, and suggest that ssDNA cleavage was an ancestral function of the Cas9 enzyme family. PMID:26545076
Case of spontaneous ventriculocisternostomy
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Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru [Hiroshima Univ. (Japan). School of Medicine; Kuwabara, Satoshi
1983-05-01
The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH/sub 2/O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy.
Directory of Open Access Journals (Sweden)
Natsumeda Manabu
2011-01-01
Full Text Available Abstract Introduction Examples of the spontaneous regression of primary intracranial germinomas can be found in the literature. We present the case of a patient with disseminated lesions of primary intracranial germinoma which synchronously shrunk following diagnostic irradiation. We will discuss whether this regression was spontaneous or radiation-induced. Case presentation A 43-year-old Japanese woman presented to our hospital complaining of memory problems over a period of one year and blurred vision over a period of three months. Following magnetic resonance imaging, she was found to have a massive lesion in the third ventricle and small lesions in the pineal region, fourth ventricle, and in the anterior horn of the left lateral ventricle. Prior to an open biopsy to confirm the pathology of the lesions, she underwent a single cranial computed tomography scan and a single cranial digital subtraction angiography for a transcranial biopsy. Fourteen days after the first magnetic resonance image - 12 and eight days after the computed tomography scan and digital subtraction angiography, respectively - a pre-operative magnetic resonance image was taken, which showed a notable synchronous shrinkage of the third ventricle tumor, as well as shrinkage of the lesions in the pineal region and in the fourth ventricle. She did not undergo steroid administration until after a biopsy that confirmed the pathological diagnosis of pure germinoma. She then underwent whole craniospinal irradiation and went into a complete remission. Conclusions In our case report, we state that diagnostic radiation can induce the regression of germinomas; this is the most reasonable explanation for the synchronous multiple regression observed in this case of germinoma. Clinicians should keep this non-spontaneous regression in mind and monitor germinoma lesions with minimal exposure to diagnostic radiation before diagnostic confirmation, and also before radiation treatment with or
Spontaneous Intracranial Hypotension without Orthostatic Headache
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Tülay Kansu
2009-03-01
Full Text Available We report 2 cases of spontaneous intracranial hypotension that presented with unilateral abducens nerve palsy, without orthostatic headache. While sixth nerve palsies improved without any intervention, subdural hematoma was detected with magnetic resonance imaging. We conclude that headache may be absent in spontaneous intracranial hypotension and spontaneous improvement of sixth nerve palsy can occur, even after the development of a subdural hematoma
DEFF Research Database (Denmark)
Yelle, Daniel J.; Kaparaju, Laxmi-Narasimha Prasad; Hunt, Christopher G.
2013-01-01
correlation spectroscopy, via an heteronuclear single quantum coherence experiment, revealed substantial lignin β-aryl ether cleavage, deacetylation via cleavage of the natural acetates at the 2-O- and 3-O-positions of xylan, and uronic acid depletion via cleavage of the (1 → 2)-linked 4-O....... g., further deacylation revealed by the depletion in ferulate and p-coumarate structures). Supplementary chemical analyses showed that the hydrothermal pretreatment increased the cellulose and lignin concentration with partial removal of extractives and hemicelluloses. The subsequent enzymatic...
Spontaneous intraorbital hematoma: case report
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Vinodan Paramanathan
2010-12-01
Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma
Ma, Haojie; Zhou, Xiaoqiang; Zhan, Zhenzhen; Wei, Daidong; Shi, Chong; Liu, Xingxing; Huang, Guosheng
2017-09-13
Copper catalyzed chemoselective cleavage of the C(CO)-C(alkyl) bond leading to C-N bond formation with chelation assistance of N-containing directing groups is described. Inexpensive Cu(ii)-acetate serves as a convenient catalyst for this transformation. This method highlights the emerging strategy to transform unactivated alkyl ketones into amides in organic synthesis and provides a new strategy for C-C bond cleavage.
Screening for spontaneous preterm birth
van Os, M.A.; van Dam, A.J.E.M.
2015-01-01
Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a
DEFF Research Database (Denmark)
Emanuelsson, O.; Nielsen, Henrik; von Heijne, Gunnar
1999-01-01
the cleavage sites given in SWISS-PROT. An analysis of 715 Arabidopsis thaliana sequences from SWISS-PROT suggests that the ChloroP method should be useful for the identification of putative transit peptides in genome-wide sequence data. The ChloroP predictor is available as a web-server at http......We present a neural network based method (ChloroP) for identifying chloroplast transit peptides and their cleavage sites. Using cross-validation, 88% of the sequences in our homology reduced training set were correctly classified as transit peptides or nontransit peptides. This performance level...
Early pregnancy angiogenic markers and spontaneous abortion
DEFF Research Database (Denmark)
Andersen, Louise B; Dechend, Ralf; Karumanchi, S Ananth
2016-01-01
BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between...... maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week ..., interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum
Fast cleavage of phycocyanobilin from phycocyanin for use in food colouring.
Roda-Serrat, Maria Cinta; Christensen, Knud Villy; El-Houri, Rime Bahij; Fretté, Xavier; Christensen, Lars Porskjær
2018-02-01
Phycocyanins from cyanobacteria are possible sources for new natural blue colourants. Their chromophore, phycocyanobilin (PCB), was cleaved from the apoprotein by solvolysis in alcohols and alcoholic aqueous solutions. In all cases two PCB isomers were obtained, while different solvent adducts were formed upon the use of different reagents. The reaction is believed to take place via two competing pathways, a concerted E2 elimination and a S N 2 nucleophilic substitution. Three cleavage methods were compared in terms of yield and purity: conventional reflux, sealed vessel heated in an oil bath, and microwave assisted reaction. The sealed vessel method is a new approach for fast cleavage of PCB from phycocyanin and gave at 120°C the same yield within 30min compared to 16h by the conventional reflux method (P<0.05). In addition the sealed vessel method resulted in improved purity compared to the other methods. Microwave irradiation increased product degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.
TRAIL-induced cleavage and inactivation of SPAK sensitizes cells to apoptosis
International Nuclear Information System (INIS)
Polek, Tara C.; Talpaz, Moshe; Spivak-Kroizman, Taly R.
2006-01-01
Ste20-related proline-alanine-rich kinase (SPAK) has been linked to various cellular processes, including proliferation, differentiation, and ion transport regulation. Recently, we showed that SPAK mediates signaling by the TNF receptor, RELT. The presence of a caspase cleavage site in SPAK prompted us to study its involvement in apoptotic signaling induced by another TNF member, TRAIL. We show that TRAIL stimulated caspase 3-like proteases that cleaved SPAK at two distinct sites. Cleavage had little effect on the activity of SPAK but removed its substrate-binding domain. In addition, TRAIL reduced the activity of SPAK in HeLa cells in a caspase-independent manner. Thus, TRAIL inhibited SPAK by two mechanisms: activation of caspases, which removed its substrate-binding domain, and caspase-independent down-regulation of SPAK activity. Furthermore, reducing the amount of SPAK by siRNA increased the sensitivity of HeLa cells to TRAIL-induced apoptosis. Thus, TRAIL down-regulation of SPAK is an important event that enhances its apoptotic effects
Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2
Energy Technology Data Exchange (ETDEWEB)
Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R., E-mail: grw7@cornell.edu
2014-07-25
Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.
Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2
International Nuclear Information System (INIS)
Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R.
2014-01-01
Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza
Spontaneous emission by moving atoms
International Nuclear Information System (INIS)
Meystre, P.; Wilkens, M.
1994-01-01
It is well known that spontaneous emission is not an intrinsic atomic property, but rather results from the coupling of the atom to the vacuum modes of the electromagnetic field. As such, it can be modified by tailoring the electromagnetic environment into which the atom can radiate. This was already realized by Purcell, who noted that the spontaneous emission rate can be enhanced if the atom placed inside a cavity is resonant with one of the cavity is resonant with one of the cavity modes, and by Kleppner, who discussed the opposite case of inhibited spontaneous emission. It has also been recognized that spontaneous emission need not be an irreversible process. Indeed, a system consisting of a single atom coupled to a single mode of the electromagnetic field undergoes a periodic exchange of excitation between the atom and the field. This periodic exchange remains dominant as long as the strength of the coupling between the atom and a cavity mode is itself dominant. 23 refs., 6 figs
Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway
Zaher, Manal S.; Rashid, Fahad; Song, Bo; Joudeh, Luay I; Sobhy, Mohamed Abdelmaboud; Tehseen, Muhammad; Hingorani, Manju M; Hamdan, Samir
2018-01-01
RNA-DNA hybrid primers synthesized by low fidelity DNA polymerase α to initiate eukaryotic lagging strand synthesis must be removed efficiently during Okazaki fragment (OF) maturation to complete DNA replication. In this process, each OF primer is displaced and the resulting 5'-single-stranded flap is cleaved by structure-specific 5'-nucleases, mainly Flap Endonuclease 1 (FEN1), to generate a ligatable nick. At least two models have been proposed to describe primer removal, namely short- and long-flap pathways that involve FEN1 or FEN1 along with Replication Protein A (RPA) and Dna2 helicase/nuclease, respectively. We addressed the question of pathway choice by studying the kinetic mechanism of FEN1 action on short- and long-flap DNA substrates. Using single molecule FRET and rapid quench-flow bulk cleavage assays, we showed that unlike short-flap substrates, which are bound, bent and cleaved within the first encounter between FEN1 and DNA, long-flap substrates can escape cleavage even after DNA binding and bending. Notably, FEN1 can access both substrates in the presence of RPA, but bending and cleavage of long-flap DNA is specifically inhibited. We propose that FEN1 attempts to process both short and long flaps, but occasional missed cleavage of the latter allows RPA binding and triggers the long-flap OF maturation pathway.
Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway
Zaher, Manal S.
2018-01-27
RNA-DNA hybrid primers synthesized by low fidelity DNA polymerase α to initiate eukaryotic lagging strand synthesis must be removed efficiently during Okazaki fragment (OF) maturation to complete DNA replication. In this process, each OF primer is displaced and the resulting 5\\'-single-stranded flap is cleaved by structure-specific 5\\'-nucleases, mainly Flap Endonuclease 1 (FEN1), to generate a ligatable nick. At least two models have been proposed to describe primer removal, namely short- and long-flap pathways that involve FEN1 or FEN1 along with Replication Protein A (RPA) and Dna2 helicase/nuclease, respectively. We addressed the question of pathway choice by studying the kinetic mechanism of FEN1 action on short- and long-flap DNA substrates. Using single molecule FRET and rapid quench-flow bulk cleavage assays, we showed that unlike short-flap substrates, which are bound, bent and cleaved within the first encounter between FEN1 and DNA, long-flap substrates can escape cleavage even after DNA binding and bending. Notably, FEN1 can access both substrates in the presence of RPA, but bending and cleavage of long-flap DNA is specifically inhibited. We propose that FEN1 attempts to process both short and long flaps, but occasional missed cleavage of the latter allows RPA binding and triggers the long-flap OF maturation pathway.
Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter
2015-12-15
Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20-24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5', but not 3'-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5' to the cleavage site, but several examples of 3'-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5'-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5'-cleavage fragments. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
A Case of Multiple Spontaneous Keloid Scars
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Abdulhadi Jfri
2015-07-01
Full Text Available Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.
Relationship between synthesis and cleavage of poliovirus-specific proteins.
Thomas, A A; Voorma, H O; Boeye, A
1983-01-01
Poliovirus proteinase was studied in vitro in lysates from poliovirus-infected HeLa cells. Preincubation of these lysates caused (i) a reduction in poliovirus proteinase activity and (ii) a partial dependence on exogenous mRNA for optimal translation. Proteins translated from endogenous poliovirus RNA in preincubated extracts from virus-infected HeLa cells are poorly cleaved. This cleavage deficiency is alleviated by adding fresh poliovirus RNA to the translation system, thus, allowing re-ini...
International Nuclear Information System (INIS)
Mori, Tomoaki; Nakamura, Kento; Masaoka, Keisuke; Fujita, Yusuke; Morisada, Ryosuke; Mori, Koichi; Tobimatsu, Takamasa; Sera, Takashi
2016-01-01
Various viruses infect animals and humans and cause a variety of diseases, including cancer. However, effective methodologies to prevent virus infection have not yet been established. Therefore, development of technologies to inactivate viruses is highly desired. We have already demonstrated that cleavage of a DNA virus genome was effective to prevent its replication. Here, we expanded this methodology to RNA viruses. In the present study, we used staphylococcal nuclease (SNase) instead of the PIN domain (PilT N-terminus) of human SMG6 as an RNA-cleavage domain and fused the SNase to a human Pumilio/fem-3 binding factor (PUF)-based artificial RNA-binding protein to construct an artificial RNA restriction enzyme with enhanced RNA-cleavage rates for influenzavirus. The resulting SNase-fusion nuclease cleaved influenza RNA at rates 120-fold greater than the corresponding PIN-fusion nuclease. The cleaving ability of the PIN-fusion nuclease was not improved even though the linker moiety between the PUF and RNA-cleavage domain was changed. Gel shift assays revealed that the RNA-binding properties of the PUF derivative used was not as good as wild type PUF. Improvement of the binding properties or the design method will allow the SNase-fusion nuclease to cleave an RNA target in mammalian animal cells and/or organisms. - Highlights: • A novel RNA restriction enzyme using SNase was developed tor cleave viral RNA. • Our enzyme cleaved influenza RNA with rates >120-fold higher rates a PIN-fusion one. • Our artificial enzyme with the L5 linker showed the highest RNA cleavage rate. • Our artificial enzyme site-selectively cleaved influenza RNA in vitro.
Spontaneous pneumothorax in silicotuberculosis of lung
International Nuclear Information System (INIS)
Kolenic, J.; Jurgova, T.; Zimacek, J.; Vajo, J.; Krchnavy, M.
1995-01-01
The authors describe the case of 62 years old man with the appearance of spontaneous pneumothorax, in whom the basic pulmonary disease was silicotuberculosis of the lung. At clinic of occupational diseases in Kosice have been evidence 965 cases of silicosis and silicotuberculosis. From 1971 they have now the first case of spontaneous pneumothorax. The authors make discussion about possible mechanical and biochemical factors, which cause relatively low incidence of spontaneous pneumothorax in silicosis of the lung. (authors)
International Nuclear Information System (INIS)
Du, Lanying; Kao, Richard Y.; Zhou, Yusen; He, Yuxian; Zhao, Guangyu; Wong, Charlotte; Jiang, Shibo; Yuen, Kwok-Yung; Jin, Dong-Yan; Zheng, Bo-Jian
2007-01-01
The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection
Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z; Campbell, Claudia M; Strain, Eric C
2014-02-01
Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation.
Spontaneous acute subdural hematoma: A rare presentation of a dural intracranial fistula.
de Aguiar, Guilherme Brasileiro; Veiga, José Carlos Esteves; Silva, João Miguel de Almeida; Conti, Mario Luiz Marques
2016-03-01
Dural arteriovenous fistulas are acquired lesions between the meningeal arteries and their associated draining veins. They may have highly variable clinical presentations and evolution, from severe neurological deficit to no or trivial symptoms. Intracranial hemorrhage occurs in less than 24% of all dural fistulas, and the bleeding is usually subarachnoid, more infrequently intracerebral, and rarely in the subdural space. Here, we present a rare case of a patient who presented with a subdural spontaneous hemorrhage. After investigation by cerebral angiography, the diagnosis of a dural arteriovenous fistula was made. The patient underwent uneventful endovascular treatment. As there are with only a few reports in the literature of such a presentation, we present this patient and perform a brief review of the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.
Zariffard, M Reza; Anastos, Kathryn; French, Audrey L; Munyazesa, Elisaphane; Cohen, Mardge; Landay, Alan L; Spear, Gregory T
2015-01-01
Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration. Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA. IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs. These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract.
Spontaneous body movements in spatial cognition
Directory of Open Access Journals (Sweden)
Sergiu eTcaci Popescu
2012-05-01
Full Text Available People often perform spontaneous body movements during spatial tasks such as giving complex directions or orienting themselves on maps. How are these spontaneous gestures related to spatial problem-solving? We measured spontaneous movements during a perspective-taking task inspired by map reading. Analyzing the motion data to isolate rotation and translation components of motion in specific geometric relation to the task, we found out that most participants executed spontaneous miniature rotations of the head that were significantly related to the main task parameter. These head rotations were as if participants were trying to align themselves with the orientation on the map either in the image plane or on the ground plane, but with tiny amplitudes, typically below 1% of the actual movements. Our results are consistent with a model of sensorimotor prediction driving spatial reasoning. The efference copy of planned movements triggers this prediction mechanism. The movements themselves may then be mostly inhibited; the small spontaneous gestures that we measure are the visible traces of these planned but inhibited actions.
Spontaneous pneumothorax in diffuse cystic lung diseases.
Cooley, Joseph; Lee, Yun Chor Gary; Gupta, Nishant
2017-07-01
Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of disorders with varying pathophysiologic mechanisms that are characterized by the presence of air-filled lung cysts. These cysts are prone to rupture, leading to the development of recurrent spontaneous pneumothoraces. In this article, we review the epidemiology, clinical features, and management DCLD-associated spontaneous pneumothorax, with a focus on lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, and pulmonary Langerhans cell histiocytosis. DCLDs are responsible for approximately 10% of apparent primary spontaneous pneumothoraces. Computed tomography screening for DCLDs (Birt-Hogg-Dubé syndrome, lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis) following the first spontaneous pneumothorax has recently been shown to be cost-effective and can help facilitate early diagnosis of the underlying disorders. Patients with DCLD-associated spontaneous pneumothorax have a very high rate of recurrence, and thus pleurodesis should be considered following the first episode of spontaneous pneumothorax in these patients, rather than waiting for a recurrent episode. Prior pleurodesis is not a contraindication to future lung transplant. Although DCLDs are uncommon, spontaneous pneumothorax is often the sentinel event that provides an opportunity for diagnosis. By understanding the burden and implications of pneumothoraces in DCLDs, clinicians can facilitate early diagnosis and appropriate management of the underlying disorders.
FEL gain optimisation and spontaneous radiation
Energy Technology Data Exchange (ETDEWEB)
Bali, L.M.; Srivastava, A.; Pandya, T.P. [Lucknow Univ. (India)] [and others
1995-12-31
Colson have evaluated FEL gains for small deviations from perfect electron beam injection, with radiation of the same polarisation as that of the wiggler fields. We find that for optimum gain the polarisation of the optical field should be the same as that of the spontaneous emission under these conditions. With a helical wiggler the axial oscillations resulting from small departures from perfect electron beam injection lead to injection dependent unequal amplitudes and phases of the spontaneous radiation in the two transverse directions. Viewed along the axis therefore the spontaneous emission is elliptically polarised. The azimuth of the ellipse varies with the difference of phase of the two transverse components of spontaneous emission but the eccentricity remains the same. With planar wigglers the spontaneous emission viewed in the axial direction is linearly polarised, again with an injection dependent azimuth. For optimum coherent gain of a radiation field its polarisation characteristics must be the same as those of the spontaneous radiation with both types of wiggler. Thus, with a helical wiggler and the data reported earlier, an increase of 10% in the FEL gain at the fundamental frequency and of 11% at the fifth harmonic has been calculated in the small gain per pass limit. Larger enhancements in gain may result from more favourable values of input parameters.
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Minji Sim
Full Text Available While identifying genes regulated by ribonuclease III (RNase III in Escherichia coli, we observed that steady-state levels of betT mRNA, which encodes a transporter mediating the influx of choline, are dependent on cellular concentrations of RNase III. In the present study, we also observed that steady-state levels of betT mRNA are dependent on RNase III activity upon exposure to osmotic stress, indicating the presence of cis-acting elements controlled by RNase III in betT mRNA. Primer extension analyses of betT mRNA revealed two tandem RNase III cleavage sites in its stem-loop region, which were biochemically confirmed via in vitro cleavage assays. Analyses of cleavage sites suggested the stochastic selection of cleavage sites by RNase III, and mutational analyses indicated that RNase III cleavage at either site individually is insufficient for efficient betT mRNA degradation. In addition, both the half-life and abundance of betT mRNA were significantly increased in association with decreased RNase III activity under hyper-osmotic stress conditions. Our findings demonstrate that betT mRNA stability is controlled by RNase III at the post-transcriptional level under conditions of osmotic stress.
Millet, Jean Kaoru; Goldstein, Monty E; Labitt, Rachael N; Hsu, Hung-Lun; Daniel, Susan; Whittaker, Gary R
2016-01-01
Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution. PMID:27999426
Spontaneous Bacterial Peritonitis in Subclinical Hypothyroidism
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Dalip Gupta
2013-11-01
Full Text Available Hypothyroidism is an uncommon cause of ascites. Here we describe a case of a 75 year-old female patient with spontaneous bacterial peritonitis and subclinical hypothyroidism that resolved with thyroid replacement and antibiotic therapy respectively. Ascitic fluid analysis revealed a gram-positive bacterium on gram staining. A review of the literature revealed just one other reported case of myxoedema ascites with concomitant spontaneous bacterial peritonitis and no case has till been reported of spontaneous bacterial peritonitis in subclinical hypothyroidism.
Low-energy cardioversion of spontaneous atrial fibrillation. Immediate and long-term results.
Lévy, S; Ricard, P; Gueunoun, M; Yapo, F; Trigano, J; Mansouri, C; Paganelli, F
1997-07-01
Recent studies have suggested that induced atrial fibrillation (AF) could be successfully terminated by using a two-catheter electrode system and low energy (energy cardioversion in spontaneous chronic and paroxysmal AF. Forty-two consecutive patients with spontaneous AF underwent low-energy electrical cardioversion. AF was chronic (> or = 1 month) with a mean duration of 9 +/- 19 months in 28 patients (group I) or paroxysmal with a history of recurrent attacks and a mean duration of the present episode of 7 +/- 16 days in 14 patients (group II). An underlying heart disease was present in 28 patients. A 3/3-ms biphasic shock was delivered between catheters positioned in the right atrium and the coronary sinus in 32 patients. In 10 patients, the left pulmonary artery branch was used. The catheters were connected to a custom external defibrillator. The shocks were synchronized to the R wave. Following a test shock of 60 V, the energy was increased in 40-V steps until a maximum of 400 V or restoration of sinus rhythm. Sinus rhythm was restored in 22 of the 28 patients (78%) of group I by using a mean leading-edge voltage of 297 +/- 57 V (mean energy 3.3 +/- 1.3 J) and in 11 of 14 patients (78%) of group II by using a mean leading-edge voltage of 223 +/- 41 V (mean energy, 1.8 +/- 0.7 J). The energy required for terminating chronic AF was significantly (P energy between two intracardiac catheters with an electrical field between the right and left atria and the protocol used is feasible in patients with persistent spontaneous AF. The technique is safe provided synchronization to the R wave is achieved. A low recurrence rate of AF was seen in patients in whom sinus rhythm was restored.
Spontaneous mutation rates and the rate-doubling dose
International Nuclear Information System (INIS)
Von Borstel, R.C.; Moustaccki, E.; Latarjet, R.
1978-01-01
The amount of radiation required to double the frequency of mutations or tumours over the rate of those that occur spontaneously is called the rate-doubling dose. An equivalent concept has been proposed for exposure to other environmental mutagens. The doubling dose concept is predicated on the assumption that all human populations have the same spontaneous mutation rate, and that this spontaneous mutation rate is known. It is now established for prokaryotes and lower eukaryotes that numerous genes control the spontaneous mutation rate, and it is likely that the same is true for human cells as well. Given that the accepted mode of evolution of human populatons is from small, isolated groups of individuals, it seems likely that each population would have a different spontaneous mutation rate. Given that a minimum of twenty genes control or affect the spontaneous mutation rate, and that each of these in turn is susceptible to spontaneously arising or environmentally induced mutations, it seems likely that every individual within a population (except for siblings from identical multiple births) will have a unique spontaneous mutation rate. If each individual in a population does have a different spontaneous mutation rate, the doubling dose concept, in rigorous terms, is fallacious. Therefore, as with other concepts of risk evaluation, the doubling dose concept is subject to criticism. Nevertheless, until we know individual spontaneous mutation rates with precision, and can evaluate risks based on this information, the doubling dose concept has a heuristic value and is needed for practical assessment of risks for defined populations. (author)
Evolution of elderly patients who underwent cardiac surgery with cardiopulmonary bypass
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Alain Moré Duarte
2016-01-01
Full Text Available Introduction: There is a steady increase in the number of elderly patients with severe cardiovascular diseases who require a surgical procedure to recover some quality of life that allows them a socially meaningful existence, despite the risks.Objectives: To analyze the behavior of elderly patients who underwent cardiac surgery with cardiopulmonary bypass.Method: A descriptive, retrospective, cross-sectional study was conducted with patients over 65 years of age who underwent surgery at the Cardiocentro Ernesto Che Guevara, in Santa Clara, from January 2013 to March 2014.Results: In the study, 73.1% of patients were men; and there was a predominance of subjects between 65 and 70 years of age, accounting for 67.3%. Coronary artery bypass graft was the most prevalent type of surgery and had the longest cardiopulmonary bypass times. Hypertension was present in 98.1% of patients. The most frequent postoperative complications were renal dysfunction and severe low cardiac output, with 44.2% and 34.6% respectively.Conclusions: There was a predominance of men, the age group of 65 to 70 years, hypertension, and patients who underwent coronary artery bypass graft with prolonged cardiopulmonary bypass. Renal dysfunction was the most frequent complication.
Discrete population balance models of random agglomeration and cleavage in polymer pyrolysis
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John E. J. Staggs
2017-05-01
Full Text Available The processes of random agglomeration and cleavage (both of which are important for the development of new models of polymer combustion, but are also applicable in a wide range of fields including atmospheric physics, radiation modelling and astrophysics are analysed using population balance methods. The evolution of a discrete distribution of particles is considered within this framework, resulting in a set of ordinary differential equations for the individual particle concentrations. Exact solutions for these equations are derived, together with moment generating functions. Application of the discrete Laplace transform (analogous to the Z-transform is found to be effective in these problems, providing both exact solutions for particle concentrations and moment generating functions. The combined agglomeration-cleavage problem is also considered. Unfortunately, it has been impossible to find an exact solution for the full problem, but a stable steady state has been identified and computed.
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Annie Nguyen
Full Text Available Cystatin C (Cys C is a small, potent, cysteine protease inhibitor. An Ala25Thr (A25T polymorphism in Cys C has been associated with both macular degeneration and late-onset Alzheimer's disease. Previously, studies have suggested that this polymorphism may compromise the secretion of Cys C. Interestingly, we found that untagged A25T, A25T tagged C-terminally with FLAG, or A25T FLAG followed by green fluorescent protein (GFP, were all secreted as efficiently from immortalized human cells as their wild-type (WT counterparts (e.g., 112%, 100%, and 88% of WT levels from HEK-293T cells, respectively. Supporting these observations, WT and A25T Cys C variants also showed similar intracellular steady state levels. Furthermore, A25T Cys C did not activate the unfolded protein response and followed the same canonical endoplasmic reticulum (ER-Golgi trafficking pathway as WT Cys C. WT Cys C has been shown to undergo signal sequence cleavage between residues Gly26 and Ser27. While the A25T polymorphism did not affect Cys C secretion, we hypothesized that it may alter where the Cys C signal sequence is preferentially cleaved. Under normal conditions, WT and A25T Cys C have the same signal sequence cleavage site after Gly26 (referred to as 'site 2' cleavage. However, in particular circumstances when the residues around site 2 are modified (such as by the presence of an N-terminal FLAG tag immediately after Gly26, or by a Gly26Lys (G26K mutation, A25T has a significantly higher likelihood than WT Cys C of alternative signal sequence cleavage after Ala20 ('site 1' or even earlier in the Cys C sequence. Overall, our results indicate that the A25T polymorphism does not cause a significant reduction in Cys C secretion, but instead predisposes the protein to be cleaved at an alternative signal sequence cleavage site if site 2 is hindered. Additional N-terminal amino acids resulting from alternative signal sequence cleavage may, in turn, affect the protease
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Chau-Chyun Sheu
2006-02-01
Full Text Available Infective endocarditis has been the major cause of morbidity and mortality among intravenous drug users (IDUs with infections, mostly involving the tricuspid valve and presenting multiple septic pulmonary embolisms. Numerous pulmonary complications of septic pulmonary embolism have been described, but only a few have reported spontaneous pneumothorax. Our patient, a 23-year-old heroin addict, was hospitalized for tricuspid endocarditis and septic pulmonary embolism. Acute onset of respiratory distress occurred on his seventh hospital day and rapidly resulted in hypoxemia. Immediate bedside chest radiograph demonstrated left pneumothorax. It was thought to be a spontaneous pneumothorax, because he had not undergone any invasive procedure before the occurrence of pneumothorax. His clinical condition improved after the insertion of an intercostal chest tube. He later underwent surgery to replace the tricuspid valve as a result of the large size of the vegetation and poor control of infection. He ultimately survived. Pneumothorax is a possible lethal complication of septic pulmonary embolism in IDUs with right-sided endocarditis and should be considered in such patients when respiratory distress occurs acutely during their hospitalization.
Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist
Huys, Raoul; Jirsa, Viktor K.; Darokhan, Ziauddin; Valentiniene, Sonata; Roland, Per E.
2016-01-01
Neurons in the primary visual cortex spontaneously spike even when there are no visual stimuli. It is unknown whether the spiking evoked by visual stimuli is just a modification of the spontaneous ongoing cortical spiking dynamics or whether the spontaneous spiking state disappears and is replaced by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization is that it avoids the need for a system reorganization following visual stimulation, and impedes the transition of spontaneous spiking to evoked spiking and the propagation of spontaneous spiking from layer 4 to layers 2–3. PMID:26778982
Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter
2015-01-01
Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20–24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5′, but not 3′-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5′ to the cleavage site, but several examples of 3′-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5′-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5′-cleavage fragments. PMID:26464441
Peritonitis - spontaneous bacterial
Spontaneous bacterial peritonitis (SBP); Ascites - peritonitis; Cirrhosis - peritonitis ... who are on peritoneal dialysis for kidney failure. Peritonitis may have other causes . These include infection from ...
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Hélène Sanfaçon
2017-04-01
Full Text Available Strawberry mottle virus (SMoV, family Secoviridae, order Picornavirales is one of several viruses found in association with strawberry decline disease in Eastern Canada. The SMoV genome consists of two positive-sense single-stranded RNAs, each encoding one large polyprotein. The RNA1 polyprotein (P1 includes the domains for a putative helicase, a VPg, a 3C-like cysteine protease and an RNA-dependent RNA polymerase at its C-terminus, and one or two protein domains at its N-terminus. The RNA2 polyprotein (P2 is predicted to contain the domains for a movement protein (MP and one or several coat proteins at its N-terminus, and one or more additional domains for proteins of unknown function at its C-terminus. The RNA1-encoded 3C-like protease is presumed to cleave the two polyproteins in cis (P1 and in trans (P2. Using in vitro processing assays, we systematically scanned the two polyproteins for cleavage sites recognized by this protease. We identified five cis-cleavage sites in P1, with cleavage between the putative helicase and VPg domains being the most efficient. The presence of six protein domains in the SMoV P1, including two upstream of the putative helicase domain, is a feature shared with nepoviruses but not with comoviruses. Results from trans-cleavage assays indicate that the RNA1-encoded 3C-like protease recognized a single cleavage site, which was between the predicted MP and coat protein domains in the P2 polyprotein. The cleavage site consensus sequence for the SMoV 3C-like protease is AxE (E or Q/(G or S.
International Nuclear Information System (INIS)
Mikheev, V.L.; Tret'yakova, S.P.; Golovchenko, A.N.; Timofeeva, O.V.; Hussonnois, M.; Le Naour, C.
1998-01-01
The low limit of the 226 Ra spontaneous fission half-life corresponding to T 1/2 ≥ 4 · 10 18 years is measured. The 226 Ra spontaneous fission probability proved to be about 50 times less than the value expected from the known systematics, connecting the ratios of theα-decay and spontaneous fission probabilities with the fissility parameter Z 2 /A. It is shown that the probabilities of spontaneous fission, α-decay and cluster decay can be systematized in the same way according to the difference between the decay products Coulomb energy near the scission point and decay energy Q
Dorsomedial prefontal cortex supports spontaneous thinking per se.
Raij, T T; Riekki, T J J
2017-06-01
Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Maternal smoking predicts the risk of spontaneous abortion
DEFF Research Database (Denmark)
Nielsen, Ann; Hannibal, Charlotte Gerd; Lindekilde, Bodil Eriksen
2006-01-01
BACKGROUND: Few studies have examined smoking prior to pregnancy and the occurrence of spontaneous abortion, as most studies have addressed the risk of spontaneous abortion in relation to smoking during pregnancy. However, results are not entirely consistent. The aim of the present study...... was to assess the risk of spontaneous abortion considering smoking prior to pregnancy. METHODS: We performed a nested case-control study using prospective data from a population-based cohort comprising 11,088 women aged 20-29 years. From this cohort, women who experienced either a spontaneous abortion (n=343......) or who gave birth (n=1,578) during follow-up were selected. Associations between self-reported smoking at enrollment and subsequent spontaneous abortion were analyzed by means of multiple logistic regression. RESULTS: The risk of spontaneous abortion in relation to pre-pregnancy smoking showed a clear...
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Parag Chevli
2014-09-01
Full Text Available Spontaneous coronary artery dissection (SCAD is a rare cause of acute myocardial infarction that is more common in younger patients (under age 50 and in women. Although the etiology is not known, some predisposing conditions to SCAD are well known and include Marfan syndrome, pregnancy and peripartum state, drug abuse, and some anatomical abnormalities of the coronary arteries such as aneurysms and severe kinking. We describe a case of SCAD in a young woman who presented with sudden onset of chest pain and was admitted for the treatment of acute coronary syndrome. The coronary angiography showed dissection of the left anterior descending artery. The patient underwent successful percutaneous transluminal coronary angioplasty and stent placement.
Spontaneous chylothorax complicating small cell lung cancer – Review of aetiology and diagnosis
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S. Hanina
2015-01-01
Full Text Available We report the first case of spontaneous chylothorax complicating small cell lung cancer. A 52 year old female presented with exertional dyspnoea, left-sided chest and neck pain, and dysphagia. The chest X-ray on admission revealed a large left-sided pleural effusion. A subsequent CT chest showed a large anterior mediastinal mass with a left brachiocephalic and jugular vein thrombosis. The patient underwent medical thoracoscopy with chest drain insertion, which drained pleural fluid high in triglycerides, consistent with a chylothorax. Due to its uncommon nature, the management of chylothorax is not well defined. Alongside the case report, we provide a review of aetiology, mechanism and diagnosis with a brief summary of treatment options.
Micromechanisms and toughness for cleavage fracture of steel
International Nuclear Information System (INIS)
Rosenfield, A.R.; Majumdar, B.S.
1987-01-01
A complete understanding of the fracture mechanisms of steel in the ductile/brittle transition region requires analysis not only of crack initiation, but also of crack propagation. This paper reviews micrographic and fractographic experiments that give insight into both phenomena, and suggests a frame-work through which both may be related. Unstable cleavage crack initiation can occur after some blunting of the original fatigue precrack or after some stable crack growth. In either event, instability appears to be triggered by the fracture of a brittle micro-constituent ahead of the precrack. The large scatter in reported K IC values within the transition region reflects the size distribution and relative scarcity of these 'trigger' particles. While a large number of models have attempted to correlate toughness in the ductile/brittle transition regime to events occurring ahead of the crack tip, surprisingly little attention has been paid to events occurring behind the crack front. Fractographic evidence as well as metallographic sectioning of arrested cracks show that the mechanism of rapid crack propagation by cleavage is affected strongly by partial crack-plane deflection which leaves unbroken ligaments in its wake. The tearing of these ligaments by dimple-rupture is the dominant energy-absorbing mechanism. Etch-pit experiments using an Fe-Si alloy show that the crack-tip stress intensity based on plastic zone size is extremely low. It is suggested that the mechanism of crack arrest should be modeled using a sharp crack which is restrained by a distribution of discrete pinching forces along its faces. The same model is applied to crack initiation. (orig.)
Osteonecrosis or spontaneous fractures following renal transplantation
International Nuclear Information System (INIS)
Andresen, J.; Nielsen, H.E.; Aarhus Univ.
1981-01-01
31 renal transplant recipients with posttransplant development of osteonecrosis or spontaneous fractures were evaluated with regard to age, duration of dialysis before transplantation. Determination of metacarpal bone mass at the time of transplantation and registration of bone resorption and soft tissue calcification at the time of transplantation and at the time of onset of osteonecrosis and spontaneous fractures were made. Apart from the increased mean age in patients with spontaneous fractures no difference was seen between the groups. Osteonecrosis and spontaneous fractures occurred in areas of trabecular bone. It seems most likely that after renal transplantation the patients show bone complications of different localization. (orig.) [de
A Case of Spontaneously Resolved Bilateral Primary Spontaneous Pneumothorax
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Hasan Kahraman
2014-03-01
Full Text Available A condition of intrapleural air-space accumulation in individuals without any history of trauma or lung disease is called as primary spontaneous pneumothorax (PSP. Sixteen-years-old male patient admitted with complains of chest pain and dyspnea beginning 3 day ago. On physical examination, severity of breath sounds decreased on right side. Chest radiograph was taken and right-sided pneumothorax was detected and tube thoracostomy was inserted. Two months ago the patient referred to a doctor with similar complaints and physical examination and chest radiograph were reported as normal. The radiograph was retrospectively examined and bilateral PSP was detected. We presented the case duo to spontaneous recovery of bilateral PSP is seen very rarely and so contributes data to the literature. In patients admitted to the clinic with chest pain and shortness of breath, pneumothorax should be considered at differential diagnosis.
Cleavage and protection of locked nucleic acid-modified DNA by restriction endonucleases
DEFF Research Database (Denmark)
Crouzier, Lucile; Dubois, Camille; Wengel, Jesper
2012-01-01
Locked nucleic acid (LNA) is one of the most prominent nucleic acid analogues reported so far. We herein for the first time report cleavage by restriction endonuclease of LNA-modified DNA oligonucleotides. The experiments revealed that RsaI is an efficient enzyme capable of recognizing and cleaving...
Wong, W M; Tam, T Cc; Wong, M Ky; Lui, M Ms; Ip, M Sm; Lam, D Cl
2016-08-01
Malignant pleural effusion can be recurrent despite active anti-cancer treatment. Significant malignant pleural effusion leads to debilitating dyspnoea and worsening quality of life in patients with advanced cancer. An indwelling pleural catheter offers a novel means to manage recurrent malignant pleural effusion and may remove the need for repeated thoracocentesis. Spontaneous pleurodesis is another unique advantage of indwelling pleural catheter placement but the factors associated with its occurrence are not clearly established. The aims of this study were to explore the safety of an indwelling pleural catheter in the management of symptomatic recurrent malignant pleural effusion, and to identify the factors associated with spontaneous pleurodesis. This case series with internal comparisons was conducted in the Division of Respiratory Medicine, Department of Medicine, Queen Mary Hospital, Hong Kong. All patients who underwent insertion of an indwelling pleural catheter from the initiation of such service from January 2010 to December 2014 were included for data analysis. Patients were monitored until December 2014, with the last catheter inserted in July 2014. Between 2010 and 2014, a total of 23 indwelling pleural catheters were inserted in 22 consecutive patients with malignant pleural effusion, including 15 (65.2%) cases with malignant pleural effusion as a result of metastatic lung cancer. Ten (43.5%) cases achieved minimal output according to defined criteria, in five of whom the pleural catheter was removed without subsequent re-accumulation of effusion (ie spontaneous pleurodesis). Factors associated with minimal output were the absence of trapped lung (P=0.036), shorter time from first appearance of malignant pleural effusion to catheter insertion (P=0.017), and longer time from catheter insertion till patient's death or end of study (P=0.007). An indwelling pleural catheter provides a safe means to manage symptomatic malignant pleural effusion
Maternal underweight and the risk of spontaneous abortion
DEFF Research Database (Denmark)
Helgstrand, Stine; Andersen, Anne-Marie Nybo
2005-01-01
BACKGROUND: To evaluate the risk of spontaneous abortion in relation to maternal pre-pregnant underweight. METHODS: The study was designed as a cohort study within the framework of the Danish National Birth Cohort (DNBC). The participants were a total of 23 821 women recruited consecutively...... spontaneous abortion. Relative risk of spontaneous abortion was calculated as Hazard Ratios using Cox regression with delayed entry. RESULTS: The outcome measure was spontaneous abortion. The hazard ratio for spontaneous abortion in women with a pre-pregnant body mass index (BMI) below 18.5 was 1.24 (95......% confidence limits 0.95-1.63) compared to women with pre-pregnant BMI 18.5-24.9. Women with a BMI of 25 or more had a smaller increase in risk of spontaneous abortion. Adjustment for maternal age, parity, previous miscarriages, and lifestyle factors did not affect the estimates substantially, neither did...
Cleavage sites in the polypeptide precursors of poliovirus protein P2-X
International Nuclear Information System (INIS)
Selmer, B.L.; Hanecak, R.; Anderson, C.W.; Wimmer, E.
1981-01-01
Partial amino-terminal sequence analysis has been performed on the three major polypeptide products (P2-3b, P2-5b, and P2-X) from the central region (P2) of the poliovirus polyprotein, and this analysis precisely locates the amino termini of these products with respect to the nucleotide sequence of the poliovirus RNA genome. Like most of the products of the replicase region (P3), the amino termini of P2-5b and P2-X are generated by cleavage between glutamine and glycine residues. Thus, P2-5b and P2-X are probably both produced by the action of a singly (virus-encoded.) proteinase. The amino terminus of P2-3b, on the other hand, is produced by a cleavage between the carboxy-terminal tyrosine of VP1 and the glycine encoded by nucleotides 3381-3383. This result may suggest that more than one proteolytic activity is required for the complete processing of the poliovirus polyprotein
Adriana Santos, Carla; Fonseca, Jorge; Brito, José; Fernandes, Tânia; Gonçalves, Luísa; Sousa Guerreiro, António
2014-01-01
Background and aims: Dysphagic patients who underwent endoscopic gastrostomy (PEG) usually present protein-energy malnutrition, but little is known about micronutrient malnutrition. The aim of the present study was the evaluation of serum zinc in patients who underwent endoscopic gastrostomy and its relationship with serum proteins, whole blood zinc, and the nature of underlying disorder. Methods: From patients that underwent gastrostomy a blood sample was obtained minutes before the procedur...
International Nuclear Information System (INIS)
Galiy, P.V.; Musyanovych, A.V.; Nenchuk, T.M.
2005-01-01
The results of the quantitative X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) of the interface carbon layer formation on the cleavage surfaces of the layered semiconductor In 4 Se 3 crystals are presented. The carbon coating formation occurs as the result of interaction of the air and residual gases atmosphere in ultra high vacuum (UHV) Auger spectrometer chamber with atomic clean interlayer cleavage surfaces of the crystals. The kinetics and peculiarities of interfacial carbon layer formation on the cleavage surfaces of the crystals, elemental and phase composition of the interface have been studied by quantitative XPS, AES and mass-spectroscopy
Edelman, Benjamin; Geradin, Damien
Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors
International Nuclear Information System (INIS)
Nohmi, Takehiko; Battista, J.R.; Dodson, L.A.; Walker, G.C.
1988-01-01
The products of the SOS-regulated umuDC operon are required for most UV and chemical mutagenesis in Escherichia coli. It has been shown that the UmuD protein shares homology with LexA, the repressor of the SOS genes. In this paper the authors describe a series of genetic experiments that indicate that the purpose of RecA-mediated cleavage of UmuD at its bond between Cys-24 and Gly-25 is to activate UmuD for its role in mutagenesis and that the COOH-terminal fragment of UmuD is necessary and sufficient for the role of UmuD in UV mutagenesis. Other genetic experiments are presented that (i) support the hypothesis that the primary role of Ser-60 in UmuD function is to act as a nucleophile in the RecA-mediated cleavage reaction and (ii) raise the possibility that RecA has a third role in UV mutagenesis besides mediating the cleavage of LexA and UmuD
International Nuclear Information System (INIS)
Sriram, Bandi; Thakral, Deepshi; Panda, Subrat Kumar
2003-01-01
The 3' end of hepatitis E virus (HEV) contains cis-acting regulatory element, which plays an important role in viral replication. To develop specific replication inhibitor at the molecular level, mono- and di-hammerhead ribozymes (Rz) were designed and synthesized against the conserved 3' end sequences of HEV, which cleave at nucleotide positions 7125 and 7112/7125, respectively. Di-hammerhead ribozyme with two catalytic motifs in tandem was designed to cleave simultaneously at two sites spaced 13 nucleotides apart, which increases the overall cleavage efficiency and prevents the development of escape mutants. Specific cleavage products were obtained with both the ribozymes in vitro at physiological conditions. The inactive control ribozymes showed no cleavage. The ribozymes showed specific inhibition of HEV 3' end fused-luciferase reporter gene expression by ∼37 and ∼60%, respectively in HepG2 cells. These results demonstrate a feasible approach to inhibit the HEV replication to a limited extent by targeting the cis-acting 3' end of HEV with hammerhead ribozymes
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Gina Zavaleta Espejo
2013-09-01
Full Text Available In this study we evaluated the effect of Albendazole at different concentrations and exposure times on the process of fertilization and early cleavage in Tetrapygus niger "sea urchin". Each experimental group consisted of 200 mL, of previously filtered seawater at pH 7.3 and temperature of 20 ± 2 °C, plus five drops of eggs and two drops of spermatozoa exposed to different concentrations of Albendazole 400 ppm, 800 ppm and 1200 ppm. Determining the effect of Albendazole was conducted by counting the number of cones of fertilization, as well as the number of cleaving embryos with normal and abnormal. The ANOVA and multiple comparison test Tukey averages showed significant differences between the treatments, namely that increasing the concentration of Albendazole fertilization rate decreases and increases the percentage of embryos with abnormal cleavage, so therefore concluded that the Albendazole at different concentrations and exposure times affects the process of fertilization and early cleavage in T, niger "sea urchin"
A case of spontaneous ventriculocisternostomy
International Nuclear Information System (INIS)
Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru; Kuwabara, Satoshi.
1983-01-01
The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH 2 O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy. (J.P.N.)
Kristensen, Thea; Normann, Preben; Gullberg, Maria; Fahnøe, Ulrik; Polacek, Charlotta; Rasmussen, Thomas Bruun; Belsham, Graham J
2017-03-01
The foot-and-mouth disease virus (FMDV) capsid precursor, P1-2A, is cleaved by FMDV 3C protease to yield VP0, VP3, VP1 and 2A. Cleavage of the VP1/2A junction is the slowest. Serotype O FMDVs with uncleaved VP1-2A (having a K210E substitution in VP1; at position P2 in cleavage site) have been described previously and acquired a second site substitution (VP1 E83K) during virus rescue. Furthermore, introduction of the VP1 E83K substitution alone generated a second site change at the VP1/2A junction (2A L2P, position P2' in cleavage site). These virus adaptations have now been analysed using next-generation sequencing to determine sub-consensus level changes in the virus; this revealed other variants within the E83K mutant virus population that changed residue VP1 K210. The construction of serotype A viruses with a blocked VP1/2A cleavage site (containing K210E) has now been achieved. A collection of alternative amino acid substitutions was made at this site, and the properties of the mutant viruses were determined. Only the presence of a positively charged residue at position P2 in the cleavage site permitted efficient cleavage of the VP1/2A junction, consistent with analyses of diverse FMDV genome sequences. Interestingly, in contrast to the serotype O virus results, no second site mutations occurred within the VP1 coding region of serotype A viruses with the blocked VP1/2A cleavage site. However, some of these viruses acquired changes in the 2C protein that is involved in enterovirus morphogenesis. These results have implications for the testing of potential antiviral agents targeting the FMDV 3C protease.
Energy Technology Data Exchange (ETDEWEB)
Zhang, Shaoguang; Appel, Aaron M.; Bullock, R. Morris
2017-05-18
Controlling the heterolytic cleavage of the H-H bond of dihydrogen is critically important in catalytic hydrogenations and in the catalytic oxidation of H2. We show how the rate of reversible heterolytic cleavage of H2 can be controlled over nearly four orders of magnitude at 25 °C, from 2.1 × 103 s-1 to ≥107 s-1. Bifunctional Mo complexes, [CpMo(CO)(κ3-P2N2)]+ (P2N2 = 1,5-diaza-3,7-diphosphacyclooctane with alkyl/aryl groups on N and P), have been developed for heterolytic cleavage of H2 into a proton and a hydride, akin to Frustrated Lewis Pairs. The H-H bond cleavage is enabled by the basic amine in the second coordination sphere. The products of heterolytic cleavage of H2, Mo hydride complexes bearing protonated amines, [CpMo(H)(CO)(P2N2H)]+, were characterized by spectroscopic studies and by X-ray crystallography. Variable temperature 1H, 15N and 2-D 1H-1H ROESY NMR spectra indicated rapid exchange of the proton and hydride. The exchange rates are in the order [CpMo(H)(CO)(PPh2NPh2H)]+ > [CpMo(H)(CO)(PtBu2NPh2H)]+ > [CpMo(H)(CO)(PPh2NBn2H)]+ > [CpMo(H)(CO)(PtBu2NBn2H)]+ > [CpMo(H)(CO)(PtBu2NtBu2H)]+. The pKa values determined in acetonitrile range from 9.3 to 17.7, and show a linear correlation with the logarithm of the exchange rates. Thus the exchange dynamics are controlled through the relative acidity of the [CpMo(H)(CO)(P2N2H)]+ and [CpMo(H2)(CO)(P2N2)]+ isomers, providing a design principle for controlling heterolytic cleavage of H2.
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Guiyun Zhang
2017-01-01
Full Text Available Background and Purpose. Spontaneous vertebral artery dissection (SVAD is an important reason for posterior-circulation-ischemic stroke in the young and middle-aged population. Although some previous reports reveal a favorable outcome with conservative therapy, it is still controversial in the treatment of SVAD in some specific patients. Herein, we present our 10 years of clinical experience for SVAD at this location. Material and Methods. 20 patients with 20 SVADs in V2 and V3 segments were retrospectively studied. Clinical manifestations and imageology materials were collected and analyzed. All the patients underwent anticoagulation except for one patient because of contraindication. 14 patients underwent Wingspan stents implantation with general anesthesia. Results. In our sample, ischemia (infarction or transient ischemic attack, TIA was found in all the patients. Angiographic stenosis and dissection aneurysm were the most common findings in the segments mentioned above. 19 of the patients (95% got the excellent imageological and clinical outcomes. Conclusions. According to our experience in this group, although anticoagulation is effective in vertebral artery dissection, interventional therapy for SVADs in V2 and/or V3 segments is preferred in some specific patients. Stent with higher radial supporting and flexibility, such as Wingspan stent, is suggested.
Alkali metal control over N-N cleavage in iron complexes.
Grubel, Katarzyna; Brennessel, William W; Mercado, Brandon Q; Holland, Patrick L
2014-12-03
Though N2 cleavage on K-promoted Fe surfaces is important in the large-scale Haber-Bosch process, there is still ambiguity about the number of Fe atoms involved during the N-N cleaving step and the interactions responsible for the promoting ability of K. This work explores a molecular Fe system for N2 reduction, particularly focusing on the differences in the results obtained using different alkali metals as reductants (Na, K, Rb, Cs). The products of these reactions feature new types of Fe-N2 and Fe-nitride cores. Surprisingly, adding more equivalents of reductant to the system gives a product in which the N-N bond is not cleaved, indicating that the reducing power is not the most important factor that determines the extent of N2 activation. On the other hand, the results suggest that the size of the alkali metal cation can control the number of Fe atoms that can approach N2, which in turn controls the ability to achieve N2 cleavage. The accumulated results indicate that cleaving the triple N-N bond to nitrides is facilitated by simultaneous approach of least three low-valent Fe atoms to a single molecule of N2.
Quantifying emissions from spontaneous combustion
Energy Technology Data Exchange (ETDEWEB)
NONE
2013-09-01
Spontaneous combustion can be a significant problem in the coal industry, not only due to the obvious safety hazard and the potential loss of valuable assets, but also with respect to the release of gaseous pollutants, especially CO2, from uncontrolled coal fires. This report reviews methodologies for measuring emissions from spontaneous combustion and discusses methods for quantifying, estimating and accounting for the purpose of preparing emission inventories.
Heavily T2-weighted MR myelography vs CT myelography in spontaneous intracranial hypotension.
Wang, Y-F; Lirng, J-F; Fuh, J-L; Hseu, S-S; Wang, S-J
2009-12-01
To assess the diagnostic accuracy of heavily T2-weighted magnetic resonance myelography (MRM) in patients with spontaneous intracranial hypotension (SIH). Patients with SIH were recruited prospectively, and first underwent MRM and then computed tomographic myelography (CTM). The results of MRM were validated with the gold standard, CTM, focusing on 1) CSF leaks along the nerve roots, 2) epidural CSF collections, and 3) high-cervical (C1-3) retrospinal CSF collections. Comparisons of these 3 findings between the 2 studies were made by kappa statistics and agreement rates. Targeted epidural blood patches (EBPs) were placed at the levels of CSF leaks if supportive treatment failed. Nineteen patients (6 men and 13 women, mean age 37.9 +/- 8.6 years) with SIH completed the study. MRM did not differ from CTM in the detection rates of CSF leaks along the nerve roots (84% vs 74%, p = 0.23), high-cervical retrospinal CSF collections (32% vs 16%, p = 0.13), and epidural CSF collections (89% vs 79%, p = 0.20). MRM demonstrated more spinal levels of CSF leaks (2.2 +/- 1.7 vs 1.5 +/- 1.5, p = 0.011) and epidural collections (12.2 +/- 5.9 vs 7.1 +/- 5.8, p localizing CSF leaks for patients with spontaneous intracranial hypotension. This noninvasive technique may be an alternative to computed tomographic myelography before targeted epidural blood patches.
Feng, Tao; Nyffenegger, Christian; Højrup, Peter; Vidal-Melgosa, Silvia; Yan, Kok-Phen; Fangel, Jonatan Ulrik; Meyer, Anne S; Kirpekar, Finn; Willats, William G; Mikkelsen, Jørn D
2014-12-01
Compared to other plant cell wall-degrading enzymes, proteases are less well understood. In this study, the extracellular metalloprotease Prt1 from Pectobacterium carotovorum (formerly Erwinia carotovora) was expressed in Escherichia coli and characterized with respect to N-terminal processing, thermal stability, substrate targets, and cleavage patterns. Prt1 is an autoprocessing protease with an N-terminal signal pre-peptide and a pro-peptide which has to be removed in order to activate the protease. The sequential cleavage of the N-terminus was confirmed by mass spectrometry (MS) fingerprinting and N-terminus analysis. The optimal reaction conditions for the activity of Prt1 on azocasein were at pH 6.0, 50 °C. At these reaction conditions, K M was 1.81 mg/mL and k cat was 1.82 × 10(7) U M(-1). The enzyme was relatively stable at 50 °C with a half-life of 20 min. Ethylenediaminetetraacetic acid (EDTA) treatment abolished activity; Zn(2+) addition caused regain of the activity, but Zn(2+)addition decreased the thermal stability of the Prt1 enzyme presumably as a result of increased proteolytic autolysis. In addition to casein, the enzyme catalyzed degradation of collagen, potato lectin, and plant extensin. Analysis of the cleavage pattern of different substrates after treatment with Prt1 indicated that the protease had a substrate cleavage preference for proline in substrate residue position P1 followed by a hydrophobic residue in residue position P1' at the cleavage point. The activity of Prt1 against plant cell wall structural proteins suggests that this enzyme might become an important new addition to the toolbox of cell-wall-degrading enzymes for biomass processing.
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Tong Guo
2012-10-01
Full Text Available Abstract Objectives This study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population. Study design We compared the clinical results of embryo transfer on the 3rd (cleavage stage or 5th (blastocyst stage day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates. Results Our data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05 and implantation rate (31.8% vs 31.2%, p>0.05 in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05. Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8% and implantation rate (47% compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively. For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p Conclusions In an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic Chinese patients.
Tong, Guo Qing; Cao, Shan Ren; Wu, Xun; Zhang, Jun Qiang; Cui, Ji; Heng, Boon Chin; Ling, Xiu Feng
2012-10-05
This study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population. We compared the clinical results of embryo transfer on the 3rd (cleavage stage) or 5th (blastocyst stage) day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates. Our data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05) and implantation rate (31.8% vs 31.2%, p>0.05) in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05). Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8%) and implantation rate (47%) compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively). For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p<0.05). However, the cumulative multiple pregnancy rates showed no significant difference between the two groups. In an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic Chinese patients.
Kwong, M. Y.; Harris, R. J.
1994-01-01
Under favorable conditions, Asp or Asn residues can undergo rearrangement to a succinimide (cyclic imide), which may also serve as an intermediate for deamidation and/or isoaspartate formation. Direct identification of such succinimides by peptide mapping is hampered by their lability at neutral and alkaline pH. We determined that incubation in 2 M hydroxylamine, 0.2 M Tris buffer, pH 9, for 2 h at 45 degrees C will specifically cleave on the C-terminal side of succinimides without cleavage at Asn-Gly bonds; yields are typically approximately 50%. N-terminal sequence analysis can then be used to identify an internal sequence generated by cleavage of the succinimide, hence identifying the succinimide site. PMID:8142891
Coronavirus 3CL(pro) proteinase cleavage sites: Possible relevance to SARS virus pathology
DEFF Research Database (Denmark)
Kiemer, Lars; Lund, Ole; Brunak, Søren
2004-01-01
the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection...
Location of Ruptured Bullae in Secondary Spontaneous Pneumothorax
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Jinseok Choi
2017-12-01
Full Text Available Background: The surgical treatment of secondary spontaneous pneumothorax (SSP can be complicated by fragile lung parenchyma. The preoperative prediction of air leakage could help prevent intraoperative lung in-jury during manipulation of the lung. Common sites of bulla development and ruptured bullae were inves-tigated based on computed tomography (CT and intraoperative findings. Methods: The study enrolled 208 patients with SSP who underwent air leak control through video-assisted thoracoscopic surgery (VATS. We retrospectively reviewed the sites of bulla development on preoperative CT and the rupture sites during VATS. Results: Of the 135 cases of right-sided SSP, the most common rupture site was the apical segment (31.9%, followed by the azygoesophageal recess (27.4%. Of the 75 cases on the left side, the most com-mon rupture site was the apical segment (24.0%, followed by the anterior basal segment (17.3%. Conclusion: The azygoesophageal recess and parenchyma along the cardiac border were common sites of bul-la development and rupture. Studies of respiratory lung motion to measure the pleural pressure at the lung surface could help to determine the relationship between cardiogenic and diaphragmatic movement and bulla formation or rupture.
Recent Advances in Ring-Opening Functionalization of Cycloalkanols by C-C σ-Bond Cleavage.
Wu, Xinxin; Zhu, Chen
2018-06-01
Cycloalkanols prove to be privileged precursors for the synthesis of distally substituted alkyl ketones and polycyclic aromatic hydrocarbons (PAHs) by virtue of cleavage of their cyclic C-C bonds. Direct functionalization of cyclobutanols to build up other chemical bonds (e. g., C-F, C-Cl, C-Br, C-N, C-S, C-Se, C-C, etc.) has been achieved by using the ring-opening strategy. Mechanistically, the C-C cleavage of cyclobutanols can be involved in two pathways: (a) transition-metal catalyzed β-carbon elimination; (b) radical-mediated 'radical clock'-type ring opening. The recent advances of our group for the ring-opening functionalization of tertiary cycloalkanols are described in this account. © 2018 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
De Lorenzi, Valentina; Sarra Ferraris, Gian Maria; Madsen, Jeppe B; Lupia, Michela; Andreasen, Peter A; Sidenius, Nicolai
2016-07-01
Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. © 2016 The Authors.
ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.
Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique
2016-07-15
The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.
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Nicole Hofmann
Full Text Available ABCA3 is a lipid transporter in the limiting membrane of lamellar bodies in alveolar type II cells. Mutations in the ABCA3 gene cause respiratory distress syndrome in new-borns and childhood interstitial lung disease. ABCA3 is N-terminally cleaved by an as yet unknown protease, a process believed to regulate ABCA3 activity.The exact site where ABCA3 is cleaved was localized using mass spectrometry (MS. Proteases involved in ABCA3 processing were identified using small molecule inhibitors and siRNA mediated gene knockdown. Results were verified by in vitro digestion of a synthetic peptide substrate mimicking ABCA3's cleavage region, followed by MS analysis.We found that cleavage of ABCA3 occurs after Lys174 which is located in the proteins' first luminal loop. Inhibition of cathepsin L and, to a lesser extent, cathepsin B resulted in attenuation of ABCA3 cleavage. Both enzymes showed activity against the ABCA3 peptide in vitro with cathepsin L being more active.We show here that, like some other proteins of the lysosomal membrane, ABCA3 is a substrate of cathepsin L. Therefore, cathepsin L may represent a potential target to therapeutically influence ABCA3 activity in ABCA3-associated lung disease.
Park, Kyoung Taek
2014-01-01
Secondary spontaneous pneumothorax is difficult to treat and has been thought to have high morbidity and mortality rate due to the underlying diseases and presence of comorbidities in the patients. However, early surgical intervention will be beneficial if it is tolerable by the patient. In the surgical approach for treating pneumothorax, video-assisted thoracoscopic surgery (VATS) may reduce the postoperative drainage period and hospital stay compared with open thoracotomy. A retrospective review of the clinical data of 40 patients with secondary spontaneous pneumothorax who underwent open thoracotomy (n = 20) or two-port VATS (n = 20) between January 2008 and December 2012 was performed. Postoperative drainage period of open thoracotomy group and two-port VATS group was 9.85 ± 5.28 and 6.75 ± 2.45, respectively, with a significant inter-group difference. Postoperative hospital stay was 11.8 ± 5.12 in the open thoracotomy group and 8.25 ± 2.88 in the two-port VATS group, with a significant inter-group difference. Recurrence rate and postoperative complication rate were not significant between the two groups. In selected patients with secondary spontaneous pneumothorax treated with surgical approach, two-port VATS resulted in shorter postoperative drainage period and hospital stay compared with open thoracotomy.
Megarectumsigma underwent surgery for chronic faecal impact action
International Nuclear Information System (INIS)
Canessa, C.; Gomez del Valle, M.; Caraballo, M.
2002-01-01
Seven patients with megarectumsigma underwent surgery for chronic faecal impaction,reviewing clinical diagnosis, aetiology and medical and surgical management.It is suggested medical management of chronic faecal impaction trying to achieve elective surgery.The curative surgery should include the resection of all pathologic bowel, but in Duhamel procedure and its modifications distal rectal tran section should be at the peritoneal reflection.Habr-Gama modification has shown to be technically easier and it has been communicated good functional results.Local unfavourable conditions may be resolve by staged surgery,which allows outline definitive bowel reconstruction after functional assessment
Spontaneous calf haematoma: case report.
Zubaidah, N H; Liew, N C
2014-02-01
Spontaneous calf haematoma is a rare condition and few case reports have been published in the English literature. Common conditions like deep vein thrombosis and traumatic gastrocnemius muscle tear need to be considered when a patient presents with unilateral calf swelling and tenderness. Ultrasound and Magnetic Resonance Imaging are essential for confirmation of diagnosis. The purpose of this paper is to report on a rare case of spontaneous calf hematoma and its diagnosis and management.
DNA-binding, DNA cleavage and cytotoxicity studies of two anthraquinone derivatives.
Gholivand, M B; Kashanian, S; Peyman, H
2012-02-15
The interaction of native calf thymus DNA (CT-DNA) with two anthraquinones including quinizarin (1,4-dihydroxy anthraquinone) and danthron (1,8-dihydroxy anthraquinone) in a mixture of 0.04M Brittone-Robinson buffer and 50% of ethanol were studied at physiological pH by spectrofluorometric and cyclic voltammetry techniques. The former technique was used to calculate the binding constants of anthraquinones-DNA complexes at different temperatures. Thermodynamic study indicated that the reactions of both anthraquinone-DNA systems are predominantly entropically driven. Furthermore, the binding mechanisms on the reaction of the two anthraquinones with DNA and the effect of ionic strength on the fluorescence property of the system have also been investigated. The results of the experiments indicated that the binding modes of quinizarin and danthron with DNA were evaluated to be groove binding. Moreover, the cytotoxic activity of both compounds against human chronic myelogenous leukemia K562 cell line and DNA cleavage were investigated. The results indicated that these compounds slightly cleavage pUC18 plasmid DNA and showed minor antitumor activity against K562 (human chronic myeloid leukemia) cell line. Copyright © 2011 Elsevier B.V. All rights reserved.
Du, Bingnan; Wang, Wenmin; Wang, Yang; Qi, Zhenghang; Tian, Jiaqi; Zhou, Jie; Wang, Xiaochen; Han, Jianlin; Ma, Jing; Pan, Yi
2018-02-16
A Cu-catalyzed cascade oxidative radical process of β-keto sulfones with alcohols has been achieved by using oxygen as an oxidant. In this reaction, β-keto sulfones were converted into sulfinate esters under the oxidative conditions via cleavage of C-S bond. Experimental and computational studies demonstrate that a new pathway is involved in this reaction, which proceeds through the formation of the key four-coordinated Cu II intermediate, O-O bond homolysis induced C-S bond cleavage and Cu-catalyzed esterification to form the final products. This reaction provides a new strategy to sulfonate esters and enriches the research content of C-S bond cleavage and transformations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
International Nuclear Information System (INIS)
Raleigh, J.A.; Kremers, W.; Whitehouse, R.
1975-01-01
Irradiation of the dinucleoside monophosphates ApA and dApA in deoxygenated solution leads to a preferential cleavage of the 3' end of the internucleotide bond. Cleavage at the 3' bond is favored to the extent of 2 to 1 over 5' cleavage. Oxygen and nitroaromatic compounds inhibit 3' bond breaking in ApA and dApA in agreement with earlier findings from studies of 3'- and 5'-mononucleotides. In contrast to the mononucleotide results, no enhancement of 5' cleavage is observed for ApA and dApA irradiated in the presence of oxygen or the nitroaromatic additives. The over-all effect of the additives is to decrease the combined (3' and 5') yield of internucleotide bond breaking in ApA and dApA. This phenomenon is also observed for polyadenylic acid in the presence of the nitroaromatics. Oxygen marginally enhances internucleotide bond breaking in polyadenylic acid (factor 1.1) over that seen in deoxygenated solution. Postirradiation alkaline hydrolysis of dApA leads to further ester cleavage revealing the presence of radiation-induced alkali-labile bonds. The number of these bonds decreases in the order oxygen greater than nitrofurans greater than nitrobenzenes approximately irradiation in the absence of additives
F. VON HAYEK’S THEORY OF SPONTANEOUS ORDER
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О. Nesterenko
2013-04-01
Full Text Available The essence and the genesis of spontaneous order are disclosed in the context of critical analysis of constructivism. The author’s approach to the definition of the characteristic features of the spontaneous order is proposed. The dichotomy of the order is revealed towards the economic sphere in form of spontaneous order and organization.
Spontaneous pneumomediastinum after bench press training.
Nishino, Tomoya
2017-04-01
Spontaneous pneumomediastinum is often associated with asthma and mainly affects adolescent males with a tall, thin body habitus. A 17-year-old man complained of chest and pharyngeal pain after bench press training and spontaneous pneumomediastinum was diagnosed. It should be considered in the differential diagnosis of chest pain of uncertain cause.
Mischkowski, Dorothee; Glöckner, Andreas
2016-01-01
Cooperation is essential for the success of societies and there is an ongoing debate whether individuals have therefore developed a general spontaneous tendency to cooperate or not. Findings that cooperative behavior is related to shorter decision times provide support for the spontaneous cooperation effect, although contrary results have also been reported. We show that cooperative behavior is better described as person × situation interaction, in that there is a spontaneous cooperation effect for prosocial but not for proself persons. In three studies, one involving population representative samples from the US and Germany, we found that cooperation in a public good game is dependent on an interaction between individuals’ social value orientation and decision time. Increasing deliberation about the dilemma situation does not affect persons that are selfish to begin with, but it is related to decreasing cooperation for prosocial persons that gain positive utility from outcomes of others and score high on the related general personality trait honesty/humility. Our results demonstrate that the spontaneous cooperation hypothesis has to be qualified in that it is limited to persons with a specific personality and social values. Furthermore, they allow reconciling conflicting previous findings by identifying an important moderator for the effect. PMID:26876773
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Asuman Celikbilek
2013-01-01
Full Text Available Background and Purpose: Stroke, which remains the third leading cause of death after heart disease and cancer in developed countries, is a disorder causing permanent neurologic disability. Even though, hemorrhagic strokes are seen less than the ischemic type, they are more fatal. We studied the risk factors for spontaneous intra-cerebral hemorrhage (ICH to direct the proper preventive treatment modalities and the effects of these factors on mortality as well as applied therapeutic strategies on survival. Materials and Methods: The archive records of 106 patients (60 male, 46 female who were diagnosed with spontaneous ICH in Baskent University Hospital, Ankara, between January 2003 and September 2008, were assessed retrospectively. Results: The mean age was found as 62.5. The most frequent risk factor was hypertension (73.5%; 69.2% of these hypertensive patients had uncontrolled blood pressure levels. The mortality rate was detected as 34.9% and patients were found to die approximately within 9 days after ICH. Older age, increased hemorrhage volume, ventricular extension of hemorrhage, and the presence of midline shift were found to significantly correlate with increased mortality (P < 0.05. Patients who underwent surgical therapy showed a longer survival rate (P = 0.016; however, no association was found between medical and surgical therapy in terms of mortality (P = 0.555. Conclusion: The results of this study suggest that effective control of blood pressure is important in the prevention of spontaneous ICH; clinical and radiological findings with treatment modalities influencing mortality should be carefully managed.
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Lin PY
2015-10-01
Full Text Available Pao-Yen Lin1,2 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 2Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Abstract: Evidence has supported the role of brain-derived neurotrophic factor (BDNF in antidepressant effect. The precursor of BDNF (proBDNF often exerts opposing biological effects on mature BDNF (mBDNF. Hence, the balance between proBDNF and mBDNF might be critical in total neurotrophic effects, leading to susceptibility to or recovery from depression. In the current study, we measured the protein expression levels of proBDNF, and its proteolytic products, truncated BDNF, and mBDNF, in human SH-SY5Y cells treated with different antidepressants. We found that the treatment significantly increased the production of mBDNF, but decreased the production of truncated BDNF and proBDNF. These results support that antidepressants can promote proBDNF cleavage. Further studies are needed to clarify whether proBDNF cleavage plays a role in antidepressant mechanisms. Keywords: antidepressant, mature BDNF, neurotrophic effect, proBDNF cleavage
Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites
DEFF Research Database (Denmark)
Nielsen, Henrik; Engelbrecht, Jacob; Brunak, Søren
1997-01-01
We have developed a new method for the identification of signal peptides and their cleavage based on neural networks trained on separate sets of prokaryotic and eukaryotic sequence. The method performs significantly better than previous prediction schemes and can easily be applied on genome...
Hadidi, Ahmed; Subotic, Ulrike; Goeppl, Maximilian; Waag, Karl-L
2008-07-01
The aim of this study is to assess the value of early elective cesarean delivery for patients with gastroschisis in comparison with late spontaneous delivery. Analysis of infants with gastroschisis admitted between 1986 and 2006 at a tertiary care center was performed. The findings were analyzed statistically. Eighty-six patients were involved in the study. This included 15 patients who underwent emergency cesarean delivery (EM CD group) because of fetal distress and/or bowel ischemia. The remaining 71 patients born electively were stratified into 4 groups. The early elective cesarean delivery (ECD) group included 23 patients born by ECD before 36 weeks; late vaginal delivery (LVD) group included 23 patients who had LVD after 36 weeks; 24 patients had LCD after 36 weeks because of delayed diagnosis that resulted in late referral; and 1 patient had early spontaneous vaginal delivery (EVD group) before 36 weeks. The mean time to start oral feeding, incidence of complications, and primary closure were significantly better in the ECD group than in the LVD group. The duration of ventilation and the length of stay were shorter in ECD group, but the difference was not statistically significant. Elective cesarean delivery before 36 weeks allows earlier enteral feeding and is associated with less complications and higher incidence of primary closure (statistically significant).
Change in radiosensitivity on the development of sea urchin eggs during the early cleavage stage, 2
International Nuclear Information System (INIS)
Nakamura, Izumi
1975-01-01
The effect of cysteamine on the fluctuation of X-ray sensitivity during early cleavage stage of sea urchin eggs expressed by pluteus formation rate was examined. Sea urchin eggs were very resistant to radiation immediately after insemination or after S phase of the cleavage. When irradiation was given just prior to S phase or in the phase of cytokinesis, the eggs were very sensitive. In these sensitive stages, existence of cysteamine during X-irradiation apparently protected eggs against radiation effect. Dose modifying factor increased linearly from 1.8 to 3.4 with increasing dose of cysteamine (25mM-75mM) added. (auth.)
Multi scale study of the plasticity at low temperature in α-iron: application for the cleavage
International Nuclear Information System (INIS)
Chaussidon, J.
2007-10-01
An accident inside a nuclear power plant may lead to the cleavage of the nuclear vessel made of bainitic steel. In order to understand the origin of this fracture, we studied BCC-iron plasticity at low temperature using numerical simulations at different scales. Molecular Dynamics simulations show the high dependency of screw dislocation motion with temperature and stress. Results from these simulations were added to experiment data to develop a new Dislocation Dynamics code dedicated to BCC iron at low temperature. The code was used to model plasticity into a ferritic lath for various temperatures. This work confirms that cleavage is favoured by low temperatures. (author)
Wongkongkathep, Piriya; Li, Huilin; Zhang, Xing; Loo, Rachel R Ogorzalek; Julian, Ryan R; Loo, Joseph A
2015-11-15
The application of ion pre-activation with 266 nm ultraviolet (UV) laser irradiation combined with electron capture dissociation (ECD) is demonstrated to enhance top-down mass spectrometry sequence coverage of disulfide bond containing proteins. UV-based activation can homolytically cleave a disulfide bond to yield two separated thiol radicals. Activated ECD experiments of insulin and ribonuclease A containing three and four disulfide bonds, respectively, were performed. UV-activation in combination with ECD allowed the three disulfide bonds of insulin to be cleaved and the overall sequence coverage to be increased. For the larger sized ribonuclease A with four disulfide bonds, irradiation from an infrared laser (10.6 µm) to disrupt non-covalent interactions was combined with UV-activation to facilitate the cleavage of up to three disulfide bonds. Preferences for disulfide bond cleavage are dependent on protein structure and sequence. Disulfide bonds can reform if the generated radicals remain in close proximity. By varying the time delay between the UV-activation and the ECD events, it was determined that disulfide bonds reform within 10-100 msec after their UV-homolytic cleavage.
Jaisi, Deb P; Li, Hui; Wallace, Adam F; Paudel, Prajwal; Sun, Mingjing; Balakrishna, Avula; Lerch, Robert N
2016-11-16
Degradation of glyphosate in the presence of manganese oxide and UV light was analyzed using phosphate oxygen isotope ratios and density function theory (DFT). The preference of C-P or C-N bond cleavage was found to vary with changing glyphosate/manganese oxide ratios, indicating the potential role of sorption-induced conformational changes on the composition of intermediate degradation products. Isotope data confirmed that one oxygen atom derived solely from water was incorporated into the released phosphate during glyphosate degradation, and this might suggest similar nucleophilic substitution at P centers and C-P bond cleavage both in manganese oxide- and UV light-mediated degradation. The DFT results reveal that the C-P bond could be cleaved by water, OH - or • OH, with the energy barrier opposing bond dissociation being lowest in the presence of the radical species, and that C-N bond cleavage is favored by the formation of both nitrogen- and carbon-centered radicals. Overall, these results highlight the factors controlling the dominance of C-P or C-N bond cleavage that determines the composition of intermediate/final products and ultimately the degradation pathway.
Di-µ-hydroxo Bridge Cleavage Reactions between [Co(nta)(µ-OH)] 2 ...
African Journals Online (AJOL)
NJD
2004-04-22
Apr 22, 2004 ... subsequent rate determining steps to form presumably a ligand-substituted, mono-bridged complex, [(nta)(OH)Co-µ-. OH-Co(nta)(L)]2– (L = py/dmap). The latter decomposes rapidly to form the products. The preferred pathway for these bridge cleavage seemed to be the reaction of the mono-µ-hydroxo-.
Spontaneous ischaemic stroke in dogs
DEFF Research Database (Denmark)
Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.
2013-01-01
Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....
Spontaneity and international marketing performance
Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.
2016-01-01
The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...
A study of complex defects failing by fatigue, ductile tearing and cleavage
International Nuclear Information System (INIS)
Bezensek, B.; Ren, Z.; Hancock, J.W.
2001-01-01
Defect assessment procedures ensure the structural integrity of plant, which may contain complex defects. The present work addresses complex defects with re-entrant sectors, which develop from the interaction of two co-planar surface breaking defects in fatigue. Experimental studies show rapid fatigue growth and amplified crack driving forces in the re-entrant sector. This leads to the rapid evolution of the complex crack into a bounding semielliptical defect. Experiments involving ductile tearing of cracks with a re-entrant sector show that tearing initiates in the re-entrant sector and that the defect evolves into a bounding semielliptical defect. Cleavage failures of defects with re-entrant sectors indicate the re-characterisation procedure is only conservative after invoking constraint arguments. The study confirms the conservatism inherent in the re-characterisation rules of assessment procedures, such as BS 7910 [1] and ASME Section XI [2] for complex defects extending by fatigue or ductile tearing. A potentially non-conservative situation exists for defects with re-entrant sectors failing by cleavage at small fractions of the limit load.(author)
Analysis of the Spontaneous Abortion in Chinese Married Women
Institute of Scientific and Technical Information of China (English)
高尔生; 邓新清; 何更生; 方可娟; 唐威; 楼超华
1994-01-01
The spontaneous abortion is a common type of pregnant outcomes. The spontaneous abortion rate can be used to indicate the women's fecundity and the level of the reproductive health. It is also a sensitive indicator for determing the social, economic, and health status and prenatal care. To explore the preventive method for spontaneous abortion and improve women's health level, it is important to evaluate the status of spontaneous abortion and to determine the factors affecting
Marlin, Jerry W; Chang, Yu-Wen E; Ober, Margaret; Handy, Amy; Xu, Wenhao; Jakobi, Rolf
2011-06-01
p21-Activated protein kinase 2 (PAK-2) has both anti- and pro-apoptotic functions depending on its mechanism of activation. Activation of full-length PAK-2 by the monomeric GTPases Cdc42 or Rac stimulates cell survival, whereas caspase activation of PAK-2 to the PAK-2p34 fragment is involved in the apoptotic response. In this study we use functional knockout of PAK-2 and gene replacement with the caspase cleavage-deficient PAK-2D212N mutant to differentiate the biological functions of full-length PAK-2 and caspase-activated PAK-2p34. Knockout of PAK-2 results in embryonic lethality at early stages before organ development, whereas replacement with the caspase cleavage-deficient PAK-2D212N results in viable and healthy mice, indicating that early embryonic lethality is caused by deficiency of full-length PAK-2 rather than lack of caspase activation to the PAK-2p34 fragment. However, deficiency of caspase activation of PAK-2 decreased spontaneous cell death of primary mouse embryonic fibroblasts and increased cell growth at high cell density. In contrast, stress-induced cell death by treatment with the anti-cancer drug cisplatin was not reduced by deficiency of caspase activation of PAK-2, but switched from an apoptotic to a nonapoptotic, caspase-independent mechanism. Homozygous PAK-2D212N primary mouse embryonic fibroblasts that lack the ability to generate the proapoptotic PAK-2p34 show less activation of the effector caspase 3, 6, and 7, indicating that caspase activation of PAK-2 amplifies the apoptotic response through a positive feedback loop resulting in more activation of effector caspases.
Cabrera, Lucas G G; Santos, Aline F; Andrade, Ursulla V; Guedes, Carlos Ivan A; Oliveira, Sandra M V L; Chang, Marilene R; Mendes, Rinaldo P; Paniago, Anamaria M M
2017-02-01
Paracoccidioidomycosis (PCM) is the most important systemic mycosis in Latin America. About 80% of PCM patients are present with its chronic form. The lungs are affected in most patients with the chronic form; however, pleural involvement has rarely been reported. We describe nine cases of PCM that presented with lung involvement and spontaneous pneumothorax. All patients, except one whose condition was not investigated, were smokers. PCM was diagnosed during the pneumothorax episode in three patients, and from 3 to 16 years before the pneumothorax episode in six patients. A total of six patients underwent chest drainage and one died as a direct result of the pneumothorax. We suggest that pneumothorax, although rare, should be considered in PCM patients who present with suddenly worsening dyspnoea. PCM should also be investigated in cases of pneumothorax in adult men from mycosis-endemic areas. © 2016 Blackwell Verlag GmbH.
DEFF Research Database (Denmark)
Heinz, Andrea; Jung, Michael C; Duca, Laurent
2010-01-01
To provide a basis for the development of approaches to treat elastin-degrading diseases, the aim of this study was to investigate the degradation of the natural substrate tropoelastin by the elastinolytic matrix metalloproteinases MMP-7, MMP-9, and MMP-12 and to compare the cleavage site...
High-fat diet feeding causes rapid, non-apoptotic cleavage of caspase-3 in astrocytes.
Guyenet, Stephan J; Nguyen, Hong T; Hwang, Bang H; Schwartz, Michael W; Baskin, Denis G; Thaler, Joshua P
2013-05-28
Astrocytes respond to multiple forms of central nervous system (CNS) injury by entering a reactive state characterized by morphological changes and a specific pattern of altered protein expression. Termed astrogliosis, this response has been shown to strongly influence the injury response and functional recovery of CNS tissues. This pattern of CNS inflammation and injury associated with astrogliosis has recently been found to occur in the energy homeostasis centers of the hypothalamus during diet-induced obesity (DIO) in rodent models, but the characterization of the astrocyte response remains incomplete. Here, we report that astrocytes in the mediobasal hypothalamus respond robustly and rapidly to purified high-fat diet (HFD) feeding by cleaving caspase-3, a protease whose cleavage is often associated with apoptosis. Although obesity develops in HFD-fed rats by day 14, caspase-3 cleavage occurs by day 3, prior to the development of obesity, suggesting the possibility that it could play a causal role in the hypothalamic neuropathology and fat gain observed in DIO. Caspase-3 cleavage is not associated with an increase in the rate of apoptosis, as determined by TUNEL staining, suggesting it plays a non-apoptotic role analogous to the response to excitotoxic neuron injury. Our results indicate that astrocytes in the mediobasal hypothalamus respond rapidly and robustly to HFD feeding, activating caspase-3 in the absence of apoptosis, a process that has the potential to influence the course of DIO. Copyright © 2013 Elsevier B.V. All rights reserved.
Spontaneous Vesicle Recycling in the Synaptic Bouton
Directory of Open Access Journals (Sweden)
Sven eTruckenbrodt
2014-12-01
Full Text Available The trigger for synaptic vesicle exocytosis is Ca2+, which enters the synaptic bouton following action potential stimulation. However, spontaneous release of neurotransmitter also occurs in the absence of stimulation in virtually all synaptic boutons. It has long been thought that this represents exocytosis driven by fluctuations in local Ca2+ levels. The vesicles responding to these fluctuations are thought to be the same ones that release upon stimulation, albeit potentially triggered by different Ca2+ sensors. This view has been challenged by several recent works, which have suggested that spontaneous release is driven by a separate pool of synaptic vesicles. Numerous articles appeared during the last few years in support of each of these hypotheses, and it has been challenging to bring them into accord. We speculate here on the origins of this controversy, and propose a solution that is related to developmental effects. Constitutive membrane traffic, needed for the biogenesis of vesicles and synapses, is responsible for high levels of spontaneous membrane fusion in young neurons, probably independent of Ca2+. The vesicles releasing spontaneously in such neurons are not related to other synaptic vesicle pools and may represent constitutively releasing vesicles (CRVs rather than bona fide synaptic vesicles. In mature neurons, constitutive traffic is much dampened, and the few remaining spontaneous release events probably represent bona fide spontaneously releasing synaptic vesicles (SRSVs responding to Ca2+ fluctuations, along with a handful of CRVs that participate in synaptic vesicle turnover.
Spontaneous Atraumatic Mediastinal Hemorrhage
Directory of Open Access Journals (Sweden)
Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd
2013-04-01
Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.
Spontaneous Retropharyngeal Emphysema: A Case Report | Chi ...
African Journals Online (AJOL)
... is a rare clinical condition in pediatric otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia, and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema. Keywords: Iatrogenic injury, retropharyngeal emphysema, spontaneous retropharyngeal emphysem, trauma ...
Spontaneous regression of pulmonary bullae
International Nuclear Information System (INIS)
Satoh, H.; Ishikawa, H.; Ohtsuka, M.; Sekizawa, K.
2002-01-01
The natural history of pulmonary bullae is often characterized by gradual, progressive enlargement. Spontaneous regression of bullae is, however, very rare. We report a case in which complete resolution of pulmonary bullae in the left upper lung occurred spontaneously. The management of pulmonary bullae is occasionally made difficult because of gradual progressive enlargement associated with abnormal pulmonary function. Some patients have multiple bulla in both lungs and/or have a history of pulmonary emphysema. Others have a giant bulla without emphysematous change in the lungs. Our present case had treated lung cancer with no evidence of local recurrence. He had no emphysematous change in lung function test and had no complaints, although the high resolution CT scan shows evidence of underlying minimal changes of emphysema. Ortin and Gurney presented three cases of spontaneous reduction in size of bulla. Interestingly, one of them had a marked decrease in the size of a bulla in association with thickening of the wall of the bulla, which was observed in our patient. This case we describe is of interest, not only because of the rarity with which regression of pulmonary bulla has been reported in the literature, but also because of the spontaneous improvements in the radiological picture in the absence of overt infection or tumor. Copyright (2002) Blackwell Science Pty Ltd
Spontaneous Dissection of the Superior Mesenteric Artery
International Nuclear Information System (INIS)
Sheldon, Patrick J.; Esther, James B.; Sheldon, Elana L.; Sparks, Steven R.; Brophy, David P.; Oglevie, Steven B.
2001-01-01
Spontaneous dissection of the superior mesenteric artery (SMA) is a rare occurrence, especially when not associated with aortic dissection. Currently, only 28 cases appear to have been reported. Due to the scarcity of cases in the literature, the natural history of isolated, spontaneous SMA dissection is unclear. CT has been reported to be useful for the initial diagnosis of SMA dissection [2-5]. We present two recent cases of spontaneous SMA dissection in which enhanced spiral CT was instrumental in following the disease process and guiding clinical decision making
Endometriosis-related spontaneous diaphragmatic rupture.
Triponez, Frédéric; Alifano, Marco; Bobbio, Antonio; Regnard, Jean-François
2010-10-01
Non-traumatic, spontaneous diaphragmatic rupture is a rare event whose pathophysiology is not known. We report the case of endometriosis-related spontaneous rupture of the right diaphragm with intrathoracic herniation of the liver, gallbladder and colon. We hypothesize that the invasiveness of endometriotic tissue caused diaphragm fragility, which finally lead to its complete rupture without traumatic event. The treatment consisted of a classical management of diaphragmatic rupture, with excision of the endometriotic nodule followed by medical ovarian suppression for six months.
International Nuclear Information System (INIS)
Harada, Satoshi; Sato, Ryuichi; Nakamura, Ryuji; Oikawa, Hiroshi; Oikawa, Hirobumi; Ohgi, Shie; Tamakawa, Yoshiharu; Yanagisawa, Toru
2000-01-01
Purpose: The correlation between the frequency of spontaneous and radiation-induced apoptosis, and the precedence between those for predicting prognosis were studied at clinical level. Methods and Materials: Twenty-one patients (mean age, 65.8 years; 16 men and 5 women) with bladder cancer (transitional cell carcinoma Grade 3, T3bN0M0, Stage IIIb) underwent intraoperative radiotherapy: single 30-Gy 12-MV electron beam irradiation to bladder, followed by total cystectomy 6 h after irradiation. The specimens of pretreatment and irradiated bladder cancer were assayed for apoptosis, using TUNEL staining with counter staining of hematoxylin. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells and multiplying by 100. The Pearson's linear fitting was used to test the correlation between spontaneous and radiation-induced apoptosis. The Kaplan-Meier product-limit estimation was used for overall survival (OS) and freedom from recurrence (FFR). The precedence between spontaneous and radiation-induced apoptosis for predicting the clinical prognosis was estimated using the proportional hazard regression. Results: The mean AI of spontaneous and radiation-induced apoptosis was 1.18 ± 0.16 and 2.63 ± 0.45, respectively, which was significantly different. There was strong correlation between spontaneous and radiation-induced apoptosis (r 2 = 0.864, adjusted r 2 = 0.857). Radiation-induced apoptosis was estimated by equitation: y (radiation-induced apoptosis) = 2.67 x (spontaneous apoptosis) -0.52. However, the proportional hazard regression test indicated that only spontaneous apoptosis was significant for predicting OS and FFR (vertical bar t vertical bar > 0.2), but radiation-induced apoptosis was not. Conclusion: Estimating AI in radiation-induced apoptosis from AI in spontaneous apoptosis is possible. However, spontaneous apoptosis is more accurate in predicting clinical prognosis
Directory of Open Access Journals (Sweden)
Hessy Novita
2016-12-01
Full Text Available Penanggulangan penyakit ikan dapat dilakukan dengan cara meningkatkan kekebalan tubuh ikan melalui program vaksinasi. Namun vaksinasi tidak tepat untuk udang, karena udang tidak mempunyai immunological memory seperti ikan. Oleh karena itu, perlindungan udang terhadap serangan penyakit viral dengan menggunakan RNA interference (RNAi. Teknologi RNAi digunakan untuk menghalangi (interfere proses replikasi infectious myonecrosis virus (IMNV pada udang vaname dengan cara menon-aktifkan gen putative cleavage protein 1 (PCP-1, yang berfungsi dalam pembentukan capsid dan proses transkripsi RNA IMNV. Penelitian ini bertujuan untuk melakukan kloning gen putative cleavage protein 1 dalam rangka perakitan teknologi RNAi untuk pengendalian penyakit IMNV pada udang vaname. Tahapan penelitian meliputi koleksi sampel, isolasi RNA, sintesis cDNA, amplifikasi PCR, purifikasi DNA, transformasi, isolasi plasmid, serta sekuensing dan analisis data. Hasil isolasi plasmid cDNA PCP-1 memperlihatkan semua koloni bakteri terseleksi ternyata membawa plasmid hasil insersi DNA gen PCP–1, hasil sekuen dengan nilai homologinya mencapai 100% dan 99% yang dibandingkan dengan sekuen di Genebank. Hasil penelitian menunjukkan bahwa kloning gen putative cleavage protein 1 (PCP-1 dari udang vaname yang terserang Infectious Myonecrosis Virus berhasil dikloning yang nantinya digunakan untuk perakitan RNAi. The prevention of fish diseases can be done by increasing of the fish immune through vaccination programs. However, the vaccination can not be done for the shrimp,due to the absence of immunological memory. Therefore, the protection of shrimp against viral diseases was done by using of RNA interference (RNAi. RNAi technology is used to interfere infectious myonecrosis virus (IMNV replication process on white shrimp by disabling of putative cleavage protein 1 (PCP-1gene, which functions in capsid formation and RNA transcription process. The study was conducted to perform putative
Spontaneous Scalarization: Dead or Alive?
Berti, Emanuele; Crispino, Luis; Gerosa, Davide; Gualtieri, Leonardo; Horbatsch, Michael; Macedo, Caio; Okada da Silva, Hector; Pani, Paolo; Sotani, Hajime; Sperhake, Ulrich
2015-04-01
In 1993, Damour and Esposito-Farese showed that a wide class of scalar-tensor theories can pass weak-field gravitational tests and exhibit nonperturbative strong-field deviations away from General Relativity in systems involving neutron stars. These deviations are possible in the presence of ``spontaneous scalarization,'' a phase transition similar in nature to spontaneous magnetization in ferromagnets. More than twenty years after the original proposal, binary pulsar experiments have severely constrained the possibility of spontaneous scalarization occurring in nature. I will show that these experimental constraints have important implications for the torsional oscillation frequencies of neutron stars and for the so-called ``I-Love-Q'' relations in scalar-tensor theories. I will also argue that there is still hope to observe strong scalarization effects, despite the strong experimental bounds on the original mechanism. In particular, I will discuss two mechanisms that could produce strong scalarization in neutron stars: anisotropy and multiscalarization. This work was supported by NSF CAREER Award PHY-1055103.
Czech Academy of Sciences Publication Activity Database
Zubáčová, Z.; Novák, L.; Bublíková, J.; Vacek, V.; Fousek, Jan; Rídl, Jakub; Tachezy, J.; Doležal, P.; Vlček, Čestmír; Hampl, V.
2013-01-01
Roč. 8, č. 3 (2013), e55417 E-ISSN 1932-6203 R&D Projects: GA ČR GAP506/12/1010 Institutional support: RVO:68378050 Keywords : transcriptome sequencing * Trimastix * mitochondrion -like organelle * glycine cleavage complex Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.534, year: 2013
Detection of target phonemes in spontaneous and read speech.
Mehta, G; Cutler, A
1988-01-01
Although spontaneous speech occurs more frequently in most listeners' experience than read speech, laboratory studies of human speech recognition typically use carefully controlled materials read from a script. The phonological and prosodic characteristics of spontaneous and read speech differ considerably, however, which suggests that laboratory results may not generalise to the recognition of spontaneous speech. In the present study listeners were presented with both spontaneous and read speech materials, and their response time to detect word-initial target phonemes was measured. Responses were, overall, equally fast in each speech mode. However, analysis of effects previously reported in phoneme detection studies revealed significant differences between speech modes. In read speech but not in spontaneous speech, later targets were detected more rapidly than targets preceded by short words. In contrast, in spontaneous speech but not in read speech, targets were detected more rapidly in accented than in unaccented words and in strong than in weak syllables. An explanation for this pattern is offered in terms of characteristic prosodic differences between spontaneous and read speech. The results support claims from previous work that listeners pay great attention to prosodic information in the process of recognising speech.
Spontaneous CP violation on the lattice
Laine, Mikko
2000-01-01
At finite temperatures around the electroweak phase transition, the thermodynamics of the MSSM can be described by a three-dimensional two Higgs doublet effective theory. This effective theory has a phase where CP is spontaneously violated. We study spontaneous CP violation with non-perturbative lattice simulations, and analyse whether one could end up in this phase for any physical MSSM parameter values.
Çatlı, Gönül; Alparslan, Caner; Can, P Şule; Akbay, Sinem; Kelekçi, Sefa; Atik, Tahir; Özyılmaz, Berk; Dündar, Bumin N
2015-06-01
46,XY pure gonadal dysgenesis (Swyer syndrome) is characterized by normal female genitalia at birth. It usually first becomes apparent in adolescence with delayed puberty and amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation. A fifteen-year-old girl presented to our clinic with the complaint of primary amenorrhea. On physical examination, her external genitals were completely female. Breast development and pubic hair were compatible with Tanner stage V. Hormonal evaluation revealed a hypergonadotropic state despite a normal estrogen level. Chromosome analysis revealed a 46,XY karyotype. Pelvic ultrasonography showed small gonads and a normal sized uterus for age. SRY gene expression was confirmed by multiplex polymerase chain reaction. Direct sequencing on genomic DNA did not reveal a mutation in the SRY, SF1 and WT1 genes. After the diagnosis of Swyer syndrome was made, the patient started to have spontaneous menstrual cycles and therefore failed to attend her follow-up visits. After nine months, the patient underwent diagnostic laparoscopy. Frozen examination of multiple biopsies from gonad tissues revealed gonadoblastoma. With this report, we emphasize the importance of performing karyotype analysis, which is diagnostic for Swyer syndrome, in all cases with primary or secondary amenorrhea even in the presence of normal breast development. We also suggest that normal pubertal development in patients with Swyer syndrome may be associated with the presence of a hormonally active tumor.
Spontaneous pneumothorax associated with lung cancer
International Nuclear Information System (INIS)
Sung, Dong Wook; Jung, Seung Hyae; Yoon, Yup; Lim, Jae Hoon; Cho, Kyu Soek; Yang, Moon Ho
1991-01-01
Spontaneous pneumothorax is a rare manifestation of lung cancer. Eight cases of pneumothorax found in 1648 patients with lung cancer from 1979-1990 are reported. Histopathologic types of cancer were adenocarcinoma in three cases, squamous cell carcinoma in two cases, bronchioloalveolar carcinoma in two cases, and metastatic renal cell carcinoma in one case. The primary tumor mass was not found even after thoracotomy in two cases. Spontaneous pneumothorax occurred on the ipsilateral side of the cancer. All the patients were more than 40 years old with a history of smoking 1-2 packs a day for 20 to 50 years, and had chronic lung diseases. The authors emphasize that bronchogenic carcinoma may be one of the causes of spontaneous pneumothorax in appropriate clinical settings
The timing of pronuclear formation, DNA synthesis and cleavage in the human 1-cell embryo.
Capmany, G; Taylor, A; Braude, P R; Bolton, V N
1996-05-01
The timing of pronuclear formation and breakdown, DNA synthesis and cleavage during the first cell cycle of human embryogenesis are described. Pronuclei formed between 3 and 10 h post-insemination (hpi; median 8 hpi). S-phase commenced between 8 and 14 hpi, and was completed between 10 and 18 hpi. M-phase was observed between 22 and 31 hpi (median duration 3 h), and cleavage to the 2-cell stage took place between 25 and 33 hpi. The timing of the same events was determined in 1-cell embryos derived from re-inseminated human oocytes that had failed to fertilize during therapeutic in-vitro fertilization (IVF). In these embryos, pronuclei formed between 3 and 8 h post-re-insemination (hpr-i), coinciding with the beginning of S-phase. While S-phase was completed as early as 10 hpr-i in some embryos, it extended until at least 16 hpr-i in others. Pronuclear breakdown and cleavage occurred from 23 and 26 hpr-i respectively; however, they did not occur in some embryos until after 46 hpr-i. The results demonstrate a markedly greater degree of variation in the timing of these events in embryos derived from re-inseminated oocytes compared with embryos derived from conventional IVF, and thus throw into question the validity of using the former as models for studies of the first cell cycle of human embryogenesis.
Spontaneous generation in medieval Jewish philosophy and theology.
Gaziel, Ahuva
2012-01-01
The concept of life forms emerging from inanimate matter--spontaneous generation--was widely accepted until the nineteenth century. Several medieval Jewish scholars acknowledged this scientific theory in their philosophical and religious contemplations. Quite interestingly, it served to reinforce diverse, or even opposite, theological conclusions. One approach excluded spontaneously-generated living beings form the biblical account of creation or the story of the Deluge. Underlying this view is an understanding that organisms that generate spontaneously evolve continuously in nature and, therefore, do not require divine intervention in their formation or survival during disastrous events. This naturalistic position reduces the miraculous dimension of reality. Others were of the opinion that spontaneous generation is one of the extraordinary marvels exhibited in this world and, accordingly, this interpretation served to accentuate the divine aspect of nature. References to spontaneous generation also appear in legal writings, influencing practical applications such as dietary laws and actions forbidden on the Sabbath.
Frusciante, Sarah; Diretto, Gianfranco; Bruno, Mark; Ferrante, Paola; Pietrella, Marco; Prado-Cabrero, Alfonso; Rubio-Moraga, Á ngela L.; Beyer, Peter D.; Gó mez-Gó mez, Lourdes; Al-Babili, Salim; Giuliano, Giovanni
2014-01-01
Crocus sativus stigmas are the source of the saffron spice and accumulate the apocarotenoids crocetin, crocins, picrocrocin, and safranal, responsible for its color, taste, and aroma. Through deep transcriptome sequencing, we identified a novel dioxygenase, carotenoid cleavage dioxygenase 2 (CCD2), expressed early during stigma development and closely related to, but distinct from, the CCD1 dioxygenase family. CCD2 is the only identified member of a novel CCD clade, presents the structural features of a bona fide CCD, and is able to cleave zeaxanthin, the presumed precursor of saffron apocarotenoids, both in Escherichia coli and in maize endosperm. The cleavage products, identified through high-resolution mass spectrometry and comigration with authentic standards, are crocetin dialdehyde and crocetin, respectively. In vitro assays show that CCD2 cleaves sequentially the 7,8 and 7′,8′ double bonds adjacent to a 3-OH-β-ionone ring and that the conversion of zeaxanthin to crocetin dialdehyde proceeds via the C30 intermediate 3-OH-β-apo-8′-carotenal. In contrast, zeaxanthin cleavage dioxygenase (ZCD), an enzyme previously claimed to mediate crocetin formation, did not cleave zeaxanthin or 3-OH-β-apo-8′-carotenal in the test systems used. Sequence comparison and structure prediction suggest that ZCD is an N-truncated CCD4 form, lacking one blade of the β-propeller structure conserved in all CCDs. These results constitute strong evidence that CCD2 catalyzes the first dedicated step in crocin biosynthesis. Similar to CCD1, CCD2 has a cytoplasmic localization, suggesting that it may cleave carotenoids localized in the chromoplast outer envelope.
Frusciante, Sarah
2014-08-05
Crocus sativus stigmas are the source of the saffron spice and accumulate the apocarotenoids crocetin, crocins, picrocrocin, and safranal, responsible for its color, taste, and aroma. Through deep transcriptome sequencing, we identified a novel dioxygenase, carotenoid cleavage dioxygenase 2 (CCD2), expressed early during stigma development and closely related to, but distinct from, the CCD1 dioxygenase family. CCD2 is the only identified member of a novel CCD clade, presents the structural features of a bona fide CCD, and is able to cleave zeaxanthin, the presumed precursor of saffron apocarotenoids, both in Escherichia coli and in maize endosperm. The cleavage products, identified through high-resolution mass spectrometry and comigration with authentic standards, are crocetin dialdehyde and crocetin, respectively. In vitro assays show that CCD2 cleaves sequentially the 7,8 and 7′,8′ double bonds adjacent to a 3-OH-β-ionone ring and that the conversion of zeaxanthin to crocetin dialdehyde proceeds via the C30 intermediate 3-OH-β-apo-8′-carotenal. In contrast, zeaxanthin cleavage dioxygenase (ZCD), an enzyme previously claimed to mediate crocetin formation, did not cleave zeaxanthin or 3-OH-β-apo-8′-carotenal in the test systems used. Sequence comparison and structure prediction suggest that ZCD is an N-truncated CCD4 form, lacking one blade of the β-propeller structure conserved in all CCDs. These results constitute strong evidence that CCD2 catalyzes the first dedicated step in crocin biosynthesis. Similar to CCD1, CCD2 has a cytoplasmic localization, suggesting that it may cleave carotenoids localized in the chromoplast outer envelope.
Spontaneous low-frequency oscillations in cerebral vessels
DEFF Research Database (Denmark)
Schytz, Henrik W; Hansson, Andreas; Phillip, Dorte
2010-01-01
). Analysis of CA by measurement of spontaneous oscillations in the low-frequency spectrum in cerebral vessels might be a useful tool for assessing risk and investigating different treatment strategies in carotid artery disease (CAD) and stroke. We reviewed studies exploring spontaneous oscillations...
Smit, JM; Klimstra, WB; Ryman, KD; Bittman, R; Johnston, RE; Wilschut, J
2001-01-01
The spike glycoprotein E2 of Sindbis virus (SIN) is synthesized in the infected cell as a PE2 precursor protein, which matures through cleavage by a cellular furin-like protease. Previous work has shown that SIN mutants impaired in PE2 cleavage are noninfectious on BHK-21 cells, the block in
Directory of Open Access Journals (Sweden)
Esdras Marques Lins
2013-12-01
Full Text Available BACKGROUND: Atherosclerosis is the main cause of peripheral artery occlusive disease (PAOD of the lower limbs. Patients with PAOD often also have obstructive atherosclerosis in other arterial sites, mainly the coronary arteries. This means that patients who undergo infrainguinal bypass to treat critical ischemia have a higher risk of AMI. There are, however, few reports in the literature that have assessed this risk properly. OBJECTIVE: The aim of this study was to determine the incidence of acute myocardial infarction in patients who underwent infrainguinal bypass to treat critical ischemia of the lower limbs caused by PAOD. MATERIAL AND METHODS: A total of 64 patients who underwent 82 infrainguinal bypass operations, from February 2011 to July 2012 were studied. All patients had electrocardiograms and troponin I blood assays during the postoperative period (within 72 hours. RESULTS: There were abnormal ECG findings and elevated blood troponin I levels suggestive of AMI in five (6% of the 82 operations performed. All five had conventional surgery. The incidence of AMI as a proportion of the 52 conventional surgery cases was 9.6%. Two patients died. CONCLUSION: There was a 6% AMI incidence among patients who underwent infrainguinal bypass due to PAOD. Considering only cases operated using conventional surgery, the incidence of AMI was 9.6%.
International Nuclear Information System (INIS)
Tosi, M.E.; Reilly, B.E.; Anderson, D.L.
1975-01-01
Each of the 12 neck appendages of the Bacillus subtilis bacteriophage phi 29 consists of a single protein molecular weight of about 75,000, and on the mature virion the appendages are assembled to the lower of two collars. The appendage protein is cleaved from a percursor protein, P(J), with a molecular weight of about 88,000. This cleavage is independent of neck assembly, occurring during infection by mutants that cannot synthesize the proteins of the upper and lower collars of the neck. The cleaved form of the appendage protein is efficiently complemented in vitro to particles lacking appendages. Thus, cleavage of the appendage precursor protein apparently does not occur in situ on the maturing virus
Spontaneous rupture of vaginal enterocele
DEFF Research Database (Denmark)
Svendsen, J H; Galatius, H; Hansen, P K
1985-01-01
Spontaneous rupture of an enterocele is a rare complication. Only 24 cases including the present case have been reported in the literature. The patients were elderly and had had at least one vaginal operation. The patients were remarkably unaffected symptomatically on admission.......Spontaneous rupture of an enterocele is a rare complication. Only 24 cases including the present case have been reported in the literature. The patients were elderly and had had at least one vaginal operation. The patients were remarkably unaffected symptomatically on admission....
International Nuclear Information System (INIS)
Li Jiahua; Liu Jibing; Qi Chunchao; Chen Aixi
2006-01-01
We investigate the features of the spontaneous emission spectra in a coherently driven cold five-level atomic system by means of a radio frequency (rf) or microwave field driving a hyperfine transition within the ground state. It is shown that a few interesting phenomena such as spectral-line narrowing, spectral-line enhancement, spectral-line suppression, and spontaneous emission quenching can be realized by modulating the frequency and intensity of the rf-driving field in our system. In the dressed-state picture of the coupling and rf-driving fields, we find that this coherently driven atomic system has three close-lying levels so that multiple spontaneously generated coherence (SGC) arises. Our considered atomic model can be found in real atoms, such as rubidium or sodium, so a corresponding experiment can be done to observe the expected phenomena related to SGC reported by Fountoulakis et al. [Phys. Rev. A 73, 033811 (2006)], since no rigorous conditions are required
A new class of spontaneously polarized materials
DEFF Research Database (Denmark)
Field, David; Plekan, Oksana; Cassidy, Andrew
2011-01-01
Very large electric fields form spontaneously within films of seemingly prosaic chemicals such as nitrous oxide or propane.We describe how the discovery of this unexpected phenomenon took place and how we attempt to understand the nature of the new class of spontaneously polarized materials...
Spontaneous rupture of choledochal cyst: case report
International Nuclear Information System (INIS)
Shin, Ho Seob; Nam, Kyung Jin; Lee, Jin Hwa; Kim, Chan Sung; Choi, Jong Cheol; Oh, Jong Young
2002-01-01
Spontaneous rupture of a choledochal cyst leading to biliary peritonitis is a rare complication which can be fatal if not promptly diagnosed. The authors report the ultrasound and CT findings of two cases of spontaneous choledochal cystic rupture and the biliary peritonitis which ensued
Spontaneous rupture of choledochal cyst: case report
Energy Technology Data Exchange (ETDEWEB)
Shin, Ho Seob; Nam, Kyung Jin; Lee, Jin Hwa; Kim, Chan Sung; Choi, Jong Cheol; Oh, Jong Young [Dong-a University College of Medicine, Pusan (Korea, Republic of)
2002-11-01
Spontaneous rupture of a choledochal cyst leading to biliary peritonitis is a rare complication which can be fatal if not promptly diagnosed. The authors report the ultrasound and CT findings of two cases of spontaneous choledochal cystic rupture and the biliary peritonitis which ensued.
Photo-induced DNA cleavage and cytotoxicity of a ruthenium(II) arene anticancer complex
Czech Academy of Sciences Publication Activity Database
Brabec, Viktor; Prachařová, J.; Štěpánková, Jana; Sadler, P. J.; Kašpárková, Jana
2016-01-01
Roč. 160, JUL2016 (2016), s. 149-155 ISSN 0162-0134 R&D Projects: GA ČR(CZ) GA14-21053S; GA MŠk(CZ) LD14019 Institutional support: RVO:68081707 Keywords : Ruthenium anticancer complex * DNA cleavage * Phototoxicity Subject RIV: BO - Biophysics Impact factor: 3.348, year: 2016
Cleavage of cohesin rings coordinates the separation of centrioles and chromatids.
Schöckel, Laura; Möckel, Martin; Mayer, Bernd; Boos, Dominik; Stemmann, Olaf
2011-07-10
Cohesin pairs sister chromatids by forming a tripartite Scc1-Smc1-Smc3 ring around them. In mitosis, cohesin is removed from chromosome arms by the phosphorylation-dependent prophase pathway. Centromeric cohesin is protected by shugoshin 1 and protein phosphatase 2A (Sgo1-PP2A) and opened only in anaphase by separase-dependent cleavage of Scc1 (refs 4-6). Following chromosome segregation, centrioles loosen their tight orthogonal arrangement, which licenses later centrosome duplication in S phase. Although a role of separase in centriole disengagement has been reported, the molecular details of this process remain enigmatic. Here, we identify cohesin as a centriole-engagement factor. Both premature sister-chromatid separation and centriole disengagement are induced by ectopic activation of separase or depletion of Sgo1. These unscheduled events are suppressed by expression of non-cleavable Scc1 or inhibition of the prophase pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the corresponding site-specific protease triggers centriole disengagement. Separation of centrioles can alternatively be induced by ectopic cleavage of an engineered Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and are coordinated with each other by dual use of the cohesin ring complex.
A transcript cleavage factor of Mycobacterium tuberculosis important for its survival.
Directory of Open Access Journals (Sweden)
Arnab China
Full Text Available After initiation of transcription, a number of proteins participate during elongation and termination modifying the properties of the RNA polymerase (RNAP. Gre factors are one such group conserved across bacteria. They regulate transcription by projecting their N-terminal coiled-coil domain into the active center of RNAP through the secondary channel and stimulating hydrolysis of the newly synthesized RNA in backtracked elongation complexes. Rv1080c is a putative gre factor (MtbGre in the genome of Mycobacterium tuberculosis. The protein enhanced the efficiency of promoter clearance by lowering abortive transcription and also rescued arrested and paused elongation complexes on the GC rich mycobacterial template. Although MtbGre is similar in domain organization and shares key residues for catalysis and RNAP interaction with the Gre factors of Escherichia coli, it could not complement an E. coli gre deficient strain. Moreover, MtbGre failed to rescue E. coli RNAP stalled elongation complexes, indicating the importance of specific protein-protein interactions for transcript cleavage. Decrease in the level of MtbGre reduced the bacterial survival by several fold indicating its essential role in mycobacteria. Another Gre homolog, Rv3788 was not functional in transcript cleavage activity indicating that a single Gre is sufficient for efficient transcription of the M. tuberculosis genome.
Microbial mineralization of ring-substituted anilines through an ortho-cleavage pathway.
Zeyer, J; Wasserfallen, A; Timmis, K N
1985-08-01
Moraxella sp. strain G is able to utilize as sole source of carbon and nitrogen aniline, 4-fluoroaniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline (PCA), and 4-bromoaniline but not 4-iodoaniline, 4-methylaniline, 4-methoxyaniline, or 3,4-dichloroaniline. The generation time on PCA was 6 h. The pathway for the degradation of PCA was investigated by analysis of catabolic intermediates and enzyme activities. Mutants of strain G were isolated to enhance the accumulation of specific pathway intermediates. PCA was converted by an aniline oxygenase to 4-chlorocatechol, which in turn was degraded via a modified ortho-cleavage pathway. Synthesis of the aniline oxygenase was inducible by various anilines. This enzyme exhibited a broad substrate specificity. Its specific activity towards substituted anilines seemed to be correlated more with the size than with the electron-withdrawing effect of the substituent and was very low towards anilines having substituents larger than iodine or a methyl group. The initial enzyme of the modified ortho-cleavage pathway, catechol 1,2-dioxygenase, had similar characteristics to those of corresponding enzymes of pathways for the degradation of chlorobenzoic acid and chlorophenol, that is, a broad substrate specificity and high activity towards chlorinated and methylated catechols.
Spontaneous symmetry breaking and its cosmological consequences
International Nuclear Information System (INIS)
Kobzarev, I.Yu.
1975-01-01
The concept of symmetry and of the spontaneous symmetry breaking are presented in popular form as applied to quantum physics. Though the presence of the spontaneous symmetry breaking is not proved directly for interactions of elementary particles, on considering the hypothesis of its presence as applied to the hot Universe theory a possibility of obtaining rather uncommon cosmological consequences is discussed. In particular, spontaneous symmetry breaking of vacuum and the rather hot Universe lead necessarily to the presence of the domain structure of the Universe with the surfase energy at the domain interface in the form of a real physical object
Shared risk aversion in spontaneous and induced abortion.
Catalano, Ralph; Bruckner, Tim A; Karasek, Deborah; Adler, Nancy E; Mortensen, Laust H
2016-05-01
Does the incidence of spontaneous abortion correlate positively over conception cohorts with the incidence of non-clinically indicated induced abortion as predicted by shared risk aversion? We find that the number of spontaneous and non-clinically indicated induced abortions correlates in conception cohorts, suggesting that risk aversion affects both the conscious and non-conscious mechanisms that control parturition. Much literature speculates that natural selection conserved risk aversion because the trait enhanced Darwinian fitness. Risk aversion, moreover, supposedly influences all decisions including those that individuals can and cannot report making. We argue that these circumstances, if real, would manifest in conscious and non-conscious decisions to invest in prospective offspring, and therefore affect incidence of induced and spontaneous abortion over time. Using data from Denmark, we test the hypothesis that monthly conception cohorts yielding unexpectedly many non-clinically indicated induced abortions also yield unexpectedly many spontaneous abortions. The 180 month test period (January 1995 through December 2009), yielded 1 351 800 gestations including 156 780 spontaneous as well as 233 280 induced abortions 9100 of which were clinically indicated. We use Box-Jenkins transfer functions to adjust the incidence of spontaneous and non-clinically indicated induced abortions for autocorrelation (including seasonality), cohort size, and fetal as well as gestational anomalies over the 180-month test period. We use cross-correlation to test our hypothesized association. We find a positive association between spontaneous and non-clinically indicated induced abortions. This suggests, consistent with our theory, that mothers of conception cohorts that yielded more spontaneous abortions than expected opted more frequently than expected for non-clinically indicated induced abortion. Limitations of our work include that even the world's best registration system
Demangeat, Gerard; Greif, Charles; Hemmer, O; Fritsch, C
1990-01-01
Tomato black ring virus RNA-1 was translated in a rabbit reticulocyte lysate. The primary translation product of Mr 250K, which corresponds to its whole coding capacity, was synthesized within 45 min and, during further incubation in the translation medium, was proteolytically processed. Essentially, four cleavage products (P190, P120, P60 and P50) were detected and located within P250 by pulse-chase and immunoprecipitation experiments. P190 is an intermediate cleavage product which is furthe...
Group theory of spontaneous symmetry breaking
International Nuclear Information System (INIS)
Ghaboussi, F.
1987-01-01
The connection between the minimality of the Higgs field potential and the maximal little groups of its representation obtained by spontaneous symmetry breaking is analyzed. It is shown that for several representations the lowest minimum of the potential is related to the maximal little group of those representations. Furthermore, a practical necessity criterion is given for the representation of the Higgs field needed for spontaneous symmetry breaking
Probing Electron-Induced Bond Cleavage at the Single-Molecule Level Using DNA Origami Templates
DEFF Research Database (Denmark)
Keller, Adrian Clemens; Bald, Ilko; Rotaru, Alexandru
2012-01-01
Low-energy electrons (LEEs) play an important role in nanolithography, atmospheric chemistry, and DNA radiation damage. Previously, the cleavage of specific chemical bonds triggered by LEEs has been demonstrated in a variety of small organic molecules such as halogenated benzenes and DNA nucleoba...
Liu, Yudong; Zheng, Haiyan; Guo, Pingping; Feng, Shuxian; Zhou, Xingyu; Ye, Desheng; Chen, Xin; Chen, Shiling
2017-02-01
The aim of this study was to explore the association of the DNA-methyltransferase (DNMT)-3A and DNMT3B promoter polymorphisms with the risk of human spontaneous abortion after assisted reproduction techniques (ARTs) and natural conception. We collected tissues from women who underwent abortion procedures: (a) chorionic villus samples (CVS) and muscle samples (MS) from spontaneous abortions conceived by ART and natural cycle (study group), n = 152; and (b) CVS and MS from normal early pregnancy and second trimester (control group), n = 155. The single-nucleotide polymorphism (SNP) -448A > G in the DNMT3A promoter region and -149C/T polymorphism of DNMT3B were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. The allele frequency of -448A among pregnancy loss group and control group was 34.2 % vs. 16.5 %, respectively. Compared with GG carriers, the DNMT3A -448AA homozygotes had an about 16-fold increased risk of spontaneous abortion [odds ratio (OR) = 16.130, 95 % confidence interval (CI), 3.665-70.984], and AG heterozygotes had an OR of 2.027 (95 % CI, 1.247-3.293). However, the distribution of -448A > G in individuals derived from ART pregnancies was not statistically significantly compared with those derived from spontaneous pregnancies (P = 0.661). For DNMT3B, we observed genotype frequencies of 100 % (TT) in the study group and the control group. The DNMT3A -448A > G polymorphism may be a novel functional SNP and contribute to its genetic susceptibility to spontaneous abortion in Chinese women, and ART may not affect the distribution of -448A > G in pregnancy loss and normal pregnancy. The observed TT genotype of DMNT3B suggests that this is the predominant genotype of this population. The findings provide new insights into the etiology of human spontaneous abortion.
International Nuclear Information System (INIS)
Herrera, Carolina; Klasse, Per Johan; Michael, Elizabeth; Kake, Shivani; Barnes, Kelly; Kibler, Christopher W.; Campbell-Gardener, Lila; Si, Zhihai; Sodroski, Joseph; Moore, John P.; Beddows, Simon
2005-01-01
Endoproteolytic processing of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoproteins is an obligate part of the biosynthetic pathway that generates functional, fusion-competent Env complexes, which are then incorporated into infectious virions. We have examined the influence of cleavage on Env-specific antibody reactivity, Env incorporation into pseudovirions, and the infectivity and neutralization sensitivity of Env-pseudotyped viruses. To do so, we have used both incompletely processed wild-type (Wt) Env and engineered, cleavage-defective Env mutants. We find that there is no simple association between antibody reactivity to cell surface-expressed Env, and the ability of the same antibody to neutralize virus pseudotyped with the same Env proteins. One explanation for the absence of such an association is the diverse array of Env species present on the surface of transiently transfected cells. We also confirm that cleavage-defective mutants are antigenically different from Wt Env. These findings have implications for the use of Env binding assays as predictors of neutralizing activity, and for the development of cleavage-defective Env trimers for use as subunit immunogens
Spontaneous polyploidization in cucumber.
Ramírez-Madera, Axel O; Miller, Nathan D; Spalding, Edgar P; Weng, Yiqun; Havey, Michael J
2017-07-01
This is the first quantitative estimation of spontaneous polyploidy in cucumber and we detected 2.2% polyploids in a greenhouse study. We provide evidence that polyploidization is consistent with endoreduplication and is an on-going process during plant growth. Cucumber occasionally produces polyploid plants, which are problematic for growers because these plants produce misshaped fruits with non-viable seeds. In this study, we undertook the first quantitative study to estimate the relative frequency of spontaneous polyploids in cucumber. Seeds of recombinant inbred lines were produced in different environments, plants were grown in the field and greenhouse, and flow cytometry was used to establish ploidies. From 1422 greenhouse-grown plants, the overall relative frequency of spontaneous polyploidy was 2.2%. Plants possessed nuclei of different ploidies in the same leaves (mosaic) and on different parts of the same plant (chimeric). Our results provide evidence of endoreduplication and polysomaty in cucumber, and that it is an on-going and dynamic process. There was a significant effect (p = 0.018) of seed production environment on the occurrence of polyploid plants. Seed and seedling traits were not accurate predictors of eventual polyploids, and we recommend that cucumber producers rogue plants based on stature and leaf serration to remove potential polyploids.
Directory of Open Access Journals (Sweden)
Ramesh Tati
2017-02-01
Full Text Available Adequate cleavage of von Willebrand factor (VWF prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3, cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.
Leu, Chia-Hsing; Yang, Mei-Lin; Chung, Nai-Hui; Huang, Yen-Jang; Su, Yu-Chu; Chen, Yi-Cheng; Lin, Chia-Cheng; Shieh, Gia-Shing; Chang, Meng-Ya; Wang, Shainn-Wei; Chang, Yao; Chao, Julie; Chao, Lee
2015-01-01
Proteolytic cleavage of the hemagglutinin (HA) of influenza virus by host trypsin-like proteases is required for viral infectivity. Some serine proteases are capable of cleaving influenza virus HA, whereas some serine protease inhibitors (serpins) inhibit the HA cleavage in various cell types. Kallikrein-related peptidase 1 (KLK1, also known as tissue kallikrein) is a widely distributed serine protease. Kallistatin, a serpin synthesized mainly in the liver and rapidly secreted into the circulation, forms complexes with KLK1 and inhibits its activity. Here, we investigated the roles of KLK1 and kallistatin in influenza virus infection. We show that the levels of KLK1 increased, whereas those of kallistatin decreased, in the lungs of mice during influenza virus infection. KLK1 cleaved H1, H2, and H3 HA molecules and consequently enhanced viral production. In contrast, kallistatin inhibited KLK1-mediated HA cleavage and reduced viral production. Cells transduced with the kallistatin gene secreted kallistatin extracellularly, which rendered them more resistant to influenza virus infection. Furthermore, lentivirus-mediated kallistatin gene delivery protected mice against lethal influenza virus challenge by reducing the viral load, inflammation, and injury in the lung. Taking the data together, we determined that KLK1 and kallistatin contribute to the pathogenesis of influenza virus by affecting the cleavage of the HA peptide and inflammatory responses. This study provides a proof of principle for the potential therapeutic application of kallistatin or other KLK1 inhibitors for influenza. Since proteolytic activation also enhances the infectivity of some other viruses, kallistatin and other kallikrein inhibitors may be explored as antiviral agents against these viruses. PMID:26149981
Luczo, Jasmina M.; Stambas, John; Durr, Peter A.; Michalski, Wojtek P.
2015-01-01
Summary The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio‐economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host‐pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:26467906
Spontaneous Achilles tendon rupture in alkaptonuria | Mohammed ...
African Journals Online (AJOL)
Spontaneous Achilles tendon ruptures are uncommon. We present a 46-year-old man with spontaneous Achilles tendon rupture due to ochronosis. To our knowledge, this has not been previously reported in Sudan literature. The tendon of the reported patient healed well after debridement and primary repairs.
Spontaneous magnetization in high-density quark matter
DEFF Research Database (Denmark)
Tsue, Yasuhiko; da Providência, João; Providência, Constanca
2015-01-01
It is shown that spontaneous magnetization occurs due to the anomalous magnetic moments of quarks in high-density quark matter under the tensor-type four-point interaction. The spin polarized condensate for each flavor of quark appears at high baryon density, which leads to the spontaneous magnet...
Children's Spontaneous Vocalisations during Play: Aesthetic Dimensions
Countryman, June; Gabriel, Martha; Thompson, Katherine
2016-01-01
This paper explores the phenomenon of spontaneous vocalisations in the self-chosen, unstructured outdoor play of children aged 3-12. Spontaneous vocalisations encompass the whole range of children's unprompted, natural, expressive vocal soundings beyond spoken language. Non-participant observations at childcare centres and on elementary school…
Spontaneous baryogenesis from asymmetric inflaton
International Nuclear Information System (INIS)
Takahashi, Fuminobu
2015-10-01
We propose a variant scenario of spontaneous baryogenesis from asymmetric inflaton based on current-current interactions between the inflaton and matter fields with a non-zero B-L charge. When the inflaton starts to oscillate around the minimum after inflation, it may lead to excitation of a CP-odd component, which induces an effective chemical potential for the B-L number through the current-current interactions. We study concrete inflation models and show that the spontaneous baryogenesis scenario can be naturally implemented in the chaotic inflation in supergravity.
Lim, Siew Fung; Lee, Song Liang; Chiow, Adrian Kah Heng; Foo, Chek Siang; Wong, Andrew Siang Yih; Tan, Su-Ming
2012-01-01
The acute abdomen accounts for up to 40% of all emergency surgical hospital admissions and a large proportion are secondary to gastrointestinal perforation. Studies have shown the superiority of the abdominal CT over upright chest radiographs in demonstrating free intraperitoneal air. Spontaneous perforated pyometra is a rare cause of the surgical acute abdomen with free intraperitoneal air. Only 38 cases have been reported worldwide. We report 2 cases of spontaneously perforated pyometra in our hospital's general surgery department. Both underwent exploratory laparotomy: one had a total hysterectomy and bilateral salpingo-oophorectomy, while the other had an evacuation of the uterine cavity, primary repair of uterine perforation and a peritoneal washout. A literature search was conducted and all reported cases reviewed in order to describe the clinical presentations and management of the condition. Of the 40 cases to date, including 2 of our cases, the most common presenting symptoms were abdominal pain (97.5%), fever (37.5%) and vomiting (25.0%). The main indication for exploratory laparotomy was pneumoperitoneum (97.5%). Pyometra is an unusual but serious condition in elderly women presenting with an acute abdomen. A high index of suspicion is needed to make the appropriate diagnosis.
Fracture mechanics and physics approach to cleavage analysis in bcc monocrystals
International Nuclear Information System (INIS)
Ivanova, V.S.; Plastinin, V.M.
1980-01-01
On monocrystals of molybdenum obtained by electron--beam zone melting studied are the bonds between micro-and macroparameters of fracture controlling the limit state. Monocrystals of three orientations have been studied, namely >001 110 111<. Confirmed is an important role of plastic deformation in the (110) family planes at cleavage forming in the (100) family planes. A correlation connection is established between threshold value of the stress intensity coefficient and activation energy of plastic deformation
Directory of Open Access Journals (Sweden)
Tsuyuka Sugiishi
2015-12-01
Full Text Available This short review highlights the copper-mediated fluoroalkylation using perfluoroalkylated carboxylic acid derivatives. Carbon–carbon bond cleavage of perfluoroalkylated carboxylic acid derivatives takes place in fluoroalkylation reactions at high temperature (150–200 °C or under basic conditions to generate fluoroalkyl anion sources for the formation of fluoroalkylcopper species. The fluoroalkylation reactions, which proceed through decarboxylation or tetrahedral intermediates, are useful protocols for the synthesis of fluoroalkylated aromatics.
Qi, Yue; Lu, Jiarui; Lai, Wenzhen
2016-05-26
To elucidate the reaction mechanism of the ring cleavage of homogentisate by homogentisate dioxygenase, quantum mechanical/molecular mechanical (QM/MM) calculations were carried out by using two systems in different protonation states of the substrate C2 hydroxyl group. When the substrate C2 hydroxyl group is ionized (the ionized pathway), the superoxo attack on the substrate is the rate-limiting step in the catalytic cycle, with a barrier of 15.9 kcal/mol. Glu396 was found to play an important role in stabilizing the bridge species and its O-O cleavage product by donating a proton via a hydrogen-bonded water molecule. When the substrate C2 hydroxyl group is not ionized (the nonionized pathway), the O-O bond cleavage of the bridge species is the rate-limiting step, with a barrier of 15.3 kcal/mol. The QM/MM-optimized geometries for the dioxygen and alkylperoxo complexes using the nonionized model (for the C2 hydroxyl group) are in agreement with the experimental crystal structures, suggesting that the C2 hydroxyl group is more likely to be nonionized.
Racial Cleavage in Local Voting: The Case of School and Tax Issue Referendums.
Button, James
1993-01-01
Explores voting behavior of African Americans and whites in local school and tax referenda to determine whether racial conflict is still a primal factor in noncandidate elections. Results for voters in 5 counties in Florida (over 1,699,000 voters) reveal African-American underregistration and the continuing importance of racial cleavage. (SLD)
Czech Academy of Sciences Publication Activity Database
Sokolová, R.; Giannarelli, S.; Fanelli, N.; Pospíšil, Lubomír
2017-01-01
Roč. 49, SI C (2017), s. 134-138 ISSN 0324-1130 Institutional support: RVO:61388963 Keywords : electrochemical impedance spectroscopy * rate constant * self-protonation * faradaic phase angle * halogen cleavage * EC processes fitting Subject RIV: CG - Electrochemistry OBOR OECD: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis) Impact factor: 0.238, year: 2016
Spontaneous onset of Complex Regional Pain Syndrome
de Rooij, A.M.; Perez, R.S.G.M.; Huygen, F.J.; van Eijs, F.; van Kleef, M.; Bauer, M.C.R.; van Hilten, J.J.; Marinus, J.
2010-01-01
Complex Regional Pain Syndrome (CRPS) usually develops after a noxious event, but spontaneous onsets have been described in 3-11% of the cases. The existence of spontaneous-onset CRPS is highly debated and the aim of the present study was therefore to compare the phenotypic characteristics of CRPS
Spatial diversity of spontaneous activity in the cortex
Directory of Open Access Journals (Sweden)
Andrew Yong-Yi Tan
2015-09-01
Full Text Available The neocortex is a layered sheet across which a basic organization is thought to widely apply. The variety of spontaneous activity patterns is similar throughout the cortex, consistent with the notion of a basic cortical organization. However, the basic organization is only an outline which needs adjustments and additions to account for the structural and functional diversity across cortical layers and areas. Such diversity suggests that spontaneous activity is spatially diverse in any particular behavioral state. Accordingly, this review summarizes the laminar and areal diversity in cortical activity during fixation and slow oscillations, and the effects of attention, anesthesia and plasticity on the cortical distribution of spontaneous activity. Among questions that remain open, characterizing the spatial diversity in spontaneous membrane potential may help elucidate how differences in circuitry among cortical regions supports their varied functions. More work is also needed to understand whether cortical spontaneous activity not only reflects cortical circuitry, but also contributes to determining the outcome of plasticity, so that it is itself a factor shaping the functional diversity of the cortex.
Liu, Sheng-Hung; Lin, Chao-Hsiung; Liang, Fong-Ping; Chen, Pei-Fen; Kuo, Cheng-Deng; Alam, Mohd Mujahid; Maiti, Barnali; Hung, Shih-Kai; Chi, Chin-Wen; Sun, Chung-Ming; Fu, Shu-Ling
2014-01-15
Andrographolide is a diterpenoid compound isolated from Andrographis paniculata that exhibits anticancer activity. We previously reported that andrographolide suppressed v-Src-mediated cellular transformation by promoting the degradation of Src. In the present study, we demonstrated the involvement of Hsp90 in the andrographolide-mediated inhibition of Src oncogenic activity. Using a proteomics approach, a cleavage fragment of Hsp90α was identified in andrographolide-treated cells. The concentration- and time-dependent induction of Hsp90 cleavage that accompanied the reduction in Src was validated in RK3E cells transformed with either v-Src or a human truncated c-Src variant and treated with andrographolide. In cancer cells, the induction of Hsp90 cleavage by andrographolide and its structural derivatives correlated well with decreased Src levels, the suppression of transformation, and the induction of apoptosis. Moreover, the andrographolide-induced Hsp90 cleavage, Src degradation, inhibition of transformation, and induction of apoptosis were abolished by a ROS inhibitor, N-acetyl-cysteine. Notably, Hsp90 cleavage, decreased levels of Bcr-Abl (another known Hsp90 client protein), and the induction of apoptosis were also observed in human K562 leukemia cells treated with andrographolide or its active derivatives. Together, we demonstrated a novel mechanism by which andrographolide suppressed cancer malignancy that involved inhibiting Hsp90 function and reducing the levels of Hsp90 client proteins. Our results broaden the molecular basis of andrographolide-mediated anticancer activity. Copyright © 2013 Elsevier Inc. All rights reserved.
Marshak, Stephen; Alkmim, Fernando F.; Whittington, Alan; Pedrosa-Soares, Antônio Carlos
2006-01-01
The Araçuaí orogen of eastern Brazil is one of many Brasiliano/Pan African orogens formed during the Neoproterozoic assembly of Gondwana. Its western edge, bordering the São Francisco craton, is the Serra do Espinhaço fold-thrust belt, in which top-up-to-the-west (reverse-sense) faults, west-verging folds (F 1), and east-dipping spaced to phyllitic cleavage (S 1) developed. We have found that the kinematics of deformation changes markedly at the hinterland margin of this fold-thrust belt. Here, beneath a plateau known as the Chapada Acauã, metadiamictite and fine-grained pelitic schist comprise an east-dipping belt that contains an assemblage of structures indicative of top-down-to-the-east (normal-sense) shear. This assemblage includes a cascade of F 2 folds that refold F 1 folds and verge down the dip of the belt's enveloping surfaces, vertical tension gashes, and top-down-to-the-east rotated clasts. Based on the presence of these structures, we propose that the plateau exposes a regional-scale normal-sense shear zone, here called the Chapada Acauã shear zone (CASZ). Because F 2 folds refold F 1 folds, normal-sense shear in the CASZ occurred subsequent to initial west-verging thrusting. Considering this timing of motion in the CASZ, we suggest that the zone accommodated displacement of the internal zone of the Araçuaí orogen down, relative to its foreland fold-thrust belt, and thus played a role in extensional collapse of the orogen. The CASZ trends parallel to preserved thrusts to the west, and thus may represent an inverted thrust fault. Notably, throughout the CASZ, S 1 schistosity has been overprinted by a pervasive, west-dipping asymmetric crenulation cleavage (S 2). The sigmoid shape of S 1 surfaces in S 2 microlithons require that slip on each S 2 surface was top-down-to-the-west. S 2 cleavage is axial-planar to the down-dip verging F 2 folds. Based on its geometry, we suggest that S 2 cleavage initiated either as an antithetic extensional
Socioeconomic position and the risk of spontaneous abortion
DEFF Research Database (Denmark)
Norsker, Filippa Nyboe; Espenhain, Laura; rogvi, Sofie
2012-01-01
To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion.......To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion....
Spontaneous indices are inconsistent with arterial baroreflex gain.
Lipman, Ruth D; Salisbury, Julie K; Taylor, J Andrew
2003-10-01
Spontaneously occurring, parallel fluctuations in arterial pressure and heart period are frequently used as indices of baroreflex function. Despite the convenience of spontaneous indices, their relation to the arterial baroreflex remains unclear. Therefore, in 97 volunteers, we derived 5 proposed indices (sequence method, alpha-index, transfer function, low-frequency transfer function, and impulse response function), compared them with arterial baroreflex gain (by the modified Oxford pharmacologic technique), and examined their relation to carotid distensibility and respiratory sinus arrhythmia. The subjects comprised men and women (n=41) aged 25 to 86 years, 30% of whom had established coronary artery disease. Generally, the indices were correlated with each other (except alpha-index and low-frequency transfer function) and with baroreflex gain. However, the Bland-Altman method demonstrated that the spontaneous indices had limits of agreement as large as the baroreflex gain itself. Even in individuals within the lowest tertile of baroreflex gain for whom baroreflex gain appears to be the most clinically relevant, spontaneous indices failed to relate to baroreflex gain. In fact, for these individuals, there was no correlation between any index and baroreflex gain. Forward stepwise linear regression showed that all spontaneous indices and baroreflex gain were related to respiratory sinus arrhythmia, but only baroreflex gain was related to carotid distensibility. Therefore, these data suggest that spontaneous indices are inadequate estimates of gain and are inconsistent with arterial baroreflex function.
Englebretsen, D.R; Choma, C.T.; Robillard, G.T.
1998-01-01
Nα-haloacetylated peptides made by Fmoc solid phase synthesis survived cleavage when EDT was used as a cleavage component. Two segments of a desgned transmembrane protein, one bromoacetylated, the other containing a cysteine, and each bearing a "solubilising tail" peptide, were synthesised by Fmoc
Spontaneous vertebral dissection: Clinical, conventional angiographic, CT, and MR findings
Energy Technology Data Exchange (ETDEWEB)
Provenzale, J.M.; Morgenlander, J.C. [Duke Univ. Medical Center, Durham, NC (United States); Gress, D. [Univ. of California, San Francisco, CA (United States)
1996-03-01
The purpose of this study was to determine if typical clinical and neuroradiologic patterns exist in patients with spontaneous vertebral artery (VA) dissection. The medical records and neuroradiologic examinations of 14 patients with spontaneous VA dissection were reviewed. The medical records were examined to exclude patients with a history of trauma and to record evidence of a nontratimatic precipitating event ({open_quotes}trivial trauma{close_quotes}) and presence of possible risk factors such as hypertension. All patients under-went conventional angiography, 13 either CT or MRI (II both CT and MRI), and 3 MRA. Conventional arteriograrris were evaluated for dissection site, evidence of fibromuscular dysplasia, luminal stenosis or occlusion, and pseudoaneurysm formation, CT examinations for the presence of infarction or subarachnoid hemorrhage, MR examinations for the presence of infarction or arterial signal abnormality, and MR angiograms for abnormality of the arterial signal column. Seven patients had precipitating events within 24 h of onset of symptoms that may have been causative of dissection and five had hypertension. At catheter angiography, two patients had dissections in two arteries (both VAs in one patient, VA and internal carotid artery in one patient), giving a total of 15 VAs with dissection. Dissection sites included V1 in four patients, V2 in one patient, V3 in three patients, V4 in six patients, and both V3 and V4 in one patient. Luminal stenosis was present in 13 VAs, occlusion in 2, pseudoaneurysm in 1, and evidence of fibromuscular dysplasia in 1. Posterior circulation infarcts were found on CT or MR in five patients. Subarachnoid hemorrhage was found on CT in two patients and by lumbar puncture alone in two patients. Abnormal periarterial signal on MRI was seen in three patients. MRA demonstrated absent VA signal in one patient, pseudoaneurysm in one, and a false-negative examination in one.
Spontaneous biloma: Report of two cases with review of the literature
Directory of Open Access Journals (Sweden)
ANUBHAV GOEL
2018-05-01
Full Text Available Biloma is the collection of bile outside the biliary tree and can be intra or extra hepatic. It is most commonly iatrogenic, secondary to surgery or percutaneous transhepatic procedures or secondary to abdominal trauma. Spontaneous bilomas are very rarely described in the literature. CASE REPORT A 32 years old female presented as lump abdomen in epigastric region. Blood investigations were normal. Chest radiographs were unremarkable. Ultrasound examination revealed two cystic lesion in relation to left lobe of liver and cholelithiasis with choledocholithiasis. Ultrasound guided pigtail catheter drainage of the collection was done. ERCP failed to manage the choledocholithiasis. CBD exploration with choledocholithotomy and T-tube drainage and cholecystectomy was done. The postoperative period was uneventful, and the T-tube was removed on the 10th day after a normal T-tube cholangiogram. CASE 2 32 year old female admitted in emergency with complain of acute pain in abdomen since 2 days. Ultrasound shows contracted gallbladder withstone along with focal collection in perihepatic and peri gallbladder region extending into subcutaneous plane with cbd stone.. Ultrasound guided pigtail catheter drainage of the collection was done. After 5 days she underwent ERCP by which cbd stones were cleared. Elective laparoscopic cholecystectomy was done. CONCLUSION A high index of clinical suspicion is necessary for prompt recognition and its proper management. Percutaneous treatment should be considered as the first-line option for patients with spontaneous biloma. In cases of persistent bile leaks, endoscopic biliary drainage and endoscopic sphincterotomy with or without stent placement should be performed. Surgery is now performed only in cases with a persistent bile leak or for treatment of an underlying disease.
Distinct spontaneous shrinkage of a sporadic vestibular schwannoma
DEFF Research Database (Denmark)
Huang, Xiaowen; Cayé-Thomasen, Per; Stangerup, Sven-Eric
2013-01-01
on "shrinkage" or "negative growth" or "regression" or "involution" of the tumor were selected, and the contents on the rate, extent and mechanism of spontaneous tumor shrinkage were extracted and reviewed. The reported rate of spontaneous shrinkage of vestibular schwannoma is 5-10% of patients managed......We present a case with outspoken spontaneous vestibular schwannoma shrinkage and review the related literature. The patient was initially diagnosed with a left-sided, intrameatal vestibular schwannoma, which subsequently grew into the cerebello-pontine angle (CPA), followed by total shrinkage...... of the CPA component without any intervention over a 12-year observation period. The literature on spontaneous tumor shrinkage was retrieved by searching the subject terms "vestibular schwannoma, conservative management" in PubMed/MEDLINE database, without a time limit. Of the published data, the articles...
Yoshida, Takeshi; Uchiyama, Akinori; Matsuura, Nariaki; Mashimo, Takashi; Fujino, Yuji
2012-05-01
We investigated whether potentially injurious transpulmonary pressure could be generated by strong spontaneous breathing and exacerbate lung injury even when plateau pressure is limited to ventilation, each combined with weak or strong spontaneous breathing effort. Inspiratory pressure for low tidal volume ventilation was set at 10 cm H2O and tidal volume at 6 mL/kg. For moderate tidal volume ventilation, the values were 20 cm H2O and 7-9 mL/kg. The groups were: low tidal volume ventilation+spontaneous breathingweak, low tidal volume ventilation+spontaneous breathingstrong, moderate tidal volume ventilation+spontaneous breathingweak, and moderate tidal volume ventilation+spontaneous breathingstrong. Each group had the same settings for positive end-expiratory pressure of 8 cm H2O. Respiratory variables were measured every 60 mins. Distribution of lung aeration and alveolar collapse were histologically evaluated. Low tidal volume ventilation+spontaneous breathingstrong showed the most favorable oxygenation and compliance of respiratory system, and the best lung aeration. By contrast, in moderate tidal volume ventilation+spontaneous breathingstrong, the greatest atelectasis with numerous neutrophils was observed. While we applied settings to maintain plateau pressure at ventilation+spontaneous breathingstrong, transpulmonary pressure rose >33 cm H2O. Both minute ventilation and respiratory rate were higher in the strong spontaneous breathing groups. Even when plateau pressure is limited to mechanical ventilation, transpulmonary pressure and tidal volume should be strictly controlled to prevent further lung injury.
Uncoupling of Protease trans-Cleavage and Helicase Activities in Pestivirus NS3.
Zheng, Fengwei; Lu, Guoliang; Li, Ling; Gong, Peng; Pan, Zishu
2017-11-01
The nonstructural protein NS3 from the Flaviviridae family is a multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å 2 intramolecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the NS3-NS4A cis -cleavage event. Although this conformation is incompatible with protease trans -cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo Our work reveals important features of protease-helicase coordination in pestivirus NS3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein. IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis -cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through different
Starkey, Jessica D.; Yamamoto, Masakazu; Yamamoto, Shoko; Goldhamer, David J.
2011-01-01
The developmental potential of skeletal muscle stem cells (satellite cells) remains controversial. The authors investigated satellite cell developmental potential in single fiber and clonal cultures derived from MyoDiCre/+;R26REYFP/+ muscle, in which essentially all satellite cells are permanently labeled. Approximately 60% of the clones derived from cells that co-purified with muscle fibers spontaneously underwent adipogenic differentiation. These adipocytes stained with Oil-Red-O and expressed the terminal differentiation markers, adipsin and fatty acid binding protein 4, but did not express EYFP and were therefore not of satellite cell origin. Satellite cells mutant for either MyoD or Myf-5 also maintained myogenic programming in culture and did not adopt an adipogenic fate. Incorporation of additional wash steps prior to muscle fiber plating virtually eliminated the non-myogenic cells but did not reduce the number of adherent Pax7+ satellite cells. More than half of the adipocytes observed in cultures from Tie2-Cre mice were recombined, further demonstrating a non-satellite cell origin. Under adipogenesis-inducing conditions, satellite cells accumulated cytoplasmic lipid but maintained myogenic protein expression and did not fully execute the adipogenic differentiation program, distinguishing them from adipocytes observed in muscle fiber cultures. The authors conclude that skeletal muscle satellite cells are committed to myogenesis and do not spontaneously adopt an adipogenic fate. PMID:21339173
DEFF Research Database (Denmark)
Senior, BW; Batten, MR; Kilian, Mogens
2002-01-01
All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were const...... constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases....
Taha, Mohamed; Latt, Htun; Al-Khafaji, Jaafar; Ali, Mohamed; Seher, Richard
2018-01-01
Background : Spontaneous coronary artery dissection (SCAD) is increasingly recognized as an important cause of myocardial infarction and sudden death. Although some correlations have been noted in relation to aetiology, no direct causes have been identified in a large number of patients. Most of the patients are women in peripartum period or of childbearing age, with few if any risk factors for coronary heart disease. In men, however, risk factors for atherosclerosis are more prevalent in cases of SCAD Case report : We report a case of a 43-years-old healthy male, with no known risk factors, who presented with ischemic chest pain and elevated troponin levels. He underwent an emergent percutaneous transluminal coronary angiography which revealed a total occlusion of the left anterior descending artery at its origin with an evidence of spontaneous dissection as the cause of the occlusion, which was subsequently treated with placement of a drug-eluting stent and thrombectomy from the distal occluded portion. This case highlights the importance of including spontaneous coronary artery dissection as a cause of ischemic cardiac insults and illustrates the approach to treatment. Conclusion : Internists should have a low threshold of clinical suspicion for SCAD especially in a young patient with no known risk factors and should know the importance of emergency in management.
Cigarette, alcohol, and caffeine consumption: risk factors for spontaneous abortion
DEFF Research Database (Denmark)
Rasch, Vibeke
2003-01-01
OBJECTIVE: To study the association between cigarette, alcohol, and caffeine consumption and the occurrence of spontaneous abortion. METHODS: The study population consisted of 330 women with spontaneous abortion and 1168 pregnant women receiving antenatal care. A case-control design was utilized;...... units alcohol per week and 375 mg or more caffeine per day during pregnancy may increase the risk of spontaneous abortion.......OBJECTIVE: To study the association between cigarette, alcohol, and caffeine consumption and the occurrence of spontaneous abortion. METHODS: The study population consisted of 330 women with spontaneous abortion and 1168 pregnant women receiving antenatal care. A case-control design was utilized......; cases were defined as women with a spontaneous abortion in gestational week 6-16 and controls as women with a live fetus in gestational week 6-16. The variables studied comprise age, parity, occupational situation, cigarette, alcohol, and caffeine consumption. The association between cigarette, alcohol...
Hahn, Veronika; Mikolasch, Annett; Schauer, Frieder
2014-02-01
Laccases are able to mediate both cleavage and synthesis processes. The basis for this dual reaction capability lies in the property of the enzyme laccase to oxidize phenolic, and to some extent non-phenolic substances, to reactive radicals which can undergo on the one hand separations of small substitutents or large molecule parts from the parent compound and on the other hand coupling reactions with other radicals or molecules which are not themselves oxidizable by laccase. The cleavage of the non-phenolic compound 4-morpholinoaniline as well as the deamination of 4-aminophenol and the dechlorination of 4-chlorophenol resulted in the formation of 1,4-hydroquinone which is immediately oxidized by laccase to 1,4-benzoquinone. The formation of the 1,4-hydroquinone/1,4-benzoquinone is the rate limiting step for the synthesis of the heteromolecular dimers and trimers composed of 1,4-benzoquinone and one or two molecules of morpholine. In addition to the synthesis of new compounds from the cleavage products, 4-morpholinoaniline polymerized probably via azo groups and C-N bonds to a homomolecular dimer and trimer. Similarities and differences in cleavage and synthesis reactions catalyzed by the low redox potential laccase of Myceliophthora thermophila (0.46 V) and the high redox potential laccase of Pycnoporus cinnabarinus (0.79 V) were determined. In addition, the dependency of the cleavage and synthesis efficiencies on the (a) structure and redox potential of the laccase, (b) structure and redox potential of the substrate, (c) pH value of the buffer used, (d) incubation temperature, (e) solvent concentration, and (f) laccase activity is discussed in general.
Walker, S Hunter; Taylor, Amber D; Muddiman, David C
2013-06-30
Traditionally, free oligosaccharide internal standards are used to account for variability in glycan relative quantification experiments by mass spectrometry. However, a more suitable internal standard would be a glycoprotein, which could also control for enzymatic cleavage efficiency, allowing for more accurate quantitative experiments. Hydrophobic, hydrazide N-linked glycan reagents (both native and stable-isotope labeled) are used to derivatize and differentially label N-linked glycan samples for relative quantification, and the samples are analyzed by a reversed-phase liquid chromatography chip system coupled online to a Q-Exactive mass spectrometer. The inclusion of two internal standards, maltoheptaose (previously used) and horseradish peroxidase (HRP) (novel), is studied to demonstrate the effectiveness of using a glycoprotein as an internal standard in glycan relative quantification experiments. HRP is a glycoprotein containing a xylosylated N-linked glycan, which is unique from mammalian N-linked glycans. Thus, the internal standard xylosylated glycan could be detected without interference to the sample. Additionally, it was shown that differences in cleavage efficiency can be detected by monitoring the HRP glycan. In a sample where cleavage efficiency variation is minimal, the HRP glycan performs as well as maltoheptaose. Because the HRP glycan performs as well as maltoheptaose but is also capable of correcting and accounting for cleavage variability, it is a more versatile internal standard and will be used in all subsequent biological studies. Because of the possible lot-to-lot variation of an enzyme, differences in biological matrix, and variable enzyme activity over time, it is a necessity to account for glycan cleavage variability in glycan relative quantification experiments. Copyright © 2013 John Wiley & Sons, Ltd.
Spontaneous Hedonic Reactions to Social Media Cues.
van Koningsbruggen, Guido M; Hartmann, Tilo; Eden, Allison; Veling, Harm
2017-05-01
Why is it so difficult to resist the desire to use social media? One possibility is that frequent social media users possess strong and spontaneous hedonic reactions to social media cues, which, in turn, makes it difficult to resist social media temptations. In two studies (total N = 200), we investigated less-frequent and frequent social media users' spontaneous hedonic reactions to social media cues using the Affect Misattribution Procedure-an implicit measure of affective reactions. Results demonstrated that frequent social media users showed more favorable affective reactions in response to social media (vs. control) cues, whereas less-frequent social media users' affective reactions did not differ between social media and control cues (Studies 1 and 2). Moreover, the spontaneous hedonic reactions to social media (vs. control) cues were related to self-reported cravings to use social media and partially accounted for the link between social media use and social media cravings (Study 2). These findings suggest that frequent social media users' spontaneous hedonic reactions in response to social media cues might contribute to their difficulties in resisting desires to use social media.
Energy Technology Data Exchange (ETDEWEB)
Kim, Jinsil; Ha, Hye-Jeong [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Kim, Sujin [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113 (Korea, Republic of); Choi, Ah-Reum [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Lee, Sook-Jeong [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Hoe, Kwang-Lae, E-mail: kwanghoe@cnu.ac.kr [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Kim, Dong-Uk, E-mail: kimdongu@kribb.re.kr [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of)
2015-12-25
Lipid homeostasis in mammalian cells is regulated by sterol regulatory element-binding protein (SREBP) transcription factors that are activated through sequential cleavage by Golgi Site-1 and Site-2 proteases. Fission yeast SREBP, Sre1, engages a different mechanism involving the Golgi Dsc E3 ligase complex, but it is not clearly understood exactly how Sre1 is proteolytically cleaved and activated. In this study, we screened the Schizosaccharomyces pombe non-essential haploid deletion collection to identify missing components of the Sre1 cleavage machinery. Our screen identified an additional component of the SREBP pathway required for Sre1 proteolysis named rhomboid protein 2 (Rbd2). We show that an rbd2 deletion mutant fails to grow under hypoxic and hypoxia-mimetic conditions due to lack of Sre1 activity and that this growth phenotype is rescued by Sre1N, a cleaved active form of Sre1. We found that the growth inhibition phenotype under low oxygen conditions is specific to the strain with deletion of rbd2, not any other fission yeast rhomboid-encoding genes. Our study also identified conserved residues of Rbd2 that are required for Sre1 proteolytic cleavage. All together, our results suggest that Rbd2 is a functional SREBP protease with conserved residues required for Sre1 cleavage and provide an important piece of the puzzle to understand the mechanisms for Sre1 activation and the regulation of various biological and pathological processes involving SREBPs. - Highlights: • An rbd2-deleted yeast strain shows defects in growth in response to low oxygen levels. • rbd2-deficient cells fail to generate cleaved Sre1 (Sre1N) under hypoxic conditions. • Expression of Sre1N rescues the rbd2 deletion mutant growth phenotype. • Rbd2 contains conserved residues potentially critical for catalytic activity. • Mutation of the conserved Rbd2 catalytic residues leads to defects in Sre1 cleavage.
Spontaneous globe luxation associated with chronic obstructive pulmonary disease
Directory of Open Access Journals (Sweden)
M Ashok Kumar
2012-01-01
Full Text Available Spontaneous globe luxation is a rarely reported condition which can lead to complications like optic neuropathy. Common causes are thyroid eye disease, shallow orbit and floppy eyelid syndrome. We report a case of spontaneous globe luxation with the onset and severity associated with chronic obstructive pulmonary disease (COPD. To our knowledge, this is the first case of spontaneous globe luxation associated with COPD.
Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes
Liu, Ming; Lara-Lemus, Roberto; Shan, Shu-ou; Wright, Jordan; Haataja, Leena; Barbetti, Fabrizio; Guo, Huan; Larkin, Dennis; Arvan, Peter
2012-01-01
Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an improper site, producing two subpopulations of molecules. Both show impaired oxidative folding and are retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER exit of coexpressed wild-type proinsulin, accounting for its dominant-negative behavior. Upon increased expression of ER–oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative folding of wild-type proinsulin improves, accelerating its ER export and increasing wild-type insulin production. We conclude that the efficiency of SP cleavage is linked to the oxidation of (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of the mutant as well as that of coexpressed wild-type proinsulin. Improving oxidative folding of wild-type proinsulin may provide a feasible way to rescue insulin production in patients with MIDY. PMID:22357960
Directory of Open Access Journals (Sweden)
André Weiss
Full Text Available EspPα and EspI are serine protease autotransporters found in enterohemorrhagic Escherichia coli. They both belong to the SPATE autotransporter family and are believed to contribute to pathogenicity via proteolytic cleavage and inactivation of different key host proteins during infection. Here, we describe the specific cleavage and functional inactivation of serine protease inhibitors (serpins by EspPα and compare this activity with the related SPATE EspI. Serpins are structurally related proteins that regulate vital protease cascades, such as blood coagulation and inflammatory host response. For the rapid determination of serpin cleavage sites, we applied direct MALDI-TOF-MS or ESI-FTMS analysis of coincubations of serpins and SPATE proteases and confirmed observed cleavage positions using in-gel-digest of SDS-PAGE-separated degradation products. Activities of both serpin and SPATE protease were assessed in a newly developed photometrical assay using chromogenic peptide substrates. EspPα cleaved the serpins α1-protease inhibitor (α1-PI, α1-antichymotrypsin, angiotensinogen, and α2-antiplasmin. Serpin cleavage led to loss of inhibitory function as demonstrated for α1-PI while EspPα activity was not affected. Notably, EspPα showed pronounced specificity and cleaved procoagulatory serpins such as α2-antiplasmin while the anticoagulatory antithrombin III was not affected. Together with recently published research, this underlines the interference of EspPα with hemostasis or inflammatory responses during infection, while the observed interaction of EspI with serpins is likely to be not physiologically relevant. EspPα-mediated serpin cleavage occurred always in flexible loops, indicating that this structural motif might be required for substrate recognition.
Directory of Open Access Journals (Sweden)
Marijke De Bock
2015-01-01
Full Text Available The coordination of tissue function is mediated by gap junctions (GJs that enable direct cell-cell transfer of metabolic and electric signals. GJs are formed by connexin (Cx proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels (HCs in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein-protein interactions and posttranslational modifications that predominantly take place in the C-terminal domain of Cx43. Matrix metalloproteases (MMPs are a major group of zinc-dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP-Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.
Thomson, J B; Lilley, D M
1999-01-01
In the natural form of the hairpin ribozyme the two loop-carrying duplexes that comprise the majority of essential bases for activity form two adjacent helical arms of a four-way RNA junction. In the present work we have manipulated the sequence around the junction in a way known to perturb the global folding properties. We find that replacement of the junction by a different sequence that has the same conformational properties as the natural sequence gives closely similar reaction rate and Arrhenius activation energy for the substrate cleavage reaction. By comparison, rotation of the natural sequence in order to alter the three-dimensional folding of the ribozyme leads to a tenfold reduction in the kinetics of cleavage. Replacement with the U1 four-way junction that is resistant to rotation into the antiparallel structure required to allow interaction between the loops also gives a tenfold reduction in cleavage rate. The results indicate that the conformation of the junction has a major influence on the catalytic activity of the ribozyme. The results are all consistent with a role for the junction in the provision of a framework by which the loops are presented for interaction in order to create the active form of the ribozyme. PMID:10024170
Valle, Marcello; Guimarães, Fernando; Cavagnoli, Melissa; Sampaio, Marcos; Geber, Selmo
2012-12-01
The role of cryopreservation in assisted reproductive technology programs has increased within the last years allowing the transfer of a limited number of embryos and the storage of the remaining for future use. The reduction in the number of transferred embryos decreases the frequency of multiple pregnancy rates and of ovarian hyperstimulation syndrome while the cumulative pregnancy rate can be maximized. Moreover, as not all embryos will survive the warming process more cleavage stage embryos are warmed to improve selection for transfer. Therefore, surplus good quality cleavage stage embryos and/or blastocysts must be re-vitrified for further transfer to achieve pregnancy. To our knowledge, there have been no reports demonstrating that human embryos can be successfully vitrified/warmed twice at the cleavage stage. Thus we report two successful pregnancies and deliveries of healthy babies after transfer of embryos that were twice vitrified/warmed at 2-4 cells stage. Copyright © 2012 Elsevier Inc. All rights reserved.
Surgical management of spontaneous hypertensive brainstem hemorrhage
Directory of Open Access Journals (Sweden)
Bal Krishna Shrestha
2015-09-01
Full Text Available Spontaneous hypertensive brainstem hemorrhage is the spontaneous brainstem hemorrhage associated with long term hypertension but not having definite focal or objective lesion. It is a catastrophic event which has a poor prognosis and usually managed conservatively. It is not uncommon, especially in eastern Asian populations, accounting approximately for 10% of the intracerebral hemorrhage. Before the advent of computed tomography, the diagnosis of brainstem hemorrhage was usually based on the clinical picture or by autopsy and believed to be untreatable via surgery. The introduction of computed tomography permitted to categorize the subtypes of brainstem hemorrhage with more predicted outcome. Continuous ongoing developments in the stereotactic surgery and microsurgery have added more specific surgical management in these patients. However, whether to manage conservatively or promptly with surgical evacuation of hematoma is still a controversy. Studies have shown that an accurate prognostic assessment based on clinical and radiological features on admission is critical for establishing a reasonable therapeutic approach. Some authors have advocate conservative management, whereas others have suggested the efficacy of surgical treatment in brainstem hemorrhage. With the widening knowledge in microsurgical techniques as well as neuroimaging technology, there seems to have more optimistic hope of surgical management of spontaneous hypertensive brainstem hemorrhage for better prognosis. Here we present five cases of severe spontaneous hypertensive brainstem hemorrhage patients who had undergone surgery; and explore the possibilities of surgical management in patients with the spontaneous hypertensive brainstem hemorrhage.
Active hippocampal networks undergo spontaneous synaptic modification.
Directory of Open Access Journals (Sweden)
Masako Tsukamoto-Yasui
Full Text Available The brain is self-writable; as the brain voluntarily adapts itself to a changing environment, the neural circuitry rearranges its functional connectivity by referring to its own activity. How the internal activity modifies synaptic weights is largely unknown, however. Here we report that spontaneous activity causes complex reorganization of synaptic connectivity without any external (or artificial stimuli. Under physiologically relevant ionic conditions, CA3 pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable slow oscillations of membrane potential, alternating between the so-called UP and DOWN states. The generation of slow oscillations did not require fast synaptic transmission, but their patterns were coordinated by local circuit activity. In the course of generating spontaneous activity, individual neurons acquired bidirectional long-lasting synaptic modification. The spontaneous synaptic plasticity depended on a rise in intracellular calcium concentrations of postsynaptic cells, but not on NMDA receptor activity. The direction and amount of the plasticity varied depending on slow oscillation patterns and synapse locations, and thus, they were diverse in a network. Once this global synaptic refinement occurred, the same neurons now displayed different patterns of spontaneous activity, which in turn exhibited different levels of synaptic plasticity. Thus, active networks continuously update their internal states through ongoing synaptic plasticity. With computational simulations, we suggest that with this slow oscillation-induced plasticity, a recurrent network converges on a more specific state, compared to that with spike timing-dependent plasticity alone.
Xu, Han; Miao, Bei; Zhang, Minhua; Chen, Yifei; Wang, Lichang
2017-10-04
The performance of transition metal catalysts for ethanol oxidation reaction (EOR) in direct ethanol fuel cells (DEFCs) may be greatly affected by their oxidation. However, the specific effect and catalytic mechanism for EOR of transition metal oxides are still unclear and deserve in-depth exploitation. Copper as a potential anode catalyst can be easily oxidized in air. Thus, in this study, we investigated C-C and C-H bond cleavage reactions of CH x CO (x = 1, 2, 3) species in EOR on Cu 2 O(111) using PBE+U calculations, as well as the specific effect of +U correction on the process of adsorption and reaction on Cu 2 O(111). It was revealed that the catalytic performance of Cu 2 O(111) for EOR was restrained compared with that of Cu(100). Except for the C-H cleavage of CH 2 CO, all the reaction barriers for C-C and C-H cleavage were higher than those on Cu(100). The most probable pathway for CH 3 CO to CHCO on Cu 2 O(111) was the continuous dehydrogenation reaction. Besides, the barrier for C-C bond cleavage increased due to the loss of H atoms in the intermediate. Moreover, by the comparison of the traditional GGA/PBE method and the PBE+U method, it could be concluded that C-C cleavage barriers would be underestimated without +U correction, while C-H cleavage barriers would be overestimated. +U correction was proved to be necessary, and the reaction barriers and the values of the Hubbard U parameter had a proper linear relationship.
Shared risk aversion in spontaneous and induced abortion
DEFF Research Database (Denmark)
Catalano, Ralph; Bruckner, Tim A.; Karasek, Deborah
2016-01-01
spontaneous and non-clinically indicated induced abortions. This suggests, consistent with our theory, that mothers of conception cohorts that yielded more spontaneous abortions than expected opted more frequently than expected for non-clinically indicated induced abortion. LIMITATIONS, REASONS FOR CAUTION...
Spontaneous passage of long, sharp gastrointestinal foreign body in a child.
Karthikeyan, Vilvapathy Senguttuvan; Ansari, Mohammed Gaffoor; Suresh, Ramasamy; Easwaran, Bettaiyagowder
2015-01-19
Foreign body (FB) ingestion is a common problem in children. Up to 90% of these FBs pass spontaneously. FBs reaching the stomach usually pass out spontaneously. Exceptions to this spontaneous passage include a long FB that cannot cross the pylorus, duodenum or ileocaecal junction. We present a case of a 9-year boy who accidentally ingested a long paper pin, which spontaneously passed in 26 h. This case is being reported to highlight the successful spontaneous passage of a 4 cm long sharp foreign body in a child. 2015 BMJ Publishing Group Ltd.
Fast cleavage of phycocyanobilin from phycocyanin for use in food colouring
DEFF Research Database (Denmark)
Roda-Serrat, Maria Cinta; Christensen, Knud Villy; El-Houri, Rime
2018-01-01
Phycocyanins from cyanobacteria are possible sources for new natural blue colourants. Their chromophore, phycocyanobilin (PCB), was cleaved from the apoprotein by solvolysis in alcohols and alcoholic aqueous solutions. In all cases two PCB isomers were obtained, while different solvent adducts were......, and microwave assisted reaction. The sealed vessel method is a new approach for fast cleavage of PCB from phycocyanin and gave at 120°C the same yield within 30 min compared to 16 hours by the conventional reflux method (P
Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart
2014-10-13
Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.
Detection of target phonemes in spontaneous and read speech
Mehta, G.; Cutler, A.
1988-01-01
Although spontaneous speech occurs more frequently in most listeners’ experience than read speech, laboratory studies of human speech recognition typically use carefully controlled materials read from a script. The phonological and prosodic characteristics of spontaneous and read speech differ considerably, however, which suggests that laboratory results may not generalize to the recognition of spontaneous and read speech materials, and their response time to detect word-initial target phonem...
Effect of using pump on postoperative pleural effusion in the patients that underwent CABG
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Mehmet Özülkü
2015-08-01
Full Text Available Abstract Objective: The present study investigated effect of using pump on postoperative pleural effusion in patients who underwent coronary artery bypass grafting. Methods: A total of 256 patients who underwent isolated coronary artery bypass grafting surgery in the Cardiovascular Surgery clinic were enrolled in the study. Jostra-Cobe (Model 043213 105, VLC 865, Sweden heart-lung machine was used in on-pump coronary artery bypass grafting. Off-pump coronary artery bypass grafting was performed using Octopus and Starfish. Proximal anastomoses to the aorta in both on-pump and off-pump techniques were performed by side clamps. The patients were discharged from the hospital between postoperative day 6 and day 11. Results: The incidence of postoperative right pleural effusion and bilateral pleural effusion was found to be higher as a count in Group 1 (on-pump as compared to Group 2 (off-pump. But the difference was not statistically significant [P>0.05 for right pleural effusion (P=0.893, P>0.05 for bilateral pleural effusion (P=0.780]. Left pleural effusion was encountered to be lower in Group 2 (off-pump. The difference was found to be statistically significant (P<0.05, P=0.006. Conclusion: Under the light of these results, it can be said that left pleural effusion is less prevalent in the patients that underwent off-pump coronary artery bypass grafting when compared to the patients that underwent on-pump coronary artery bypass grafting.
International Nuclear Information System (INIS)
Headlam, H.A.; Davies, M.J.; Mortimer, A.; Easton, C.J.
2000-01-01
Full text: Exposure of proteins to radicals in the presence of O 2 brings about multiple changes including side-chain oxidation, backbone fragmentation, cross-linking, unfolding, changes in hydrophobicity and conformation, altered susceptibility to proteolytic enzymes and formation of new reactive groups (e.g. hydroperoxides and 3,4-dihydroxyphenylalanine). All of these processes can result in loss of structural or enzymatic activity. The mechanisms that give rise to backbone cleavage are only partly understood. Whilst it is known that direct hydrogen atom abstraction at a-carbon sites gives backbone cleavages it has also been proposed that initial attack at side-chain sites might also give rise to backbone cleavage. In this study we have examined whether initial attack at the β- (C-3) position can give rise to α-carbon radicals (and hence backbone cleavage) via the formation, and subsequent β- scission, of C-3 alkoxyl radicals. This process has been observed previously with protected amino acids in organic solvents (J. Chem. Soc. Perkin Trans. 2, 1997, 503-507) but the occurrence of such reactions with proteins in aqueous solution has not been explored. Alkoxyl radicals were generated at the C-3 position of a variety of protected amino acids and small peptides by two methods: metal-ion catalysed decomposition of hydroperoxides formed as a result of γ-radiolysis in the presence of O 2 , and UV photolysis of nitrate esters. In most cases radicals have been detected by EPR spectroscopy using nitroso and nitrone spin traps, which can be assigned by comparison with literature data to α-carbon radicals; in some case assignments were confirmed by the generation of the putative species by other routes. With Ala peptide hydroperoxides and nitrate esters, and MNP as the spin trap, the major radical detected in each case has been assigned to the adduct of an α-carbon radical with partial structure - NH- . CH-C(O) - consistent with the rapid occurrence of the above
Hahn, Peter J; Lai, Zhi-Wei; Nevaldine, Barbara; Schiff, Ninel; Fiore, Nancy C; Silverstone, Allen E
2003-11-01
We have quantified the emergence of early chromatin breaks during the signal transduction phase of apoptosis in mouse thymocytes after treatment with either ionizing radiation or dexamethasone. Dexamethasone at 1 microM can induce significant levels of DNA breaks (equivalent to the amount induced directly by 7.5 Gy ionizing radiation) within 0.5 h of treatment. The execution phase of apoptosis was not observed until 4-6 h after the same treatment. The presence of the Bcl2 transgene under the control of the p56lck promoter almost completely inhibited apoptosis up to 24 h after treatment, but it had virtually no effect on the early chromatin cleavage occurring in the first 6 h. Ionizing radiation induced chromatin cleavage both directly by damaging DNA and indirectly with kinetics similar to the induction of chromatin cleavage by dexamethasone. The presence of the Bcl2 transgene had no effect on the direct or indirect radiation-induced cleavage in the first 6 h, but after the first 6 h, the Bcl2 gene inhibited further radiation-induced chromatin cleavage. These results suggest that endonucleases are activated within minutes of treatment with either dexamethasone or ionizing radiation as part of the very early signal transduction phase of apoptosis, and prior to the irreversible commitment to cell death.
Ultrafast spectroscopy on DNA-cleavage by endonuclease in molecular crowding.
Singh, Priya; Choudhury, Susobhan; Dutta, Shreyasi; Adhikari, Aniruddha; Bhattacharya, Siddhartha; Pal, Debasish; Pal, Samir Kumar
2017-10-01
The jam-packed intracellular environments differ the activity of a biological macromolecule from that in laboratory environments (in vitro) through a number of mechanisms called molecular crowding related to structure, function and dynamics of the macromolecule. Here, we have explored the structure, function and dynamics of a model enzyme protein DNase I in molecular crowing of polyethylene glycol (PEG; MW 3350). We have used steady state and picosecond resolved dynamics of a well-known intercalator ethidium bromide (EB) in a 20-mer double-stranded DNA (dsDNA) to monitor the DNA-cleavage by the enzyme in absence and presence PEG. We have also labelled the enzyme by a well-known fluorescent probe 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) to study the molecular mechanism of the protein-DNA association through exited state relaxation of the probe in absence (dictated by polarity) and presence of EB in the DNA (dictated by Förster resonance energy transfer (FRET)). The overall and local structures of the protein in presence of PEG have been followed by circular dichroism and time resolved polarization gated spectroscopy respectively. The enhanced dynamical flexibility of protein in presence of PEG as revealed from excited state lifetime and polarization gated anisotropy of ANS has been correlated with the stronger DNA-binding for the higher nuclease activity. We have also used conventional experimental strategy of agarose gel electrophoresis to monitor DNA-cleavage and found consistent results of enhanced nuclease activities both on synthetic 20-mer oligonucleotide and long genomic DNA from calf thymus. Copyright © 2017 Elsevier B.V. All rights reserved.
Effect of women's age on embryo morphology, cleavage rate and competence-A multicenter cohort study
DEFF Research Database (Denmark)
Grøndahl, Marie Louise; Christiansen, Sofie Lindgren; Kesmodel, Ulrik Schiøler
2017-01-01
This multicenter cohort study on embryo assessment and outcome data from 11,744 IVF/ICSI cycles with 104,830 oocytes and 42,074 embryos, presents the effect of women's age on oocyte, zygote, embryo morphology and cleavage parameters, as well as cycle outcome measures corrected for confounding.......0001) with increasing age. Maternal age had no effect on cleavage parameters or on the morphology of the embryo day 2 post insemination. Interestingly, initial hCG value after single embryo transfer followed by ongoing pregnancy was increased with age in both IVF (p = 0.007) and ICSI (p = 0.001) cycles. For the first...... time, we show that a woman's age does impose a significant footprint on early embryo morphological development (3PN). In addition, the developmentally competent embryos were associated with increased initial hCG values as the age of the women increased. Further studies are needed to elucidate...
Q-feber som årsag til spontan abort
DEFF Research Database (Denmark)
Nielsen, Stine Yde; Mølbak, Kåre; Hjøllund, Niels Henrik
2011-01-01
Q-fever is a zoonotic infection. Pregnant women constitute a specific risk group as the infection may cause spontaneous abortion, intrauterine death, growth retardation, oligohydramnios and premature birth. A 39 year-old veterinarian had a spontaneous abortion in pregnancy week seven. During the ...
Spontaneously broken global symmetries and cosmology
International Nuclear Information System (INIS)
Shafi, Q.; Vilenkin, A.
1984-01-01
Phase transitions associated with spontaneously broken global symmetries, in case these occur in nature, can have important cosmological implications. This is illustrated through two examples. The first one shows how the spontaneous breaking of a global U(1) symmetry, present, for instance, in the minimal SU(5) model, can lead to an inflationary phase. The second example illustrates how topologically stable strings associated with the breaking of U(1) symmetry make an appearance at (or near) the end of the inflationary era
Flow Friction or Spontaneous Ignition?
Stoltzfus, Joel M.; Gallus, Timothy D.; Sparks, Kyle
2012-01-01
"Flow friction," a proposed ignition mechanism in oxygen systems, has proved elusive in attempts at experimental verification. In this paper, the literature regarding flow friction is reviewed and the experimental verification attempts are briefly discussed. Another ignition mechanism, a form of spontaneous combustion, is proposed as an explanation for at least some of the fire events that have been attributed to flow friction in the literature. In addition, the results of a failure analysis performed at NASA Johnson Space Center White Sands Test Facility are presented, and the observations indicate that spontaneous combustion was the most likely cause of the fire in this 2000 psig (14 MPa) oxygen-enriched system.
Spontaneously broken abelian gauge invariant supersymmetric model
International Nuclear Information System (INIS)
Mainland, G.B.; Tanaka, K.
A model is presented that is invariant under an Abelian gauge transformation and a modified supersymmetry transformation. This model is broken spontaneously, and the interplay between symmetry breaking, Goldstone particles, and mass breaking is studied. In the present model, spontaneously breaking the Abelian symmetry of the vacuum restores the invariance of the vacuum under a modified supersymmetry transformation. (U.S.)
Ultrarapid mutation detection by multiplex, solid-phase chemical cleavage
Energy Technology Data Exchange (ETDEWEB)
Rowley, G.; Saad, S.; Giannelli, F.; Green, P.M. [Guy`s & St. Thomas`s Hospitals, London (United Kingdom)
1995-12-10
The chemical cleavage of mismatches in heteroduplexes formed by probe and test DNA detects and locates any sequence change in long DNA segments ({approximately}1.8 kb), and its efficiency has been well tested in the analysis of both average (e.g., coagulation factor IX) and large, complex genes (e.g., coagulation factor VIII and dystrophin). In the latter application RT/PCR products allow the examination of all essential sequences of the gene in a minimum number of reactions. We use two specific chemical reactants (hydroxylamine and osmium tetroxide) and piperidine cleavage of the above procedure to develop a very fast mutation screening method. This is based on: (1) 5{prime} or internal fluorescent labeling to allow concurrent screening of three to four DNA fragments and (2) solid-phase chemistry to use a microliter format and reduce the time required for the procedure, from amplification of sequence to gel loading inclusive, to one person-working-day. We test the two variations of the method, one entailing 5{prime} labeling of probe DNA and the other uniform labeling of both probe and target DNA, by detecting 114 known hemophilia B (coagulation factor IX) mutations and by analyzing 129 new patients. Uniform labeling of both probe and target DNA prior to formation of the heteroduplexes leads to almost twofold redundancy in the ability to detect mutations. Alternatively, the latter procedure may offer very efficient though less than 100% screening for sequence changes with only hydroxylamine. The full method with two chemical reactions (hydroxylamine and osmium tetroxide) should allow one person to screen with virtually 100% accuracy more than 300 kb of sequence in three ABI 373 gels in 1 day. 26 refs., 7 figs., 1 tab.
Spontaneous Perforation of Pyometra: A Case Report
Directory of Open Access Journals (Sweden)
2006-01-01
Full Text Available Pyometra is the accumulation of purulent material in the uterine cavity. Its reported incidence is 0.01–0.5% in gynecologic patients; however, as far as elderly patients are concerned, its incidence is 13.6% [3]. The most common cause of pyometra is malignant diseases of genital tract and the consequences of their treatment (radiotherapy. Other causes are benign tumors like leiomyoma, endometrial polyps, senile cervicitis, cervical occlusion after surgery, puerperal infections, and congenital cervical anomalies. Spontaneous rupture of the uterus is an extremely rare complication of pyometra. To our knowledge, only 21 cases of spontaneous perforation of pyometra have been reported in English literature since 1980. This paper reports an additional case of spontaneous uterine rupture.
Photooxidative cleavage of 4(1H)-quinolinones to 2-acylaminobenzoic acids and derivatives
Energy Technology Data Exchange (ETDEWEB)
Staskun, B. (University of the Witwatersrand, Johannesburg (South Africa). Dept. of Chemistry); Foote, C.S. (California Univ., Los Angeles (USA). Dept. of Chemistry)
1984-12-01
4(1H)-Quinolinones undergo oxidative cleavage to afford the corresponding 2-acylaminobenzoic acids when subjected to dye-sensitized photooxygenation in methanol-aqueous sodium hydroxide solution. The derived 2-aminobenzoic acid was the predominant product in certain instances. The reaction, with singlet oxygen suggested as the active species, provides an alternative methodology for access to nuclear- substituted anthranilic acids and derivatives.
Sui, Hai-juan; Zhang, Ling-ling; Liu, Zhou; Jin, Ying
2015-01-01
Aim: The proteolytic cleavage of Tau is involved in Aβ-induced neuronal dysfunction and cell death. In this study, we investigated whether atorvastatin could prevent Tau cleavage and hence prevent Aβ1–42 oligomer (AβO)-induced neurotoxicity in cultured cortical neurons. Methods: Cultured rat hippocampal neurons were incubated in the presence of AβOs (1.25 μmol/L) with or without atorvastatin pretreatment. ATP content and LDH in the culture medium were measured to assess the neuronal viability. Caspase-3/7 and calpain protease activities were detected. The levels of phospho-Akt, phospho-Erk1/2, phospho-GSK3β, p35 and Tau proteins were measured using Western blotting. Results: Treatment of the neurons with AβO significantly decreased the neuronal viability, induced rapid activation of calpain and caspase-3/7 proteases, accompanied by Tau degradation and relatively stable fragments generated in the neurons. AβO also suppressed Akt and Erk1/2 kinase activity, while increased GSK3β and Cdk5 activity in the neurons. Pretreatment with atorvastatin (0.5, 1, 2.5 μmol/L) dose-dependently inhibited AβO-induced activation of calpain and caspase-3/7 proteases, and effectively diminished the generation of Tau fragments, attenuated synaptic damage and increased neuronal survival. Atorvastatin pretreatment also prevented AβO-induced decreases in Akt and Erk1/2 kinase activity and the increases in GSK3β and Cdk5 kinase activity. Conclusion: Atorvastatin prevents AβO-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting calpain- and caspase-mediated Tau cleavage. PMID:25891085
Spontaneous regression of metastases from malignant melanoma: a case report
DEFF Research Database (Denmark)
Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin
2008-01-01
A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases......; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence...
Directory of Open Access Journals (Sweden)
Arthur César de Medeiros Alves
Full Text Available ABSTRACT Objective: The aim of this systematic review was to analyze the short and long-term spontaneous dentoalveolar changes of the mandibular dental arch after slow (SME or rapid (RME maxillary expansion in the mixed and early permanent dentitions. Methods: An electronic search was performed in the following databases: PubMed/Medline, Cochrane Library, Scopus, Embase and Web of Science. Eligibility criteria for article selection included randomized controlled trials and prospective studies written in English, with no restriction of year of publication, involving patients who underwent SME or RME during the mixed or early permanent dentitions. A double-blind search of articles was performed by two reviewers. Initially, the title and the abstract of the studies were read, and their references were also hand-searched for possible missing studies. A methodological quality scoring scale was used to analyze the selected articles. Results: The search retrieved 373 articles, but only 6 were selected for review after application of the eligibility and exclusion criteria. Non-clinically significant spontaneous dentoalveolar changes of approximately 1mm were found in the mandibular dental arch in the short and long-term, after slow or rapid maxillary expansions. Furthermore, no significant differences were found between treated and control groups. Conclusions: There is enough evidence to conclude that negligible short and long-term spontaneous dentoalveolar changes tend to occur in the mandibular dental arch after SME or RME in the mixed and early permanent dentitions. More randomized studies with appropriate control group are required to better evaluate this issue.
Bruschi, Maurizio; Tiberti, Matteo; Guerra, Alessandro; De Gioia, Luca
2014-02-05
A comparative analysis of a series of DFT models of [NiFe]-hydrogenases, ranging from minimal NiFe clusters to very large systems including both the first and second coordination sphere of the bimetallic cofactor, was carried out with the aim of unraveling which stereoelectronic properties of the active site of [NiFe]-hydrogenases are crucial for efficient H2 binding and cleavage. H2 binding to the Ni-SIa redox state is energetically favored (by 4.0 kcal mol(-1)) only when H2 binds to Ni, the NiFe metal cluster is in a low spin state, and the Ni cysteine ligands have a peculiar seesaw coordination geometry, which in the enzyme is stabilized by the protein environment. The influence of the Ni coordination geometry on the H2 binding affinity was then quantitatively evaluated and rationalized analyzing frontier molecular orbitals and populations. Several plausible reaction pathways leading to H2 cleavage were also studied. It turned out that a two-step pathway, where H2 cleavage takes place on the Ni-SIa redox state of the enzyme, is characterized by very low reaction barriers and favorable reaction energies. More importantly, the seesaw coordination geometry of Ni was found to be a key feature for facile H2 cleavage. The discovery of the crucial influence of the Ni coordination geometry on H2 binding and activation in the active site of [NiFe]-hydrogenases could be exploited in the design of novel biomimetic synthetic catalysts.
Novel folliculin (FLCN) mutation and familial spontaneous pneumothorax.
Zhu, J-F; Shen, X-Q; Zhu, F; Tian, L
2017-01-01
Familial spontaneous pneumothorax is one of the characteristics of Birt-Hogg-Dubé syndrome (BHDS), which is an autosomal dominant disease caused by the mutation of folliculin (FLCN). To investigate the mutation of FLCN gene in a familial spontaneous pneumothorax. Prospective case study. Clinical and genetic data of a Chinese family with four patients who presented spontaneous pneumothorax in the absence of skin lesions or renal tumors were collected. CT scan of patient's lung was applied for observation of pneumothorax. DNA sequencing of the coding exons (4-14 exons) of FLCN was performed for all 11 members of the family and 100 unrelated healthy controls. CT scan of patient's lung showed spontaneous pneumothorax. A mutation (c. 510C > G) that leads to a premature stop codon (p. Y170X) was found in the proband using DNA sequencing of coding exons (4-14 exons) of FLCN. This mutation was also observed in the other affected members of the family. A nonsense mutation of FLCN was found in a spontaneous pneumothorax family. Our results expand the mutational spectrum of FLCN in patients with BHDS. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
False localizing sign of cervico-thoracic CSF leak in spontaneous intracranial hypotension.
Schievink, Wouter I; Maya, M Marcel; Chu, Ray M; Moser, Franklin G
2015-06-16
Spontaneous spinal CSF leaks are an important cause of new-onset headaches. Such leaks are reported to be particularly common at the cervico-thoracic junction. The authors undertook a study to determine the significance of these cervico-thoracic CSF leaks. The patient population consisted of a consecutive group of 13 patients who underwent surgery for CSF leak repair based on CT myelography showing CSF extravasation at the cervico-thoracic junction but without any evidence of an underlying structural lesion. The mean age of the 9 women and 4 men was 41.2 years. Extensive extrathecal longitudinal CSF collections were demonstrated in 11 patients. At surgery, small leaking arachnoid cysts were found in 2 patients. In the remaining 11 patients, no clear source of CSF leakage could be identified at surgery. Resolution of symptoms was achieved in both patients with leaking arachnoid cysts, but in only 3 of the 11 patients with negative intraoperative findings. Postoperative spinal imaging was performed in 9 of the 11 patients with negative intraoperative findings and showed persistence of the longitudinal intraspinal extradural CSF. Further imaging revealed the site of the CSF leak to be ventral to the thoracic spinal cord. Five of these patients underwent microsurgical repair of the ventral CSF leak with resolution of symptoms in all 5 patients. Cervico-thoracic extravasation of dye on myelography does not necessarily indicate the site of the CSF leak. Treatment directed at this site should not be expected to have a high probability of sustained improvement of symptoms. © 2015 American Academy of Neurology.
Spontaneous remission of post-transplant recurrent focal and segmental glomerulosclerosis
Directory of Open Access Journals (Sweden)
Bassam Saeed
2011-01-01
Full Text Available A 12-year-old girl with a history of steroid and cyclosporine (CsA resistant nephrotic syndrome owing to focal and segmental glomerulosclerosis (FSGS has progressed to end-stage renal disease (ESRD for which she underwent hemodialysis for 18 months before she successfully received a fully matched kidney transplant from her sister at the age of nine years. The post transplantation (Tx period was marked by an early and massive proteinuria indicating recurrent FSGS for which she received 12 sessions of plasmapheresis (PP; unfortunately, she did not appear to have any response to the PP therapy; thereafter, a conservative management comprising essentially enalapril and losartan has been initiated and was also not successful during the first four months, however, a very gradual response has been noticed to occur after five months of conservative therapy and ultimately, the patient attained complete remission after 21 months of treatment. Amazingly, 15 months after discontinuation of enalapril and losartan, she remained in a complete and sustained remission with a good renal allograft function. To the best of our knowledge, this is the first case ever reported in the literature of a "spontaneous" remission of post transplant recurrent FSGS.
The shallow flaw effect and the local approach to cleavage fracture
International Nuclear Information System (INIS)
Moinereau, D.
1996-10-01
The capability of Beremin model to explain the shallow flaw effect in cleavage fracture is evaluated. Numerous two-dimensional finite element calculations are performed on several cracked specimens (cladded and un-cladded specimens with different values of a/W ratio) submitted to mechanical or thermal loading. The behavior of different specimens is examined using the Weibull stress σ w versus stress intensity factor K J curves. The stress fields and plastic zones at the crack tip are also compared on respective cracked specimens. (K.A.)
Imaging of early spontaneous osteonecrosis and osteoarthritis of the knee
International Nuclear Information System (INIS)
Kusayama, Takeshi; Tomatsu, Taisuke
1999-01-01
In this paper, the available of MRI in diagnosis on early spontaneous osteonecrosis and osteoarthritis was investigated. Subjects were 5 cases (5 knees) with spontaneous osteonecrosis (stage 1 in Koshino's classification) and 96 cases (104 knees) in osteoarthritis who were more than 50 years old. Patients with an early spontaneous osteonecrosis were elderly females and had night pain and severe spontaneous pain. On MRI, lesions of all cases were clearly detected in early stage. On the other hand, only 47 of 104 knees (45%) were detected in patients with osteoarthritis, and mirror lesions at shank sides were detected in 45 of 47 knees. These results suggest that it is possible to diagnose early spontaneous osteonecrosis from osteoarthritis by MRI image with the clue to mirror lesion at shank sides, incidence, stage, etc. On the diagnosis of early spontaneous osteonecrosis, MRI image should be performed as soon as possible if a patient was older, had no anamnesis of lesions, and no changes by the X-ray radiography in spite of severe pain of the knee joints. (K.H.)
Spontaneous infected biloma: case report | Kimani | East African ...
African Journals Online (AJOL)
Biloma is defined as any collection of bile outside the biliary tree. It mainly results from surgical complications and abdominal trauma. Spontaneous biloma is extremely rare and is occasionally associated with choledocholithiasis. This report describes a case of spontaneous biloma diagnosed radiologically and confirmed at ...
Spontaneous resolution of post-traumatic chronic subdural hematoma
African Journals Online (AJOL)
Here, we present a case of spontaneously resolved post-traumatic bilateral chronic subdural hematoma within a period of one month in a 55-year-old male and we discuss the probable mechanisms of pathophysiology in the spontaneous resolution of chronic subdural hematoma. Keywords: Antiaggregation therapy, chronic ...
Henkin, Stanislav; Negrotto, Sara M; Tweet, Marysia S; Kirmani, Salman; Deyle, David R; Gulati, Rajiv; Olson, Timothy M; Hayes, Sharonne N
2016-06-01
Spontaneous coronary artery dissection (SCAD) is an under-recognised but important cause of myocardial infarction and sudden cardiac death. We sought to determine the role of medical and molecular genetic screening for connective tissue disorders in patients with SCAD. We performed a single-centre retrospective descriptive analysis of patients with spontaneous coronary artery disease who had undergone medical genetics evaluation 1984-2014 (n=116). The presence or absence of traits suggestive of heritable connective tissue disease was extracted. Genetic testing for connective tissue disorders and/or aortopathies, if performed, is also reported. Of the 116 patients (mean age 44.2 years, 94.8% women and 41.4% with non-coronary fibromuscular dysplasia (FMD)), 59 patients underwent genetic testing, of whom 3 (5.1%) received a diagnosis of connective tissue disorder: a 50-year-old man with Marfan syndrome; a 43-year-old woman with vascular Ehlers-Danlos syndrome and FMD; and a 45-year-old woman with vascular Ehlers-Danlos syndrome. An additional 12 patients (20.3%) had variants of unknown significance, none of which was thought to be a definite disease-causing mutation based on in silico analyses. Only a minority of patients with SCAD who undergo genetic evaluation have a likely pathogenic mutation identified on gene panel testing. Even fewer exhibit clinical features of connective tissue disorder. These findings underscore the need for further studies to elucidate the molecular mechanisms of SCAD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Surgical Intervention for Primary Spontaneous Pneumothorax in Pediatric Population: When and Why?
Yeung, Fanny; Chung, Patrick H Y; Hung, Esther L Y; Yuen, Chi Sum; Tam, Paul K H; Wong, Kenneth K Y
2017-08-01
Spontaneous pneumothorax in pediatric patients is relatively uncommon. The management strategy varies in different centers due to dearth of evidence-based pediatric guidelines. In this study, we reviewed our experience of thoracoscopic management of primary spontaneous pneumothorax (PSP) in children and identified risk factors associated with postoperative air leakage and recurrence. We performed a retrospective analysis of pediatric patients who had PSP and underwent surgical management in our institution between April 2008 and March 2015. Demographic data, radiological findings, interventions, and surgical outcomes were analyzed. A total of 92 patients with 110 thoracoscopic surgery for PSP were identified. The indications for surgery were failed nonoperative management with persistent air leakage in 32.7%, recurrent ipsilateral pneumothorax in 36.4%, first contralateral pneumothorax in 14.5%, bilateral pneumothorax in 10%, and significant hemopneumothorax in 5.5%. Bulla was identified in 101 thoracoscopy (91.8%) with stapled bullectomy performed. 14.5% patients had persistent postoperative air leakage and treated with reinsertion of thoracostomy tube and chemical pleurodesis. 17.3% patients had postoperative recurrence occurred at mean time of 11 months. Operation within 7 days of symptoms onset was associated with less postoperative air leakage (P = .04). Bilateral pneumothorax and those with abnormal radiographic features had significantly more postoperative air leakage (P = .002, P < .01 respectively) and recurrence (P < .01, P = .007). Early thoracoscopic mechanical pleurodesis and stapled bullectomy after thoracostomy tube insertion could be offered as a primary option for management of large PSP in pediatric population, since most of these patients had bulla identified as the culprit of the disease.
Spontaneous symmetry breaking in N=3 supergravity
International Nuclear Information System (INIS)
Zinov'ev, Yu.M.
1986-01-01
The possibility of the spontaneous symmetry breaking without a cosmological term in N=3 supergravity is investigated. A new, dual version of N=3 supergravity - U(3)-supergravity is constructed. Such a theory is shown to admit a spontaneous supersymmetry breaking without a cosmological term and with three arbitrary scales, including partial super-Higgs effect N=3 → N=2 and N=3 → N=1
Symmetry restoration in spontaneously broken induced gravity
International Nuclear Information System (INIS)
Amati, D.; Russo, J.
1990-01-01
We investigate the recuperation of expected invariant behaviours in a non-metric gravity theory in which the full general relativistic invariance is broken spontaneously. We show how dangerous increasing energy behaviours of physical amplitudes cancel in a highly non-trivial way. This evidences the expected loss of the vacuum generated scale in the UV regime and gives support for the consistency of spontaneously broken gravity theories. (orig.)
[Bacterial vaginosis and spontaneous preterm birth].
Brabant, G
2016-12-01
To determine if bacterial vaginosis is a marker for risk of spontaneous preterm delivery and if its detection and treatment can reduce this risk. Consultation of the database Pubmed/Medline, Science Direct, and international guidelines of medical societies. Bacterial vaginosis (BV) is a dysbiosis resulting in an imbalance in the vaginal flora through the multiplication of anaerobic bacteria and jointly of a disappearance of well-known protective Lactobacilli. His diagnosis is based on clinical Amsel criteria and/or a Gram stain with establishment of the Nugent score. The prevalence of the BV extraordinarily varies according to ethnic and/or geographical origin (4-58 %), in France, it is close to 7 % in the first trimester of pregnancy (EL2). The link between BV and spontaneous premature delivery is low with an odds ratio between 1.5 and 2 in the most recent studies (EL3). Metronidazole or clindamycin is effective to treat BV (EL3). It is recommended to prescribe one of these antibiotics in the case of symptomatic BV (Professional Consensus). The testing associated with the treatment of BV in the global population showed no benefit in the prevention of the risk of spontaneous preterm delivery (EL2). Concerning low-risk asymptomatic population (defined by the absence of antecedent of premature delivery), it has been failed profit to track and treat the BV in the prevention of the risk of spontaneous preterm delivery (EL1). Concerning the high-risk population (defined by a history of preterm delivery), it has been failed profit to track and treat the VB in the prevention of the risk of spontaneous preterm delivery (EL3). However, in the sub population of patients with a history of preterm delivery occurred in a context of materno-fetal bacterial infection, there may be a benefit to detect and treat early and systematically genital infection, and in particular the BV (Professional Consensus). The screening and treatment of BV during pregnancy in asymptomatic low
International Nuclear Information System (INIS)
Beausoleil, Michel S; Schulze, Erika B; Goodale, David; Postenka, Carl O; Allan, Alison L
2011-01-01
Osteopontin (OPN) is a secreted phosphoprotein often overexpressed at high levels in the blood and primary tumors of breast cancer patients. OPN contains two integrin-binding sites and a thrombin cleavage domain located in close proximity to each other. To study the role of the thrombin cleavage site of OPN, MDA-MB-468 human breast cancer cells were stably transfected with either wildtype OPN (468-OPN), mutant OPN lacking the thrombin cleavage domain (468-ΔTC) or an empty vector (468-CON) and assessed for in vitro and in vivo functional differences in malignant/metastatic behavior. All three cell lines were found to equivalently express thrombin, tissue factor, CD44, αvβ5 integrin and β1 integrin. Relative to 468-OPN and 468-CON cells, 468-ΔTC cells expressing OPN with a deleted thrombin cleavage domain demonstrated decreased cell adhesion (p < 0.001), decreased mRNA expression of MCAM, maspin and TRAIL (p < 0.01), and increased uPA expression and activity (p < 0.01) in vitro. Furthermore, injection of 468-ΔTC cells into the mammary fat pad of nude mice resulted in decreased primary tumor latency time (p < 0.01) and increased primary tumor growth and lymph node metastatic burden (p < 0.001) compared to 468-OPN and 468-CON cells. The results presented here suggest that expression of thrombin-uncleavable OPN imparts an early tumor formation advantage as well as a metastatic advantage for breast cancer cells, possibly due to increased proteolytic activity and decreased adhesion and apoptosis. Clarification of the mechanisms responsible for these observations and the translation of this knowledge into the clinic could ultimately provide new therapeutic opportunities for combating breast cancer
Nickel-Catalyzed Synthesis of Primary Aryl and Heteroaryl Amines via C–O Bond Cleavage
Yue, Huifeng
2017-03-13
A nickel-catalyzed protocol for the conversion of aryl and heteroaryl alcohol derivatives to primary and secondary aromatic amines via C(sp2)-O bond cleavage is described. The new amination protocol can be applied to a range of substrates bearing diverse functional groups and uses readily available benzophenone imines as an effective nitrogen source.
Nickel-Catalyzed Synthesis of Primary Aryl and Heteroaryl Amines via C–O Bond Cleavage
Yue, Huifeng; Guo, Lin; Liu, Xiangqian; Rueping, Magnus
2017-01-01
A nickel-catalyzed protocol for the conversion of aryl and heteroaryl alcohol derivatives to primary and secondary aromatic amines via C(sp2)-O bond cleavage is described. The new amination protocol can be applied to a range of substrates bearing diverse functional groups and uses readily available benzophenone imines as an effective nitrogen source.
Energy Technology Data Exchange (ETDEWEB)
Bando, N.; Kidena, K.; Murata, S.; Nomura, M. [Osaka University, Osaka (Japan). Faculty of Engineering
1996-10-28
In this paper, bond cleavage reactions are discussed in relation to the softening and solubilization of coal. Were used 9,10-dihydroanthracene (DHA) and 9,10-dihydrophenanthrene (DHP) as models of hydrogen donating compounds in coal, and bibenzyl, 1,2-diethane, benzylphenylether, and 1,5-dibenzylnaphthalene were used as models of bridge structure compounds. They were compared mutually, as to reactivity of coal against DHA and DHP. For the homolytic cleavage of bridges, DHA with excellent radical supplement performance provided excellent hydrogen donating performance. While, for the ipso-position cleavage of bridges, it was found that DHP can act as an effective hydrogen donor. For the reaction between coal and hydrogenated aromatic compounds, cleavage of relatively weak bonds, such as ether linkage and dimethylene linkage, occurred at about 380{degree}C, and hydrogen from DHA or DHP was consumed. On the other hand, the results suggested that the cleavage reaction at ipso-position affected by hydrogen donating solvent is also important at temperature range around 420{degree}C. 2 refs., 3 figs., 1 tab.
Spontaneous Gamma Activity in Schizophrenia.
Hirano, Yoji; Oribe, Naoya; Kanba, Shigenobu; Onitsuka, Toshiaki; Nestor, Paul G; Spencer, Kevin M
2015-08-01
A major goal of translational neuroscience is to identify neural circuit abnormalities in neuropsychiatric disorders that can be studied in animal models to facilitate the development of new treatments. Oscillations in the gamma band (30-100 Hz) of the electroencephalogram have received considerable interest as the basic mechanisms underlying these oscillations are understood, and gamma abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased spontaneous broadband gamma power, but this phenomenon has not been identified clearly in patients with SZ. To examine spontaneous gamma power and its relationship to evoked gamma oscillations in the auditory cortex of patients with SZ. We performed a cross-sectional study including 24 patients with chronic SZ and 24 matched healthy control participants at the Veterans Affairs Boston Healthcare System from January 1, 2009, through December 31, 2012. Electroencephalograms were obtained during auditory steady-state stimulation at multiple frequencies (20, 30, and 40 Hz) and during a resting state in 18 participants in each group. Electroencephalographic activity in the auditory cortex was estimated using dipole source localization. Auditory steady-state response (ASSR) measures included the phase-locking factor and evoked power. Spontaneous gamma power was measured as induced (non-phase-locked) gamma power in the ASSR data and as total gamma power in the resting-state data. The ASSR phase-locking factor was reduced significantly in patients with SZ compared with controls for the 40-Hz stimulation (mean [SD], 0.075 [0.028] vs 0.113 [0.065]; F1,46 = 6.79 [P = .012]) but not the 20- or the 30-Hz stimulation (0.042 [0.038] vs 0.043 [0.034]; F1,46 = 0.006 [P = .938] and 0.084 [0.040] vs 0.098 [0.050]; F1,46 = 1.605 [P = .212], respectively), repeating previous findings. The mean [SD] broadband-induced (30
Merkel Cell Carcinoma with Spontaneous Regression: A Case Report and Immunohistochemical Study
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Hitoshi Terui
2016-02-01
Full Text Available Merkel cell carcinoma (MCC is an aggressive neuroendocrine carcinoma that only rarely regresses spontaneously. Since little is known about the immunological mechanisms involved in the spontaneous regression of MCC, we describe a case of MCC with spontaneous regression and employed immunohistochemical staining for cytotoxic and immunosuppressive molecules to investigate possible mechanisms involved in the spontaneous regression of MCC. Interestingly, compared to conventional MCC, tumor-infiltrating lymphocytes in MCC with spontaneous regression contained higher numbers of CD8+ cells and granulysin-bearing cells and lower numbers of CD206+ cells. Our present study suggests one of the possible reasons for the spontaneous regression of MCC.
Spontaneous poisoning by Prosopis juliflora (Leguminosae) in sheep
The aim of this paper is to describe the first report of clinical, epidemiological and pathological aspects of spontaneous poisoning by Prosopis juliflora in sheep. Of a total of 500 sheep at risk, two adult male sheep were affected; one died spontaneously and the other animal was examined, euthaniz...
Zhao, Gang; He, Chunlin; Yin, Ping; Imler, Gregory H; Parrish, Damon A; Shreeve, Jean'ne M
2018-03-14
The exploitation of C-C activation to facilitate chemical reactions is well-known in organic chemistry. Traditional strategies in homogeneous media rely upon catalyst-activated or metal-mediated C-C bonds leading to the design of new processes for applications in organic chemistry. However, activation of a C-C bond, compared with C-H bond activation, is a more challenging process and an underdeveloped area because thermodynamics does not favor insertion into a C-C bond in solution. Carbon-carbon bond cleavage through loss of an oxime moiety has not been reported. In this paper, a new observation of self-coupling via C-C bond cleavage with concomitant loss of oxime in the absence of metals (either metal-complex mediation or catalysis) results in dihydroxylammonium 5,5-bistetrazole-1,10-diolate (TKX-50) as well as N, N'-([3,3'-bi(1,2,4-oxadiazole)]-5,5'-diyl)dinitramine, a potential candidate for a new generation of energetic materials.
EMMPRIN Modulates Epithelial Barrier Function through a MMP–Mediated Occludin Cleavage
Huet, Eric; Vallée, Benoit; Delbé, Jean; Mourah, Samia; Prulière-Escabasse, Virginie; Tremouilleres, Magali; Kadomatsu, Kenji; Doan, Serge; Baudouin, Christophe; Menashi, Suzanne; Gabison, Eric E.
2011-01-01
Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. PMID:21777561
On spontaneous breakdown in Σ-models
International Nuclear Information System (INIS)
Ivanov, E.A.
1975-01-01
The group theory aspects of spontaneous breakdown in linear Σ-models are discussed. General conditions are formulated under which multiplet of group G (compact or noncompact) is suitable for constructing the Σ-model with a given subgroup of stability of vacuum. It is shown that the Σ-models of spontaneously broken space-time symmetries can be constructed in general only if some extra coordinates are introduced in addition to an ordinary 4-coordinate xsub(μ). The connection between Σ-models of internal symmetries and appropriate nonlinear realizations has also been investigated
Cavity enhanced rephased amplified spontaneous emission
International Nuclear Information System (INIS)
A Williamson, Lewis; J Longdell, Jevon
2014-01-01
Amplified spontaneous emission is usually treated as an incoherent noise process. Recent theoretical and experimental work using rephasing optical pulses has shown that rephased amplified spontaneous emission (RASE) is a potential source of wide bandwidth time-delayed entanglement. Due to poor echo efficiency the plain RASE protocol does not in theory achieve perfect entanglement. Experiments done to date show a very small amount of entanglement at best. Here we show that RASE can, in principle, produce perfect multimode time-delayed two mode squeezing when the active medium is placed inside a Q-switched cavity. (paper)
Ursel, Christian; Fandrich, Uwe; Hoffmann, Anita; Sieg, Torsten; Ihling, Christian; Stubbs, Milton T
2013-08-01
Dorsoventral patterning during Drosophila melanogaster embryogenesis is mediated by a well-defined gradient of the mature NGF-like ligand Spätzle. Easter, the ultimate protease of a ventrally-restricted serine protease cascade, plays a key role in the regulation of the morphogenic gradient, catalyzing the activation cleavage of proSpätzle. As a result of alternative splicing, proSpätzle exists in multiple isoforms, almost all of which differ only in their prodomain. Although this domain is unstructured in isolation, it has a stabilizing influence on the mature cystine knot domain and is involved in the binding to the Toll receptor. Here, we report the expression and refolding of Easter, and show that the renatured enzyme performs the activation cleavage of two Spätzle isoforms. We determine the affinity of the prodomain for the cystine knot domain, and show that Easter performs a previously unknown secondary cleavage in each prodomain.
The influence of spontaneous activity on stimulus processing in primary visual cortex.
Schölvinck, M L; Friston, K J; Rees, G
2012-02-01
Spontaneous activity in the resting human brain has been studied extensively; however, how such activity affects the local processing of a sensory stimulus is relatively unknown. Here, we examined the impact of spontaneous activity in primary visual cortex on neuronal and behavioural responses to a simple visual stimulus, using functional MRI. Stimulus-evoked responses remained essentially unchanged by spontaneous fluctuations, combining with them in a largely linear fashion (i.e., with little evidence for an interaction). However, interactions between spontaneous fluctuations and stimulus-evoked responses were evident behaviourally; high levels of spontaneous activity tended to be associated with increased stimulus detection at perceptual threshold. Our results extend those found in studies of spontaneous fluctuations in motor cortex and higher order visual areas, and suggest a fundamental role for spontaneous activity in stimulus processing. Copyright © 2011. Published by Elsevier Inc.
Bogema, Daniel R; Deutscher, Ania T; Woolley, Lauren K; Seymour, Lisa M; Raymond, Benjamin B A; Tacchi, Jessica L; Padula, Matthew P; Dixon, Nicholas E; Minion, F Chris; Jenkins, Cheryl; Walker, Mark J; Djordjevic, Steven P
2012-01-01
Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50(P146), P40(P146), and P85(P146) that reside on the cell surface. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) identified a semitryptic peptide that delineated a major cleavage site in Mhp684. Cleavage occurred at the phenylalanine residue within sequence (672)ATEF↓QQ(677), consistent with a cleavage motif resembling S/T-X-F↓X-D/E recently identified in Mhp683 and other P97/P102 family members. Biotinylated surface proteins recovered by avidin chromatography and separated by two-dimensional gel electrophoresis (2-D GE) showed that more-extensive endoproteolytic cleavage of P146 occurs. Recombinant fragments F1(P146)-F3(P146) that mimic P50(P146), P40(P146), and P85(P146) were constructed and shown to bind porcine epithelial cilia and biotinylated heparin with physiologically relevant affinity. Recombinant versions of F3(P146) generated from M. hyopneumoniae strain J and 232 sequences strongly bind porcine plasminogen, and the removal of their respective C-terminal lysine and arginine residues significantly reduces this interaction. These data reveal that P146 is an extensively processed, multifunctional adhesin of M. hyopneumoniae. Extensive cleavage coupled with variable cleavage efficiency provides a mechanism by which M. hyopneumoniae regulates protein topography. Vaccines used to control Mycoplasma
Pneumomediastino espontâneo: Asma Spontaneous pneumomediastinum: Asthma
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Marcelo Cunha Fatureto
2008-06-01
Full Text Available Pneumomediastino é definido como a presença de ar livre no mediastino, sendo que o espontâneo ocorre na ausência de enfermidades ou factores precipitantes. É raro em adultos, sendo mais frequente em recém-nascidos. Contudo, ocorre mais em adultos jovens, sendo 8:1 a relação entre homens e mulheres. Constitui achado raro na asma, representando 1% dos casos. Os sintomas mais frequentes são dor torácica e dispneia. O diagnóstico é feito com exames de imagem, como radiografia e tomografia computadorizada de tórax. O tratamento de escolha é conservador, não operatório, com prognóstico favorável na maioria dos casos. O nosso propósito é relatar um caso desta patologia em jovem atendido em nosso serviço com quadro de dor torácica e dispneia, sendo submetido a exames complementares e feito o diagnóstico de pneumomediastino espontâneo. O doente foi submetido a tratamento conservador com excelente evolução clínica. No momento encontra-se assintomático, em acompanhamento ambulatorial.Pneumomediastinum is defined as the presence of free air in the mediastinum, and the spontaneous occurs in the absence of diseases or precipitating factors. It is rare in adults, and it is more frequent in newborns. However, it occurs more in young adults, with an 8:1 relationship between men and women. It constitutes a rare finding in asthma, representing 1% of the cases. More frequent symptoms are chest pain and dyspnea. Diagnosis is made with image examinations, such as radiography and chest computed tomography. Treatment of choice is conservative, nonoperative, with a favourable prognosis in the majority of the cases. Our aim is to report a case of this pathology in a young adult seen in our service with chest pain and dyspnea. He underwent complementary examinations and the diagnosis was spontaneous pneumo-mediastinum. This patient was submitted to a conservative treatment with excellent clinical evolution. At the moment, he is asymptomatic and
Outcome of Patients Underwent Emergency Department Thoracotomy and Its Predictive Factors
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Shahram Paydar
2014-08-01
Full Text Available Introduction: Emergency department thoracotomy (EDT may serve as the last survival chance for patients who arrive at hospital in extremis. It is considered as an effective tool for improvement of traumatic patients’ outcome. The present study was done with the goal of assessing the outcome of patients who underwent EDT and its predictive factors. Methods: In the present study, medical charts of 50 retrospective and 8 prospective cases underwent emergency department thoracotomy (EDT were reviewed during November 2011 to June 2013. Comparisons between survived and died patients were performed by Mann-Whitney U test and the predictive factors of EDT outcome were measured using multivariate logistic regression analysis. P < 0.05 considered statistically significant. Results: Fifty eight cases of EDT were enrolled (86.2% male. The mean age of patients was 43.27±19.85 years with the range of 18-85. The mean time duration of CPR was recorded as 37.12±12.49 minutes. Eleven cases (19% were alive to be transported to OR (defined as ED survived. The mean time of survival in ED survived patients was 223.5±450.8 hours. More than 24 hours survival rate (late survived was 6.9% (4 cases. Only one case (1.7% survived to discharge from hospital (mortality rate=98.3%. There were only a significant relation between ED survival and SBP, GCS, CPR duration, and chest trauma (p=0.04. The results demonstrated that initial SBP lower than 80 mmHg (OR=1.03, 95% CI: 1.001-1.05, p=0.04 and presence of chest trauma (OR=2.6, 95% CI: 1.75-3.16, p=0.02 were independent predictive factors of EDT mortality. Conclusion: The findings of the present study showed that the survival rate of trauma patients underwent EDT was 1.7%. In addition, it was defined that falling systolic blood pressure below 80 mmHg and blunt trauma of chest are independent factors that along with poor outcome.
New Perspectives on Spontaneous Brain Activity: Dynamic Networks and Energy Matter.
Tozzi, Arturo; Zare, Marzieh; Benasich, April A
2016-01-01
Spontaneous brain activity has received increasing attention as demonstrated by the exponential rise in the number of published article on this topic over the last 30 years. Such "intrinsic" brain activity, generated in the absence of an explicit task, is frequently associated with resting-state or default-mode networks (DMN)s. The focus on characterizing spontaneous brain activity promises to shed new light on questions concerning the structural and functional architecture of the brain and how they are related to "mind". However, many critical questions have yet to be addressed. In this review, we focus on a scarcely explored area, specifically the energetic requirements and constraints of spontaneous activity, taking into account both thermodynamical and informational perspectives. We argue that the "classical" definitions of spontaneous activity do not take into account an important feature, that is, the critical thermodynamic energetic differences between spontaneous and evoked brain activity. Spontaneous brain activity is associated with slower oscillations compared with evoked, task-related activity, hence it exhibits lower levels of enthalpy and "free-energy" (i.e., the energy that can be converted to do work), thus supporting noteworthy thermodynamic energetic differences between spontaneous and evoked brain activity. Increased spike frequency during evoked activity has a significant metabolic cost, consequently, brain functions traditionally associated with spontaneous activity, such as mind wandering, require less energy that other nervous activities. We also review recent empirical observations in neuroscience, in order to capture how spontaneous brain dynamics and mental function can be embedded in a non-linear dynamical framework, which considers nervous activity in terms of phase spaces, particle trajectories, random walks, attractors and/or paths at the edge of the chaos. This takes us from the thermodynamic free-energy, to the realm of "variational
Spontaneous Intracerebral Hemorrhage: Computed Tomographic Characteristics and Outcome
Directory of Open Access Journals (Sweden)
Aimara de la Caridad Vergara Santos
2015-12-01
Full Text Available Background: strokes are the third leading cause of death among adults and 10-15 % of them are due to spontaneous intracerebral hemorrhage. Objective: to characterize spontaneous intracerebral hemorrhage through computed tomography scan and its outcome. Methods: a case series study was conducted comprising patients diagnosed with spontaneous intracerebral hemorrhage admitted to the Arnaldo Milián Castro Provincial University Hospital in Villa Clara from January 2009 to January 2010. Tomographic variables of interest were derived from evaluation of spontaneous intracerebral hematomas. Results: fifty-nine cases of spontaneous intracerebral hemorrhage were studied, 23 were located in lobar regions, 4 had severe midline shift, and 2 showed volume greater than 80 ml. Eight out of eleven with extension into the ventricular system had an unfavorable outcome. Among those with thalamic hemorrhage, patients with diameter larger than 4cm and extension into the ventricular system died. Patients with putaminal hemorrhage larger than 4 cm and posterior fossa hematoma with hydrocephalus had a poor outcome, as well as most individuals (55 with other mass effects. Most lobar hematomas (14 out of 23 had a satisfactory outcome, unlike cerebellar and brainstem hematomas. Conclusions: tomographic variables that had a negative impact on the outcome were: volume greater than 80 ml, severe midline shift, diameter larger than 4 cm, extension into the ventricular system, hydrocephalus, other signs of mass effect and brainstem location.
Directory of Open Access Journals (Sweden)
Maho eMorishima-Kawashima
2014-11-01
Full Text Available Amyloid β-protein (Aβ plays a central role in the pathogenesis of Alzheimer’s disease, the most common age-associated neurodegenerative disorder. Aβ is generated through intramembrane proteolysis of the β-carboxyl terminal fragment (βCTF of β-amyloid precursor protein (APP by γ-secretase. The initial cleavage by γ-secretase occurs in the membrane/cytoplasm boundary of the βCTF, liberating the APP intracellular domain (AICD. The remaining βCTFs, which are truncated at the C-terminus (longer Aβs, are then cropped sequentially in a stepwise manner, predominantly at three residue intervals, to generate Aβ. There are two major Aβ product lines which generate Aβ40 and Aβ42 with concomitant release of three and two tripeptides, respectively. Additionally, many alternative cleavages occur, releasing peptides with three to six residues. These modulate the Aβ product lines and define the species and quantity of Aβ generated. Here, we review our current understanding of the intramembrane cleavage of the βCTF by γ-secretase, which may contribute to the future goal of developing an efficient therapeutic strategy for Alzheimer’s disease.
Bozeman, Trevor C; Nanjunda, Rupesh; Tang, Chenhong; Liu, Yang; Segerman, Zachary J; Zaleski, Paul A; Wilson, W David; Hecht, Sidney M
2012-10-31
Recent studies involving DNAs bound strongly by bleomycins have documented that such DNAs are degraded by the antitumor antibiotic with characteristics different from those observed when studying the cleavage of randomly chosen DNAs in the presence of excess Fe·BLM. In the present study, surface plasmon resonance has been used to characterize the dynamics of BLM B(2) binding to a strongly bound hairpin DNA, to define the effects of Fe(3+), salt, and temperature on BLM-DNA interaction. One strong primary DNA binding site, and at least one much weaker site, were documented. In contrast, more than one strong cleavage site was found, an observation also made for two other hairpin DNAs. Evidence is presented for BLM equilibration between the stronger and weaker binding sites in a way that renders BLM unavailable to other, less strongly bound DNAs. Thus, enhanced binding to a given site does not necessarily result in increased DNA degradation at that site; i.e., for strongly bound DNAs, the facility of DNA cleavage must involve other parameters in addition to the intrinsic rate of C-4' H atom abstraction from DNA sugars.
Devers, Emanuel A.; Branscheid, Anja; May, Patrick; Krajinski, Franziska
2011-01-01
The majority of plants are able to form the arbuscular mycorrhizal (AM) symbiosis in association with AM fungi. During symbiosis development, plant cells undergo a complex reprogramming resulting in profound morphological and physiological changes. MicroRNAs (miRNAs) are important components of the regulatory network of plant cells. To unravel the impact of miRNAs and miRNA-mediated mRNA cleavage on root cell reprogramming during AM symbiosis, we carried out high-throughput (Illumina) sequencing of small RNAs and degradome tags of Medicago truncatula roots. This led to the annotation of 243 novel miRNAs. An increased accumulation of several novel and conserved miRNAs in mycorrhizal roots suggest a role of these miRNAs during AM symbiosis. The degradome analysis led to the identification of 185 root transcripts as mature miRNA and also miRNA*-mediated mRNA cleavage targets. Several of the identified miRNA targets are known to be involved in root symbioses. In summary, the increased accumulation of specific miRNAs and the miRNA-mediated cleavage of symbiosis-relevant genes indicate that miRNAs are an important part of the regulatory network leading to symbiosis development. PMID:21571671
Directory of Open Access Journals (Sweden)
Antoine Marmignon
2014-08-01
Full Text Available During somatic differentiation, physiological DNA double-strand breaks (DSB can drive programmed genome rearrangements (PGR, during which DSB repair pathways are mobilized to safeguard genome integrity. Because of their unique nuclear dimorphism, ciliates are powerful unicellular eukaryotic models to study the mechanisms involved in PGR. At each sexual cycle, the germline nucleus is transmitted to the progeny, but the somatic nucleus, essential for gene expression, is destroyed and a new somatic nucleus differentiates from a copy of the germline nucleus. In Paramecium tetraurelia, the development of the somatic nucleus involves massive PGR, including the precise elimination of at least 45,000 germline sequences (Internal Eliminated Sequences, IES. IES excision proceeds through a cut-and-close mechanism: a domesticated transposase, PiggyMac, is essential for DNA cleavage, and DSB repair at excision sites involves the Ligase IV, a specific component of the non-homologous end-joining (NHEJ pathway. At the genome-wide level, a huge number of programmed DSBs must be repaired during this process to allow the assembly of functional somatic chromosomes. To understand how DNA cleavage and DSB repair are coordinated during PGR, we have focused on Ku, the earliest actor of NHEJ-mediated repair. Two Ku70 and three Ku80 paralogs are encoded in the genome of P. tetraurelia: Ku70a and Ku80c are produced during sexual processes and localize specifically in the developing new somatic nucleus. Using RNA interference, we show that the development-specific Ku70/Ku80c heterodimer is essential for the recovery of a functional somatic nucleus. Strikingly, at the molecular level, PiggyMac-dependent DNA cleavage is abolished at IES boundaries in cells depleted for Ku80c, resulting in IES retention in the somatic genome. PiggyMac and Ku70a/Ku80c co-purify as a complex when overproduced in a heterologous system. We conclude that Ku has been integrated in the Paramecium
Spontaneous perseverative turning in rats with radiation-induced hippocampal damage
International Nuclear Information System (INIS)
Mickley, G.A.; Ferguson, J.L.; Nemeth, T.J.; Mulvihill, M.A.; Alderks, C.E.
1989-01-01
This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage
The effects of age and divided attention on spontaneous recognition.
Anderson, Benjamin A; Jacoby, Larry L; Thomas, Ruthann C; Balota, David A
2011-05-01
Studies of recognition typically involve tests in which the participant's memory for a stimulus is directly questioned. There are occasions however, in which memory occurs more spontaneously (e.g., an acquaintance seeming familiar out of context). Spontaneous recognition was investigated in a novel paradigm involving study of pictures and words followed by recognition judgments on stimuli with an old or new word superimposed over an old or new picture. Participants were instructed to make their recognition decision on either the picture or word and to ignore the distracting stimulus. Spontaneous recognition was measured as the influence of old vs. new distracters on target recognition. Across two experiments, older adults and younger adults placed under divided-attention showed a greater tendency to spontaneously recognize old distracters as compared to full-attention younger adults. The occurrence of spontaneous recognition is discussed in relation to ability to constrain retrieval to goal-relevant information.
Association between Nutritional Status with Spontaneous Abortion
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Rahimeh Ahmadi
2016-11-01
Full Text Available Background: Spontaneous abortion is the most common adverse pregnancy outcome. We aimed to investigate a possible link between nutrient deficiencies and the risk of spontaneous abortion. Materials and Methods: This case-control study included the case group (n=331 experiencing a spontaneous abortion before 14 weeks of pregnancy and the control group (n=331 who were healthy pregnant women over 14 weeks of pregnancy. The participants filled out Food Frequency Questionnaire (FFQ, in which they reported their frequency of consumption for a given serving of each food item during the past three months, on a daily, weekly or monthly basis. The reported frequency for each food item was converted to a daily intake. Then, consumption of nutrients was compared between the two groups. Results: There are significant differences between the two groups regarding consumed servings/day of vegetables, bread and cereal, meat, poultry, fish, eggs, beans, fats, oils and dairy products (P=0.012, P<0.001, P=0.004, P<0.001, P=0.019, respectively. There are significant differences between the two groups in all micronutrient including folic acid, iron, vitamin C, vitamin B6, vitamin B12 and zinc (P<0.001. Conclusion: Poor nutrientions may be correlated with increased risk of spontaneous abortion
International Nuclear Information System (INIS)
Kim, Su Zy; Park, Chan Hee; Soo, Joo In; Pai, Moon Sun; Yoon, Suk Nam; Kim, Jang Sung
1997-01-01
Spontaneous intracranial hypotension (SIH) typically occurs without an obvious cause. However, it can be seen following the lumbar puncture, craniotomy, or spinal surgery. Also listed are contributing factors such as sneezing, coughing, intercourse or minor fall. Spontaneous spinal CSF leaks are not common, but are now increasingly recognized as a cause of postural headache associated with intracranial hypotension. The purpose of our study was to evaluate the role of RN cisternography in the diagnosis of SIH cuased by spinal CSF leakage. Four patients with clinical suspicion of SIH (Group I) and six patients as normal control (Group II) underwent RN cisternography. RN cisternography in Group II was done for various reasons, such as hydrocephalus, syringomyelia and memory loss. Group I consisted of the patients who presented with postural headache, as well as additional symptoms, such as nausea, vomiting, dizziness, tinnitus and eyeball pain. The age range of these patients was 27 - 67 years. Lumbar puncture and CSF examinations were performed in Group I more than once and showed typical findings of low CSF pressure and slightly elevated protein level. Brain MRI (4/4), Cervico-thoracic spine MRI (3/4) were also performed. On gadolinium-enhanced brain MRI, enhancement of the meninges which is the most characteristic radiographic finding in intracranial hypotension was found in all patients of Group I. But, cervico-thoracic spin MRI was nonspecific. None of Group I had contrast myelography because of the patient's refusal. Group I and Group II underwent radionuclide cisternography following lumbar subarachnoid injection of 99mTc-DTPA (1-2mCi). The scans were taken in 2, 5, 24 hours later using single head gamma camera equipped with LEAP. Entire spinal region in posterior view and head in frontal and lateral views were obtained. The cisternography of Group I showed the CSF leakage or diverticulum at the level of cervico-thoracic junction(3/4) and mid-thoracic level (1
Energy Technology Data Exchange (ETDEWEB)
Kim, Su Zy; Park, Chan Hee; Soo, Joo In; Pai, Moon Sun; Yoon, Suk Nam; Kim, Jang Sung [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)
1997-07-01
Spontaneous intracranial hypotension (SIH) typically occurs without an obvious cause. However, it can be seen following the lumbar puncture, craniotomy, or spinal surgery. Also listed are contributing factors such as sneezing, coughing, intercourse or minor fall. Spontaneous spinal CSF leaks are not common, but are now increasingly recognized as a cause of postural headache associated with intracranial hypotension. The purpose of our study was to evaluate the role of RN cisternography in the diagnosis of SIH cuased by spinal CSF leakage. Four patients with clinical suspicion of SIH (Group I) and six patients as normal control (Group II) underwent RN cisternography. RN cisternography in Group II was done for various reasons, such as hydrocephalus, syringomyelia and memory loss. Group I consisted of the patients who presented with postural headache, as well as additional symptoms, such as nausea, vomiting, dizziness, tinnitus and eyeball pain. The age range of these patients was 27 - 67 years. Lumbar puncture and CSF examinations were performed in Group I more than once and showed typical findings of low CSF pressure and slightly elevated protein level. Brain MRI (4/4), Cervico-thoracic spine MRI (3/4) were also performed. On gadolinium-enhanced brain MRI, enhancement of the meninges which is the most characteristic radiographic finding in intracranial hypotension was found in all patients of Group I. But, cervico-thoracic spin MRI was nonspecific. None of Group I had contrast myelography because of the patient's refusal. Group I and Group II underwent radionuclide cisternography following lumbar subarachnoid injection of 99mTc-DTPA (1-2mCi). The scans were taken in 2, 5, 24 hours later using single head gamma camera equipped with LEAP. Entire spinal region in posterior view and head in frontal and lateral views were obtained. The cisternography of Group I showed the CSF leakage or diverticulum at the level of cervico-thoracic junction(3/4) and mid
Energy Technology Data Exchange (ETDEWEB)
Kim, Su Zy; Park, Chan Hee; Soo, Joo In; Pai, Moon Sun; Yoon, Suk Nam; Kim, Jang Sung [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)
1997-07-01
Spontaneous intracranial hypotension (SIH) typically occurs without an obvious cause. However, it can be seen following the lumbar puncture, craniotomy, or spinal surgery. Also listed are contributing factors such as sneezing, coughing, intercourse or minor fall. Spontaneous spinal CSF leaks are not common, but are now increasingly recognized as a cause of postural headache associated with intracranial hypotension. The purpose of our study was to evaluate the role of RN cisternography in the diagnosis of SIH cuased by spinal CSF leakage. Four patients with clinical suspicion of SIH (Group I) and six patients as normal control (Group II) underwent RN cisternography. RN cisternography in Group II was done for various reasons, such as hydrocephalus, syringomyelia and memory loss. Group I consisted of the patients who presented with postural headache, as well as additional symptoms, such as nausea, vomiting, dizziness, tinnitus and eyeball pain. The age range of these patients was 27 - 67 years. Lumbar puncture and CSF examinations were performed in Group I more than once and showed typical findings of low CSF pressure and slightly elevated protein level. Brain MRI (4/4), Cervico-thoracic spine MRI (3/4) were also performed. On gadolinium-enhanced brain MRI, enhancement of the meninges which is the most characteristic radiographic finding in intracranial hypotension was found in all patients of Group I. But, cervico-thoracic spin MRI was nonspecific. None of Group I had contrast myelography because of the patient's refusal. Group I and Group II underwent radionuclide cisternography following lumbar subarachnoid injection of 99mTc-DTPA (1-2mCi). The scans were taken in 2, 5, 24 hours later using single head gamma camera equipped with LEAP. Entire spinal region in posterior view and head in frontal and lateral views were obtained. The cisternography of Group I showed the CSF leakage or diverticulum at the level of cervico-thoracic junction(3/4) and mid-thoracic level (1
Mir, Aamir; Chen, Ji; Robinson, Kyle; Lendy, Emma; Goodman, Jaclyn; Neau, David; Golden, Barbara L.
2016-01-01
The hammerhead ribozyme is a self-cleaving RNA broadly dispersed across all kingdoms of life. Although it was the first of the small, nucleolytic ribozymes discovered, the mechanism by which it catalyzes its reaction remains elusive. The nucleobase of G12 is well positioned to be a general base, but it is unclear if or how this guanine base becomes activated for proton transfer. Metal ions have been implicated in the chemical mechanism, but no interactions between divalent metal ions and the cleavage site have been observed crystallographically. To better understand how this ribozyme functions, we have solved crystal structures of wild-type and G12A mutant ribozymes. We observe a pH-dependent conformational change centered around G12, consistent with this nucleotide becoming deprotonated. Crystallographic and kinetic analysis of the G12A mutant reveals a Zn2+ specificity switch suggesting a direct interaction between a divalent metal ion and the purine at position 12. The metal ion specificity switch and the pH–rate profile of the G12A mutant suggest that the minor imino tautomer of A12 serves as the general base in the mutant ribozyme. We propose a model in which the hammerhead ribozyme rearranges prior to the cleavage reaction, positioning two divalent metal ions in the process. The first metal ion, positioned near G12, becomes directly coordinated to the O6 keto oxygen, to lower the pKa of the general base and organize the active site. The second metal ion, positioned near G10.1, bridges the N7 of G10.1 and the scissile phosphate and may participate directly in the cleavage reaction. PMID:26398724
International Nuclear Information System (INIS)
Rumlova, Michaela; Ruml, Tomas; Pohl, Jan; Pichova, Iva
2003-01-01
Processing of Gag polyproteins by viral protease (PR) leads to reorganization of immature retroviral particles and formation of a ribonucleoprotein core. In some retroviruses, such as HIV and RSV, cleavage of a spacer peptide separating capsid and nucleocapsid proteins is essential for the core formation. We show here that no similar spacer peptide is present in the capsid-nucleocapsid (CA-NC) region of Mason-Pfizer monkey virus (M-PMV) and that the CA protein is cleaved in vitro by the PR within the major homology region (MHR) and the NC protein in several sites at the N-terminus. The CA cleavage product was also identified shortly after penetration of M-PMV into COS cells, suggesting that the protease-catalyzed cleavage is involved in core disintegration
Simulating spontaneously generated coherence in a four-level atomic system
International Nuclear Information System (INIS)
Li Aijun; Gao Jinyue; Wu Jinhui; Wang Lei
2005-01-01
We study the spontaneous emission property of a four-level atomic system driven by two coherent fields. By numerical calculations in the bare state picture, we show that such interesting phenomena as extremely narrow peaks and spontaneous emission quenching can be realized, which are well understood by qualitative explanations in the partially and fully dressed state pictures. Especially, this coherently driven atomic system has two close-lying levels in the partially dressed state picture so that spontaneously generated coherence arises. Using our considered scheme it is feasible to carry out experiments based on spontaneously generated coherence because all rigorous requirements have been avoided in the bare state picture
Fluorescence-based high-throughput screening of dicer cleavage activity.
Podolska, Katerina; Sedlak, David; Bartunek, Petr; Svoboda, Petr
2014-03-01
Production of small RNAs by ribonuclease III Dicer is a key step in microRNA and RNA interference pathways, which employ Dicer-produced small RNAs as sequence-specific silencing guides. Further studies and manipulations of microRNA and RNA interference pathways would benefit from identification of small-molecule modulators. Here, we report a study of a fluorescence-based in vitro Dicer cleavage assay, which was adapted for high-throughput screening. The kinetic assay can be performed under single-turnover conditions (35 nM substrate and 70 nM Dicer) in a small volume (5 µL), which makes it suitable for high-throughput screening in a 1536-well format. As a proof of principle, a small library of bioactive compounds was analyzed, demonstrating potential of the assay.
Lee, Michael S; Nguyen, Heajung; Shlofmitz, Richard
2017-02-01
We analyzed the incidence of bradycardia and the safety of patients with severely calcified coronary lesions who underwent orbital atherectomy without the insertion of a temporary pacemaker. The presence of severely calcified coronary lesions can increase the complexity of percutaneous coronary intervention due to the difficulty in advancing and optimally expanding the stent. High-pressure inflations to predilate calcified lesions may cause angiographic complications like perforation and dissection. Suboptimal stent expansion is associated with stent thrombosis and restenosis. Orbital atherectomy safely and effectively modifies calcified plaque to facilitate optimal stent expansion. The incidence of bradycardia in orbital atherectomy is unknown. Fifty consecutive patients underwent orbital atherectomy from February 2014 to September 2016 at our institution, none of whom underwent insertion of a temporary pacemaker. The final analysis included 47 patients in this retrospective study as 3 patients were excluded because of permanent pacemaker implantation. The primary endpoint was significant bradycardia, defined as bradycardia requiring emergent pacemaker placement or a heart rate pacemaker appears to be safe.
Interprofessional learning, impression management, and spontaneity in the acute healthcare setting.
Bell, Elaine; McAllister, Sue; Ward, Paul R; Russell, Alison
2016-09-01
Spontaneous learning is integral to definitions of interprofessional learning (IPL) because it has been suggested that spontaneous learning can be deeply connected with the work that people do in collaboration with colleagues via their professional networks. However, its nature and the processes involved are not well understood. Goffman's theory of impression management offers a useful theoretical framework to consider the way in which interaction in the workplace connects to spontaneous learning. This article explores the current literature to investigate the usefulness of this framework to better understand and identify spontaneous learning in the workplace. Aspects such as the connections between spontaneous learning occurring in formal and informal work activities, the spaces in which it occurs, and the influence of professional networking are considered. It is proposed that research directed to developing a better understanding of the nature of spontaneous learning in IPL will assist in connecting this learning to formal IPL curricula, enhancing IPL and patient outcomes.
Spontaneity and Equilibrium III: A History of Misinformation
Raff, Lionel M.
2014-01-01
Necessary and sufficient criteria for reaction spontaneity in a given direction and for spontaneity of finite transformations in single-reaction, closed systems are developed. The criteria are general in that they hold for reactions conducted under either conditions of constant T and p or constant T and V. These results are illustrated using a…
Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic add residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host ce...
Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy
Directory of Open Access Journals (Sweden)
Alexander L. Pan
2012-01-01
Full Text Available Spontaneous coronary artery dissection is a rare condition, usually presenting as an acute coronary syndrome, and is often seen in states associated with high systemic estrogen levels such as pregnancy or oral contraceptive use. While topical hormonal replacement therapy may result in increased estrogen levels similar to those documented with oral contraceptive use, there are no reported cases of spontaneous coronary dissection with topical hormonal replacement therapy. We describe a 53-year-old female who developed two spontaneous coronary dissections while on topical hormonal replacement therapy. The patient had no other risk factors for coronary dissection. After withdrawal from topical hormonal therapy, our patient has done well and has not had recurrent coronary artery dissections over a one-year follow-up period. The potential contributory role of topical hormonal therapy as a cause of spontaneous coronary dissection should be recognized.