Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.

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Karin Voordeckers

2015-11-01

Full Text Available Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.

Unexpected findings and promoting monocausal claims, a cautionary tale.

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Copeland, Samantha Marie

2017-10-01

Stories of serendipitous discoveries in medicine incorrectly imply that the path from an unexpected observation to major discovery is straightforward or guaranteed. In this paper, I examine a case from the field of research about chronic fatigue syndrome (CFS). In Norway, an unexpected positive result during clinical care has led to the development of a research programme into the potential for the immunosuppressant drug rituximab to relieve the symptoms of CFS. The media and public have taken up researchers' speculations that their research results indicate a causal mechanism for CFS - consequently, patients now have great hope that 'the cause' of CFS has been found, and thus, a cure is sure to follow. I argue that a monocausal claim cannot be correctly asserted, either on the basis of the single case of an unexpected, although positive, result or on the basis of the empirical research that has followed up on that result. Further, assertion and promotion of this claim will have specific harmful effects: it threatens to inappropriately narrow the scope of research on CFS, might misdirect research altogether, and could directly and indirectly harm patients. Therefore, the CFS case presents a cautionary tale, illustrating the risks involved in drawing a theoretical hypothesis from an unexpected observation. Further, I draw attention to the tendency in contemporary clinical research with CFS to promote new research directions on the basis of reductive causal models of that syndrome. Particularly, in the case of CFS research, underdetermination and causal complexity undermine the potential value of a monocausal claim. In sum, when an unexpected finding occurs in clinical practice or medical research, the value of following up on that finding is to be found not in the projected value of a singular causal relationship inferred from the finding but rather in the process of research that follows. © 2016 John Wiley & Sons, Ltd.

Metatranscriptomic analysis of a high-sulfide aquatic spring reveals insights into sulfur cycling and unexpected aerobic metabolism

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Anne M. Spain

2015-09-01

Full Text Available Zodletone spring is a sulfide-rich spring in southwestern Oklahoma characterized by shallow, microoxic, light-exposed spring water overlaying anoxic sediments. Previously, culture-independent 16S rRNA gene based diversity surveys have revealed that Zodletone spring source sediments harbor a highly diverse microbial community, with multiple lineages putatively involved in various sulfur-cycling processes. Here, we conducted a metatranscriptomic survey of microbial populations in Zodletone spring source sediments to characterize the relative prevalence and importance of putative phototrophic, chemolithotrophic, and heterotrophic microorganisms in the sulfur cycle, the identity of lineages actively involved in various sulfur cycling processes, and the interaction between sulfur cycling and other geochemical processes at the spring source. Sediment samples at the spring’s source were taken at three different times within a 24-h period for geochemical analyses and RNA sequencing. In depth mining of datasets for sulfur cycling transcripts revealed major sulfur cycling pathways and taxa involved, including an unexpected potential role of Actinobacteria in sulfide oxidation and thiosulfate transformation. Surprisingly, transcripts coding for the cyanobacterial Photosystem II D1 protein, methane monooxygenase, and terminal cytochrome oxidases were encountered, indicating that genes for oxygen production and aerobic modes of metabolism are actively being transcribed, despite below-detectable levels (<1 µM of oxygen in source sediment. Results highlight transcripts involved in sulfur, methane, and oxygen cycles, propose that oxygenic photosynthesis could support aerobic methane and sulfide oxidation in anoxic sediments exposed to sunlight, and provide a viewpoint of microbial metabolic lifestyles under conditions similar to those seen during late Archaean and Proterozoic eons.

Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing.

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Hoyte, Ashley C; Jamin, Augusta V; Koneru, Pratibha C; Kobe, Matthew J; Larue, Ross C; Fuchs, James R; Engelman, Alan N; Kvaratskhelia, Mamuka

2017-12-01

The pyridine-based multimerization selective HIV-1 integrase (IN) inhibitors (MINIs) are a distinct subclass of allosteric IN inhibitors. MINIs potently inhibit HIV-1 replication during virion maturation by inducing hyper- or aberrant IN multimerization but are largely ineffective during the early steps of viral replication. Here, we investigated the mechanism for the evolution of a triple IN substitution (T124N/V165I/T174I) that emerges in cell culture with a representative MINI, KF116. We show that HIV-1 NL4-3(IN T124N/V165I/T174I) confers marked (>2000-fold) resistance to KF116. Two IN substitutions (T124N/T174I) directly weaken inhibitor binding at the dimer interface of the catalytic core domain but at the same time markedly impair HIV-1 replication capacity. Unexpectedly, T124N/T174I IN substitutions inhibited proteolytic processing of HIV-1 polyproteins Gag and Gag-Pol, resulting in immature virions. Strikingly, the addition of the third IN substitution (V165I) restored polyprotein processing, virus particle maturation, and significant levels of replication capacity. These results reveal an unanticipated role of IN for polyprotein proteolytic processing during virion morphogenesis. The complex evolutionary pathway for the emergence of resistant viruses, which includes the need for the compensatory V165I IN substitution, highlights a relatively high genetic barrier exerted by MINI KF116. Additionally, we have solved the X-ray structure of the drug-resistant catalytic core domain protein, which provides means for rational development of second-generation MINIs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Vine vigor, yield and grape quality assessment by airborne remote sensing over three years: Analysis of unexpected relationships in cv. Tempranillo

Energy Technology Data Exchange (ETDEWEB)

Bonilla, I.; Martinez de Toda, F.; Martínez-Casasnovas, J.A.

2015-07-01

The prediction of grape composition is becoming more important due to the need of reducing the current levels of alcohol and pH of the wines, a problem that is exacerbated by climate change. This work presents a 3-year study of the spatial variability of grape composition in a rainfed Tempranillo vineyard located in Rioja (Spain). It is based on the acquisition of multispectral imagery at véraison (start of the ripening process); and zoning based on NDVI, to assess its performance for zonal management. The results reveal a high spatial variability within the plot, with a stable pattern over the years, even with very different climate conditions. NDVI was a good predictor of vegetative growth variables. However, the prediction of grape composition was more complex. Unexpectedly, anthocyanins were found to be higher in the highest vigor zone, which is probably related to the effects of climate change. This unexpected relationship is particularly discussed in the article. (Author)

Unexpected strong attraction in the presence of continuum bound state

International Nuclear Information System (INIS)

Delfino, A.; Frederico, T.

1992-06-01

The result of few-particle ground-state calculation employing a two-particle non-local potential supporting a continuum bound state in addition to a negative-energy bound state has occasionally revealed unexpected large attraction in producing a very strongly bound ground state. In the presence of the continuum bound state the difference of phase shift between zero and infinite energies has an extra jump of φ as in the presence of an additional bound state. The wave function of the continuum bound state is identical with that of a strongly bound negative-energy state, which leads us to postulate a pseudo bound state in the two-particle system in order to explain the unexpected attraction. The role of the Pauli forbidden states is expected to be similar to these pseudo states. (author)

Unexpected brain finding in pre-autopsy postmortem CT.

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Chatzaraki, Vasiliki; Bolliger, Stephan A; Thali, Michael J; Eggert, Sebastian; Ruder, Thomas D

2017-09-01

A case is presented in which pre-autopsy postmortem computed tomography (PMCT) revealed an unexpected brain abscess with a related frontal sinusitis and an erosion of the posterior wall of the frontal sinus. PMCT findings enabled the forensic pathologists to adapt protective measures during autopsy and protect their health from infection. Pre-autopsy PMCT has been also useful in the early differential diagnosis procedure. The complementary use of postmortem imaging and autopsy can improve the quality of forensic death investigations.

Investigating Initial Disclosures and Reactions to Unexpected, Positive HPV Diagnosis.

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Smith, Rachel A; Hernandez, Rachael; Catona, Danielle

2014-07-01

Initial disclosures of health conditions are critical communication moments. Existing research focuses on disclosers; integrating confidants into studies of initial disclosures is needed. Guided by the disclosure decision-making model (DD-MM; Greene, 2009), this study examined what diagnosed persons and confidants may say when faced with unexpected test results and unexpected disclosures, respectively. Participants ( N = 151) recorded an audio-visual message for another person, after imagining that they or the other person had just received unexpected, positive HPV test results. The qualitative analysis revealed four themes: (1) impression management and social distance, (2) invisible symptoms and advice regarding future disclosures, (3) expressing and acknowledging emotional reactions, and (4) misunderstandings and lacking knowledge about HPV. These findings suggested that DD-MM may be a relevant framework for understanding not only when disclosers share, but what disclosers and confidants say in early conversations about new diagnoses. While disclosers' and confidants' messages showed marked similarities, important differences appeared. For example, confidants focused on assuaging disclosers' fear about the consequences, whereas disclosers expressed distress related to their uncertainty about the prognosis of an HPV infection and how to prepare for next steps. The discussion highlighted implications for the DD-MM, HPV disclosures, and future interventions.

Unexpected high plasma cobalamin

DEFF Research Database (Denmark)

Arendt, Johan F B; Nexo, Ebba

2013-01-01

It is well-established that more than 8% of patients examined for vitamin B12 deficiency unexpectedly have increased plasma levels of the vitamin, but so far there are no guidelines for the clinical interpretation of such findings. In this review, we summarise known associations between high plasma...... cobalamin binding proteins, transcobalamin and haptocorrin. Based on current knowledge, we suggest a strategy for the clinical interpretation of unexpected high plasma cobalamin. Since a number of the associated diseases are critical and life-threatening, the strategy promotes the concept of 'think...

Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

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Trey K Sato

2016-10-01

Full Text Available The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3, a component of MAP Kinase (MAPK signaling (HOG1, a regulator of Protein Kinase A (PKA signaling (IRA2, and a scaffolding protein for mitochondrial iron-sulfur (Fe-S cluster biogenesis (ISU1. Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

Science.gov (United States)

Sato, Trey K; Tremaine, Mary; Parreiras, Lucas S; Hebert, Alexander S; Myers, Kevin S; Higbee, Alan J; Sardi, Maria; McIlwain, Sean J; Ong, Irene M; Breuer, Rebecca J; Avanasi Narasimhan, Ragothaman; McGee, Mick A; Dickinson, Quinn; La Reau, Alex; Xie, Dan; Tian, Mingyuan; Reed, Jennifer L; Zhang, Yaoping; Coon, Joshua J; Hittinger, Chris Todd; Gasch, Audrey P; Landick, Robert

2016-10-01

The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3), a component of MAP Kinase (MAPK) signaling (HOG1), a regulator of Protein Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1). Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

Unexpected uncertainty, volatility and decision-making

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Amy Rachel Bland

2012-06-01

Full Text Available The study of uncertainty in decision making is receiving greater attention in the fields of cognitive and computational neuroscience. Several lines of evidence are beginning to elucidate different variants of uncertainty. Particularly, risk, ambiguity and expected and unexpected forms of uncertainty are well articulated in the literature. In this article we review both empirical and theoretical evidence arguing for the potential distinction between three forms of uncertainty; expected uncertainty, unexpected uncertainty and volatility. Particular attention will be devoted to exploring the distinction between unexpected uncertainty and volatility which has been less appreciated in the literature. This includes evidence from computational modelling, neuromodulation, neuroimaging and electrophysiological studies. We further address the possible differentiation of cognitive control mechanisms used to deal with these forms of uncertainty. Particularly we explore a role for conflict monitoring and the temporal integration of information into working memory. Finally, we explore whether the Dual Modes of Control theory provides a theoretical framework for understanding the distinction between unexpected uncertainty and volatility.

Patterns of unexpected in-hospital deaths: a root cause analysis

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Curry J Paul

2011-02-01

Full Text Available Abstract Background Respiratory alarm monitoring and rapid response team alerts on hospital general floors are based on detection of simple numeric threshold breaches. Although some uncontrolled observation trials in select patient populations have been encouraging, randomized controlled trials suggest that this simplistic approach may not reduce the unexpected death rate in this complex environment. The purpose of this review is to examine the history and scientific basis for threshold alarms and to compare thresholds with the actual pathophysiologic patterns of evolving death which must be timely detected. Methods The Pubmed database was searched for articles relating to methods for triggering rapid response teams and respiratory alarms and these were contrasted with the fundamental timed pathophysiologic patterns of death which evolve due to sepsis, congestive heart failure, pulmonary embolism, hypoventilation, narcotic overdose, and sleep apnea. Results In contrast to the simplicity of the numeric threshold breach method of generating alerts, the actual patterns of evolving death are complex and do not share common features until near death. On hospital general floors, unexpected clinical instability leading to death often progresses along three distinct patterns which can be designated as Types I, II and III. Type I is a pattern comprised of hyperventilation compensated respiratory failure typical of congestive heart failure and sepsis. Here, early hyperventilation and respiratory alkalosis can conceal the onset of instability. Type II is the pattern of classic CO2 narcosis. Type III occurs only during sleep and is a pattern of ventilation and SPO2 cycling caused by instability of ventilation and/or upper airway control followed by precipitous and fatal oxygen desaturation if arousal failure is induced by narcotics and/or sedation. Conclusion The traditional threshold breach method of detecting instability on hospital wards was not

Conjunctival lymphangioma in a 4-year-old girl revealed tuberous sclerosis complex

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Freiberg, Florentina Joyce

2016-09-01

Full Text Available Background: To present a case of conjunctival lymphangioma in a girl with tuberous sclerosis complex.Methods/results: A 4-year-old girl presented with a relapsing cystic lesion of the bulbar conjunctiva in the right eye with string-of-pearl-like dilation of lymphatic vessels and right-sided facial swelling with mild pain. Best-corrected vision was not impaired. Examination of the skin revealed three hypomelanotic macules and a lumbal Shagreen patch. Magnetic resonance imaging (MRI findings displayed minimal enhancement of buccal fat on the right side. Cranial and orbital MRI showed signal enhancement in the right cortical and subcortical areas. Genetic analysis revealed a heterozygous deletion encompassing exon 1 and 2 of the gene (tuberous sclerosis complex 1 gene, confirming the diagnosis of tuberous sclerosis complex.Conclusion: In conjunctival lymphangioma, tuberous sclerosis complex should be considered as the primary disease.

Theory of mind for processing unexpected events across contexts.

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Dungan, James A; Stepanovic, Michael; Young, Liane

2016-08-01

Theory of mind, or mental state reasoning, may be particularly useful for making sense of unexpected events. Here, we investigated unexpected behavior across both social and non-social contexts in order to characterize the precise role of theory of mind in processing unexpected events. We used functional magnetic resonance imaging to examine how people respond to unexpected outcomes when initial expectations were based on (i) an object's prior behavior, (ii) an agent's prior behavior and (iii) an agent's mental states. Consistent with prior work, brain regions for theory of mind were preferentially recruited when people first formed expectations about social agents vs non-social objects. Critically, unexpected vs expected outcomes elicited greater activity in dorsomedial prefrontal cortex, which also discriminated in its spatial pattern of activity between unexpected and expected outcomes for social events. In contrast, social vs non-social events elicited greater activity in precuneus across both expected and unexpected outcomes. Finally, given prior information about an agent's behavior, unexpected vs expected outcomes elicited an especially robust response in right temporoparietal junction, and the magnitude of this difference across participants correlated negatively with autistic-like traits. Together, these findings illuminate the distinct contributions of brain regions for theory of mind for processing unexpected events across contexts. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Astrocyte Ca2+ signalling: an unexpected complexity

OpenAIRE

Volterra, Andrea; Liaudet, Nicolas; Savtchouk, Iaroslav

2014-01-01

Astrocyte Ca(2+) signalling has been proposed to link neuronal information in different spatial-temporal dimensions to achieve a higher level of brain integration. However, some discrepancies in the results of recent studies challenge this view and highlight key insufficiencies in our current understanding. In parallel, new experimental approaches that enable the study of astrocyte physiology at higher spatial-temporal resolution in intact brain preparations are beginning to reveal an unexpec...

Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

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Couturier Marie

2012-02-01

Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

Autistic Traits Affect P300 Response to Unexpected Events, regardless of Mental State Inferences

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Mitsuhiko Ishikawa

2017-01-01

Full Text Available Limited use of contextual information has been suggested as a way of understanding cognition in people with autism spectrum disorder (ASD. However, it has also been argued that individuals with ASD may have difficulties inferring others’ mental states. Here, we examined how individuals with different levels of autistic traits respond to contextual deviations by measuring event-related potentials that reflect context usage. The Autism Spectrum Quotient (AQ was used to quantify autistic-like traits in 28 university students, and 19 participants were defined as Low or High AQ groups. To additionally examine inferences about mental state, two belief conditions (with or without false belief were included. Participants read short stories in which the final sentence included either an expected or an unexpected word and rated the word’s degree of deviation from expectation. P300 waveform analysis revealed that unexpected words were associated with larger P300 waveforms for the Low AQ group, but smaller P300 responses in the High AQ group. Additionally, AQ social skill subscores were positively correlated with evaluation times in the Unexpected condition, whether a character’s belief was false or not. This suggests that autistic traits can affect responses to unexpected events, possibly because of decreased availability of context information.

Gastrointestinal causes of sudden unexpected death: A review.

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Menezes, Ritesh G; Ahmed, Saba; Pasha, Syed Bilal; Hussain, Syed Ather; Fatima, Huda; Kharoshah, Magdy A; Madadin, Mohammed

2018-01-01

Gastrointestinal conditions are a less common cause of sudden unexpected death when compared to other conditions such as cardiovascular conditions, but they are equally important. Various congenital and acquired gastrointestinal conditions that have resulted in sudden unexpected death are discussed. The possible lethal mechanisms behind each condition, along with any associated risk factors or secondary diseases, have been described. Through this article, we aim to highlight the need for physicians to prevent death in such conditions by ensuring that subclinical cases are diagnosed correctly before it is too late and by providing timely and efficacious treatment to the patient concerned. In addition, this review would certainly benefit the forensic pathologist while dealing with cases of sudden unexpected death due to gastrointestinal causes. This article is a review of the major gastrointestinal causes of sudden unexpected death. In addition, related fatal cases encountered occasionally in forensic autopsy practice are also included. There are several unusual and rare causes of life-threatening gastrointestinal bleeding that may lead to sudden unexpected death to cover all the entities in detail. Nevertheless, this article is a general guide to the topic of gastrointestinal causes of sudden unexpected death.

The unexpected in primary care: a multicenter study on the emergence of unvoiced patient agenda.

NARCIS (Netherlands)

Peltenburg, M.; Fischer, J.E.; Bahrs, O.; Dulmen, S. van; Brink-Muinen, A. van den

2004-01-01

PURPOSE: Within the time constraints of a typical physician-patient encounter, the full patient agenda will rarely be voiced. Unexpectedly revealed issues that were neither on the patient's list of items for discussion nor anticipated by the physician constitute an emerging agenda. We aimed to

VNTR analysis reveals unexpected genetic diversity within Mycoplasma agalactiae, the main causative agent of contagious agalactia

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Ayling Roger D

2008-11-01

Full Text Available Abstract Background Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. Results We have developed variable number tandem repeat (VNTR analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE and random amplified polymorphic DNA (RAPD analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. Conclusion VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.

In-Depth Glyco-Peptidomics Approach Reveals Unexpected Diversity of Glycosylated Peptides and Atypical Post-Translational Modifications in Dendroaspis angusticeps Snake Venom.

Science.gov (United States)

Degueldre, Michel; Echterbille, Julien; Smargiasso, Nicolas; Damblon, Christian; Gouin, Charlotte; Mourier, Gilles; Gilles, Nicolas; De Pauw, Edwin; Quinton, Loïc

2017-11-18

Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA), the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors. This study aims to demonstrate that the knowledge of venom composition is still limited and that animal venoms contain unexpected diversity and surprises. A previous study has shown that Dendroaspis angusticeps venom contains not only a cocktail of classical toxins, but also small glycosylated peptides. Following this work, a deep exploration of DA glycopeptidome by a dual nano liquid chromatography coupled to electrospray ionization mass spectrometry (nanoLC-ESI-MS) and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) analyses was initiated. This study reveals unsuspected structural diversity of compounds such as 221 glycopeptides, displaying different glycan structures. Sequence alignments underline structural similarities with natriuretic peptides already characterized in Elapidae venoms. Finally, the presence of an S -cysteinylation and hydroxylation of proline on four glycopeptides, never described to date in snake venoms, is also revealed by proteomics and affined by nuclear magnetic resonance (NMR) experiments.

In-Depth Glyco-Peptidomics Approach Reveals Unexpected Diversity of Glycosylated Peptides and Atypical Post-Translational Modifications in Dendroaspis angusticeps Snake Venom

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Michel Degueldre

2017-11-01

Full Text Available Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA, the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors. This study aims to demonstrate that the knowledge of venom composition is still limited and that animal venoms contain unexpected diversity and surprises. A previous study has shown that Dendroaspis angusticeps venom contains not only a cocktail of classical toxins, but also small glycosylated peptides. Following this work, a deep exploration of DA glycopeptidome by a dual nano liquid chromatography coupled to electrospray ionization mass spectrometry (nanoLC-ESI-MS and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS analyses was initiated. This study reveals unsuspected structural diversity of compounds such as 221 glycopeptides, displaying different glycan structures. Sequence alignments underline structural similarities with natriuretic peptides already characterized in Elapidae venoms. Finally, the presence of an S-cysteinylation and hydroxylation of proline on four glycopeptides, never described to date in snake venoms, is also revealed by proteomics and affined by nuclear magnetic resonance (NMR experiments.

Water in stars: expected and unexpected

Science.gov (United States)

Tsuji, T.; Aoki, W.; Ohnaka, K.

1999-03-01

We have confirmed the presence of water in the early M giant α Cet (M1.5III) and supergiant KK Per (M2Iab) by the highest resolution grating mode of SWS, but this result is quite unexpected from present model atmospheres. In late M giant and supergiant stars, water observed originates partly in the photosphere as expected by the model atmospheres, but ISO SWS has revealed that the 2.7 mic\\ absorption bands appear to be somewhat stronger than predicted while 6.5 mic\\ bands weaker, indicating the contamination by an emission component. In the mid-infrared region extending to 45 mic, pure rotation lines of hho\\ appear as distinct emission on the high resolution SWS spectra of 30g Her (M7III) and S Per (M4-7Ia), along with the dust emission at 10, 13, 20 mic\\ and a new unidentified feature at 30 mic. Thus, together with the dust, water contributes to the thermal balance of the outer atmosphere already in the mid-infrared. The excitation temperature of hho\\ gas is estimated to be 500 - 1000 K. In view of this result for late M (super)giants, unexpected water observed in early M (super)giants should also be of non-photospheric in origin. Thus, ISO has finally established the presence of a new component of the outer atmosphere - a warm molecular envelope - in red giant and supergiant stars from early to late types. Such a rather warm molecular envelope will be a site of various activities such as chemical reactions, dust formation, mass-outflow etc.

Combining complexity measures of EEG data: multiplying measures reveal previously hidden information.

Science.gov (United States)

Burns, Thomas; Rajan, Ramesh

2015-01-01

Many studies have noted significant differences among human electroencephalograph (EEG) results when participants or patients are exposed to different stimuli, undertaking different tasks, or being affected by conditions such as epilepsy or Alzheimer's disease. Such studies often use only one or two measures of complexity and do not regularly justify their choice of measure beyond the fact that it has been used in previous studies. If more measures were added to such studies, however, more complete information might be found about these reported differences. Such information might be useful in confirming the existence or extent of such differences, or in understanding their physiological bases. In this study we analysed publically-available EEG data using a range of complexity measures to determine how well the measures correlated with one another. The complexity measures did not all significantly correlate, suggesting that different measures were measuring unique features of the EEG signals and thus revealing information which other measures were unable to detect. Therefore, the results from this analysis suggests that combinations of complexity measures reveal unique information which is in addition to the information captured by other measures of complexity in EEG data. For this reason, researchers using individual complexity measures for EEG data should consider using combinations of measures to more completely account for any differences they observe and to ensure the robustness of any relationships identified.

Costly hide and seek pays: unexpected consequences of deceit in a social dilemma

International Nuclear Information System (INIS)

Szolnoki, Attila; Perc, Matjaž

2014-01-01

Deliberate deceptiveness intended to gain an advantage is commonplace in human and animal societies. In a social dilemma, an individual may only pretend to be a cooperator to elicit cooperation from others, while in reality he is a defector. With this as motivation, we study a simple variant of the evolutionary prisoner's dilemma game entailing deceitful defectors and conditional cooperators that lifts the veil on the impact of such two-faced behavior. Defectors are able to hide their true intentions at a personal cost, while conditional cooperators are probabilistically successful at identifying defectors and act accordingly. By focusing on the evolutionary outcomes in structured populations, we observe a number of unexpected and counterintuitive phenomena. We show that deceitful behavior may fare better if it is costly, and that a higher success rate of identifying defectors does not necessarily favor cooperative behavior. These results are rooted in the spontaneous emergence of cycling dominance and spatial patterns that give rise to fascinating phase transitions, which in turn reveal the hidden complexity behind the evolution of deception. (paper)

Quantum coherence spectroscopy reveals complex dynamics in bacterial light-harvesting complex 2 (LH2).

Science.gov (United States)

Harel, Elad; Engel, Gregory S

2012-01-17

Light-harvesting antenna complexes transfer energy from sunlight to photosynthetic reaction centers where charge separation drives cellular metabolism. The process through which pigments transfer excitation energy involves a complex choreography of coherent and incoherent processes mediated by the surrounding protein and solvent environment. The recent discovery of coherent dynamics in photosynthetic light-harvesting antennae has motivated many theoretical models exploring effects of interference in energy transfer phenomena. In this work, we provide experimental evidence of long-lived quantum coherence between the spectrally separated B800 and B850 rings of the light-harvesting complex 2 (LH2) of purple bacteria. Spectrally resolved maps of the detuning, dephasing, and the amplitude of electronic coupling between excitons reveal that different relaxation pathways act in concert for optimal transfer efficiency. Furthermore, maps of the phase of the signal suggest that quantum mechanical interference between different energy transfer pathways may be important even at ambient temperature. Such interference at a product state has already been shown to enhance the quantum efficiency of transfer in theoretical models of closed loop systems such as LH2.

Unexpected allergic reactions to food, a prospective study

NARCIS (Netherlands)

Michelsen-Huisman, A.D.; Os-Medendorp, H. van; Versluis, A.; Kruizinga, A.G.; Castenmiller, J.J.M.; Noteborn, H.P.J.M.; Houben, G.F.; Knulst, A.C.

2013-01-01

Unexpected reactions occur in patients with food allergy, but frequency data are scare. This prospective study investigates the frequency, severity and causes of unexpected allergic reactions to food in adults with a doctor's diagnosed food allergy. Participants complete an online questionnaire

Protein-carbohydrate complex reveals circulating metastatic cells in a microfluidic assay

KAUST Repository

Simone, Giuseppina

2013-02-11

Advances in carbohydrate sequencing technologies reveal the tremendous complexity of the glycome and the role that glycomics might have to bring insight into the biological functions. Carbohydrate-protein interactions, in particular, are known to be crucial to most mammalian physiological processes as mediators of cell adhesion and metastasis, signal transducers, and organizers of protein interactions. An assay is developed here to mimic the multivalency of biological complexes that selectively and sensitively detect carbohydrate-protein interactions. The binding of β-galactosides and galectin-3 - a protein that is correlated to the progress of tumor and metastasis - is examined. The efficiency of the assay is related to the expression of the receptor while anchoring to the interaction\\'s strength. Comparative binding experiments reveal molecular binding preferences. This study establishes that the assay is robust to isolate metastatic cells from colon affected patients and paves the way to personalized medicine. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protein-carbohydrate complex reveals circulating metastatic cells in a microfluidic assay

KAUST Repository

Simone, Giuseppina; Malara, Natalia Maria; Trunzo, Valentina; Perozziello, Gerardo; Neužil, Pavel; Francardi, Marco; Roveda, Laura; Renne, Maria; Prati, Ubaldo; Mollace, Vincenzo; Manz, Andreas; Di Fabrizio, Enzo M.

2013-01-01

Advances in carbohydrate sequencing technologies reveal the tremendous complexity of the glycome and the role that glycomics might have to bring insight into the biological functions. Carbohydrate-protein interactions, in particular, are known to be crucial to most mammalian physiological processes as mediators of cell adhesion and metastasis, signal transducers, and organizers of protein interactions. An assay is developed here to mimic the multivalency of biological complexes that selectively and sensitively detect carbohydrate-protein interactions. The binding of β-galactosides and galectin-3 - a protein that is correlated to the progress of tumor and metastasis - is examined. The efficiency of the assay is related to the expression of the receptor while anchoring to the interaction's strength. Comparative binding experiments reveal molecular binding preferences. This study establishes that the assay is robust to isolate metastatic cells from colon affected patients and paves the way to personalized medicine. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Subtle spectral effects accompanying the assembly of bacteriochlorophylls into cyclic light harvesting complexes revealed by high-resolution fluorescence spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Rätsep, Margus, E-mail: margus.ratsep@ut.ee; Pajusalu, Mihkel, E-mail: mihkel.pajusalu@ut.ee; Linnanto, Juha Matti, E-mail: juha.matti.linnanto@ut.ee [Institute of Physics, University of Tartu, Riia 142, 51014 Tartu (Estonia); Freiberg, Arvi, E-mail: arvi.freiberg@ut.ee [Institute of Physics, University of Tartu, Riia 142, 51014 Tartu, Estonia and Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu (Estonia)

2014-10-21

We have observed that an assembly of the bacteriochloropyll a molecules into B850 and B875 groups of cyclic bacterial light-harvesting complexes LH2 and LH1, respectively, results an almost total loss of the intra-molecular vibronic structure in the fluorescence spectrum, and simultaneously, an essential enhancement of its phonon sideband due to electron-phonon coupling. While the suppression of the vibronic coupling in delocalized (excitonic) molecular systems is predictable, as also confirmed by our model calculations, a boost of the electron-phonon coupling is rather unexpected. The latter phenomenon is explained by exciton self-trapping, promoted by mixing the molecular exciton states with charge transfer states between the adjacent chromophores in the tightly packed B850 and B875 arrangements. Similar, although less dramatic trends were noted for the light-harvesting complexes containing chlorophyll pigments.

Unexpected pathological findings after laparoscopic cholecystectomy - analysis of 1131 cases.

Science.gov (United States)

Bartosiak, Katarzyna; Liszka, Maciej; Drazba, Tomasz; Paśnik, Krzysztof; Janik, Michal R

2018-03-01

Gallbladder specimens are routinely sent for histopathological examination after cholecystectomy in order to rule out the presence of unexpected pathological findings. To establish the overall incidence of unexpected pathological findings in patients who underwent laparoscopic cholecystectomy for symptomatic gallbladder disease and determine whether the macroscopic appearance of the gallbladder in ultrasound examination could be a valid method for identifying patients with gallbladder malignancy. A retrospective study was conducted between 2013 and 2015. All histological reports (n = 1131) after cholecystectomy were searched for unexpected pathological findings. In cases where unexpected pathological findings were identified the additional analysis of preoperative abdominal ultrasound examination (USG) was done to determine the usefulness of USG in diagnosis of gallbladder malignancy. Of the 1131 patients included in the study, 356 (31.47%) were male and 774 (68.43%) were female. Unexpected pathological findings were present in 21 cases. The overall incidence of unexpected pathological findings was 1.86%. Only in 5 patients were suspicious appearances of gallbladder observed in preoperative ultrasound examination. In 16 patients there was no suspicion of malignancy. The positive predictive value of USG was 0.238. The incidence of unexpected pathological findings after laparoscopic cholecystectomy was 1.86%. Ultrasonography has low positive predictive value for identifying patients with malignant findings in a gallbladder specimen.

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

Energy Technology Data Exchange (ETDEWEB)

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.; Wu, Dick; Zhao, Minglei; Südhof, Thomas C.; Brunger, Axel T.

2017-08-16

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for the primed pre-fusion state. Ca2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. The tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.

42 CFR 493.861 - Standard; Unexpected antibody detection.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Unexpected antibody detection. 493.861 Section 493.861 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN..., Or Any Combination of These Tests § 493.861 Standard; Unexpected antibody detection. (a) Failure to...

Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

Science.gov (United States)

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-07-09

There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

Directory of Open Access Journals (Sweden)

Stefan Koelsch

Full Text Available BACKGROUND: There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: This study investigates event-related brain potentials (ERPs, skin conductance responses (SCRs and heart rate (HR elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression, we also created versions without variations in tempo and loudness (without musical expression to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing and an N5 (reflecting processing of meaning information in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses. The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function differed between the expressive and the non-expressive condition. CONCLUSIONS/SIGNIFICANCE: These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

Unexpected observations of muons from Cygnus X-3

International Nuclear Information System (INIS)

Elbert, J.W.

1986-01-01

One surface experiment (Kiel) and two underground experiments (Soudan and Mt. Blanc) have detected unexpectedly large fluxes of cosmic ray muons from the approximate direction of Cygnus X-3, with signals showing the precise period of the system. The muon signals cannot be produced by any known type of elementary particle unless unexpected processes are involved

Cognitive Readiness: Preparing for the Unexpected

National Research Council Canada - National Science Library

Fletcher, J. D

2004-01-01

.... Anticipated operational requirements can be decomposed into specific tasks, conditions, and standards, but how should individuals, teams, and units prepare for the unexpected, which, by definition...

Citizen science reveals unexpected continental-scale evolutionary change in a model organism.

Directory of Open Access Journals (Sweden)

Jonathan Silvertown

2011-04-01

Full Text Available Organisms provide some of the most sensitive indicators of climate change and evolutionary responses are becoming apparent in species with short generation times. Large datasets on genetic polymorphism that can provide an historical benchmark against which to test for recent evolutionary responses are very rare, but an exception is found in the brown-lipped banded snail (Cepaea nemoralis. This species is sensitive to its thermal environment and exhibits several polymorphisms of shell colour and banding pattern affecting shell albedo in the majority of populations within its native range in Europe. We tested for evolutionary changes in shell albedo that might have been driven by the warming of the climate in Europe over the last half century by compiling an historical dataset for 6,515 native populations of C. nemoralis and comparing this with new data on nearly 3,000 populations. The new data were sampled mainly in 2009 through the Evolution MegaLab, a citizen science project that engaged thousands of volunteers in 15 countries throughout Europe in the biggest such exercise ever undertaken. A known geographic cline in the frequency of the colour phenotype with the highest albedo (yellow was shown to have persisted and a difference in colour frequency between woodland and more open habitats was confirmed, but there was no general increase in the frequency of yellow shells. This may have been because snails adapted to a warming climate through behavioural thermoregulation. By contrast, we detected an unexpected decrease in the frequency of Unbanded shells and an increase in the Mid-banded morph. Neither of these evolutionary changes appears to be a direct response to climate change, indicating that the influence of other selective agents, possibly related to changing predation pressure and habitat change with effects on micro-climate.

Novel binding motif and new flexibility revealed by structural analyses of a pyruvate dehydrogenase-dihydrolipoyl acetyltransferase subcomplex from the Escherichia coli pyruvate dehydrogenase multienzyme complex.

Science.gov (United States)

Arjunan, Palaniappa; Wang, Junjie; Nemeria, Natalia S; Reynolds, Shelley; Brown, Ian; Chandrasekhar, Krishnamoorthy; Calero, Guillermo; Jordan, Frank; Furey, William

2014-10-24

The Escherichia coli pyruvate dehydrogenase multienzyme complex contains multiple copies of three enzymatic components, E1p, E2p, and E3, that sequentially carry out distinct steps in the overall reaction converting pyruvate to acetyl-CoA. Efficient functioning requires the enzymatic components to assemble into a large complex, the integrity of which is maintained by tethering of the displaced, peripheral E1p and E3 components to the E2p core through non-covalent binding. We here report the crystal structure of a subcomplex between E1p and an E2p didomain containing a hybrid lipoyl domain along with the peripheral subunit-binding domain responsible for tethering to the core. In the structure, a region at the N terminus of each subunit in the E1p homodimer previously unseen due to crystallographic disorder was observed, revealing a new folding motif involved in E1p-E2p didomain interactions, and an additional, unexpected, flexibility was discovered in the E1p-E2p didomain subcomplex, both of which probably have consequences in the overall multienzyme complex assembly. This represents the first structure of an E1p-E2p didomain subcomplex involving a homodimeric E1p, and the results may be applicable to a large range of complexes with homodimeric E1 components. Results of HD exchange mass spectrometric experiments using the intact, wild type 3-lipoyl E2p and E1p are consistent with the crystallographic data obtained from the E1p-E2p didomain subcomplex as well as with other biochemical and NMR data reported from our groups, confirming that our findings are applicable to the entire E1p-E2p assembly. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Novel Binding Motif and New Flexibility Revealed by Structural Analyses of a Pyruvate Dehydrogenase-Dihydrolipoyl Acetyltransferase Subcomplex from the Escherichia coli Pyruvate Dehydrogenase Multienzyme Complex*

Science.gov (United States)

Arjunan, Palaniappa; Wang, Junjie; Nemeria, Natalia S.; Reynolds, Shelley; Brown, Ian; Chandrasekhar, Krishnamoorthy; Calero, Guillermo; Jordan, Frank; Furey, William

2014-01-01

The Escherichia coli pyruvate dehydrogenase multienzyme complex contains multiple copies of three enzymatic components, E1p, E2p, and E3, that sequentially carry out distinct steps in the overall reaction converting pyruvate to acetyl-CoA. Efficient functioning requires the enzymatic components to assemble into a large complex, the integrity of which is maintained by tethering of the displaced, peripheral E1p and E3 components to the E2p core through non-covalent binding. We here report the crystal structure of a subcomplex between E1p and an E2p didomain containing a hybrid lipoyl domain along with the peripheral subunit-binding domain responsible for tethering to the core. In the structure, a region at the N terminus of each subunit in the E1p homodimer previously unseen due to crystallographic disorder was observed, revealing a new folding motif involved in E1p-E2p didomain interactions, and an additional, unexpected, flexibility was discovered in the E1p-E2p didomain subcomplex, both of which probably have consequences in the overall multienzyme complex assembly. This represents the first structure of an E1p-E2p didomain subcomplex involving a homodimeric E1p, and the results may be applicable to a large range of complexes with homodimeric E1 components. Results of HD exchange mass spectrometric experiments using the intact, wild type 3-lipoyl E2p and E1p are consistent with the crystallographic data obtained from the E1p-E2p didomain subcomplex as well as with other biochemical and NMR data reported from our groups, confirming that our findings are applicable to the entire E1p-E2p assembly. PMID:25210042

Phylogenetic analysis of glycerol 3-phosphate acyltransferases in opisthokonts reveals unexpected ancestral complexity and novel modern biosynthetic components.

Directory of Open Access Journals (Sweden)

Heather C Smart

Full Text Available Glycerolipid synthesis represents a central metabolic process of all forms of life. In the last decade multiple genes coding for enzymes responsible for the first step of the pathway, catalyzed by glycerol 3-phosphate acyltransferase (GPAT, have been described, and characterized primarily in model organisms like Saccharomyces cerevisiae and mice. Notoriously, the fungal enzymes share low sequence identity with their known animal counterparts, and the nature of their homology is unclear. Furthermore, two mitochondrial GPAT isoforms have been described in animal cells, while no such enzymes have been identified in Fungi. In order to determine if the yeast and mammalian GPATs are representative of the set of enzymes present in their respective groups, and to test the hypothesis that metazoan orthologues are indeed absent from the fungal clade, a comparative genomic and phylogenetic analysis was performed including organisms spanning the breadth of the Opisthokonta supergroup. Surprisingly, our study unveiled the presence of 'fungal' orthologs in the basal taxa of the holozoa and 'animal' orthologues in the basal holomycetes. This includes a novel clade of fungal homologues, with putative peroxisomal targeting signals, of the mitochondrial/peroxisomal acyltransferases in Metazoa, thus potentially representing an undescribed metabolic capacity in the Fungi. The overall distribution of GPAT homologues is suggestive of high relative complexity in the ancestors of the opisthokont clade, followed by loss and sculpting of the complement in the descendent lineages. Divergence from a general versatile metabolic model, present in ancestrally deduced GPAT complements, points to distinctive contributions of each GPAT isoform to lipid metabolism and homeostasis in contemporary organisms like humans and their fungal pathogens.

Rural families' interpretations of experiencing unexpected transition in the wake of a natural disaster.

Science.gov (United States)

Fernandes, Gisele Cristina Manfrini; Boehs, Astrid Eggert; Denham, Sharon A; Nitschke, Rosane Gonçalves; Martini, Jussara Gue

2017-02-13

Natural disasters affect populations in various parts of the world. The impacts of disasters can cause many problems to the health of people and disruption to family life, potentially leading to an unexpected transition. The objective of this paper is to present the unexpected transitional experiences of rural families following a natural disaster. A multiple case study of six families was conducted with children and adolescents in a rural area affected by a 2008 disaster in southern Brazil. For data collection, we used participant observation, narrative interviews, genograms, ecomaps and an instrument called calendar routine. The analysis of the data resulted in different family interpretations about the changes resulting from the storm and compared life before and after the disaster. The loss of homes and loved ones, migration, unemployment, and losses from the farm were the main changes associated with new development tasks. The experiences of family transition after the disaster revealed that losses influenced social lives, daily routines and the preservation of cultural values.

77 FR 21389 - Unexpected Urgent Refugee and Migration Needs

Science.gov (United States)

2012-04-10

... April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the... 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the ``Act''), as amended, (22 U.S.C... United States Emergency Refugee and Migration Assistance Fund, for the purpose of meeting unexpected and...

Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex

DEFF Research Database (Denmark)

Laursen, Nick Stub; Andersen, Kasper Røjkjær; Braren, Ingke

2011-01-01

with a protease subunit (Bb or C2a). We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. The structures reveal a parallel two-point attachment between C5 and CVF, where the presence of SSL7 only...

Unexpected findings after surgery for suspected appendicitis rarely change treatment in pediatric patients; Results from a cohort study.

Science.gov (United States)

Gorter, Ramon R; van Amstel, Paul; van der Lee, Johanna H; van der Voorn, Patick; Bakx, Roel; Heij, Hugo A

2017-08-01

To determine if non-operative treatment is safe in children with acute appendicitis, we evaluated the incidence of unexpected findings after an appendectomy in children, and the influence they have on subsequent treatment. A historical cohort study (January 2004-December 2014) was performed including children, aged 0-17 years, who underwent an appendectomy for the suspicion of acute appendicitis. Patients were divided based upon histopathological examination. Unexpected findings were reviewed, as well as the subsequent treatment plan. In total 484 patients were included in this study. In the overall group, unexpected findings were noted in 10 (2.1%) patients of which two patients intra-operatively with a non-inflamed appendix (Ileitis terminalis N=1 and ovarian torsion N=1) and in 8 patients on histopathological examination. The latter group consisted of 4 patients with concomitant simple appendicitis (parasitic infection N=3 and Walthard cell rest N=1), two with concomitant complex appendicitis (carcinoid N=1 and parasitic infection N=1) and two patients with a non-inflamed appendix (endometriosis N=1 and parasitic infection N=1). Treatment was changed in 4 patients (appendicitis, as the occurrence of unexpected findings was low, with extremely few necessary changes of the treatment plan because of serious findings. Prognosis study. Level 2 (retrospective cohort study). Copyright © 2017 Elsevier Inc. All rights reserved.

Micro-CT scan reveals an unexpected high-volume and interconnected pore network in a Cretaceous Sanagasta dinosaur eggshell.

Science.gov (United States)

Hechenleitner, E Martín; Grellet-Tinner, Gerald; Foley, Matthew; Fiorelli, Lucas E; Thompson, Michael B

2016-03-01

The Cretaceous Sanagasta neosauropod nesting site (La Rioja, Argentina) was the first confirmed instance of extinct dinosaurs using geothermal-generated heat to incubate their eggs. The nesting strategy and hydrothermal activities at this site led to the conclusion that the surprisingly 7 mm thick-shelled eggs were adapted to harsh hydrothermal microenvironments. We used micro-CT scans in this study to obtain the first three-dimensional microcharacterization of these eggshells. Micro-CT-based analyses provide a robust assessment of gas conductance in fossil dinosaur eggshells with complex pore canal systems, allowing calculation, for the first time, of the shell conductance through its thickness. This novel approach suggests that the shell conductance could have risen during incubation to seven times more than previously estimated as the eggshell erodes. In addition, micro-CT observations reveal that the constant widening and branching of pore canals form a complex funnel-like pore canal system. Furthermore, the high density of pore canals and the presence of a lateral canal network in the shell reduce the risks of pore obstruction during the extended incubation of these eggs in a relatively highly humid and muddy nesting environment. © 2016 The Author(s).

Screening of random peptide library of hemagglutinin from pandemic 2009 A(H1N1 influenza virus reveals unexpected antigenically important regions.

Directory of Open Access Journals (Sweden)

Wanghui Xu

Full Text Available The antigenic structure of the membrane protein hemagglutinin (HA from the 2009 A(H1N1 influenza virus was dissected with a high-throughput screening method using complex antisera. The approach involves generating yeast cell libraries displaying a pool of random peptides of controllable lengths on the cell surface, followed by one round of fluorescence-activated cell sorting (FACS against antisera from mouse, goat and human, respectively. The amino acid residue frequency appearing in the antigenic peptides at both the primary sequence and structural level was determined and used to identify "hot spots" or antigenically important regions. Unexpectedly, different antigenic structures were seen for different antisera. Moreover, five antigenic regions were identified, of which all but one are located in the conserved HA stem region that is responsible for membrane fusion. Our findings are corroborated by several recent studies on cross-neutralizing H1 subtype antibodies that recognize the HA stem region. The antigenic peptides identified may provide clues for creating peptide vaccines with better accessibility to memory B cells and better induction of cross-neutralizing antibodies than the whole HA protein. The scheme used in this study enables a direct mapping of the antigenic regions of viral proteins recognized by antisera, and may be useful for dissecting the antigenic structures of other viral proteins.

[Development of the unexpected reality scale for childcare training].

Science.gov (United States)

Matsuda, Yuko; Shitara, Saeko; Hamada, Shoko

2016-10-01

This study aimed to develop a scale for unexpected reality for childcare training (Study 1) and examine the change and influence it exerts on the efficacy of preschool teachers (Study 2). In Study 1, the sample consisted of 571 university and junior college students enrolled in a childcare course. After exploratory factor analysis, four factors were extracted: “actual feelings for childcare as a field of study,” “difficulties faced during involvement with children,” “negative aspects of the childcare worker,” and “severity of work.” The study’s scale was shown to be internally consistent and valid. In Study 2, the sample consisted of 122 junior college students enrolled in a childcare course. The results showed that the high-scoring groups of each unexpected reality subscales experienced less unexpected reality in the subsequent training session. Moreover, the results of multiple regression showed that preschool teacher efficacy was predicted positively by “actual feelings for childcare as a field of study” and negatively by “difficulties faced during involvement with children.” Thus, we suggest that for effective pre- and post-guidance of childcare training, unexpected realities should be considered.

Biogenesis of the yeast cytochrome bc1 complex.

Science.gov (United States)

Zara, Vincenzo; Conte, Laura; Trumpower, Bernard L

2009-01-01

The mitochondrial respiratory chain is composed of four different protein complexes that cooperate in electron transfer and proton pumping across the inner mitochondrial membrane. The cytochrome bc1 complex, or complex III, is a component of the mitochondrial respiratory chain. This review will focus on the biogenesis of the bc1 complex in the mitochondria of the yeast Saccharomyces cerevisiae. In wild type yeast mitochondrial membranes the major part of the cytochrome bc1 complex was found in association with one or two copies of the cytochrome c oxidase complex. The analysis of several yeast mutant strains in which single genes or pairs of genes encoding bc1 subunits had been deleted revealed the presence of a common set of bc1 sub-complexes. These sub-complexes are represented by the central core of the bc1 complex, consisting of cytochrome b bound to subunit 7 and subunit 8, by the two core proteins associated with each other, by the Rieske protein associated with subunit 9, and by those deriving from the unexpected interaction of each of the two core proteins with cytochrome c1. Furthermore, a higher molecular mass sub-complex is that composed of cytochrome b, cytochrome c1, core protein 1 and 2, subunit 6, subunit 7 and subunit 8. The identification and characterization of all these sub-complexes may help in defining the steps and the molecular events leading to bc1 assembly in yeast mitochondria.

Structural imaging biomarkers of sudden unexpected death in epilepsy.

Science.gov (United States)

Wandschneider, Britta; Koepp, Matthias; Scott, Catherine; Micallef, Caroline; Balestrini, Simona; Sisodiya, Sanjay M; Thom, Maria; Harper, Ronald M; Sander, Josemir W; Vos, Sjoerd B; Duncan, John S; Lhatoo, Samden; Diehl, Beate

2015-10-01

Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies. The Author (2015). Published by Oxford University Press on behalf of the Guarantors of

An unexpected clade of South American ground beetles (Coleoptera, Carabidae, Bembidion).

Science.gov (United States)

Maddison, David R

2014-01-01

Phylogenetic relationships of the Antiperyphanes Complex of the genus Bembidion are inferred using DNA sequences from seven genes (two nuclear ribosomal, four nuclear protein coding, and one mitochondrial protein coding). Redefined subgenera within the complex are each well-supported as monophyletic. Most striking was the discovery that a small set of morphologically and ecologically heterogeneous species formed a clade, here called subgenus Nothonepha. This unexpected result was corroborated by the discovery of deep pits in the lateral body wall (in the mesepisternum) of all Nothonepha, a trait unique within Bembidion. These pits are filled with a waxy substance in ethanol-preserved specimens. In one newly discovered species (Bembidion tetrapholeon sp. n., described here), these pits are so deep that their projections into the body cavity from the two sides touch each other internally. These structures in Bembidion (Nothonepha) are compared to very similar mesepisternal pits which have convergently evolved in two other groups of carabid beetles. The function of these thoracic pits is unknown. Most members of subgenus Nothonepha have in addition similar but smaller pits in the abdomen. A revised classification is proposed for the Antiperyphanes Complex.

An unexpected clade of South American ground beetles (Coleoptera, Carabidae, Bembidion

Directory of Open Access Journals (Sweden)

David Maddison

2014-06-01

Full Text Available Phylogenetic relationships of the Antiperyphanes Complex of the genus Bembidion are inferred using DNA sequences from seven genes (two nuclear ribosomal, four nuclear protein coding, and one mitochondrial protein coding. Redefined subgenera within the complex are each well-supported as monophyletic. Most striking was the discovery that a small set of morphologically and ecologically heterogeneous species formed a clade, here called subgenus Nothonepha. This unexpected result was corroborated by the discovery of deep pits in the lateral body wall (in the mesepisternum of all Nothonepha, a trait unique within Bembidion. These pits are filled with a waxy substance in ethanol-preserved specimens. In one newly discovered species (Bembidion tetrapholeon sp. n., described here, these pits are so deep that their projections into the body cavity from the two sides touch each other internally. These structures in Bembidion (Nothonepha are compared to very similar mesepisternal pits which have convergently evolved in two other groups of carabid beetles. The function of these thoracic pits is unknown. Most members of subgenus Nothonepha have in addition similar but smaller pits in the abdomen. A revised classification is proposed for the Antiperyphanes Complex.

Out of Mind, Out of Sight: Unexpected Scene Elements Frequently Go Unnoticed Until Primed.

Science.gov (United States)

Slavich, George M; Zimbardo, Philip G

2013-12-01

The human visual system employs a sophisticated set of strategies for scanning the environment and directing attention to stimuli that can be expected given the context and a person's past experience. Although these strategies enable us to navigate a very complex physical and social environment, they can also cause highly salient, but unexpected stimuli to go completely unnoticed. To examine the generality of this phenomenon, we conducted eight studies that included 15 different experimental conditions and 1,577 participants in all. These studies revealed that a large majority of participants do not report having seen a woman in the center of an urban scene who was photographed in midair as she was committing suicide. Despite seeing the scene repeatedly, 46 % of all participants failed to report seeing a central figure and only 4.8 % reported seeing a falling person. Frequency of noticing the suicidal woman was highest for participants who read a narrative priming story that increased the extent to which she was schematically congruent with the scene. In contrast to this robust effect of inattentional blindness , a majority of participants reported seeing other peripheral objects in the visual scene that were equally difficult to detect, yet more consistent with the scene. Follow-up qualitative analyses revealed that participants reported seeing many elements that were not actually present, but which could have been expected given the overall context of the scene. Together, these findings demonstrate the robustness of inattentional blindness and highlight the specificity with which different visual primes may increase noticing behavior.

Rural families' interpretations of experiencing unexpected transition in the wake of a natural disaster

Directory of Open Access Journals (Sweden)

Gisele Cristina Manfrini Fernandes

Full Text Available Abstract: Natural disasters affect populations in various parts of the world. The impacts of disasters can cause many problems to the health of people and disruption to family life, potentially leading to an unexpected transition. The objective of this paper is to present the unexpected transitional experiences of rural families following a natural disaster. A multiple case study of six families was conducted with children and adolescents in a rural area affected by a 2008 disaster in southern Brazil. For data collection, we used participant observation, narrative interviews, genograms, ecomaps and an instrument called calendar routine. The analysis of the data resulted in different family interpretations about the changes resulting from the storm and compared life before and after the disaster. The loss of homes and loved ones, migration, unemployment, and losses from the farm were the main changes associated with new development tasks. The experiences of family transition after the disaster revealed that losses influenced social lives, daily routines and the preservation of cultural values.

Unexpected marked seizure improvement in paediatric epilepsy surgery candidates

DEFF Research Database (Denmark)

Hoei-Hansen, Christina E; Mathiasen, René; Uldall, Peter

2017-01-01

PURPOSE: Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number...... of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. METHODS: We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. RESULTS......: At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number...

An unexpected phosphate binding site in Glyceraldehyde 3-Phosphate Dehydrogenase: Crystal structures of apo, holo and ternary complex of Cryptosporidium parvum enzyme

Energy Technology Data Exchange (ETDEWEB)

Cook, William J; Senkovich, Olga; Chattopadhyay, Debasish; (UAB)

2009-06-08

occupies an unexpected site not seen before and the phosphate binding loop remains in the substrate-free conformation. Orientation of the substrate with respect to the active site histidine and serine (in the mutant enzyme) also varies in different subunits. The structures of the C. parvum GAPDH ternary complex and other GAPDH complexes demonstrate the plasticity of the substrate binding site. We propose that the active site of GAPDH can accommodate the substrate in multiple conformations at multiple locations during the initial encounter. However, the C-3 phosphate group clearly prefers the 'new Pi' site for initial binding in the active site.

An unexpected phosphate binding site in Glyceraldehyde 3-Phosphate Dehydrogenase: Crystal structures of apo, holo and ternary complex of Cryptosporidium parvum enzyme

Directory of Open Access Journals (Sweden)

Chattopadhyay Debasish

2009-02-01

Full Text Available Abstract Background The structure, function and reaction mechanism of glyceraldehyde 3-phosphate dehydrogenase (GAPDH have been extensively studied. Based on these studies, three anion binding sites have been identified, one 'Ps' site (for binding the C-3 phosphate of the substrate and two sites, 'Pi' and 'new Pi', for inorganic phosphate. According to the original flip-flop model, the substrate phosphate group switches from the 'Pi' to the 'Ps' site during the multistep reaction. In light of the discovery of the 'new Pi' site, a modified flip-flop mechanism, in which the C-3 phosphate of the substrate binds to the 'new Pi' site and flips to the 'Ps' site before the hydride transfer, was proposed. An alternative model based on a number of structures of B. stearothermophilus GAPDH ternary complexes (non-covalent and thioacyl intermediate proposes that in the ternary Michaelis complex the C-3 phosphate binds to the 'Ps' site and flips from the 'Ps' to the 'new Pi' site during or after the redox step. Results We determined the crystal structure of Cryptosporidium parvum GAPDH in the apo and holo (enzyme + NAD state and the structure of the ternary enzyme-cofactor-substrate complex using an active site mutant enzyme. The C. parvum GAPDH complex was prepared by pre-incubating the enzyme with substrate and cofactor, thereby allowing free movement of the protein structure and substrate molecules during their initial encounter. Sulfate and phosphate ions were excluded from purification and crystallization steps. The quality of the electron density map at 2Å resolution allowed unambiguous positioning of the substrate. In three subunits of the homotetramer the C-3 phosphate group of the non-covalently bound substrate is in the 'new Pi' site. A concomitant movement of the phosphate binding loop is observed in these three subunits. In the fourth subunit the C-3 phosphate occupies an unexpected site not seen before and the phosphate binding loop remains in

Unexpected findings at imaging: Predicting frequency in various types of studies

International Nuclear Information System (INIS)

Lumbreras, Blanca; Gonzalez-Alvarez, Isabel; Lorente, Ma Fernanda; Calbo, Jorge; Aranaz, Jesus; Hernandez-Aguado, Ildefonso

2010-01-01

Objective: The objective was to evaluate the prevalence and associated variables of unsuspected findings from imaging tests in clinical practice. Material and Methods: Cross-sectional study of patients referred for an imaging test in 2006. Two independent radiologists classified the imaging tests according to the presence or absence of an unexpected finding in relation with the causes that prompted the test (kappa = 0.95). A thorough chart review of these patients was carried out as a quality control. Results: Out of 3259 patients in the study, 488 revealed unsuspected findings (15.0%). The prevalence of abnormal findings varied according to age: from 20.4% (150/734) in the over 74-group to 9.0% (76/847) in the under 43-group. The largest prevalence was in the category of infectious diseases (14/49, 28.6%) and in CT (260/901, 28.9%) and ultrasound (138/668, 20.7%). Studies showing moderate clinical information on the referral form were less likely to show unexpected findings than those with null or minor information (OR 0.51; 95% CI 0.36-0.73). Conclusion: Clinicians should expect the frequency of diseases detectable by imaging to increase in the future. Further research with follow-up of these findings is needed to estimate the effect of imaging technologies on final health outcomes.

Unexpected findings at imaging: Predicting frequency in various types of studies

Energy Technology Data Exchange (ETDEWEB)

Lumbreras, Blanca [Public Health Department, Miguel Hernandez University (Spain); CIBER en Epidemiologia y Salud Publica (Spain)], E-mail: blumbreras@umh.es; Gonzalez-Alvarez, Isabel [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: gonzalez_isa@gva.es; Lorente, Ma Fernanda [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: MARFERLORENTE@telefonica.net; Calbo, Jorge [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: jocalma@hotmail.com; Aranaz, Jesus [Preventive Medicine Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: aranaz_jes@gva.es; Hernandez-Aguado, Ildefonso [Public Health Department, Miguel Hernandez University (Spain); CIBER en Epidemiologia y Salud Publica (Spain)], E-mail: ihernandez@umh.es

2010-04-15

Objective: The objective was to evaluate the prevalence and associated variables of unsuspected findings from imaging tests in clinical practice. Material and Methods: Cross-sectional study of patients referred for an imaging test in 2006. Two independent radiologists classified the imaging tests according to the presence or absence of an unexpected finding in relation with the causes that prompted the test (kappa = 0.95). A thorough chart review of these patients was carried out as a quality control. Results: Out of 3259 patients in the study, 488 revealed unsuspected findings (15.0%). The prevalence of abnormal findings varied according to age: from 20.4% (150/734) in the over 74-group to 9.0% (76/847) in the under 43-group. The largest prevalence was in the category of infectious diseases (14/49, 28.6%) and in CT (260/901, 28.9%) and ultrasound (138/668, 20.7%). Studies showing moderate clinical information on the referral form were less likely to show unexpected findings than those with null or minor information (OR 0.51; 95% CI 0.36-0.73). Conclusion: Clinicians should expect the frequency of diseases detectable by imaging to increase in the future. Further research with follow-up of these findings is needed to estimate the effect of imaging technologies on final health outcomes.

Unexpected consequences of control: competitive vs. predator release in a four-species assemblage of invasive mammals.

Science.gov (United States)

Ruscoe, Wendy A; Ramsey, David S L; Pech, Roger P; Sweetapple, Peter J; Yockney, Ivor; Barron, Mandy C; Perry, Mike; Nugent, Graham; Carran, Roger; Warne, Rodney; Brausch, Chris; Duncan, Richard P

2011-10-01

Invasive species are frequently the target of eradication or control programmes to mitigate their impacts. However, manipulating single species in isolation can lead to unexpected consequences for other species, with outcomes such as mesopredator release demonstrated both theoretically and empirically in vertebrate assemblages with at least two trophic levels. Less is known about the consequences of species removal in more complex assemblages where a greater number of interacting invaders increases the potential for selective species removal to result in unexpected changes in community structure. Using a replicated Before-After Control-Impact field experiment with a four-species assemblage of invasive mammals we show that species interactions in the community are dominated by competition rather than predation. There was no measurable response of two mesopredators (rats and mice) following control of the top predator (stoats), but there was competitive release of rats following removal of a herbivore (possums), and competitive release of mice following removal of rats. © 2011 Blackwell Publishing Ltd/CNRS.

Unexpected Translations in Urban Policy Mobility

DEFF Research Database (Denmark)

Zapata, Patrik; Zapata Campos, Maria José

2015-01-01

such as prototypes in order to travel. It was made mobile via relational sites or situations providing safe and accessible connections with Chureca residents. Paradoxically, these places also allowed extraordinary connections between actors located in different scales and spaces, facilitating unexpected local...

Unexpected Translations in Urban Policy Mobility

DEFF Research Database (Denmark)

Zapata, Patrik; Zapata Campos, Maria José

such as prototypes in order to travel. It was made mobile via relational sites or situations providing safe and accessible connections with Chureca residents. Paradoxically, these places also allowed extraordinary connections between actors located in different scales and spaces, facilitating unexpected local...

Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly

Science.gov (United States)

Cottee, Matthew A; Muschalik, Nadine; Wong, Yao Liang; Johnson, Christopher M; Johnson, Steven; Andreeva, Antonina; Oegema, Karen; Lea, Susan M; Raff, Jordan W; van Breugel, Mark

2013-01-01

Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel proline recognition domain that forms a 1:1 complex with a short, highly conserved target motif in STIL. Crystal structures of this complex reveal an unusual, all-β structure adopted by the TCP domain and explain how a microcephaly mutation in CPAP compromises complex formation. Through point mutations, we demonstrate that complex formation is essential for centriole duplication in vivo. Our studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAP–STIL interaction constitutes a conserved key step in centriole biogenesis. DOI: http://dx.doi.org/10.7554/eLife.01071.001 PMID:24052813

Unexpected Expectations The Curiosities of a Mathematical Crystal Ball

CERN Document Server

Wapner, Leonard M

2012-01-01

Unexpected Expectations: The Curiosities of a Mathematical Crystal Ball explores how paradoxical challenges involving mathematical expectation often necessitate a reexamination of basic premises. The author takes you through mathematical paradoxes associated with seemingly straightforward applications of mathematical expectation and shows how these unexpected contradictions may push you to reconsider the legitimacy of the applications. The book requires only an understanding of basic algebraic operations and includes supplemental mathematical background in chapter appendices. After a history o

On the unexpected oscillation of the total cross section for excitation in He2+ + H collisions

International Nuclear Information System (INIS)

Schultz, D.R.; Reinhold, C.O.; Krstic, P.S.

1996-01-01

Recent calculations and measurements have revealed unexpected oscillations of the total cross section for excitation in low- to intermediate-energy He 2+ + H collisions. A physical explanation of this behavior is given here stemming from analysis of classical trajectory Monte Carlo simulations, molecular orbital close coupling calculations, and solution of the time-dependent Schroedinger equation on a numerical lattice. These results indicate that the observed behavior should be characteristic of a wide range of reactions in ion-atom collisions

Multilayer Stochastic Block Models Reveal the Multilayer Structure of Complex Networks

Directory of Open Access Journals (Sweden)

Toni Vallès-Català

2016-03-01

Full Text Available In complex systems, the network of interactions we observe between systems components is the aggregate of the interactions that occur through different mechanisms or layers. Recent studies reveal that the existence of multiple interaction layers can have a dramatic impact in the dynamical processes occurring on these systems. However, these studies assume that the interactions between systems components in each one of the layers are known, while typically for real-world systems we do not have that information. Here, we address the issue of uncovering the different interaction layers from aggregate data by introducing multilayer stochastic block models (SBMs, a generalization of single-layer SBMs that considers different mechanisms of layer aggregation. First, we find the complete probabilistic solution to the problem of finding the optimal multilayer SBM for a given aggregate-observed network. Because this solution is computationally intractable, we propose an approximation that enables us to verify that multilayer SBMs are more predictive of network structure in real-world complex systems.

An investigation into the causes of unexpected intra-operative transoesophageal echocardiography findings.

Science.gov (United States)

Skinner, H J; Mahmoud, A; Uddin, A; Mathew, T

2012-04-01

There is uncertainty regarding echocardiography before cardiac surgery, especially with regard to timing and disease progression as well as potential errors. We investigated the causes of unexpected intra-operative transoesophageal echocardiography findings by performing a 33-month audit. We found that there were 50/797 (6%) unexpected findings that led to an alteration in surgical strategy in 34 (4%) patients. Of the unexpected findings, 25 (50%) were unrelated to pre-operative pathology. After reviewing pre-operative studies and reports, unexpected findings were found to be due to: reporting errors in 20 patients (44%); limitations in transthoracic compared to transoesophageal echocardiography in 14 patients (30%); disease progression in 10 patients (22%); and inter-observer variability in two patients (4%). We identified six reports out of 797 (0.8%) that contained potentially serious errors. Surgical management changed in 18/20 (90%) patients in whom the unexpected change was due to reporting error, compared to 16/30 (53%) patients whose pre-operative echocardiogram was correctly reported (p = 0.006). Our study suggests that pre-operative echocardiography reporting errors are common and important. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

Unexpectedly large charge radii of neutron-rich calcium isotopes

CERN Document Server

Garcia Ruiz, R F; Blaum, K; Ekström, A; Frömmgen, N; Hagen, G; Hammen, M; Hebeler, K; Holt, J D; Jansen, G R; Kowalska, M; Kreim, K; Nazarewicz, W; Neugart, R; Neyens, G; Nörtershäuser, W; Papenbrock, T; Papuga, J; Schwenk, A; Simonis, J; Wendt, K A; Yordanov, D T

2016-01-01

Despite being a complex many-body system, the atomic nucleus exhibits simple structures for certain ‘magic’ numbers of protons and neutrons. The calcium chain in particular is both unique and puzzling: evidence of doubly magic features are known in 40,48Ca, and recently suggested in two radioactive isotopes, 52,54Ca. Although many properties of experimentally known calcium isotopes have been successfully described by nuclear theory, it is still a challenge to predict the evolution of their charge radii. Here we present the first measurements of the charge radii of 49,51,52Ca, obtained from laser spectroscopy experiments at ISOLDE, CERN. The experimental results are complemented by state-of-the-art theoretical calculations. The large and unexpected increase of the size of the neutron-rich calcium isotopes beyond N = 28 challenges the doubly magic nature of 52Ca and opens new intriguing questions on the evolution of nuclear sizes away from stability, which are of importance for our understanding of neutron-...

Cannibalistic-morph Tiger Salamanders in unexpected ecological contexts

Science.gov (United States)

McLean, Kyle I.; Stockwell, Craig A.; Mushet, David M.

2016-01-01

Barred tiger salamanders [Ambystoma mavortium (Baird, 1850)] exhibit two trophic morphologies; a typical and a cannibalistic morph. Cannibalistic morphs, distinguished by enlarged vomerine teeth, wide heads, slender bodies, and cannibalistic tendencies, are often found where conspecifics occur at high density. During 2012 and 2013, 162 North Dakota wetlands and lakes were sampled for salamanders. Fifty-one contained A. mavortium populations; four of these contained cannibalistic morph individuals. Two populations with cannibalistic morphs occurred at sites with high abundances of conspecifics. However, the other two populations occurred at sites with unexpectedly low conspecific but high fathead minnow [Pimephales promelas (Rafinesque, 1820)] abundances. Further, no typical morphs were observed in either of these later two populations, contrasting with earlier research suggesting cannibalistic morphs only occur at low frequencies in salamander populations. Another anomaly of all four populations was the occurrence of cannibalistic morphs in permanent water sites, suggesting their presence was due to factors other than faster growth allowing them to occupy ephemeral habitats. Therefore, our findings suggest environmental factors inducing the cannibalistic morphism may be more complex than previously thought.

Unexpected dramatic increase in CD4+ cell count in a patient with AIDS after enfuvirtide treatment despite persistent viremia and resistance mutations.

Science.gov (United States)

Soria, Alessandro; Cavarelli, Mariangela; Sala, Stefania; Alessandrini, Anna Ida; Scarlatti, Gabriella; Lazzarin, Adriano; Castagna, Antonella

2008-06-01

An unexpected dramatic immune recovery was observed in a patient with full-blown AIDS receiving enfuvirtide-based antiretroviral therapy after multiple treatment failures. A complex interplay of viral and host factors, including the control of X4 viruses and proviral burden, may favor immune restoration with HIV neutralizing activity, despite persistent viremia.

Unexpected Coexisting Myocardial Infarction Detected by Delayed Enhancement MRI

Directory of Open Access Journals (Sweden)

Edouard Gerbaud

2009-01-01

Full Text Available We report a case of an unexpected coexisting anterior myocardial infarction detected by delayed enhancement MRI in a 41-year-old man following a presentation with a first episode of chest pain during inferior acute myocardial infarction. This second necrotic area was not initially suspected because there were no ECG changes in the anterior leads and the left descending coronary artery did not present any significant stenoses on emergency coronary angiography. Unrecognised myocardial infarction may carry important prognostic implications. CMR is currently the best imaging technique to detect unexpected infarcts.

The accrual anomaly - focus on changes in specific unexpected accruals results in new evidence

DEFF Research Database (Denmark)

Schøler, Finn

are specifically analyzed, namely the unexpected inventory accrual component and the unexpected accounts receivable accrual component, i.e. changes in accruals not motivated by corresponding changes in company activity-level. Additionally and for comparison, the accounting accruals are split into expected...... and unexpected accruals, estimated by the extended Jones model like in both some US-analyses and some international studies of the accrual anomaly phenomenon. It is found that the persistence of earnings is decreasing in the magnitude of the unexpected accrual components of earnings and that the persistence...... of current earnings performance is particularly decreasing in the magnitude of unexpected changes in inventory. The special accrual parts are related to the perceptions of earnings persistence implicit in the market prices, and it is found that the differences in earnings persistence are not rationally...

Understanding and revisiting the most complex perovskite system via atomistic simulations

Science.gov (United States)

Yang, Yali; Xu, Bin; Xu, Changsong; Ren, Wei; Bellaiche, Laurent

2018-05-01

A first-principles-based effective Hamiltonian is developed and used, along with direct ab initio techniques, to investigate finite-temperature properties of the system commonly coined the most complex perovskite, that is NaNbO3. Such simulations successfully reproduce the existence of seven different phases in its phase diagram. The decomposition of the total energy of this effective Hamiltonian into different terms, altogether with the values of the parameters associated with these terms, also allow us to shed some light into puzzling features of such a compound. Examples include revealing the microscopic reasons of why R 3 c is its ground state and why it solely adopts in-phase tiltings at high temperatures versus complex nanotwins for intermediate temperatures. The results of the computations also call for a revisiting of the so-called P ,R , and S states, in the sense that an unexpected and previously overlooked inhomogeneous electrical polarization is numerically found in the P state while complex tiltings associated with the simultaneous condensation of several k points are predicted for the controversial R and S phases.

Bah humbug: Unexpected Christmas cards and the reciprocity norm.

Science.gov (United States)

Meier, Brian P

2016-01-01

The reciprocity norm refers to the expectation that people will help those who helped them. A well-known study revealed that the norm is strong with Christmas cards, with 20% of people reciprocating a Christmas card received from a stranger. I attempted to conceptually replicate and extend this effect. In Study 1, 755 participants received a Christmas card supposedly from a more- versus less-similar stranger. The reciprocation rate was unexpectedly low (2%), which did not allow for a test of a similarity effect. Two potential reasons for this low rate were examined in Study 2 in which 494 participants reported their likelihood of reciprocating a Christmas card from a stranger as well as their felt suspicions/threat about the card and their frequency of e-mail use. Reciprocation likelihood was negatively correlated with perceived threat/suspicion and e-mail use. It appears that reciprocating a gift from a stranger in offline settings may be less likely than expected.

454 sequencing reveals extreme complexity of the class II Major Histocompatibility Complex in the collared flycatcher

Directory of Open Access Journals (Sweden)

Gustafsson Lars

2010-12-01

Full Text Available Abstract Background Because of their functional significance, the Major Histocompatibility Complex (MHC class I and II genes have been the subject of continuous interest in the fields of ecology, evolution and conservation. In some vertebrate groups MHC consists of multiple loci with similar alleles; therefore, the multiple loci must be genotyped simultaneously. In such complex systems, understanding of the evolutionary patterns and their causes has been limited due to challenges posed by genotyping. Results Here we used 454 amplicon sequencing to characterize MHC class IIB exon 2 variation in the collared flycatcher, an important organism in evolutionary and immuno-ecological studies. On the basis of over 152,000 sequencing reads we identified 194 putative alleles in 237 individuals. We found an extreme complexity of the MHC class IIB in the collared flycatchers, with our estimates pointing to the presence of at least nine expressed loci and a large, though difficult to estimate precisely, number of pseudogene loci. Many similar alleles occurred in the pseudogenes indicating either a series of recent duplications or extensive concerted evolution. The expressed alleles showed unambiguous signals of historical selection and the occurrence of apparent interlocus exchange of alleles. Placing the collared flycatcher's MHC sequences in the context of passerine diversity revealed transspecific MHC class II evolution within the Muscicapidae family. Conclusions 454 amplicon sequencing is an effective tool for advancing our understanding of the MHC class II structure and evolutionary patterns in Passeriformes. We found a highly dynamic pattern of evolution of MHC class IIB genes with strong signals of selection and pronounced sequence divergence in expressed genes, in contrast to the apparent sequence homogenization in pseudogenes. We show that next generation sequencing offers a universal, affordable method for the characterization and, in perspective

Unexpected Binding Mode of a Potent Indeno[1,2-b]indole-Type Inhibitor of Protein Kinase CK2 Revealed by Complex Structures with the Catalytic Subunit CK2α and Its Paralog CK2α′

Directory of Open Access Journals (Sweden)

Jennifer Hochscherf

2017-12-01

Full Text Available Protein kinase CK2, a member of the eukaryotic protein kinase superfamily, is associated with cancer and other human pathologies and thus an attractive drug target. The indeno[1,2-b]indole scaffold is a novel lead structure to develop ATP-competitive CK2 inhibitors. Some indeno[1,2-b]indole-based CK2 inhibitors additionally obstruct ABCG2, an ABC half transporter overexpressed in breast cancer and co-responsible for drug efflux and resistance. Comprehensive derivatization studies revealed substitutions of the indeno[1,2-b]indole framework that boost either the CK2 or the ABCG2 selectivity or even support the dual inhibition potential. The best indeno[1,2-b]indole-based CK2 inhibitor described yet (IC50 = 25 nM is 5-isopropyl-4-(3-methylbut-2-enyl-oxy-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (4p. Herein, we demonstrate the membrane permeability of 4p and describe co-crystal structures of 4p with CK2α and CK2α′, the paralogs of human CK2 catalytic subunit. As expected, 4p occupies the narrow, hydrophobic ATP site of CK2α/CK2α′, but surprisingly with a unique orientation: its hydrophobic substituents point towards the solvent while its two oxo groups are hydrogen-bonded to a hidden water molecule. An equivalent water molecule was found in many CK2α structures, but never as a critical mediator of ligand binding. This unexpected binding mode is independent of the interdomain hinge/helix αD region conformation and of the salt content in the crystallization medium.

Beyond Contagion: Reality Mining Reveals Complex Patterns of Social Influence.

Directory of Open Access Journals (Sweden)

Aamena Alshamsi

Full Text Available Contagion, a concept from epidemiology, has long been used to characterize social influence on people's behavior and affective (emotional states. While it has revealed many useful insights, it is not clear whether the contagion metaphor is sufficient to fully characterize the complex dynamics of psychological states in a social context. Using wearable sensors that capture daily face-to-face interaction, combined with three daily experience sampling surveys, we collected the most comprehensive data set of personality and emotion dynamics of an entire community of work. From this high-resolution data about actual (rather than self-reported face-to-face interaction, a complex picture emerges where contagion (that can be seen as adaptation of behavioral responses to the behavior of other people cannot fully capture the dynamics of transitory states. We found that social influence has two opposing effects on states: adaptation effects that go beyond mere contagion, and complementarity effects whereby individuals' behaviors tend to complement the behaviors of others. Surprisingly, these effects can exhibit completely different directions depending on the stable personality or emotional dispositions (stable traits of target individuals. Our findings provide a foundation for richer models of social dynamics, and have implications on organizational engineering and workplace well-being.

Beyond Contagion: Reality Mining Reveals Complex Patterns of Social Influence.

Science.gov (United States)

Alshamsi, Aamena; Pianesi, Fabio; Lepri, Bruno; Pentland, Alex; Rahwan, Iyad

2015-01-01

Contagion, a concept from epidemiology, has long been used to characterize social influence on people's behavior and affective (emotional) states. While it has revealed many useful insights, it is not clear whether the contagion metaphor is sufficient to fully characterize the complex dynamics of psychological states in a social context. Using wearable sensors that capture daily face-to-face interaction, combined with three daily experience sampling surveys, we collected the most comprehensive data set of personality and emotion dynamics of an entire community of work. From this high-resolution data about actual (rather than self-reported) face-to-face interaction, a complex picture emerges where contagion (that can be seen as adaptation of behavioral responses to the behavior of other people) cannot fully capture the dynamics of transitory states. We found that social influence has two opposing effects on states: adaptation effects that go beyond mere contagion, and complementarity effects whereby individuals' behaviors tend to complement the behaviors of others. Surprisingly, these effects can exhibit completely different directions depending on the stable personality or emotional dispositions (stable traits) of target individuals. Our findings provide a foundation for richer models of social dynamics, and have implications on organizational engineering and workplace well-being.

Geometric Mechanics Reveals Optimal Complex Terrestrial Undulation Patterns

Science.gov (United States)

Gong, Chaohui; Astley, Henry; Schiebel, Perrin; Dai, Jin; Travers, Matthew; Goldman, Daniel; Choset, Howie; CMU Team; GT Team

Geometric mechanics offers useful tools for intuitively analyzing biological and robotic locomotion. However, utility of these tools were previously restricted to systems that have only two internal degrees of freedom and in uniform media. We show kinematics of complex locomotors that make intermittent contacts with substrates can be approximated as a linear combination of two shape bases, and can be represented using two variables. Therefore, the tools of geometric mechanics can be used to analyze motions of locomotors with many degrees of freedom. To demonstrate the proposed technique, we present studies on two different types of snake gaits which utilize combinations of waves in the horizontal and vertical planes: sidewinding (in the sidewinder rattlesnake C. cerastes) and lateral undulation (in the desert specialist snake C. occipitalis). C. cerastes moves by generating posteriorly traveling body waves in the horizontal and vertical directions, with a relative phase offset equal to +/-π/2 while C. occipitalismaintains a π/2 offset of a frequency doubled vertical wave. Geometric analysis reveals these coordination patterns enable optimal movement in the two different styles of undulatory terrestrial locomotion. More broadly, these examples demonstrate the utility of geometric mechanics in analyzing realistic biological and robotic locomotion.

A new fossil from the mid-Paleocene of New Zealand reveals an unexpected diversity of world's oldest penguins

Science.gov (United States)

Mayr, Gerald; De Pietri, Vanesa L.; Paul Scofield, R.

2017-04-01

We describe leg bones of a giant penguin from the mid-Paleocene Waipara Greensand of New Zealand. The specimens were found at the type locality of Waimanu manneringi and together with this species they constitute the oldest penguin fossils known to date. Tarsometatarsus dimensions indicate a species that reached the size of Anthropornis nordenskjoeldi, one of the largest known penguin species. Stem group penguins therefore attained a giant size very early in their evolution, with this gigantism existing for more than 30 million years. The new fossils are from a species that is phylogenetically more derived than Waimanu, and the unexpected coexistence of Waimanu with more derived stem group Sphenisciformes documents a previously unknown diversity amongst the world's oldest penguins. The characteristic tarsometatarsus shape of penguins evolved early on, and the significant morphological disparity between Waimanu and the new fossil conflicts with recent Paleocene divergence estimates for penguins, suggesting an older, Late Cretaceous, origin.

A new fossil from the mid-Paleocene of New Zealand reveals an unexpected diversity of world's oldest penguins.

Science.gov (United States)

Mayr, Gerald; De Pietri, Vanesa L; Paul Scofield, R

2017-04-01

We describe leg bones of a giant penguin from the mid-Paleocene Waipara Greensand of New Zealand. The specimens were found at the type locality of Waimanu manneringi and together with this species they constitute the oldest penguin fossils known to date. Tarsometatarsus dimensions indicate a species that reached the size of Anthropornis nordenskjoeldi, one of the largest known penguin species. Stem group penguins therefore attained a giant size very early in their evolution, with this gigantism existing for more than 30 million years. The new fossils are from a species that is phylogenetically more derived than Waimanu, and the unexpected coexistence of Waimanu with more derived stem group Sphenisciformes documents a previously unknown diversity amongst the world's oldest penguins. The characteristic tarsometatarsus shape of penguins evolved early on, and the significant morphological disparity between Waimanu and the new fossil conflicts with recent Paleocene divergence estimates for penguins, suggesting an older, Late Cretaceous, origin.

Chemical genetics analysis of an aniline mustard anticancer agent reveals complex I of the electron transport chain as a target.

Science.gov (United States)

Fedeles, Bogdan I; Zhu, Angela Y; Young, Kellie S; Hillier, Shawn M; Proffitt, Kyle D; Essigmann, John M; Croy, Robert G

2011-09-30

The antitumor agent 11β (CAS 865070-37-7), consisting of a DNA-damaging aniline mustard linked to an androgen receptor (AR) ligand, is known to form covalent DNA adducts and to induce apoptosis potently in AR-positive prostate cancer cells in vitro; it also strongly prevents growth of LNCaP xenografts in mice. The present study describes the unexpectedly strong activity of 11β against the AR-negative HeLa cells, both in cell culture and tumor xenografts, and uncovers a new mechanism of action that likely explains this activity. Cellular fractionation experiments indicated that mitochondria are the major intracellular sink for 11β; flow cytometry studies showed that 11β exposure rapidly induced oxidative stress, mitochondria being an important source of reactive oxygen species (ROS). Additionally, 11β inhibited oxygen consumption both in intact HeLa cells and in isolated mitochondria. Specifically, 11β blocked uncoupled oxygen consumption when mitochondria were incubated with complex I substrates, but it had no effect on oxygen consumption driven by substrates acting downstream of complex I in the mitochondrial electron transport chain. Moreover, 11β enhanced ROS generation in isolated mitochondria, suggesting that complex I inhibition is responsible for ROS production. At the cellular level, the presence of antioxidants (N-acetylcysteine or vitamin E) significantly reduced the toxicity of 11β, implicating ROS production as an important contributor to cytotoxicity. Collectively, our findings establish complex I inhibition and ROS generation as a new mechanism of action for 11β, which supplements conventional DNA adduct formation to promote cancer cell death.

Nationwide survey of rotavirus-associated encephalopathy and sudden unexpected death in Japan.

Science.gov (United States)

Kawamura, Yoshiki; Ohashi, Masahiro; Ihira, Masaru; Hashimoto, Shuji; Taniguchi, Koki; Yoshikawa, Tetsushi

2014-08-01

Rotavirus can cause severe complications such as encephalopathy/encephalitis and sudden unexpected death. The incidence of rotavirus-associated encephalopathy/encephalitis or sudden unexpected death remains unknown. To clarify the clinical features of rotavirus-associated encephalitis/encephalopathy and sudden unexpected death, we conducted a nationwide survey in Japan. A two-part questionnaire was designed to determine the number of the cases and the clinical features of severe cases of rotavirus infection, including encephalitis/encephalopathy and sudden unexpected death, between 2009 and 2011. Of the 1365 questionnaires sent to hospitals, 963 (70.5%) were returned and eligible for analysis. We determined 58 cases of rotavirus-associated encephalitis/encephalopathy and 7 cases of sudden unexpected death. These patients were diagnosed with rotavirus infection by immunochromatography. Although 36/58 (62.1%) encephalitis/encephalopathy patients had no sequelae, 15/58 (25.9%) patients had neurological sequelae, and 7/58 (12.1%) patients had fatal outcomes. Pleocytosis was observed in 9/40 (22.5%) patients and cerebrospinal fluid protein levels were elevated in only 4/40 (10%) patients. Elevated lactate dehydrogenase (LDH) (>500 IU/L) or acidemia (pHdeath were 44.0 and 4.9 cases in Japan, respectively. Elevated LDH (>500 IU/L) or acidemia (pH<7.15) were related to a poor prognosis of the encephalitis/encephalopathy. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Risk, unexpected uncertainty, and estimation uncertainty: Bayesian learning in unstable settings.

Directory of Open Access Journals (Sweden)

Elise Payzan-LeNestour

Full Text Available Recently, evidence has emerged that humans approach learning using Bayesian updating rather than (model-free reinforcement algorithms in a six-arm restless bandit problem. Here, we investigate what this implies for human appreciation of uncertainty. In our task, a Bayesian learner distinguishes three equally salient levels of uncertainty. First, the Bayesian perceives irreducible uncertainty or risk: even knowing the payoff probabilities of a given arm, the outcome remains uncertain. Second, there is (parameter estimation uncertainty or ambiguity: payoff probabilities are unknown and need to be estimated. Third, the outcome probabilities of the arms change: the sudden jumps are referred to as unexpected uncertainty. We document how the three levels of uncertainty evolved during the course of our experiment and how it affected the learning rate. We then zoom in on estimation uncertainty, which has been suggested to be a driving force in exploration, in spite of evidence of widespread aversion to ambiguity. Our data corroborate the latter. We discuss neural evidence that foreshadowed the ability of humans to distinguish between the three levels of uncertainty. Finally, we investigate the boundaries of human capacity to implement Bayesian learning. We repeat the experiment with different instructions, reflecting varying levels of structural uncertainty. Under this fourth notion of uncertainty, choices were no better explained by Bayesian updating than by (model-free reinforcement learning. Exit questionnaires revealed that participants remained unaware of the presence of unexpected uncertainty and failed to acquire the right model with which to implement Bayesian updating.

Unexpected complications of bonded mandibular lingual retainers.

NARCIS (Netherlands)

Katsaros, C.; Livas, C.; Renkema, A.M.

2007-01-01

INTRODUCTION: The flexible spiral wire (FSW) retainer is the most frequently used type of fixed retainer bonded on all 6 anterior teeth. Our aim in this article was to demonstrate unexpected posttreatment changes in the labiolingual position of the mandibular anterior teeth associated with the use

Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex

DEFF Research Database (Denmark)

Laursen, Nick Stub; Andersen, Kasper Røjkjær; Braren, Ingke

2011-01-01

with a protease subunit (Bb or C2a). We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. The structures reveal a parallel two-point attachment between C5 and CVF, where the presence of SSL7 only...... slightly affects the C5-CVF interface, explaining the IgA dependence for SSL7-mediated inhibition of C5 cleavage. CVF functions as a relatively rigid binding scaffold inducing a conformational change in C5, which positions its cleavage site in proximity to the serine protease Bb. A general model...

Operational Shock Complexity Theory

Science.gov (United States)

2005-05-26

Theory : Recommendations For The National Strategy To Defeat Terrorism.” Student Issue Paper, Center for Strategic Leadership , US Army War College, July...Lens of Complexity Theory : Recommendations For The National Strategy To Defeat Terrorism.” (Student Issue Paper, Center for Strategic Leadership , US...planners managed to cause confusion in the enemy’s internal model by operating in an unexpected manner. 140 Glenn E. James, “Chaos Theory : The

A "present" for the future: the unexpected value of rediscovery.

Science.gov (United States)

Zhang, Ting; Kim, Tami; Brooks, Alison Wood; Gino, Francesca; Norton, Michael I

2014-10-01

Although documenting everyday activities may seem trivial, four studies reveal that creating records of the present generates unexpected benefits by allowing future rediscoveries. In Study 1, we used a time-capsule paradigm to show that individuals underestimate the extent to which rediscovering experiences from the past will be curiosity provoking and interesting in the future. In Studies 2 and 3, we found that people are particularly likely to underestimate the pleasure of rediscovering ordinary, mundane experiences, as opposed to extraordinary experiences. Finally, Study 4 demonstrates that underestimating the pleasure of rediscovery leads to time-inconsistent choices: Individuals forgo opportunities to document the present but then prefer rediscovering those moments in the future to engaging in an alternative fun activity. Underestimating the value of rediscovery is linked to people's erroneous faith in their memory of everyday events. By documenting the present, people provide themselves with the opportunity to rediscover mundane moments that may otherwise have been forgotten. © The Author(s) 2014.

77 FR 42947 - Unexpected Urgent Refugee and Migration Needs

Science.gov (United States)

2012-07-20

... unexpected and urgent refugee and migration needs, including by contributions to international, governmental, and nongovernmental organizations and payment of administrative expenses of the Bureau of Population...

Single-molecule spectroscopy reveals photosynthetic LH2 complexes switch between emissive states.

Science.gov (United States)

Schlau-Cohen, Gabriela S; Wang, Quan; Southall, June; Cogdell, Richard J; Moerner, W E

2013-07-02

Photosynthetic organisms flourish under low light intensities by converting photoenergy to chemical energy with near unity quantum efficiency and under high light intensities by safely dissipating excess photoenergy and deleterious photoproducts. The molecular mechanisms balancing these two functions remain incompletely described. One critical barrier to characterizing the mechanisms responsible for these processes is that they occur within proteins whose excited-state properties vary drastically among individual proteins and even within a single protein over time. In ensemble measurements, these excited-state properties appear only as the average value. To overcome this averaging, we investigate the purple bacterial antenna protein light harvesting complex 2 (LH2) from Rhodopseudomonas acidophila at the single-protein level. We use a room-temperature, single-molecule technique, the anti-Brownian electrokinetic trap, to study LH2 in a solution-phase (nonperturbative) environment. By performing simultaneous measurements of fluorescence intensity, lifetime, and spectra of single LH2 complexes, we identify three distinct states and observe transitions occurring among them on a timescale of seconds. Our results reveal that LH2 complexes undergo photoactivated switching to a quenched state, likely by a conformational change, and thermally revert to the ground state. This is a previously unobserved, reversible quenching pathway, and is one mechanism through which photosynthetic organisms can adapt to changes in light intensities.

Reaction of cyanide with Pt-nucleobase complexes: preparative, spectroscopic, and structural studies. Unexpected stability of Pt-thymine and Pt-uracil complexes

International Nuclear Information System (INIS)

Raudaschl-Sieber, G.; Lippert, B.

1985-01-01

In order to improve the understanding of the nature of the strongly bound cisplatin on DNA, the reactivity of a large number of complexes of cis-(NH 3 ) 2 Pt/sup II/ with the model nucleobases, 9-ethylguanine, 9-methyladenine, 1-methylcytisine, 1-methylthymine, and i-methyluracil, toward a large excess of cyanide was studied. The behavior of Pt-nucleobase complexes toward CN - is compared with that of simple Pt-amine complexes, and reactions of thiourea with two selected nucleobase complexes is reported. The relevance of these findings with respect to substitution reactions of Pt-nucleobase complexes and the nature of the tightly DNA-bound Pt, which cannot be removed by excess KCN, is discussed

Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review.

Science.gov (United States)

Versluis, A; Knulst, A C; Kruizinga, A G; Michelsen, A; Houben, G F; Baumert, J L; van Os-Medendorp, H

2015-02-01

Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary. © 2014 John Wiley & Sons Ltd.

Lysosomal multienzyme complex: pros and cons of working together.

Science.gov (United States)

Bonten, Erik J; Annunziata, Ida; d'Azzo, Alessandra

2014-06-01

The ubiquitous distribution of lysosomes and their heterogeneous protein composition reflects the versatility of these organelles in maintaining cell homeostasis and their importance in tissue differentiation and remodeling. In lysosomes, the degradation of complex, macromolecular substrates requires the synergistic action of multiple hydrolases that usually work in a stepwise fashion. This catalytic machinery explains the existence of lysosomal enzyme complexes that can be dynamically assembled and disassembled to efficiently and quickly adapt to the pool of substrates to be processed or degraded, adding extra tiers to the regulation of the individual protein components. An example of such a complex is the one composed of three hydrolases that are ubiquitously but differentially expressed: the serine carboxypeptidase, protective protein/cathepsin A (PPCA), the sialidase, neuraminidase-1 (NEU1), and the glycosidase β-galactosidase (β-GAL). Next to this 'core' complex, the existence of sub-complexes, which may contain additional components, and function at the cell surface or extracellularly, suggests as yet unexplored functions of these enzymes. Here we review how studies of basic biological processes in the mouse models of three lysosomal storage disorders, galactosialidosis, sialidosis, and GM1-gangliosidosis, revealed new and unexpected roles for the three respective affected enzymes, Ppca, Neu1, and β-Gal, that go beyond their canonical degradative activities. These findings have broadened our perspective on their functions and may pave the way for the development of new therapies for these lysosomal storage disorders.

Unexpected secoiridoid glucosides from Manulea corymbosa.

Science.gov (United States)

Gousiadou, Chrysoula; Kokubun, Tetsuo; Gotfredsen, Charlotte H; Jensen, Søren R

2014-03-28

From an extract of Manulea corymbosa were isolated four known secoiridoid glucosides (1-4), 10 new monoterpenoid esters of secologanol, namely, manuleosides A-I (5-11, 13, and 14) and dimethyl rhodanthoside A (12), and four new phenylpropanoid esters of carbocyclic iridoid glucosides, manucorymbosides I-IV (15-18). Also, the caffeoyl phenylethanoid glycoside verbascoside was isolated. The presence of secoiridoids apparently derived from loganic acid in the family Scrophulariaceae is unprecedented and greatly unexpected.

Why don't you like me? Midfrontal theta power in response to unexpected peer rejection feedback.

Science.gov (United States)

van der Molen, M J W; Dekkers, L M S; Westenberg, P M; van der Veen, F M; van der Molen, M W

2017-02-01

Social connectedness theory posits that the brain processes social rejection as a threat to survival. Recent electrophysiological evidence suggests that midfrontal theta (4-8Hz) oscillations in the EEG provide a window on the processing of social rejection. Here we examined midfrontal theta dynamics (power and inter-trial phase synchrony) during the processing of social evaluative feedback. We employed the Social Judgment paradigm in which 56 undergraduate women (mean age=19.67 years) were asked to communicate their expectancies about being liked vs. disliked by unknown peers. Expectancies were followed by feedback indicating social acceptance vs. rejection. Results revealed a significant increase in EEG theta power to unexpected social rejection feedback. This EEG theta response could be source-localized to brain regions typically reported during activation of the saliency network (i.e., dorsal anterior cingulate cortex, insula, inferior frontal gyrus, frontal pole, and the supplementary motor area). Theta phase dynamics mimicked the behavior of the time-domain averaged feedback-related negativity (FRN) by showing stronger phase synchrony for feedback that was unexpected vs. expected. Theta phase, however, differed from the FRN by also displaying stronger phase synchrony in response to rejection vs. acceptance feedback. Together, this study highlights distinct roles for midfrontal theta power and phase synchrony in response to social evaluative feedback. Our findings contribute to the literature by showing that midfrontal theta oscillatory power is sensitive to social rejection but only when peer rejection is unexpected, and this theta response is governed by a widely distributed neural network implicated in saliency detection and conflict monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiography after unexpected death in infants and children compared to autopsy

International Nuclear Information System (INIS)

Lange, Charlotte de; Stake, Gunnar; Vege, Aashild

2007-01-01

Postmortem radiography may reveal skeletal and soft-tissue abnormalities of importance for the diagnosis of cause of death. To review the radiographs of children under 3 years of age who had died suddenly and unexpectedly. To compare the radiological and autopsy findings evaluating possible differences in children dying of SIDS and of an explainable cause. A total of 110 consecutive skeletal surveys performed between 1998 and 2002 were reviewed. All but one were performed before autopsy and comprised AP views of the appendicular and axial skeleton and thorax/abdomen, lateral views of the axial skeleton and thorax, and two oblique views of the ribs. Radiography and autopsy findings were compared. Causes of death were classified as SIDS/borderline SIDS (n = 52) and non-SIDS (n = 58), with one case of abuse. In 102 infants there were 150 pathological findings, 88 involving the chest, 24 skeletal, and 38 miscellaneous findings. The radiological-pathological agreement was poor concerning pulmonary findings. Skeletal findings were sometimes important for the final diagnosis. Radiography revealed many skeletal and soft-tissue findings. Pulmonary pathology was most frequently found, but showed poor agreement with autopsy findings. Recognizing skeletal findings related to abuse is important, as these may escape recognition at autopsy. (orig.)

Experimental and Computational Study of an Unexpected Iron-Catalyzed Carboetherification by Cooperative Metal and Ligand Substrate Interaction and Proton Shuttling

KAUST Repository

El-Sepelgy, Osama; Brzozowska, Aleksandra; Azofra, Luis Miguel; Jang, Yoon Kyung; Cavallo, Luigi; Rueping, Magnus

2017-01-01

An iron-catalyzed cycloisomerization of allenols to deoxygenated pyranose glycals has been developed. Combined experimental and computational studies show that the iron complex exhibits a dual catalytic role in that the non-innocent cyclopentadienone ligand acts as proton shuttle by initial hydrogen abstraction from the alcohol and by facilitating protonation and deprotonation events in the isomerization and demetalation steps. Molecular orbital analysis provides insight into the unexpected and selective formation of the 3,4-dihydro-2H-pyran.

Experimental and Computational Study of an Unexpected Iron-Catalyzed Carboetherification by Cooperative Metal and Ligand Substrate Interaction and Proton Shuttling

KAUST Repository

El-Sepelgy, Osama

2017-09-26

An iron-catalyzed cycloisomerization of allenols to deoxygenated pyranose glycals has been developed. Combined experimental and computational studies show that the iron complex exhibits a dual catalytic role in that the non-innocent cyclopentadienone ligand acts as proton shuttle by initial hydrogen abstraction from the alcohol and by facilitating protonation and deprotonation events in the isomerization and demetalation steps. Molecular orbital analysis provides insight into the unexpected and selective formation of the 3,4-dihydro-2H-pyran.

Complexity and time asymmetry of heart rate variability are altered in acute mental stress.

Science.gov (United States)

Visnovcova, Z; Mestanik, M; Javorka, M; Mokra, D; Gala, M; Jurko, A; Calkovska, A; Tonhajzerova, I

2014-07-01

We aimed to study the complexity and time asymmetry of short-term heart rate variability (HRV) as an index of complex neurocardiac control in response to stress using symbolic dynamics and time irreversibility methods. ECG was recorded at rest and during and after two stressors (Stroop, arithmetic test) in 70 healthy students. Symbolic dynamics parameters (NUPI, NCI, 0V%, 1V%, 2LV%, 2UV%), and time irreversibility indices (P%, G%, E) were evaluated. Additionally, HRV magnitude was quantified by linear parameters: spectral powers in low (LF) and high frequency (HF) bands. Our results showed a reduction of HRV complexity in stress (lower NUPI with both stressors, lower NCI with Stroop). Pattern classification analysis revealed significantly higher 0V% and lower 2LV% with both stressors, indicating a shift in sympathovagal balance, and significantly higher 1V% and lower 2UV% with Stroop. An unexpected result was found in time irreversibility: significantly lower G% and E with both stressors, P% index significantly declined only with arithmetic test. Linear HRV analysis confirmed vagal withdrawal (lower HF) with both stressors; LF significantly increased with Stroop and decreased with arithmetic test. Correlation analysis revealed no significant associations between symbolic dynamics and time irreversibility. Concluding, symbolic dynamics and time irreversibility could provide independent information related to alterations of neurocardiac control integrity in stress-related disease.

Complexity and time asymmetry of heart rate variability are altered in acute mental stress

International Nuclear Information System (INIS)

Visnovcova, Z; Mestanik, M; Javorka, M; Mokra, D; Calkovska, A; Tonhajzerova, I; Gala, M; Jurko, A

2014-01-01

We aimed to study the complexity and time asymmetry of short-term heart rate variability (HRV) as an index of complex neurocardiac control in response to stress using symbolic dynamics and time irreversibility methods. ECG was recorded at rest and during and after two stressors (Stroop, arithmetic test) in 70 healthy students. Symbolic dynamics parameters (NUPI, NCI, 0V%, 1V%, 2LV%, 2UV%), and time irreversibility indices (P%, G%, E) were evaluated. Additionally, HRV magnitude was quantified by linear parameters: spectral powers in low (LF) and high frequency (HF) bands. Our results showed a reduction of HRV complexity in stress (lower NUPI with both stressors, lower NCI with Stroop). Pattern classification analysis revealed significantly higher 0V% and lower 2LV% with both stressors, indicating a shift in sympathovagal balance, and significantly higher 1V% and lower 2UV% with Stroop. An unexpected result was found in time irreversibility: significantly lower G% and E with both stressors, P% index significantly declined only with arithmetic test. Linear HRV analysis confirmed vagal withdrawal (lower HF) with both stressors; LF significantly increased with Stroop and decreased with arithmetic test. Correlation analysis revealed no significant associations between symbolic dynamics and time irreversibility. Concluding, symbolic dynamics and time irreversibility could provide independent information related to alterations of neurocardiac control integrity in stress-related disease. (paper)

Impact of unexpected events, shocking news, and rumors on foreign exchange market dynamics

Science.gov (United States)

McDonald, Mark; Suleman, Omer; Williams, Stacy; Howison, Sam; Johnson, Neil F.

2008-04-01

The dynamical response of a population of interconnected objects, when exposed to external perturbations, is of great interest to physicists working on complex systems. Here we focus on human systems, by analyzing the dynamical response of the world’s financial community to various types of unexpected events—including the 9/11 terrorist attacks as they unfolded on a minute-by-minute basis. For the unfolding events of 9/11, our results show that there was a gradual collective understanding of what was happening, rather than an immediate realization. More generally, we find that for news items which are not simple economic statements—and hence whose implications for the market are not immediately obvious—there are periods of collective discovery during which opinions seem to vary in a remarkably synchronized way.

Multilocus phylogeny of the avian family Alaudidae (larks) reveals complex morphological evolution, non-monophyletic genera and hidden species diversity.

Science.gov (United States)

Alström, Per; Barnes, Keith N; Olsson, Urban; Barker, F Keith; Bloomer, Paulette; Khan, Aleem Ahmed; Qureshi, Masood Ahmed; Guillaumet, Alban; Crochet, Pierre-André; Ryan, Peter G

2013-12-01

The Alaudidae (larks) is a large family of songbirds in the superfamily Sylvioidea. Larks are cosmopolitan, although species-level diversity is by far largest in Africa, followed by Eurasia, whereas Australasia and the New World have only one species each. The present study is the first comprehensive phylogeny of the Alaudidae. It includes 83.5% of all species and representatives from all recognised genera, and was based on two mitochondrial and three nuclear loci (in total 6.4 kbp, although not all loci were available for all species). In addition, a larger sample, comprising several subspecies of some polytypic species was analysed for one of the mitochondrial loci. There was generally good agreement in trees inferred from different loci, although some strongly supported incongruences were noted. The tree based on the concatenated multilocus data was overall well resolved and well supported by the data. We stress the importance of performing single gene as well as combined data analyses, as the latter may obscure significant incongruence behind strong nodal support values. The multilocus tree revealed many unpredicted relationships, including some non-monophyletic genera (Calandrella, Mirafra, Melanocorypha, Spizocorys). The tree based on the extended mitochondrial data set revealed several unexpected deep divergences between taxa presently treated as conspecific (e.g. within Ammomanes cinctura, Ammomanes deserti, Calandrella brachydactyla, Eremophila alpestris), as well as some shallow splits between currently recognised species (e.g. Certhilauda brevirostris-C. semitorquata-C. curvirostris; Calendulauda barlowi-C. erythrochlamys; Mirafra cantillans-M. javanica). Based on our results, we propose a revised generic classification, and comment on some species limits. We also comment on the extraordinary morphological adaptability in larks, which has resulted in numerous examples of parallel evolution (e.g. in Melanocorypha mongolica and Alauda leucoptera [both

Proteomic amino-termini profiling reveals targeting information for protein import into complex plastids.

Directory of Open Access Journals (Sweden)

Pitter F Huesgen

Full Text Available In organisms with complex plastids acquired by secondary endosymbiosis from a photosynthetic eukaryote, the majority of plastid proteins are nuclear-encoded, translated on cytoplasmic ribosomes, and guided across four membranes by a bipartite targeting sequence. In-depth understanding of this vital import process has been impeded by a lack of information about the transit peptide part of this sequence, which mediates transport across the inner three membranes. We determined the mature N-termini of hundreds of proteins from the model diatom Thalassiosira pseudonana, revealing extensive N-terminal modification by acetylation and proteolytic processing in both cytosol and plastid. We identified 63 mature N-termini of nucleus-encoded plastid proteins, deduced their complete transit peptide sequences, determined a consensus motif for their cleavage by the stromal processing peptidase, and found evidence for subsequent processing by a plastid methionine aminopeptidase. The cleavage motif differs from that of higher plants, but is shared with other eukaryotes with complex plastids.

Unexpected Secoiridoid Glucosides from Manulea corymbosa

DEFF Research Database (Denmark)

Gousiadou, Chrysoula; Kokubun, Tetsuo; Gotfredsen, Charlotte Held

2014-01-01

From an extract of Manulea corymbosa were isolated four known secoiridoid glucosides (1–4), 10 new monoterpenoid esters of secologanol, namely, manuleosides A–I (5–11, 13, and 14) and dimethyl rhodanthoside A (12), and four new phenylpropanoid esters of carbocyclic iridoid glucosides, manucorymbo......, manucorymbosides I–IV (15–18). Also, the caffeoyl phenylethanoid glycoside verbascoside was isolated. The presence of secoiridoids apparently derived from loganic acid in the family Scrophulariaceae is unprecedented and greatly unexpected....

Circadian variation in unexpected postoperative death

DEFF Research Database (Denmark)

Rosenberg, J; Pedersen, M H; Ramsing, T

1992-01-01

Unexpected deaths still occur following major surgical procedures. The cause is often unknown but may be cardiac or thromboembolic in nature. Postoperative ischaemia, infarction and sudden cardiac death may be triggered by episodic or constant arterial hypoxaemia, which increases during the night...... deaths occurred at night-time. These results suggest a need for further studies of sleep- and respiration-related effects on postoperative nocturnal cardiac function. The efficacy of monitoring during this apparent high-risk period should be evaluated....

New product trial, use of edibles, and unexpected highs among marijuana and hashish users in Colorado.

Science.gov (United States)

Allen, Jane A; Davis, Kevin C; Duke, Jennifer C; Nonnemaker, James M; Bradfield, Brian R; Farrelly, Matthew C

2017-07-01

This study examines the relationships between trial of new marijuana or hashish products and unexpected highs, and use of edible products and unexpected highs. We conducted an online survey of 634 adult, past-year marijuana users in Colorado. We used logistic regression models to examine the relationship between new product trial or edible use and unexpected highs. In the first year that recreational marijuana was legal in Colorado, 71.4% of respondents tried a new marijuana or hashish product, and 53.6% used an edible product. Trial of new products was associated with greater odds of experiencing an unexpected high after controlling for age, gender, education, mental health status, current marijuana or hashish use, and mean amount of marijuana or hashish consumed in the past month (OR=2.13, pmarijuana or hashish products, or use edible marijuana or hashish products, are at greater risk for an unexpected high. It is possible that some negative outcomes associated with marijuana use and unexpected highs may be averted through a better understanding of how to use product packaging to communicate with consumers. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

Directory of Open Access Journals (Sweden)

Takahiro Tsujikawa

2017-04-01

Full Text Available Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8+ T cells expressing T cell exhaustion markers. These data highlight the utility of in situ immune monitoring for patient stratification and provide digital image processing pipelines to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to improve biomarker discovery and assessment.

Proteomic investigation of aphid honeydew reveals an unexpected diversity of proteins.

Directory of Open Access Journals (Sweden)

Ahmed Sabri

Full Text Available Aphids feed on the phloem sap of plants, and are the most common honeydew-producing insects. While aphid honeydew is primarily considered to comprise sugars and amino acids, its protein diversity has yet to be documented. Here, we report on the investigation of the honeydew proteome from the pea aphid Acyrthosiphon pisum. Using a two-Dimensional Differential in-Gel Electrophoresis (2D-Dige approach, more than 140 spots were isolated, demonstrating that aphid honeydew also represents a diverse source of proteins. About 66% of the isolated spots were identified through mass spectrometry analysis, revealing that the protein diversity of aphid honeydew originates from several organisms (i.e. the host aphid and its microbiota, including endosymbiotic bacteria and gut flora. Interestingly, our experiments also allowed to identify some proteins like chaperonin, GroEL and Dnak chaperones, elongation factor Tu (EF-Tu, and flagellin that might act as mediators in the plant-aphid interaction. In addition to providing the first aphid honeydew proteome analysis, we propose to reconsider the importance of this substance, mainly acknowledged to be a waste product, from the aphid ecology perspective.

Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

International Nuclear Information System (INIS)

Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans

2014-01-01

Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed

Of ants and men the unexpected side effects of complexity in society

CERN Document Server

Green, David G

2014-01-01

Why do things go wrong? Why, despite all the planning and care in the world, do things go from bad to worse? This book argues that it is because we are like the ants. Just as ants create an anthill without being aware of it, unintended side effects of human activity create all manner of social trends and crises. The book traces the way these trends emerge and the role they play in some of the major issues of our time. One of the greatest challenges today is the complexity of our social and economic systems. Every action has side effects that people often ignore or fail to see. The book examines the ways in which limitations in our thinking and behaviour lead to unintended side effects. It looks at the role played by complex networks of interactions. Finally, it looks at the way side effects of new technologies, especially computers and communication, have created an Information Revolution, the full repercussions of which are yet to be seen. In our race to create new technologies and sustain indefinite economi...

Comprehensive study of unexpected microscope condensers formed in sample arrangements commonly used in optical microscopy.

Science.gov (United States)

Desai, Darshan B; Aldawsari, Mabkhoot Mudith S; Alharbi, Bandar Mohammed H; Sen, Sanchari; Grave de Peralta, Luis

2015-09-01

We show that various setups for optical microscopy which are commonly used in biomedical laboratories behave like efficient microscope condensers that are responsible for observed subwavelength resolution. We present a series of experiments and simulations that reveal how inclined illumination from such unexpected condensers occurs when the sample is perpendicularly illuminated by a microscope's built-in white-light source. In addition, we demonstrate an inexpensive add-on optical module that serves as an efficient and lightweight microscope condenser. Using such add-on optical module in combination with a low-numerical-aperture objective lens and Fourier plane imaging microscopy technique, we demonstrate detection of photonic crystals with a period nearly eight times smaller than the Rayleigh resolution limit.

Identification of Uranyl Surface Complexes an Ferrihydrite: Advanced EXAFS Data Analysis and CD-MUSIC Modeling

NARCIS (Netherlands)

Rossberg, A.; Ulrich, K.U.; Weiss, S.; Tsushima, S.; Hiemstra, T.; Scheinost, A.C.

2009-01-01

Previous spectroscopic research suggested that uranium(VI) adsorption to iron oxides is dominated by ternary uranyl-carbonato surface complexes across an unexpectedly wide pH range. Formation of such complexes would have a significant impact on the sorption behavior and mobility of uranium in

Group 4 Transition-Metal Complexes of an Aniline–Carbene–Phenol Ligand

KAUST Repository

Despagnet-Ayoub, Emmanuelle

2013-05-24

Attempts to install a tridentate aniline-NHC-phenol (NCO) ligand on titanium and zirconium led instead to complexes resulting from unexpected rearrangement pathways that illustrate common behavior in carbene-early- transition-metal chemistry. © 2013 American Chemical Society.

Transmitter receptors reveal segregation of the arcopallium/amygdala complex in pigeons (Columba livia).

Science.gov (United States)

Herold, Christina; Paulitschek, Christina; Palomero-Gallagher, Nicola; Güntürkün, Onur; Zilles, Karl

2018-02-15

At the beginning of the 20th century it was suggested that a complex group of nuclei in the avian posterior ventral telencephalon is comparable to the mammalian amygdala. Subsequent findings, however, revealed that most of these structures share premotor characteristics, while some indeed constitute the avian amygdala. These developments resulted in 2004 in a change of nomenclature of these nuclei, which from then on were named arcopallial or amygdala nuclei and referred to as the arcopallium/amygdala complex. The structural basis for the similarities between avian and mammalian arcopallial and amygdala subregions is poorly understood. Therefore, we analyzed binding site densities for glutamatergic AMPA, NMDA and kainate, GABAergic GABA A , muscarinic M 1 , M 2 and nicotinic acetylcholine (nACh; α 4 β 2 subtype), noradrenergic α 1 and α 2 , serotonergic 5-HT 1A and dopaminergic D 1/5 receptors using quantitative in vitro receptor autoradiography combined with a detailed analysis of the cyto- and myelo-architecture. Our approach supports a segregation of the pigeon's arcopallium/amygdala complex into the following subregions: the arcopallium anterius (AA), the arcopallium ventrale (AV), the arcopallium dorsale (AD), the arcopallium intermedium (AI), the arcopallium mediale (AM), the arcopallium posterius (AP), the nucleus posterioris amygdalopallii pars basalis (PoAb) and pars compacta (PoAc), the nucleus taeniae amgygdalae (TnA) and the area subpallialis amygdalae (SpA). Some of these subregions showed further subnuclei and each region of the arcopallium/amygdala complex are characterized by a distinct multi-receptor density expression. Here we provide a new detailed map of the pigeon's arcopallium/amygdala complex and compare the receptor architecture of the subregions to their possible mammalian counterparts. © 2017 Wiley Periodicals, Inc.

Lifting an unexpectedly heavy object : the effects on low-back loading and balance loss

NARCIS (Netherlands)

van der Burg, J C; van Dieën, J H; Toussaint, H M

OBJECTIVE: This study evaluates the effects of lifting an unexpectedly heavy object on low-back loading and loss of balance. BACKGROUND: It is often suggested that lifting an unexpectedly heavy object may be a major risk factor for low-back pain. This may lead to an increase in muscle activation,

Working memory representations persist in the face of unexpected task alterations.

Science.gov (United States)

Swan, Garrett; Wyble, Brad; Chen, Hui

2017-07-01

It is well known that information can be held in memory while performing other tasks concurrently, such as remembering a color or number during a separate visual search task. However, it is not clear what happens to stored information in the face of unexpected tasks, such as the surprise questions that are often used in experiments related to inattentional and change blindness. Does the unpredicted shift in task context cause memory representations to be cleared in anticipation of new information? To answer this question, we ran two experiments where the task unexpectedly switched partway through the experiment with a surprise question. Half of the participants were asked to report the same attribute (Exp. 1 = Identity, Exp. 2 = Color) of a target stimulus in both presurprise and postsurprise trials, while for the other half, the reported attribute switched from identity to color (Exp. 1) or vice versa (Exp. 2). Importantly, all participants had to read an unexpected set of instructions and respond differently on the surprise trial. Accuracy on the surprise trial was higher for the same-attribute groups than the different-attribute groups. Furthermore, there was no difference in reaction time on the surprise trial between the two groups. These results suggest that information participants expected to report can survive an encounter with an unexpected task. The implication is that failures to report information on a surprise trial in many experiments reflect genuine differences in memory encoding, rather than forgetting or overwriting induced by the surprise question.

Acinetobacter baumannii FolD ligand complexes --potent inhibitors of folate metabolism and a re-evaluation of the structure of LY374571.

Science.gov (United States)

Eadsforth, Thomas C; Maluf, Fernando V; Hunter, William N

2012-12-01

The bifunctional N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclohydrolase (DHCH or FolD), which is widely distributed in prokaryotes and eukaryotes, is involved in the biosynthesis of folate cofactors that are essential for growth and cellular development. The enzyme activities represent a potential antimicrobial drug target. We have characterized the kinetic properties of FolD from the Gram-negative pathogen Acinetobacter baumanni and determined high-resolution crystal structures of complexes with a cofactor and two potent inhibitors. The data reveal new details with respect to the molecular basis of catalysis and potent inhibition. A unexpected finding was that our crystallographic data revealed a different structure for LY374571 (an inhibitor studied as an antifolate) than that previously published. The implications of this observation are discussed. © 2012 The Authors Journal compilation © 2012 FEBS.

A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.

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Masakazu Kohda

2016-01-01

Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.

Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

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Scott B Vafai

Full Text Available Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS. Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.

Fatigue life analysis of unexpected failure in a lamellar TiAl alloy

Energy Technology Data Exchange (ETDEWEB)

Chan, K.S.

1999-07-01

Unexpected catastrophic failure occurred in specimens of a lamellar TiAl alloy tested by axial fatigue. The failure initiated at locations away from artificial defects introduced to the specimens as crack starters. Fractographic examination of the fracture surface revealed the presence of featureless, low-energy facets that suggested the catastrophic crack may have initiated in one or more large grains that cleaved on a cleavage plane or an interface. A crack growth analysis of fatigue life of the test specimens suggested that the catastrophic crack propagated at stress intensity levels below the large crack threshold. Furthermore, the catastrophic crack propagated at rates that were higher than the average rates exhibited by small cracks, as well as by the large crack under equivalent stress intensity ranges. Because of this, the conventional life prediction approach based on the large crack growth data grossly overpredicted the fatigue life.

Mathematics Placement Test: Typical Results with Unexpected Outcomes

Science.gov (United States)

Ingalls, Victoria

2011-01-01

Based on the results of a prior case-study analysis of mathematics placement at one university, the mathematics department developed and piloted a mathematics placement test. This article describes the implementation process for a mathematics placement test and further analyzes the test results for the pilot group. As an unexpected result, the…

Unexpected Convergent Evolution of Nasal Domes between Pleistocene Bovids and Cretaceous Hadrosaur Dinosaurs.

Science.gov (United States)

O'Brien, Haley D; Faith, J Tyler; Jenkins, Kirsten E; Peppe, Daniel J; Plummer, Thomas W; Jacobs, Zenobia L; Li, Bo; Joannes-Boyau, Renaud; Price, Gilbert; Feng, Yue-Xing; Tryon, Christian A

2016-02-22

The fossil record provides tangible, historical evidence for the mode and operation of evolution across deep time. Striking patterns of convergence are some of the strongest examples of these operations, whereby, over time, similar environmental and/or behavioral pressures precipitate similarity in form and function between disparately related taxa. Here we present fossil evidence for an unexpected convergence between gregarious plant-eating mammals and dinosaurs. Recent excavations of Late Pleistocene deposits on Rusinga Island, Kenya, have uncovered a catastrophic assemblage of the wildebeest-like bovid Rusingoryx atopocranion. Previously known from fragmentary material, these new specimens reveal large, hollow, osseous nasal crests: a craniofacial novelty for mammals that is remarkably comparable to the nasal crests of lambeosaurine hadrosaur dinosaurs. Using adult and juvenile material from this assemblage, as well as computed tomographic imaging, we investigate this convergence from morphological, developmental, functional, and paleoenvironmental perspectives. Our detailed analyses reveal broad parallels between R. atopocranion and basal Lambeosaurinae, suggesting that osseous nasal crests may require a highly specific combination of ontogeny, evolution, and environmental pressures in order to develop. Copyright © 2016 Elsevier Ltd. All rights reserved.

High rates of hybridisation reveal fragile reproductive barriers between endangered Australian sea snakes

DEFF Research Database (Denmark)

Sanders, Kate L; Redsted Rasmussen, Arne; Guinea, Michael L.

2014-01-01

designations, but revealed high frequencies of hybrids on all four reefs and individuals of pure A. fuscus ancestry only at Scott and (historically) Ashmore. Most unexpectedly, 95% of snakes sampled at Hibernia were hybrids that resembled A. laevis in phenotype, revealing a collapse of reproductive barriers...... (‘reverse speciation’) at this reef. These results have dire implications for the conservation status of A. fuscus, and highlight the fragility of reproductive barriers in a recent marine radiation....

The processing of unexpected positive response outcomes in the mediofrontal cortex.

Science.gov (United States)

Ferdinand, Nicola K; Mecklinger, Axel; Kray, Jutta; Gehring, William J

2012-08-29

The human mediofrontal cortex, especially the anterior cingulate cortex, is commonly assumed to contribute to higher cognitive functions like performance monitoring. How exactly this is achieved is currently the subject of lively debate but there is evidence that an event's valence and its expectancy play important roles. One prominent theory, the reinforcement learning theory by Holroyd and colleagues (2002, 2008), assigns a special role to feedback valence, while the prediction of response-outcome (PRO) model by Alexander and Brown (2010, 2011) claims that the mediofrontal cortex is sensitive to unexpected events regardless of their valence. However, paradigms examining this issue have included confounds that fail to separate valence and expectancy. In the present study, we tested the two competing theories of performance monitoring by using an experimental task that separates valence and unexpectedness of performance feedback. The feedback-related negativity of the event-related potential, which is commonly assumed to be a reflection of mediofrontal cortex activity, was elicited not only by unexpected negative feedback, but also by unexpected positive feedback. This implies that the mediofrontal cortex is sensitive to the unexpectedness of events in general rather than their valence and by this supports the PRO model.

DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

Science.gov (United States)

Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

2015-10-01

The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unexpected pathological findings in skills training and assessing skills

NARCIS (Netherlands)

Boendermaker, PM; Pols, J; Scherpbier, AJJA

This article draws attention to unexpected pathological findings encountered by students and teachers when examining one another and/or simulated patients in skips training and assessment sessions. Although no literature on the subject was found it appears to be not uncommon far students and

Predictive ethoinformatics reveals the complex migratory behaviour of a pelagic seabird, the Manx Shearwater

Science.gov (United States)

Freeman, Robin; Dean, Ben; Kirk, Holly; Leonard, Kerry; Phillips, Richard A.; Perrins, Chris M.; Guilford, Tim

2013-01-01

Understanding the behaviour of animals in the wild is fundamental to conservation efforts. Advances in bio-logging technologies have offered insights into the behaviour of animals during foraging, migration and social interaction. However, broader application of these systems has been limited by device mass, cost and longevity. Here, we use information from multiple logger types to predict individual behaviour in a highly pelagic, migratory seabird, the Manx Shearwater (Puffinus puffinus). Using behavioural states resolved from GPS tracking of foraging during the breeding season, we demonstrate that individual behaviours can be accurately predicted during multi-year migrations from low cost, lightweight, salt-water immersion devices. This reveals a complex pattern of migratory stopovers: some involving high proportions of foraging, and others of rest behaviour. We use this technique to examine three consecutive years of global migrations, revealing the prominence of foraging behaviour during migration and the importance of highly productive waters during migratory stopover. PMID:23635496

First NMR observation of 47Ti and 49Ti in cyclopentadienyl complexes

International Nuclear Information System (INIS)

Dormond, A.; Fauconet, M.; Leblanc, J.C.; Moise, C.

1984-01-01

47 Ti and 49 Ti NMR spectra of some mono and biscyclopentadienyl complexes are reported for the first time. The resonances span a relatively large range: electron donating substituents on the cyclopentadienyl ring cause an unexpected downfield shift. (author)

Structural and functional characterization of an archaeal clustered regularly interspaced short palindromic repeat (CRISPR)-associated complex for antiviral defense (CASCADE).

Science.gov (United States)

Lintner, Nathanael G; Kerou, Melina; Brumfield, Susan K; Graham, Shirley; Liu, Huanting; Naismith, James H; Sdano, Matthew; Peng, Nan; She, Qunxin; Copié, Valérie; Young, Mark J; White, Malcolm F; Lawrence, C Martin

2011-06-17

In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA. The Escherichia coli "CRISPR-associated complex for antiviral defense" (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2-Cas5a complex is sufficient to bind crRNA and complementary ssDNA. The structure of Csa2 reveals a crescent-shaped structure unexpectedly composed of a modified RNA-recognition motif and two additional domains present as insertions in the RNA-recognition motif. Conserved residues indicate potential crRNA- and target DNA-binding sites, and the H160A variant shows significantly reduced affinity for crRNA. We propose a general subunit architecture for CASCADE in other bacteria and Archaea.

A dual contribution to the involuntary semantic processing of unexpected spoken words.

Science.gov (United States)

Parmentier, Fabrice B R; Turner, Jacqueline; Perez, Laura

2014-02-01

Sounds are a major cause of distraction. Unexpected to-be-ignored auditory stimuli presented in the context of an otherwise repetitive acoustic background ineluctably break through selective attention and distract people from an unrelated visual task (deviance distraction). This involuntary capture of attention by deviant sounds has been hypothesized to trigger their semantic appraisal and, in some circumstances, interfere with ongoing performance, but it remains unclear how such processing compares with the automatic processing of distractors in classic interference tasks (e.g., Stroop, flanker, Simon tasks). Using a cross-modal oddball task, we assessed the involuntary semantic processing of deviant sounds in the presence and absence of deviance distraction. The results revealed that some involuntary semantic analysis of spoken distractors occurs in the absence of deviance distraction but that this processing is significantly greater in its presence. We conclude that the automatic processing of spoken distractors reflects 2 contributions, one that is contingent upon deviance distraction and one that is independent from it.

Deep Neural Networks Reveal a Gradient in the Complexity of Neural Representations across the Ventral Stream.

Science.gov (United States)

Güçlü, Umut; van Gerven, Marcel A J

2015-07-08

Converging evidence suggests that the primate ventral visual pathway encodes increasingly complex stimulus features in downstream areas. We quantitatively show that there indeed exists an explicit gradient for feature complexity in the ventral pathway of the human brain. This was achieved by mapping thousands of stimulus features of increasing complexity across the cortical sheet using a deep neural network. Our approach also revealed a fine-grained functional specialization of downstream areas of the ventral stream. Furthermore, it allowed decoding of representations from human brain activity at an unsurpassed degree of accuracy, confirming the quality of the developed approach. Stimulus features that successfully explained neural responses indicate that population receptive fields were explicitly tuned for object categorization. This provides strong support for the hypothesis that object categorization is a guiding principle in the functional organization of the primate ventral stream. Copyright © 2015 the authors 0270-6474/15/3510005-10$15.00/0.

An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq

Science.gov (United States)

2010-05-01

MILITARY MEDICINE, 175,5:367,2010 An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq CPT Jeremy B. Fisher, SP USA *; CPT...Christopher E. Curtis, MC USAt 188143 ABSTRACT Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Cases have been...Turkey.3-S We report an unexpected case of Lyme disease from Iraq. CASE REPORT A 28-year-old active duty Army male, on a deployment to northern Iraq

The Investigation of Unexpected Arsenic Compounds Observed in Routine Biological Monitoring Urinary Speciation Analysis

Directory of Open Access Journals (Sweden)

Elizabeth Leese

2017-05-01

Full Text Available This study investigates the identity of two unexpected arsenic species found separately in a number of urine samples sent to the Health and Safety Executive’s Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite, As3+; arsenate, As5+; monomethylarsonic acid, MMA5+; and dimethylarsinic acid, DMA5+. Micro liquid chromatography coupled to inductively coupled plasma mass spectrometry (µLC-ICP-MS and electrospray time of flight tandem mass spectrometry (ESI-QqTOF-MS/MS were used to identify the two arsenic peaks by comparison to several characterized arsenicals: arsenocholine, AC; trimethyl arsine oxide, TMAO; dimethylarsenoacetate, DMAA; dimethylarsenoethanol, DMAE; thio-dimethylarsinate, thio-DMA; thio-dimethylarsenoacetate, thio-DMAA and thio-dimethylarsenoethanol, thio-DMAE. The results from both the ICP-MS and ESI-QqTOF-MS/MS investigations indicate that the unexpected arsenic species termed peak 1 was thio-DMA. While the unexpected arsenic species termed peak 2 has yet to be identified, this investigation shows that it was not AC, TMAO, DMAA, DMAE, thio-DMA, thio-DMAA or thio-DMAE. This study demonstrates the incidence of unexpected arsenic species in both routine and non-routine urine samples from both workers and hospital patients.

Process improvement methodologies uncover unexpected gaps in stroke care.

Science.gov (United States)

Kuner, Anthony D; Schemmel, Andrew J; Pooler, B Dustin; Yu, John-Paul J

2018-01-01

Background The diagnosis and treatment of acute stroke requires timed and coordinated effort across multiple clinical teams. Purpose To analyze the frequency and temporal distribution of emergent stroke evaluations (ESEs) to identify potential contributory workflow factors that may delay the initiation and subsequent evaluation of emergency department stroke patients. Material and Methods A total of 719 sentinel ESEs with concurrent neuroimaging were identified over a 22-month retrospective time period. Frequency data were tabulated and odds ratios calculated. Results Of all ESEs, 5% occur between 01:00 and 07:00. ESEs were most frequent during the late morning and early afternoon hours (10:00-14:00). Unexpectedly, there was a statistically significant decline in the frequency of ESEs that occur at the 14:00 time point. Conclusion Temporal analysis of ESEs in the emergency department allowed us to identify an unexpected decrease in ESEs and through process improvement methodologies (Lean and Six Sigma) and identify potential workflow elements contributing to this observation.

Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition

Energy Technology Data Exchange (ETDEWEB)

Wang, Hui; Klein, Michael G.; Snell, Gyorgy; Lane, Weston; Zou, Hua; Levin, Irena; Li, Ke; Sang, Bi-Ching (Takeda Cali)

2016-07-01

Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2δ) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2δ, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2δ structure reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2δ into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction.

Synthesis and structural characterization of an unusual heterometallic europium(III) amidinate complex

International Nuclear Information System (INIS)

Sroor, Farid M.; Hrib, Cristian G.; Hilfert, Liane; Edelmann, Frank T.

2015-01-01

The reaction of EuI_2(THF)_2 with 3 equiv. of the recently discovered lithium-cyclopropylethinylamidinate Li[c-C_3H_5-C≡C-C(NCy)_2] (1) (Cy = cyclohexyl) unexpectedly afforded the heterometallic europium(III) amidinate complex [{c-C_3H_5-C≡C-C(NCy)_2}Li{c-C_3H_5-C≡C-C(NCy)_2}_2Eu(μ-I)_2Li(THF)_2] (2) in the form of bright yellow, air- and moisture-sensitive crystals. An X-ray diffraction study of 2 revealed several unusual structural features. It comprises a double ''ate'' complex of the tentative trivalent europium(III) bis(cyclopropylethinylamidinate) derivative [c-C_3H_5-C≡C-C(NCy)_2]_2Eu"I"I"II. ''Ate'' complex formation occurred not only through retention of one equiv. of lithium iodide but also through addition of one equiv. of Li[c-C_3H_5-C≡C-C(NCy)_2]. The Li atom in the iodo-bridged Eu(μ-I)_2Li(THF)_2 part of the molecule is tetrahedrally coordinated, whereas the second lithium atom is only tricoordinate through the presence of a rare monodentate (dangling) amidinate ligand. (Copyright copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Membrane bioreactor wastewater treatment plants reveal diverse yeast and protist communities of potential significance in biofouling.

Science.gov (United States)

Liébana, Raquel; Arregui, Lucía; Belda, Ignacio; Gamella, Luis; Santos, Antonio; Marquina, Domingo; Serrano, Susana

2015-01-01

The yeast community was studied in a municipal full-scale membrane bioreactor wastewater treatment plant (MBR-WWTP). The unexpectedly high diversity of yeasts indicated that the activated sludge formed a suitable environment for them to proliferate, with cellular concentrations of 2.2 ± 0.8 × 10(3) CFU ml(-1). Sixteen species of seven genera were present in the biological reactor, with Ascomycetes being the most prevalent group (93%). Most isolates were able to grow in a synthetic wastewater medium, adhere to polyethylene surfaces, and develop biofilms of variable complexity. The relationship between yeast populations and the protists in the MBR-WWTP was also studied, revealing that some protist species preyed on and ingested yeasts. These results suggest that yeast populations may play a role in the food web of a WWTP and, to some extent, contribute to membrane biofouling in MBR systems.

Dealing with unexpected events : efficient and safe solutions to emergent repair on NPP

Energy Technology Data Exchange (ETDEWEB)

Liekens Massazza, I.

2015-07-01

Nuclear Facilities are constantly challenged with unexpected events occurring on Primary Circuit components. A solution must be deployed quickly to minimize impact on the scheduled outage duration while guaranteeing safety, quality and ALARA standards. AREVA NP has demonstrated worldwide recognized capabilities and expertise through efficient management of various unexpected forced events through the time. Turnkey packaged solutions which are proposed are based on proven technics which can be quickly adapted and qualified to the specific problem, resulting in customers’ full satisfaction. (Author)

Terminal parent phosphanide and phosphinidene complexes of zirconium(IV)

Energy Technology Data Exchange (ETDEWEB)

Stafford, Hannah; Rookes, Thomas M.; Wildman, Elizabeth P.; Wooles, Ashley J.; Liddle, Stephen T. [School of Chemistry, The University of Manchester (United Kingdom); Balazs, Gabor; Scheer, Manfred [Institute of Inorganic Chemistry, University of Regensburg (Germany)

2017-06-19

The reaction of [Zr(Tren{sup DMBS})(Cl)] [Zr1; Tren{sup DMBS}=N(CH{sub 2}CH{sub 2}NSiMe{sub 2}Bu{sup t}){sub 3}] with NaPH{sub 2} gave the terminal parent phosphanide complex [Zr(Tren{sup DMBS})(PH{sub 2})] [Zr2; Zr-P=2.690(2) Aa]. Treatment of Zr2 with one equivalent of KCH{sub 2}C{sub 6}H{sub 5} and two equivalents of benzo-15-crown-5 ether (B15C5) afforded an unprecedented example (outside of matrix isolation) of a structurally authenticated transition-metal terminal parent phosphinidene complex [Zr(Tren{sup DMBS})(PH)][K(B15C5){sub 2}] [Zr3; Zr=P=2.472(2) Aa]. DFT calculations reveal a polarized-covalent Zr=P double bond, with a Mayer bond order of 1.48, and together with IR spectroscopic data also suggest an agostic-type Zr..HP interaction [ angle {sub ZrPH}=66.7 ] which is unexpectedly similar to that found in cryogenic, spectroscopically observed phosphinidene species. Surprisingly, computational data suggest that the Zr=P linkage is similarly polarized, and thus as covalent, as essentially isostructural U=P and Th=P analogues. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

Gastric Adenomyoma: The Unexpected Mimicker

Directory of Open Access Journals (Sweden)

Marcela Adriana Duran Álvarez

2017-01-01

Full Text Available Gastric adenomyoma is a rare benign tumor composed of epithelial structures and smooth muscle stroma. Here, we report an unusual case of gastric adenomyoma mostly composed of smooth muscle that was incidentally found during a laparoscopic intervention. On radiology, it mimicked an acquired hypertrophic pyloric stenosis in an adult patient, and pathologically it resembled a pure smooth muscle hamartoma. Complete submission of the lesion for histology was necessary to find the epithelial component and make the right diagnosis. As a mimicker of benign and malignant entities, gastric adenomyoma is usually an unexpected finding after surgery. The aim of this report is to analyze this adenomyoma variant in the setting of an unexplained thickening of the gastric wall, with explanations concerning histogenesis and biological potential.

Platinum(II/palladium(II complexes with n-propyldithiocarbamate and 2,2′-bipyridine: synthesis, characterization, biological activity and interaction with calf thymus DNA

Directory of Open Access Journals (Sweden)

Hassan Mansouri-Torshizi

2014-12-01

Full Text Available Two Pd(II and Pt(II complexes ([Pt(bpy(pr-dtc]Br and [Pd(bpy(pr-dtc]Br, where bpy=2, 2′-bipyridine and pr-dtc = n-propyldithiocarbamate were synthesized and characterized by elemental analysis (CHN, molar conductivity measurements, Fourier transform infrared, 1H nuclear magnetic resonance and UV–visible techniques. In these complexes, the dithiocarbamato ligand coordinates to Pt(II or Pd(II center as bidentate with two sulfur atoms. The binding of these complexes to calf thymus DNA (CT-DNA was investigated using various physicochemical methods such as spectrophotometric, spectrofluorometric and gel filtration technique. The experimental results indicate that Pt(II and Pd(II complexes interact with CT-DNA in the intercalative mode. Both complexes unexpectedly denatured DNA at low concentration. Gel filtration studies indicated that the binding of complexes with DNA is strong enough and does not break readily. The cytotoxic activity of these metal complexes has been tested against human cell tumor lines (K562 and revealed much lower 50% cytotoxic concentration (Cc50 less than that of cisplatin. Several binding and thermodynamic parameters are also described.

Effects of Muscle Fatigue, Creep, and Musculoskeletal Pain on Neuromuscular Responses to Unexpected Perturbation of the Trunk: A Systematic Review.

Science.gov (United States)

Abboud, Jacques; Lardon, Arnaud; Boivin, Frédéric; Dugas, Claude; Descarreaux, Martin

2016-01-01

Introduction: Trunk neuromuscular responses have been shown to adapt under the influence of muscle fatigue, as well as spinal tissue creep or even with the presence of low back pain (LBP). Despite a large number of studies exploring how these external perturbations affect the spinal stability, characteristics of such adaptations remains unclear. Aim: The purpose of this systematic review was to assess the quality of evidence of studies investigating trunk neuromuscular responses to unexpected trunk perturbation. More specifically, the targeted neuromuscular responses were trunk muscle activity reflex and trunk kinematics under the influence of muscle fatigue, spinal creep, and musculoskeletal pain. Methods: A research of the literature was conducted in Pubmed, Embase, and Sport-Discus databases using terms related to trunk neuromuscular reflex responses, measured by electromyography (baseline activity, reflex latency, and reflex amplitude) and/or trunk kinematic, in context of unexpected external perturbation. Moreover, independent variables must be either trunk muscle fatigue or spinal tissue creep or LBP. All included articles were scored for their electromyography methodology based on the "Surface Electromyography for the Non-Invasive Assessment of Muscles (SENIAM)" and the "International Society of Electrophysiology and Kinesiology (ISEK)" recommendations whereas overall quality of articles was scored using a specific quality checklist modified from the Quality Index. Meta-analysis was performed on reflex latency variable. Results: A final set of 29 articles underwent quality assessments. The mean quality score was 79%. No effect of muscle fatigue on erector spinae reflex latency following an unexpected perturbation, nor any other distinctive effects was found for back muscle fatigue and reflex parameters. As for spinal tissue creep effects, no alteration was found for any of the trunk reflex variables. Finally, the meta-analysis revealed an increased erector

Unexpected formation and crystal structure of tetrakis(1H-pyrazole-κN2palladium(II dichloride

Directory of Open Access Journals (Sweden)

Thomas Wagner

2014-12-01

Full Text Available The title salt, [Pd(C3H4N24]Cl2, was obtained unexpectedly by the reaction of palladium(II dichloride with equimolar amounts of 1-chloro-1-nitro-2,2,2-tris(pyrazolylethane in methanol solution. The Pd2+ cation is located on an inversion centre and has a square-planar coordination sphere defined by four N atoms of four neutral pyrazole ligands. The average Pd—N distance is 2.000 (2 Å. The two chloride anions are not coordinating to Pd2+. They are connected to the complex cations through N—H...Cl hydrogen bonds. In addition, C—H...Cl hydrogen bonds are observed, leading to a three-dimensional linkage of cations and anions.

Communication of Unexpected and Significant Findings on Chest Radiographs With an Automated PACS Alert System.

LENUS (Irish Health Repository)

Hayes, Sara A

2014-08-01

An integral part of realizing the enormous potential of imaging in patient care is close communication between radiologists and referring physicians. One key element of this process is the communication of unexpected significant findings. The authors examined the performance of a PACS-based alert system in the appropriate communication of reports containing unexpected significant findings to referring physicians.

Mitochondrial DNA reveals unexpected diversity of chubs (genus Squalius; Cypriniformes, Actinopterygii in the Adriatic basin

Directory of Open Access Journals (Sweden)

Ivana Buj

2015-12-01

Full Text Available The genus Squalius comprises more than 40 species inhabiting various freshwater habitats. They are distributed in Europe and Asia, with particularly high diversity recorded in the Mediterranean area. The taxonomic status of many populations is still matter of debate. With this investigation we aimed to help in resolving taxonomic uncertainties of the chubs distributed in the Adriatic basin in Croatia and Bosnia and Herzegovina. Phylogenetic reconstruction based on mitochondrial gene for cytochrome b revealed high diversity of chubs in the investigated area. Two evolutionary independent lineages are revealed: the first one comprising species Sq. svallize, Sq. tenellus, Sq. illyricus and Sq. zrmanjae; whereas the second lineage corresponds with Sq. squalus. High intraspecific structuring of Sq. squalus was detected, implying necessity of taxonomic revision of that species. Based on the obtained results, most important aspects of the evolutionary history of the genus Squalius in the Adriatic basin will be discussed and evolutionary significant units identified.

RNAi screen reveals an Abl kinase-dependent host cell pathway involved in Pseudomonas aeruginosa internalization.

Directory of Open Access Journals (Sweden)

Julia F Pielage

2008-03-01

Full Text Available Internalization of the pathogenic bacterium Pseudomonas aeruginosa by non-phagocytic cells is promoted by rearrangements of the actin cytoskeleton, but the host pathways usurped by this bacterium are not clearly understood. We used RNAi-mediated gene inactivation of approximately 80 genes known to regulate the actin cytoskeleton in Drosophila S2 cells to identify host molecules essential for entry of P. aeruginosa. This work revealed Abl tyrosine kinase, the adaptor protein Crk, the small GTPases Rac1 and Cdc42, and p21-activated kinase as components of a host signaling pathway that leads to internalization of P. aeruginosa. Using a variety of complementary approaches, we validated the role of this pathway in mammalian cells. Remarkably, ExoS and ExoT, type III secreted toxins of P. aeruginosa, target this pathway by interfering with GTPase function and, in the case of ExoT, by abrogating P. aeruginosa-induced Abl-dependent Crk phosphorylation. Altogether, this work reveals that P. aeruginosa utilizes the Abl pathway for entering host cells and reveals unexpected complexity by which the P. aeruginosa type III secretion system modulates this internalization pathway. Our results furthermore demonstrate the applicability of using RNAi screens to identify host signaling cascades usurped by microbial pathogens that may be potential targets for novel therapies directed against treatment of antibiotic-resistant infections.

Lipid clustering correlates with membrane curvature as revealed by molecular simulations of complex lipid bilayers.

Directory of Open Access Journals (Sweden)

Heidi Koldsø

2014-10-01

Full Text Available Cell membranes are complex multicomponent systems, which are highly heterogeneous in the lipid distribution and composition. To date, most molecular simulations have focussed on relatively simple lipid compositions, helping to inform our understanding of in vitro experimental studies. Here we describe on simulations of complex asymmetric plasma membrane model, which contains seven different lipids species including the glycolipid GM3 in the outer leaflet and the anionic lipid, phosphatidylinositol 4,5-bisphophate (PIP2, in the inner leaflet. Plasma membrane models consisting of 1500 lipids and resembling the in vivo composition were constructed and simulations were run for 5 µs. In these simulations the most striking feature was the formation of nano-clusters of GM3 within the outer leaflet. In simulations of protein interactions within a plasma membrane model, GM3, PIP2, and cholesterol all formed favorable interactions with the model α-helical protein. A larger scale simulation of a model plasma membrane containing 6000 lipid molecules revealed correlations between curvature of the bilayer surface and clustering of lipid molecules. In particular, the concave (when viewed from the extracellular side regions of the bilayer surface were locally enriched in GM3. In summary, these simulations explore the nanoscale dynamics of model bilayers which mimic the in vivo lipid composition of mammalian plasma membranes, revealing emergent nanoscale membrane organization which may be coupled both to fluctuations in local membrane geometry and to interactions with proteins.

Many unexpected abdominal findings on staging computed tomography in patients with colorectal cancer

DEFF Research Database (Denmark)

Holmsted, Kim; Nørring, Keld; Laustrup, Lene Collatz

2011-01-01

; an issue that was previously studied in relation to CT colonography, but not in relation to staging CT with intravenous contrast in CRC patients. The aim of the present study was to evaluate the number and significance of such unexpected findings on staging CTs in CRC patients.......Computed tomography (CT) was proven to be superior to preoperative abdominal ultrasound in the preoperative setting for detection of hepatic metastases from colorectal cancer (CRC). The higher sensitivity of CT has resulted in a number of unexpected abdominal findings of varying importance...

Unexpected nitrile formation in bio-based mesoporous materials (Starbons®).

Science.gov (United States)

Attard, Jennifer; Milescu, Roxana; Budarin, Vitaliy; Matharu, Avtar S; Clark, James H

2018-01-16

The bio-based mesoporous materials made from polysaccharides, Starbons® can be modified by two different routes to give high levels of N-content, unexpectedly including significant quantities of nitrile groups which can improve the materials performance in applications including metal capture.

Complex (Nonstandard) Six-Layer Polytypes of Lizardite Revealed from Oblique-Texture Electron Diffraction Patterns

International Nuclear Information System (INIS)

Zhukhlistov, A.P.; Zinchuk, N.N.; Kotel'nikov, D.D.

2004-01-01

Association of simple (1T and 3R) and two complex (nonstandard) orthogonal polytypes of the serpentine mineral lizardite from the Catoca kimberlite pipe (West Africa) association is revealed from oblique-texture electron diffraction patterns. A six-layer polytype with an ordered superposition of equally oriented layers (notation 3 2 3 2 3 4 3 4 3 6 3 6 or ++ - -00) belonging to the structural group A and a three-layer (336 or I,I,II) or a six-layer (336366 or I,I,II,I,II,II) polytype with alternating oppositely oriented layers and semi-disordered structure are identified using polytype analysis

Endocranial Casts of Pre-Mammalian Therapsids Reveal an Unexpected Neurological Diversity at the Deep Evolutionary Root of Mammals.

Science.gov (United States)

Benoit, Julien; Fernandez, Vincent; Manger, Paul R; Rubidge, Bruce S

2017-01-01

The origin and evolution of the mammalian brain has long been the focus of scientific enquiry. Conversely, little research has focused on the palaeoneurology of the stem group of Mammaliaformes, the Permian and Triassic non-mammaliaform Therapsida (NMT). This is because the majority of the NMT have a non-ossified braincase, making the study of their endocranial cast (sometimes called the "fossil brain") problematic. Thus, descriptions of the morphology and size of NMT endocranial casts have been based largely on approximations rather than reliable determination. Accordingly, here we use micro-CT scans of the skulls of 1 Dinocephalia and 3 Biarmosuchia, which are NMT with a fully ossified braincase and thus a complete endocast. For the first time, our work enables the accurate determination of endocranial shape and size in NMT. This study suggests that NMT brain size falls in the upper range of the reptilian and amphibian variation. Brain size in the dicynodont Kawingasaurus is equivalent to that of early Mammaliaformes, whereas the Dinocephalia show evidence of a secondary reduction of brain size. In addition, unlike other NMT in which the endocast has a tubular shape and its parts are arranged in a linear manner, the biarmosuchian endocast is strongly flexed at the level of the midbrain, creating a near right angle between the fore- and hindbrain. These data highlight an unexpected diversity of endocranial size and morphology in NMT, features that are usually considered conservative in this group. © 2017 S. Karger AG, Basel.

Polytypism and unexpected strong interlayer coupling in two-dimensional layered ReS2

Science.gov (United States)

Qiao, Xiao-Fen; Wu, Jiang-Bin; Zhou, Linwei; Qiao, Jingsi; Shi, Wei; Chen, Tao; Zhang, Xin; Zhang, Jun; Ji, Wei; Tan, Ping-Heng

2016-04-01

Anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and application potential, offer one more dimension than isotropic 2D materials to tune their physical properties. Various physical properties of 2D multi-layer materials are modulated by varying their stacking orders owing to significant interlayer vdW coupling. Multilayer rhenium disulfide (ReS2), a representative anisotropic 2D material, was expected to be randomly stacked and lack interlayer coupling. Here, we demonstrate two stable stacking orders, namely isotropic-like (IS) and anisotropic-like (AI) N layer (NL, N > 1) ReS2 are revealed by ultralow- and high-frequency Raman spectroscopy, photoluminescence and first-principles density functional theory calculation. Two interlayer shear modes are observed in AI-NL-ReS2 while only one shear mode appears in IS-NL-ReS2, suggesting anisotropic- and isotropic-like stacking orders in IS- and AI-NL-ReS2, respectively. This explicit difference in the observed frequencies identifies an unexpected strong interlayer coupling in IS- and AI-NL-ReS2. Quantitatively, the force constants of them are found to be around 55-90% of those of multilayer MoS2. The revealed strong interlayer coupling and polytypism in multi-layer ReS2 may stimulate future studies on engineering physical properties of other anisotropic 2D materials by stacking orders.Anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and application potential, offer one more dimension than isotropic 2D materials to tune their physical properties. Various physical properties of 2D multi-layer materials are modulated by varying their stacking orders owing to significant interlayer vdW coupling. Multilayer rhenium disulfide (ReS2), a representative anisotropic 2D material, was expected to be randomly stacked and lack interlayer coupling. Here, we demonstrate two stable stacking orders, namely isotropic-like (IS) and

Arctic driftwood reveals unexpectedly rich fungal diversity

Czech Academy of Sciences Publication Activity Database

Blanchette, R.A.; Held, B.W.; Hellmann, L.; Millman, L.; Büntgen, Ulf

2016-01-01

Roč. 23, OCT (2016), s. 58-65 ISSN 1754-5048 R&D Projects: GA MŠk(CZ) EE2.3.20.0248 Institutional support: RVO:67179843 Keywords : Ascomycota * Basidiomycota * Biodegradation * Community ecology * Greenland * Iceland * its * Russia * Soft rot * Taxonomy * Wood decay Subject RIV: EH - Ecology, Behaviour Impact factor: 3.219, year: 2016

A Rac1--GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium

Energy Technology Data Exchange (ETDEWEB)

Prehna, G.; Stebbins, C

2007-01-01

The Rho family of small GTPases represent well characterized signaling molecules that regulate many cellular functions such as actin cytoskeletal arrangement and the cell cycle by acting as molecular switches. A Rac1-GDP-Zn complex has been crystallized in space group P3221 and its crystal structure has been solved at 1.9 {angstrom} resolution. These trigonal crystals reveal the unexpected ability of Rac1 to coordinate Zn atoms in a tetrahedral fashion by use of its biologically relevant switch I and switch II regions. Upon coordination of zinc, the switch I region is stabilized in the GDP-bound conformation and contributes to a Rac1 trimer in the asymmetric unit. Zinc coordination causes switch II to adopt a novel conformation with a symmetry-related molecule. Additionally, zinc was found to displace magnesium from its octahedral coordination at switch I, although GDP binding remained stable. This structure represents the first reported Rac1-GDP-Zn complex, which further underscores the conformational flexibility and versatility of the small GTPase switch regions.

A Rac1-GDP Trimer Complex Binds Zinc with Tetrahedral and Octahedral Coordination, Displacing Magnesium

Energy Technology Data Exchange (ETDEWEB)

Prehna,G.; Stebbins, E.

2007-01-01

The Rho family of small GTPases represent well characterized signaling molecules that regulate many cellular functions such as actin cytoskeletal arrangement and the cell cycle by acting as molecular switches. A Rac1-GDP-Zn complex has been crystallized in space group P3{sub 2}21 and its crystal structure has been solved at 1.9 {angstrom} resolution. These trigonal crystals reveal the unexpected ability of Rac1 to coordinate Zn atoms in a tetrahedral fashion by use of its biologically relevant switch I and switch II regions. Upon coordination of zinc, the switch I region is stabilized in the GDP-bound conformation and contributes to a Rac1 trimer in the asymmetric unit. Zinc coordination causes switch II to adopt a novel conformation with a symmetry-related molecule. Additionally, zinc was found to displace magnesium from its octahedral coordination at switch I, although GDP binding remained stable. This structure represents the first reported Rac1-GDP-Zn complex, which further underscores the conformational flexibility and versatility of the small GTPase switch regions.

Unexpected sneezing after a peribulbar injection in a patient for ...

African Journals Online (AJOL)

... anaesthetic in awake patients. We present a case report of an awake elderly male who experienced unexpected continuous sneezing immediately after the removal of the needle used for the peribulbar block, which was subsequently relieved with pheniramine maleate. Keywords: peribulbar block, pheniramine maleate, ...

Fatal invasive aspergillosis: a rare co-infection with an unexpected image presentation in a patient with dengue shock syndrome.

Science.gov (United States)

Wang, Hui-Ching; Chang, Ko; Lu, Po-Liang; Tsai, Kun-Bow; Chen, Huang-Chi

2017-03-01

Pulmonary infiltration and pleural effusion caused by permeability syndrome are the hallmark of pulmonary manifestation of dengue cases. We report a 95-year-old chronic obstructive pulmonary disease case having dengue shock syndrome. Chest X-ray examination revealed diffuse lung infiltration. However, bilateral pneumotoceles were unexpectedly found in computed tomography (CT) images. Dengue virus type 2 infection was confirmed by virus culture, serology and reverse transcriptase-polymerase chain reaction. Profound shock with bilateral lung infiltration developed rapidly in 2 days with supportive care and empirical ampicillin/ sulbactam. Bronchoscopy revealed a whitish plaque over bilateral upper bronchi. Biopsy via bronchoscopy revealed moulds with vascular invasion. Culture of bronchial alveolar lavage yielded Aspergillus flavus. The patient died despite amphotericin B treatment, which was started since finding the whitish plaque with bronchoscopy examination. Besides to considering capillary leakage syndrome, our case report and literature review alert clinicians that CT and bronchoscopy may help to identify the true pathogen though all cases with concurrent dengue and Aspergillus infections had fatal outcomes. © 2015 John Wiley & Sons Ltd.

Unexpected inhibition of CO₂ gas hydrate formation in dilute TBAB solutions and the critical role of interfacial water structure

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Ngoc N.; Nguyen, Anh V.; Nguyen, Khoi T.; Rintoul, Llew; Dang, Liem X.

2016-12-01

Gas hydrates formed under moderated conditions open up novel approaches to tackling issues related to energy supply, gas separation, and CO₂ sequestration. Several additives like tetra-n-butylammonium bromide (TBAB) have been empirically developed and used to promote gas hydrate formation. Here we report unexpected experimental results which show that TBAB inhibits CO₂ gas hydrate formation when used at minuscule concentration. We also used spectroscopic techniques and molecular dynamics simulation to gain further insights and explain the experimental results. They have revealed the critical role of water alignment at the gas-water interface induced by surface adsorption of tetra-n-butylammonium cation (TBA⁺) which gives rise to the unexpected inhibition of dilute TBAB solution. The water perturbation by TBA⁺ in the bulk is attributed to the promotion effect of high TBAB concentration on gas hydrate formation. We explain our finding using the concept of activation energy of gas hydrate formation. Our results provide a step toward to mastering the control of gas hydrate formation.

13C ENDOR Spectroscopy of Lipoxygenase-Substrate Complexes Reveals the Structural Basis for C-H Activation by Tunneling.

Science.gov (United States)

Horitani, Masaki; Offenbacher, Adam R; Carr, Cody A Marcus; Yu, Tao; Hoeke, Veronika; Cutsail, George E; Hammes-Schiffer, Sharon; Klinman, Judith P; Hoffman, Brian M

2017-02-08

In enzymatic C-H activation by hydrogen tunneling, reduced barrier width is important for efficient hydrogen wave function overlap during catalysis. For native enzymes displaying nonadiabatic tunneling, the dominant reactive hydrogen donor-acceptor distance (DAD) is typically ca. 2.7 Å, considerably shorter than normal van der Waals distances. Without a ground state substrate-bound structure for the prototypical nonadiabatic tunneling system, soybean lipoxygenase (SLO), it has remained unclear whether the requisite close tunneling distance occurs through an unusual ground state active site arrangement or by thermally sampling conformational substates. Herein, we introduce Mn 2+ as a spin-probe surrogate for the SLO Fe ion; X-ray diffraction shows Mn-SLO is structurally faithful to the native enzyme. 13 C ENDOR then reveals the locations of 13 C10 and reactive 13 C11 of linoleic acid relative to the metal; 1 H ENDOR and molecular dynamics simulations of the fully solvated SLO model using ENDOR-derived restraints give additional metrical information. The resulting three-dimensional representation of the SLO active site ground state contains a reactive (a) conformer with hydrogen DAD of ∼3.1 Å, approximately van der Waals contact, plus an inactive (b) conformer with even longer DAD, establishing that stochastic conformational sampling is required to achieve reactive tunneling geometries. Tunneling-impaired SLO variants show increased DADs and variations in substrate positioning and rigidity, confirming previous kinetic and theoretical predictions of such behavior. Overall, this investigation highlights the (i) predictive power of nonadiabatic quantum treatments of proton-coupled electron transfer in SLO and (ii) sensitivity of ENDOR probes to test, detect, and corroborate kinetically predicted trends in active site reactivity and to reveal unexpected features of active site architecture.

COMBINED DELAY AND GRAPH EMBEDDING OF EPILEPTIC DISCHARGES IN EEG REVEALS COMPLEX AND RECURRENT NONLINEAR DYNAMICS.

Science.gov (United States)

Erem, B; Hyde, D E; Peters, J M; Duffy, F H; Brooks, D H; Warfield, S K

2015-04-01

The dynamical structure of the brain's electrical signals contains valuable information about its physiology. Here we combine techniques for nonlinear dynamical analysis and manifold identification to reveal complex and recurrent dynamics in interictal epileptiform discharges (IEDs). Our results suggest that recurrent IEDs exhibit some consistent dynamics, which may only last briefly, and so individual IED dynamics may need to be considered in order to understand their genesis. This could potentially serve to constrain the dynamics of the inverse source localization problem.

Molecular Fluoride-Bridged 3d-4f Complexes and Their Magnetic Properties

DEFF Research Database (Denmark)

Pedersen, K. S.; Bendix, J.

2016-01-01

trifluorides with very high lattice enthalpies, building block approaches are not limited to robust systems and use of labile transition metal fluoride complexes has met with unexpected success. The physical properties of fluoride-bridged 3d-4f systems are crucially dependent on coordination geometries, which...... be utilized efficiently in tailored synthesis of polynuclear complexes and extended structures. In particular, the strong affinity of the lanthanides for fluoride makes it a good choice for directed synthesis of mixed lanthanide-transition metal complexes. Despite the competition from formation of lanthanide...

Comparative interactomics: analysis of arabidopsis 14-3-3 complexes reveals highly conserved 14-3-3 interactions between humans and plants.

Science.gov (United States)

Paul, Anna-Lisa; Liu, Li; McClung, Scott; Laughner, Beth; Chen, Sixue; Ferl, Robert J

2009-04-01

As a first step in the broad characterization of plant 14-3-3 multiprotein complexes in vivo, stringent and specific antibody affinity purification was used to capture 14-3-3s together with their interacting proteins from extracts of Arabidopsis cell suspension cultures. Approximately 120 proteins were identified as potential in vivo 14-3-3 interacting proteins by mass spectrometry of the recovered complexes. Comparison of the proteins in this data set with the 14-3-3 interacting proteins from a similar study in human embryonic kidney cell cultures revealed eight interacting proteins that likely represent reasonably abundant, fundamental 14-3-3 interaction complexes that are highly conserved across all eukaryotes. The Arabidopsis 14-3-3 interaction data set was also compared to a yeast in vivo 14-3-3 interaction data set. Four 14-3-3 interacting proteins are conserved in yeast, humans, and Arabidopsis. Comparisons of the data sets based on biochemical function revealed many additional similarities in the human and Arabidopsis data sets that represent conserved functional interactions, while also leaving many proteins uniquely identified in either Arabidopsis or human cells. In particular, the Arabidopsis interaction data set is enriched for proteins involved in metabolism.

Children and Trauma: Unexpected Resistance and Justice in Film and Drawings

Directory of Open Access Journals (Sweden)

Cheri M. Robinson

2018-02-01

Full Text Available This transnational study examines representations of and by children—whether literal wounds, psychological ones, or wounds transmitted through drawings—that manifest their capacity for unexpected resistance and justice. It considers the Mexican-American director Guillermo del Toro’s use of hauntings and wounds to explore violence during the 1936–1939 Spanish Civil War in the film El espinazo del diablo [The Devil’s Backbone] (2001 and its intersections on strategic and theoretical levels with the traumatic in archival children’s drawings produced during the 1976–1983 Argentine military dictatorship. The drawings illustrate the violence perpetrated against the child artists’ families and were produced in exile for the human rights organization COSOFAM. Utilizing diverse theories from film and trauma studies, among others, this article analyzes key scenes in El espinazo exhibiting commonalities with representations of traumatic violence in the children’s drawings, revealing that, in fiction and in fact, a strategic “showing” of the traumatic wound is designed to remind others of the imperative to intervene in situations of extreme violence, to appeal to/for justice, and to effectively testify from the inside.

Effect of High-Carbohydrate Diet on Plasma Metabolome in Mice with Mitochondrial Respiratory Chain Complex III Deficiency

Directory of Open Access Journals (Sweden)

Jayasimman Rajendran

2016-11-01

Full Text Available Mitochondrial disorders cause energy failure and metabolic derangements. Metabolome profiling in patients and animal models may identify affected metabolic pathways and reveal new biomarkers of disease progression. Using liver metabolomics we have shown a starvation-like condition in a knock-in (Bcs1lc.232A>G mouse model of GRACILE syndrome, a neonatal lethal respiratory chain complex III dysfunction with hepatopathy. Here, we hypothesized that a high-carbohydrate diet (HCD, 60% dextrose will alleviate the hypoglycemia and promote survival of the sick mice. However, when fed HCD the homozygotes had shorter survival (mean ± SD, 29 ± 2.5 days, n = 21 than those on standard diet (33 ± 3.8 days, n = 30, and no improvement in hypoglycemia or liver glycogen depletion. We investigated the plasma metabolome of the HCD- and control diet-fed mice and found that several amino acids and urea cycle intermediates were increased, and arginine, carnitines, succinate, and purine catabolites decreased in the homozygotes. Despite reduced survival the increase in aromatic amino acids, an indicator of liver mitochondrial dysfunction, was normalized on HCD. Quantitative enrichment analysis revealed that glycine, serine and threonine metabolism, phenylalanine and tyrosine metabolism, and urea cycle were also partly normalized on HCD. This dietary intervention revealed an unexpected adverse effect of high-glucose diet in complex III deficiency, and suggests that plasma metabolomics is a valuable tool in evaluation of therapies in mitochondrial disorders.

Definition of Sudden Infant Death and Sudden Intrauterine Unexpected Death Syndromes (SIDS and SIUDS with Regard to the Anatomo-Pathological Examination

Directory of Open Access Journals (Sweden)

Giulia Ottaviani

2016-09-01

Full Text Available Crib death, or sudden infant death syndrome (SIDS, is the most frequent form of death in the first year of life, striking one baby in every 1,700–2,000. Yet despite advances in maternal-infant care, sudden intrauterine unexplained/unexpected death syndrome (SIUDS, has a six-eightfold greater incidence than that of SIDS. Frequent congenital abnormalities, likely morphological substrates for SIDS-SIUDS, were detected, mainly represented by alterations of the cardiac conduction system, such as accessory pathways and abnormal resorptive degeneration, and hypoplasia/agenesis of the vital brainstem structures. On the basis of these considerations, the new common definition of the SIDS-SIUDS complex is The sudden death of a fetus after the 25th gestational week or infant under one year of age which is unexpected by history and remains unexplained after a thorough case investigation, including examination of the death scene, performance of a general autopsy and examination of the fetal adnexa. Therefore, given that the general autopsy does not disclose any cause of death, a more in-depth histopathological analysis of the cardiac conduction system and autonomic nervous system by specialized pathologists will become necessary.

Global terrestrial water storage connectivity revealed using complex climate network analyses

Science.gov (United States)

Sun, A. Y.; Chen, J.; Donges, J.

2015-07-01

Terrestrial water storage (TWS) exerts a key control in global water, energy, and biogeochemical cycles. Although certain causal relationship exists between precipitation and TWS, the latter quantity also reflects impacts of anthropogenic activities. Thus, quantification of the spatial patterns of TWS will not only help to understand feedbacks between climate dynamics and the hydrologic cycle, but also provide new insights and model calibration constraints for improving the current land surface models. This work is the first attempt to quantify the spatial connectivity of TWS using the complex network theory, which has received broad attention in the climate modeling community in recent years. Complex networks of TWS anomalies are built using two global TWS data sets, a remote sensing product that is obtained from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, and a model-generated data set from the global land data assimilation system's NOAH model (GLDAS-NOAH). Both data sets have 1° × 1° grid resolutions and cover most global land areas except for permafrost regions. TWS networks are built by first quantifying pairwise correlation among all valid TWS anomaly time series, and then applying a cutoff threshold derived from the edge-density function to retain only the most important features in the network. Basinwise network connectivity maps are used to illuminate connectivity of individual river basins with other regions. The constructed network degree centrality maps show the TWS anomaly hotspots around the globe and the patterns are consistent with recent GRACE studies. Parallel analyses of networks constructed using the two data sets reveal that the GLDAS-NOAH model captures many of the spatial patterns shown by GRACE, although significant discrepancies exist in some regions. Thus, our results provide further measures for constraining the current land surface models, especially in data sparse regions.

When an Object Appears Unexpectedly: Object Circumvention in Adults.

Science.gov (United States)

Wilmut, Kate; Du, Wenchong; Barnett, Anna L

2017-01-01

Obstacles often appear unexpectedly in our pathway and these require us to make immediate adjustments. Despite how regularly we encounter such situations only few studies have considered how we adjust to unexpected obstacles in the pathway that require us to walk around them. The authors considered how adults adjust to the possibility of an obstacle appearing and then also how foot placement is adjusted to circumvent an obstacle. Fifteen healthy adults walked down an 11-m walkway, initially they were told this was a clear pathway and nothing in the environment would change (no gate), they then performed a series of trials in which a gate may (gate close) or may not (gate open) partially obstruct their pathway. The authors found that mediolateral trunk velocity and acceleration was significantly increased when there was the possibility of an obstacle but before the obstacle appeared. This demonstrates an adaptive walking strategy that seems to enable healthy young adults to successfully circumvent obstacles. The authors also categorized foot placement adjustments and found that adults favored making shorter and wider steps away from the obstacle. They suggest this combination of adjustments allows participants to maintain stability while successfully circumventing the obstacle.

Polycomb complexes act redundantly to repress genomic repeats and genes

DEFF Research Database (Denmark)

Leeb, Martin; Pasini, Diego; Novatchkova, Maria

2010-01-01

Polycomb complexes establish chromatin modifications for maintaining gene repression and are essential for embryonic development in mice. Here we use pluripotent embryonic stem (ES) cells to demonstrate an unexpected redundancy between Polycomb-repressive complex 1 (PRC1) and PRC2 during...... the formation of differentiated cells. ES cells lacking the function of either PRC1 or PRC2 can differentiate into cells of the three germ layers, whereas simultaneous loss of PRC1 and PRC2 abrogates differentiation. On the molecular level, the differentiation defect is caused by the derepression of a set...

Frequentie en oorzaak van onverwachte allergische reacties op voedsel [Frequency and cause of unexpected allergic reactions to food

NARCIS (Netherlands)

Michelsen-Huisman, A.D.; Os-Medendorp, H. van; Versluis, A.; Kruizinga, A.G.; Castenmiller, J.J.M.; Noteborn, H.P.J.M.; Houben, G.F.; Knulst, A.C.

2014-01-01

Unexpected reactions occur in patients with food allergy, but frequency data are scare. This prospective study investigates the frequency, severity and causes of unexpected allergic reactions to food in adults with a doctor's diagnosed food allergy. Participants complete an online questionnaire

Principles of assembly reveal a periodic table of protein complexes.

Science.gov (United States)

Ahnert, Sebastian E; Marsh, Joseph A; Hernández, Helena; Robinson, Carol V; Teichmann, Sarah A

2015-12-11

Structural insights into protein complexes have had a broad impact on our understanding of biological function and evolution. In this work, we sought a comprehensive understanding of the general principles underlying quaternary structure organization in protein complexes. We first examined the fundamental steps by which protein complexes can assemble, using experimental and structure-based characterization of assembly pathways. Most assembly transitions can be classified into three basic types, which can then be used to exhaustively enumerate a large set of possible quaternary structure topologies. These topologies, which include the vast majority of observed protein complex structures, enable a natural organization of protein complexes into a periodic table. On the basis of this table, we can accurately predict the expected frequencies of quaternary structure topologies, including those not yet observed. These results have important implications for quaternary structure prediction, modeling, and engineering. Copyright © 2015, American Association for the Advancement of Science.

Complex evolutionary patterns revealed by mitochondrial genomes of the domestic horse.

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Ning, T; Li, J; Lin, K; Xiao, H; Wylie, S; Hua, S; Li, H; Zhang, Y-P

2014-01-01

The domestic horse is the most widely used and important stock and recreational animal, valued for its strength and endurance. The energy required by the domestic horse is mainly supplied by mitochondria via oxidative phosphorylation. Thus, selection may have played an essential role in the evolution of the horse mitochondria. Besides, demographic events also affect the DNA polymorphic pattern on mitochondria. To understand the evolutionary patterns of the mitochondria of the domestic horse, we used a deep sequencing approach to obtain the complete sequences of 15 mitochondrial genomes, and four mitochondrial gene sequences, ND6, ATP8, ATP6 and CYTB, collected from 509, 363, 363 and 409 domestic horses, respectively. Evidence of strong substitution rate heterogeneity was found at nonsynonymous sites across the genomes. Signatures of recent positive selection on mtDNA of domestic horse were detected. Specifically, five amino acids in the four mitochondrial genes were identified as the targets of positive selection. Coalescentbased simulations imply that recent population expansion is the most probable explanation for the matrilineal population history for domestic horse. Our findings reveal a complex pattern of non-neutral evolution of the mitochondrial genome in the domestic horses.

Complex realities : community engagement for a paediatric randomized controlled malaria vaccine trial in Kilifi, Kenya

NARCIS (Netherlands)

Angwenyi, Vibian; Kamuya, Dorcas; Mwachiro, Dorothy; Kalama, Betty; Marsh, Vicki; Njuguna, Patricia; Molyneux, Sassy

2014-01-01

BACKGROUND: Community engagement (CE) is increasingly promoted for biomedical research conducted in resource poor settings for both intrinsic and instrumental purposes. Given the potential importance of CE, but also complexities and possibility of unexpected negative outcomes, there is need for more

Responding In-the-Moment: Learning to Prepare for the Unexpected

Science.gov (United States)

Mason, John

2015-01-01

Becoming aware of something unexpected can be a form of awakening: sharpening attention, enriching noticing, opening up fresh possibilities of action, and educating awareness so as to enable a sensitive response to similar situations in the future. However it can also trigger tunnel vision (few if any actions available) or freezing (no actions…

Early Neolithic water wells reveal the world's oldest wood architecture.

Science.gov (United States)

Tegel, Willy; Elburg, Rengert; Hakelberg, Dietrich; Stäuble, Harald; Büntgen, Ulf

2012-01-01

The European Neolithization ~6000-4000 BC represents a pivotal change in human history when farming spread and the mobile style of life of the hunter-foragers was superseded by the agrarian culture. Permanent settlement structures and agricultural production systems required fundamental innovations in technology, subsistence, and resource utilization. Motivation, course, and timing of this transformation, however, remain debatable. Here we present annually resolved and absolutely dated dendroarchaeological information from four wooden water wells of the early Neolithic period that were excavated in Eastern Germany. A total of 151 oak timbers preserved in a waterlogged environment were dated between 5469 and 5098 BC and reveal unexpectedly refined carpentry skills. The recently discovered water wells enable for the first time a detailed insight into the earliest wood architecture and display the technological capabilities of humans ~7000 years ago. The timbered well constructions made of old oak trees feature an unopened tree-ring archive from which annually resolved and absolutely dated environmental data can be culled. Our results question the principle of continuous evolutionary development in prehistoric technology, and contradict the common belief that metal was necessary for complex timber constructions. Early Neolithic craftsmanship now suggests that the first farmers were also the first carpenters.

Early Neolithic water wells reveal the world's oldest wood architecture.

Directory of Open Access Journals (Sweden)

Willy Tegel

Full Text Available The European Neolithization ~6000-4000 BC represents a pivotal change in human history when farming spread and the mobile style of life of the hunter-foragers was superseded by the agrarian culture. Permanent settlement structures and agricultural production systems required fundamental innovations in technology, subsistence, and resource utilization. Motivation, course, and timing of this transformation, however, remain debatable. Here we present annually resolved and absolutely dated dendroarchaeological information from four wooden water wells of the early Neolithic period that were excavated in Eastern Germany. A total of 151 oak timbers preserved in a waterlogged environment were dated between 5469 and 5098 BC and reveal unexpectedly refined carpentry skills. The recently discovered water wells enable for the first time a detailed insight into the earliest wood architecture and display the technological capabilities of humans ~7000 years ago. The timbered well constructions made of old oak trees feature an unopened tree-ring archive from which annually resolved and absolutely dated environmental data can be culled. Our results question the principle of continuous evolutionary development in prehistoric technology, and contradict the common belief that metal was necessary for complex timber constructions. Early Neolithic craftsmanship now suggests that the first farmers were also the first carpenters.

Effects of unexpected lateral mass placement on trunk loading in lifting

NARCIS (Netherlands)

van der Burg, J.C.E.; Kingma, I.; van Dieen, J.H.

2003-01-01

Study Design. A repeated measurements experiment of spinal loading in healthy subjects. Objectives. To test whether unexpected lateral mass placement increases low back loading and trunk movement when subjects are lifting a mass in upright posture. Summary of Background Data. Epidemiologic studies

Long-Term Adaptations to Unexpected Surface Perturbations: Postural Control During Stance and Gait in Train Conductors.

Science.gov (United States)

Baumgart, Christian; Hoppe, Matthias Wilhelm; Freiwald, Jürgen

2016-01-01

The authors aimed to evaluate the differences in postural control during stance and gait between train conductors and controls. Twenty-one train conductors and 21 office workers performed 6 unilateral and bilateral balance tests on stable and unstable surfaces as well as a gait analysis. In the balance tests, the mean velocity of the center of pressure and unstable surface was measured. In the bilateral balance tests the selected stance width was measured. During gait the length, width, frequency, and velocity of the steps were calculated from the ground reaction forces. Train conductors showed a significantly greater step width during gait (15.4 ± 4.7 vs. 13.0 ± 3.4 cm; p = .035) and stance width during the bilateral stance on the unstable surface (21.0 ± 5.1 vs. 17.8 ± 3.7 cm; p = .026) than the office workers, while no differences were revealed in balance variables. The revealed differences between train conductors and office workers may represent task-specific feedforward control strategies, which increase the base of support and may be helpful to resist unexpected perturbations in trains.

Lower incidence of unexpected in-hospital death after interprofessional implementation of a bedside track-and-trigger system

DEFF Research Database (Denmark)

Bunkenborg, Gitte; Samuelson, Karin Samuelsonkarin; Poulsen, Ingrid

2014-01-01

In-hospital patients may suffer unexpected death because of suboptimal monitoring. Early recognition of deviating physiological parameters may enable staff to prevent unexpected in-hospital death. The aim of this study was to evaluate short- and long-term effects of systematic interprofessional u...... of early warning scoring, structured observation charts, and clinical algorithms for bedside action....

Fournier gangrene and unexpected death.

Science.gov (United States)

Bury, Danielle; Byard, Roger W

2012-11-01

Fournier gangrene represents a rare but progressive perineal infection that may result in rapid death. A 70-year-old man with poorly controlled diabetes mellitus and alcohol abuse is reported who was found unexpectedly dead. He had last been contacted the night before his death. At autopsy, the most striking finding was deep necrotic ulceration of the scrotum with exposure of underlying deep muscles and testicles, with blood cultures positive for Escherichia coli. Death was, therefore, attributed to necrotic ulceration/gangrene of the perineum (Fournier gangrene) that was due to E. coli sepsis with underlying contributing factors of diabetes mellitus and alcoholism. In addition there was morbid obesity (body mass index 46.9), cirrhosis of the liver, and marked focal coronary artery atherosclerosis with significant cardiomegaly. Fournier gangrene may be an extremely aggressive condition that can result in rapid death, as was demonstrated by the rapid progression in the reported case. © 2012 American Academy of Forensic Sciences.

Single molecule analysis of c-myb alternative splicing reveals novel classifiers for precursor B-ALL.

Directory of Open Access Journals (Sweden)

Ye E Zhou

Full Text Available The c-Myb transcription factor, a key regulator of proliferation and differentiation in hematopoietic and other cell types, has an N-terminal DNA binding domain and a large C-terminal domain responsible for transcriptional activation, negative regulation and determining target gene specificity. Overexpression and rearrangement of the c-myb gene (MYB has been reported in some patients with leukemias and other types of cancers, implicating activated alleles of c-myb in the development of human tumors. Alternative RNA splicing can produce variants of c-myb with qualitatively distinct transcriptional activities that may be involved in transformation and leukemogenesis. Here, by performing a detailed, single molecule assay we found that c-myb alternative RNA splicing was elevated and much more complex in leukemia samples than in cell lines or CD34+ hematopoietic progenitor cells from normal donors. The results revealed that leukemia samples express more than 60 different c-myb splice variants, most of which have multiple alternative splicing events and were not detectable by conventional microarray or PCR approaches. For example, the single molecule assay detected 21 and 22 splice variants containing the 9B and 9S exons, respectively, most of which encoded unexpected variant forms of c-Myb protein. Furthermore, the detailed analysis identified some splice variants whose expression correlated with poor survival in a small cohort of precursor B-ALL samples. Our findings indicate that single molecule assays can reveal complexities in c-myb alternative splicing that have potential as novel biomarkers and could help explain the role of c-Myb variants in the development of human leukemia.

Next of kin’s experiences of sudden and unexpected death from stroke - a study of narratives

Science.gov (United States)

2013-01-01

Background Death always evokes feelings in those close to the afflicted person. When death comes suddenly the time for preparation is minimal and the next of kin have to cope with the situation despite their own sorrow. The suddenness is found to be stressful for the next of kin and communication both with healthcare professionals and information about what has happened has been found helpful. The aim of this study was to illuminate the experiences of next of kin from the sudden and unexpected death of a relative from acute stroke. Methods Data was collected over a 12-month period in 2009–2010. Twelve next of kin of patients cared for in stroke units who died suddenly and unexpectedly from stroke were interviewed using a narrative method. The narratives were analyzed using narrative thematic analysis. Results Three themes emerged showing facets of next of kin’s experiences of a relative’s sudden and unexpected death from stroke: Divided feelings about the sudden and unexpected death; Perception of time and directed attention when keeping vigil; Contradictions and arbitrary memories when searching for understanding. Conclusions To have to live in the aftermath of severe stroke is absolute horror in people’s imagination and death is seen as the lesser of two evils. The sudden and unexpected death totally pervades the next of kin’s life, directs their attention to the dying person and even causes them to forget themselves and their own needs, and leads to difficulties in information intake. It is a challenge for the healthcare professionals to be able to identify the individual needs of the next of kin in this situation. PMID:23590246

High-resolution crystal structure of Streptococcus pyogenes β-NAD+ glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface

International Nuclear Information System (INIS)

Yoon, Ji Young; An, Doo Ri; Yoon, Hye-Jin; Kim, Hyoun Sook; Lee, Sang Jae; Im, Ha Na; Jang, Jun Young; Suh, Se Won

2013-01-01

The crystal structure of the complex between the C-terminal domain of Streptococcus pyogenes β-NAD + glycohydrolase and an endogenous inhibitor for SPN was determined at 1.70 Å. It reveals that the interface between the two proteins is highly rich in water molecules. One of the virulence factors produced by Streptococcus pyogenes is β-NAD + glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38–451) and the full-length IFS (residues 1–161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPN ct –IFS complex, which consists of the SPN C-terminal domain (SPN ct ; residues 193–451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70 Å resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPN ct and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope

Unexpected flood loss correlations across Europe

Science.gov (United States)

Booth, Naomi; Boyd, Jessica

2017-04-01

Floods don't observe country borders, as highlighted by major events across Europe that resulted in heavy economic and insured losses in 1999, 2002, 2009 and 2013. Flood loss correlations between some countries occur along multi-country river systems or between neighbouring nations affected by the same weather systems. However, correlations are not so obvious and whilst flooding in multiple locations across Europe may appear independent, for a re/insurer providing cover across the continent, these unexpected correlations can lead to high loss accumulations. A consistent, continental-scale method that allows quantification and comparison of losses, and identifies correlations in loss between European countries is therefore essential. A probabilistic model for European river flooding was developed that allows estimation of potential losses to pan-European property portfolios. By combining flood hazard and exposure information in a catastrophe modelling platform, we can consider correlations between river basins across Europe rather than being restricted to country boundaries. A key feature of the model is its statistical event set based on extreme value theory. Using historical river flow data, the event set captures spatial and temporal patterns of flooding across Europe and simulates thousands of events representing a full range of possible scenarios. Some known correlations were identified, such as between neighbouring Belgium and Luxembourg where 28% of events that affect either country produce a loss in both. However, our model identified some unexpected correlations including between Austria and Poland, and Poland and France, which are geographically distant. These correlations in flood loss may be missed by traditional methods and are key for re/insurers with risks in multiple countries. The model also identified that 46% of European river flood events affect more than one country. For more extreme events with a return period higher than 200 years, all events

Sudden unexpected death in children with a previously diagnosed cardiovascular disorder

NARCIS (Netherlands)

Polderman, Florens N.; Cohen, Joeri; Blom, Nico A.; Delhaas, Tammo; Helbing, Wim A.; Lam, Jan; Sobotka-Plojhar, Marta A.; Temmerman, Arno M.; Sreeram, Narayanswani

2004-01-01

BACKGROUND: It is known that children with previously diagnosed heart defects die suddenly. The causes of death are often unknown. OBJECTIVE: The aim of the study was to identify all infants and children within the Netherlands with previously diagnosed heart disease who had a sudden unexpected death

Sudden unexpected death in children with a previously diagnosed cardiovascular disorder

NARCIS (Netherlands)

Polderman, F.N.; Cohen, Joeri; Blom, N.A.; Delhaas, T.; Helbing, W.A.; Lam, J.; Sobotka-Plojhar, M.A.; Temmerman, Arno M.; Sreeram, N.

2004-01-01

Background: It is known that children with previously diagnosed heart defects die suddenly. The causes of death are often unknown. Objective: The aim of the study was to identify all infants and children within the Netherlands with previously diagnosed heart disease who had a sudden unexpected death

Genetic networking of the Bemisia tabaci cryptic species complex reveals pattern of biological invasions.

Directory of Open Access Journals (Sweden)

Paul De Barro

Full Text Available BACKGROUND: A challenge within the context of cryptic species is the delimitation of individual species within the complex. Statistical parsimony network analytics offers the opportunity to explore limits in situations where there are insufficient species-specific morphological characters to separate taxa. The results also enable us to explore the spread in taxa that have invaded globally. METHODOLOGY/PRINCIPAL FINDINGS: Using a 657 bp portion of mitochondrial cytochrome oxidase 1 from 352 unique haplotypes belonging to the Bemisia tabaci cryptic species complex, the analysis revealed 28 networks plus 7 unconnected individual haplotypes. Of the networks, 24 corresponded to the putative species identified using the rule set devised by Dinsdale et al. (2010. Only two species proposed in Dinsdale et al. (2010 departed substantially from the structure suggested by the analysis. The analysis of the two invasive members of the complex, Mediterranean (MED and Middle East - Asia Minor 1 (MEAM1, showed that in both cases only a small number of haplotypes represent the majority that have spread beyond the home range; one MEAM1 and three MED haplotypes account for >80% of the GenBank records. Israel is a possible source of the globally invasive MEAM1 whereas MED has two possible sources. The first is the eastern Mediterranean which has invaded only the USA, primarily Florida and to a lesser extent California. The second are western Mediterranean haplotypes that have spread to the USA, Asia and South America. The structure for MED supports two home range distributions, a Sub-Saharan range and a Mediterranean range. The MEAM1 network supports the Middle East - Asia Minor region. CONCLUSION/SIGNIFICANCE: The network analyses show a high level of congruence with the species identified in a previous phylogenetic analysis. The analysis of the two globally invasive members of the complex support the view that global invasion often involve very small portions of

Pupil dilation during recognition memory: Isolating unexpected recognition from judgment uncertainty.

Science.gov (United States)

Mill, Ravi D; O'Connor, Akira R; Dobbins, Ian G

2016-09-01

Optimally discriminating familiar from novel stimuli demands a decision-making process informed by prior expectations. Here we demonstrate that pupillary dilation (PD) responses during recognition memory decisions are modulated by expectations, and more specifically, that pupil dilation increases for unexpected compared to expected recognition. Furthermore, multi-level modeling demonstrated that the time course of the dilation during each individual trial contains separable early and late dilation components, with the early amplitude capturing unexpected recognition, and the later trailing slope reflecting general judgment uncertainty or effort. This is the first demonstration that the early dilation response during recognition is dependent upon observer expectations and that separate recognition expectation and judgment uncertainty components are present in the dilation time course of every trial. The findings provide novel insights into adaptive memory-linked orienting mechanisms as well as the general cognitive underpinnings of the pupillary index of autonomic nervous system activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Audit of radiology communication systems for critical, urgent, and unexpected significant findings.

Science.gov (United States)

Duncan, K A; Drinkwater, K J; Dugar, N; Howlett, D C

2016-03-01

To determine the compliance of UK radiology departments and trusts/healthcare organisations with National Patient Safety Agency and Royal College of Radiologist's published guidance on the communication of critical, urgent, and unexpected significant radiological findings. A questionnaire was sent to all UK radiology department audit leads asking for details of their current departmental policy regarding the issuing of alerts; use of automated electronic alert systems; methods of notification of clinicians of critical, urgent, and unexpected significant radiological findings; monitoring of results receipt; and examples of the more common types of serious pathologies for which alerts were issued. One hundred and fifty-four of 229 departments (67%) responded. Eighty-eight percent indicated that they had a policy in place for the communication of critical, urgent, and unexpected significant radiological findings. Only 34% had an automated electronic alert system in place and only 17% had a facility for service-wide electronic tracking of radiology reports. In only 11 departments with an electronic acknowledgement system was someone regularly monitoring the read rate. There is wide variation in practice across the UK with regard to the communication and monitoring of reports with many departments/trusts not fully compliant with published UK guidance. Despite the widespread use of electronic systems, only a minority of departments/trusts have and use electronic tracking to ensure reports have been read and acted upon. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A theoretical lens for revealing the complexity of chronic care

NARCIS (Netherlands)

Borgermans, L.; de Maeseneer, J.; Wollersheim, H.; Vrijhoef, H.J.M.; Devroey, D.

2013-01-01

The increasing prevalence of co-occurring multiple chronic conditions in an aging population has influenced the debate on complexity in chronic care and nowadays provides an impetus to the reform of numerous health systems. This article presents a theoretical lens for understanding the complexity of

Thallium-201 accumulation in cerebral candidiasis: Unexpected finding on SPECT

International Nuclear Information System (INIS)

Tonami, N.; Matsuda, H.; Ooba, H.; Yokoyama, K.; Hisada, K.; Ikeda, K.; Yamashita, J.

1990-01-01

The authors present an unexpected finding of Tl-201 uptake in the intracerebral lesions due to candidiasis. SPECT demonstrated the extent of the lesions and a high target-to-background ratio. The regions where abnormal Tl-201 accumulation was seen were nearly consistent with CT scans of those enhanced by a contrast agent. After treatment, most of the abnormal Tl-201 accumulation disappeared

Thallium-201 accumulation in cerebral candidiasis: Unexpected finding on SPECT

Energy Technology Data Exchange (ETDEWEB)

Tonami, N.; Matsuda, H.; Ooba, H.; Yokoyama, K.; Hisada, K.; Ikeda, K.; Yamashita, J. (Kanazawa Univ. (Japan))

1990-06-01

The authors present an unexpected finding of Tl-201 uptake in the intracerebral lesions due to candidiasis. SPECT demonstrated the extent of the lesions and a high target-to-background ratio. The regions where abnormal Tl-201 accumulation was seen were nearly consistent with CT scans of those enhanced by a contrast agent. After treatment, most of the abnormal Tl-201 accumulation disappeared.

Openness to the unexpected: Our Pathways to Careers in a Federal Research Laboratory.

Science.gov (United States)

Newman, Kurt R.; Bunnell, David B.; Hondorp, Darryl W.; Taylor, William W.; Lynch, Abigail J.; Léonard, Nancy J.

2014-01-01

Many fisheries professionals may not be in the job they originally envisioned for themselves when they began their undergraduate studies. Rather, their current positions could be the result of unexpected, opportunistic, or perhaps even “lucky” open doors that led them down an unexpected path. In many cases, a mentor helped facilitate the unforeseen trajectory. We offer three unique stories about joining a federal fisheries research laboratory, from the perspective of a scientist, a joint manager-scientist, and a manager. We also use our various experiences to form recommendations that should help the next generation of fisheries professionals succeed in any stop along their journey, including being open to opportunities, setting high expectations, and finding a strong and supportive team environment to work in.

Forced-rupture of cell-adhesion complexes reveals abrupt switch between two brittle states

Science.gov (United States)

Toan, Ngo Minh; Thirumalai, D.

2018-03-01

Cell adhesion complexes (CACs), which are activated by ligand binding, play key roles in many cellular functions ranging from cell cycle regulation to mediation of cell extracellular matrix adhesion. Inspired by single molecule pulling experiments using atomic force spectroscopy on leukocyte function-associated antigen-1 (LFA-1), expressed in T-cells, bound to intercellular adhesion molecules (ICAM), we performed constant loading rate (rf) and constant force (F) simulations using the self-organized polymer model to describe the mechanism of ligand rupture from CACs. The simulations reproduce the major experimental finding on the kinetics of the rupture process, namely, the dependence of the most probable rupture forces (f*s) on ln rf (rf is the loading rate) exhibits two distinct linear regimes. The first, at low rf, has a shallow slope, whereas the slope at high rf is much larger, especially for a LFA-1/ICAM-1 complex with the transition between the two occurring over a narrow rf range. Locations of the two transition states (TSs) extracted from the simulations show an abrupt change from a high value at low rf or constant force, F, to a low value at high rf or F. This unusual behavior in which the CACs switch from one brittle (TS position is a constant over a range of forces) state to another brittle state is not found in forced-rupture in other protein complexes. We explain this novel behavior by constructing the free energy profiles, F(Λ)s, as a function of a collective reaction coordinate (Λ), involving many key charged residues and a critical metal ion (Mg2+). The TS positions in F(Λ), which quantitatively agree with the parameters extracted using the Bell-Evans model, change abruptly at a critical force, demonstrating that it, rather than the molecular extension, is a good reaction coordinate. Our combined analyses using simulations performed in both the pulling modes (constant rf and F) reveal a new mechanism for the two loading regimes observed in the

Platinum-nanoparticle-supported core-shell polymer nanospheres with unexpected water stability and facile further modification

Science.gov (United States)

Yuan, Conghui; Xu, Yiting; Luo, Weiang; Zeng, Birong; Qiu, Wuhui; Liu, Jie; Huang, Huiling; Dai, Lizong

2012-05-01

Core-shell nanospheres (CSNSs) with hydrophobic cores and hydrophilic shells were fabricated via a simple mini-emulsion polymerization for the stabilization of platinum nanoparticles (Pt-NPs). The CSNSs showed extremely high loading capacity of Pt-NPs (the largest loading amount of the Pt-NPs was about 49.2 wt%). Importantly, the Pt-NPs/CSNSs nanocomposites had unexpected stability in aqueous solution. DLS results revealed that the CSNSs loaded with Pt-NPs exhibited almost no aggregation after standing for a long time . However, the Pt-NPs immobilized on the CSNSs were not straitlaced: they could transport and redistribute between CSNSs freely when the environmental temperature was higher than the melting point of the CSNS shell. Owing to their excellent stability in aqueous solution, the surface of the Pt-NPs/CSNSs nanocomposites could be further decorated easily. For example, polyaniline (PANI)-coated Pt-NPs/CSNSs, nickel (Ni)-coated Pt-NPs/CSNSs and PANI/Pt-NPs dual-layer hollow nanospheres were facilely fabricated from the Pt-NPs/CSNS nanocomposites.

Platinum-nanoparticle-supported core–shell polymer nanospheres with unexpected water stability and facile further modification

International Nuclear Information System (INIS)

Yuan Conghui; Xu Yiting; Luo Weiang; Zeng Birong; Qiu Wuhui; Liu Jie; Dai Lizong; Huang Huiling

2012-01-01

Core–shell nanospheres (CSNSs) with hydrophobic cores and hydrophilic shells were fabricated via a simple mini-emulsion polymerization for the stabilization of platinum nanoparticles (Pt-NPs). The CSNSs showed extremely high loading capacity of Pt-NPs (the largest loading amount of the Pt-NPs was about 49.2 wt%). Importantly, the Pt-NPs/CSNSs nanocomposites had unexpected stability in aqueous solution. DLS results revealed that the CSNSs loaded with Pt-NPs exhibited almost no aggregation after standing for a long time . However, the Pt-NPs immobilized on the CSNSs were not straitlaced: they could transport and redistribute between CSNSs freely when the environmental temperature was higher than the melting point of the CSNS shell. Owing to their excellent stability in aqueous solution, the surface of the Pt-NPs/CSNSs nanocomposites could be further decorated easily. For example, polyaniline (PANI)-coated Pt-NPs/CSNSs, nickel (Ni)-coated Pt-NPs/CSNSs and PANI/Pt-NPs dual-layer hollow nanospheres were facilely fabricated from the Pt-NPs/CSNS nanocomposites. (paper)

Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors

Science.gov (United States)

Giner, Xavier C; Cotnoir-White, David; Mader, Sylvie; Lévesque, Daniel

2017-01-01

Retinoid X receptors (RXR) play a role as master regulators due to their capacity to form heterodimers with other nuclear receptors. Accordingly, retinoid signaling is involved in multiple biological processes, including development, cell differentiation, metabolism and cell death. However, the role and functions of RXR in different heterodimer complexes remain unsolved, mainly because most RXR drugs (called rexinoids) are not selective to specific heterodimer complexes. This also strongly limits the use of rexinoids for specific therapeutic approaches. In order to better characterize rexinoids at specific nuclear receptor complexes, we have developed and optimized luciferase protein complementation-based Bioluminescence Resonance Energy Transfer (BRET) assays, which can directly measure recruitment of a co-activator motif fused to yellow fluorescent protein (YFP) by specific nuclear receptor dimers. To validate the assays, we compared rexinoid modulation of co-activator recruitment by RXR homodimer, and heterodimers Nur77/RXR and Nurr1/RXR. Results reveal that some rexinoids display selective co-activator recruitment activities with homo- or hetero-dimer complexes. In particular, SR11237 (BMS649) has increased potency for recruitment of co-activator motif and transcriptional activity with the Nur77/RXR heterodimer compared to other complexes. This technology should prove useful to identify new compounds with specificity for individual dimeric species formed by nuclear receptors. PMID:26148973

Unpredictable Root Canal Morphology: Expect the Unexpected

Directory of Open Access Journals (Sweden)

Sohez J Makani

2015-01-01

Full Text Available Background: A maxillary first molar with more than four canals is an interesting example of anatomic variations, especially when two of these canals are detected, with separate apical foramen in the distal root. The inability to locate the unexpected canals of various anatomical configuration and subsequently treat them , may lead to therapeutic failures. Endodontic retreatment is usually the modality of choice in such cases. This report describes a case of a maxillary first molar with five canals (two mesial canals in mesial root, two distal canals in two distal roots and a palatal canal in palatal root. Additionally it shows a rare anatomic configuration and emphasizes the importance of identifying additional canals.

A propensity score analysis of the impact of surgical intervention on unexpected 30-day readmission following admission for subdural hematoma.

Science.gov (United States)

Franko, Lynze R; Sheehan, Kyle M; Roark, Christopher D; Joseph, Jacob R; Burke, James F; Rajajee, Venkatakrishna; Williamson, Craig A

2017-12-22

OBJECTIVE Subdural hematoma (SDH) is a common disease that is increasingly being managed nonoperatively. The all-cause readmission rate for SDH has not previously been described. This study seeks to describe the incidence of unexpected 30-day readmission in a cohort of patients admitted to an academic neurosurgical center. Additionally, the relationship between operative management, clinical outcome, and unexpected readmission is explored. METHODS This is an observational study of 200 consecutive adult patients with SDH admitted to the neurosurgical ICU of an academic medical center. Demographic information, clinical characteristics, and treatment strategies were compared between readmitted and nonreadmitted patients. Multivariable logistic regression, weighted by the inverse probability of receiving surgery using propensity scores, was used to evaluate the association between operative management and unexpected readmission. RESULTS Of 200 total patients, 18 (9%) died during hospitalization and were not included in the analysis. Overall, 48 patients (26%) were unexpectedly readmitted within 30 days. Sixteen patients (33.3%) underwent SDH evacuation during their readmission. Factors significantly associated with unexpected readmission were nonoperative management (72.9% vs 54.5%, p = 0.03) and female sex (50.0% vs 32.1%, p = 0.03). In logistic regression analysis weighted by the inverse probability of treatment and including likely confounders, surgical management was not associated with likelihood of a good outcome at hospital discharge, but was associated with significantly reduced odds of unexpected readmission (OR 0.19, 95% CI 0.08-0.49). CONCLUSIONS Over 25% of SDH patients admitted to an academic neurosurgical ICU were unexpectedly readmitted within 30 days. Nonoperative management does not affect outcome at hospital discharge but is significantly associated with readmission, even when accounting for the probability of treatment by propensity score weighted

Connected magma plumbing system between Cerro Negro and El Hoyo Complex, Nicaragua revealed by gravity survey

Science.gov (United States)

MacQueen, Patricia; Zurek, Jeffrey; Williams-Jones, Glyn

2016-11-01

Cerro Negro, near León, Nicaragua is a young, relatively small basaltic cinder cone volcano that has been unusually active during its short lifespan. Multiple explosive eruptions have deposited significant amounts of ash on León and the surrounding rural communities. While a number of studies investigate the geochemistry and stress regime of the volcano, subsurface structures have only been studied by diffuse soil gas surveys. These studies have raised several questions as to the proper classification of Cerro Negro and its relation to neighboring volcanic features. To address these questions, we collected 119 gravity measurements around Cerro Negro volcano in an attempt to delineate deep structures at the volcano. The resulting complete Bouguer anomaly map revealed local positive gravity anomalies (wavelength 0.5 to 2 km, magnitude +4 mGal) and regional positive (10 km wavelength, magnitudes +10 and +8 mGal) and negative (12 and 6 km wavelength, magnitudes -18 and -13 mGal) Bouguer anomalies. Further analysis of these gravity data through inversion has revealed both local and regional density anomalies that we interpret as intrusive complexes at Cerro Negro and in the Nicaraguan Volcanic Arc. The local density anomalies at Cerro Negro have a density of 2700 kg m-3 (basalt) and are located between -250 and -2000 m above sea level. The distribution of recovered density anomalies suggests that eruptions at Cerro Negro may be tapping an interconnected magma plumbing system beneath El Hoyo, Cerro La Mula, and Cerro Negro, and more than seven other proximal volcanic features, implying that Cerro Negro should be considered the newest cone of a Cerro Negro-El Hoyo volcanic complex.

Unexpected Anal Squamous Cells Carcinoma after Open Hemorrhoidectomy

Directory of Open Access Journals (Sweden)

Navarra Luca

2015-01-01

Full Text Available We report a case of unexpected anal squamous cells carcinoma found in hemorrhoidectomy specimen. The patient had a 3-year history of prolapsing hemorrhoids. A prolapsing hemorrhoid was present at eleven o’clock in lithotomy. Milligan-Morgan was performed and gross examination of the specimen was unremarkable. Histopathologic evaluation showed noninvasive squamous cells carcinoma. The present case report evidences the opportunity of routine histopathologic analysis of hemorrhoidal specimens particularly in case of long-standing prolapse. Questions arise in the option of those techniques where no specimens are collected or tissue is excised far from deceased area.

Unexpected death holograms: Animitas urban appeal in Chile

Directory of Open Access Journals (Sweden)

Lautaro Ojeda Ledesma

2011-01-01

Full Text Available This paper aims at performing an integral analysis of the relation between popular religiousness and urban space in Chilean animitas [little shrines] practices. In order to do this, we propose a multipurpose analysis scheme, holding the concept of "unexpected death hologram". This scheme puts forward three supplementary classifications: animita as a holographic subject, as a holographic object and as a holographic place. Finally, these three classifications supplemented by interviews and topologic analyses show almost all the sociospatial factors present in this practice, accounting for the urban importance that this type of popular practice has

Alopecia associated with unexpected leakage from electron cone

Energy Technology Data Exchange (ETDEWEB)

Wen, B.C.; Pennington, E.C.; Hussey, D.H.; Jani, S.K.

1989-06-01

Excessive irradiation due to unexpected leakage was found on a patient receiving electron beam therapy. The cause of this leakage was analyzed and the amount of leakage was measured for different electron beam energies. The highest leakage occurred with a 6 x 6 cm cone using a 12 MeV electron beam. The leakage dose measured along the side of the cone could be as great as 40%. Until the cones are modified or redesigned, it is advised that all patient setups be carefully reviewed to assure that no significant patient areas are in the side scatter region.

Precision grip responses to unexpected rotational perturbations scale with axis of rotation.

Science.gov (United States)

De Gregorio, Michael; Santos, Veronica J

2013-04-05

It has been established that rapid, pulse-like increases in precision grip forces ("catch-up responses") are elicited by unexpected translational perturbations and that response latency and strength scale according to the direction of linear slip relative to the hand as well as gravity. To determine if catch-up responses are elicited by unexpected rotational perturbations and are strength-, axis-, and/or direction-dependent, we imposed step torque loads about each of two axes which were defined relative to the subject's hand: the distal-proximal axis away from and towards the subject's palm, and the grip axis which connects the two fingertips. Precision grip responses were dominated initially by passive mechanics and then by active, unimodal catch-up responses. First dorsal interosseous activity, marking the start of the catch-up response, began 71-89 ms after the onset of perturbation. The onset latency, shape, and duration (217-231 ms) of the catch-up response were not affected by the axis, direction, or magnitude of the rotational perturbation, while strength was scaled by axis of rotation and slip conditions. Rotations about the grip axis that tilted the object away from the palm and induced rotational slip elicited stronger catch-up responses than rotations about the distal-proximal axis that twisted the object between the digits. To our knowledge, this study is the first to investigate grip responses to unexpected torque loads and to show characteristic, yet axis-dependent, catch-up responses for conditions other than pure linear slip. Copyright © 2013 Elsevier Ltd. All rights reserved.

The complex synthesis and solid state chemistry of ceria-lanthana solid solutions prepared via a hexamethylenetetramine precipitation

International Nuclear Information System (INIS)

Fleming, P.G.; Holmes, J.D.; Otway, D.J.; Morris, M.A.

2011-01-01

Mixed oxide solid solutions are becoming ever more commercially important across a range of applications. However, their synthesis can be problematical. Here, we show that ceria-lanthana solid solutions can be readily prepared via simple precipitation using hexamethylenetetramine. However, the solution chemistry can be complex, which results in the precipitated particles having a complex structure and morphology. Great care must be taken in both the synthesis and characterisation to quantify the complexity of the product. Even very high heat treatments were not able to produce highly homogeneous materials and X-ray diffractions reveals the non-equilibrium form of particles prepared in this way. Unexpected crystal structures are revealed including a new metastable cubic La 2 O 3 phase. - Graphical abstract: The suggested mechanism for the formation of dual fluorite phase particles, where Step 1 corresponds to room temperature aging, Step 2; heating the solution to 90 deg. C, Step 3; cooling of the solution to room temperature, Step 4; calcination to 500 deg. C, Step 5; calcination to 700 deg. C and Step 6; calcination to 1300 deg. C. The terminology of e.g. La 1-x Ce x (OH) 3 is used to indicate the formation of a mixed oxy-hydroxy participate rather than a definitive assignment of stoichiometry. Similarly, La 1-y Ce y O 2 only implies a mixed solid solution. Highlights: → Mol% of prepared Ce-La oxides did not follow that of reactant mol%. → Complex reaction pathway found to be dependent on metal solution concentrations. → At certain concentrations core shell particles were found to form. → A reaction model was produced based on cationic solubility. → Report lanthana solubility higher than previously reported in CeO 2 .

Mistletoe lectin I in complex with galactose and lactose reveals distinct sugar-binding properties

International Nuclear Information System (INIS)

Mikeska, Ruth; Wacker, Roland; Arni, Raghuvir; Singh, Tej P.; Mikhailov, Albert; Gabdoulkhakov, Azat; Voelter, Wolfgang; Betzel, Christian

2004-01-01

The structures of mistletoe lectin I in complex with lactose and galactose reveal differences in binding by the two known sites in subdomains α1 and γ2 and suggest the presence of a third low-affinity site in subdomain β1. The structures of mistletoe lectin I (ML-I) from Viscum album complexed with lactose and galactose have been determined at 2.3 Å resolution and refined to R factors of 20.9% (R free = 23.6%) and 20.9 (R free = 24.6%), respectively. ML-I is a heterodimer and belongs to the class of ribosome-inactivating proteins of type II, which consist of two chains. The A-chain has rRNA N-glycosidase activity and irreversibly inhibits eukaryotic ribosomes. The B-chain is a lectin and preferentially binds to galactose-terminated glycolipids and glycoproteins on cell membranes. Saccharide binding is performed by two binding sites in subdomains α1 and γ2 of the ML-I B-chain separated by ∼62 Å from each other. The favoured binding of galactose in subdomain α1 is achieved via hydrogen bonds connecting the 4-hydroxyl and 3-hydroxyl groups of the sugar moiety with the side chains of Asp23B, Gln36B and Lys41B and the main chain of 26B. The aromatic ring of Trp38B on top of the preferred binding pocket supports van der Waals packing of the apolar face of galactose and stabilizes the sugar–lectin complex. In the galactose-binding site II of subdomain γ2, Tyr249B provides the hydrophobic stacking and the side chains of Asp235B, Gln238B and Asn256B are hydrogen-bonding partners for galactose. In the case of the galactose-binding site I, the 2-hydroxyl group also stabilizes the sugar–protein complex, an interaction thus far rarely detected in galactose-specific lectins. Finally, a potential third low-affinity galactose-binding site in subunit β1 was identified in the present ML-I structures, in which a glycerol molecule from the cryoprotectant buffer has bound, mimicking the sugar compound

Single muscle fiber proteomics reveals unexpected mitochondrial specialization

DEFF Research Database (Denmark)

Murgia, Marta; Nagaraj, Nagarjuna; Deshmukh, Atul S

2015-01-01

and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype-specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type-resolved proteomes can be applied to a variety of physiological and pathological conditions...

Teach Students to Dig for Understanding Using an Unexpected Technological Shovel

Science.gov (United States)

Lake, Susan E. L.

2004-01-01

Online genealogy tools is an unexpected resource as these tools not only serve valuable for genealogy research, but also can be used by students to learn about their country's past and learn to use primary materials to draw conclusions. Some of these Online sources like the 1880 census available at www.ancestry.com, www.thepastwhispers.com, which…

All Intimate Grammars Leak: Reflections on "Indian Languages in Unexpected Places"

Science.gov (United States)

Kroskrity, Paul V.

2011-01-01

In this discussion of a set of studies that fits the trope of "Indian Languages in Unexpected Places," I explore the obvious necessity of developing a relevant notion of linguistic "leakage" following a famous image from the writings of the linguistic anthropologist Edward Sapir. Though in its original use, the concept applied more to the order of…

The Neuro-Complex: Some Comments and Convergences

Directory of Open Access Journals (Sweden)

Paul Martin

2011-10-01

Full Text Available In this short think-piece we trace the newly emerging and rapidly expanding dimensions and dynamics of the “neuro-complex.” What this amounts to, we suggest, are a series of bio or neuro “convergences” of sorts regarding the brain and mental worlds, which in turn are traceable through what we term the bio-psych, pharma-psych, subjectivity-selves, wellness-enhancement, and the neuroculture-neurofutures relational nexuses. These issues are then illustrated through two brief case studies regarding brain scanning technologies and the problems and prospects of cognitive enhancement. The paper concludes with some final reflections on these matters and a call for further research in this rich and challenging domain as the neuro-complex continues to expand in expected and unexpected, yet equally rich and fascinating, ways.

A complex scenario of tuberculosis transmission is revealed through genetic and epidemiological surveys in Porto.

Science.gov (United States)

Rito, Teresa; Matos, Carlos; Carvalho, Carlos; Machado, Henrique; Rodrigues, Gabriela; Oliveira, Olena; Ferreira, Eduarda; Gonçalves, Jorge; Maio, Lurdes; Morais, Clara; Ramos, Helena; Guimarães, João Tiago; Santos, Catarina L; Duarte, Raquel; Correia-Neves, Margarida

2018-01-25

Tuberculosis (TB) incidence is decreasing worldwide and eradication is becoming plausible. In low-incidence countries, intervention on migrant populations is considered one of the most important strategies for elimination. However, such measures are inappropriate in European areas where TB is largely endemic, such as Porto in Portugal. We aim to understand transmission chains in Porto through a genetic characterization of Mycobacterium tuberculosis strains and through a detailed epidemiological evaluation of cases. We genotyped the M. tuberculosis strains using the MIRU-VNTR system. We performed an evolutionary reconstruction of the genotypes with median networks, used in this context for the first time. TB cases from a period of two years were evaluated combining genetic, epidemiological and georeferencing information. The data reveal a unique complex scenario in Porto where the autochthonous population acts as a genetic reservoir of M. tuberculosis diversity with discreet episodes of transmission, mostly undetected using classical epidemiology alone. Although control policies have been successful in decreasing incidence in Porto, the discerned complexity suggests that, for elimination to be a realistic goal, strategies need to be adjusted and coupled with a continuous genetic characterization of strains and detailed epidemiological evaluation, in order to successfully identify and interrupt transmission chains.

An Approach to Human Error Hazard Detection of Unexpected Situations in NPPs

Energy Technology Data Exchange (ETDEWEB)

Park, Sangjun; Oh, Yeonju; Shin, Youmin; Lee, Yong-Hee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

Fukushima accident is a typical complex event including the extreme situations induced by the succeeding earthquake, tsunami, explosion, and human errors. And it is judged with incomplete cause of system build-up same manner, procedure as a deficiency of response manual, education and training, team capability and the discharge of operator from human engineering point of view. Especially, the guidelines of current operating NPPs are not enough including countermeasures to the human errors at the extreme situations. Therefore, this paper describes a trial to detect the hazards of human errors at extreme situation, and to define the countermeasures that can properly response to the human error hazards when an individual, team, organization, and working entities that encounter the extreme situation in NPPs. In this paper we try to propose an approach to analyzing and extracting human error hazards for suggesting additional countermeasures to the human errors in unexpected situations. They might be utilized to develop contingency guidelines, especially for reducing the human error accident in NPPs. But the trial application in this study is currently limited since it is not easy to find accidents cases in detail enough to enumerate the proposed steps. Therefore, we will try to analyze as more cases as possible, and consider other environmental factors and human error conditions.

An Approach to Human Error Hazard Detection of Unexpected Situations in NPPs

International Nuclear Information System (INIS)

Park, Sangjun; Oh, Yeonju; Shin, Youmin; Lee, Yong-Hee

2015-01-01

Fukushima accident is a typical complex event including the extreme situations induced by the succeeding earthquake, tsunami, explosion, and human errors. And it is judged with incomplete cause of system build-up same manner, procedure as a deficiency of response manual, education and training, team capability and the discharge of operator from human engineering point of view. Especially, the guidelines of current operating NPPs are not enough including countermeasures to the human errors at the extreme situations. Therefore, this paper describes a trial to detect the hazards of human errors at extreme situation, and to define the countermeasures that can properly response to the human error hazards when an individual, team, organization, and working entities that encounter the extreme situation in NPPs. In this paper we try to propose an approach to analyzing and extracting human error hazards for suggesting additional countermeasures to the human errors in unexpected situations. They might be utilized to develop contingency guidelines, especially for reducing the human error accident in NPPs. But the trial application in this study is currently limited since it is not easy to find accidents cases in detail enough to enumerate the proposed steps. Therefore, we will try to analyze as more cases as possible, and consider other environmental factors and human error conditions

Non-canonical TAF complexes regulate active promoters in human embryonic stem cells.

Science.gov (United States)

Maston, Glenn A; Zhu, Lihua Julie; Chamberlain, Lynn; Lin, Ling; Fang, Minggang; Green, Michael R

2012-11-13

The general transcription factor TFIID comprises the TATA-box-binding protein (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find, unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all TAFs are expressed. Directed and global chromatin immunoprecipitation analyses reveal an unprecedented promoter occupancy pattern: most active genes are bound by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a previously undescribed complex comprising TAFs 2, 6, 7, 11 and TBP. Altering the composition of hESC TAFs, either by depleting TAFs that are present or ectopically expressing TAFs that are absent, results in misregulated expression of pluripotency genes and induction of differentiation. Thus, the selective expression and use of TAFs underlies the ability of hESCs to self-renew.DOI:http://dx.doi.org/10.7554/eLife.00068.001.

Interpretation of laser desorption mass spectra of unexpected inorganic species found in a cosmetic sample of forensic interest: fingernail polish.

Science.gov (United States)

O'Neill, Emily; Harrington, Danielle; Allison, John

2009-08-01

When analytes containing color are irradiated with a pulsed UV laser in the ion source of a mass spectrometer, molecules such as dyes or pigments absorb energy, resulting in their desorption and ionization. This method, laser desorption mass spectrometry (LDMS), has been used successfully to analyze colorants of forensic interest in a wide variety of materials. Here, we present and interpret the most complex of such spectra obtained to date from a sample of fingernail polish. Interpretation of the spectrum provides a unique opportunity to characterize the laser desorption mass spectra of some unexpected inorganic materials found in cosmetics, such as "broken glass", cyanide compounds, and heavy metals. Also, the possibility of a useful forensic database of LDMS spectra of fingernail polishes is considered.

The biology of strigolactones

KAUST Repository

Ruyter-Spira, Carolien P.; Al-Babili, Salim; Van Der Krol, Sander; Bouwmeester, Harro J J

2013-01-01

biosynthesis, which has revealed the unexpected simplicity of the originally postulated complex pathway. Moreover, the discovery and localization of a strigolactone exporter sheds new light on putative strigolactone fluxes to the rhizosphere as well as within

75 FR 67015 - Unexpected Urgent Refugee And Migration Needs Resulting From Flooding InPakistan

Science.gov (United States)

2010-11-01

... September 3, 2010 Unexpected Urgent Refugee And Migration Needs Resulting From Flooding InPakistan... humanitarian needs resulting from recent devastating flooding in Pakistan. You are authorized and directed to...

Evaluating the Nature of So-Called S*-State Feature in Transient Absorption of Carotenoids in Light-Harvesting Complex 2 (LH2) from Purple Photosynthetic Bacteria.

Science.gov (United States)

Niedzwiedzki, Dariusz M; Hunter, C Neil; Blankenship, Robert E

2016-11-03

Carotenoids are a class of natural pigments present in all phototrophic organisms, mainly in their light-harvesting proteins in which they play roles of accessory light absorbers and photoprotectors. Extensive time-resolved spectroscopic studies of these pigments have revealed unexpectedly complex photophysical properties, particularly for carotenoids in light-harvesting LH2 complexes from purple bacteria. An ambiguous, optically forbidden electronic excited state designated as S* has been postulated to be involved in carotenoid excitation relaxation and in an alternative carotenoid-to-bacteriochlorophyll energy transfer pathway, as well as being a precursor of the carotenoid triplet state. However, no definitive and satisfactory origin of the carotenoid S* state in these complexes has been established, despite a wide-ranging series of studies. Here, we resolve the ambiguous origin of the carotenoid S* state in LH2 complex from Rba. sphaeroides by showing that the S* feature can be seen as a combination of ground state absorption bleaching of the carotenoid pool converted to cations and the Stark spectrum of neighbor neutral carotenoids, induced by temporal electric field brought by the carotenoid cation-bacteriochlorophyll anion pair. These findings remove the need to assign an S* state, and thereby significantly simplify the photochemistry of carotenoids in these photosynthetic antenna complexes.

High-resolution crystal structure of Streptococcus pyogenes β-NAD{sup +} glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface

Energy Technology Data Exchange (ETDEWEB)

Yoon, Ji Young; An, Doo Ri; Yoon, Hye-Jin [Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, Hyoun Sook [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-742 (Korea, Republic of); Lee, Sang Jae [Seoul National University, Seoul 151-742 (Korea, Republic of); Im, Ha Na; Jang, Jun Young [Seoul National University, Seoul 151-747 (Korea, Republic of); Suh, Se Won, E-mail: sewonsuh@snu.ac.kr [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-747 (Korea, Republic of)

2013-11-01

The crystal structure of the complex between the C-terminal domain of Streptococcus pyogenes β-NAD{sup +} glycohydrolase and an endogenous inhibitor for SPN was determined at 1.70 Å. It reveals that the interface between the two proteins is highly rich in water molecules. One of the virulence factors produced by Streptococcus pyogenes is β-NAD{sup +} glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38–451) and the full-length IFS (residues 1–161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPN{sub ct}–IFS complex, which consists of the SPN C-terminal domain (SPN{sub ct}; residues 193–451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70 Å resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPN{sub ct} and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope.

The strategic control of prospective memory monitoring in response to complex and probabilistic contextual cues.

Science.gov (United States)

Bugg, Julie M; Ball, B Hunter

2017-07-01

Participants use simple contextual cues to reduce deployment of costly monitoring processes in contexts in which prospective memory (PM) targets are not expected. This study investigated whether this strategic monitoring pattern is observed in response to complex and probabilistic contextual cues. Participants performed a lexical decision task in which words or nonwords were presented in upper or lower locations on screen. The specific condition was informed that PM targets ("tor" syllable) would occur only in words in the upper location, whereas the nonspecific condition was informed that targets could occur in any location or word type. Context was blocked such that word type and location changed every 8 trials. In Experiment 1, the specific condition used the complex contextual cue to reduce monitoring in unexpected contexts relative to the nonspecific condition. This pattern largely was not evidenced when the complex contextual cue was probabilistic (Experiment 2). Experiment 3 confirmed that strategic monitoring is observed for a complex cue that is deterministic, but not one that is probabilistic. Additionally, Experiments 1 and 3 demonstrated a disadvantage associated with strategic monitoring-namely, that the specific condition was less likely to respond to a PM target in an unexpected context. Experiment 3 provided evidence that this disadvantage is attributable to impaired noticing of the target. The novel findings suggest use of a complex contextual cue per se is not a boundary condition for the strategic, context-specific allocation of monitoring processes to support prospective remembering; however, strategic monitoring is constrained by the predictive utility of the complex contextual cue.

Survey of large protein complexes D. vulgaris reveals great structural diversity

Energy Technology Data Exchange (ETDEWEB)

Han, B.-G.; Dong, M.; Liu, H.; Camp, L.; Geller, J.; Singer, M.; Hazen, T. C.; Choi, M.; Witkowska, H. E.; Ball, D. A.; Typke, D.; Downing, K. H.; Shatsky, M.; Brenner, S. E.; Chandonia, J.-M.; Biggin, M. D.; Glaeser, R. M.

2009-08-15

An unbiased survey has been made of the stable, most abundant multi-protein complexes in Desulfovibrio vulgaris Hildenborough (DvH) that are larger than Mr {approx} 400 k. The quaternary structures for 8 of the 16 complexes purified during this work were determined by single-particle reconstruction of negatively stained specimens, a success rate {approx}10 times greater than that of previous 'proteomic' screens. In addition, the subunit compositions and stoichiometries of the remaining complexes were determined by biochemical methods. Our data show that the structures of only two of these large complexes, out of the 13 in this set that have recognizable functions, can be modeled with confidence based on the structures of known homologs. These results indicate that there is significantly greater variability in the way that homologous prokaryotic macromolecular complexes are assembled than has generally been appreciated. As a consequence, we suggest that relying solely on previously determined quaternary structures for homologous proteins may not be sufficient to properly understand their role in another cell of interest.

Simultaneous repair of abdominal aortic aneurysm and resection of unexpected, associated abdominal malignancies.

Science.gov (United States)

Illuminati, Giulio; Calio', Francesco G; D'Urso, Antonio; Lorusso, Riccardo; Ceccanei, Gianluca; Vietri, Francesco

2004-12-15

The management of unexpected intra-abdominal malignancy, discovered at laparotomy for elective treatment of an abdominal aortic aneurysm (AAA), is controversial. It is still unclear whether both conditions should be treated simultaneously or a staged approach is to be preferred. To contribute in improving treatment guidelines, we retrospectively reviewed the records of patients undergoing laparotomy for elective AAA repair. From January 1994 to March 2003, 253 patients underwent elective, trans-peritoneal repair of an AAA. In four patients (1.6%), an associated, unexpected neoplasm was detected at abdominal exploration, consisting of one renal, one gastric, one ileal carcinoid, and one ascending colon tumor. All of them were treated at the same operation, after aortic repair and careful isolation of the prosthetic graft. The whole series' operative mortality was 3.6%. None of the patients simultaneously treated for AAA and tumor resection died in the postoperative period. No graft-related infections were observed. Simultaneous treatment of AAA and tumor did not prolong significantly the mean length of stay in the hospital, compared to standard treatment of AAA alone. Except for malignancies of organs requiring major surgical resections, simultaneous AAA repair and resection of an associated, unexpected abdominal neoplasm can be safely performed, in most of the patients, sparing the need for a second procedure. Endovascular grafting of the AAA can be a valuable tool in simplifying simultaneous treatment, or in staging the procedures with a very short delay.

Incidentally found and unexpected tumors discovered by MRI examination for temporomandibular joint arthrosis

International Nuclear Information System (INIS)

Yanagi, Yoshinobu; Asaumi, Jun-ichi; Maki, Yuu; Murakami, Jun; Hisatomi, Miki; Matsuzaki, Hidenobu; Konouchi, Hironobu; Honda, Yosutoshi; Kishi, Kanji

2003-01-01

We examined the frequency of incidentally found or unexpected tumors discovered at the time of magnetic resonance imaging (MRI) examinations in the temporomandibular joint (TMJ) region for patients with suspicion of TMJ arthrosis. Five MR images (T1-weighted transverse scout image and proton density and T2-weighted oblique sagittal images at the open and closed mouth) were acquired. In 2776 MRI examinations of TMJ arthrosis, two tumors were discovered. They consisted of an adenoid cystic carcinoma in the deep portion of the parotid gland, and a malignant tumor extending from the infratemporal fossa to the parapharyngeal space. The rate of incidentally founded or unexpected tumors in TMJ examinations was low (0.072%), but the two tumors found were malignant tumors, and therefore, scout image should be carefully examined, not only used for positing the slice

Incidentally found and unexpected tumors discovered by MRI examination for temporomandibular joint arthrosis

Energy Technology Data Exchange (ETDEWEB)

Yanagi, Yoshinobu; Asaumi, Jun-ichi E-mail: asaumi@md.okayama-u.ac.jp; Maki, Yuu; Murakami, Jun; Hisatomi, Miki; Matsuzaki, Hidenobu; Konouchi, Hironobu; Honda, Yosutoshi; Kishi, Kanji

2003-07-01

We examined the frequency of incidentally found or unexpected tumors discovered at the time of magnetic resonance imaging (MRI) examinations in the temporomandibular joint (TMJ) region for patients with suspicion of TMJ arthrosis. Five MR images (T1-weighted transverse scout image and proton density and T2-weighted oblique sagittal images at the open and closed mouth) were acquired. In 2776 MRI examinations of TMJ arthrosis, two tumors were discovered. They consisted of an adenoid cystic carcinoma in the deep portion of the parotid gland, and a malignant tumor extending from the infratemporal fossa to the parapharyngeal space. The rate of incidentally founded or unexpected tumors in TMJ examinations was low (0.072%), but the two tumors found were malignant tumors, and therefore, scout image should be carefully examined, not only used for positing the slice.

76 FR 14271 - Unexpected Urgent Refugee and Migration Needs Related to Libya

Science.gov (United States)

2011-03-16

... March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya Memorandum for the... States, including section 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the ``Act''), as... million from the United States Emergency Refugee and Migration Assistance Fund, for the purpose of meeting...

Two conformational states of the membrane-associated Bacillus thuringiensis Cry4Ba δ-endotoxin complex revealed by electron crystallography: Implications for toxin-pore formation

International Nuclear Information System (INIS)

Ounjai, Puey; Unger, Vinzenz M.; Sigworth, Fred J.; Angsuthanasombat, Chanan

2007-01-01

The insecticidal nature of Cry δ-endotoxins produced by Bacillus thuringiensis is generally believed to be caused by their ability to form lytic pores in the midgut cell membrane of susceptible insect larvae. Here we have analyzed membrane-associated structures of the 65-kDa dipteran-active Cry4Ba toxin by electron crystallography. The membrane-associated toxin complex was crystallized in the presence of DMPC via detergent dialysis. Depending upon the charge of the adsorbed surface, 2D crystals of the oligomeric toxin complex have been captured in two distinct conformations. The projection maps of those crystals have been generated at 17 A resolution. Both complexes appeared to be trimeric; as in one crystal form, its projection structure revealed a symmetrical pinwheel-like shape with virtually no depression in the middle of the complex. The other form revealed a propeller-like conformation displaying an obvious hole in the center region, presumably representing the toxin-induced pore. These crystallographic data thus demonstrate for the first time that the 65-kDa activated Cry4Ba toxin in association with lipid membranes could exist in at least two different trimeric conformations, conceivably implying the closed and open states of the pore

Audit of radiology communication systems for critical, urgent, and unexpected significant findings

International Nuclear Information System (INIS)

Duncan, K.A.; Drinkwater, K.J.; Dugar, N.; Howlett, D.C.

2016-01-01

Aim: To determine the compliance of UK radiology departments and trusts/healthcare organisations with National Patient Safety Agency and Royal College of Radiologist's published guidance on the communication of critical, urgent, and unexpected significant radiological findings. Materials and methods: A questionnaire was sent to all UK radiology department audit leads asking for details of their current departmental policy regarding the issuing of alerts; use of automated electronic alert systems; methods of notification of clinicians of critical, urgent, and unexpected significant radiological findings; monitoring of results receipt; and examples of the more common types of serious pathologies for which alerts were issued. Results: One hundred and fifty-four of 229 departments (67%) responded. Eighty-eight percent indicated that they had a policy in place for the communication of critical, urgent, and unexpected significant radiological findings. Only 34% had an automated electronic alert system in place and only 17% had a facility for service-wide electronic tracking of radiology reports. In only 11 departments with an electronic acknowledgement system was someone regularly monitoring the read rate. Conclusion: There is wide variation in practice across the UK with regard to the communication and monitoring of reports with many departments/trusts not fully compliant with published UK guidance. Despite the widespread use of electronic systems, only a minority of departments/trusts have and use electronic tracking to ensure reports have been read and acted upon. - Highlights: • UK wide audit of communication of significant radiology results. • 88% of departments have a communication policy in place. • 34% of departments have an automated electronic alert system. • 17% of Trusts have facility for service wide electronic tracking of radiology reports.

13C-NMR reveals glycerol as an unexpected major metabolite of the protozoan parasite Trichomonas vaginalis

International Nuclear Information System (INIS)

Chapman, A.; Lloyd, D.; Linstead, D.J.; Williams, J.

1985-01-01

13 C-NMR has been used to study the kinetics of the formation of metabolites from [l- 13 C]glucose in intact cells of Trichomonas vaginalis during anaerobic incubation. As well as the expected metabolites lactate and acetate, this technique revealed glycerol as an additional major product, present in amounts equimolar with acetate. The formation of glycerol is readily explained in terms of the need to maintain redox balance. This protozoan now joins the small group of organisms which are known to produce glycerol as a result of normal metabolic activities. (Auth.)

Copper imbalances in ruminants and humans: unexpected common ground.

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Suttle, Neville F

2012-09-01

Ruminants are more vulnerable to copper deficiency than humans because rumen sulfide generation lowers copper availability from forage, increasing the risk of conditions such as swayback in lambs. Molybdenum-rich pastures promote thiomolybdate (TM) synthesis and formation of unabsorbable Cu-TM complexes, turning risk to clinical reality (hypocuprosis). Selection pressures created ruminant species with tolerance of deficiency but vulnerability to copper toxicity in alien environments, such as specific pathogen-free units. By contrast, cases of copper imbalance in humans seemed confined to rare genetic aberrations of copper metabolism. Recent descriptions of human swayback and the exploratory use of TM for the treatment of Wilson's disease, tumor growth, inflammatory diseases, and Alzheimer's disease have created unexpected common ground. The incidence of pre-hemolytic copper poisoning in specific pathogen-free lambs was reduced by an infection with Mycobacterium avium that left them more responsive to treatment with TM but vulnerable to long-term copper depletion. Copper requirements in ruminants and humans may need an extra allowance for the "copper cost" of immunity to infection. Residual cuproenzyme inhibition in TM-treated lambs and anomalies in plasma copper composition that appeared to depend on liver copper status raise this question "can chelating capacity be harnessed without inducing copper-deficiency in ruminants or humans?" A model of equilibria between exogenous (TM) and endogenous chelators (e.g., albumin, metallothionein) is used to predict risk of exposure and hypocuprosis; although risk of natural exposure in humans is remote, vulnerability to TM-induced copper deficiency may be high. Biomarkers of TM impact are needed, and copper chaperones for inhibited cuproenzymes are prime candidates.

Investigating Teachers' Appraisal of Unexpected Moments and Underlying Values: An Exploratory Case in the Context of Changing Mathematics Classroom Discourse

Science.gov (United States)

Cavanna, Jillian M.; Herbel-Eisenmann, Beth; Seah, Wee Tiong

2015-01-01

This article provides an exploratory case study that examines what one teacher indicated as unexpected as she worked to become more purposeful about her classroom discourse practices. We found that she highlighted three areas as being unexpected: (1) aspects of lesson enactment; (2) characteristics of student learning and (3) her own…

Mitochondrial genomes reveal recombination in the presumed asexual Fusarium oxysporum species complex.

Science.gov (United States)

Brankovics, Balázs; van Dam, Peter; Rep, Martijn; de Hoog, G Sybren; J van der Lee, Theo A; Waalwijk, Cees; van Diepeningen, Anne D

2017-09-18

The Fusarium oxysporum species complex (FOSC) contains several phylogenetic lineages. Phylogenetic studies identified two to three major clades within the FOSC. The mitochondrial sequences are highly informative phylogenetic markers, but have been mostly neglected due to technical difficulties. A total of 61 complete mitogenomes of FOSC strains were de novo assembled and annotated. Length variations and intron patterns support the separation of three phylogenetic species. The variable region of the mitogenome that is typical for the genus Fusarium shows two new variants in the FOSC. The variant typical for Fusarium is found in members of all three clades, while variant 2 is found in clades 2 and 3 and variant 3 only in clade 2. The extended set of loci analyzed using a new implementation of the genealogical concordance species recognition method support the identification of three phylogenetic species within the FOSC. Comparative analysis of the mitogenomes in the FOSC revealed ongoing mitochondrial recombination within, but not between phylogenetic species. The recombination indicates the presence of a parasexual cycle in F. oxysporum. The obstacles hindering the usage of the mitogenomes are resolved by using next generation sequencing and selective genome assemblers, such as GRAbB. Complete mitogenome sequences offer a stable basis and reference point for phylogenetic and population genetic studies.

Hunting for unexpected post-translational modifications by spectral library searching with tier-wise scoring.

Science.gov (United States)

Ma, Chun Wai Manson; Lam, Henry

2014-05-02

Discovering novel post-translational modifications (PTMs) to proteins and detecting specific modification sites on proteins is one of the last frontiers of proteomics. At present, hunting for post-translational modifications remains challenging in widely practiced shotgun proteomics workflows due to the typically low abundance of modified peptides and the greatly inflated search space as more potential mass shifts are considered by the search engines. Moreover, most popular search methods require that the user specifies the modification(s) for which to search; therefore, unexpected and novel PTMs will not be detected. Here a new algorithm is proposed to apply spectral library searching to the problem of open modification searches, namely, hunting for PTMs without prior knowledge of what PTMs are in the sample. The proposed tier-wise scoring method intelligently looks for unexpected PTMs by allowing mass-shifted peak matches but only when the number of matches found is deemed statistically significant. This allows the search engine to search for unexpected modifications while maintaining its ability to identify unmodified peptides effectively at the same time. The utility of the method is demonstrated using three different data sets, in which the numbers of spectrum identifications to both unmodified and modified peptides were substantially increased relative to a regular spectral library search as well as to another open modification spectral search method, pMatch.

Unexpected properties of Radim-type radon monitors

International Nuclear Information System (INIS)

Plch, J.; Burian, I.; Jilek, K.; Vosahlik, J.

2004-01-01

The results of numerous experiments carried out using Radim-type monitors are summarized. The monitor, which is based on collection of ions on the surface of a semiconductor detector in an electric field, exhibits enormous efficiency in collecting ions, which attains a value of 70% in the optimum case. The collection efficiency exhibits low dependence on the humidity: the efficiency decreases by 7.4% when the humidity changes from 50 to 90%. The dependence on the humidity is linear to 10% - in contradiction with the published results. The work gives the experimentally determined decreases in the presence of smoke and VOCs, which are acceptable even when the smoke and VOC concentrations are enormous. The results are analyzed and an attempt was made to theoretically explain these unexpected results. (author)

The Complexome of Dehalococcoides mccartyi Reveals Its Organohalide Respiration-Complex Is Modular

Directory of Open Access Journals (Sweden)

Katja Seidel

2018-06-01

Full Text Available Dehalococcoides mccartyi strain CBDB1 is a slow growing strictly anaerobic microorganism dependent on halogenated compounds as terminal electron acceptor for anaerobic respiration. Indications have been described that the membrane-bound proteinaceous organohalide respiration complex of strain CBDB1 is functional without quinone-mediated electron transfer. We here study this multi-subunit protein complex in depth in regard to participating protein subunits and interactions between the subunits using blue native gel electrophoresis coupled to mass spectrometric label-free protein quantification. Applying three different solubilization modes to detach the respiration complex from the membrane we describe different solubilization snapshots of the organohalide respiration complex. The results demonstrate the existence of a two-subunit hydrogenase module loosely binding to the rest of the complex, tight binding of the subunit HupX to OmeA and OmeB, predicted to be the two subunits of a molybdopterin-binding redox subcomplex, to form a second module, and the presence of two distinct reductive dehalogenase module variants with different sizes. In our data we obtained biochemical evidence for the specificity between a reductive dehalogenase RdhA (CbdbA80 and its membrane anchor protein RdhB (CbdbB3. We also observed weak interactions between the reductive dehalogenase and the hydrogenase module suggesting a not yet recognized contact surface between these two modules. Especially an interaction between the two integral membrane subunits OmeB and RdhB seems to promote the integrity of the complex. With the different solubilization strengths we observe successive disintegration of the complex into its subunits. The observed architecture would allow the association of different reductive dehalogenase modules RdhA/RdhB with the other two protein complex modules when the strain is growing on different electron acceptors. In the search for other respiratory

Structural and functional insights into the malaria parasite moving junction complex.

Directory of Open Access Journals (Sweden)

Brigitte Vulliez-Le Normand

Full Text Available Members of the phylum Apicomplexa, which include the malaria parasite Plasmodium, share many features in their invasion mechanism in spite of their diverse host cell specificities and life cycle characteristics. The formation of a moving junction (MJ between the membranes of the invading apicomplexan parasite and the host cell is common to these intracellular pathogens. The MJ contains two key parasite components: the surface protein Apical Membrane Antigen 1 (AMA1 and its receptor, the Rhoptry Neck Protein (RON complex, which is targeted to the host cell membrane during invasion. In particular, RON2, a transmembrane component of the RON complex, interacts directly with AMA1. Here, we report the crystal structure of AMA1 from Plasmodium falciparum in complex with a peptide derived from the extracellular region of PfRON2, highlighting clear specificities of the P. falciparum RON2-AMA1 interaction. The receptor-binding site of PfAMA1 comprises the hydrophobic groove and a region that becomes exposed by displacement of the flexible Domain II loop. Mutations of key contact residues of PfRON2 and PfAMA1 abrogate binding between the recombinant proteins. Although PfRON2 contacts some polymorphic residues, binding studies with PfAMA1 from different strains show that these have little effect on affinity. Moreover, we demonstrate that the PfRON2 peptide inhibits erythrocyte invasion by P. falciparum merozoites and that this strong inhibitory potency is not affected by AMA1 polymorphisms. In parallel, we have determined the crystal structure of PfAMA1 in complex with the invasion-inhibitory peptide R1 derived by phage display, revealing an unexpected structural mimicry of the PfRON2 peptide. These results identify the key residues governing the interactions between AMA1 and RON2 in P. falciparum and suggest novel approaches to antimalarial therapeutics.

Critical Neural Substrates for Correcting Unexpected Trajectory Errors and Learning from Them

Science.gov (United States)

Mutha, Pratik K.; Sainburg, Robert L.; Haaland, Kathleen Y.

2011-01-01

Our proficiency at any skill is critically dependent on the ability to monitor our performance, correct errors and adapt subsequent movements so that errors are avoided in the future. In this study, we aimed to dissociate the neural substrates critical for correcting unexpected trajectory errors and learning to adapt future movements based on…

Structure of UreG/UreF/UreH Complex Reveals How Urease Accessory Proteins Facilitate Maturation of Helicobacter pylori Urease

Science.gov (United States)

Fong, Yu Hang; Wong, Ho Chun; Yuen, Man Hon; Lau, Pak Ho; Chen, Yu Wai; Wong, Kam-Bo

2013-01-01

Urease is a metalloenzyme essential for the survival of Helicobacter pylori in acidic gastric environment. Maturation of urease involves carbamylation of Lys219 and insertion of two nickel ions at its active site. This process requires GTP hydrolysis and the formation of a preactivation complex consisting of apo-urease and urease accessory proteins UreF, UreH, and UreG. UreF and UreH form a complex to recruit UreG, which is a SIMIBI class GTPase, to the preactivation complex. We report here the crystal structure of the UreG/UreF/UreH complex, which illustrates how UreF and UreH facilitate dimerization of UreG, and assembles its metal binding site by juxtaposing two invariant Cys66-Pro67-His68 metal binding motif at the interface to form the (UreG/UreF/UreH)2 complex. Interaction studies revealed that addition of nickel and GTP to the UreG/UreF/UreH complex releases a UreG dimer that binds a nickel ion at the dimeric interface. Substitution of Cys66 and His68 with alanine abolishes the formation of the nickel-charged UreG dimer. This nickel-charged UreG dimer can activate urease in vitro in the presence of the UreF/UreH complex. Static light scattering and atomic absorption spectroscopy measurements demonstrated that the nickel-charged UreG dimer, upon GTP hydrolysis, reverts to its monomeric form and releases nickel to urease. Based on our results, we propose a mechanism on how urease accessory proteins facilitate maturation of urease. PMID:24115911

Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

Science.gov (United States)

Fassihi, Hiva; Sethi, Mieran; Fawcett, Heather; Wing, Jonathan; Chandler, Natalie; Mohammed, Shehla; Craythorne, Emma; Morley, Ana M. S.; Lim, Rongxuan; Turner, Sally; Henshaw, Tanya; Garrood, Isabel; Giunti, Paola; Hedderly, Tammy; Abiona, Adesoji; Naik, Harsha; Harrop, Gemma; McGibbon, David; Jaspers, Nicolaas G. J.; Botta, Elena; Nardo, Tiziana; Stefanini, Miria; Young, Antony R.; Sarkany, Robert P. E.; Lehmann, Alan R.

2016-01-01

Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID:26884178

Differential network analysis reveals evolutionary complexity in secondary metabolism of Rauvolfia serpentina over Catharanthus roseus

Directory of Open Access Journals (Sweden)

Shivalika Pathania

2016-08-01

Full Text Available Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Towards these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These mechanisms may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of Rauvolfia serpentina, and key genes that contribute towards diversification of specific metabolites.

Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus.

Science.gov (United States)

Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S

2016-01-01

Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites.

Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion.

Science.gov (United States)

Rosenthal, Sara Brin; Twomey, Colin R; Hartnett, Andrew T; Wu, Hai Shan; Couzin, Iain D

2015-04-14

Coordination among social animals requires rapid and efficient transfer of information among individuals, which may depend crucially on the underlying structure of the communication network. Establishing the decision-making circuits and networks that give rise to individual behavior has been a central goal of neuroscience. However, the analogous problem of determining the structure of the communication network among organisms that gives rise to coordinated collective behavior, such as is exhibited by schooling fish and flocking birds, has remained almost entirely neglected. Here, we study collective evasion maneuvers, manifested through rapid waves, or cascades, of behavioral change (a ubiquitous behavior among taxa) in schooling fish (Notemigonus crysoleucas). We automatically track the positions and body postures, calculate visual fields of all individuals in schools of ∼150 fish, and determine the functional mapping between socially generated sensory input and motor response during collective evasion. We find that individuals use simple, robust measures to assess behavioral changes in neighbors, and that the resulting networks by which behavior propagates throughout groups are complex, being weighted, directed, and heterogeneous. By studying these interaction networks, we reveal the (complex, fractional) nature of social contagion and establish that individuals with relatively few, but strongly connected, neighbors are both most socially influential and most susceptible to social influence. Furthermore, we demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur. Consequently, despite the intrinsic stochasticity of individual behavior, establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.

Intersubject information mapping: revealing canonical representations of complex natural stimuli

Directory of Open Access Journals (Sweden)

Nikolaus Kriegeskorte

2015-03-01

Full Text Available Real-world time-continuous stimuli such as video promise greater naturalism for studies of brain function. However, modeling the stimulus variation is challenging and introduces a bias in favor of particular descriptive dimensions. Alternatively, we can look for brain regions whose signal is correlated between subjects, essentially using one subject to model another. Intersubject correlation mapping (ICM allows us to find brain regions driven in a canonical manner across subjects by a complex natural stimulus. However, it requires a direct voxel-to-voxel match between the spatiotemporal activity patterns and is thus only sensitive to common activations sufficiently extended to match up in Talairach space (or in an alternative, e.g. cortical-surface-based, common brain space. Here we introduce the more general approach of intersubject information mapping (IIM. For each brain region, IIM determines how much information is shared between the subjects' local spatiotemporal activity patterns. We estimate the intersubject mutual information using canonical correlation analysis applied to voxels within a spherical searchlight centered on each voxel in turn. The intersubject information estimate is invariant to linear transforms including spatial rearrangement of the voxels within the searchlight. This invariance to local encoding will be crucial in exploring fine-grained brain representations, which cannot be matched up in a common space and, more fundamentally, might be unique to each individual – like fingerprints. IIM yields a continuous brain map, which reflects intersubject information in fine-grained patterns. Performed on data from functional magnetic resonance imaging (fMRI of subjects viewing the same television show, IIM and ICM both highlighted sensory representations, including primary visual and auditory cortices. However, IIM revealed additional regions in higher association cortices, namely temporal pole and orbitofrontal cortex. These

Data Mining and Complex Problems: Case Study in Composite Materials

Science.gov (United States)

Rabelo, Luis; Marin, Mario

2009-01-01

Data mining is defined as the discovery of useful, possibly unexpected, patterns and relationships in data using statistical and non-statistical techniques in order to develop schemes for decision and policy making. Data mining can be used to discover the sources and causes of problems in complex systems. In addition, data mining can support simulation strategies by finding the different constants and parameters to be used in the development of simulation models. This paper introduces a framework for data mining and its application to complex problems. To further explain some of the concepts outlined in this paper, the potential application to the NASA Shuttle Reinforced Carbon-Carbon structures and genetic programming is used as an illustration.

Sudden unexpected death under acute influence of cannabis.

Science.gov (United States)

Hartung, Benno; Kauferstein, Silke; Ritz-Timme, Stefanie; Daldrup, Thomas

2014-04-01

The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Test-potentiated learning: three independent replications, a disconfirmed hypothesis, and an unexpected boundary condition.

Science.gov (United States)

Wissman, Kathryn T; Rawson, Katherine A

2018-04-01

Arnold and McDermott [(2013). Test-potentiated learning: Distinguishing between direct and indirect effects of testing. Journal of Experimental Psychology: Learning, Memory, and Cognition, 39, 940-945] isolated the indirect effects of testing and concluded that encoding is enhanced to a greater extent following more versus fewer practice tests, referred to as test-potentiated learning. The current research provided further evidence for test-potentiated learning and evaluated the covert retrieval hypothesis as an alternative explanation for the observed effect. Learners initially studied foreign language word pairs and then completed either one or five practice tests before restudy occurred. Results of greatest interest concern performance on test trials following restudy for items that were not correctly recalled on the test trials that preceded restudy. Results replicate Arnold and McDermott (2013) by demonstrating that more versus fewer tests potentiate learning when trial time is limited. Results also provide strong evidence against the covert retrieval hypothesis concerning why the effect occurs (i.e., it does not reflect differential covert retrieval during pre-restudy trials). In addition, outcomes indicate that the magnitude of the test-potentiated learning effect decreases as trial length increases, revealing an unexpected boundary condition to test-potentiated learning.

The vital few meet the trivial many: unexpected use patterns in a monographs collection.

Science.gov (United States)

Eldredge, J D

1998-01-01

PURPOSE: To test three related hypotheses about monographs circulation at academic health sciences libraries: (1) Juran's "Vital Few" Principle, sometimes incorrectly referred to as the "Pareto Principle"; (2) most (> 30%) new monographs will not circulate within four years; and, (3) Trueswell's 20/80 rule concerning intensity of monographs circulation. METHODS: Retrospective circulation study conducted at a major academic health sciences library in November 1997 on monographs acquired during 1993, utilizing an online review file. RESULTS: Unexpectedly, most monographs (84%) had circulated at least once in the four years following acquisition. Combining circulation and in-house data revealed that 90.7% of the monographs acquired in 1993 had been used at least once. Small percentages of these monographs produced disproportionately high circulation levels. CONCLUSION: Monographs circulation rates confirm Juran's Vital Few principle. Most monographs circulated at least once in contrast to results reported by the Pittsburgh Study or other studies reported by Hardesty and Fenske. The results do not comply with Trueswell's 20/80 ratio rule. Further research needs to investigate the effects of low students to books ratios and problem-based learning (PBL) curricula upon monographs utilization. PMID:9803291

The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models.

Science.gov (United States)

Ikegami, Keisuke; Yoshimura, Takashi

2017-10-01

Thyroid hormones (TH) are important for development, growth, and metabolism. It is also clear that the synthesis and secretion of TH are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our understanding of the roles and regulatory mechanisms of TH. The animals' bodies develop through coordinated timing of cell division and differentiation. Studies of frog metamorphosis led to the discovery of TH and their role in development. However, to adapt to rhythmic environmental changes, animals also developed various endocrine rhythms. Studies of rodents clarified the neural and molecular mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds have a sophisticated seasonal adaptation mechanism, and recent studies of quail revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the seasonal regulation of reproduction. Interestingly, this mechanism is conserved in mammals. Thus, we review how animal studies have shaped our general understanding of the HPT axis in relation to biological rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.

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Turkington, Hannah L; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin; Hale, Benjamin G

2018-03-01

Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The

Unexpected Cartilage Phenotype in CD4-Cre-Conditional SOS-Deficient Mice.

Science.gov (United States)

Guittard, Geoffrey; Gallardo, Devorah L; Li, Wenmei; Melis, Nicolas; Lui, Julian C; Kortum, Robert L; Shakarishvili, Nicholas G; Huh, Sunmee; Baron, Jeffrey; Weigert, Roberto; Kramer, Joshua A; Samelson, Lawrence E; Sommers, Connie L

2017-01-01

RAS signaling is central to many cellular processes and SOS proteins promote RAS activation. To investigate the role of SOS proteins in T cell biology, we crossed Sos1 f/f Sos2 -/- mice to CD4-Cre transgenic mice. We previously reported an effect of these mutations on T cell signaling and T cell migration. Unexpectedly, we observed nodules on the joints of greater than 90% of these mutant mice at 5 months of age, especially on the carpal joints. As the mice aged further, some also displayed joint stiffness, hind limb paralysis, and lameness. Histological analysis indicated that the abnormal growth in joints originated from dysplastic chondrocytes. Second harmonic generation imaging of the carpal nodules revealed that nodules were encased by rich collagen fibrous networks. Nodules formed in mice also deficient in RAG2, indicating that conventional T cells, which undergo rearrangement of the T cell antigen receptor, are not required for this phenotype. CD4-Cre expression in a subset of cells, either immune lineage cells (e.g., non-conventional T cells) or non-immune lineage cells (e.g., chondrocytes) likely mediates the dramatic phenotype observed in this study. Disruptions of genes in the RAS signaling pathway are especially likely to cause this phenotype. These results also serve as a cautionary tale to those intending to use CD4-Cre transgenic mice to specifically delete genes in conventional T cells.

Failure of large transformation projects from the viewpoint of complex adaptive systems: Management principles for dealing with project dynamics

NARCIS (Netherlands)

Janssen, M.; Voort, H. van der; Veenstra, A.F.E. van

2015-01-01

Many large transformation projects do not result in the outcomes desired or envisioned by the stakeholders. This type of project is characterised by dynamics which are both caused by and result of uncertainties and unexpected behaviour. In this paper a complex adaptive system (CAS) view was adopted

Preserved scleral patch graft for unexpected extreme scleral thinning found at the scleral buckling procedure: A case report

Directory of Open Access Journals (Sweden)

Spela Stunf

2011-01-01

Full Text Available Pre-existing scleral pathology is an important risk factor for globe rupture during scleral buckling procedures. We report here, the surgical management of an unexpected scleral pathology found at the scleral buckling procedure in a retinal detachment patient. A 77-year-old white female with retinal detachment underwent a scleral buckling procedure. The surgery was converted into a scleral graft procedure, as extreme scleral thinning was found intraoperatively. An alcohol-preserved donor sclera graft was used. The second surgery for definitive retinal alignment was performed two weeks later. The presented case of an unexpected scleral pathology in a retinal detachment patient was managed with a combination of scleral grafting and pars plana vitrectomy, without any major complications. The anatomical outcome was excellent and the scleral rupture was prevented; the visual outcome was satisfactory. A conversion of the scleral buckling procedure into a scleral graft procedure has proved to be safe and effective for unexpected scleral pathology.

Tourism Stocks in Times of Crises: An Econometric Investigation of Unexpected Non-macroeconomic Factors

NARCIS (Netherlands)

A. Zopiatis (Anastasios); C.S. Savva (Christos); N. Lambertides (Neophytos); M.J. McAleer (Michael)

2017-01-01

textabstractFollowing the recent terrorist attacks in Paris, the European media emphatically pronounced that billions of Euros were wiped from tourism related stocks. The theoretical relationship of the industry with such unexpected non-macro incidents received moderate academic coverage.

Unprecedented high-resolution view of bacterial operon architecture revealed by RNA sequencing.

Science.gov (United States)

Conway, Tyrrell; Creecy, James P; Maddox, Scott M; Grissom, Joe E; Conkle, Trevor L; Shadid, Tyler M; Teramoto, Jun; San Miguel, Phillip; Shimada, Tomohiro; Ishihama, Akira; Mori, Hirotada; Wanner, Barry L

2014-07-08

We analyzed the transcriptome of Escherichia coli K-12 by strand-specific RNA sequencing at single-nucleotide resolution during steady-state (logarithmic-phase) growth and upon entry into stationary phase in glucose minimal medium. To generate high-resolution transcriptome maps, we developed an organizational schema which showed that in practice only three features are required to define operon architecture: the promoter, terminator, and deep RNA sequence read coverage. We precisely annotated 2,122 promoters and 1,774 terminators, defining 1,510 operons with an average of 1.98 genes per operon. Our analyses revealed an unprecedented view of E. coli operon architecture. A large proportion (36%) of operons are complex with internal promoters or terminators that generate multiple transcription units. For 43% of operons, we observed differential expression of polycistronic genes, despite being in the same operons, indicating that E. coli operon architecture allows fine-tuning of gene expression. We found that 276 of 370 convergent operons terminate inefficiently, generating complementary 3' transcript ends which overlap on average by 286 nucleotides, and 136 of 388 divergent operons have promoters arranged such that their 5' ends overlap on average by 168 nucleotides. We found 89 antisense transcripts of 397-nucleotide average length, 7 unannotated transcripts within intergenic regions, and 18 sense transcripts that completely overlap operons on the opposite strand. Of 519 overlapping transcripts, 75% correspond to sequences that are highly conserved in E. coli (>50 genomes). Our data extend recent studies showing unexpected transcriptome complexity in several bacteria and suggest that antisense RNA regulation is widespread. Importance: We precisely mapped the 5' and 3' ends of RNA transcripts across the E. coli K-12 genome by using a single-nucleotide analytical approach. Our resulting high-resolution transcriptome maps show that ca. one-third of E. coli operons are

Incidence of sudden unexpected death in epilepsy in community-based cohort in China.

Science.gov (United States)

Ge, Yan; Ding, Ding; Zhang, Qing; Yang, Bin; Wang, Taiping; Li, Beixu; Wang, Jie; Luo, Jianfeng; Kwan, Patrick; Wang, Wenzhi; Hong, Zhen; Sander, Josemir W

2017-11-01

Sudden unexpected death in epilepsy (SUDEP) is associated with the high premature mortality observed among people with epilepsy. It is, however, considered a rare event in China, probably because of lack of awareness and limitation of studies in the country. We aimed to provide some initial estimation of the burden of SUDEP in China. We established a large Chinese community-based cohort of people with epilepsy between January 2010 and December 2011. For any participant who died during follow-up, detailed information on cause of death was obtained using a specifically designed Verbal Autopsy Questionnaire. All cases were reviewed by a multidisciplinary expert panel and reinvestigated if necessary. Sudden unexpected death in epilepsy incidence rates were estimated and case details provided. The cohort consisted of 1562 people and during a median 5years follow-up, 72 deaths were reported. The all-causes death incidence was 11.23 (95% CI 8.86-14.07) per 1000 person-years. Fifteen died suddenly and unexpectedly in a reasonable state of health in the week preceding death. We recorded detailed information of these 15 deaths. Thirteen were considered to be probable SUDEP and two possible SUDEP. The incidence of probable SUDEP was 2.03 (95% CI 1.13-3.38) per 1000 person-years, and the incidence of all suspected (probable and possible) SUDEP was 2.34 (95% CI 1.36-3.77) per 1000 person-years. The incidence of SUDEP was relatively high among Chinese people with epilepsy when compared with that in previous community-based studies from high-income countries. The burden of SUDEP in China requires further assessments. Copyright © 2017 Elsevier Inc. All rights reserved.

Rethinking the longitudinal stream temperature paradigm: region-wide comparison of thermal infrared imagery reveals unexpected complexity of river temperatures

Science.gov (United States)

We used an extensive dataset of remotely sensed summertime river temperature to compare longitudinal profiles (temperature versus distance) for 54 rivers in the Pacific Northwest. We evaluated (1) how often profiles fit theoretical expectations of asymptotic downstream warming, a...

Revealing the Structural Complexity of Component Interactions of Topic-Specific PCK when Planning to Teach

Science.gov (United States)

Mavhunga, Elizabeth

2018-04-01

Teaching pedagogical content knowledge (PCK) at a topic-specific level requires clarity on the content-specific nature of the components employed, as well as the specific features that bring about the desirable depth in teacher explanations. Such understanding is often hazy; yet, it influences the nature of teacher tasks and learning opportunities afforded to pre-service teachers in a teaching program. The purpose of this study was twofold: firstly, to illuminate the emerging complexity when content-specific components of PCK interact when planning to teach a chemistry topic; and secondly, to identify the kinds of teacher tasks that promote the emergence of such complexity. Data collected were content representations (CoRes) in chemical equilibrium accompanied by expanded lesson outlines from 15 pre-service teachers in their final year of study towards a first degree in teaching (B Ed). The analysis involved extraction of episodes that exhibited component interaction by using a qualitative in-depth analysis method. The results revealed the structure in which the components of PCK in a topic interact among each other to be linear, interwoven, or a combination of the two. The interwoven interactions contained multiple components that connected explanations on different aspects of a concept, all working in a complementary manner. The most sophisticated component interactions emerged from teacher tasks on descriptions of a lesson sequence and a summary of a lesson. Recommendations in this study highlight core practices for making pedagogical transformation of topic content knowledge more accessible.

Frequency, severity and causes of unexpected allergic reactions to food: A systematic literature review

NARCIS (Netherlands)

Versluis, A.; Knulst, A.C.; Kruizinga, A.G.; Michelsen, A.; Houben, G.F.; Baumert, J.L.; Os-Medendorp, H. van

2015-01-01

Summary: Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to

Frequency, severity and causes of unexpected allergic reactions to food : A systematic literature review

NARCIS (Netherlands)

Versluis, A.; Knulst, A. C.; Kruizinga, A. G.; Michelsen, A.; Houben, G. F.; Baumert, J. L.; van Os-Medendorp, H.

2015-01-01

Summary: Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to

Operational planning optimization of steam power plants considering equipment failure in petrochemical complex

International Nuclear Information System (INIS)

Luo, Xianglong; Zhang, Bingjian; Chen, Ying; Mo, Songping

2013-01-01

Highlights: ► We develop a systematic programming methodology to address equipment failure. ► We classify different operation conditions into real periods and virtual periods. ► The formulated MILP models guarantee cost reduction and enough operation safety. ► The consideration of reserving operation redundancy is effective. - Abstract: One or more interconnected steam power plants (SPPs) are constructed in a petrochemical complex to supply utility energy to the process. To avoid large economic penalties or process shutdowns, these SPPs should be flexible and reliable enough to meet the process energy requirement under varying conditions. Unexpected utility equipment failure is inevitable and difficult to be predicted. Most of the conventional methods are based on the assumption that SPPs do not experience any kind of equipment failure. Unfortunately, a process shutdown cannot be avoided when equipment fails unexpectedly. In this paper, a systematic methodology is presented to minimize the total cost under normal conditions while reserving enough flexibility and safety for unexpected equipment failure conditions. The proposed method transforms the different conditions into real periods to indicate normal scenarios and virtual periods to indicate unexpected equipment failure scenarios. The optimization strategy incorporating various operation redundancy scheduling, the transition constraints from equipment failure conditions to normal conditions, and the boiler load increase behavior modeling are presented to save cost and guarantee operation safety. A detailed industrial case study shows that the proposed systematic methodology is effective and practical in coping with equipment failure conditions with only few additional cost penalties

Crystal structure of Clostridium botulinum whole hemagglutinin reveals a huge triskelion-shaped molecular complex.

Science.gov (United States)

Amatsu, Sho; Sugawara, Yo; Matsumura, Takuhiro; Kitadokoro, Kengo; Fujinaga, Yukako

2013-12-06

Clostridium botulinum HA is a component of the large botulinum neurotoxin complex and is critical for its oral toxicity. HA plays multiple roles in toxin penetration in the gastrointestinal tract, including protection from the digestive environment, binding to the intestinal mucosal surface, and disruption of the epithelial barrier. At least two properties of HA contribute to these roles: the sugar-binding activity and the barrier-disrupting activity that depends on E-cadherin binding of HA. HA consists of three different proteins, HA1, HA2, and HA3, whose structures have been partially solved and are made up mainly of β-strands. Here, we demonstrate structural and functional reconstitution of whole HA and present the complete structure of HA of serotype B determined by x-ray crystallography at 3.5 Å resolution. This structure reveals whole HA to be a huge triskelion-shaped molecule. Our results suggest that whole HA is functionally and structurally separable into two parts: HA1, involved in recognition of cell-surface carbohydrates, and HA2-HA3, involved in paracellular barrier disruption by E-cadherin binding.

Crown Ether Complexes of Alkali-Metal Chlorides from SO2.

Science.gov (United States)

Reuter, Kirsten; Rudel, Stefan S; Buchner, Magnus R; Kraus, Florian; von Hänisch, Carsten

2017-07-18

The structures of alkali-metal chloride SO 2 solvates (Li-Cs) in conjunction with 12-crown-4 or 1,2-disila-12-crown-4 show strong discrepancies, despite the structural similarity of the ligands. Both types of crown ethers form 1:1 complexes with LiCl to give [Li(1,2-disila-12-crown-4)(SO 2 Cl)] (1) and [Li(12-crown-4)Cl]⋅4 SO 2 (2). However, 1,2-disila-12-crown-4 proved unable to coordinate cations too large for the cavity diameter, for example, by the formation of sandwich-type complexes. As a result, 12-crown-4 reacts exclusively with the heavier alkali-metal chlorides NaCl, KCl and RbCl. Compounds [Na(12-crown-4) 2 ]Cl⋅4 SO 2 (3) and [M(12-crown-4) 2 (SO 2 )]Cl⋅4 SO 2 (4: M=K; 5: M=Rb) all showed S-coordination to the chloride ions through four SO 2 molecules. Compounds 4 and 5 additionally exhibit the first crystallographically confirmed non-bridging O,O'-coordination mode of SO 2 . Unexpectedly, the disila-crown ether supports the dissolution of RbCl and CsCl in the solvent and gives the homoleptic SO 2 -solvated alkali-metal chlorides [MCl⋅3 SO 2 ] (6: M=Rb; 7: M=Cs), which incorporate bridging μ-O,O'-coordinating moieties and the unprecedented side-on O,O'-coordination mode. All compounds were characterised by single-crystal X-ray diffraction. The crown ether complexes were additionally studied by using NMR spectroscopy, and the presence of SO 2 at ambient temperature was revealed by IR spectroscopy of the neat compounds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sudden and unexpected childhood deaths investigated at the Pretoria Medico-Legal Laboratory, South Africa, 2007 - 2011.

Science.gov (United States)

Van Deventer, B S; Rossouw, S H; Du Toit-Prinsloo, L

2016-09-06

 Sudden and unexpected death is well known to occur in infants, and although sudden deaths are less frequent after the first birthday, they still account for a significant proportion of childhood deaths. In 2009, 1.9% of the total deaths in the USA were childhood deaths. In South Africa (SA) this proportion was much higher at 11.85%. According to the law, sudden and unexpected deaths are generally investigated as unnatural deaths. Establishing an exact underlying anatomical cause of death will depend on available resources and can be difficult in a substantial proportion of cases.  A retrospective descriptive case audit was conducted at the Pretoria Medico-Legal Laboratory (PMLL), SA, from 1 January 2007 through to 31 December 2011. All children aged 1 - 18 years who died suddenly and unexpectedly were included.  Ninety-eight cases were identified, which constituted nearly 1% of total admissions to the PMLL. The majority of the deaths were of children aged 1 - 5 years, and the male/female ratio was 1.04:1. In the largest proportion of cases (n=28, 28.6%), the medicolegal investigation, including autopsy and ancillary investigations, did not establish an underlying anatomical cause of death. In the cases where a cause of death was established, pneumonia was the most common diagnosis (n=22, 22.4%).  The fact that the cause of the largest proportion of deaths could not be ascertained emphasises the need for consideration of additional investigative techniques, such as molecular/genetic screening, which have provided an underlying cause of death in a significant number of cases in other countries. There is a lack of published research on the causes and incidence of sudden unexpected deaths in children in SA, and further research in this area is needed.

Sudden unexpected death in infancy in Denmark

DEFF Research Database (Denmark)

Winkel, Bo Gregers; Holst, Anders Gaarsdal; Theilade, Juliane

2011-01-01

Abstract Background. Incidence of sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS) differs among studies and non-autopsied cases are difficult to assess. Objectives. To investigate causes of sudden death in infancy in a nationwide setting. Validate the use...... of the ICD-10 code for SIDS (R95) in the Danish Cause of Death registry. Design. A retrospective analysis of all infant deaths (death certificates and autopsy reports were read. Results. We identified 192 SUDI cases (10% of total deaths, 0.42 per 1000 births......) with autopsy performed in 87% of cases. In total, 49% of autopsied SUDI cases were defined as SIDS (5% of all deaths, 0.22 per 1000 births); Cardiac cause of death was denoted in 24% of cases. The Danish Cause of Death Registry misclassified 30% of SIDS cases. Conclusions. A large proportion of infant deaths...

Machine learning and complex-network for personalized and systems biomedicine

KAUST Repository

Cannistraci, Carlo Vittorio

2016-01-27

The talk will begin with an introduction on using machine learning to discover hidden information and unexpected patterns in large biomedical datasets. Then, recent results on the use of complex network theory in biomedicine and neuroscience will be discussed. In particular, metagenomics and metabolomics data, approaches for drug-target repositioning, functional/structural MR connectomes and gut-brain axis data will be presented. The conclusion will outline the novel and exciting perspectives offered by the translation of these methods from systems biology to systems medicine.

The creative use of unexpected responses in the hypnotherapy of patients with conversion disorders

NARCIS (Netherlands)

Moene, F.C.; Hoogduin, C.A.L.

1999-01-01

In a previously completed empirical study examining the use of hypnosis in a comprehensive treatment program with 85 patients who suffered motor conversion symptoms, 16 patients were reported by their therapists to have had unusual and unexpected responses during hypnosis. This article summarizes

Acidity enhancement of unsaturated bases of group 15 by association with borane and beryllium dihydride. Unexpected boron and beryllium Brønsted acids.

Science.gov (United States)

Martín-Sómer, Ana; Mó, Otilia; Yáñez, Manuel; Guillemin, Jean-Claude

2015-01-21

The intrinsic acidity of CH2[double bond, length as m-dash]CHXH2, HC[triple bond, length as m-dash]CXH2 (X = N, P, As, Sb) derivatives and of their complexes with BeH2 and BH3 has been investigated by means of high-level density functional theory and molecular orbital ab initio calculations, using as a reference the ethyl saturated analogues. The acidity of the free systems steadily increases down the group for the three series of derivatives, ethyl, vinyl and ethynyl. The association with both beryllium dihydride and borane leads to a very significant acidity enhancement, being larger for BeH2 than for BH3 complexes. This acidity enhancement, for the unsaturated compounds, is accompanied by a change in the acidity trends down the group, which do not steadily decrease but present a minimum value for both the vinyl- and the ethynyl-phosphine. When the molecule acting as the Lewis acid is beryllium dihydride, the π-type complexes in which the BeH2 molecules interact with the double or triple bond are found, in some cases, to be more stable, in terms of free energies, than the conventional complexes in which the attachment takes place at the heteroatom, X. The most important finding, however, is that P, As, and Sb ethynyl complexes with BeH2 do not behave as P, As, or Sb Brønsted acids, but unexpectedly as Be acids.

Unexpected Symmetry in the Nodal Structure of the He Atom

International Nuclear Information System (INIS)

Bressanini, Dario; Reynolds, Peter J.

2005-01-01

The nodes of even simple wave functions are largely unexplored. Motivated by their importance to quantum simulations of fermionic systems, we have found unexpected symmetries in the nodes of several atoms and molecules. Here, we report on helium. We find that in both ground and excited states the nodes have simple forms. In particular, they have higher symmetry than the wave functions they come from. It is of great interest to understand the source of these new symmetries. For the quantum simulations that motivated the study, these symmetries may help circumvent the fermion sign problem

Manganese-Catalyzed C−H Functionalizations: Hydroarylations and Alkenylations Involving an Unexpected Heteroaryl Shift

KAUST Repository

Wang, Chengming

2017-06-24

A manganese-catalyzed regio- and stereoselective hydroarylation of allenes is reported. The C−H functionalization method provides access to various alkenylated indoles in excellent yields. Moreover, a hydroarylation/cyclization cascade involving an unexpected C−N bond cleavage and aryl shift has been developed, which provides a new synthetic approach to substituted pyrroloindolones.

Manganese-Catalyzed C−H Functionalizations: Hydroarylations and Alkenylations Involving an Unexpected Heteroaryl Shift

KAUST Repository

Wang, Chengming; Wang, Ai; Rueping, Magnus

2017-01-01

A manganese-catalyzed regio- and stereoselective hydroarylation of allenes is reported. The C−H functionalization method provides access to various alkenylated indoles in excellent yields. Moreover, a hydroarylation/cyclization cascade involving an unexpected C−N bond cleavage and aryl shift has been developed, which provides a new synthetic approach to substituted pyrroloindolones.

Viral Transmission Dynamics at Single-Cell Resolution Reveal Transiently Immune Subpopulations Caused by a Carrier State Association.

Directory of Open Access Journals (Sweden)

William Cenens

2015-12-01

Full Text Available Monitoring the complex transmission dynamics of a bacterial virus (temperate phage P22 throughout a population of its host (Salmonella Typhimurium at single cell resolution revealed the unexpected existence of a transiently immune subpopulation of host cells that emerged from peculiarities preceding the process of lysogenization. More specifically, an infection event ultimately leading to a lysogen first yielded a phage carrier cell harboring a polarly tethered P22 episome. Upon subsequent division, the daughter cell inheriting this episome became lysogenized by an integration event yielding a prophage, while the other daughter cell became P22-free. However, since the phage carrier cell was shown to overproduce immunity factors that are cytoplasmically inherited by the P22-free daughter cell and further passed down to its siblings, a transiently resistant subpopulation was generated that upon dilution of these immunity factors again became susceptible to P22 infection. The iterative emergence and infection of transiently resistant subpopulations suggests a new bet-hedging strategy by which viruses could manage to sustain both vertical and horizontal transmission routes throughout an infected population without compromising a stable co-existence with their host.

GlcNAc-1-P-transferase–tunicamycin complex structure reveals basis for inhibition of N-glycosylation

Energy Technology Data Exchange (ETDEWEB)

Yoo, Jiho; Mashalidis, Ellene H.; Kuk, Alvin C. Y.; Yamamoto, Kazuki; Kaeser, Benjamin; Ichikawa, Satoshi; Lee, Seok-Yong

2018-02-19

N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders. The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin. Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT. Our understanding of how tunicamycin inhibits N-linked glycosylation and efforts to selectively target MraY are hampered by a lack of structural information. Here we present crystal structures of human GPT in complex with tunicamycin. In conclusion, structural and functional analyses reveal the difference between GPT and MraY in their mechanisms of inhibition by tunicamycin. We demonstrate that this difference could be exploited to design MraY-specific inhibitors as potential antibiotics.

Recall of Others' Actions after Incidental Encoding Reveals Episodic-like Memory in Dogs.

Science.gov (United States)

Fugazza, Claudia; Pogány, Ákos; Miklósi, Ádám

2016-12-05

The existence of episodic memory in non-human animals is a debated topic that has been investigated using different methodologies that reflect diverse theoretical approaches to its definition. A fundamental feature of episodic memory is recalling after incidental encoding, which can be assessed if the recall test is unexpected [1]. We used a modified version of the "Do as I Do" method [2], relying on dogs' ability to imitate human actions, to test whether dogs can rely on episodic memory when recalling others' actions from the past. Dogs were first trained to imitate human actions on command. Next, they were trained to perform a simple training exercise (lying down), irrespective of the previously demonstrated action. This way, we substituted their expectation to be required to imitate with the expectation to be required to lie down. We then tested whether dogs recalled the demonstrated actions by unexpectedly giving them the command to imitate, instead of lying down. Dogs were tested with a short (1 min) and a long (1 hr) retention interval. They were able to recall the demonstrated actions after both intervals; however, their performance declined more with time compared to conditions in which imitation was expected. These findings show that dogs recall past events as complex as human actions even if they do not expect the memory test, providing evidence for episodic-like memory. Dogs offer an ideal model to study episodic memory in non-human species, and this methodological approach allows investigating memory of complex, context-rich events. VIDEO ABSTRACT. Copyright © 2016 Elsevier Ltd. All rights reserved.

The unexpected product of Diels-Alder reaction between "indanocyclon" and maleimide

Science.gov (United States)

Dobrowolski, Michał A.; Roszkowski, Piotr; Struga, Marta; Szulczyk, Daniel

2017-02-01

A heterocyclic compound commonly known as "indanocyclon" undergoes an unexpected Diels-Alder addition with maleimide. The resulting product has been isolated and characterized in order to get an information about its structure and possible mechanism of the reaction. Extensive comparison of single crystal properties of 3-(2,8-dioxo-1,3-diphenyl-2,8-dihydrocyclopenta[a]inden-8a(1H)-yl)pyrrolidine-2,5-dione and favorable product of the reaction has been also performed.

Unexpectedly slow decrease of Chernobyl-derived radiocesium in air and deposition in Bavaria/Germany

International Nuclear Information System (INIS)

Bunzl, K.; Hoetzl, H.; Rosner, G.; Winkler, R.

1995-01-01

In this paper we analyze the corresponding data observed after the termination of the fresh fallout of Chernobyl-derived 137 Cs, and discuss possible reasons for the unexpectedly slow decrease of radiocesium in the air and in the total deposition to the ground. (SR)

Unexpectedly slow decrease of Chernobyl-derived radiocesium in air and deposition in Bavaria/Germany

Energy Technology Data Exchange (ETDEWEB)

Bunzl, K. [GSF-Forschungszentrum fuer Umwelt und Gesundheit, Neuherberg (Germany); Hoetzl, H. [GSF-Forschungszentrum fuer Umwelt und Gesundheit, Neuherberg (Germany); Rosner, G. [Inst. fuer Strahlenschutz, Oberschleissheim (Germany); Winkler, R. [Inst. fuer Strahlenschutz, Oberschleissheim (Germany)

1995-09-01

In this paper we analyze the corresponding data observed after the termination of the fresh fallout of Chernobyl-derived {sup 137}Cs, and discuss possible reasons for the unexpectedly slow decrease of radiocesium in the air and in the total deposition to the ground. (SR)

Unexpectedly high burden of rotavirus gastroenteritis in very young infants

Directory of Open Access Journals (Sweden)

Reilly Megan

2010-06-01

Full Text Available Abstract Background The highest incidence of rotavirus gastroenteritis has generally been reported in children 6-24 months of age. Young infants are thought to be partially protected by maternal antibodies acquired transplacentally or via breast milk. The purpose of our study was to assess the age distribution of children with confirmed community-acquired rotavirus gastroenteritis presenting to an urban referral hospital. Methods Children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by ELISA (followed by genotyping if ELISA-positive since the 1994-95 epidemic season. Results Over the last 12 rotavirus seasons prior to the introduction of the pentavalent rotavirus vaccine in 2006, stool specimens from 1646 patients tested positive for community-acquired rotavirus infection. Gender or age was not recorded in 6 and 5 cases, respectively. Overall, 58% of the cases occurred in boys. G1 was the predominant VP7 serotype, accounting for 72% of cases. The median (IQR age was 11 (5-21 months. A total of 790 (48% cases occurred in children outside the commonly quoted peak age range, with 27% in infants 24 months of age. A total of 220 (13% cases occurred during the first 3 months of life, and the highest number of episodes per month of age [97 (6%] was observed during the second month of life. Conclusions The incidence of community-acquired rotavirus gastroenteritis monitored over 12 seasons in the prevaccine era at a major university hospital was nearly constant for each month of age during the first year of life, revealing an unexpectedly high incidence of symptomatic rotavirus disease in infants

Complex socio-technical systems: Characterization and management guidelines.

Science.gov (United States)

Righi, Angela Weber; Saurin, Tarcisio Abreu

2015-09-01

Although ergonomics has paid increasing attention to the perspective of complexity, methods for its operationalization are scarce. This study introduces a framework for the operationalization of the "attribute view" of complexity, which involves: (i) the delimitation of the socio-technical system (STS); (ii) the description of four complexity attributes, namely a large number of elements in dynamic interactions, a wide diversity of elements, unexpected variability, and resilience; (iii) the assessment of six management guidelines, namely design slack, give visibility to processes and outcomes, anticipate and monitor the impacts of small changes, monitor the gap between prescription and practice, encourage diversity of perspectives when making decisions, and create an environment that supports resilience; and (iv) the identification of leverage points for improving the STS design, based on both the analysis of relationships among the attributes and their classification as irreducible/manageable complexity, and liability/asset. The use of the framework is illustrated by the study of an emergency department of a University hospital. Data collection involved analysis of documents, observations of work at the front-line, interviews with employees, and the application of questionnaires. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Willingness and ability to pay for unexpected dental expenses by Finnish adults

Directory of Open Access Journals (Sweden)

Widström Eeva

2012-08-01

Full Text Available Abstract Background Since 2002, adults have been able to choose oral health care services in the public sector or in the private sector in Finland. Though various subsidies for care exist in both sectors, the Public Dental Service (PDS is a cheaper option for the patient but, on the other hand, there are no waiting lists for private care. The aim of this study was to assess middle-aged adults' use of dental services, willingness to pay (WTP and ability to pay (ATP for unexpected, urgent dental treatment. Methods Postal questionnaires on use of dental services were sent to a random sample of 1500 47-59 year old adults living in three large municipalities in the Helsinki region. The initial response rate was 65.8%. Two hypothetical scenarios were presented: "What would be the highest price you would be prepared to pay to have a lost filling replaced immediately, or, at the latest, the day after losing the filling?" and " How much could you pay for unexpected dental expenses at two weeks notice, if you suddenly needed more comprehensive treatment?" Logistic regression analysis was used to analyse factors related to WTP and ATP. Results Most respondents (89.6% had visited a dentist recently and a majority (76.1% had used private services. For immediate replacement of a lost filling, almost all respondents (93.2% were willing to pay the lower price charged in the PDS and 46.2% were willing to pay the private fee. High income and no subjective need for dental treatment were positively associated with the probability of paying a higher price. Most respondents (93.0% were able to pay a low fee, EUR 50 and almost half (41.6% at least EUR 300 for unexpected treatment at short notice. High income and male sex were associated with high ATP. Conclusion There was a strong and statistically significant relationship between income and WTP and ATP for urgent dental care, indicating that access to publicly provided services improved equity for persons with low

Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy

Directory of Open Access Journals (Sweden)

Costin Leu

2015-09-01

Full Text Available Sudden unexpected death in epilepsy (SUDEP represents the most severe degree of the spectrum of epilepsy severity and is the commonest cause of epilepsy-related premature mortality. The precise pathophysiology and the genetic architecture of SUDEP remain elusive. Aiming to elucidate the genetic basis of SUDEP, we analysed rare, protein-changing variants from whole-exome sequences of 18 people who died of SUDEP, 87 living people with epilepsy and 1479 non-epilepsy disease controls. Association analysis revealed a significantly increased genome-wide polygenic burden per individual in the SUDEP cohort when compared to epilepsy (P = 5.7 × 10−3 and non-epilepsy disease controls (P = 1.2 × 10−3. The polygenic burden was driven both by the number of variants per individual, and over-representation of variants likely to be deleterious in the SUDEP cohort. As determined by this study, more than a thousand genes contribute to the observed polygenic burden within the framework of this study. Subsequent gene-based association analysis revealed five possible candidate genes significantly associated with SUDEP or epilepsy, but no one single gene emerges as common to the SUDEP cases. Our findings provide further evidence for a genetic susceptibility to SUDEP, and suggest an extensive polygenic contribution to SUDEP causation. Thus, an overall increased burden of deleterious variants in a highly polygenic background might be important in rendering a given individual more susceptible to SUDEP. Our findings suggest that exome sequencing in people with epilepsy might eventually contribute to generating SUDEP risk estimates, promoting stratified medicine in epilepsy, with the eventual aim of reducing an individual patient's risk of SUDEP.

Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy.

Science.gov (United States)

Leu, Costin; Balestrini, Simona; Maher, Bridget; Hernández-Hernández, Laura; Gormley, Padhraig; Hämäläinen, Eija; Heggeli, Kristin; Schoeler, Natasha; Novy, Jan; Willis, Joseph; Plagnol, Vincent; Ellis, Rachael; Reavey, Eleanor; O'Regan, Mary; Pickrell, William O; Thomas, Rhys H; Chung, Seo-Kyung; Delanty, Norman; McMahon, Jacinta M; Malone, Stephen; Sadleir, Lynette G; Berkovic, Samuel F; Nashef, Lina; Zuberi, Sameer M; Rees, Mark I; Cavalleri, Gianpiero L; Sander, Josemir W; Hughes, Elaine; Helen Cross, J; Scheffer, Ingrid E; Palotie, Aarno; Sisodiya, Sanjay M

2015-09-01

Sudden unexpected death in epilepsy (SUDEP) represents the most severe degree of the spectrum of epilepsy severity and is the commonest cause of epilepsy-related premature mortality. The precise pathophysiology and the genetic architecture of SUDEP remain elusive. Aiming to elucidate the genetic basis of SUDEP, we analysed rare, protein-changing variants from whole-exome sequences of 18 people who died of SUDEP, 87 living people with epilepsy and 1479 non-epilepsy disease controls. Association analysis revealed a significantly increased genome-wide polygenic burden per individual in the SUDEP cohort when compared to epilepsy (P = 5.7 × 10(- 3)) and non-epilepsy disease controls (P = 1.2 × 10(- 3)). The polygenic burden was driven both by the number of variants per individual, and over-representation of variants likely to be deleterious in the SUDEP cohort. As determined by this study, more than a thousand genes contribute to the observed polygenic burden within the framework of this study. Subsequent gene-based association analysis revealed five possible candidate genes significantly associated with SUDEP or epilepsy, but no one single gene emerges as common to the SUDEP cases. Our findings provide further evidence for a genetic susceptibility to SUDEP, and suggest an extensive polygenic contribution to SUDEP causation. Thus, an overall increased burden of deleterious variants in a highly polygenic background might be important in rendering a given individual more susceptible to SUDEP. Our findings suggest that exome sequencing in people with epilepsy might eventually contribute to generating SUDEP risk estimates, promoting stratified medicine in epilepsy, with the eventual aim of reducing an individual patient's risk of SUDEP.

Antiferromagnetic exchange in meta-phenylene bridged bis(tris-o-iminosemiquinonato)metal complexes

International Nuclear Information System (INIS)

Dei, A.; Gatteschi, D.; Sangregorio, C.; Sorace, L.; Vaz, M.G.F.

2004-01-01

By reaction of the ligand N,N' bis(3,5-di-tert-butyl-2-hydroxyphenyl)-1,3-phenylenediamine (1), with Fe, Co or Mn salts, three complexes were synthesized where the bis-bidentate ligand is in the bis-semiquinonato oxidation state. Although the m-phenylene linker is known to afford ferromagnetic coupling in diradicals, the antiferromagnetic interaction of intramolecular origin we observed is not unexpected, given the large torsion angles between the semiquinonato and the m-phenylene planes

Antiferromagnetic exchange in meta-phenylene bridged bis(tris-o-iminosemiquinonato)metal complexes

Energy Technology Data Exchange (ETDEWEB)

Dei, A. E-mail: andrea.dei@unifi.it; Gatteschi, D.; Sangregorio, C.; Sorace, L.; Vaz, M.G.F

2004-05-01

By reaction of the ligand N,N' bis(3,5-di-tert-butyl-2-hydroxyphenyl)-1,3-phenylenediamine (1), with Fe, Co or Mn salts, three complexes were synthesized where the bis-bidentate ligand is in the bis-semiquinonato oxidation state. Although the m-phenylene linker is known to afford ferromagnetic coupling in diradicals, the antiferromagnetic interaction of intramolecular origin we observed is not unexpected, given the large torsion angles between the semiquinonato and the m-phenylene planes.

Novel multiplex PCR reveals multiple trypanosomatid species infecting North American bumble bees (Hymenoptera: Apidae: Bombus).

Science.gov (United States)

Tripodi, Amber D; Szalanski, Allen L; Strange, James P

2018-03-01

Crithidia bombi and Crithidia expoeki (Trypanosomatidae) are common parasites of bumble bees (Bombus spp.). Crithidia bombi was described in the 1980s, and C. expoeki was recently discovered using molecular tools. Both species have cosmopolitan distributions among their bumble bee hosts, but there have been few bumble bee studies that have identified infections to species since the original description of C. expoeki in 2010. Morphological identification of species is difficult due to variability within each stage of their complex lifecycles, although they can be easily differentiated through DNA sequencing. However, DNA sequencing can be expensive, particularly with many samples to diagnose. In order to reliably and inexpensively distinguish Crithidia species for a large-scale survey, we developed a multiplex PCR protocol using species-specific primers with a universal trypanosomatid primer set to detect unexpected relatives. We applied this method to 356 trypanosomatid-positive bumble bees from North America as a first-look at the distribution and host range of each parasite in the region. Crithidia bombi was more common (90.2%) than C. expoeki (21.3%), with most C. expoeki-positive samples existing as co-infections with C. bombi (13.8%). This two-step detection method also revealed that 2.2% samples were positive for trypanosmatids that were neither C. bombi nor C. expoeki. Sequencing revealed that two individuals were positive for C. mellificae, one for Lotmaria passim, and three for two unclassified trypanosomatids. This two-step method is effective in diagnosing known bumble bee infecting Crithidia species, and allowing for the discovery of unknown potential symbionts. Published by Elsevier Inc.

Conformational Complexity in the LH2 Antenna of the Purple Sulfur Bacterium Allochromatium vinosum Revealed by Hole-Burning Spectroscopy.

Science.gov (United States)

Kell, Adam; Jassas, Mahboobe; Acharya, Khem; Hacking, Kirsty; Cogdell, Richard J; Jankowiak, Ryszard

2017-06-15

This work discusses the protein conformational complexity of the B800-850 LH2 complexes from the purple sulfur bacterium Allochromatium vinosum, focusing on the spectral characteristics of the B850 chromophores. Low-temperature B850 absorption and the split B800 band shift blue and red, respectively, at elevated temperatures, revealing isosbestic points. The latter indicates the presence of two (unresolved) conformations of B850 bacteriochlorophylls (BChls), referred to as conformations 1 and 2, and two conformations of B800 BChls, denoted as B800 R and B800 B . The energy differences between average site energies of conformations 1 and 2, and B800 R and B800 B are similar (∼200 cm -1 ), suggesting weak and strong hydrogen bonds linking two major subpopulations of BChls and the protein scaffolding. Although conformations 1 and 2 of the B850 chromophores, and B800 R and B800 B , exist in the ground state, selective excitation leads to 1 → 2 and B800 R → B800 B phototransformations. Different static inhomogeneous broadening is revealed for the lowest energy exciton states of B850 (fwhm ∼195 cm -1 ) and B800 R (fwhm ∼140 cm -1 ). To describe the 5 K absorption spectrum and the above-mentioned conformations, we employ an exciton model with dichotomous protein conformation disorder. We show that both experimental data and the modeling study support a two-site model with strongly and weakly hydrogen-bonded B850 and B800 BChls, which under illumination undergo conformational changes, most likely caused by proton dynamics.

Unexpected radionuclide uptake due to calcification in muscles

International Nuclear Information System (INIS)

Khier, A.

1999-01-01

Full text: A male patient aged 27 years was injected with 1000 MBq of 99 Tc m -MDP. The patient was an active man indulging in contact sport. He presented with lower back and pelvic pain. Spot pictures were made of the pelvis, lumbar spine and femurs. Unexpected active radionuclide uptake in the muscles was seen. In the delayed static images, there was focal accumulation of tracer uptake in the muscles overlying the mid-shaft of the left femur consistent with myositis ossificans. Myositis ossificans is a benign ossifying process that is generally solitary and well circumscribed. It is most commonly found in the muscles but it may occur in other connective tissues, especially tendons and subcutaneous fat. This was presumably associated with chronic muscular injuries contracted during sports activity

Ombud's Corner: unexpected turn in the conversation?

CERN Multimedia

Sudeshna Datta-Cockerill

2014-01-01

Regular informal conversations with colleagues play a very important part in weaving the fabric of team spirit. They allow us to build the working relationships that are vital to the success of our projects and to create an environment of good will that is instrumental in averting potential conflict or crises. However, sometimes they can come with unexpected surprises…   Eric and his colleagues always meet on Monday mornings to have coffee together, before starting the working week. This is a very privileged moment for the team when there are no formal barriers or professional concerns: Mary may talk about a film that she saw at the weekend, Eric often goes hiking in the Jura with his friend Stefan, Hans has always got a story about his son’s prowess on the school football team and occasionally there is a bit of special news such as Louisa’s recent marriage, Pierre’s baby’s christening or Claude’s daughter’s graduation&...

Superior shoulder suspensory complex fracture dislocation case report

International Nuclear Information System (INIS)

Lidgett, T.; Bate, E.; Pittock, L.

2017-01-01

Background: Acromioclavicular joint dislocation can be more complex than it first appears. The presented case had an unusual combination of injuries to the superior shoulder suspensory complex, which yielded some interesting learning points. Case summary: The injuries were sustained after a fall from a push bike and included acromioclavicular dislocation with coracoid process, clavicle and acromion process fractures. These were identified on the initial X-ray examination, which was followed by computed tomography for surgical planning. The injuries were successfully treated by internal fixation. Conclusion: The unexpected complexity of the injuries could have led to subtle but important findings being overlooked. This case highlights the importance of a thorough search strategy, consideration of injury biomechanics and knowledge of associated injuries. - Highlights: • Search for associated fractures in acromioclavicular joint dislocation. • Assess the clavicle, acromion process and coracoid process in particular. • Do not end the shoulder X-ray examination after seeing one injury. • Both axial and cranially angulated anteroposterior projections are beneficial. • Acromioclavicular joint fracture dislocation treatment may require further research.

Essential and Unexpected Role of YY1 to Promote Mesodermal Cardiac Differentiation

Science.gov (United States)

Gregoire, Serge; Karra, Ravi; Passer, Derek; Deutsch, Marcus-Andre; Krane, Markus; Feistritzer, Rebecca; Sturzu, Anthony; Domian, Ibrahim; Saga, Yumiko; Wu, Sean M.

2013-01-01

Rational Cardiogenesis is regulated by a complex interplay between transcription factors. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). Objective To identify novel regulators of mesodermal cardiac lineage commitment. Methods and Results We performed a bioinformatic-based transcription factor binding site analysis on upstream promoter regions of genes that are enriched in embryonic stem cell (ESC)-derived CPCs. From 32 candidate transcription factors screened, we found that YY1, a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with Gata4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by ESC-based assays where we show that the overexpression of YY1 enhanced the cardiogenic differentiation of ESCs into CPCs. Conclusion These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes. PMID:23307821

Function and regulation of the Mediator complex.

Science.gov (United States)

Conaway, Ronald C; Conaway, Joan Weliky

2011-04-01

Over the past few years, advances in biochemical and genetic studies of the structure and function of the Mediator complex have shed new light on its subunit architecture and its mechanism of action in transcription by RNA polymerase II (pol II). The development of improved methods for reconstitution of recombinant Mediator subassemblies is enabling more in-depth analyses of basic features of the mechanisms by which Mediator interacts with and controls the activity of pol II and the general initiation factors. The discovery and characterization of multiple, functionally distinct forms of Mediator characterized by the presence or absence of the Cdk8 kinase module have led to new insights into how Mediator functions in both Pol II transcription activation and repression. Finally, progress in studies of the mechanisms by which the transcriptional activation domains (ADs) of DNA binding transcription factors target Mediator have brought to light unexpected complexities in the way Mediator participates in signal transduction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Quantum transport through complex networks - from light-harvesting proteins to semiconductor devices

Energy Technology Data Exchange (ETDEWEB)

Kreisbeck, Christoph

2012-06-18

Electron transport through small systems in semiconductor devices plays an essential role for many applications in micro-electronics. One focus of current research lies on establishing conceptually new devices based on ballistic transport in high mobility AlGaAs/AlGa samples. In the ballistic regime, the transport characteristics are determined by coherent interference effects. In order to guide experimentalists to an improved device design, the characterization and understanding of intrinsic device properties is crucial. We develop a time-dependent approach that allows us to simulate experimentally fabricated, complex devicegeometries with an extension of up to a few micrometers. Particularly, we explore the physical origin of unexpected effects that have been detected in recent experiments on transport through Aharonov-Bohm waveguide-interferometers. Such interferometers can be configured as detectors for transfer properties of embedded quantum systems. We demonstrate that a four-terminal waveguide-ring is a suitable setup for measuring the transmission phase of a harmonic quantum dot. Quantum effects are not restricted exclusively to artificial devices but have been found in biological systems as well. Pioneering experiments reveal quantum effects in light-harvesting complexes, the building blocks of photosynthesis. We discuss the Fenna-Matthews-Olson complex, which is a network of coupled bacteriochlorophylls. It acts as an energy wire in the photosynthetic apparatus of green sulfur bacteria. Recent experimental findings suggest that energy transfer takes place in the form of coherent wave-like motion, rather than through classical hopping from one bacteriochlorophyll to the next. However, the question of why and how coherent transfer emerges in light-harvesting complexes is still open. The challenge is to merge seemingly contradictory features that are observed in experiments on two-dimensional spectroscopy into a consistent theory. Here, we provide such a

Redox-dependent substrate-cofactor interactions in the Michaelis-complex of a flavin-dependent oxidoreductase

Science.gov (United States)

Werther, Tobias; Wahlefeld, Stefan; Salewski, Johannes; Kuhlmann, Uwe; Zebger, Ingo; Hildebrandt, Peter; Dobbek, Holger

2017-07-01

How an enzyme activates its substrate for turnover is fundamental for catalysis but incompletely understood on a structural level. With redox enzymes one typically analyses structures of enzyme-substrate complexes in the unreactive oxidation state of the cofactor, assuming that the interaction between enzyme and substrate is independent of the cofactors oxidation state. Here, we investigate the Michaelis complex of the flavoenzyme xenobiotic reductase A with the reactive reduced cofactor bound to its substrates by X-ray crystallography and resonance Raman spectroscopy and compare it to the non-reactive oxidized Michaelis complex mimics. We find that substrates bind in different orientations to the oxidized and reduced flavin, in both cases flattening its structure. But only authentic Michaelis complexes display an unexpected rich vibrational band pattern uncovering a strong donor-acceptor complex between reduced flavin and substrate. This interaction likely activates the catalytic ground state of the reduced flavin, accelerating the reaction within a compressed cofactor-substrate complex.

Tracking Glideosome-associated protein 50 reveals the development and organization of the inner membrane complex of Plasmodium falciparum.

Science.gov (United States)

Yeoman, Jeffrey A; Hanssen, Eric; Maier, Alexander G; Klonis, Nectarios; Maco, Bohumil; Baum, Jake; Turnbull, Lynne; Whitchurch, Cynthia B; Dixon, Matthew W A; Tilley, Leann

2011-04-01

The most deadly of the human malaria parasites, Plasmodium falciparum, has different stages specialized for invasion of hepatocytes, erythrocytes, and the mosquito gut wall. In each case, host cell invasion is powered by an actin-myosin motor complex that is linked to an inner membrane complex (IMC) via a membrane anchor called the glideosome-associated protein 50 (PfGAP50). We generated P. falciparum transfectants expressing green fluorescent protein (GFP) chimeras of PfGAP50 (PfGAP50-GFP). Using immunoprecipitation and fluorescence photobleaching, we show that C-terminally tagged PfGAP50-GFP can form a complex with endogenous copies of the linker protein PfGAP45 and the myosin A tail domain-interacting protein (MTIP). Full-length PfGAP50-GFP is located in the endoplasmic reticulum in early-stage parasites and then redistributes to apical caps during the formation of daughter merozoites. In the final stage of schizogony, the PfGAP50-GFP profile extends further around the merozoite surface. Three-dimensional (3D) structured illumination microscopy reveals the early-stage IMC as a doubly punctured flat ellipsoid that separates to form claw-shaped apposed structures. A GFP fusion of PfGAP50 lacking the C-terminal membrane anchor is misdirected to the parasitophorous vacuole. Replacement of the acid phosphatase homology domain of PfGAP50 with GFP appears to allow correct trafficking of the chimera but confers a growth disadvantage.

Characteristics of unexpected protein bands in multiple myeloma patients after autologous stem cell transplantation.

Science.gov (United States)

Kim, Soo-Kyung; Jeong, Tae-Dong; Kim, So Young; Lee, Woochang; Chun, Sail; Suh, Cheol Won; Min, Won-Ki

2014-05-01

The aim of this study is to investigate the characteristics of unexpected protein bands (UPBs) in patients with multiple myeloma (MM). Individuals diagnosed with MM (n=193) were enrolled. Their medical records and IFE patterns were reviewed. Of the patients that underwent ASCT, 54% developed UPBs. The median time for UPB appearance and duration was 1.8 and 5.7months, respectively. IFE revealed 74.1% of UPBs to be of the immunoglobulin G type and 72.2% to be of the κ-type. At UPB appearance, 42.6% of patients were defined as sCR or CR, and 50.0% of the patients satisfying the CR criteria had an abnormal FLC ratio. Of the patients who developed UPBs, five relapsed. Among these, four patients showed disappearance of the previous IFE oligoclonality and reappearance of the original paraprotein at relapse. Close follow-up of UPBs is critical for evaluating MM therapeutic response and disease progression. The presence of monoclonal bands may indicate relapse of disease, but in the vast majority of cases with UPBs, it does not; instead, it most likely represents a transient phenomenon caused by the immune response. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Unexpectedly high piezoelectricity of Sm-doped lead zirconate titanate in the Curie point region.

Science.gov (United States)

Seshadri, Shruti B; Nolan, Michelle M; Tutuncu, Goknur; Forrester, Jennifer S; Sapper, Eva; Esteves, Giovanni; Granzow, Torsten; Thomas, Pam A; Nino, Juan C; Rojac, Tadej; Jones, Jacob L

2018-03-07

Large piezoelectric coefficients in polycrystalline lead zirconate titanate (PZT) are traditionally achieved through compositional design using a combination of chemical substitution with a donor dopant and adjustment of the zirconium to titanium compositional ratio to meet the morphotropic phase boundary (MPB). In this work, a different route to large piezoelectricity is demonstrated. Results reveal unexpectedly high piezoelectric coefficients at elevated temperatures and compositions far from the MPB. At temperatures near the Curie point, doping with 2 at% Sm results in exceptionally large piezoelectric coefficients of up to 915 pm/V. This value is approximately twice those of other donor dopants (e.g., 477 pm/V for Nb and 435 pm/V for La). Structural changes during the phase transitions of Sm-doped PZT show a pseudo-cubic phase forming ≈50 °C below the Curie temperature. Possible origins of these effects are discussed and the high piezoelectricity is posited to be due to extrinsic effects. The enhancement of the mechanism at elevated temperatures is attributed to the coexistence of tetragonal and pseudo-cubic phases, which enables strain accommodation during electromechanical deformation and interphase boundary motion. This work provides insight into possible routes for designing high performance piezoelectrics which are alternatives to traditional methods relying on MPB compositions.

75 FR 67013 - Unexpected Urgent Refugee and Migration Needs Resulting from Violence in Kyrgyzstan

Science.gov (United States)

2010-11-01

... August 26, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from Violence in Kyrgyzstan... laws of the United States, including section 2(c)(1) of the Migration and Refugee Assistance Act of... amount not to exceed $9.5 million from the United States Emergency Refugee and Migration Assistance Fund...

Differences in investigations of sudden unexpected deaths in young people in a nationwide setting

DEFF Research Database (Denmark)

Winkel, Bo Gregers; Holst, Anders Gaarsdal; Theilade, Juliane

2012-01-01

BACKGROUND: Inherited disease may be causative in many young sudden unexpected death cases. Autopsy is essential in the counselling of the bereaved, as the family of the victim may be at risk too. In a nationwide setting operating under the same set of laws, we hypothesized that regional differen...

[Tissue-specific nucleoprotein complexes].

Science.gov (United States)

Riadnova, I Iu; Shataeva, L K; Khavinson, V Kh

2000-01-01

A method of isolation of native nucleorprotein complexes from cattle cerebral cortex, thymus, and liver was developed. Compositions of these complexes were studied by means of gel-chromatography and ion-exchange chromatography. These preparations were shown to consist of several fractions of proteins and their complexes differ by molecular mass and electro-chemical properties. Native nucleoprotein complexes revealed high tissue specific activity, which was not species-specific.

Cationic bis-N-heterocyclic carbene (NHC) ruthenium complex: Structure and application as latent catalyst in olefin metathesis

KAUST Repository

Rouen, Mathieu

2014-09-11

An unexpected cationic bis-N-heterocyclic carbene (NHC) benzylidene ether based ruthenium complex (2 a) was prepared through the double incorporation of an unsymmetrical unsaturated N-heterocyclic carbene (U2-NHC) ligand that bore an N-substituted cyclododecyl side chain. The isolation and full characterization (including X-ray diffraction studies) of key synthetic intermediates along with theoretical calculations allowed us to understand the mechanism of the overall cationization process. Finally, the newly developed complex 2 a displayed interesting latent behavior during ring-closing metathesis, which could be "switched on" under acidic conditions.

Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation

Directory of Open Access Journals (Sweden)

Mukerji Joya

2012-06-01

Full Text Available Abstract Background HIV-1 Nef protein contributes to pathogenesis via multiple functions that include enhancement of viral replication and infectivity, alteration of intracellular trafficking, and modulation of cellular signaling pathways. Nef stimulates formation of tunneling nanotubes and virological synapses, and is transferred to bystander cells via these intercellular contacts and secreted microvesicles. Nef associates with and activates Pak2, a kinase that regulates T-cell signaling and actin cytoskeleton dynamics, but how Nef promotes nanotube formation is unknown. Results To identify Nef binding partners involved in Pak2-association dependent Nef functions, we employed tandem mass spectrometry analysis of Nef immunocomplexes from Jurkat cells expressing wild-type Nef or Nef mutants defective for the ability to associate with Pak2 (F85L, F89H, H191F and A72P, A75P in NL4-3. We report that wild-type, but not mutant Nef, was associated with 5 components of the exocyst complex (EXOC1, EXOC2, EXOC3, EXOC4, and EXOC6, an octameric complex that tethers vesicles at the plasma membrane, regulates polarized exocytosis, and recruits membranes and proteins required for nanotube formation. Additionally, Pak2 kinase was associated exclusively with wild-type Nef. Association of EXOC1, EXOC2, EXOC3, and EXOC4 with wild-type, but not mutant Nef, was verified by co-immunoprecipitation assays in Jurkat cells. Furthermore, shRNA-mediated depletion of EXOC2 in Jurkat cells abrogated Nef-mediated enhancement of nanotube formation. Using bioinformatic tools, we visualized protein interaction networks that reveal functional linkages between Nef, the exocyst complex, and the cellular endocytic and exocytic trafficking machinery. Conclusions Exocyst complex proteins are likely a key effector of Nef-mediated enhancement of nanotube formation, and possibly microvesicle secretion. Linkages revealed between Nef and the exocyst complex suggest a new paradigm of

Risk Management and Uncertainty in Large Complex Public Projects

DEFF Research Database (Denmark)

Neerup Themsen, Tim; Harty, Chris; Tryggestad, Kjell

Governmental actors worldwide are promoting risk management as a rational approach to man-age uncertainty and improve the abilities to deliver large complex projects according to budget, time plans, and pre-set project specifications: But what do we know about the effects of risk management...... on the abilities to meet such objectives? Using Callon’s (1998) twin notions of framing and overflowing we examine the implementation of risk management within the Dan-ish public sector and the effects this generated for the management of two large complex pro-jects. We show how the rational framing of risk...... management have generated unexpected costly outcomes such as: the undermining of the longer-term value and societal relevance of the built asset, the negligence of the wider range of uncertainties emerging during project processes, and constraining forms of knowledge. We also show how expert accountants play...

Simultaneous measurement of amyloid fibril formation by dynamic light scattering and fluorescence reveals complex aggregation kinetics.

Directory of Open Access Journals (Sweden)

Aaron M Streets

Full Text Available An apparatus that combines dynamic light scattering and Thioflavin T fluorescence detection is used to simultaneously probe fibril formation in polyglutamine peptides, the aggregating subunit associated with Huntington's disease, in vitro. Huntington's disease is a neurodegenerative disorder in a class of human pathologies that includes Alzheimer's and Parkinson's disease. These pathologies are all related by the propensity of their associated protein or polypeptide to form insoluble, β-sheet rich, amyloid fibrils. Despite the wide range of amino acid sequence in the aggregation prone polypeptides associated with these diseases, the resulting amyloids display strikingly similar physical structure, an observation which suggests a physical basis for amyloid fibril formation. Thioflavin T fluorescence reports β-sheet fibril content while dynamic light scattering measures particle size distributions. The combined techniques allow elucidation of complex aggregation kinetics and are used to reveal multiple stages of amyloid fibril formation.

75 FR 34617 - Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks for...

Science.gov (United States)

2010-06-18

... unexpected and urgent refugee and migration needs, including by contributions to international, governmental, and nongovernmental organizations and payment of administrative expenses of the Bureau of Population...

Sudden Unexpected Death During Sleep in Familial Dysautonomia: A Case-Control Study.

Science.gov (United States)

Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Perez, Miguel A; Spalink, Christy L; Kaufmann, Horacio

2017-08-01

Sudden unexpected death during sleep (SUDS) is the most common cause of death in patients with familial dysautonomia (FD), an autosomal recessive disease characterized by sensory and autonomic dysfunction. It remains unknown what causes SUDS in these patients and who is at highest risk. We tested the hypothesis that SUDS in FD is linked to sleep-disordered breathing. We retrospectively identified patients with FD who died suddenly and unexpectedly during sleep and had undergone polysomnography within the 18-month period before death. For each case, we sampled one age-matched surviving subject with FD that had also undergone polysomnography within the 18-month period before study. Data on polysomnography, EKG, ambulatory blood pressure monitoring, arterial blood gases, blood count, and metabolic panel were analyzed. Thirty-two deceased cases and 31 surviving controls were included. Autopsy was available in six cases. Compared with controls, participants with SUDS were more likely to be receiving treatment with fludrocortisone (odds ratio [OR]; 95% confidence interval) (OR 29.7; 4.1-213.4), have untreated obstructive sleep apnea (OR 17.4; 1.5-193), and plasma potassium levels Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Subxiphoid complex uniportal video-assisted major pulmonary resections.

Science.gov (United States)

Gonzalez-Rivas, Diego; Lirio, Francisco; Sesma, Julio; Abu Akar, Firas

2017-01-01

In recent years, the search for a less invasive and thus, less painful approach has driven technical innovation in modern thoracic surgery. In this context, subxiphoid uniportal approach has emerged as an alternative to avoid intercostal space manipulation and decrease postoperative pain and intercostal nerve chronic impairment. Subxiphoid uniportal major lung resections have been safe and effective procedures when performed by experienced surgeons even in complex cases or unexpected intraoperative situations. We present six of these surgical scenarios such as big tumors, incomplete or absent fissures, hilar calcified lymph nodes, active bleeding and massive adhesions to show the feasibility of subxiphoid approach to manage even these conditions.

An account of cognitive flexibility and inflexibility for a complex dynamic task

OpenAIRE

De Obeso Orendain, Alberto; Wood, Sharon

2012-01-01

Problem solving involves adapting known problem solving methods and strategies to the task at hand (Schunn & Reder, 2001) and cognitive flexibility is considered to be “the human ability to adapt the cognitive processing strategies to face new and unexpected conditions of the environment” (Cañas et al., 2005, p. 95). This work presents an ACT-R 6.0 model of complex problem solving behavior for the dynamic microworld game FireChief (Omodei & Wearing, 1995) that models the performance of partic...

Switch I-dependent allosteric signaling in a G-protein chaperone-B12 enzyme complex.

Science.gov (United States)

Campanello, Gregory C; Lofgren, Michael; Yokom, Adam L; Southworth, Daniel R; Banerjee, Ruma

2017-10-27

G-proteins regulate various processes ranging from DNA replication and protein synthesis to cytoskeletal dynamics and cofactor assimilation and serve as models for uncovering strategies deployed for allosteric signal transduction. MeaB is a multifunctional G-protein chaperone, which gates loading of the active 5'-deoxyadenosylcobalamin cofactor onto methylmalonyl-CoA mutase (MCM) and precludes loading of inactive cofactor forms. MeaB also safeguards MCM, which uses radical chemistry, against inactivation and rescues MCM inactivated during catalytic turnover by using the GTP-binding energy to offload inactive cofactor. The conserved switch I and II signaling motifs used by G-proteins are predicted to mediate allosteric regulation in response to nucleotide binding and hydrolysis in MeaB. Herein, we targeted conserved residues in the MeaB switch I motif to interrogate the function of this loop. Unexpectedly, the switch I mutations had only modest effects on GTP binding and on GTPase activity and did not perturb stability of the MCM-MeaB complex. However, these mutations disrupted multiple MeaB chaperone functions, including cofactor editing, loading, and offloading. Hence, although residues in the switch I motif are not essential for catalysis, they are important for allosteric regulation. Furthermore, single-particle EM analysis revealed, for the first time, the overall architecture of the MCM-MeaB complex, which exhibits a 2:1 stoichiometry. These EM studies also demonstrate that the complex exhibits considerable conformational flexibility. In conclusion, the switch I element does not significantly stabilize the MCM-MeaB complex or influence the affinity of MeaB for GTP but is required for transducing signals between MeaB and MCM. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Crystal structure of the enzyme-product complex reveals sugar ring distortion during catalysis by family 63 inverting α-glycosidase.

Science.gov (United States)

Miyazaki, Takatsugu; Nishikawa, Atsushi; Tonozuka, Takashi

2016-12-01

Glycoside hydrolases are divided into two groups, known as inverting and retaining enzymes, based on their hydrolytic mechanisms. Glycoside hydrolase family 63 (GH63) is composed of inverting α-glycosidases, which act mainly on α-glucosides. We previously found that Escherichia coli GH63 enzyme, YgjK, can hydrolyze 2-O-α-d-glucosyl-d-galactose. Two constructed glycosynthase mutants, D324N and E727A, which catalyze the transfer of a β-glucosyl fluoride donor to galactose, lactose, and melibiose. Here, we determined the crystal structures of D324N and E727A soaked with a mixture of glucose and lactose at 1.8- and 2.1-Å resolutions, respectively. Because glucose and lactose molecules are found at the active sites in both structures, it is possible that these structures mimic the enzyme-product complex of YgjK. A glucose molecule found at subsite -1 in both structures adopts an unusual 1 S 3 skew-boat conformation. Comparison between these structures and the previously determined enzyme-substrate complex structure reveals that the glucose pyranose ring might be distorted immediately after nucleophilic attack by a water molecule. These structures represent the first enzyme-product complex for the GH63 family, as well as the structurally-related glycosidases, and it may provide insight into the catalytic mechanism of these enzymes. Copyright © 2016 Elsevier Inc. All rights reserved.

Nuclear fission - the unexpected discovery seventy years ago

International Nuclear Information System (INIS)

Weis, Michael

2008-01-01

Seventy years ago, on December 17, 1938, Otto Hahn, Lise Meitner, and Fritz Strassmann discovered nuclear fission. It was a serendipitous discovery resulting from the consistent pursuit, for many years, of occasionally unexpected radiochemical experimental findings. Hardly any other scientific discovery has had such direct bearing on our life, changing our view of the world. It over-threw the tenet of physics, believed to be incontestable, that the atom was indivisible. The use of nuclear power it has made possible has given rise to immense benefits, but it has also allowed mankind's most dreadful weapon so far to be developed. All this is ample reason seventy years later to recall the discovery, the discoverers and their times. It will also be shown what later generations have made of this discovery, and what economic and ecological prospects it continues to hold. (orig.)

Subclinical hyperthyroidism and sudden unexpected death in epilepsy.

Science.gov (United States)

Scorza, Fulvio A; Arida, Ricardo M; Cysneiros, Roberta M; Terra, Vera C; de Albuquerque, Marly; Machado, Hélio R; Cavalheiro, Esper A

2010-04-01

Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. In parallel, several studies have shown a link between hormones and epilepsy. However, exact knowledge regarding the association of thyroid hormones and epilepsy is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease, we propose in this paper that SUDEP, at least in some cases, could be related with subclinical thyroid dysfunction. (c) 2009 Elsevier Ltd. All rights reserved.

Structures of Rotavirus Reassortants Demonstrate Correlation of Altered Conformation of the VP4 Spike and Expression of Unexpected VP4-Associated Phenotypes

Science.gov (United States)

Pesavento, Joseph B.; Billingsley, Angela M.; Roberts, Ed J.; Ramig, Robert F.; Prasad, B. V. Venkataram

2003-01-01

Numerous prior studies have indicated that viable rotavirus reassortants containing structural proteins of heterologous parental origin may express unexpected phenotypes, such as changes in infectivity and immunogenicity. To provide a structural basis for alterations in phenotypic expression, a three-dimensional structural analysis of these reassortants was conducted. The structures of the reassortants show that while VP4 generally maintains the parental structure when moved to a heterologous protein background, in certain reassortants, there are subtle alterations in the conformation of VP4. The alterations in VP4 conformation correlated with expression of unexpected VP4-associated phenotypes. Interactions between heterologous VP4 and VP7 in reassortants expressing unexpected phenotypes appeared to induce the conformational alterations seen in VP4. PMID:12584352

Complex dynamics of semantic memory access in reading.

Science.gov (United States)

Baggio, Giosué; Fonseca, André

2012-02-07

Understanding a word in context relies on a cascade of perceptual and conceptual processes, starting with modality-specific input decoding, and leading to the unification of the word's meaning into a discourse model. One critical cognitive event, turning a sensory stimulus into a meaningful linguistic sign, is the access of a semantic representation from memory. Little is known about the changes that activating a word's meaning brings about in cortical dynamics. We recorded the electroencephalogram (EEG) while participants read sentences that could contain a contextually unexpected word, such as 'cold' in 'In July it is very cold outside'. We reconstructed trajectories in phase space from single-trial EEG time series, and we applied three nonlinear measures of predictability and complexity to each side of the semantic access boundary, estimated as the onset time of the N400 effect evoked by critical words. Relative to controls, unexpected words were associated with larger prediction errors preceding the onset of the N400. Accessing the meaning of such words produced a phase transition to lower entropy states, in which cortical processing becomes more predictable and more regular. Our study sheds new light on the dynamics of information flow through interfaces between sensory and memory systems during language processing.

Sympatric Asian felid phylogeography reveals a major Indochinese-Sundaic divergence.

Science.gov (United States)

Luo, Shu-Jin; Zhang, Yue; Johnson, Warren E; Miao, Lin; Martelli, Paolo; Antunes, Agostinho; Smith, James L D; O'Brien, Stephen J

2014-04-01

The dynamic geological and climatological history of Southeast Asia has spawned a complex array of ecosystems and 12 of the 37 known cat species, making it the most felid-rich region in the world. To examine the evolutionary histories of these poorly studied fauna, we compared phylogeography of six species (leopard cat Prionailurus bengalensis, fishing cat P. viverrinus, Asiatic golden cat Pardofelis temminckii, marbled cat P. marmorata, tiger Panthera tigris and leopard P. pardus) by sequencing over 5 kb of DNA each from 445 specimens at multiple loci of mtDNA, Y and X chromosomes. All species except the leopard displayed significant phylogenetic partitions between Indochina and Sundaland, with the central Thai-Malay Peninsula serving as the biogeographic boundary. Concordant mtDNA and nuclear DNA genealogies revealed deep Indochinese-Sundaic divergences around 2 MYA in both P. bengalensis and P. marmorata comparable to previously described interspecific distances within Felidae. The divergence coincided with serial sea level rises during the late Pliocene and early Pleistocene, and was probably reinforced by repeated isolation events associated with environmental changes throughout the Pleistocene. Indochinese-Sundaic differentiations within P. tigris and P. temminckii were more recent at 72-108 and 250-1570 kya, respectively. Overall, these results illuminate unexpected, deep vicariance events in Southeast Asian felids and provide compelling evidence of species-level distinction between the Indochinese and Sundaic populations in the leopard cat and marbled cat. Broader sampling and further molecular and morphometric analyses of these species will be instrumental in defining conservation units and effectively preserving Southeast Asian biodiversity. © 2014 John Wiley & Sons Ltd.

Sunburn as a Cause of Unexpected Neutrophilia in a Healthy Pregnant Woman

OpenAIRE

Harper, Robert

2018-01-01

Background. Neutrophilia has a broad differential diagnosis and represents a systemic response to an infection or other inflammatory pathologies. Case. A 31-year-old woman, Gravida 3, Para 2 at 28 weeks of gestation, presented to the day assessment unit following routine blood tests that showed an unexpected marked neutrophilia. The underlying cause of the neutrophilia was sunburn. The sunburn recovered and her neutrophil count spontaneously normalised. Conclusion. Clinicians can add sunburn ...

Dynamic Asset Allocation Strategies Based on Volatility, Unexpected Volatility and Financial Turbulence

OpenAIRE

Grimsrud, David Borkner

2015-01-01

Masteroppgave økonomi og administrasjon- Universitetet i Agder, 2015 This master thesis looks at unexpected volatility- and financial turbulence’s predictive ability, and exploit these measures of financial risk, together with volatility, to create three dynamic asset allocation strategies, and test if they can outperform a passive and naively diversified buy-and-hold strategy. The idea with the dynamic strategies is to increase the portfolio return by keeping the portfolio risk at a low a...

Epilepsy and risk of death and sudden unexpected death in the young

DEFF Research Database (Denmark)

Holst, Anders Gaarsdal; Winkel, Bo Gregers; Risgaard, Bjarke

2013-01-01

Patients with epilepsy are at increased risk of premature death from all causes and likely also from sudden unexplained death (SUD). Many patients with epilepsy have significant comorbidity, and it is unclear how much of the increased risk can be explained by epilepsy itself. We aimed to chart...... the incidence of sudden unexpected death in epilepsy (SUDEP) and estimate the risk of death from all causes and SUD conferred by epilepsy independently....

Prevalence of incidental or unexpected findings on low-dose CT performed during routine SPECT/CT nuclear medicine studies

International Nuclear Information System (INIS)

Yap, Kelvin Kwok-Ho; Sutherland, Tom; Shafik-Eid, Raymond; Taubman, Kim; Schlicht, Stephen; Ramaseshan, Ganeshan

2015-01-01

In nuclear medicine, single-photon-emission computed tomography (SPECT) is often combined with ‘simultaneous’ low-dose CT (LDCT) to provide complementary anatomical and functional correlation. As a consequence, numerous incidental and unexpected findings may be detected on LDCT. Recognition of these findings and appropriate determination of their relevance can add to the utility of SPECT/CT. We aimed to evaluate the prevalence and categorise the relevance of incidental and unexpected findings on LDCT scans performed as part of routine SPECT/CT studies. All available LDCT scans performed as part of SPECT/CT studies at St. Vincent's Hospital Melbourne in the year 2013 were retrospectively reviewed. Two qualified radiologists independently reviewed the studies and any previous available imaging and categorised any detected incidental findings. A total of 2447 LDCT studies were reviewed. The relevance of the findings was classified according to a modified version of a scale used in the Colonography Reporting and Data System: E1 = normal or normal variant (28.0%); E2 = clinically unimportant (63.5%); E3 = likely unimportant or incompletely characterised (6.2%); E4 = potentially important (2.5%). Imaging specialists need to be cognisant of incidental and unexpected findings present on LDCT studies performed as part of SPECT/CT. Appropriate categorisation of findings and communication of potentially important findings to referring clinicians should form part of routine practice. The overall prevalence of potentially significant incidental and unexpected findings in our series was 8.7% (E3, 6.2%; E4, 2.5%) and was comparable to rates in other published imaging series.

Adaptation to sudden unexpected loading of the low back - the effects of repeated trials

DEFF Research Database (Denmark)

Skotte, J.H.; Fallentin, N.; Pedersen, Mogens Theisen

2004-01-01

The purpose of this study was to investigate short-term changes in reactions to sudden unexpected loading of the low back. The study utilized a set-up where a horizontal force of 58 N pointing forward suddenly was applied to the upper part of the subject's trunk. EMG activity from the erector...

Structural rearrangement of the intracellular domains during AMPA receptor activation

DEFF Research Database (Denmark)

Zachariassen, Linda Grønborg; Katchan, Ljudmila; Jensen, Anna Guldvang

2016-01-01

-clamp fluorometry of the double- and single-insert constructs showed that both the intracellular C-terminal domain (CTD) and the loop region between the M1 and M2 helices move during activation and the CTD is detached from the membrane. Our time-resolved measurements revealed unexpectedly complex fluorescence...

Unexpected storm-time nightside plasmaspheric density enhancement at low L shell

Science.gov (United States)

Chu, X.; Bortnik, J.; Denton, R. E.; Yue, C.

2017-12-01

We have developed a three-dimensional dynamic electron density (DEN3D) model in the inner magnetosphere using a neural network approach. The DEN3D model can provide spatiotemporal distribution of the electron density at any location and time that spacecraft observations are not available. Given DEN3D's good performance in predicting the structure and dynamic evolution of the plasma density, the salient features of the DEN3D model can be used to gain further insight into the physics. For instance, the DEN3D models can be used to find unusual phenomena that are difficult to detect in observations or simulations. We report, for the first time, an unexpected plasmaspheric density increase at low L shell regions on the nightside during the main phase of a moderate storm during 12-16 October 2004, as opposed to the expected density decrease due to storm-time plasmaspheric erosion. The unexpected density increase is first discovered in the modeled electron density distribution using the DEN3D model, and then validated using in-situ density measurements obtained from the IMAGE satellite. The density increase was likely caused by increased earthward transverse field plasma transport due to enhanced nightside ExB drift, which coincided with enhanced solar wind electric field and substorm activity. This is consistent with the results of physics-based simulation SAMI3 model which show earthward enhanced plasma transport and electron density increase at low L shells during storm main phase.

Structures of Adnectin/Protein Complexes Reveal an Expanded Binding Footprint

Energy Technology Data Exchange (ETDEWEB)

Ramamurthy, Vidhyashankar; Krystek, Jr., Stanley R.; Bush, Alexander; Wei, Anzhi; Emanuel, Stuart L.; Gupta, Ruchira Das; Janjua, Ahsen; Cheng, Lin; Murdock, Melissa; Abramczyk, Bozena; Cohen, Daniel; Lin, Zheng; Morin, Paul; Davis, Jonathan H.; Dabritz, Michael; McLaughlin, Douglas C.; Russo, Katie A.; Chao, Ginger; Wright, Martin C.; Jenny, Victoria A.; Engle, Linda J.; Furfine, Eric; Sheriff, Steven (BMS)

2014-10-02

Adnectins are targeted biologics derived from the tenth type III domain of human fibronectin ({sup 10}Fn3), a member of the immunoglobulin superfamily. Target-specific binders are selected from libraries generated by diversifying the three {sup 10}Fn3 loops that are analogous to the complementarity determining regions of antibodies. The crystal structures of two Adnectins were determined, each in complex with its therapeutic target, EGFR or IL-23. Both Adnectins bind different epitopes than those bound by known monoclonal antibodies. Molecular modeling suggests that some of these epitopes might not be accessible to antibodies because of the size and concave shape of the antibody combining site. In addition to interactions from the Adnectin diversified loops, residues from the N terminus and/or the {beta} strands interact with the target proteins in both complexes. Alanine-scanning mutagenesis confirmed the calculated binding energies of these {beta} strand interactions, indicating that these nonloop residues can expand the available binding footprint.

Airflow patterns in complex workplaces

International Nuclear Information System (INIS)

Mishima, J.; Selby, J.M.; Lynch, T.P.; Langer, G.; Vallario, E.J.

1987-01-01

There are many considerations in obtaining an accurate evaluation of aerosols. One aspect that has been neglected is the study of airflow patterns within the workplace. In many nuclear facilities, the operations performed required extensive equipment (e.g., glove boxes, piping) that create complex arrangements of physical barriers to flow. To provide samples of the airborne materials, particularly particles, knowledge of these complex airflow patterns is required for sampler placement. Recent studies have shown that materials introduced into the air flow within a workplace act as plumes embedded in major airflow streams. Portions of the plumes can recycle through the ventilated area, be lost to dead air pockets, or exhaust through unusual, unexpected outlets. Unusual flow patterns are observed even in relatively uncomplicated arrangements of equipment. This behavior must be factored into sampling/monitoring programs for evaluation of the airborne hazard to personnel within the workplace consistent with the objective of the program. Other factors that also must be considered to provide valid samples of airborne particulate materials are objectives of the sampling program, characteristics of the airborne particulate materials, nonsegregatory transport for the extracted materials, and requirements for the measurement techniques used

Crystal structure of a small heat-shock protein from Xylella fastidiosa reveals a distinct high-order structure.

Science.gov (United States)

Fonseca, Emanuella Maria Barreto; Scorsato, Valéria; Dos Santos, Marcelo Leite; Júnior, Atilio Tomazini; Tada, Susely Ferraz Siqueira; Dos Santos, Clelton Aparecido; de Toledo, Marcelo Augusto Szymanski; de Souza, Anete Pereira; Polikarpov, Igor; Aparicio, Ricardo

2017-04-01

Citrus variegated chlorosis is a disease that attacks economically important citrus plantations and is caused by the plant-pathogenic bacterium Xylella fastidiosa. In this work, the structure of a small heat-shock protein from X. fastidiosa (XfsHSP17.9) is reported. The high-order structures of small heat-shock proteins from other organisms are arranged in the forms of double-disc, hollow-sphere or spherical assemblies. Unexpectedly, the structure reported here reveals a high-order architecture forming a nearly square cavity.

A case-crossover analyses of fine particulate matter and out-of-hospital sudden unexpected death

Science.gov (United States)

Out-of-hospital sudden unexpected deaths (OHSUD) are natural deaths that occur without obvious underlying causes and account for nearly 1 in 6 deaths in the United States. Ambient air pollution is known to be causally related to overall mortality, therefore, we hypothesized that ...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to the Continuing Conflict in Pakistan

Science.gov (United States)

2010-01-01

... 3 The President 1 2010-01-01 2010-01-01 false Unexpected Urgent Refugee and Migration Needs Related to the Continuing Conflict in Pakistan Presidential Documents Other Presidential Documents... to the Continuing Conflict in Pakistan Memorandum for the Secretary of State By the authority vested...

Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

Directory of Open Access Journals (Sweden)

Tod W Reeder

Full Text Available Squamate reptiles (lizards and snakes are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa. Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia. These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses without considering the possible impact of molecular data on their placement.

Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

Science.gov (United States)

Reeder, Tod W; Townsend, Ted M; Mulcahy, Daniel G; Noonan, Brice P; Wood, Perry L; Sites, Jack W; Wiens, John J

2015-01-01

Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement.

Integrated Analyses Resolve Conflicts over Squamate Reptile Phylogeny and Reveal Unexpected Placements for Fossil Taxa

Science.gov (United States)

Reeder, Tod W.; Townsend, Ted M.; Mulcahy, Daniel G.; Noonan, Brice P.; Wood, Perry L.; Sites, Jack W.; Wiens, John J.

2015-01-01

Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement. PMID:25803280

Unexpected Relationships and Inbreeding in HapMap Phase III Populations

Science.gov (United States)

Stevens, Eric L.; Baugher, Joseph D.; Shirley, Matthew D.; Frelin, Laurence P.; Pevsner, Jonathan

2012-01-01

Correct annotation of the genetic relationships between samples is essential for population genomic studies, which could be biased by errors or omissions. To this end, we used identity-by-state (IBS) and identity-by-descent (IBD) methods to assess genetic relatedness of individuals within HapMap phase III data. We analyzed data from 1,397 individuals across 11 ethnic populations. Our results support previous studies (Pemberton et al., 2010; Kyriazopoulou-Panagiotopoulou et al., 2011) assessing unknown relatedness present within this population. Additionally, we present evidence for 1,657 novel pairwise relationships across 9 populations. Surprisingly, significant Cotterman's coefficients of relatedness K1 (IBD1) values were detected between pairs of known parents. Furthermore, significant K2 (IBD2) values were detected in 32 previously annotated parent-child relationships. Consistent with a hypothesis of inbreeding, regions of homozygosity (ROH) were identified in the offspring of related parents, of which a subset overlapped those reported in previous studies (Gibson et al. 2010; Johnson et al. 2011). In total, we inferred 28 inbred individuals with ROH that overlapped areas of relatedness between the parents and/or IBD2 sharing at a different genomic locus between a child and a parent. Finally, 8 previously annotated parent-child relationships had unexpected K0 (IBD0) values (resulting from a chromosomal abnormality or genotype error), and 10 previously annotated second-degree relationships along with 38 other novel pairwise relationships had unexpected IBD2 (indicating two separate paths of recent ancestry). These newly described types of relatedness may impact the outcome of previous studies and should inform the design of future studies relying on the HapMap Phase III resource. PMID:23185369

Perched Lava Pond Complex on South Rift of Axial Volcano Revealed in AUV Mapping

Science.gov (United States)

Paduan, J. B.; Clague, D. A.; Caress, D. W.; Thomas, H. J.

2013-12-01

An extraordinary lava pond complex is located on Axial Volcano's distal south rift. It was discovered in EM300 multibeam bathymetry collected in 1998, and explored and sampled with ROVs Tiburon in 2005 and Doc Ricketts in 2013. It was surveyed with the MBARI Mapping AUV D. Allan B. in 2011, in a complicated mission first flying above the levees at constant depth, then skimming ~5 m over the levees at a different constant depth to survey the floors, then twice switching to constant altitude mode to map outside the ponds. The AUV navigation was adjusted using the MB-System tool mbnavadjust so that bathymetric features match in overlapping and crossing swaths. The ~1-m resolution AUV bathymetry reveals extremely rough terrain, where low-resolution EM300 data had averaged acoustic returns and obscured details of walls, floors, a breach and surrounding flows, and gives context to the ROV observations and samples. The 6 x 1.5 km pond complex has 4 large and several smaller drained ponds with rims 67 to 106 m above the floors. The combined volume before draining was 0.56 km3. The ponds overflowed to build lobate-flow levees with elongate pillows draping outer flanks, then drained, leaving lava veneer on vertical inner walls. Levee rim depths vary by only 10 m and are deeper around the southern ponds. Deep collapse-pits in the levees suggest porosity of pond walls. The eastern levee of the northeastern pond breached, draining the interconnected ponds, and fed thick, rapidly-emplaced, sheet-flows along the complex's east side. These flows travelled at least 5.5 km down-rift and have 19-33 m deep drained ponds. They extended up-rift as well, forming a 10 x 2.5 km ponded flow with level 'bathtub rings' as high as 35 m above the floor marking that flow's high-stand. Despite the breach, at least 0.066 km3 of the molten interior of the large ponds also drained back down the eruptive fissures, as the pond floors are deeper than the sill and sea floor outside the complex. Tumulus

Unexpected findings of a female team in Xochimilco, Mexico.

Science.gov (United States)

Martínez-Salgado, C

1999-01-01

This is a reflection about the methodological circumstances that led the author to certain unexpected information during the course of a qualitative approach to the perception of health problems of a group of poor families in the south of Mexico City. Special attention is paid to the influence of the research team composition (four women with different professional backgrounds, ages, marital statuses, and styles of personal interaction) and the psychoanalytic technique that influenced the study. The inclusion of people of different ages, professions, and personality traits proved extremely valuable both as a means of widening the possibilities for empathetic relations between the research group and the population studied and for increasing the shades of meaning that the team was able to capture.

Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

Energy Technology Data Exchange (ETDEWEB)

Rockel, Beate [Department of Molecular Structural Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried (Germany); Schmaler, Tilo; Huang, Xiaohua [Division of Molecular Biology, Department of General, Visceral, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany); Dubiel, Wolfgang, E-mail: Wolfgang.dubiel@charite.de [Division of Molecular Biology, Department of General, Visceral, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany)

2014-07-25

Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts

Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

International Nuclear Information System (INIS)

Rockel, Beate; Schmaler, Tilo; Huang, Xiaohua; Dubiel, Wolfgang

2014-01-01

Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts

A student's perspective of managing data collection in a complex qualitative study.

Science.gov (United States)

Dowse, Eileen Mary; van der Riet, Pamela; Keatinge, Diana Rosemary

2014-11-01

To highlight from a doctoral student's perspective some of the unexpected and challenging issues that may arise when collecting data in a complex, qualitative study. Using a qualitative approach to undertaking a PhD requires commitment to the research topic, the acquisition of a variety of research skills and the development of expertise in writing. Despite close research supervision and guidance, the first author of this paper experienced unexpected hurdles when collecting data. This article highlights these hurdles and compares them with similar and dissimilar challenges raised by a social researcher with 30 years' experience (White 2012). The first author's experience of field research during her PhD candidature. Informed by a critical theoretical perspective, a snowballing technique was used to examine issues related to data collection by a doctoral student in a qualitative research study. The first author found the logistics of qualitative data collection, concerns about transparency, role confusion and power differentials with participants, and the effective use of video recording technology, unexpectedly challenging. Many of these issues are highlighted in the literature and/or during research supervision. However, the student researcher remains a novice when entering the field. It is often only on reflection after encountering the hurdle that the student recognises future pre-emptive or alternative methods of data collection. The challenges faced as a doctoral student managing the data collection phase of the study concurred with White's discussion of some of the 'real life challenges that novice researchers might face' (2012). Specific guidance and prudence are needed by research students to know when enough data have been collected for manageable analysis within the limits of candidature. Use of reflexivity and mindfulness practised by the student during this phase assisted the ability to reflect, respond and learn from issues as they arose and aim for a

Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex

Science.gov (United States)

Zhou, Mowei; Yan, Jing; Romano, Christine A.; Tebo, Bradley M.; Wysocki, Vicki H.; Paša-Tolić, Ljiljana

2018-01-01

Manganese oxidation is an important biogeochemical process that is largely regulated by bacteria through enzymatic reactions. However, the detailed mechanism is poorly understood due to challenges in isolating and characterizing these unknown enzymes. A manganese oxidase, Mnx, from Bacillus sp. PL-12 has been successfully overexpressed in active form as a protein complex with a molecular mass of 211 kDa. We have recently used surface induced dissociation (SID) and ion mobility-mass spectrometry (IM-MS) to release and detect folded subcomplexes for determining subunit connectivity and quaternary structure. The data from the native mass spectrometry experiments led to a plausible structural model of this multicopper oxidase, which has been difficult to study by conventional structural biology methods. It was also revealed that each Mnx subunit binds a variable number of copper ions. Becasue of the heterogeneity of the protein and limited mass resolution, ambiguities in assigning some of the observed peaks remained as a barrier to fully understanding the role of metals and potential unknown ligands in Mnx. In this study, we performed SID in a modified Fourier transform-ion cyclotron resonance (FTICR) mass spectrometer. The high mass accuracy and resolution offered by FTICR unveiled unexpected artificial modifications on the protein that had been previously thought to be iron bound species based on lower resolution spectra. Additionally, isotopically resolved spectra of the released subcomplexes revealed the metal binding stoichiometry at different structural levels. This method holds great potential for in-depth characterization of metalloproteins and protein-ligand complexes. [Figure not available: see fulltext.

When Field Experiments Yield Unexpected Results: Lessons Learned from Measuring Selection in White Sands Lizards

Science.gov (United States)

Hardwick, Kayla M.; Harmon, Luke J.; Hardwick, Scott D.; Rosenblum, Erica Bree

2015-01-01

Determining the adaptive significance of phenotypic traits is key for understanding evolution and diversification in natural populations. However, evolutionary biologists have an incomplete understanding of how specific traits affect fitness in most populations. The White Sands system provides an opportunity to study the adaptive significance of traits in an experimental context. Blanched color evolved recently in three species of lizards inhabiting the gypsum dunes of White Sands and is likely an adaptation to avoid predation. To determine whether there is a relationship between color and susceptibility to predation in White Sands lizards, we conducted enclosure experiments, quantifying survivorship of Holbrookia maculate exhibiting substrate-matched and substrate-mismatched phenotypes. Lizards in our study experienced strong predation. Color did not have a significant effect on survival, but we found several unexpected relationships including variation in predation over small spatial and temporal scales. In addition, we detected a marginally significant interaction between sex and color, suggesting selection for substrate matching may be stronger for males than females. We use our results as a case study to examine six major challenges frequently encountered in field-based studies of natural selection, and suggest that insight into the complexities of selection often results when experiments turn out differently than expected. PMID:25714838

X-ray structure of a transition state analog complex reveals the molecular origins of the catalytic power and substrate specificity of acetylcholinesterase

Energy Technology Data Exchange (ETDEWEB)

Harel, M.; Silman, I. [Weizmann Inst. of Science, Rehovot (Israel); Quinn, D.M.; Nair, H.K. [Univ. of Iowa, Iowa City, IA (United States); Sussman, J.L. [Weizmann Inst. of Science, Rehovot (Israel)]|[Brookhaven National Lab., Upton, NY (United States)

1996-03-13

The structure of a complex of Torpedo californica acetylcholinesterase with the transition state analog inhibitor m-(N, N,N-trimethylammonio)-2,2,2-trifluoroacetophenone has been solved by X-ray crystallographic methods to 2.8 A resolution. Since the inhibitor binds to the enzyme about 10{sup 10}-fold more tightly than the substrate acetylcholine, this complex provides a visual accounting of the enzyme-ligand interactions that provide the molecular basis for the catalytic power of acetylcholinesterase. The acetyl ester hydrolytic specificity of the enzyme is revealed by the interaction of the CF{sub 3} function of the transition state analog with a concave binding site comprised of the residues G119, W233, F288, F290, and F331. The highly geometrically convergent array of enzyme-ligand interactions visualized in the complex described herein envelopes the acylation transition state and sequesters it from solvent, this being consistent with the location of the active site at the bottom of a deep and narrow gorge. 82 refs., 5 figs.

Challenging Ideals of Reciprocity in Undergraduate Teaching: The Unexpected Benefits of Unpredictable Cross-Cultural Fieldwork

Science.gov (United States)

Hammersley, Laura A.; Bilous, Rebecca H.; James, Sarah W.; Trau, Adam M.; Suchet-Pearson, Sandie

2014-01-01

Geographers are increasingly grappling with the theoretical and practical implications of integrating an ethics of reciprocity into undergraduate learning and teaching. This paper draws on the unexpected experiences of a third-year human geography research methods fieldtrip to examine the process of balancing undergraduate student learning and…

The γ Dor stars as revealed by Kepler: A key to reveal deep-layer rotation in A and F stars

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Salmon S. J. A. J.

2017-01-01

Full Text Available The γ Dor pulsating stars present high-order gravity modes, which make them important targets in the intermediate-and low-mass main-sequence region of the Hertzsprung-Russell diagram. Whilst we have only access to rotation in the envelope of the Sun, the g modes of γ Dor stars can in principle deliver us constraints on the inner layers. With the puzzling discovery of unexpectedly low rotation rates in the core of red giants, the γ Dor stars appear now as unique targets to explore internal angular momentum transport in the progenitors of red giants. Yet, the γ Dor pulsations remain hard to detect from the ground for their periods are close to 1 day. While the CoRoT space mission first revealed intriguing frequency spectra, the almost uninterrupted 4-year photometry from the Kepler mission eventually shed a new light on them. It revealed regularities in the spectra, expected to bear signature of physical processes, including rotation, in the shear layers close to the convective core. We present here the first results of our effort to derive exploitable seismic diagnosis for mid- to fast rotators among γ Dor stars. We confirm their potential to explore the rotation history of this early phase of stellar evolution.

Unexpected nonlinear effects and critical coupling in NbN superconducting microwave resonators

International Nuclear Information System (INIS)

Abdo, B.; Buks, E.

2004-01-01

Full Text:In this work, we have designed and fabricated several NbN superconducting stripline microwave resonators sputtered on sapphire substrates. The low temperature response exhibits strong and unexpected nonlinear effects, including sharp jumps as the frequency or poser are varied, frequency hysteresis loops changing direction as the input power is varied, and others. Contrary to some other superconducting resonators, a simple model of a one-dimensional Duffing resonator cannot account for the experimental results. Whereas the physical origin of the unusual nonlinear response of our samples remains an open question, our intensive experimental study of these effects under varying conditions provides some important insight. We consider a hypothesis according to which Josephson junctions forming weak links between the grains of the NbN are responsible for the observed behavior. We show that most of the experimental results are qualitatively consistent with such hypothesis. While revealing the underlying physics remains an outstanding challenge for future research, the utilization of the unusual nonlinear response for some novel applications is already demonstrated in the present work. In particular an operate the resonator as an inter modulation amplifier and find that the gain can be as high as 15 dB. To the best of our knowledge, inter modulation gain greater than unity has not been reported before in the scientific literature. In another application we demonstrate for the first time that the coupling between the resonator and its feed line can be made amplitude dependent. This novel mechanism allows us to tune the resonator into critical coupling conditions

Evaluation of the Factors Concerning the Unexpected Pregnancy of Women who Applied to the Mother and Child Care and Family Planning Center of Van Province

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Sebahat Gucuk

2012-02-01

Full Text Available Introduction: The purpose of this study is to evaluate the experiences of unexpected pregnancy and the related factors of the women who have applied to our center. Material and Method: The study was planned as a descriptive study which enrolled women in the age range of 15-49 on the basis of volunteerism who have applied to the Mother and Child Care and Family Planning Center of Van Province. The participants were administered a survey in which certain situations were questioned, such as age, educational background, age at first labor, income status, number of living children, miscarriage status, unexpected pregnancy status, the presence of trying to undergo an abortion with alternative methods, and the state of receiving consultancy service on pre- and post-pregnancy family planning. Results: The more increased the educational level of 399 women enrolled in the study, the more significant reduction in unexpected pregnancies was detected (P=0.001. When the educational background and the use of alternative methods to have an abortion were compared, the illiterate women were found to use alternative methods (37.6% at a significantly high ratio (p=0.0001. The average of children number of women with at least one unexpected pregnancy was significantly high (p=0.0001. While the ratio of receiving consultancy on post-pregnancy family planning from health care personnel of the women with unexpected pregnancy was 79.5%, a ratio of 97.9% was detected for the women with planned pregnancy which was significantly different (p=0.0001. Conclusion: The health care personnel may reduce the unexpected pregnancies by training women on family planning in a simple, understandable way and by trying to increase health literacy by taking the dominant social rules in our region into consideration. We consider that the primary healthcare will be more effective and result oriented through newly applied Family Practice in our region. Key Words: Unexpected pregnancy

Sunburn as a Cause of Unexpected Neutrophilia in a Healthy Pregnant Woman

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Robert Harper

2018-01-01

Full Text Available Background. Neutrophilia has a broad differential diagnosis and represents a systemic response to an infection or other inflammatory pathologies. Case. A 31-year-old woman, Gravida 3, Para 2 at 28 weeks of gestation, presented to the day assessment unit following routine blood tests that showed an unexpected marked neutrophilia. The underlying cause of the neutrophilia was sunburn. The sunburn recovered and her neutrophil count spontaneously normalised. Conclusion. Clinicians can add sunburn to the broad differential diagnosis of neutrophilia.

Alcohol-catalyzed photoreduction of iron-porphyrin complexes revealed by resonance raman and absorption spectroscopies

Science.gov (United States)

Ogura, T.; Fidler, V.; Ozaki, Y.; Kitagawa, T.

1990-06-01

Photoreduction of Fe III(OEP) (2-MeIm) (OEP is octaethylporphyrin; 2-MeIm is 2-methylimidazole) was found to be catalyzed by a trace amount of MeOH present in Ch 2Cl 2 as a stabilizer. The absence of either 2-MeIm or MeOH in the CH 2Cl 2 solution of Fe III(OEP) X (X is Cl -, Br - or I -) leads to no photoreduction. The presence of MeOH in the Fe III(OEP) (2-MeIm) solution results in the appearance of a new absorption band at 585 nm, and when Raman scattering was excited at 590 nm, a new Raman band appeared at 524 cm -. This band exhibited an upshift by 4 cm - with 54Fe(OEP) (2-MeIm)(CH 3OH) and a downshift by 12 cm -1 with 56Fe(OEP)(2-MeIm) (CD 3OD) and was therefore assigned to the Fe III-MeOH stretching vibration. The excitation profile of this band gave a peak around 585 nm and accordingly, the new absorption band at 584 nm was assigned to a charge-transfer (CT) band from MeOH to the Fe III ion. It was most unexpected that the photoreduction did not occur upon laser illumination within the CT band.

Unexpected perturbations training improves balance control and voluntary stepping times in older adults - a double blind randomized control trial.

Science.gov (United States)

Kurz, Ilan; Gimmon, Yoav; Shapiro, Amir; Debi, Ronen; Snir, Yoram; Melzer, Itshak

2016-03-04

Falls are common among elderly, most of them occur while slipping or tripping during walking. We aimed to explore whether a training program that incorporates unexpected loss of balance during walking able to improve risk factors for falls. In a double-blind randomized controlled trial 53 community dwelling older adults (age 80.1±5.6 years), were recruited and randomly allocated to an intervention group (n = 27) or a control group (n = 26). The intervention group received 24 training sessions over 3 months that included unexpected perturbation of balance exercises during treadmill walking. The control group performed treadmill walking with no perturbations. The primary outcome measures were the voluntary step execution times, traditional postural sway parameters and Stabilogram-Diffusion Analysis. The secondary outcome measures were the fall efficacy Scale (FES), self-reported late life function (LLFDI), and Performance-Oriented Mobility Assessment (POMA). Compared to control, participation in intervention program that includes unexpected loss of balance during walking led to faster Voluntary Step Execution Times under single (p = 0.002; effect size [ES] =0.75) and dual task (p = 0.003; [ES] = 0.89) conditions; intervention group subjects showed improvement in Short-term Effective diffusion coefficients in the mediolateral direction of the Stabilogram-Diffusion Analysis under eyes closed conditions (p = 0.012, [ES] = 0.92). Compared to control there were no significant changes in FES, LLFDI, and POMA. An intervention program that includes unexpected loss of balance during walking can improve voluntary stepping times and balance control, both previously reported as risk factors for falls. This however, did not transferred to a change self-reported function and FES. ClinicalTrials.gov NCT01439451 .

The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy

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Arnauld eSergé

2016-05-01

Full Text Available The plasma membrane delimits the cell, which is the basic unit of living organisms, and is also a privileged site for cell communication with the environment. Cell adhesion can occur through cell-cell and cell-matrix contacts. Adhesion proteins such as integrins and cadherins also constitute receptors for inside-out and outside-in signaling within proteolipidic platforms. Adhesion molecule targeting and stabilization relies on specific features such as preferential segregation by the sub-membrane cytoskeleton meshwork and within membrane proteolipidic microdomains. This review presents an overview of the recent insights brought by the latest developments in microscopy, to unravel the molecular remodeling occurring at cell contacts. The dynamic aspect of cell adhesion was recently highlighted by super-resolution videomicroscopy, also named videonanoscopy. By circumventing the diffraction limit of light, nanoscopy has allowed the monitoring of molecular localization and behavior at the single-molecule level, on fixed and living cells. Accessing molecular-resolution details such as quantitatively monitoring components entering and leaving cell contacts by lateral diffusion and reversible association has revealed an unexpected plasticity. Adhesion structures can be highly specialized, such as focal adhesion in motile cells, as well as immune and neuronal synapses. Spatiotemporal reorganization of adhesion molecules, receptors and adaptors directly relates to structure/function modulation. Assembly of these supramolecular complexes is continuously balanced by dynamic events, remodeling adhesions on various timescales, notably by molecular conformation switches, lateral diffusion within the membrane and endo/exocytosis. Pathological alterations in cell adhesion are involved in cancer evolution, through cancer stem cell interaction with stromal niches, growth, extravasation and metastasis.

Unexpected Maternal Convulsion: An Idiopathic Case of Posterior Reversible Encephalopathy Syndrome after Delivery

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Jila Agah

2016-01-01

Full Text Available Posterior reversible encephalopathy syndrome (PRES is associated with various clinical manifestations such as headache, blurred vision, confusion and tonic-clonic convulsion. Some of the predisposing factors for PRES include hypertensive encephalopathy, preeclampsia and eclampsia, lupus erythematosus, thrombotic thrombocytopenic purpura and long-term use of immunosuppressive drugs. This condition rarely occurs after normotensive and uneventful pregnancies. Several theories have been proposed on the etiology of PRES. For instance, endothelial injury and brain edema have been reported as possible causes of PRES. Although PRES is a temporary condition, proper and timely management of the disorder in the acute phase is critical for the prevention of permanent neurological complications. During pregnancy, PRES is normally accompanied with hypertension. In this paper, we present a rare case of PRES in a normotensive pregnancy in a 25-year-old parturient woman (Gravida 2, Ab 1. The patient unexpectedly manifested symptoms of tonic-clonic convulsion one hour after an uneventful vaginal delivery, which were successfully managed. According to our observations, PRES has various clinical manifestations with unexpected occurrence in some cases. Therefore, it is recommended that maternity centers be well-equipped with resuscitation tools, emergency drugs and expert staff so as to manage unforeseen PRES efficiently and prevent permanent maternal neurological complications and mortality.

Unexpected structure in the E2 quasicontinuum spectrum of 154Dy

International Nuclear Information System (INIS)

Holzmann, R.; Khoo, T.L.; Ma, W.C.

1988-01-01

The evolution of the γ quasicontinuum spectrum with neutron number has been investigated in the sequence of dysprosium isotopes /sup 152,154,156/Dy. The three nuclei display a pronounced collective E2 component. In 154 Dy this component shows an unexpected splitting into two distinct parts, signifying a structural change along the γ cascade. The E2 and statistical components can be reproduced in simple γ cascade calculations; in 152 Dy and 156 Dy only rotational bands were included, whereas in 154 Dy additional vibration-like transitions were required to reproduce the two E2 peaks. 11 refs., 2 figs

Evidence for the robustness of protein complexes to inter-species hybridization.

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Jean-Baptiste Leducq

Full Text Available Despite the tremendous efforts devoted to the identification of genetic incompatibilities underlying hybrid sterility and inviability, little is known about the effect of inter-species hybridization at the protein interactome level. Here, we develop a screening platform for the comparison of protein-protein interactions (PPIs among closely related species and their hybrids. We examine in vivo the architecture of protein complexes in two yeast species (Saccharomyces cerevisiae and Saccharomyces kudriavzevii that diverged 5-20 million years ago and in their F1 hybrids. We focus on 24 proteins of two large complexes: the RNA polymerase II and the nuclear pore complex (NPC, which show contrasting patterns of molecular evolution. We found that, with the exception of one PPI in the NPC sub-complex, PPIs were highly conserved between species, regardless of protein divergence. Unexpectedly, we found that the architecture of the complexes in F1 hybrids could not be distinguished from that of the parental species. Our results suggest that the conservation of PPIs in hybrids likely results from the slow evolution taking place on the very few protein residues involved in the interaction or that protein complexes are inherently robust and may accommodate protein divergence up to the level that is observed among closely related species.

76 FR 53295 - Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa

Science.gov (United States)

2011-08-25

...-12 of August 8, 2011--Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa... Migration Needs Related to the Horn of Africa Memorandum for the Secretary of State By the authority vested... Department of State, related to the humanitarian crisis in the Horn of Africa. You are authorized and...

Unexpectedly high catch-and-release rates in European marine recreational fisheries: implications for science and management

DEFF Research Database (Denmark)

Ferter, Keno; Weltersbach, Marc Simon; Strehlow, Harry Vincent

2013-01-01

Unexpectedly high catch-and-release rates in European marine recreational fisheries: implications for science and management. – ICES Journal of Marine Science, 70: .While catch-and-release (C&R) is a well-known practice in several European freshwater recreational fisheries, studies on the magnitu...

Synthesis and Luminescence Properties of Iridium(III Azide- and Triazole-Bisterpyridine Complexes

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Timothy W. Schmidt

2013-07-01

Full Text Available We describe here the synthesis of azide-functionalised iridium(III bisterpyridines using the “chemistry on the complex” strategy. The resulting azide-complexes are then used in the copper(I-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition “click chemistry” reaction to from the corresponding triazole-functionalised iridium(III bisterpyridines. The photophysical characteristics, including lifetimes, of these compounds were also investigated. Interestingly, oxygen appears to have very little effect on the lifetime of these complexes in aqueous solutions. Unexpectedly, sodium ascorbate acid appears to quench the luminescence of triazole-functionalised iridium(III bisterpyridines, but this effect can be reversed by the addition of copper(II sulfate, which is known to oxidize ascorbate under aerobic conditions. The results demonstrate that iridium(III bisterpyridines can be functionalized for use in “click chemistry” facilitating the use of these photophysically interesting complexes in the modification of polymers or surfaces, to highlight just two possible applications.

Small RNA sequence analysis of adenovirus VA RNA-derived miRNAs reveals an unexpected serotype-specific difference in structure and abundance.

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Wael Kamel

Full Text Available Human adenoviruses (HAds encode for one or two highly abundant virus-associated RNAs, designated VA RNAI and VA RNAII, which fold into stable hairpin structures resembling miRNA precursors. Here we show that the terminal stem of the VA RNAs originating from Ad4, Ad5, Ad11 and Ad37, all undergo Dicer dependent processing into virus-specific miRNAs (so-called mivaRNAs. We further show that the mivaRNA duplex is subjected to a highly asymmetric RISC loading with the 3'-strand from all VA RNAs being the favored strand, except for the Ad37 VA RNAII, where the 5'-mivaRNAII strand was preferentially assembled into RISC. Although the mivaRNA seed sequences are not fully conserved between the HAds a bioinformatics prediction approach suggests that a large fraction of the VA RNAII-, but not the VA RNAI-derived mivaRNAs still are able to target the same cellular genes. Using small RNA deep sequencing we demonstrate that the Dicer processing event in the terminal stem of the VA RNAs is not unique and generates 3'-mivaRNAs with a slight variation of the position of the 5' terminal nucleotide in the RISC loaded guide strand. Also, we show that all analyzed VA RNAs, except Ad37 VA RNAI and Ad5 VA RNAII, utilize an alternative upstream A start site in addition to the classical +1 G start site. Further, the 5'-mivaRNAs with an A start appears to be preferentially incorporated into RISC. Although the majority of mivaRNA research has been done using Ad5 as the model system our analysis demonstrates that the mivaRNAs expressed in Ad11- and Ad37-infected cells are the most abundant mivaRNAs associated with Ago2-containing RISC. Collectively, our results show an unexpected variability in Dicer processing of the VA RNAs and a serotype-specific loading of mivaRNAs into Ago2-based RISC.

Unexpected and just missed: the separate influence of the appraisals of expectancy and proximity on negative emotions.

Science.gov (United States)

Bossuyt, Evelien; Moors, Agnes; De Houwer, Jan

2014-04-01

Previous research has suggested that a goal-incongruent outcome leads to more intense negative emotions when it is unexpected and close to a goal-congruent outcome. Until now, however, no studies have disentangled the influence of the appraisals of expectancy and proximity on emotions. We experimentally manipulated each of these variables in 3 slot machine experiments and measured emotions via differences in motivation (i.e., the tendency to repair the goal incongruence) and feelings (i.e., disappointment, frustration, and anger). The experiments consisted of a series of trials that each started with the sequential presentation of 3 symbols. In case of a win trial, all symbols were equal (e.g., AAA) and the participant gained 10 cents; in case of a loss trial, one or more of the symbols differed and the participant gained 0 cents. Three different loss trials were compared: unexpected proximal ones (e.g., AAB), expected proximal ones (e.g., ABA), and expected distal ones (e.g., ABC). The tendency to repair was measured online via behavior as well as retrospectively via self-reports; feelings were measured retrospectively (Experiments 1 and 2) or online (Experiment 3). Unexpected losses seemed to increase the tendency to repair as well as feelings of disappointment (in all experiments) and feelings of frustration and anger (in Experiments 1 and 3). Proximal losses increased only the tendency to repair (in all experiments). This suggests that the appraisals of expectancy and proximity have a distinct influence on emotions.

Complexity science and leadership in healthcare.

Science.gov (United States)

Burns, J P

2001-10-01

The emerging field of complexity science offers an alternative leadership strategy for the chaotic, complex healthcare environment. A survey revealed that healthcare leaders intuitively support principles of complexity science. Leadership that uses complexity principles offers opportunities in the chaotic healthcare environment to focus less on prediction and control and more on fostering relationships and creating conditions in which complex adaptive systems can evolve to produce creative outcomes.

Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding Histone Deacetylase Inhibitors with Picomolar Affinities

DEFF Research Database (Denmark)

Kitir, Betül; Maolanon, Alex R.; Ohm, Ragnhild G.

2017-01-01

medicines. Therefore, detailed mechanistic information and precise characterization of the chemical probes used to investigate the effects of HDAC enzymes are vital. We interrogated Nature's arsenal of macrocyclic nonribosomal peptide HDAC inhibitors by chemical synthesis and evaluation of more than 30...... natural products and analogues. This furnished surprising trends in binding affinities for the various macrocycles, which were then exploited for the design of highly potent class I and IIb HDAC inhibitors. Furthermore, thorough kinetic investigation revealed unexpected inhibitory mechanisms of important...

Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity

International Nuclear Information System (INIS)

Gunn, Shelly; Gorre, Mercedes; Mohammed, Mansoor; Yeh, I-Tien; Lytvak, Irina; Tirtorahardjo, Budi; Dzidic, Natasha; Zadeh, Soheila; Kim, Jaeweon; McCaskill, Chris; Lim, Lony

2010-01-01

HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin), remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods. In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE) tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms. Array-based comparative genomic hybridization (array CGH) analysis of chromosome 17 resolved HER2 gene status in [20/20] (100%) of cases and revealed additional chromosome 17 copy number changes in [18/20] (90%) of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to 'ratio skewing' caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability. These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17 abnormalities in these cases suggests that the two

Age-related changes in posture response under a continuous and unexpected perturbation.

Science.gov (United States)

Tsai, Yi-Ching; Hsieh, Lin-Fen; Yang, Saiwei

2014-01-22

Aging is a critical factor to influence the functional performance during daily life. Without an appropriate posture control response when experiencing an unexpected external perturbation, fall may occur. A novel six-degree-of freedom platform with motion control protocol was designed to provide a real-life simulation of unexpected disturbance in order to discriminate the age-related changes of the balance control and the recovery ability. Twenty older adults and 20 healthy young adults participated in the study. The subjects stood barefoot on the novel movable platform, data of the center of mass (COM) excursion, joint rotation angle and electromyography (EMG) were recorded and compared. The results showed that the older adults had similar patterns of joint movement and COM excursion as the young adults during the balance reactive-recovery. However, larger proximal joint rotation in elderly group induced larger COM sway envelop and therefore loss of the compensatory strategy of posture recovery. The old adults also presented a lower muscle power. In order to keep an adequate joint stability preventing from falling, the EMG activity was increased, but the asymmetric pattern might be the key reason of unstable postural response. This novel design of moveable platform and test protocol comprised the computerized dynamic posturography (CDP) demonstrate its value to assess the possible sensory, motor, and central adaptive impairments to balance control and could be the training tool for posture inability person. © 2013 Elsevier Ltd. All rights reserved.

Genome-wide analyses of the Bemisia tabaci species complex reveal contrasting patterns of admixture and complex demographic histories.

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S Elfekih

Full Text Available Once considered a single species, the whitefly, Bemisia tabaci, is a complex of numerous morphologically indistinguishable species. Within the last three decades, two of its members (MED and MEAM1 have become some of the world's most damaging agricultural pests invading countries across Europe, Africa, Asia and the Americas and affecting a vast range of agriculturally important food and fiber crops through both feeding-related damage and the transmission of numerous plant viruses. For some time now, researchers have relied on a single mitochondrial gene and/or a handful of nuclear markers to study this species complex. Here, we move beyond this by using 38,041 genome-wide Single Nucleotide Polymorphisms, and show that the two invasive members of the complex are closely related species with signatures of introgression with a third species (IO. Gene flow patterns were traced between contemporary invasive populations within MED and MEAM1 species and these were best explained by recent international trade. These findings have profound implications for delineating the B. tabaci species status and will impact quarantine measures and future management strategies of this global pest.

Unexpected optical limiting properties from MoS2 nanosheets modified by a semiconductive polymer.

Science.gov (United States)

Zhao, Min; Chang, Meng-Jie; Wang, Qiang; Zhu, Zhen-Tong; Zhai, Xin-Ping; Zirak, Mohammad; Moshfegh, Alireza Z; Song, Ying-Lin; Zhang, Hao-Li

2015-08-07

Direct solvent exfoliation of bulk MoS2 with the assistance of poly(3-hexylthiophene) (P3HT) produces a novel two-dimensional organic/inorganic semiconductor hetero-junction. The obtained P3HT-MoS2 nanohybrid exhibits unexpected optical limiting properties in contrast to the saturated absorption behavior of both P3HT and MoS2, showing potential in future photoelectric applications.

Cobalt-catalyzed hydrogenation of esters to alcohols: unexpected reactivity trend indicates ester enolate intermediacy.

Science.gov (United States)

Srimani, Dipankar; Mukherjee, Arup; Goldberg, Alexander F G; Leitus, Gregory; Diskin-Posner, Yael; Shimon, Linda J W; Ben David, Yehoshoa; Milstein, David

2015-10-12

The atom-efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious-metal-based catalysts, with few exceptions. Presented here is the first cobalt-catalyzed hydrogenation of esters to the corresponding alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Single-Cell Biochemistry Approach Reveals PAR Complex Dynamics during Cell Polarization.

Science.gov (United States)

Dickinson, Daniel J; Schwager, Francoise; Pintard, Lionel; Gotta, Monica; Goldstein, Bob

2017-08-21

Regulated protein-protein interactions are critical for cell signaling, differentiation, and development. For the study of dynamic regulation of protein interactions in vivo, there is a need for techniques that can yield time-resolved information and probe multiple protein binding partners simultaneously, using small amounts of starting material. Here we describe a single-cell protein interaction assay. Single-cell lysates are generated at defined time points and analyzed using single-molecule pull-down, yielding information about dynamic protein complex regulation in vivo. We established the utility of this approach by studying PAR polarity proteins, which mediate polarization of many animal cell types. We uncovered striking regulation of PAR complex composition and stoichiometry during Caenorhabditis elegans zygote polarization, which takes place in less than 20 min. PAR complex dynamics are linked to the cell cycle by Polo-like kinase 1 and govern the movement of PAR proteins to establish polarity. Our results demonstrate an approach to study dynamic biochemical events in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Unexpected allelic heterogeneity and spectrum of mutations in Fowler syndrome revealed by next-generation exome sequencing.

Science.gov (United States)

Lalonde, Emilie; Albrecht, Steffen; Ha, Kevin C H; Jacob, Karine; Bolduc, Nathalie; Polychronakos, Constantin; Dechelotte, Pierre; Majewski, Jacek; Jabado, Nada

2010-08-01

Protein coding genes constitute approximately 1% of the human genome but harbor 85% of the mutations with large effects on disease-related traits. Therefore, efficient strategies for selectively sequencing complete coding regions (i.e., "whole exome") have the potential to contribute our understanding of human diseases. We used a method for whole-exome sequencing coupling Agilent whole-exome capture to the Illumina DNA-sequencing platform, and investigated two unrelated fetuses from nonconsanguineous families with Fowler Syndrome (FS), a stereotyped phenotype lethal disease. We report novel germline mutations in feline leukemia virus subgroup C cellular-receptor-family member 2, FLVCR2, which has recently been shown to cause FS. Using this technology, we identified three types of genetic abnormalities: point-mutations, insertions-deletions, and intronic splice-site changes (first pathogenic report using this technology), in the fetuses who both were compound heterozygotes for the disease. Although revealing a high level of allelic heterogeneity and mutational spectrum in FS, this study further illustrates the successful application of whole-exome sequencing to uncover genetic defects in rare Mendelian disorders. Of importance, we show that we can identify genes underlying rare, monogenic and recessive diseases using a limited number of patients (n=2), in the absence of shared genetic heritage and in the presence of allelic heterogeneity.

Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

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Faure Claudine

2007-10-01

Full Text Available Abstract Background: The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAα proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R. v-ErbA transforms erythroid progenitors in vitro by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor. However, v-ErbA target genes involved in its transforming activity still remain to be identified. Results: By using Serial Analysis of Gene Expression (SAGE, we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/transcription and unexpected (protein metabolism functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA. Conclusion: This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.

Does plant architectural complexity increase with increasing habitat complexity? A test with a pioneer shrub in the Brazilian Cerrado

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FAO Silveira

Full Text Available Understanding variation in plant traits in heterogeneous habitats is important to predict responses to changing environments, but trait-environment associations are poorly known along ecological gradients. We tested the hypothesis that plant architectural complexity increases with habitat complexity along a soil fertility gradient in a Cerrado (Neotropical savanna area in southeastern Brazil. Plant architecture and productivity (estimated as the total number of healthy infructescences of Miconia albicans (SW. Triana were examined in three types of vegetation which together form a natural gradient of increasing soil fertility, tree density and canopy cover: grasslands (campo sujo, CS, shrublands (cerrado sensu strico, CE and woodlands (cerradão, CD. As expected, plants growing at the CS were shorter and had a lower branching pattern, whereas plants at the CD were the tallest. Unexpectedly, however, CD plants did not show higher architectural complexity compared to CE plants. Higher architectural similarity between CE and CD plants compared to similarity between CS and CE plants suggests reduced expression of functional architectural traits under shade. Plants growing at the CE produced more quaternary shoots, leading to a larger number of infructescences. This higher plant productivity in CE indicates that trait variation in ecological gradients is more complex than previously thought. Nematode-induced galls accounted for fruit destruction in 76.5% infructescences across physiognomies, but percentage of attack was poorly related to architectural variables. Our data suggest shade-induced limitation in M. albicans architecture, and point to complex phenotypic variation in heterogeneous habitats in Neotropical savannas.

Unexpected temporal evolution of atomic spectral lines of aluminum in a laser induced breakdown spectroscopy experiment

International Nuclear Information System (INIS)

Saad, Rawad; L'Hermite, Daniel; Bousquet, Bruno

2014-01-01

The temporal evolution of the laser induced breakdown (LIBS) signal of a pure aluminum sample was studied under nitrogen and air atmospheres. In addition to the usual decrease of signal due to plasma cooling, unexpected temporal evolutions were observed for a spectral lines of aluminum, which revealed the existence of collisional energy transfer effects. Furthermore, molecular bands of AlN and AlO were observed in the LIBS spectra, indicating recombination of aluminum with the ambient gas. Within the experimental conditions reported in this study, both collisional energy transfer and recombination processes occurred around 1.5 μs after the laser shot. This highlights the possible influence of collisional and chemical effects inside the plasma that can play a role on LIBS signals. - Highlights: • Persistence of two Al I lines related to the 61,844 cm −1 energy level only under nitrogen atmosphere. • Collisional energy transfer effect exists between aluminum and nitrogen. • Observation of molecular band of AlN (under nitrogen) and AlO (under air) after a delay time of 1.5 µs. • 20% of oxygen in air is sufficient to annihilate both the collisional energy transfer effect and the AlN molecular formation

Transfusion rate and prevalence of unexpected red blood cell alloantibodies in women undergoing hysterectomy for benign disease

DEFF Research Database (Denmark)

Thoestesen, Lisbeth M; Rasmussen, Kjeld L; Lauszus, Finn F

2011-01-01

To determine transfusion rates, risk factors for transfusion and the prevalence of unexpected red blood cell alloantibodies in women undergoing hysterectomy for benign disease. In addition, we aimed to evaluate the necessity of the pretransfusion testing for red blood cell alloantibodies....

Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium

International Nuclear Information System (INIS)

Leung, Cleo; Utokaparch, Soraya; Sharma, Arpeeta; Yu, Carol; Abraham, Thomas; Borchers, Christoph; Bernatchez, Pascal

2011-01-01

Highlights: ► Bi-directional (inward and outward) movement of GFP-dysferlin in COS-7 cells. ► Dysferlin interacts with key signaling proteins for transcytosis in EC. ► Dysferlin mediates trafficking of vesicles carrying protein cargos in EC. -- Abstract: Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles. Emerging evidence reveal the unexpected expression of dysferlin in non-muscle, non-mechanically active tissues, such as endothelial cells, which cast doubts over the belief that ferlin proteins act exclusively as membrane repair proteins. We and others have shown that deficient trafficking of membrane bound proteins in dysferlin-deficient cells, suggesting that dysferlin might mediate trafficking of client proteins. Herein, we describe the intracellular trafficking and movement of GFP-dysferlin positive vesicles in unfixed reconstituted cells using live microscopy. By performing GST pull-down assays followed by mass spectrometry, we identified dysferlin binding protein complexes in human vascular endothelial cells. Together, our data further support the claims that dysferlin not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling.

Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium

Energy Technology Data Exchange (ETDEWEB)

Leung, Cleo; Utokaparch, Soraya; Sharma, Arpeeta; Yu, Carol; Abraham, Thomas; Borchers, Christoph [UBC James Hogg Research Centre, Institute for Heart and Lung Health, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia (Canada); University of Victoria - Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia (Canada); Bernatchez, Pascal, E-mail: pbernatc@mail.ubc.ca [UBC James Hogg Research Centre, Institute for Heart and Lung Health, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia (Canada); University of Victoria - Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia (Canada)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Bi-directional (inward and outward) movement of GFP-dysferlin in COS-7 cells. Black-Right-Pointing-Pointer Dysferlin interacts with key signaling proteins for transcytosis in EC. Black-Right-Pointing-Pointer Dysferlin mediates trafficking of vesicles carrying protein cargos in EC. -- Abstract: Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles. Emerging evidence reveal the unexpected expression of dysferlin in non-muscle, non-mechanically active tissues, such as endothelial cells, which cast doubts over the belief that ferlin proteins act exclusively as membrane repair proteins. We and others have shown that deficient trafficking of membrane bound proteins in dysferlin-deficient cells, suggesting that dysferlin might mediate trafficking of client proteins. Herein, we describe the intracellular trafficking and movement of GFP-dysferlin positive vesicles in unfixed reconstituted cells using live microscopy. By performing GST pull-down assays followed by mass spectrometry, we identified dysferlin binding protein complexes in human vascular endothelial cells. Together, our data further support the claims that dysferlin not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling.

The own and social effects of an unexpected income shock: Evidence from the Dutch Postcode Lottery

NARCIS (Netherlands)

Kuhn, P.J.; Kooreman, P.; Soetevent, A.R.; Kapteyn, A.

2008-01-01

In the Dutch Postcode Lottery a postal code (19 households on average) is randomly selected weekly, and prizes - consisting of cash and a new BMW - are awarded to lottery participants living in that postal code. On average, this generates a temporary, unexpected income shock equal to about eight

Understanding unexpected courses of multiple sclerosis among patients using complementary and alternative medicine: A travel from recipient to explorer

Directory of Open Access Journals (Sweden)

Anita Salamonsen

2010-07-01

Full Text Available Complementary and alternative medicine (CAM is frequently used by patients with multiple sclerosis (MS. Some MS patients experience unexpected improvements of symptoms, which they relate to their use of CAM. The aim of this study was to obtain knowledge and develop understandings of such self-defined unexpected improvement of MS symptoms. Two cases were constructed based on documents and 12 qualitative interviews. Our aim was not to make generalisations from the cases, but to transfer knowledge as working hypotheses. We identified four health-related change processes: the process of losing bodily competence; the process of developing responsibility; the process of taking control; and the process of choosing CAM. The patients explained unexpected improvements in their MS symptoms as results of their own efforts including their choice and use of CAM. In our theoretical interpretations, we found the patients’ redefinition of history, the concept of treatment and the importance of conventional health care to be essential, and leading to a change of patients’ position towards conventional health care from recipients to explorers. The explorers can be perceived as boundary walkers reflecting limitations within the conventional health care system and as initiators regarding what MS patients find useful in CAM.

Unexpectedly rapid evolution of mandibular shape in hominins.

Science.gov (United States)

Raia, P; Boggioni, M; Carotenuto, F; Castiglione, S; Di Febbraro, M; Di Vincenzo, F; Melchionna, M; Mondanaro, A; Papini, A; Profico, A; Serio, C; Veneziano, A; Vero, V A; Rook, L; Meloro, C; Manzi, G

2018-05-09

Members of the hominins - namely the so-called 'australopiths' and the species of the genus Homo - are known to possess short and deep mandibles and relatively small incisors and canines. It is commonly assumed that this suite of traits evolved in early members of the clade in response to changing environmental conditions and increased consumption of though food items. With the emergence of Homo, the functional meaning of mandible shape variation is thought to have been weakened by technological advancements and (later) by the control over fire. In contrast to this expectation, we found that mandible shape evolution in hominins is exceptionally rapid as compared to any other primate clade, and that the direction and rate of shape change (from the ape ancestor) are no different between the australopiths and Homo. We deem several factors including the loss of honing complex, canine reduction, and the acquisition of different diets may have concurred in producing such surprisingly high evolutionary rates. This study reveals the evolution of mandibular shape in hominins has strong morpho-functional and ecological significance attached.

Interlimb communication following unexpected changes in treadmill velocity during human walking

DEFF Research Database (Denmark)

Stevenson, Andrew James Thomas; Geertsen, Svend Sparre; Sinkjær, Thomas

2015-01-01

Interlimb reflexes play an important role in human walking, particularly when dynamic stability is threatened by external perturbations or changes in the walking surface. Interlimb reflexes have recently been demonstrated in the contralateral biceps femoris (cBF) following knee joint rotations...... applied to the ipsilateral leg (iKnee) during the late stance phase of human gait (Stevenson et al. 2013). This interlimb reflex likely acts to slow the forward progression of the body in order to maintain dynamic stability following the perturbations. We examined this hypothesis by unexpectedly...... to slow the forward progression of the body and maintaining dynamic stability during walking, thus signifying a functional role for interlimb reflexes....

Unexpected Interactions between Agricultural and Forest Sectors through International Trade: Wood Pallets and Agricultural Exports in Costa Rica

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Isaline Jadin

2016-12-01

Full Text Available International market forces have played an increasingly important role in shaping land use dynamics through complex supply chains. In Costa Rica, the shift from a net loss to a net gain in forest cover was facilitated by forest plantations and the replacement of extensive cropland and pastures by export-oriented, high-yielding crops. However, agricultural intensification generated several feedbacks affecting forests. We analyzed the interactions between Costa Rica’s agricultural and forestry sectors associated with the use of wood pallets for commodity exports over 1985–2013. Wood pallets for growing agricultural exports created a demand for domestic tree plantations. The annual land demand for tree plantations to produce these wood pallets increased by 669%, reaching 17,606 ha in 2013 and representing 28% of the increase in demand for cropland for agricultural exports over 1994–2013. Wood supplied from plantations failed to fully substitute for wood from natural forests, only allowing for a relative substitution and preventing a major sparing of these forests. The dominant use of wood from plantations for production of low-value pallets de-incentivized investments in sustainable plantations. We showed that, beyond the typical interactions between agriculture and forestry through direct competition for land, international trade generated unexpected feedback where agricultural activities and supply chains affected forestry by triggering new demand and profound changes in forestry management. Land systems behave as complex systems, calling for integrated approaches to study the outcomes of forest conservation, reforestation programs, and development of land-based businesses.

Cooperativity of complex salt bridges

OpenAIRE

Gvritishvili, Anzor G.; Gribenko, Alexey V.; Makhatadze, George I.

2008-01-01

The energetic contribution of complex salt bridges, in which one charged residue (anchor residue) forms salt bridges with two or more residues simultaneously, has been suggested to have importance for protein stability. Detailed analysis of the net energetics of complex salt bridge formation using double- and triple-mutant cycle analysis revealed conflicting results. In two cases, it was shown that complex salt bridge formation is cooperative, i.e., the net strength of the complex salt bridge...

A novel polyamine allosteric site of SpeG from Vibrio cholerae is revealed by its dodecameric structure.

Science.gov (United States)

Filippova, Ekaterina V; Kuhn, Misty L; Osipiuk, Jerzy; Kiryukhina, Olga; Joachimiak, Andrzej; Ballicora, Miguel A; Anderson, Wayne F

2015-03-27

Spermidine N-acetyltransferase, encoded by the gene speG, catalyzes the initial step in the degradation of polyamines and is a critical enzyme for determining the polyamine concentrations in bacteria. In Escherichia coli, studies have shown that SpeG is the enzyme responsible for acetylating spermidine under stress conditions and for preventing spermidine toxicity. Not all bacteria contain speG, and many bacterial pathogens have developed strategies to either acquire or silence it for pathogenesis. Here, we present thorough kinetic analyses combined with structural characterization of the VCA0947 SpeG enzyme from the important human pathogen Vibrio cholerae. Our studies revealed the unexpected presence of a previously unknown allosteric site and an unusual dodecameric structure for a member of the Gcn5-related N-acetyltransferase superfamily. We show that SpeG forms dodecamers in solution and in crystals and describe its three-dimensional structure in several ligand-free and liganded structures. Importantly, these structural data define the first view of a polyamine bound in an allosteric site of an N-acetyltransferase. Kinetic characterization of SpeG from V. cholerae showed that it acetylates spermidine and spermine. The behavior of this enzyme is complex and exhibits sigmoidal curves and substrate inhibition. We performed a detailed non-linear regression kinetic analysis to simultaneously fit families of substrate saturation curves to uncover a simple kinetic mechanism that explains the apparent complexity of this enzyme. Our results provide a fundamental understanding of the bacterial SpeG enzyme, which will be key toward understanding the regulation of polyamine levels in bacteria during pathogenesis. Copyright © 2015. Published by Elsevier Ltd.

Meditation effects within the hippocampal complex revealed by voxel-based morphometry and cytoarchitectonic probabilistic mapping

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Eileen eLuders

2013-07-01

Full Text Available Scientific studies addressing anatomical variations in meditators’ brains have emerged rapidly over the last few years, where significant links are most frequently reported with respect to gray matter (GM. To advance prior work, this study examined GM characteristics in a large sample of 100 subjects (50 meditators, 50 controls, where meditators have been practicing close to twenty years, on average. A standard, whole-brain voxel-based morphometry approach was applied and revealed significant meditation effects in the vicinity of the hippocampus, showing more GM in meditators than in controls as well as positive correlations with the number of years practiced. However, the hippocampal complex is regionally segregated by architecture, connectivity, and functional relevance. Thus, to establish differential effects within the hippocampal formation (cornu ammonis, fascia dentate, entorhinal cortex, subiculum as well as the hippocampal-amygdaloid transition area, we utilized refined cytoarchitectonic probabilistic maps of (peri- hippocampal subsections. Significant meditation effects were observed within the subiculum specifically. Since the subiculum is known to play a key role in stress regulation and meditation is an established form of stress reduction, these GM findings may reflect neuronal preservation in long-term meditators – perhaps due to an attenuated release of stress hormones and decreased neurotoxicity.

Meditation effects within the hippocampal complex revealed by voxel-based morphometry and cytoarchitectonic probabilistic mapping

Science.gov (United States)

Luders, Eileen; Kurth, Florian; Toga, Arthur W.; Narr, Katherine L.; Gaser, Christian

2013-01-01

Scientific studies addressing anatomical variations in meditators' brains have emerged rapidly over the last few years, where significant links are most frequently reported with respect to gray matter (GM). To advance prior work, this study examined GM characteristics in a large sample of 100 subjects (50 meditators, 50 controls), where meditators have been practicing close to 20 years, on average. A standard, whole-brain voxel-based morphometry approach was applied and revealed significant meditation effects in the vicinity of the hippocampus, showing more GM in meditators than in controls as well as positive correlations with the number of years practiced. However, the hippocampal complex is regionally segregated by architecture, connectivity, and functional relevance. Thus, to establish differential effects within the hippocampal formation (cornu ammonis, fascia dentata, entorhinal cortex, subiculum) as well as the hippocampal-amygdaloid transition area, we utilized refined cytoarchitectonic probabilistic maps of (peri-) hippocampal subsections. Significant meditation effects were observed within the subiculum specifically. Since the subiculum is known to play a key role in stress regulation and meditation is an established form of stress reduction, these GM findings may reflect neuronal preservation in long-term meditators—perhaps due to an attenuated release of stress hormones and decreased neurotoxicity. PMID:23847572

Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.

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Peter Rellos

2010-07-01

Full Text Available Long-term potentiation (LTP, a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM-dependent kinase II (CaMKII. CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.

Spontaneous abortion and unexpected death: a critical discussion of Marquis on abortion.

Science.gov (United States)

Coleman, Mary Clayton

2013-02-01

In his classic paper, 'Why abortion is immoral', Don Marquis argues that what makes killing an adult seriously immoral is that it deprives the victim of the valuable future he/she would have otherwise had. Moreover, Marquis contends, because abortion deprives a fetus of the very same thing, aborting a fetus is just as seriously wrong as killing an adult. Marquis' argument has received a great deal of critical attention in the two decades since its publication. Nonetheless, there is a potential challenge to it that seems to have gone unnoticed. A significant percentage of fetuses are lost to spontaneous abortion. Once we bring this fact to our attention, it becomes less clear whether Marquis can use his account of the wrongness of killing to show that abortion is the moral equivalent of murder. In this paper, I explore the relevance of the rate of spontaneous abortion to Marquis' classic anti-abortion argument. I introduce a case I call Unexpected Death in which someone is about to commit murder, but, just as the would-be murderer is about to strike, his would-be victim dies unexpectedly. I then ask: what does Marquis' account of killing imply about the moral status of what the would-be murderer was about to do? I consider four responses Marquis could give to this question, and I examine what implications these responses have for Marquis' strategy of using his account of the wrongness of killing an adult to show that abortion is in the same moral category.

Ultrafast dissociation: An unexpected tool for probing molecular dynamics

International Nuclear Information System (INIS)

Morin, Paul; Miron, Catalin

2012-01-01

Highlights: ► Ultrafast dissociation has been investigated by means of XPS and mass spectrometry. ► The interplay between electron relaxation and molecular dynamics is evidenced. ► Extension toward polyatomics, clusters, adsorbed molecules is considered. ► Quantum effects (spectral hole, angular effects) evidence the molecular field anisotropy. -- Abstract: Ultrafast dissociation following core–shell excitation into an antibonding orbital led to the early observation in HBr of atomic Auger lines associated to the decay of dissociated excited atoms. The purpose of this article is to review the very large variety of systems where such a situation has been encountered, extending from simple diatomic molecules toward more complex systems like polyatomics, clusters, or adsorbed molecules. Interestingly, this phenomenon has revealed an extremely rich and powerful tool for probing nuclear dynamics and its subtle interplay with electron relaxation occurring on a comparable time scale. Consequently this review covers a surprisingly large period, starting in 1986 and still ongoing.

Differential RNA-seq, Multi-Network Analysis and Metabolic Regulation Analysis of Kluyveromyces marxianus Reveals a Compartmentalised Response to Xylose.

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Du Toit W P Schabort

Full Text Available We investigated the transcriptomic response of a new strain of the yeast Kluyveromyces marxianus, in glucose and xylose media using RNA-seq. The data were explored in a number of innovative ways using a variety of networks types, pathway maps, enrichment statistics, reporter metabolites and a flux simulation model, revealing different aspects of the genome-scale response in an integrative systems biology manner. The importance of the subcellular localisation in the transcriptomic response is emphasised here, revealing new insights. As was previously reported by others using a rich medium, we show that peroxisomal fatty acid catabolism was dramatically up-regulated in a defined xylose mineral medium without fatty acids, along with mechanisms to activate fatty acids and transfer products of β-oxidation to the mitochondria. Notably, we observed a strong up-regulation of the 2-methylcitrate pathway, supporting capacity for odd-chain fatty acid catabolism. Next we asked which pathways would respond to the additional requirement for NADPH for xylose utilisation, and rationalised the unexpected results using simulations with Flux Balance Analysis. On a fundamental level, we investigated the contribution of the hierarchical and metabolic regulation levels to the regulation of metabolic fluxes. Metabolic regulation analysis suggested that genetic level regulation plays a major role in regulating metabolic fluxes in adaptation to xylose, even for the high capacity reactions, which is unexpected. In addition, isozyme switching may play an important role in re-routing of metabolic fluxes in subcellular compartments in K. marxianus.

ERP correlates of unexpected word forms in a picture–word study of infants and adults

Science.gov (United States)

Duta, M.D.; Styles, S.J.; Plunkett, K.

2012-01-01

We tested 14-month-olds and adults in an event-related potentials (ERPs) study in which pictures of familiar objects generated expectations about upcoming word forms. Expected word forms labelled the picture (word condition), while unexpected word forms mismatched by either a small deviation in word medial vowel height (mispronunciation condition) or a large deviation from the onset of the first speech segment (pseudoword condition). Both infants and adults showed sensitivity to both types of unexpected word form. Adults showed a chain of discrete effects: positivity over the N1 wave, negativity over the P2 wave (PMN effect) and negativity over the N2 wave (N400 effect). Infants showed a similar pattern, including a robust effect similar to the adult P2 effect. These observations were underpinned by a novel visualisation method which shows the dynamics of the ERP within bands of the scalp over time. The results demonstrate shared processing mechanisms across development, as even subtle deviations from expected word forms were indexed in both age groups by a reduction in the amplitude of characteristic waves in the early auditory evoked potential. PMID:22483072

Genome re-sequencing of semi-wild soybean reveals a complex Soja population structure and deep introgression.

Directory of Open Access Journals (Sweden)

Jie Qiu

Full Text Available Semi-wild soybean is a unique type of soybean that retains both wild and domesticated characteristics, which provides an important intermediate type for understanding the evolution of the subgenus Soja population in the Glycine genus. In this study, a semi-wild soybean line (Maliaodou and a wild line (Lanxi 1 collected from the lower Yangtze regions were deeply sequenced while nine other semi-wild lines were sequenced to a 3-fold genome coverage. Sequence analysis revealed that (1 no independent phylogenetic branch covering all 10 semi-wild lines was observed in the Soja phylogenetic tree; (2 besides two distinct subpopulations of wild and cultivated soybean in the Soja population structure, all semi-wild lines were mixed with some wild lines into a subpopulation rather than an independent one or an intermediate transition type of soybean domestication; (3 high heterozygous rates (0.19-0.49 were observed in several semi-wild lines; and (4 over 100 putative selective regions were identified by selective sweep analysis, including those related to the development of seed size. Our results suggested a hybridization origin for the semi-wild soybean, which makes a complex Soja population structure.

Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding.

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Huang, Kai-Fa; Liaw, Su-Sen; Huang, Wei-Lin; Chia, Cho-Yun; Lo, Yan-Chung; Chen, Yi-Ling; Wang, Andrew H-J

2011-04-08

Aberrant pyroglutamate formation at the N terminus of certain peptides and proteins, catalyzed by glutaminyl cyclases (QCs), is linked to some pathological conditions, such as Alzheimer disease. Recently, a glutaminyl cyclase (QC) inhibitor, PBD150, was shown to be able to reduce the deposition of pyroglutamate-modified amyloid-β peptides in brain of transgenic mouse models of Alzheimer disease, leading to a significant improvement of learning and memory in those transgenic animals. Here, we report the 1.05-1.40 Å resolution structures, solved by the sulfur single-wavelength anomalous dispersion phasing method, of the Golgi-luminal catalytic domain of the recently identified Golgi-resident QC (gQC) and its complex with PBD150. We also describe the high-resolution structures of secretory QC (sQC)-PBD150 complex and two other gQC-inhibitor complexes. gQC structure has a scaffold similar to that of sQC but with a relatively wider and negatively charged active site, suggesting a distinct substrate specificity from sQC. Upon binding to PBD150, a large loop movement in gQC allows the inhibitor to be tightly held in its active site primarily by hydrophobic interactions. Further comparisons of the inhibitor-bound structures revealed distinct interactions of the inhibitors with gQC and sQC, which are consistent with the results from our inhibitor assays reported here. Because gQC and sQC may play different biological roles in vivo, the different inhibitor binding modes allow the design of specific inhibitors toward gQC and sQC.

Two-center three-electron bonding in ClNH{sub 3} revealed via helium droplet infrared laser Stark spectroscopy: Entrance channel complex along the Cl + NH{sub 3} → ClNH{sub 2} + H reaction

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Moradi, Christopher P.; Douberly, Gary E., E-mail: douberly@uga.edu [Department of Chemistry, University of Georgia, Athens, Georgia 30602-2556 (United States); Xie, Changjian; Guo, Hua [Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131 (United States); Kaufmann, Matin [Department of Physical Chemistry II, Ruhr-University Bochum, D-44801 Bochum (Germany)

2016-04-28

Pyrolytic dissociation of Cl{sub 2} is employed to dope helium droplets with single Cl atoms. Sequential addition of NH{sub 3} to Cl-doped droplets leads to the formation of a complex residing in the entry valley to the substitution reaction Cl + NH{sub 3} → ClNH{sub 2} + H. Infrared Stark spectroscopy in the NH stretching region reveals symmetric and antisymmetric vibrations of a C{sub 3v} symmetric top. Frequency shifts from NH{sub 3} and dipole moment measurements are consistent with a ClNH{sub 3} complex containing a relatively strong two-center three-electron (2c–3e) bond. The nature of the 2c–3e bonding in ClNH{sub 3} is explored computationally and found to be consistent with the complexation-induced blue shifts observed experimentally. Computations of interconversion pathways reveal nearly barrierless routes to the formation of this complex, consistent with the absence in experimental spectra of two other complexes, NH{sub 3}Cl and Cl–HNH{sub 2}, which are predicted in the entry valley to the hydrogen abstraction reaction Cl + NH{sub 3} → HCl + NH{sub 2}.

Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP.

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Yu, Qin; Hu, Liyan; Yao, Qing; Zhu, Yongqun; Dong, Na; Wang, Da-Cheng; Shao, Feng

2013-06-01

Rab GTPases are emerging targets of diverse bacterial pathogens. Here, we perform biochemical and structural analyses of LepB, a Rab GTPase-activating protein (GAP) effector from Legionella pneumophila. We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors. Exhaustive mutation analyses identify Arg444 as the arginine finger, but no catalytically essential glutamine residues. Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AlF3 support the catalytic role of Arg444, and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs. Glu449, structurally equivalent to TBC RabGAP glutamine finger in apo-LepB, undergoes a drastic movement upon Rab1 binding, which induces Rab1 Gln70 side-chain flipping towards GDP-AlF3 through a strong ionic interaction. This conformationally rearranged Gln70 acts as the catalytic cis-glutamine, therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB. Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs, particularly those from bacterial pathogens.

The Occurrence of the Recent Deadly Mexico Earthquakes was not that Unexpected

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Flores-Marquez, L.; Sarlis, N. V.; Skordas, E. S.; Varotsos, P.; Ramírez-Rojas, A.

2017-12-01

Most big Mexican earthquakes occur right along the interface between the colliding Cocos and North American plates, but the two recent deadly Mexico earthquakes, i.e., the magnitude 8.2 earthquake that struck the Mexico's Chiapas state on 7 September 2017 and the magnitude 7.1 earthquake that struck central Mexico, almost 12 days later, killing more than 400 people and reducing buildings to rubble in several States happened at two different spots in the flat-slab in the middle of the Cocos tectonic plate which is considered a geologically surprising area [1]. Here, upon considering a new type of analysis termed natural time, we show that their occurrence should not in principle puzzle scientists. Earthquakes may be considered as critical phenomena, see Ref. [2] and references therein and natural time analysis [3] uncovers an order parameter for seismicity. It has been shown [2] that the fluctuations of this order parameter exhibit a universal behavior with a probability density function (pdf), which is non-Gaussian having a left exponential tail [3]. Natural time analysis of seismicity in various tectonic regions of the Mexican Pacific Coast has been made in Ref.[4]. The study of the order parameter pdf for the Chiapas area as well as for the Guerrero area shows that the occurrence of large earthquakes in these two areas was not unexpected. References A. Witze, Deadly Mexico quakes not linked, Nature 549, 442 (2017). Varotsos PA, Sarlis NV, Skordas ES, Natural Time Analysis: The new view of time. Precursory Seismic Electric Signals, Earthquakes and other Complex Time-Series (Springer-Verlag, Berlin Heidelberg 2011) P. Varotsos et al., Similarity of fluctuations in correlated systems: the case of seismicity. Phys. Rev. E 72, 041103 (2005) A. Ramírez-Rojas and E.L. Flores-Márquez, Order parameter analysis of seismicity of the Mexican Pacific coast. Physica A, 392 2507 (2013)

Polylox barcoding reveals haematopoietic stem cell fates realized in vivo

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Rössler, Jens; Wang, Xi; Postrach, Daniel; Busch, Katrin; Rode, Immanuel; Klapproth, Kay; Dietlein, Nikolaus; Quedenau, Claudia; Chen, Wei; Sauer, Sascha; Wolf, Stephan; Höfer, Thomas; Rodewald, Hans-Reimer

2017-01-01

Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping1 has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites2, viral barcodes3, and strategies based on transposons4 and CRISPR/Cas9 genome editing5; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system6,7. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs8–10. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure. PMID:28813413

Polylox barcoding reveals haematopoietic stem cell fates realized in vivo.

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Pei, Weike; Feyerabend, Thorsten B; Rössler, Jens; Wang, Xi; Postrach, Daniel; Busch, Katrin; Rode, Immanuel; Klapproth, Kay; Dietlein, Nikolaus; Quedenau, Claudia; Chen, Wei; Sauer, Sascha; Wolf, Stephan; Höfer, Thomas; Rodewald, Hans-Reimer

2017-08-24

Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure.

Communication complexity and information complexity

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Pankratov, Denis

Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.

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Wu, Daichao; Guo, Ming; Philips, Michael A; Qu, Lingzhi; Jiang, Longying; Li, Jun; Chen, Xiaojuan; Chen, Zhuchu; Chen, Lin; Chen, Yongheng

2016-01-01

Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2.35 Å. LY2874455, a type I inhibitor for FGFR4, binds to the ATP-binding pocket of FGFR4 in a DFG-in active conformation with three hydrogen bonds and a number of van der Waals contacts. After alignment of the kinase domain sequence of 4 FGFRs, and superposition of the ATP binding pocket of 4 FGFRs, our structural analyses reveal that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly.

Falls-risk post-stroke: Examining contributions from paretic versus non paretic limbs to unexpected forward gait slips.

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Kajrolkar, Tejal; Bhatt, Tanvi

2016-09-06

Community-dwelling stroke survivors show a high incidence of falls with unexpected external perturbations during dynamic activities like walking. Previous evidence has demonstrated the importance of compensatory stepping to restore dynamic stability in response to perturbations in hemiparetic stroke survivors. However, these studies were limited to either stance perturbations or perturbation induced under the unaffected limb. This study aimed to compare the differences, if any, between the non-paretic and paretic sides in dynamic stability and protective stepping strategies when exposed to unexpected external perturbation during walking. Twenty hemiparetic subjects experienced an unexpected forward slip during walking on the laboratory walkway either on the paretic (n=10) or the nonparetic limb (n=10). Both groups demonstrated a backward loss of balance with a compensatory stepping response, with the nonparetic-side slip group resorting mainly to an aborted step response (60%) and the paretic-side slip group mainly exhibiting a recovery step response (90%). Although both groups showed an equal incidence of falls, the nonparetic-side slip group demonstrated a higher stability at recovery step touchdown, resulting from lower perturbation magnitudes (slip displacement and velocity) compared to the paretic-side slip group. The results indicate that the paretic side had difficulty initiating and executing a successful stepping response (nonparetic-side slip) and also in reactive limb control while in stance (paretic-side slip). Based on these results it is suggested that intervention strategies for fall-prevention in chronic stroke survivors should focus on paretic limb training for both reactive stepping and weight bearing for improving balance control for recovery from unpredictable perturbations during dynamic activities such as walking. Copyright © 2016. Published by Elsevier Ltd.

Unexpected presence of Fagus orientalis complex in Italy as inferred from 45,000-year-old DNA pollen samples from Venice lagoon.

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Paffetti, Donatella; Vettori, Cristina; Caramelli, David; Vernesi, Cristiano; Lari, Martina; Paganelli, Arturo; Paule, Ladislav; Giannini, Raffaello

2007-08-16

Phylogeographic analyses on the Western Euroasiatic Fagus taxa (F. orientalis, F. sylvatica, F. taurica and F. moesiaca) is available, however, the subdivision of Fagus spp. is unresolved and there is no consensus on the phylogeny and on the identification (both with morphological than molecular markers) of Fagus Eurasiatic taxa. For the first time molecular analyses of ancient pollen, dated at least 45,000 years ago, were used in combination with the phylogeny analysis on current species, to identify the Fagus spp. present during the Last Interglacial period in Italy. In this work we aim at testing if the trnL-trnF chloroplast DNA (cpDNA) region, that has been previously proved efficient in discriminating different Quercus taxa, can be employed in distinguishing the Fagus species and in identifying the ancient pollen. 86 populations from 4 Western Euroasistic taxa were sampled, and sequenced for the trnL-trnF region to verify the efficiency of this cpDNA region in identifying the Fagus spp.. Furthermore, Fagus crenata (2 populations), Fagus grandifolia (2 populations), Fagus japonica, Fagus hayatae, Quercus species and Castanea species were analysed to better resolve the phylogenetic inference. Our results show that this cpDNA region harbour some informative sites that allow to infer relationships among the species within the Fagaceae family. In particular, few specific and fixed mutations were able to discriminate and identify all the different Fagus species. Considering a short fragment of 176 base pairs within the trnL intron, 2 transversions were found able in distinguishing the F. orientalis complex taxa (F. orientalis, F. taurica and F. moesiaca) from the remaining Fagus spp. (F. sylvatica, F. japonica, F. hayataea, F. crenata and F. grandifolia). This permits to analyse this fragment also in ancient samples, where DNA is usually highly degraded. The sequences data indicate that the DNA recovered from ancient pollen belongs to the F. orientalis complex since

Revealing a steroid receptor ligand as a unique PPAR[gamma] agonist

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Lin, Shengchen; Han, Ying; Shi, Yuzhe; Rong, Hui; Zheng, Songyang; Jin, Shikan; Lin, Shu-Yong; Lin, Sheng-Cai; Li, Yong (Pitt); (Xiamen)

2012-06-28

Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPAR{gamma} agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPAR{gamma} target genes and promotes adipocyte differentiation, but with a lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPAR{gamma} ligand-binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-TZD PPAR{gamma} ligands in the treatment of insulin resistance.

Extreme disorder in an ultrahigh-affinity protein complex

DEFF Research Database (Denmark)

Borgia, Alessandro; Borgia, Madeleine B; Bugge, Katrine

2018-01-01

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions...... with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring...... or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex...

Learning to live with complexity.

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Sargut, Gökçe; McGrath, Rita Gunther

2011-09-01

Business life has always featured the unpredictable, the surprising, and the unexpected. But in today's hyperconnected world, complexity is the norm. Systems that used to be separate are now intertwined and interdependent, and knowing the starting conditions is no guide to predicting outcomes; too many continuously changing interactive elements are in play. Managers looking to navigate these difficulties need to adopt new approaches. They should drop outmoded forecasting tools-for example, ones that rely on averages, which are often less important than outliers. Instead, they should use models that simulate the behavior of the system. They should also make sure that their data include a good amount of future-oriented information. Risk mitigation is crucial as well. Managers should minimize the need to rely on predictions-for instance, they can give users a say in product design. They can decouple elements in a system and build in redundancy to minimize the consequences of a partial system failure, and turn to outside partners to extend their own company's capabilities. They can complement hard analysis with "soft" methods such as storytelling to make potentially important future possibilities more real. And they can make trade-offs that keep early failures small and provide the diversity of thought needed in a nimble organization faced with complexity on virtually every front.

A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth.

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Viloria, Katrina; Munasinghe, Amanda; Asher, Sharan; Bogyere, Roberto; Jones, Lucy; Hill, Natasha J

2016-11-25

SPARC is a matricellular protein that is involved in both pancreatic cancer and diabetes. It belongs to a wider family of proteins that share structural and functional similarities. Relatively little is known about this extended family, but evidence of regulatory interactions suggests the importance of a holistic approach to their study. We show that Hevin, SPOCKs, and SMOCs are strongly expressed within islets, ducts, and blood vessels, suggesting important roles for these proteins in the normal pancreas, while FSTL-1 expression is localised to the stromal compartment reminiscent of SPARC. In direct contrast to SPARC, however, FSTL-1 expression is reduced in pancreatic cancer. Consistent with this, FSTL-1 inhibited pancreatic cancer cell proliferation. The complexity of SPARC family proteins is further revealed by the detection of multiple cell-type specific isoforms that arise due to a combination of post-translational modification and alternative splicing. Identification of splice variants lacking a signal peptide suggests the existence of novel intracellular isoforms. This study underlines the importance of addressing the complexity of the SPARC family and provides a new framework to explain their controversial and contradictory effects. We also demonstrate for the first time that FSTL-1 suppresses pancreatic cancer cell growth.

A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

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Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

2016-02-01

Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

Laser-excited luminescence of trace Nd3+ impurity in LaBr3 revealed by Raman spectroscopy

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Yu, Jinqiu; Cui, Lei; He, Huaqiang; Hu, Yunsheng; Wu, Hao; Zeng, Jia; Liu, Yuzhu

2012-10-01

Unexpected additional bands with obvious non-vibrational features were observed in Raman spectra of LaBr3. Extensive study was carried out to reveal the origin of these bands. Results indicate that the additional bands correspond to laser-excited luminescence of trace Nd3+ impurity unintentionally introduced from the La2O3 raw material, which was further confirmed by Raman spectra of specially prepared Nd3+-doped LaBr3 and LaOBr samples. The luminescence properties of Nd3+ in different matrix were compared and discussed. The ultrasensitivity of Raman spectroscopy in detecting trace luminescent lanthanide ions shows good potential for analytical applications.

Low grade mosaic for a complex supernumerary ring chromosome 18 in an adult patient with multiple congenital anomalies

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Hoogeboom A Jeannette M

2010-07-01

Full Text Available Abstract Background Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities might reveal cytogenetic abnormalities of an unexpected complexity. Results We report a 24 years old male patient with lower spinal anomalies, hypospadia, bifid scrotum, cryptorchism, anal atresia, kidney stones, urethra anomalies, radial dysplasia, and a hypoplastic thumb. Some of the anomalies overlap with the VACTERL association. Chromosome analysis of cultured peripheral blood lymphocytes revealed an additional ring chromosome in 13% of the metaphases. Both parents had a normal karyotype, demonstrating the de novo origin of this ring chromosome. FISH analysis using whole chromosome paints showed that the additional chromosomal material was derived from chromosome 18. Chromosome analysis of cultured fibroblasts revealed only one cell with the supernumerary ring chromosome in the 400 analyzed. To characterize the ring chromosome in more detail peripheral blood derived DNA was analyzed using SNP-arrays. The array results indicated a 5 Mb gain of the pericentromeric region of chromosome 18q10-q11.2. FISH analysis using BAC-probes located in the region indicated the presence of 6 signals on the r(18 chromosome. In addition, microsatellite analysis demonstrated that the unique supernumerary ring chromosome was paternally derived and both normal copies showed biparental disomy. Conclusions We report on an adult patient with multiple congenital abnormalities who had in 13% of his cells a unique supernumerary ring chromosome 18 that was composed of 6 copies of the 5 Mb gene rich region of 18q11.

Complexes of alkylphenols with aluminium halides

International Nuclear Information System (INIS)

Golounin, A.V.

1997-01-01

Interaction of aluminium halides with alkylphenols is studied through the NMR method. The peculiarity of complex formation of pentamethylphenol with AlI 3 is revealed. By AlI 3 action on the pentamethylphenol the complexes are formed both of keto- and oxy form [ru

Complexities in euthanasia or physician-assisted suicide as perceived by Dutch physicians and patients' relatives.

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Snijdewind, Marianne C; van Tol, Donald G; Onwuteaka-Philipsen, Bregje D; Willems, Dick L

2014-12-01

The practice of euthanasia and physician-assisted suicide (EAS) is always complex, but some cases are more complex than others. The nature of these unusually complex cases is not known. To identify and categorize the characteristics of EAS requests that are more complex than others. We held in-depth interviews with 28 Dutch physicians about their perception of complex cases of EAS requests. We also interviewed 26 relatives of patients who had died by EAS. We used open coding and inductive analysis to identify various different aspects of the complexities described by the participants. Complexities can be categorized into relational difficulties-such as miscommunication, invisible suffering, and the absence of a process of growth toward EAS-and complexities that arise from unexpected situations, such as the capricious progress of a disease or the obligation to move the patient. The interviews showed that relatives of the patient influence the process toward EAS. First, the process toward EAS may be disrupted, causing a complex situation. Second, the course of the process toward EAS is influenced not only by the patient and his/her attending physician but also by the relatives who are involved. Communicating and clarifying expectations throughout the process may help to prevent the occurrence of unusually complex situations. Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A new unexpected feature of superdeformed nuclei: strange degeneracies and their origin

International Nuclear Information System (INIS)

Dudek, J.

1990-01-01

Unexpected similarities between the superdeformed bands found recently in many nuclei of the mass A ∼ 150 and A ∼ 190 regions and the physical sense of this discovery are discussed. These similarities manifest themselves through the existence of nearly identical sequences of transitions belonging to two neighboring nuclei, and by now numerous nuclear pairs manifesting this feature have been found. The underlying microscopic mechanism is traced back to two independent effects: a readjustment of nuclear deformation diminishing the role of alignment of the least bound nucleus, and, the pseudospin symmetry, responsible for an approximate decoupling of the orbital and the intrinsic (pseudo) spin-degrees of freedom. 9 figs

The unexpected stability of multiwall nanotubes under high pressure and shear deformation

International Nuclear Information System (INIS)

Pashkin, E. Y.; Pankov, A. M.; Kulnitskiy, B. A.; Mordkovich, V. Z.; Perezhogin, I. A.; Karaeva, A. R.; Popov, M. Y.; Sorokin, P. B.; Blank, V. D.

2016-01-01

The behavior of multiwall carbon nanotubes under a high pressure (up to 55 GPa) combined with shear deformation was studied by experimental and theoretical methods. The unexpectedly high stability of the nanotubes' structure under high stresses was observed. After the pressure was released, we observed that the nanotubes had restored their shapes. Atomistic simulations show that the hydrostatic and shear stresses affect the nanotubes' structure in a different way. It was found that the shear stress load in the multiwall nanotubes' outer walls can induce their connection and formation of an amorphized sp"3-hybridized region but internal core keeps the tubular structure.

The unexpected stability of multiwall nanotubes under high pressure and shear deformation

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Pashkin, E. Y.; Pankov, A. M.; Kulnitskiy, B. A.; Mordkovich, V. Z. [Technological Institute for Superhard and Novel Carbon Materials, 7a Centralnaya Street, Troitsk, Moscow 142190 (Russian Federation); Moscow Institute of Physics and Technology, 9 Institutsky Lane, Dolgoprudny 141700 (Russian Federation); Perezhogin, I. A. [Technological Institute for Superhard and Novel Carbon Materials, 7a Centralnaya Street, Troitsk, Moscow 142190 (Russian Federation); Lomonosov Moscow State University, Leninskie Gory, Moscow 119991 (Russian Federation); Karaeva, A. R. [Technological Institute for Superhard and Novel Carbon Materials, 7a Centralnaya Street, Troitsk, Moscow 142190 (Russian Federation); Popov, M. Y.; Sorokin, P. B.; Blank, V. D. [Technological Institute for Superhard and Novel Carbon Materials, 7a Centralnaya Street, Troitsk, Moscow 142190 (Russian Federation); Moscow Institute of Physics and Technology, 9 Institutsky Lane, Dolgoprudny 141700 (Russian Federation); National University of Science and Technology MISiS, 4 Leninskiy Prospekt, Moscow 119049 (Russian Federation)

2016-08-22

The behavior of multiwall carbon nanotubes under a high pressure (up to 55 GPa) combined with shear deformation was studied by experimental and theoretical methods. The unexpectedly high stability of the nanotubes' structure under high stresses was observed. After the pressure was released, we observed that the nanotubes had restored their shapes. Atomistic simulations show that the hydrostatic and shear stresses affect the nanotubes' structure in a different way. It was found that the shear stress load in the multiwall nanotubes' outer walls can induce their connection and formation of an amorphized sp{sup 3}-hybridized region but internal core keeps the tubular structure.

Electrocardiographic features of sudden unexpected death in epilepsy.

Science.gov (United States)

Chyou, Janice Y; Friedman, Daniel; Cerrone, Marina; Slater, William; Guo, Yu; Taupin, Daniel; O'Rourke, Sean; Priori, Silvia G; Devinsky, Orrin

2016-07-01

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. We hypothesized that electrocardiography (ECG) features may distinguish SUDEP cases from living subjects with epilepsy. Using a matched case-control design, we compared ECG studies of 12 consecutive cases of SUDEP over 10 years and 22 epilepsy controls matched for age, sex, epilepsy type (focal, generalized, or unknown/mixed type), concomitant antiepileptic, and psychotropic drug classes. Conduction intervals and prevalence of abnormal ventricular conduction diagnosis (QRS ≥110 msec), abnormal ventricular conduction pattern (QRS <110 msec, morphology of incomplete right or left bundle branch block or intraventricular conduction delay), early repolarization, and features of inherited cardiac channelopathies were assessed. Abnormal ventricular conduction diagnosis and pattern distinguished SUDEP cases from matched controls. Abnormal ventricular conduction diagnosis was present in two cases and no controls. Abnormal ventricular conduction pattern was more common in cases than controls (58% vs. 18%, p = 0.04). Early repolarization was similarly prevalent in cases and controls, but the overall prevalence exceeded that of published community-based cohorts. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Unexpected observations after mapping LongSAGE tags to the human genome

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Duret Laurent

2007-05-01

Full Text Available Abstract Background SAGE has been used widely to study the expression of known transcripts, but much less to annotate new transcribed regions. LongSAGE produces tags that are sufficiently long to be reliably mapped to a whole-genome sequence. Here we used this property to study the position of human LongSAGE tags obtained from all public libraries. We focused mainly on tags that do not map to known transcripts. Results Using a published error rate in SAGE libraries, we first removed the tags likely to result from sequencing errors. We then observed that an unexpectedly large number of the remaining tags still did not match the genome sequence. Some of these correspond to parts of human mRNAs, such as polyA tails, junctions between two exons and polymorphic regions of transcripts. Another non-negligible proportion can be attributed to contamination by murine transcripts and to residual sequencing errors. After filtering out our data with these screens to ensure that our dataset is highly reliable, we studied the tags that map once to the genome. 31% of these tags correspond to unannotated transcripts. The others map to known transcribed regions, but many of them (nearly half are located either in antisense or in new variants of these known transcripts. Conclusion We performed a comprehensive study of all publicly available human LongSAGE tags, and carefully verified the reliability of these data. We found the potential origin of many tags that did not match the human genome sequence. The properties of the remaining tags imply that the level of sequencing error may have been under-estimated. The frequency of tags matching once the genome sequence but not in an annotated exon suggests that the human transcriptome is much more complex than shown by the current human genome annotations, with many new splicing variants and antisense transcripts. SAGE data is appropriate to map new transcripts to the genome, as demonstrated by the high rate of cross

Detailed monitoring of a small but recovering population reveals sublethal effects of disease and unexpected interactions with supplemental feeding.

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Tollington, Simon; Greenwood, Andrew; Jones, Carl G; Hoeck, Paquita; Chowrimootoo, Aurélie; Smith, Donal; Richards, Heather; Tatayah, Vikash; Groombridge, Jim J

2015-07-01

Infectious diseases are widely recognized to have substantial impact on wildlife populations. These impacts are sometimes exacerbated in small endangered populations, and therefore, the success of conservation reintroductions to aid the recovery of such species can be seriously threatened by outbreaks of infectious disease. Intensive management strategies associated with conservation reintroductions can further compound these negative effects in such populations. Exploring the sublethal effects of disease outbreaks among natural populations is challenging and requires longitudinal, individual life-history data on patterns of reproductive success and other indicators of individual fitness. Long-term monitoring data concerning detailed reproductive information of the reintroduced Mauritius parakeet (Psittacula echo) population collected before, during and after a disease outbreak was investigated. Deleterious effects of an outbreak of beak and feather disease virus (BFDV) were revealed on hatch success, but these effects were remarkably short-lived and disproportionately associated with breeding pairs which took supplemental food. Individual BFDV infection status was not predicted by any genetic, environmental or conservation management factors and was not associated with any of our measures of immune function, perhaps suggesting immunological impairment. Experimental immunostimulation using the PHA (phytohaemagglutinin assay) challenge technique did, however, provoke a significant cellular immune response. We illustrate the resilience of this bottlenecked and once critically endangered, island-endemic species to an epidemic outbreak of BFDV and highlight the value of systematic monitoring in revealing inconspicuous but nonetheless substantial ecological interactions. Our study demonstrates that the emergence of such an infectious disease in a population ordinarily associated with increased susceptibility does not necessarily lead to deleterious impacts on population

Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor

Energy Technology Data Exchange (ETDEWEB)

Peng, Guiqing; Sun, Dawei; Rajashankar, Kanagalaghatta R.; Qian, Zhaohui; Holmes, Kathryn V.; Li, Fang (Cornell); (UMM-MED); (Colorado)

2011-09-28

Coronaviruses have evolved diverse mechanisms to recognize different receptors for their cross-species transmission and host-range expansion. Mouse hepatitis coronavirus (MHV) uses the N-terminal domain (NTD) of its spike protein as its receptor-binding domain. Here we present the crystal structure of MHV NTD complexed with its receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a). Unexpectedly, MHV NTD contains a core structure that has the same {beta}-sandwich fold as human galectins (S-lectins) and additional structural motifs that bind to the N-terminal Ig-like domain of mCEACAM1a. Despite its galectin fold, MHV NTD does not bind sugars, but instead binds mCEACAM1a through exclusive protein-protein interactions. Critical contacts at the interface have been confirmed by mutagenesis, providing a structural basis for viral and host specificities of coronavirus/CEACAM1 interactions. Sugar-binding assays reveal that galectin-like NTDs of some coronaviruses such as human coronavirus OC43 and bovine coronavirus bind sugars. Structural analysis and mutagenesis localize the sugar-binding site in coronavirus NTDs to be above the {beta}-sandwich core. We propose that coronavirus NTDs originated from a host galectin and retained sugar-binding functions in some contemporary coronaviruses, but evolved new structural features in MHV for mCEACAM1a binding.

Cilium transition zone proteome reveals compartmentalization and differential dynamics of ciliopathy complexes

Czech Academy of Sciences Publication Activity Database

Dean, S.; Moreira-Leite, F.; Varga, Vladimír; Gull, K.

2016-01-01

Roč. 113, č. 35 (2016), E5135-E5143 ISSN 0027-8424 Institutional support: RVO:68378050 Keywords : transition zone * cilium/flagellum * BBSome * MKS/B9 complex * trypanosome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.661, year: 2016

Whole exome sequencing in 342 congenital cardiac left sided lesion cases reveals extensive genetic heterogeneity and complex inheritance patterns

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Alexander H. Li

2017-10-01

Full Text Available Abstract Background Left-sided lesions (LSLs account for an important fraction of severe congenital cardiovascular malformations (CVMs. The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. Here, we use whole exome sequence data generated in 342 LSL cases to identify likely damaging variants in putative candidate CVM genes. Methods Using a series of bioinformatics filters, we focused on genes harboring population-rare, putative loss-of-function (LOF, and predicted damaging variants in 1760 CVM candidate genes constructed a priori from the literature and model organism databases. Gene variants that were not observed in a comparably sequenced control dataset of 5492 samples without severe CVM were then subjected to targeted validation in cases and parents. Whole exome sequencing data from 4593 individuals referred for clinical sequencing were used to bolster evidence for the role of candidate genes in CVMs and LSLs. Results Our analyses revealed 28 candidate variants in 27 genes, including 17 genes not previously associated with a human CVM disorder, and revealed diverse patterns of inheritance among LOF carriers, including 9 confirmed de novo variants in both novel and newly described human CVM candidate genes (ACVR1, JARID2, NR2F2, PLRG1, SMURF1 as well as established syndromic CVM genes (KMT2D, NF1, TBX20, ZEB2. We also identified two genes (DNAH5, OFD1 with evidence of recessive and hemizygous inheritance patterns, respectively. Within our clinical cohort, we also observed heterozygous LOF variants in JARID2 and SMAD1 in individuals with cardiac phenotypes, and collectively, carriers of LOF variants in our candidate genes had a four times higher odds of having CVM (odds ratio = 4.0, 95% confidence interval 2.5–6.5. Conclusions Our analytical strategy highlights the utility of bioinformatic resources, including human

Chemical messages in 170-year-old champagne bottles from the Baltic Sea: Revealing tastes from the past.

Science.gov (United States)

Jeandet, Philippe; Heinzmann, Silke S; Roullier-Gall, Chloé; Cilindre, Clara; Aron, Alissa; Deville, Marie Alice; Moritz, Franco; Karbowiak, Thomas; Demarville, Dominique; Brun, Cyril; Moreau, Fabienne; Michalke, Bernhard; Liger-Belair, Gérard; Witting, Michael; Lucio, Marianna; Steyer, Damien; Gougeon, Régis D; Schmitt-Kopplin, Philippe

2015-05-12

Archaeochemistry as the application of the most recent analytical techniques to ancient samples now provides an unprecedented understanding of human culture throughout history. In this paper, we report on a multiplatform analytical investigation of 170-y-old champagne bottles found in a shipwreck at the bottom of the Baltic Sea, which provides insight into winemaking practices used at the time. Organic spectroscopy-based nontargeted metabolomics and metallomics give access to the detailed composition of these wines, revealing, for instance, unexpected chemical characteristics in terms of small ion, sugar, and acid contents as well as markers of barrel aging and Maillard reaction products. The distinct aroma composition of these ancient champagne samples, first revealed during tasting sessions, was later confirmed using state-of-the-art aroma analysis techniques. After 170 y of deep sea aging in close-to-perfect conditions, these sleeping champagne bottles awoke to tell us a chapter of the story of winemaking and to reveal their extraordinary archaeometabolome and elemental diversity in the form of chemical signatures related to each individual step of champagne production.

Whole genome sequencing reveals complex evolution patterns of multidrug-resistant Mycobacterium tuberculosis Beijing strains in patients.

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Matthias Merker

Full Text Available Multidrug-resistant (MDR Mycobacterium tuberculosis complex (MTBC strains represent a major threat for tuberculosis (TB control. Treatment of MDR-TB patients is long and less effective, resulting in a significant number of treatment failures. The development of further resistances leads to extensively drug-resistant (XDR variants. However, data on the individual reasons for treatment failure, e.g. an induced mutational burst, and on the evolution of bacteria in the patient are only sparsely available. To address this question, we investigated the intra-patient evolution of serial MTBC isolates obtained from three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR-TB. Sequential isolates displayed identical IS6110 fingerprint patterns, suggesting the absence of exogenous re-infection. We utilized whole genome sequencing (WGS to screen for variations in three isolates from Patient A and four isolates from Patient B and C, respectively. Acquired polymorphisms were subsequently validated in up to 15 serial isolates by Sanger sequencing. We determined eight (Patient A and nine (Patient B polymorphisms, which occurred in a stepwise manner during the course of the therapy and were linked to resistance or a potential compensatory mechanism. For both patients, our analysis revealed the long-term co-existence of clonal subpopulations that displayed different drug resistance allele combinations. Out of these, the most resistant clone was fixed in the population. In contrast, baseline and follow-up isolates of Patient C were distinguished each by eleven unique polymorphisms, indicating an exogenous re-infection with an XDR strain not detected by IS6110 RFLP typing. Our study demonstrates that intra-patient microevolution of MDR-MTBC strains under longitudinal treatment is more complex than previously anticipated. However, a mutator phenotype was not detected. The presence of different subpopulations might confound phenotypic and

MD simulation of the Tat/Cyclin T1/CDK9 complex revealing the hidden catalytic cavity within the CDK9 molecule upon Tat binding.

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Kaori Asamitsu

Full Text Available In this study, we applied molecular dynamics (MD simulation to analyze the dynamic behavior of the Tat/CycT1/CDK9 tri-molecular complex and revealed the structural changes of P-TEFb upon Tat binding. We found that Tat could deliberately change the local flexibility of CycT1. Although the structural coordinates of the H1 and H2 helices did not substantially change, H1', H2', and H3' exhibited significant changes en masse. Consequently, the CycT1 residues involved in Tat binding, namely Tat-recognition residues (TRRs, lost their flexibility with the addition of Tat to P-TEFb. In addition, we clarified the structural variation of CDK9 in complex with CycT1 in the presence or absence of Tat. Interestingly, Tat addition significantly reduced the structural variability of the T-loop, thus consolidating the structural integrity of P-TEFb. Finally, we deciphered the formation of the hidden catalytic cavity of CDK9 upon Tat binding. MD simulation revealed that the PITALRE signature sequence of CDK9 flips the inactive kinase cavity of CDK9 into the active form by connecting with Thr186, which is crucial for its activity, thus presumably recruiting the substrate peptide such as the C-terminal domain of RNA pol II. These findings provide vital information for the development of effective novel anti-HIV drugs with CDK9 catalytic activity as the target.

Unexpected Diagnosis of Cerebral Toxoplasmosis by 16S and D2 Large-Subunit Ribosomal DNA PCR and Sequencing

DEFF Research Database (Denmark)

Kruse, Alexandra Yasmin Collin; Kvich, Lasse Andersson; Eickhardt-Dalbøge, Steffen Robert

2015-01-01

The protozoan parasite Toxoplasma gondii causes severe opportunistic infections. Here, we report an unexpected diagnosis of cerebral toxoplasmosis. T. gondii was diagnosed by 16S and D2 large-subunit (LSU) ribosomal DNA (rDNA) sequencing of a cerebral biopsy specimen and confirmed by T. gondii...

Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.

Science.gov (United States)

Cevher, Murat A; Shi, Yi; Li, Dan; Chait, Brian T; Malik, Sohail; Roeder, Robert G

2014-12-01

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.

Should I Stay or Should I Go? Attentional Disengagement from Visually Unique and Unexpected Items at Fixation

Science.gov (United States)

Brockmole, James R.; Boot, Walter R.

2009-01-01

Distinctive aspects of a scene can capture attention even when they are irrelevant to one's goals. The authors address whether visually unique, unexpected, but task-irrelevant features also tend to hold attention. Observers searched through displays in which the color of each item was irrelevant. At the start of search, all objects changed color.…

Compressive Sensing Based Bayesian Sparse Channel Estimation for OFDM Communication Systems: High Performance and Low Complexity

Science.gov (United States)

Xu, Li; Shan, Lin; Adachi, Fumiyuki

2014-01-01

In orthogonal frequency division modulation (OFDM) communication systems, channel state information (CSI) is required at receiver due to the fact that frequency-selective fading channel leads to disgusting intersymbol interference (ISI) over data transmission. Broadband channel model is often described by very few dominant channel taps and they can be probed by compressive sensing based sparse channel estimation (SCE) methods, for example, orthogonal matching pursuit algorithm, which can take the advantage of sparse structure effectively in the channel as for prior information. However, these developed methods are vulnerable to both noise interference and column coherence of training signal matrix. In other words, the primary objective of these conventional methods is to catch the dominant channel taps without a report of posterior channel uncertainty. To improve the estimation performance, we proposed a compressive sensing based Bayesian sparse channel estimation (BSCE) method which cannot only exploit the channel sparsity but also mitigate the unexpected channel uncertainty without scarifying any computational complexity. The proposed method can reveal potential ambiguity among multiple channel estimators that are ambiguous due to observation noise or correlation interference among columns in the training matrix. Computer simulations show that proposed method can improve the estimation performance when comparing with conventional SCE methods. PMID:24983012

The simple beauty of the unexpected a natural philosopher's quest for trout and the meaning of everything

CERN Document Server

Gleiser, Marcelo

2016-01-01

Marcelo Gleiser has had a passion for science and fishing since he was a boy growing up on the beaches of Rio de Janeiro. Now a world-famous theoretical physicist with hundreds of scientific articles and several books of popular science to his credit, he felt it was time to connect with nature in less theoretical ways. After seeing a fly-fishing class on the Dartmouth College green, he decided to learn to fly-fish, a hobby, he says, that teaches humility. In The Simple Beauty of the Unexpected, Gleiser travels the world to scientific conferences, fishing wherever he goes. At each stop, he ponders how in the myriad ways physics informs the act of fishing; how, in its turn, fishing serves as a lens into nature s inner workings; and how science engages with questions of meaning and spirituality, inspiring a sense of mystery and awe of the not yet known. Personal and engaging, The Simple Beauty of the Unexpected is a scientist s tribute to nature, an affirmation of humanity s deep connection with and debt to Eart...

Origin of calcite in the glacigenic Virttaankangas complex

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Nina M. Kortelainen

2007-01-01

Full Text Available Groundwaters of the glacigenic Virttaankangas complex in southern Finland are characterized by high pH values ranging up to 9.5. These values are significantly higher than those observed in silicate-rich shallow groundwater formations in crystalline bedrock areas. TheVirttaankangas sediments were discovered to contain small amounts of fine grained, dispersed calcite, which has a high tendency to increase the pH of local groundwaters. The primary goal of this study was to determine the mode of occurrence of calcite and to identifyits sources. The mineralogy of the glacigenic Virttaankangas complex was studied using material from 21 sediment drill cores. Fine-grained calcite is present in trace amounts (<< 1.4 % in the glaciofluvial and glaciolacustrine depositional units of the Virttaankangas complex. The topmost littoral sands were practically devoid of calcite. The isotope records of carbon and oxygen, the angular morphology of the grains and the uniform dispersion of calcite in the complex suggest a clastic origin for calcite, with no evidence for in-situ precipitation. In order to constrain the source of calcite, the isotopic composition of carbon and oxygen in five calcite samples was compared to the isotopic data from five carbonate rock erratics and eight crystalline bedrock samples from the region. Based on carbon and oxygen isotope ratios and chemical compositions, the dispersed calcite grains of the Virttaankangas complex appear to have been derived from the Mesoproterozoic Satakunta Formation, some 30 km NW from the Virttaankangas area. In sandstone, calcite is predominantly present as diagenetic cement in grain interspaces, concretions and interlayers. The source of detrital calcite was unexpected, as prior to this study the Satakunta sandstone hasnot been known to contain calcite.

Multilocus dataset reveals demographic histories of two peat mosses in Europe

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Hock Zsófia

2007-08-01

mutations in S. fimbriatum compared to S. squarrosum mirror unexpected differences in the demography and population history of the species. Conclusion This study represents the first detailed European wide phylodemographic investigation on bryophytes and shows how pattern of nucleotide polymorphism can reveal unexpected differences in the population history of haploid plants with seemingly similar characteristics.

γ-Irradiation and characterization of synthesized methoxybenzylpyrimidine formimidate Schiff-base and some metal-complex derivatives

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R.O. Aly

2016-09-01

The magnetic properties together with the UV–Vis reposted data revealed the octahedral coordination of the Zn- and La-complex and the tetragonal distortion geometry of the Cu-complex. The La-complexes revealed only moderate inhibition against the Gram-negative Escherichia coli, whereas the Zn-complex revealed significant inhibition. The latter showed also similar effect against the Gram-positive Bacillus subtilis and Streptococcus pyogens (ATCC-19615.

Reconstitution of active human core Mediator complex reveals a pivotal role of the MED14 subunit

Science.gov (United States)

Cevher, Murat A.; Shi, Yi; Li, Dan; Chait, Brian T.; Malik, Sohail; Roeder, Robert G.

2014-01-01

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here, we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to mass spectrometry (CX-MS). Whereas the reconstituted head and middle modules can stably associate, only with incorporation of MED14 into the bi-modular complex does it acquire basal and coactivator functions. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematically dissecting the multiple layers of functionalities associated with the Mediator complex. PMID:25383669

Development of C-lignin with G/S-lignin and lipids in orchid seed coats – an unexpected diversity exposed by ATR-FT-IR spectroscopy

DEFF Research Database (Denmark)

Barsberg, Søren Talbro; Lee, Y.-I.; Rasmussen, Hanne Nina

2018-01-01

Cite this article: Barsberg ST, Lee Y-I, Rasmussen HN. Development of C-lignin with G/S-lignin and lipids in orchid seed coats – an unexpected diversity exposed by ATR-FT-IR spectroscopy. Seed Science Research https:// doi.org/10.1017/S0960258517000344......Cite this article: Barsberg ST, Lee Y-I, Rasmussen HN. Development of C-lignin with G/S-lignin and lipids in orchid seed coats – an unexpected diversity exposed by ATR-FT-IR spectroscopy. Seed Science Research https:// doi.org/10.1017/S0960258517000344...

Sudden Unexpected Death in Epilepsy: A Retrospective Autopsy Study of 112 Epileptic Patients.

Science.gov (United States)

Esen Melez, İpek; Arslan, Murat Nihat; Melez, Deniz Oğuzhan; Şanli, Ahmet Necati; Koç, Sermet

2017-09-01

Sudden unexpected deaths comprise the most important and worthy investigation case profiles in both neurology and forensic medicine. Epilepsy, which is one of the neuropathological causes of sudden unexpected deaths, is an important disorder having mysterious aspects. The aim of this study is to make common the points of view between neurology and forensic medicine experts and to discuss the features of the findings together with the related clinical hypotheses, leading to the differential diagnosis of sudden unexpected death in epilepsy (SUDEP) by presenting autopsy findings and available medical data of patients who had a prior diagnosis of epilepsy. In Istanbul, the cases of 20334 autopsied patients who were referred to The Ministry of Justice Council of Forensic Medicine between 2007 and 2011 were identified from the complete forensic autopsy data of the city and were retrospectively reviewed. Patients who had a prior diagnosis of epilepsy were included. Both descriptive and inferential statistical analyses were performed through the parameters of demographical data, physical properties, incident features, macroscopic-microscopic autopsy findings, and cause of death initially for all cases and then separately for SUDEP cases. Among the 20334 patients, 112 were determined to have a prior diagnosis of epilepsy. A possible macroscopic and/or microscopic epileptic focus was present in 23 (20.5%) of these 112 cases. The cause of death was determined to be SUDEP in 40 (35.7%) cases, while it could not be determined in 28 (25%) cases. Among patients whose death cause was considered as SUDEP, the male-to-female ratio was 1.1:1, while the mean age was 31.5±13.9 years in males and 29.6±12.9 years in females. The presence of hypertrophy and myocardial scar tissue findings in the microscopic examination were significantly more frequent among patients determined to have died from cardiovascular diseases compared to patients in the SUDEP group (p=0.001 for each finding

Characterization and 454 pyrosequencing of Major Histocompatibility Complex class I genes in the great tit reveal complexity in a passerine system

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Sepil Irem

2012-05-01

Full Text Available Abstract Background The critical role of Major Histocompatibility Complex (Mhc genes in disease resistance and their highly polymorphic nature make them exceptional candidates for studies investigating genetic effects on survival, mate choice and conservation. Species that harbor many Mhc loci and high allelic diversity are particularly intriguing as they are potentially under strong selection and studies of such species provide valuable information as to the mechanisms maintaining Mhc diversity. However comprehensive genotyping of complex multilocus systems has been a major challenge to date with the result that little is known about the consequences of this complexity in terms of fitness effects and disease resistance. Results In this study, we genotyped the Mhc class I exon 3 of the great tit (Parus major from two nest-box breeding populations near Oxford, UK that have been monitored for decades. Characterization of Mhc class I exon 3 was adopted and bidirectional sequencing was carried using the 454 sequencing platform. Full analysis of sequences through a stepwise variant validation procedure allowed reliable typing of more than 800 great tits based on 214,357 reads; from duplicates we estimated the repeatability of typing as 0.94. A total of 862 alleles were detected, and the presence of at least 16 functional loci was shown - the highest number characterized in a wild bird species. Finally, the functional alleles were grouped into 17 supertypes based on their antigen binding affinities. Conclusions We found extreme complexity at the Mhc class I of the great tit both in terms of allelic diversity and gene number. The presence of many functional loci was shown, together with a pseudogene family and putatively non-functional alleles; there was clear evidence that functional alleles were under strong balancing selection. This study is the first step towards an in-depth analysis of this gene complex in this species, which will help

Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.

Science.gov (United States)

Sun, Ji; MacKinnon, Roderick

2017-06-01

KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I Ks ) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP 2 -free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP 2 . CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2 , and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Copyright © 2017 Elsevier Inc. All rights reserved.

High-Resolution Imaging Reveals New Features of Nuclear Export of mRNA through the Nuclear Pore Complexes

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Joseph M. Kelich

2014-08-01

Full Text Available The nuclear envelope (NE of eukaryotic cells provides a physical barrier for messenger RNA (mRNA and the associated proteins (mRNPs traveling from sites of transcription in the nucleus to locations of translation processing in the cytoplasm. Nuclear pore complexes (NPCs embedded in the NE serve as a dominant gateway for nuclear export of mRNA. However, the fundamental characterization of export dynamics of mRNPs through the NPC has been hindered by several technical limits. First, the size of NPC that is barely below the diffraction limit of conventional light microscopy requires a super-resolution microscopy imaging approach. Next, the fast transit of mRNPs through the NPC further demands a high temporal resolution by the imaging approach. Finally, the inherent three-dimensional (3D movements of mRNPs through the NPC demand the method to provide a 3D mapping of both transport kinetics and transport pathways of mRNPs. This review will highlight the recently developed super-resolution imaging techniques advanced from 1D to 3D for nuclear export of mRNPs and summarize the new features in the dynamic nuclear export process of mRNPs revealed from these technical advances.

FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end

Science.gov (United States)

Sato, Koichi; Shimomuki, Mayo; Katsuki, Yoko; Takahashi, Daisuke; Kobayashi, Wataru; Ishiai, Masamichi; Miyoshi, Hiroyuki; Takata, Minoru; Kurumizaka, Hitoshi

2016-01-01

The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork. PMID:27694619

Proteomic analysis reveals the diversity and complexity of membrane proteins in chickpea (Cicer arietinum L.

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Jaiswal Dinesh Kumar

2012-10-01

Full Text Available Abstract Background Compartmentalization is a unique feature of eukaryotes that helps in maintaining cellular homeostasis not only in intra- and inter-organellar context, but also between the cells and the external environment. Plant cells are highly compartmentalized with a complex metabolic network governing various cellular events. The membranes are the most important constituents in such compartmentalization, and membrane-associated proteins play diverse roles in many cellular processes besides being part of integral component of many signaling cascades. Results To obtain valuable insight into the dynamic repertoire of membrane proteins, we have developed a proteome reference map of a grain legume, chickpea, using two-dimensional gel electrophoresis. MALDI-TOF/TOF and LC-ESI-MS/MS analysis led to the identification of 91 proteins involved in a variety of cellular functions viz., bioenergy, stress-responsive and signal transduction, metabolism, protein synthesis and degradation, among others. Significantly, 70% of the identified proteins are putative integral membrane proteins, possessing transmembrane domains. Conclusions The proteomic analysis revealed many resident integral membrane proteins as well as membrane-associated proteins including those not reported earlier. To our knowledge, this is the first report of membrane proteome from aerial tissues of a crop plant. The findings may provide a better understanding of the biochemical machinery of the plant membranes at the molecular level that might help in functional genomics studies of different developmental pathways and stress-responses.

Language and music: differential hemispheric dominance in detecting unexpected errors in the lyrics and melody of memorized songs.

Science.gov (United States)

Yasui, Takuya; Kaga, Kimitaka; Sakai, Kuniyoshi L

2009-02-01

Using magnetoencephalography (MEG), we report here the hemispheric dominance of the auditory cortex that is selectively modulated by unexpected errors in the lyrics and melody of songs (lyrics and melody deviants), thereby elucidating under which conditions the lateralization of auditory processing changes. In experiment 1 using familiar songs, we found that the dipole strength of responses to the lyrics deviants was left-dominant at 140 ms (M140), whereas that of responses to the melody deviants was right-dominant at 130 ms (M130). In experiment 2 using familiar songs with a constant syllable or pitch, the dipole strength of frequency mismatch negativity elicited by oddballs was left-dominant. There were significant main effects of experiment (1 and 2) for the peak latencies and for the coordinates of the dipoles, indicating that the M140 and M130 were not the frequency mismatch negativity. In experiment 3 using newly memorized songs, the right-dominant M130 was observed only when the presented note was unexpected one, independent of perceiving unnatural pitch transitions (i.e., perceptual saliency) and of selective attention to the melody of songs. The consistent right-dominance of the M130 between experiments 1 and 3 suggests that the M130 in experiment 1 is due to unexpected notes deviating from well-memorized songs. On the other hand, the left-dominant M140 was elicited by lyrics deviants, suggesting the influence of top-down linguistic information and the memory of the familiar songs. We thus conclude that the left- lateralized M140 and right-lateralized M130 reflect the expectation based on top-down information of language and music, respectively.

We Reveal Ourselves to Ourselves: The New Communication Media in the Philippines

Directory of Open Access Journals (Sweden)

Raul Pertierra

2013-06-01

Full Text Available The cellphone and the Internet are very significantly changing the communication landscape in the Philippines. Concomitantly, the new media are transforming social relationships in new and unexpected ways. With the new media, not only can Filipinos more easily communicate with their relatives and friends abroad; they also have new possibilities for revealing important aspects of self-identity. Mobiles are the most important new technology introduced in the Philippines and their effects far exceed most expectations. Even relationships with the recently dead are being affected by this technology. Moreover, the new media are also transforming older communication media,helping them penetrate and influence increasing aspects of everyday life. While the emancipatory possibilities of the new communication media are promising, new divisions and inequalities are also arising. Access to communication is emerging as one of the major sources of inequality.

Synchronizability on complex networks via pinning control

Indian Academy of Sciences (India)

Keywords. Complex network; the pinning synchronization; synchronizability. ... The findings reveal the relationship between the decreasing speed of maximum eigenvalue sequence of the principal submatrices for coupling matrix and the synchronizability on complex networks via pinning control. We discuss the ...

Critical Fluctuations in Spatial Complex Networks

Science.gov (United States)

Bradde, Serena; Caccioli, Fabio; Dall'Asta, Luca; Bianconi, Ginestra

2010-05-01

An anomalous mean-field solution is known to capture the nontrivial phase diagram of the Ising model in annealed complex networks. Nevertheless, the critical fluctuations in random complex networks remain mean field. Here we show that a breakdown of this scenario can be obtained when complex networks are embedded in geometrical spaces. Through the analysis of the Ising model on annealed spatial networks, we reveal, in particular, the spectral properties of networks responsible for critical fluctuations and we generalize the Ginsburg criterion to complex topologies.

Small-angle X-ray Solution Scattering Study of the Multi-aminoacyl-tRNA Synthetase Complex Reveals an Elongated and Multi-armed particle*

Science.gov (United States)

Dias, José; Renault, Louis; Pérez, Javier; Mirande, Marc

2013-01-01

In animal cells, nine aminoacyl-tRNA synthetases are associated with the three auxiliary proteins p18, p38, and p43 to form a stable and conserved large multi-aminoacyl-tRNA synthetase complex (MARS), whose molecular mass has been proposed to be between 1.0 and 1.5 MDa. The complex acts as a molecular hub for coordinating protein synthesis and diverse regulatory signal pathways. Electron microscopy studies defined its low resolution molecular envelope as an overall rather compact, asymmetric triangular shape. Here, we have analyzed the composition and homogeneity of the native mammalian MARS isolated from rabbit liver and characterized its overall internal structure, size, and shape at low resolution by hydrodynamic methods and small-angle x-ray scattering in solution. Our data reveal that the MARS exhibits a much more elongated and multi-armed shape than expected from previous reports. The hydrodynamic and structural features of the MARS are large compared with other supramolecular assemblies involved in translation, including ribosome. The large dimensions and non-compact structural organization of MARS favor a large protein surface accessibility for all its components. This may be essential to allow structural rearrangements between the catalytic and cis-acting tRNA binding domains of the synthetases required for binding the bulky tRNA substrates. This non-compact architecture may also contribute to the spatiotemporal controlled release of some of its components, which participate in non-canonical functions after dissociation from the complex. PMID:23836901

Benefits and unexpected artifacts of biplanar digital slot-scanning imaging in children

Energy Technology Data Exchange (ETDEWEB)

Blumer, Steven L. [Nemours/A.I duPont Hospital for Children, Department of Medical Imaging, Wilmington, DE (United States); Dinan, David [Nemours Children' s Hospital, Orlando, FL (United States); Grissom, Leslie E. [Nemours/Alfred I. duPont Hospital for Children, Department of Radiology, Wilmington, DE (United States)

2014-07-15

Biplanar digital slot-scanning allows for relatively low-dose orthopedic imaging, an advantage in imaging children given the growing concerns regarding radiosensitivity. We have used this system for approximately 1 year for orthopedic imaging of the spine and lower extremities. We have noted advantages of using the digital slot-scanning system when compared with computed radiographic and standard digital radiographic imaging systems, but we also found unexpected but common imaging artifacts that are the direct result of the imaging method and that have not been reported. This pictorial essay serves to familiarize radiologists with the advantages of the digital slot-scanning system as well as imaging artifacts common with this new technology. (orig.)

Embedded Prompting May Function as Embedded Punishment: Detection of Unexpected Behavioral Processes within a Typical Preschool Teaching Strategy

Science.gov (United States)

Heal, Nicole A.; Hanley, Gregory P.

2011-01-01

This study describes an unexpected behavioral process that influenced behavior during the teaching of concepts to a 4-year-old girl. The efficacy of and preference for three strategies that varied in teacher directedness were assessed in a multielement design and concurrent-chains arrangement, respectively. The strategy that involved the most…

Cavernous malformations isolated from cranial nerves: Unexpected diagnosis?

Science.gov (United States)

Rotondo, Michele; Natale, Massimo; D'Avanzo, Raffaele; Pascale, Michela; Scuotto, Assunta

2014-11-01

Cranial nerves (CN) cavernous malformations (CMs) are lesions that are isolated from the CNs. The authors present three cases of CN CMs, for which MR was demonstrated to be critical for management, and surgical resection produced good outcomes for the patients. Surgical removal is the recommended course of action to restore or preserve neurological function and to eliminate the risk of future haemorrhage. However, the anatomical location and the complexity of nearby neural structures can make these lesions difficult to access and remove. In this study, the authors review the literature of reported cases of CN CMs to analyse the clinical and radiographic presentations, surgical approaches and neurological outcomes. A MEDLINE/Pub Med search was performed and revealed 86 cases of CN CMs. The authors report three additional cases in this study for a total of 89 cases. CMs affecting the optic nerve (CN II), oculomotor nerve (CN III), facial/vestibule-cochlear nerves (CN VII, CN VIII) have been described. The records of three patients were reviewed with respect to the lesion locations, symptoms, surgical approaches and therapeutic considerations. Clinical and radiological follow-up results are reported. Three patients (2 females, 1 male; age range 21-37 year) presented with three CN lesions. One lesion involved CN III, one lesion involved CN VII-CN VIII, and one involved CN II. The patient with the CN III lesion had a one-month history of mild right ptosis and diplopia. The patient with the CN VII-CN VIII lesion exhibited acute hearing loss and on the left and left facial paresis. The patient with the opticchiasmatic lesion presented with acute visual deterioration on the right and a left temporal field deficit in the left eye. Pterional and orbitozygomatic craniotomies were performed for the CN III lesion and the CN II lesion, and retrosigmoid craniotomy was performed for the cerebello-pontine angle lesion. All patients experienced symptom improvement after surgery. On

Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

Science.gov (United States)

Hodson, Charlotte; Purkiss, Andrew; Miles, Jennifer Anne; Walden, Helen

2014-01-01

Summary The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ∼40 E2s and ∼600 E3s giving rise to a possible ∼24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL. PMID:24389026

Structures of BmrR-Drug Complexes Reveal a Rigid Multidrug Binding Pocket And Transcription Activation Through Tyrosine Expulsion

Energy Technology Data Exchange (ETDEWEB)

Newberry, K.J.; Huffman, J.L.; Miller, M.C.; Vazquez-Laslop, N.; Neyfakh, A.A.; Brennan, R.G.

2009-05-22

BmrR is a member of the MerR family and a multidrug binding transcription factor that up-regulates the expression of the bmr multidrug efflux transporter gene in response to myriad lipophilic cationic compounds. The structural mechanism by which BmrR binds these chemically and structurally different drugs and subsequently activates transcription is poorly understood. Here, we describe the crystal structures of BmrR bound to rhodamine 6G (R6G) or berberine (Ber) and cognate DNA. These structures reveal each drug stacks against multiple aromatic residues with their positive charges most proximal to the carboxylate group of Glu-253 and that, unlike other multidrug binding pockets, that of BmrR is rigid. Substitution of Glu-253 with either alanine (E253A) or glutamine (E253Q) results in unpredictable binding affinities for R6G, Ber, and tetraphenylphosphonium. Moreover, these drug binding studies reveal that the negative charge of Glu-253 is not important for high affinity binding to Ber and tetraphenylphosphonium but plays a more significant, but unpredictable, role in R6G binding. In vitro transcription data show that E253A and E253Q are constitutively active, and structures of the drug-free E253A-DNA and E253Q-DNA complexes support a transcription activation mechanism requiring the expulsion of Tyr-152 from the multidrug binding pocket. In sum, these data delineate the mechanism by which BmrR binds lipophilic, monovalent cationic compounds and suggest the importance of the redundant negative electrostatic nature of this rigid drug binding pocket that can be used to discriminate against molecules that are not substrates of the Bmr multidrug efflux pump.

Unexpected Far-Ultraviolet Photometric Characteristics On Mimas

Science.gov (United States)

Royer, E. M.; Hendrix, A. R.

2013-12-01

While infrared and visible are the most common wavelength domains used to investigate planetary surfaces, ultraviolet (UV) data are significant and useful. Here, we present the first far-UV phase curves of Mimas, thus displaying another piece of the Saturnian System puzzle. Our preliminary results shows that, one more time, Mimas surface properties are far from what we was expected. Namely, we observe a leading hemisphere brighter than the trailing hemisphere at some far-UV wavelengths. We used the far-UV channel of the Cassini/UVIS instrument, ranging from 118 to 190 nm. Disk-integrated phase curves for the leading hemisphere and the trailing hemisphere, at 180nm, have been produced. Data points span from 0.5 to 163.5 degrees in phase angle. Mimas displays a leading hemisphere brighter than its trailing hemisphere, when theory and previous Voyager observations at longer wavelengths attest of a brighter trailing hemisphere due to the impact of the E-ring grains on this face of the satellite. Surprisingly, UVIS data show a very bright opposition effect on Mimas leading hemisphere, greater than what is observed on Tethys or Dione leading hemisphere at the same wavelength of 180 nm. Preliminary results of photometric properties modeling seem to indicate an important contribution of the coherent-backscattering process in the opposition surge. Exogenic processes such as bombardment by energetic electrons and/or E-ring grains are discussed to explain this unexpected surface property of Mimas.

Architecture of the RNA polymerase II-TFIIF complex revealed by cross-linking and mass spectrometry

DEFF Research Database (Denmark)

Chen, Zhuo Angel; Jawhari, Anass; Fischer, Lutz

2010-01-01

Higher-order multi-protein complexes such as RNA polymerase II (Pol II) complexes with transcription initiation factors are often not amenable to X-ray structure determination. Here, we show that protein cross-linking coupled to mass spectrometry (MS) has now sufficiently advanced as a tool to ex...

Severe tracheobronchial compression in a patient with Turner′s syndrome undergoing repair of a complex aorto-subclavian aneurysm: Anesthesia perspectives

Directory of Open Access Journals (Sweden)

Christopher C .C. Hudson

2014-01-01

Full Text Available We present a case of severe tracheobronchial compression from a complex aorto-subclavian aneurysm in a patient with Turner′s syndrome undergoing open surgical repair. Significant airway compression is a challenging situation and requires careful preoperative preparation, maintenance of spontaneous breathing when possible, and consideration of having an alternative source of oxygenation and circulation established prior to induction of general anesthesia. Cardiopulmonary monitoring is essential for safe general anesthesia and diagnosis of unexpected intraoperative events.

76 FR 35719 - Unexpected Urgent Refugee and Migration Needs Related to Libya and C[ocirc]te d'Ivoire

Science.gov (United States)

2011-06-20

... June 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya and C[ocirc]te d'Ivoire... laws of the United States, including section 2(c)(1) of the Migration and Refugee Assistance Act of... amount not to exceed $15 million from the United States Emergency Refugee and Migration Assistance Fund...

Evidence against barium in the mushroom Trogia venenata as a cause of sudden unexpected deaths in Yunnan, China.

Science.gov (United States)

Zhang, Ying; Li, Yanchun; Wu, Gang; Feng, Bang; Yoell, Shanze; Yu, Zefen; Zhang, Keqin; Xu, Jianping

2012-12-01

This study examined barium concentrations in the mushroom Trogia venenata, the leading culprit for sudden unexpected deaths in Yunnan, southwest China. We found that barium concentrations in T. venenata from Yunnan were low and comparable to other foods, inconsistent with barium concentrations in this mushroom as a significant contributor to these deaths.

A comparative study of ancient sedimentary DNA, pollen and macrofossils from permafrost sediments of northern Siberia reveals long-term vegetational stability

DEFF Research Database (Denmark)

Jørgensen, Tina; Haile, James Seymour; Möller, Per

2012-01-01

and the determination of indicator species to describe environmental changes. Combining data from all three proxies reveals an area continually dominated by a mosaic vegetation of tundra-steppe, pioneer and wet-indicator plants. Such vegetational stability is unexpected, given the severe climate changes taking place...... in the Northern Hemisphere during this time, with changes in average annual temperatures of >22 °C. This may explain the abundance of ice-age mammals such as horse and bison in Taymyr Peninsula during the Pleistocene and why it acted as a refugium for the last mainland woolly mammoth. Our finding reveals...... the benefits of combining sedaDNA, pollen and macrofossil for palaeovegetational reconstruction and adds to the increasing evidence suggesting large areas of the Northern Hemisphere remained ecologically stable during the Late Pleistocene....

Wikiwijs: An unexpected journey and the lessons learned towards OER

Directory of Open Access Journals (Sweden)

Robert Schuwer

2014-04-01

Full Text Available The Dutch Ministry of Education, Culture and Science has funded a five years program to encourage the use, creation and sharing of Open Educational Resources (OER by teachers from various types of education. This program is known as Wikiwijs. Ultimo 2013, the program has come to an end. As some of the assumptions at the start of Wikiwijs proved to work out in unexpected ways the lessons learned could fuel the next steps in developing Wikiwijs. Besides, other national initiatives on opening up education may also benefit from the lessons learned reported here. The main conclusion from five years Wikiwijs was that to accomplish mainstreaming OER, the Wikiwijs program should go along with other interventions that are more oriented toward prescriptive policies and regulations. In particular: the Dutch government should be more directive in persuading executive boards and teachers on schools to adopt OER as an important part of educational reform and the acquisition of 21st century skills.

Complex Tectono-Magmatic Interaction along the George V Transform Fault, South-East Indian Ridge, 140°E, and Implications for Mantle Dynamics

Science.gov (United States)

Briais, A.; Ruellan, E.; Ceuleneer, G.; Maia, M.

2017-12-01

The 300 km-offset George V Transform Fault (TF) is the westernmost of the major, right-stepping transform faults that offset the South-East Indian Ridge between 140°E and 155°E. All these TFs have multiple shear zones with intra-transform ridge segments (ITRS), mostly unmapped yet. We present the results of the analysis of geophysical and petrological data collected during the STORM cruise (South Tasmania Ocean Ridge and Mantle). The data cover the western shear zone and part of two ITRSs. They reveal a complex interaction between tectonic processes at the plate boundary and near-axis volcanic activity along and across the transform fault. The western TF shear zone consists of two segments offset by a 50 km-long, 15 km-wide, up to 2000 m-high serpentinite massif. We infer that the massif is a push-up resulting from transpression along the transform, due to the lengthening of the western ITRS, with a mechanism similar to the processes currently uplifting the mylonitic massif along the St. Paul TF in the Equatorial Atlantic (1). The western ITRS is relatively shallow and magmatically robust, which is unexpected in a TF system. The bathymetric and backscatter maps also reveal a series of recent off-axis oblique volcanic ridges. Rocks dredged on one of these ridges consist of picrites (i.e. basalts rich in olivine phenocrysts). These observations suggest that the TF there is not magma starved like many mid-ocean ridge transforms, but is the locus of significant primitive melt supply. Such an unexpected production of high-Mg melt might be related to the presence of a mantle thermal anomaly beneath the easternmost SEIR, and/or to a western flow of mantle across the TF. *STORM cruise scientific party: A. Briais, F. Barrere, C. Boulart, D. Brunelli, G. Ceuleneer, N. Ferreira, B. Hanan, C. Hémond, S. Macleod, M. Maia, A. Maillard, S. Merkuryev, S.H. Park, S. Révillon, E. Ruellan, A. Schohn, S. Watson, and Y.S. Yang. (1) Maia et al. 2016 Nature Geo. doi:10.1038/ngeo2759

Ligand complex structures of l-amino acid oxidase/monooxygenase from Pseudomonas sp. AIU 813 and its conformational change.

Science.gov (United States)

Im, Dohyun; Matsui, Daisuke; Arakawa, Takatoshi; Isobe, Kimiyasu; Asano, Yasuhisa; Fushinobu, Shinya

2018-03-01

l-Amino acid oxidase/monooxygenase from Pseudomonas sp. AIU 813 (l-AAO/MOG) catalyzes both the oxidative deamination and oxidative decarboxylation of the α-group of l-Lys to produce a keto acid and amide, respectively. l-AAO/MOG exhibits limited specificity for l-amino acid substrates with a basic side chain. We previously determined its ligand-free crystal structure and identified a key residue for maintaining the dual activities. Here, we determined the structures of l-AAO/MOG complexed with l-Lys, l-ornithine, and l-Arg and revealed its substrate recognition. Asp238 is located at the ceiling of a long hydrophobic pocket and forms a strong interaction with the terminal, positively charged group of the substrates. A mutational analysis on the D238A mutant indicated that the interaction is critical for substrate binding but not for catalytic control between the oxidase/monooxygenase activities. The catalytic activities of the D238E mutant unexpectedly increased, while the D238F mutant exhibited altered substrate specificity to long hydrophobic substrates. In the ligand-free structure, there are two channels connecting the active site and solvent, and a short region located at the dimer interface is disordered. In the l-Lys complex structure, a loop region is displaced to plug the channels. Moreover, the disordered region in the ligand-free structure forms a short helix in the substrate complex structures and creates the second binding site for the substrate. It is assumed that the amino acid substrate enters the active site of l-AAO/MOG through this route. The atomic coordinates and structure factors (codes 5YB6, 5YB7, and 5YB8) have been deposited in the Protein Data Bank (http://wwpdb.org/). 1.4.3.2 (l-amino acid oxidase), 1.13.12.2 (lysine 2-monooxygenase).

Nanoscale stiffness topography reveals structure and mechanics of the transport barrier in intact nuclear pore complexes

Science.gov (United States)

Bestembayeva, Aizhan; Kramer, Armin; Labokha, Aksana A.; Osmanović, Dino; Liashkovich, Ivan; Orlova, Elena V.; Ford, Ian J.; Charras, Guillaume; Fassati, Ariberto; Hoogenboom, Bart W.

2015-01-01

The nuclear pore complex (NPC) is the gate for transport between the cell nucleus and the cytoplasm. Small molecules cross the NPC by passive diffusion, but molecules larger than ∼5 nm must bind to nuclear transport receptors to overcome a selective barrier within the NPC. Although the structure and shape of the cytoplasmic ring of the NPC are relatively well characterized, the selective barrier is situated deep within the central channel of the NPC and depends critically on unstructured nuclear pore proteins, and is therefore not well understood. Here, we show that stiffness topography with sharp atomic force microscopy tips can generate nanoscale cross-sections of the NPC. The cross-sections reveal two distinct structures, a cytoplasmic ring and a central plug structure, which are consistent with the three-dimensional NPC structure derived from electron microscopy. The central plug persists after reactivation of the transport cycle and resultant cargo release, indicating that the plug is an intrinsic part of the NPC barrier. Added nuclear transport receptors accumulate on the intact transport barrier and lead to a homogenization of the barrier stiffness. The observed nanomechanical properties in the NPC indicate the presence of a cohesive barrier to transport and are quantitatively consistent with the presence of a central condensate of nuclear pore proteins in the NPC channel.

Gene Coexpression Analysis Reveals Complex Metabolism of the Monoterpene Alcohol Linalool in Arabidopsis Flowers[W][OPEN

Science.gov (United States)

Ginglinger, Jean-François; Boachon, Benoit; Höfer, René; Paetz, Christian; Köllner, Tobias G.; Miesch, Laurence; Lugan, Raphael; Baltenweck, Raymonde; Mutterer, Jérôme; Ullmann, Pascaline; Beran, Franziska; Claudel, Patricia; Verstappen, Francel; Fischer, Marc J.C.; Karst, Francis; Bouwmeester, Harro; Miesch, Michel; Schneider, Bernd; Gershenzon, Jonathan; Ehlting, Jürgen; Werck-Reichhart, Danièle

2013-01-01

The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus predicted to be involved in monoterpenoid metabolism. We show that all four selected genes, the two terpene synthases (TPS10 and TPS14) and the two cytochrome P450s (CYP71B31 and CYP76C3), are simultaneously expressed at anthesis, mainly in upper anther filaments and in petals. Upon transient expression in Nicotiana benthamiana, the TPS enzymes colocalize in vesicular structures associated with the plastid surface, whereas the P450 proteins were detected in the endoplasmic reticulum. Whether they were expressed in Saccharomyces cerevisiae or in N. benthamiana, the TPS enzymes formed two different enantiomers of linalool: (−)-(R)-linalool for TPS10 and (+)-(S)-linalool for TPS14. Both P450 enzymes metabolize the two linalool enantiomers to form different but overlapping sets of hydroxylated or epoxidized products. These oxygenated products are not emitted into the floral headspace, but accumulate in floral tissues as further converted or conjugated metabolites. This work reveals complex linalool metabolism in Arabidopsis flowers, the ecological role of which remains to be determined. PMID:24285789

Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron thiosemicarbazone complexes: relevance to iron-chelator-induced methemoglobinemia.

Science.gov (United States)

Basha, Maram T; Rodríguez, Carlos; Richardson, Des R; Martínez, Manuel; Bernhardt, Paul V

2014-03-01

The oxidation of oxyhemoglobin to methemoglobin has been found to be facilitated by low molecular weight iron(III) thiosemicarbazone complexes. This deleterious reaction, which produces hemoglobin protein units unable to bind dioxygen and occurs during the administration of iron chelators such as the well-known 3-aminopyridine-2-pyridinecarbaldehyde thiosemicarbazone (3-AP; Triapine), has been observed in the reaction with Fe(III) complexes of some members of the 3-AP structurally-related thiosemicarbazone ligands derived from di-2-pyridyl ketone (HDpxxT series). We have studied the kinetics of this oxidation reaction in vitro using human hemoglobin and found that the reaction proceeds with two distinct time-resolved steps. These have been associated with sequential oxidation of the two different oxyheme cofactors in the α and β protein chains. Unexpected steric and hydrogen-bonding effects on the Fe(III) complexes appear to be the responsible for the observed differences in the reaction rate across the series of HDpxxT ligand complexes used in this study.

New Limonoids from Hortia oreadica and Unexpected Coumarin from H. superba Using Chromatography over Cleaning Sephadex with Sodium Hypochlorite

Directory of Open Access Journals (Sweden)

Vanessa G.P. Severino

2014-08-01

Full Text Available Previous investigations of H. oreadica reported the presence of a wide spectrum of complex limonoids and dihydrocinnamic acids. Our interest in the Rutaceae motivated a reinvestigation of H. oreadica, H. brasiliana and H. superba searching for other secondary metabolites present in substantial amounts for taxonomic analysis. In a continuation of the investigation of the H. oreadica, three new limonoids have now been isolated 9α-hydroxyhortiolide A, 11β-hydroxyhortiolide C and 1(S*-acetoxy-7(R*-hydroxy-7-deoxoinchangin. All the isolated compounds from the Hortia species reinforce its position in the Rutaceae. With regard to limonoids the genus produces highly specialized compounds, whose structural variations do not occur in any other member of the Rutaceae, thus, it is evident from limonoid data that Hortia takes an isolated position within the family. In addition, H. superba afforded the unexpected coumarin 5-chloro-8-methoxy-psoralen, which may not be a genuine natural product. Solid-state cross-polarisation/magic-angle-spinning 13C nuclear magnetic resonance, X-Ray fluorescence and Field-emission gun scanning electron microscopy experiments show that the Sephadex LH-20 was modified after treatment with NaOCl, suggesting that when xanthotoxin (8-methoxy-psoralen was extracted from cleaning of the gel column, chlorination of the aromatic system occurred.

How Can We Explain Poverty? Case Study of Dee Reveals the Complexities

Science.gov (United States)

Seccombe, Karen

2011-01-01

Many theories have been offered to explain why people are impoverished. This article by Karen Seccombe uses the case study of "Dee," a newly single mother, to explore four of the most common: individualism, social structuralism, the culture of poverty, and fatalism. She concludes that poverty is a highly complex phenomenon, and it is likely that…

In Planta Single-Molecule Pull-Down Reveals Tetrameric Stoichiometry of HD-ZIPIII:LITTLE ZIPPER Complexes.

Science.gov (United States)

Husbands, Aman Y; Aggarwal, Vasudha; Ha, Taekjip; Timmermans, Marja C P

2016-08-01

Deciphering complex biological processes markedly benefits from approaches that directly assess the underlying biomolecular interactions. Most commonly used approaches to monitor protein-protein interactions typically provide nonquantitative readouts that lack statistical power and do not yield information on the heterogeneity or stoichiometry of protein complexes. Single-molecule pull-down (SiMPull) uses single-molecule fluorescence detection to mitigate these disadvantages and can quantitatively interrogate interactions between proteins and other compounds, such as nucleic acids, small molecule ligands, and lipids. Here, we establish SiMPull in plants using the HOMEODOMAIN LEUCINE ZIPPER III (HD-ZIPIII) and LITTLE ZIPPER (ZPR) interaction as proof-of-principle. Colocalization analysis of fluorophore-tagged HD-ZIPIII and ZPR proteins provides strong statistical evidence of complex formation. In addition, we use SiMPull to directly quantify YFP and mCherry maturation probabilities, showing these differ substantially from values obtained in mammalian systems. Leveraging these probabilities, in conjunction with fluorophore photobleaching assays on over 2000 individual complexes, we determined HD-ZIPIII:ZPR stoichiometry. Intriguingly, these complexes appear as heterotetramers, comprising two HD-ZIPIII and two ZPR molecules, rather than heterodimers as described in the current model. This surprising result raises new questions about the regulation of these key developmental factors and is illustrative of the unique contribution SiMPull is poised to make to in planta protein interaction studies. © 2016 American Society of Plant Biologists. All rights reserved.

Event-related potentials reveal early attention bias for negative, unexpected behavior

OpenAIRE

Jerónimo, R.; Volpert, H. I.; Bartholow, B. D.

2017-01-01

WOS:000395098000012 (Nº de Acesso Web of Science) Numerous studies have documented that expectancy-violating (EV) behavior (i.e., behavior that violates existing person impressions) elicits more effortful cognitive processing compared to expectancy-consistent (EC) behavior. Some studies also have shown that this effect is modulated by the valence of behavior, though this finding is inconsistent with some extant models of expectancy processes. The current research investigated whether the v...

Homozygous and compound heterozygous mutations in the FBN1 gene: unexpected findings in molecular diagnosis of Marfan syndrome.

Science.gov (United States)

Arnaud, Pauline; Hanna, Nadine; Aubart, Mélodie; Leheup, Bruno; Dupuis-Girod, Sophie; Naudion, Sophie; Lacombe, Didier; Milleron, Olivier; Odent, Sylvie; Faivre, Laurence; Bal, Laurence; Edouard, Thomas; Collod-Beroud, Gwenaëlle; Langeois, Maud; Spentchian, Myrtille; Gouya, Laurent; Jondeau, Guillaume; Boileau, Catherine

2017-02-01

Marfan syndrome (MFS) is an autosomal-dominant connective tissue disorder usually associated with heterozygous mutations in the gene encoding fibrillin-1 (FBN1). Homozygous and compound heterozygous cases are rare events and have been associated with a clinical severe presentation. Report unexpected findings of homozygosity and compound heterozygosity in the course of molecular diagnosis of heterozygous MFS and compare the findings with published cases. In the context of molecular diagnosis of heterozygous MFS, systematic sequencing of the FBN1 gene was performed in 2500 probands referred nationwide. 1400 probands carried a heterozygous mutation in this gene. Unexpectedly, among them four homozygous cases (0.29%) and five compound heterozygous cases (0.36%) were identified (total: 0.64%). Interestingly, none of these cases carried two premature termination codon mutations in the FBN1 gene. Clinical features for these carriers and their families were gathered and compared. There was a large spectrum of severity of the disease in probands carrying two mutated FBN1 alleles, but none of them presented extremely severe manifestations of MFS in any system compared with carriers of only one mutated FBN1 allele. This observation is not in line with the severe clinical features reported in the literature for four homozygous and three compound heterozygous probands. Homozygotes and compound heterozygotes were unexpectedly identified in the course of molecular diagnosis of MFS. Contrary to previous reports, the presence of two mutated alleles was not associated with severe forms of MFS. Although homozygosity and compound heterozygosity are rarely found in molecular diagnosis, they should not be overlooked, especially among consanguineous families. However, no predictive evaluation of severity should be provided. 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/.

3D complex: a structural classification of protein complexes.

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Emmanuel D Levy

2006-11-01

Full Text Available Most of the proteins in a cell assemble into complexes to carry out their function. It is therefore crucial to understand the physicochemical properties as well as the evolution of interactions between proteins. The Protein Data Bank represents an important source of information for such studies, because more than half of the structures are homo- or heteromeric protein complexes. Here we propose the first hierarchical classification of whole protein complexes of known 3-D structure, based on representing their fundamental structural features as a graph. This classification provides the first overview of all the complexes in the Protein Data Bank and allows nonredundant sets to be derived at different levels of detail. This reveals that between one-half and two-thirds of known structures are multimeric, depending on the level of redundancy accepted. We also analyse the structures in terms of the topological arrangement of their subunits and find that they form a small number of arrangements compared with all theoretically possible ones. This is because most complexes contain four subunits or less, and the large majority are homomeric. In addition, there is a strong tendency for symmetry in complexes, even for heteromeric complexes. Finally, through comparison of Biological Units in the Protein Data Bank with the Protein Quaternary Structure database, we identified many possible errors in quaternary structure assignments. Our classification, available as a database and Web server at http://www.3Dcomplex.org, will be a starting point for future work aimed at understanding the structure and evolution of protein complexes.

Unexpected Reading Dissociation in a Brazilian “nisei” with Crossed Aphasia

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P. Caramelli

1994-01-01

Full Text Available There is an increased interest in reading impairments in the Japanese language, due to its particular writing system which includes two different scripts, Kanji (logograms and Kana (phonograms. Reading dissociations between Kanji and Kana have been described, showing that each system is processed differently by the cerebral hemispheres. We describe the case of a 68 year old Brazilian “nisei” (i.e. born from Japanese parents who had knowledge of both Japanese and Portuguese. He presented an ischemic stroke affecting the right hemisphere and subsequently developed a Broca's aphasia and an unexpected reading dissociation, with an impairment in Kana reading comprehension and a good performance in Kanji and in Portuguese. These findings suggest that the patient's right and left hemispheres have assumed opposite roles not only for oral but also for written language decodification.

SCAR/WAVE: A complex issue.

Science.gov (United States)

Davidson, Andrew J; Insall, Robert H

2013-11-01

The SCAR/WAVE complex drives the actin polymerisation that underlies protrusion of the front of the cell and thus drives migration. However, it is not understood how the activity of SCAR/WAVE is regulated to generate the infinite range of cellular shape changes observed during cell motility. What are the relative roles of the subunits of the SCAR/WAVE complex? What signaling molecules do they interact with? And how does the complex integrate all this information in order to control the temporal and spatial polymerisation of actin during protrusion formation? Unfortunately, the interdependence of SCAR complex members has made genetic dissection hard. In our recent paper,(1) we describe stabilization of the Dictyostelium SCAR complex by a small fragment of Abi. Here we summarize the main findings and discuss how this approach can help reveal the inner workings of this impenetrable complex.

Maintenance of equilibrium point control during an unexpectedly loaded rapid limb movement.

Science.gov (United States)

Simmons, R W; Richardson, C

1984-06-08

Two experiments investigated whether the equilibrium point hypothesis or the mass-spring model of motor control subserves positioning accuracy during spring loaded, rapid, bi-articulated movement. For intact preparations, the equilibrium point hypothesis predicts response accuracy to be determined by a mixture of afferent and efferent information, whereas the mass-spring model predicts positioning to be under a direct control system. Subjects completed a series of load-resisted training trials to a spatial target. The magnitude of a sustained spring load was unexpectedly increased on selected trials. Results indicated positioning accuracy and applied force varied with increases in load, which suggests that the original efferent commands are modified by afferent information during the movement as predicted by the equilibrium point hypothesis.

Amygdala activity can be modulated by unexpected chord functions during music listening.

Science.gov (United States)

Koelsch, Stefan; Fritz, Thomas; Schlaug, Gottfried

2008-12-03

Numerous earlier studies have investigated the cognitive processing of musical syntax with regular and irregular chord sequences. However, irregular sequences may also be perceived as unexpected, and therefore have a different emotional valence than regular sequences. We provide behavioral data showing that irregular chord functions presented in chord sequence paradigms are perceived as less pleasant than regular sequences. A reanalysis of functional MRI data showed increased blood oxygen level-dependent signal changes bilaterally in the amygdala in response to music-syntactically irregular (compared with regular) chord functions. The combined data indicate that music-syntactically irregular events elicit brain activity related to emotional processes, and that, in addition to intensely pleasurable music or highly unpleasant music, single chord functions can also modulate amygdala activity.

Spectral simplicity of apparent complexity. II. Exact complexities and complexity spectra

Science.gov (United States)

Riechers, Paul M.; Crutchfield, James P.

2018-03-01

The meromorphic functional calculus developed in Part I overcomes the nondiagonalizability of linear operators that arises often in the temporal evolution of complex systems and is generic to the metadynamics of predicting their behavior. Using the resulting spectral decomposition, we derive closed-form expressions for correlation functions, finite-length Shannon entropy-rate approximates, asymptotic entropy rate, excess entropy, transient information, transient and asymptotic state uncertainties, and synchronization information of stochastic processes generated by finite-state hidden Markov models. This introduces analytical tractability to investigating information processing in discrete-event stochastic processes, symbolic dynamics, and chaotic dynamical systems. Comparisons reveal mathematical similarities between complexity measures originally thought to capture distinct informational and computational properties. We also introduce a new kind of spectral analysis via coronal spectrograms and the frequency-dependent spectra of past-future mutual information. We analyze a number of examples to illustrate the methods, emphasizing processes with multivariate dependencies beyond pairwise correlation. This includes spectral decomposition calculations for one representative example in full detail.

Managing uncertainty for sustainability of complex projects

DEFF Research Database (Denmark)

Brink, Tove

2017-01-01

Purpose – The purpose of this paper is to reveal how management of uncertainty can enable sustainability of complex projects. Design/methodology/approach – The research was conducted from June 2014 to May 2015 using a qualitative deductive approach among operation and maintenance actors in offshore...... wind farms. The research contains a focus group interview with 11 companies, 20 individual interviews and a seminar presenting preliminary findings with 60 participants. Findings – The findings reveal the need for management of uncertainty through two different paths. First, project management needs...... to join efforts. Research limitations/implications – Further research is needed to reveal the generalisability of the findings in other complex project contexts containing “unknown unknowns”. Practical implications – The research leads to the development of a tool for uncertainty management...

CW EPR parameters reveal cytochrome P450 ligand binding modes.

Science.gov (United States)

Lockart, Molly M; Rodriguez, Carlo A; Atkins, William M; Bowman, Michael K

2018-06-01

Cytochrome P450 (CYP) monoxygenses utilize heme cofactors to catalyze oxidation reactions. They play a critical role in metabolism of many classes of drugs, are an attractive target for drug development, and mediate several prominent drug interactions. Many substrates and inhibitors alter the spin state of the ferric heme by displacing the heme's axial water ligand in the resting enzyme to yield a five-coordinate iron complex, or they replace the axial water to yield a nitrogen-ligated six-coordinate iron complex, which are traditionally assigned by UV-vis spectroscopy. However, crystal structures and recent pulsed electron paramagnetic resonance (EPR) studies find a few cases where molecules hydrogen bond to the axial water. The water-bridged drug-H 2 O-heme has UV-vis spectra similar to nitrogen-ligated, six-coordinate complexes, but are closer to "reverse type I" complexes described in older liteature. Here, pulsed and continuous wave (CW) EPR demonstrate that water-bridged complexes are remarkably common among a range of nitrogenous drugs or drug fragments that bind to CYP3A4 or CYP2C9. Principal component analysis reveals a distinct clustering of CW EPR spectral parameters for water-bridged complexes. CW EPR reveals heterogeneous mixtures of ligated states, including multiple directly-coordinated complexes and water-bridged complexes. These results suggest that water-bridged complexes are under-represented in CYP structural databases and can have energies similar to other ligation modes. The data indicates that water-bridged binding modes can be identified and distinguished from directly-coordinated binding by CW EPR. Copyright © 2018 Elsevier Inc. All rights reserved.

New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background

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Marocchi Alessandro

2008-05-01

Full Text Available Abstract Background Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Results Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31% and from 69.1 to 86.2% (average 76.6% respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%. This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg

New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

Science.gov (United States)

Penco, Silvana; Buscema, Massimo; Patrosso, Maria Cristina; Marocchi, Alessandro; Grossi, Enzo

2008-05-30

Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial

Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.

Science.gov (United States)

Gong, Xin; Qian, Hongwu; Shao, Wei; Li, Jingxian; Wu, Jianping; Liu, Jun-Jie; Li, Wenqi; Wang, Hong-Wei; Espenshade, Peter; Yan, Nieng

2016-11-01

Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive regulators of hypoxic adaptation in fungi. SREBP C-terminus binds to the WD40 domain of SREBP cleavage-activating protein (SCAP), which confers sterol regulation by controlling the ER-to-Golgi transport of the SREBP-SCAP complex and access to the activating proteases in the Golgi. Here, we biochemically and structurally show that the carboxyl terminal domains (CTD) of Sre1 and Scp1, the fission yeast SREBP and SCAP, form a functional 4:4 oligomer and Sre1-CTD forms a dimer of dimers. The crystal structure of Sre1-CTD at 3.5 Å and cryo-EM structure of the complex at 5.4 Å together with in vitro biochemical evidence elucidate three distinct regions in Sre1-CTD required for Scp1 binding, Sre1-CTD dimerization and tetrameric formation. Finally, these structurally identified domains are validated in a cellular context, demonstrating that the proper 4:4 oligomeric complex formation is required for Sre1 activation.

Phylogenetic diversity and genotypical complexity of H9N2 influenza A viruses revealed by genomic sequence analysis.

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Guoying Dong

Full Text Available H9N2 influenza A viruses have become established worldwide in terrestrial poultry and wild birds, and are occasionally transmitted to mammals including humans and pigs. To comprehensively elucidate the genetic and evolutionary characteristics of H9N2 influenza viruses, we performed a large-scale sequence analysis of 571 viral genomes from the NCBI Influenza Virus Resource Database, representing the spectrum of H9N2 influenza viruses isolated from 1966 to 2009. Our study provides a panoramic framework for better understanding the genesis and evolution of H9N2 influenza viruses, and for describing the history of H9N2 viruses circulating in diverse hosts. Panorama phylogenetic analysis of the eight viral gene segments revealed the complexity and diversity of H9N2 influenza viruses. The 571 H9N2 viral genomes were classified into 74 separate lineages, which had marked host and geographical differences in phylogeny. Panorama genotypical analysis also revealed that H9N2 viruses include at least 98 genotypes, which were further divided according to their HA lineages into seven series (A-G. Phylogenetic analysis of the internal genes showed that H9N2 viruses are closely related to H3, H4, H5, H7, H10, and H14 subtype influenza viruses. Our results indicate that H9N2 viruses have undergone extensive reassortments to generate multiple reassortants and genotypes, suggesting that the continued circulation of multiple genotypical H9N2 viruses throughout the world in diverse hosts has the potential to cause future influenza outbreaks in poultry and epidemics in humans. We propose a nomenclature system for identifying and unifying all lineages and genotypes of H9N2 influenza viruses in order to facilitate international communication on the evolution, ecology and epidemiology of H9N2 influenza viruses.

Crystal structure of the conserved herpesvirus fusion regulator complex gH—gL

Energy Technology Data Exchange (ETDEWEB)

Chowdary, Tirumala K.; Cairns, Tina M.; Atanasiu, Doina; Cohen, Gary H.; Eisenberg, Roselyn J.; Heldwein, Ekaterina E. [UPENN; (Tufts-MED)

2015-02-09

Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH–gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH–gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH–gL activates gB for fusion, possibly through direct binding. Formation of a gB–gH–gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB–gH–gL interface a promising antiviral target.

Comparative transcriptome analysis within the Lolium/Festuca species complex reveals high sequence conservation

DEFF Research Database (Denmark)

Czaban, Adrian; Sharma, Sapna; Byrne, Stephen

2015-01-01

species from the Lolium-Festuca complex, ranging from 52,166 to 72,133 transcripts per assembly. We have also predicted a set of proteins and validated it with a high-confidence protein database from three closely related species (H. vulgare, B. distachyon and O. sativa). We have obtained gene family...... clusters for the four species using OrthoMCL and analyzed their inferred phylogenetic relationships. Our results indicate that VRN2 is a candidate gene for differentiating vernalization and non-vernalization types in the Lolium-Festuca complex. Grouping of the gene families based on their BLAST identity...... enabled us to divide ortholog groups into those that are very conserved and those that are more evolutionarily relaxed. The ratio of the non-synonumous to synonymous substitutions enabled us to pinpoint protein sequences evolving in response to positive selection. These proteins may explain some...

Molecular Epidemiology Reveals Genetic Diversity amongst Isolates of the Cryptococcus neoformans/C. gattii Species Complex in Thailand

Science.gov (United States)

Kaocharoen, Sirada; Ngamskulrungroj, Popchai; Firacative, Carolina; Trilles, Luciana; Piyabongkarn, Dumrongdej; Banlunara, Wijit; Poonwan, Natteewan; Chaiprasert, Angkana; Meyer, Wieland; Chindamporn, Ariya

2013-01-01

To gain a more detailed picture of cryptococcosis in Thailand, a retrospective study of 498 C. neoformans and C. gattii isolates has been conducted. Among these, 386, 83 and 29 strains were from clinical, environmental and veterinary sources, respectively. A total of 485 C. neoformans and 13 C. gattii strains were studied. The majority of the strains (68.9%) were isolated from males (mean age of 37.97 years), 88.5% of C. neoformans and only 37.5% of C. gattii strains were from HIV patients. URA5-RFLP and/or M13 PCR-fingerprinting analysis revealed that the majority of the isolates were C. neoformans molecular type VNI regardless of their sources (94.8%; 94.6% of the clinical, 98.8% of the environmental and 86.2% of the veterinary isolates). In addition, the molecular types VNII (2.4%; 66.7% of the clinical and 33.3% of the veterinary isolates), VNIV (0.2%; 100% environmental isolate), VGI (0.2%; 100% clinical isolate) and VGII (2.4%; 100% clinical isolates) were found less frequently. Multilocus Sequence Type (MLST) analysis using the ISHAM consensus MLST scheme for the C. neoformans/C. gattii species complex identified a total of 20 sequence types (ST) in Thailand combining current and previous data. The Thai isolates are an integrated part of the global cryptococcal population genetic structure, with ST30 for C. gattii and ST82, ST83, ST137, ST141, ST172 and ST173 for C. neoformans being unique to Thailand. Most of the C. gattii isolates were ST7 = VGIIb, which is identical to the less virulent minor Vancouver island outbreak genotype, indicating Thailand as a stepping stone in the global spread of this outbreak strain. The current study revealed a greater genetic diversity and a wider range of major molecular types being present amongst Thai cryptococcal isolates than previously reported. PMID:23861989

Unexpected Molecular Sieving Properties of Zeolitic Imidazolate Framework-8

KAUST Repository

Zhang, Chen; Lively, Ryan P.; Zhang, Ke; Johnson, Justin R.; Karvan, Oguz; Koros, William J.

2012-01-01

We studied molecular sieving properties of zeolitic imidazolate framework-8 (ZIF-8) by estimating the thermodynamically corrected diffusivities of probe molecules at 35 °C. From helium (2.6 Å) to iso-C 4H 10 (5.0 Å), the corrected diffusivity drops 14 orders of magnitude. Our results further suggest that the effective aperture size of ZIF-8 for molecular sieving is in the range of 4.0 to 4.2 Å, which is significantly larger than the XRD-derived value (3.4 Å) and between the well-known aperture size of zeolite 4A (3.8 Å) and 5A (4.3 Å). Interestingly, because of aperture flexibility, the studied C 4 hydrocarbon molecules that are larger than this effective aperture size still adsorb in the micropores of ZIF-8 with kinetic selectivities for iso-C 4H 8/iso-C 4H 10 of 180 and n-C 4H 10/iso-C 4H 10 of 2.5 × 10 6. These unexpected molecular sieving properties open up new opportunities for ZIF materials for separations that cannot be economically achieved by traditional microporous adsorbents such as synthetic zeolites. © 2012 American Chemical Society.

Unexpected Molecular Sieving Properties of Zeolitic Imidazolate Framework-8

KAUST Repository

Zhang, Chen

2012-08-16

We studied molecular sieving properties of zeolitic imidazolate framework-8 (ZIF-8) by estimating the thermodynamically corrected diffusivities of probe molecules at 35 °C. From helium (2.6 Å) to iso-C 4H 10 (5.0 Å), the corrected diffusivity drops 14 orders of magnitude. Our results further suggest that the effective aperture size of ZIF-8 for molecular sieving is in the range of 4.0 to 4.2 Å, which is significantly larger than the XRD-derived value (3.4 Å) and between the well-known aperture size of zeolite 4A (3.8 Å) and 5A (4.3 Å). Interestingly, because of aperture flexibility, the studied C 4 hydrocarbon molecules that are larger than this effective aperture size still adsorb in the micropores of ZIF-8 with kinetic selectivities for iso-C 4H 8/iso-C 4H 10 of 180 and n-C 4H 10/iso-C 4H 10 of 2.5 × 10 6. These unexpected molecular sieving properties open up new opportunities for ZIF materials for separations that cannot be economically achieved by traditional microporous adsorbents such as synthetic zeolites. © 2012 American Chemical Society.

Unexpected high-energy γ emission from decaying exotic nuclei

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A. Gottardo

2017-09-01

Full Text Available The N=52 Ga83 β decay was studied at ALTO. The radioactive 83Ga beam was produced through the ISOL photofission technique and collected on a movable tape for the measurement of γ-ray emission following β decay. While β-delayed neutron emission has been measured to be 56–85% of the decay path, in this experiment an unexpected high-energy 5–9 MeV γ-ray yield of 16(4% was observed, coming from states several MeVs above the neutron separation threshold. This result is compared with cutting-edge QRPA calculations, which show that when neutrons deeply bound in the core of the nucleus decay into protons via a Gamow–Teller transition, they give rise to a dipolar oscillation of nuclear matter in the nucleus. This leads to large electromagnetic transition probabilities which can compete with neutron emission, thus affecting the β-decay path. This process is enhanced by an excess of neutrons on the nuclear surface and may thus be a common feature for very neutron-rich isotopes, challenging the present understanding of decay properties of exotic nuclei.

Simulating Complex, Cold-region Process Interactions Using a Multi-scale, Variable-complexity Hydrological Model

Science.gov (United States)

Marsh, C.; Pomeroy, J. W.; Wheater, H. S.

2017-12-01

Accurate management of water resources is necessary for social, economic, and environmental sustainability worldwide. In locations with seasonal snowcovers, the accurate prediction of these water resources is further complicated due to frozen soils, solid-phase precipitation, blowing snow transport, and snowcover-vegetation-atmosphere interactions. Complex process interactions and feedbacks are a key feature of hydrological systems and may result in emergent phenomena, i.e., the arising of novel and unexpected properties within a complex system. One example is the feedback associated with blowing snow redistribution, which can lead to drifts that cause locally-increased soil moisture, thus increasing plant growth that in turn subsequently impacts snow redistribution, creating larger drifts. Attempting to simulate these emergent behaviours is a significant challenge, however, and there is concern that process conceptualizations within current models are too incomplete to represent the needed interactions. An improved understanding of the role of emergence in hydrological systems often requires high resolution distributed numerical hydrological models that incorporate the relevant process dynamics. The Canadian Hydrological Model (CHM) provides a novel tool for examining cold region hydrological systems. Key features include efficient terrain representation, allowing simulations at various spatial scales, reduced computational overhead, and a modular process representation allowing for an alternative-hypothesis framework. Using both physics-based and conceptual process representations sourced from long term process studies and the current cold regions literature allows for comparison of process representations and importantly, their ability to produce emergent behaviours. Examining the system in a holistic, process-based manner can hopefully derive important insights and aid in development of improved process representations.

Musical rhythm and pitch: A differential effect on auditory dynamics as revealed by the N1/MMN/P3a complex.

Science.gov (United States)

Lelo-de-Larrea-Mancera, E Sebastian; Rodríguez-Agudelo, Yaneth; Solís-Vivanco, Rodolfo

2017-06-01

Music represents a complex form of human cognition. To what extent our auditory system is attuned to music is yet to be clearly understood. Our principal aim was to determine whether the neurophysiological operations underlying pre-attentive auditory change detection (N1 enhancement (N1e)/Mismatch Negativity (MMN)) and the subsequent involuntary attentional reallocation (P3a) towards infrequent sound omissions, are influenced by differences in musical content. Specifically, we intended to explore any interaction effects that rhythmic and pitch dimensions of musical organization may have over these processes. Results showed that both the N1e and MMN amplitudes were differentially influenced by rhythm and pitch dimensions. MMN latencies were shorter for musical structures containing both features. This suggests some neurocognitive independence between pitch and rhythm domains, but also calls for further address on possible interactions between both of them at the level of early, automatic auditory detection. Furthermore, results demonstrate that the N1e reflects basic sensory memory processes. Lastly, we show that the involuntary switch of attention associated with the P3a reflects a general-purpose mechanism not modulated by musical features. Altogether, the N1e/MMN/P3a complex elicited by infrequent sound omissions revealed evidence of musical influence over early stages of auditory perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamic studies of H-Ras•GTPγS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution.

Science.gov (United States)

Vo, Uybach; Vajpai, Navratna; Embrey, Kevin J; Golovanov, Alexander P

2016-07-14

The cycling between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos. The structural/dynamic behavior of the complex formed between activated Sos and Ras at the point of the functional cycle where the nucleotide exchange is completed has not been described to date. Here we show that solution NMR spectra of H-Ras∙GTPγS mixed with a functional fragment of Sos (Sos(Cat)) at a 2:1 ratio are consistent with the formation of a rather dynamic assembly. H-Ras∙GTPγS binding was in fast exchange on the NMR timescale and retained a significant degree of molecular tumbling independent of Sos(Cat), while Sos(Cat) also tumbled largely independently of H-Ras. Estimates of apparent molecular weight from both NMR data and SEC-MALS revealed that, at most, only one H-Ras∙GTPγS molecule appears stably bound to Sos. The weak transient interaction between Sos and the second H-Ras∙GTPγS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP → GTP exchange reaction, but also explains measurable GTP → GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Overall, the data presents the first dynamic snapshot of Ras functional cycle as controlled by Sos.

The diminishing dominance of the dominant hemisphere: Language fMRI in focal epilepsy

Directory of Open Access Journals (Sweden)

Chris Tailby

2017-01-01

Our data highlight the importance of considering language as a complex task where lateralisation varies at the subhemispheric scale. This is especially important for presurgical planning for focal resections where the concept of ‘hemispheric dominance’ may be misleading. This is a precision medicine approach that enables objective evaluation of language dominance within specific brain regions and can reveal surprising and unexpected anomalies that may be clinically important for individual cases.

Harnessing complex emergent metaphors for effective communication in palliative care: a multimodal perceptual analysis of hospice patients' reports of transcendence experiences.

Science.gov (United States)

Arnold, Bruce L; Lloyd, Linda S

2014-05-01

Terminally ill patients can have unexpected, enigmatic, and profound cognitive shifts that significantly alter their perception of themselves, thereby eliminating their fear of death and dying. However, there are no systematic studies into these remarkable yet ineffable transcendence experiences. They therefore remain easily overlooked or viewed as isolated anomalies and therefore excluded from quality-of-life patient considerations. We use a multimodal methodology for identifying the prevalence and thematic properties of complex emergent metaphors patients use to report these experiences. Although previous research has pioneered the importance of understanding conventional or primary metaphors at the end of life, our findings indicate the considerable potential of more complex metaphors for reducing barriers to effective communication in palliative care.

The Capsaspora genome reveals a complex unicellular prehistory of animals.

Science.gov (United States)

Suga, Hiroshi; Chen, Zehua; de Mendoza, Alex; Sebé-Pedrós, Arnau; Brown, Matthew W; Kramer, Eric; Carr, Martin; Kerner, Pierre; Vervoort, Michel; Sánchez-Pons, Núria; Torruella, Guifré; Derelle, Romain; Manning, Gerard; Lang, B Franz; Russ, Carsten; Haas, Brian J; Roger, Andrew J; Nusbaum, Chad; Ruiz-Trillo, Iñaki

2013-01-01

To reconstruct the evolutionary origin of multicellular animals from their unicellular ancestors, the genome sequences of diverse unicellular relatives are essential. However, only the genome of the choanoflagellate Monosiga brevicollis has been reported to date. Here we completely sequence the genome of the filasterean Capsaspora owczarzaki, the closest known unicellular relative of metazoans besides choanoflagellates. Analyses of this genome alter our understanding of the molecular complexity of metazoans' unicellular ancestors showing that they had a richer repertoire of proteins involved in cell adhesion and transcriptional regulation than previously inferred only with the choanoflagellate genome. Some of these proteins were secondarily lost in choanoflagellates. In contrast, most intercellular signalling systems controlling development evolved later concomitant with the emergence of the first metazoans. We propose that the acquisition of these metazoan-specific developmental systems and the co-option of pre-existing genes drove the evolutionary transition from unicellular protists to metazoans.