Computed tomography angiography reveals the crime instrument – case report

PubMed Central

Banaszek, Anna; Guziński, Maciej; Sąsiadek, Marek

2010-01-01

Summary Background: The development of multislice CT technology enabled imaging of post-traumatic brain lesions with isotropic resolution, which led to unexpected results in the presented case Case Report: An unconscious, 49-year-old male with a suspected trauma underwent a routine CT examination of the head, which revealed an unusual intracerebral bleeding and therefore was followed by CT angiography (CTA). The thorough analysis of CTA source scans led to the detection of the bleeding cause. Conclusions: The presented case showed that a careful analysis of a CT scan allows not only to define the extent of pathological lesions in the intracranial space but it also helps to detect the crime instrument, which is of medico-legal significance. PMID:22802784

Dynamical analysis of Jovian polar observations by Juno

NASA Astrophysics Data System (ADS)

Tabataba-Vakili, Fachreddin; Orton, Glenn S.; Adriani, Alberto; Eichstaedt, Gerald; Grassi, Davide; Ingersoll, Andrew P.; Li, Cheng; Hansen, Candice; Momary, Thomas W.; Moriconi, Maria Luisa; Mura, Alessandro; Read, Peter L.; Rogers, John; Young, Roland M. B.

2017-10-01

The JunoCAM and JIRAM instruments onboard the Juno spacecraft have generated unparalleled observations of the Jovian polar regions. These observations reveal a turbulent environment with an unexpected structure of cyclonic polar vortices. We measure the wind velocity in the polar region using correlation image velocimetry of consecutive images. From this data, we calculate the kinetic energy fluxes between different length scales. An analysis of the kinetic energy spectra and eddy-zonal flow interactions may improve our understanding of the mechanisms maintaining the polar macroturbulence in the Jovian atmosphere.

Soft J-tipped guide wire-induced cardiac perforation in a patient with right ventricular lipomatosis and wall thinning.

PubMed

Hiroshima, Yuki; Tajima, Katsushi; Shiono, Yousuke; Suzuki, Ikuko; Kohno, Kei; Kato, Yuichi; Shunji, Kawamura; Kato, Takeo

2012-01-01

Cardiac tamponade caused by perforation is a rare but potentially lethal complication of central venous catheter (CVC) insertion. We herein report a case of cardiac perforation associated with the use of a soft J-tipped guide wire. Twenty minutes after the insertion of a CVC, the patient developed unexpected cardiac arrest. An autopsy revealed 400 mL of pericardial blood. The right ventricular wall was 1 mm thick with about 10 myocyte layers, which is one-third that of the normal heart. A histological analysis revealed widespread fatty infiltration of the right ventricular wall (right ventricular lipomatosis).

Should I stay or should I go? Attentional disengagement from visually unique and unexpected items at fixation.

PubMed

Brockmole, James R; Boot, Walter R

2009-06-01

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. Critically, the foveated item changed to an unexpected color (it was novel), became a color singleton (it was unique), or both. Saccade latency revealed the time required to disengage overt attention from this object. Singletons resulted in longer latencies, but only if they were unexpected. Conversely, unexpected items only delayed disengagement if they were singletons. Thus, the time spent overtly attending to an object is determined, at least in part, by task-irrelevant stimulus properties, but this depends on the confluence of expectation and visual salience. (c) 2009 APA, all rights reserved.

Mammalian skin cell biology: at the interface between laboratory and clinic.

PubMed

Watt, Fiona M

2014-11-21

Mammalian skin research represents the convergence of three complementary disciplines: cell biology, mouse genetics, and dermatology. The skin provides a paradigm for current research in cell adhesion, inflammation, and tissue stem cells. Here, I discuss recent insights into the cell biology of skin. Single-cell analysis has revealed that human epidermal stem cells are heterogeneous and differentiate in response to multiple extrinsic signals. Live-cell imaging, optogenetics, and cell ablation experiments show skin cells to be remarkably dynamic. High-throughput, genome-wide approaches have yielded unprecedented insights into the circuitry that controls epidermal stem cell fate. Last, integrative biological analysis of human skin disorders has revealed unexpected functions for elements of the skin that were previously considered purely structural. Copyright © 2014, American Association for the Advancement of Science.

Self-assembly of Zn(salphen) complexes: steric regulation, stability studies and crystallographic analysis revealing an unexpected dimeric 3,3'-t-Bu-substituted Zn(salphen) complex.

PubMed

Martínez Belmonte, Marta; Wezenberg, Sander J; Haak, Robert M; Anselmo, Daniele; Escudero-Adán, Eduardo C; Benet-Buchholz, Jordi; Kleij, Arjan W

2010-05-21

The self-assembly features of a series of (non)symmetrical Zn(salphen) complexes have been studied in detail by X-ray crystallography, NMR and UV-vis techniques. The combined data demonstrate that the stability of these dimeric assemblies and the relative position of each monomeric unit within the dinuclear structure depend on the location and combination of the aromatic ring substituents.

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

PubMed

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.

Nickel-catalyzed hydrocarboxylation of ynamides with CO2 and H2O: observation of unexpected regioselectivity.

PubMed

Doi, Ryohei; Abdullah, Iman; Taniguchi, Takahisa; Saito, Nozomi; Sato, Yoshihiro

2017-07-06

We describe the nickel-catalyzed hydrocarboxylation of ynamides with CO 2 and H 2 O to afford a variety of α-amino-α,β-unsaturated esters with high regioselectivities. The selective α-carboxylation of ynamides with this catalytic protocol is unexpected in view of the electronic bias of ynamides and is in sharp contrast to our previous study in which a stoichiometric amount of Ni(0) was used to form a β-carboxylated product exclusively. We revealed that this unexpected C-C bond formation was induced by the combination of Zn and MgBr 2 .

Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death.

PubMed

Liu, Sijia; Fu, Chunxiang; Gou, Jiqing; Sun, Liang; Huhman, David; Zhang, Yunwei; Wang, Zeng-Yu

2017-01-01

Switchgrass ( Panicum virgatum ) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O -methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT -deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance.

Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death

PubMed Central

Liu, Sijia; Fu, Chunxiang; Gou, Jiqing; Sun, Liang; Huhman, David; Zhang, Yunwei; Wang, Zeng-Yu

2017-01-01

Switchgrass (Panicum virgatum) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O-methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT-deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance. PMID:28676804

High-throughput sequencing-based analysis of endogenetic fungal communities inhabiting the Chinese Cordyceps reveals unexpectedly high fungal diversity

PubMed Central

Xia, Fei; Chen, Xin; Guo, Meng-Yuan; Bai, Xiao-Hui; Liu, Yan; Shen, Guang-Rong; Li, Yu-Ling; Lin, Juan; Zhou, Xuan-Wei

2016-01-01

Chinese Cordyceps, known in Chinese as “DongChong XiaCao”, is a parasitic complex of a fungus (Ophiocordyceps sinensis) and a caterpillar. The current study explored the endogenetic fungal communities inhabiting Chinese Cordyceps. Samples were collected from five different geographical regions of Qinghai and Tibet, and the nuclear ribosomal internal transcribed spacer-1 sequences from each sample were obtained using Illumina high-throughput sequencing. The results showed that Ascomycota was the dominant fungal phylum in Chinese Cordyceps and its soil microhabitat from different sampling regions. Among the Ascomycota, 65 genera were identified, and the abundant operational taxonomic units showed the strongest sequence similarity to Ophiocordyceps, Verticillium, Pseudallescheria, Candida and Ilyonectria Not surprisingly, the genus Ophiocordyceps was the largest among the fungal communities identified in the fruiting bodies and external mycelial cortices of Chinese Cordyceps. In addition, fungal communities in the soil microhabitats were clustered separately from the external mycelial cortices and fruiting bodies of Chinese Cordyceps from different sampling regions. There was no significant structural difference in the fungal communities between the fruiting bodies and external mycelial cortices of Chinese Cordyceps. This study revealed an unexpectedly high diversity of fungal communities inhabiting the Chinese Cordyceps and its microhabitats. PMID:27625176

Elucidation of the mechanism of homozygous deletion of 3p12-13 in the U2020 cell line reveals the unexpected involvement of other chromosomes.

PubMed

Heppell-Parton, A C; Nacheva, E; Carter, N P; Bergh, J; Ogilvie, D; Rabbitts, P H

1999-06-01

Homozygous deletions in tumor cells have been useful in the localization and validation of tumor suppressor genes. We have described a homozygous deletion in a lung cancer cell line (U2020) which is located within the most proximal of the three regions on the short arm of chromosome 3 believed to be lost in lung cancer development. Construction of a YAC contig map indicates that the deletion spans around 8 Mb, but no large deletion was apparent on conventional cytogenetic analysis of the cell line. To investigate this paradox, whole chromosome, arm-specific, and regional paints have been used. This analysis has revealed that genetic loss has occurred by complex rearrangements of chromosomes 3, rather than simple interstitial deletion. These studies emphasize the power of molecular cytogenetics to disclose unsuspected tumor-specific translocations within the extremely complex karyotypes characteristic of solid tumors.

[Analysis of an ophthalmic pathology cohort of human fetal eyes with regard to interesting findings].

PubMed

Herwig, M C; Müller, A M; Holz, F G; Loeffler, K U

2010-11-01

Information on the evaluation of prenatal ocular findings is sparse. This article provides an overview of the morphology in a cohort of human fetal eyes, with particular emphasis on interesting findings. The study investigated 216 eyes from 115 human fetuses. The majority of fetal eyes presented with a regular phenotype. Rarely, unexpected findings were discovered in fetuses with or without systemic malformations. Routine evaluation of fetal eyes reveals-albeit rarely-new aspects providing further knowledge and occasionally enabling the exact classification of syndromes.

Isolation of a Moderately Stable but Sensitive Zwitterionic Diazonium Tetrazolyl-1,2,3-triazolate.

PubMed

Klapötke, Thomas M; Krumm, Burkhard; Pflüger, Carolin

2016-07-15

An unexpected formation of a diazonium compound was observed by nitration of an amino substituted triazolyl tetrazole with mixed acid. The crystal structure determination revealed a zwitterionic diazonium tetrazolyl-1,2,3-triazolate, whose constitution was supported by NMR and vibrational spectroscopic analysis. The thermal stability and sensitivity toward impact and friction were determined. In contrast, diazotriazoles are rather unstable and are mainly handled in solution and/or low temperatures, which is not the case for this diazonium tetrazolyl-1,2,3-triazolate, being stable at ambient temperature.

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

PubMed

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.

Unexpected Formation of Early Late Heterobimetallic Complexes from Transition Metal Frustrated Lewis Pairs.

PubMed

Chapman, Andy M; Flynn, Stephanie R; Wass, Duncan F

2016-02-01

Reaction of transition metal "frustrated" Lewis pair compounds of the type [Cp2Zr(Me)(OC(CF3)2CH2P(t)Bu2)] with the low valent platinum species [Pt(norbornene)3] leads to the unexpected formation of a heterobimetallic species [Cp2Zr{ Pt(Me)}(OC(CF3)2CH2 P(t)Bu2)]. Single crystal X-ray analysis reveals an unusual T-shaped geometry at the platinum center, with a relevant C-Pt-P angle of 163.3(3)°. Treatment of this compound with PMe3 yields [Pt(PMe3)4] and regenerates the zirconium precursor. Treatment with [(Et2O)2H][B(C6F5)4] protonates off the methyl ligand to give an ether adduct at platinum. Analogous observations are made with titanium-platinum species. We propose the chemistry is best rationalized as a formal insertion of Pt(0) into a Zr-C or Ti-Cl bond.

Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity

PubMed Central

Anastassiadis, Theonie; Deacon, Sean W.; Devarajan, Karthik; Ma, Haiching; Peterson, Jeffrey R.

2011-01-01

Small-molecule protein kinase inhibitors are central tools for elucidating cellular signaling pathways and are promising therapeutic agents. Due to evolutionary conservation of the ATP-binding site, most kinase inhibitors that target this site promiscuously inhibit multiple kinases. Interpretation of experiments utilizing these compounds is confounded by a lack of data on the comprehensive kinase selectivity of most inhibitors. Here we profiled the activity of 178 commercially available kinase inhibitors against a panel of 300 recombinant protein kinases using a functional assay. Quantitative analysis revealed complex and often unexpected kinase-inhibitor interactions, with a wide spectrum of promiscuity. Many off-target interactions occur with seemingly unrelated kinases, revealing how large-scale profiling can be used to identify multi-targeted inhibitors of specific, diverse kinases. The results have significant implications for drug development and provide a resource for selecting compounds to elucidate kinase function and for interpreting the results of experiments that use them. PMID:22037377

Cattle mortality in the Thane district, India: a study of cause/effect relationships.

PubMed

Dogra, R K; Murthy, R C; Srivastava, A K; Gaur, J S; Shukla, L J; Varmani, B M

1996-02-01

An unexpected mortality of more than 300 cattle was investigated near a metal recovery factory located in a rural area of the Thane district of India. The factory was engaged in reclaiming lead, aluminum, tin, and zinc from discarded lead storage batteries and soft drink cans. The environmental samples (soil, leaves, grass, slag, water, and sediment), human blood and hair and animal samples (blood, urine, peritoneal fluid, liver, kidney, cow dung, ribs, and femur), collected for analysis revealed toxic levels of lead, cadmium, and chromium. Clinical examination of factory workers and school children revealed cough, fever, gastric problems, abdominal pain, skin lesions (scabies), and blue line on gums. Histopathological examination of animal tissues revealed chronic pathology with lead inclusion bodies in hepatocytes and renal tubules. Based on environmental, clinical, analytical, and histopathological observations, the mortality has been attributed to toxic levels of metals in the body and the malnourished status of the animals.

Progressive Primary Pulmonary Tuberculosis Presenting as the Sudden Unexpected Death in Infancy: A Case Report

PubMed Central

Dempers, Johan; Sens, Mary Ann; Wadee, Shabbir Ahmed; Kinney, Hannah C.; Odendaal, Hein J.; Wright, Colleen A.

2010-01-01

The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy and death scene investigation to exclude known causes of death. Here we report the death of a four-month-old infant in a tuberculosis endemic area that presented as a sudden unexpected death in infancy (SUDI) with no apparent explanation based on the death scene characteristics. The autopsy, however, revealed progressive primary pulmonary tuberculosis with intrathoracic adenopathy, compression of the tracheobronchial tree and miliary lesions in the liver. This case underscores the clinical difficulties in the diagnosis of infantile tuberculosis, as well as the possibility of sudden death as part of its protean manifestations. The pathology and clinical progression of tuberculosis in infants differs from older children and adults due to the immature immune response in infants. This case dramatically highlights the need for complete autopsies in all sudden and unexpected infant deaths, as well as the public health issues in a sentinel infant tuberculosis diagnosis. PMID:20705406

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

PubMed Central

Elshahed, Mostafa S.; Najar, Fares Z.; Krumholz, Lee R.

2015-01-01

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. PMID:26417542

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

PubMed

Spain, Anne M; Elshahed, Mostafa S; Najar, Fares Z; Krumholz, Lee R

2015-01-01

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.

The role of domain expertise and judgment in dealing with unexpected events

NASA Astrophysics Data System (ADS)

Kochan, Janeen Adrion

Unexpected events, particularly those creating surprise, interrupt ongoing mental and behavioral processes, creating an increased potential for unwanted outcomes to the situation. Human reactions to unexpected events vary. One can hypothesize a number of reasons for this variation, including level of domain expertise, previous experience with similar events, emotional connotation, and the contextual surround of the event. Whereas interrupting ongoing activities and focusing attention temporarily on a surprising event may be a useful evolutionary response to a threatening situation, the same process may be maladaptive in today's highly dynamic world. The purpose of this study was to investigate how different aspects of expertise affected one's ability to detect and react to an unexpected event. It was hypothesized that there were two general types of expertise, domain expertise and judgment (Hammond, 2000), which influenced one's performance on dealing with an unexpected event. The goal of the research was to parse out the relative contribution of domain expertise, so the role of judgment could be revealed. The research questions for this study were: (a) Can we identify specific knowledges and skills which enhance one's ability to deal with unexpected events? (b) Are these skills "automatically" included in domain expertise? (c) How does domain expertise improve or deter one's reaction and response to unexpected events? (d) What role does judgment play in responding to surprise? The general hypothesis was that good judgment would influence the process of surprise at different stages and in different ways than would domain expertise. The conclusions from this research indicated that good judgment had a significant positive effect in helping pilots deal with unexpected events. This was most pronounced when domain expertise was low.

ALMA Long Baseline Observations of the Dynamical Atmospheres of AGB Stars

NASA Astrophysics Data System (ADS)

Vlemmings, Wouter

2018-04-01

I will present the current status of ALMA long baseline observations of W Hya, R Leo, R Dor and Mira. We have recently obtained band 4, 6 and 7 observations of the line and continuum emission tracing the temperature and dynamics in their extended atmosphere. Our preliminary analysis confirms our previous detection of a hotspot on W Hya, and reveals unexpected lines in most of the sources, as well as possible fast rotation in the atmopshere of one of the stars. The observations show the unique power of ALMA in observing the extended stellar atmospheres.

Epilepsy-related sudden unexpected death: targeted molecular analysis of inherited heart disease genes using next-generation DNA sequencing.

PubMed

Hata, Yukiko; Yoshida, Koji; Kinoshita, Koshi; Nishida, Naoki

2017-05-01

Inherited heart disease causing electric instability in the heart has been suggested to be a risk factor for sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to reveal the correlation between epilepsy-related sudden unexpected death (SUD) and inherited heart disease. Twelve epilepsy-related SUD cases (seven males and five females, aged 11-78 years) were examined. Nine cases fulfilled the criteria of SUDEP, and three cases died by drowning. In addition to examining three major epilepsy-related genes, we used next-generation sequencing (NGS) to examine 73 inherited heart disease-related genes. We detected both known pathogenic variants and rare variants with minor allele frequencies of <0.5%. The pathogenicity of these variants was evaluated and graded by eight in silico predictive algorithms. Six known and six potential rare variants were detected. Among these, three known variants of LDB3, DSC2 and KCNE1 and three potential rare variants of MYH6, DSP and DSG2 were predicted by in silico analysis as possibly highly pathogenic in three of the nine SUDEP cases. Two of three cases with desmosome-related variants showed mild but possible significant right ventricular dysplasia-like pathology. A case with LDB3 and MYH6 variants showed hypertrabeculation of the left ventricle and severe fibrosis of the cardiac conduction system. In the three drowning death cases, one case with mild prolonged QT interval had two variants in ANK2. This study shows that inherited heart disease may be a significant risk factor for SUD in some epilepsy cases, even if pathological findings of the heart had not progressed to an advanced stage of the disease. A combination of detailed pathological examination of the heart and gene analysis using NGS may be useful for evaluating arrhythmogenic potential of epilepsy-related SUD. © 2016 International Society of Neuropathology.

Transcriptome map of plant mitochondria reveals islands of unexpected transcribed regions.

PubMed

Fujii, Sota; Toda, Takushi; Kikuchi, Shunsuke; Suzuki, Ryutaro; Yokoyama, Koji; Tsuchida, Hiroko; Yano, Kentaro; Toriyama, Kinya

2011-06-01

Plant mitochondria contain a relatively large amount of genetic information, suggesting that their functional regulation may not be as straightforward as that of metazoans. We used a genomic tiling array to draw a transcriptomic atlas of Oryza sativa japonica (rice) mitochondria, which was predicted to be approximately 490-kb long. Whereas statistical analysis verified the transcription of all previously known functional genes such as the ones related to oxidative phosphorylation, a similar extent of RNA expression was frequently observed in the inter-genic regions where none of the previously annotated genes are located. The newly identified open reading frames (ORFs) predicted in these transcribed inter-genic regions were generally not conserved among flowering plant species, suggesting that these ORFs did not play a role in mitochondrial principal functions. We also identified two partial fragments of retrotransposon sequences as being transcribed in rice mitochondria. The present study indicated the previously unexpected complexity of plant mitochondrial RNA metabolism. Our transcriptomic data (Oryza sativa Mitochondrial rna Expression Server: OsMES) is publicly accessible at [http://bioinf.mind.meiji.ac.jp/cgi-bin/gbrowse/OsMes/#search].

Mechanism of the coupling of diazonium to single-walled carbon nanotubes and its consequences.

PubMed

Schmidt, Grégory; Gallon, Salomé; Esnouf, Stéphane; Bourgoin, Jean-Philippe; Chenevier, Pascale

2009-01-01

On the tube: The coupling of diazonium ions onto single-walled carbon nanotubes is shown to proceed through a radical chain reaction by kinetic analysis of the absorption peak drop (see picture). Radical species are also revealed by ESR. Metallic (m) nanotubes play a special catalytic role in the functionalization of semiconducting (sc) nanotubes.Due to its simplicity and versatility, diazonium coupling is the most widely used method for carbon nanotube (CNT) functionalization to increase CNT processability and add new functionalities. Yet, its mechanism is so far mostly unknown. Herein, we use kinetic analysis to shed light on this complex mechanism. A free-radical chain reaction is revealed by absorption spectroscopy and ESR. Metallic CNTs are shown to play an unexpected catalytic role. The step determining the selectivity towards metallic CNTs is identified by a Hammett correlation. A mechanistic model is proposed that predicts reactivity and selectivity as a function of diazonium electrophilicity and metallic-to-semiconducting CNT ratio, thus opening perspectives of controlled high-yield functionalization and purification.

Unexpected Events Induce Motor Slowing via a Brain Mechanism for Action-Stopping with Global Suppressive Effects

PubMed Central

Aron, Adam R.

2013-01-01

When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression. PMID:24259571

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

PubMed

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.

Metatranscriptome Analysis of Aquifer Samples Reveals Unexpected Metabolic Lifestyles Relevant to Active Biogeochemical Cycling

NASA Astrophysics Data System (ADS)

Beller, H. R.; Jewell, T. N. M.; Karaoz, U.; Banfield, J. F.; Brodie, E.; Williams, K. H.

2015-12-01

Modern molecular ecology techniques are revealing the metabolic potential of uncultivated microorganisms, but there is still much to be learned about the actual biogeochemical roles of microbes that have cultivated relatives. Here, we present metatranscriptomic and metagenomic data from a field study that provides evidence of coupled redox processes that have not been documented in cultivated relatives and, indeed, represent strains with metabolic traits that are novel with respect to closely related isolates. The data come from omics analysis of groundwater samples collected during an experiment in which nitrate (a native electron acceptor) was injected into a perennially suboxic aquifer in Rifle (CO). Transcriptional data indicated that just two groups of chemolithoautotrophic bacteria accounted for a very large portion (~80%) of overall community gene expression: (1) members of the Fe(II)-oxidizing Gallionellaceae family and (2) strains of the S-oxidizing species, Sulfurimonas denitrificans. Metabolic lifestyles for Gallionellaceae strains that were novel compared to cultivated representatives included nitrate-dependent Fe(II) oxidation and S oxidation. Evidence for these metabolisms included highly correlated temporal expression in binned data of nitrate reductase (e.g., narGHI) genes (which have never been reported in Gallionellaceae genomes) and Fe(II) oxidation genes (e.g., mtoA) or S oxidation genes (e.g., dsrE, aprA). Of the two most active strains of S. denitrificans, only one showed strong expression of S oxidation genes, whereas the other was apparently using an unexpected (as-yet unidentified) primary electron donor. Transcriptional data added considerable interpretive value to this study, as (1) metagenomic data would not have highlighted these organisms, which had a disproportionately large role in community metabolism relative to their populations, and (2) co-expression of coupled pathway genes could not be predicted based solely on metagenomic data.

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

PubMed Central

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.

2015-01-01

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. PMID:26501104

New principle of chemotherapy resistance

Cancer.gov

A laboratory study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.

Angular dependence of DRAM upset susceptibility

NASA Technical Reports Server (NTRS)

Guertin, S. M.; Swift, G. M.; Edmonds, L. D.

2000-01-01

Heavy ion irradiations of two types of commercial DRAMs reveal unexpected angular responses. One device's cross section varied by two orders of magnitude with azimuthal angle. Accurate prediction of space rates requires accommodating this effect.

In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

PubMed Central

Grey, Corinne; Clément, Julie A.J.; Buard, Jérôme; Leblanc, Benjamin; Gut, Ivo; Gut, Marta; Duret, Laurent

2017-01-01

In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner. Another subset reveals DSB-independent interactions between PRDM9 and genomic sites, such as the binding sites for the insulator protein CTCF. We propose that these DSB-independent sites result from interactions between hotspot-bound PRDM9 and genomic sequences located on the chromosome axis. PMID:28336543

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

PubMed

Kramer, David A; Eldeeb, Mohamed A; Wuest, Melinda; Mercer, John; Fahlman, Richard P

2017-06-01

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organization and variation analysis of 5S rDNA in gynogenetic offspring of Carassius auratus red var. (♀) × Megalobrama amblycephala (♂).

PubMed

Qin, QinBo; Wang, Juan; Wang, YuDe; Liu, Yun; Liu, ShaoJun

2015-03-13

The offspring with 100 chromosomes (abbreviated as GRCC) have been obtained in the first generation of Carassius auratus red var. (abbreviated as RCC, 2n = 100) (♀) × Megalobrama amblycephala (abbreviated as BSB, 2n = 48) (♂), in which the females and unexpected males both are found. Chromosomal and karyotypic analysis has been reported in GRCC which gynogenesis origin has been suggested, but lack genetic evidence. Fluorescence in situ hybridization with species-specific centromere probes directly proves that GRCC possess two sets of RCC-derived chromosomes. Sequence analysis of the coding region (5S) and adjacent nontranscribed spacer (abbreviated as NTS) reveals that three types of 5S rDNA class (class I; class II and class III) in GRCC are completely inherited from their female parent (RCC), and show obvious base variations and insertions-deletions. Fluorescence in situ hybridization with the entire 5S rDNA probe reveals obvious chromosomal loci (class I and class II) variation in GRCC. This paper provides directly genetic evidence that GRCC is gynogenesis origin. In addition, our result is also reveals that distant hybridization inducing gynogenesis can lead to sequence and partial chromosomal loci of 5S rDNA gene obvious variation.

Analysis of PNGase F-resistant N-glycopeptides using SugarQb for Proteome Discoverer 2.1 reveals cryptic substrate specificities.

PubMed

Stadlmann, Johannes; Hoi, David M; Taubenschmid, Jasmin; Mechtler, Karl; Penninger, Josef M

2018-05-18

SugarQb (www.imba.oeaw.ac.at/sugarqb) is a freely available collection of computational tools for the automated identification of intact glycopeptides from high-resolution HCD MS/MS data-sets in the Proteome Discoverer environment. We report the migration of SugarQb to the latest and free version of Proteome Discoverer 2.1, and apply it to the analysis of PNGase F-resistant N-glycopeptides from mouse embryonic stem cells. The analysis of intact glycopeptides highlights unexpected technical limitations to PNGase F-dependent glycoproteomic workflows at the proteome level, and warrants a critical re-interpretation of seminal data-sets in the context of N-glycosylation-site prediction. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Chiral Drug Analysis in Forensic Chemistry: An Overview.

PubMed

Ribeiro, Cláudia; Santos, Cristiana; Gonçalves, Valter; Ramos, Ana; Afonso, Carlos; Tiritan, Maria Elizabeth

2018-01-28

Many substances of forensic interest are chiral and available either as racemates or pure enantiomers. Application of chiral analysis in biological samples can be useful for the determination of legal or illicit drugs consumption or interpretation of unexpected toxicological effects. Chiral substances can also be found in environmental samples and revealed to be useful for determination of community drug usage (sewage epidemiology), identification of illicit drug manufacturing locations, illegal discharge of sewage and in environmental risk assessment. Thus, the purpose of this paper is to provide an overview of the application of chiral analysis in biological and environmental samples and their relevance in the forensic field. Most frequently analytical methods used to quantify the enantiomers are liquid and gas chromatography using both indirect, with enantiomerically pure derivatizing reagents, and direct methods recurring to chiral stationary phases.

Exploring links between greenspace and sudden unexpected death: a spatial analysis

EPA Science Inventory

Greenspace has been increasingly recognized as having numerous health benefits. However, its effects are unknown concerning sudden unexpected death (SUD), commonly referred to as sudden cardiac death, which constitutes a large proportion of mortality in the United States. Because...

Development of a data independent acquisition mass spectrometry workflow to enable glycopeptide analysis without predefined glycan compositional knowledge.

PubMed

Lin, Chi-Hung; Krisp, Christoph; Packer, Nicolle H; Molloy, Mark P

2018-02-10

Glycoproteomics investigates glycan moieties in a site specific manner to reveal the functional roles of protein glycosylation. Identification of glycopeptides from data-dependent acquisition (DDA) relies on high quality MS/MS spectra of glycopeptide precursors and often requires manual validation to ensure confident assignments. In this study, we investigated pseudo-MRM (MRM-HR) and data-independent acquisition (DIA) as alternative acquisition strategies for glycopeptide analysis. These approaches allow data acquisition over the full MS/MS scan range allowing data re-analysis post-acquisition, without data re-acquisition. The advantage of MRM-HR over DDA for N-glycopeptide detection was demonstrated from targeted analysis of bovine fetuin where all three N-glycosylation sites were detected, which was not the case with DDA. To overcome the duty cycle limitation of MRM-HR acquisition needed for analysis of complex samples such as plasma we trialed DIA. This allowed development of a targeted DIA method to identify N-glycopeptides without pre-defined knowledge of the glycan composition, thus providing the potential to identify N-glycopeptides with unexpected structures. This workflow was demonstrated by detection of 59 N-glycosylation sites from 41 glycoproteins from a HILIC enriched human plasma tryptic digest. 21 glycoforms of IgG1 glycopeptides were identified including two truncated structures that are rarely reported. We developed a data-independent mass spectrometry workflow to identify specific glycopeptides from complex biological mixtures. The novelty is that this approach does not require glycan composition to be pre-defined, thereby allowing glycopeptides carrying unexpected glycans to be identified. This is demonstrated through the analysis of immunoglobulins in human plasma where we detected two IgG1 glycoforms that are rarely observed. Copyright © 2017 Elsevier B.V. All rights reserved.

Virtual Colonoscopy

MedlinePlus

... 75. back to the top of the page Pros Less invasive way to look for polyps Relatively quick Few complications No sedation May unexpectedly reveal treatable problems outside of the colon Cons Moderate to full bowel prep Slight discomfort when ...

Digital Storytelling: Bringing Humanistic Inquiry to Management Studies

ERIC Educational Resources Information Center

Nesteruk, Jeffrey

2015-01-01

This essay recounts how a teaching experiment with digital storytelling unexpectedly revealed how this humanistic genre enabled by contemporary technology might contribute to a more creative integration of business study with the liberal arts.

Anatomy of Brown Dwarf Atmosphere Artist Concept

NASA Image and Video Library

2013-01-08

This artist illustration shows the atmosphere of a brown dwarf called 2MASSJ22282889-431026, which was observed simultaneously by NASA Spitzer and Hubble space telescopes. The results were unexpected, revealing offset layers of material.

Crash test for the Copenhagen problem.

PubMed

Nagler, Jan

2004-06-01

The Copenhagen problem is a simple model in celestial mechanics. It serves to investigate the behavior of a small body under the gravitational influence of two equally heavy primary bodies. We present a partition of orbits into classes of various kinds of regular motion, chaotic motion, escape and crash. Collisions of the small body onto one of the primaries turn out to be unexpectedly frequent, and their probability displays a scale-free dependence on the size of the primaries. The analysis reveals a high degree of complexity so that long term prediction may become a formidable task. Moreover, we link the results to chaotic scattering theory and the theory of leaking Hamiltonian systems.

Novel Functional Properties of Drosophila CNS Glutamate Receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yan; Dharkar, Poorva; Han, Tae-Hee

Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation bymore » its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation.« less

Chemical messages in 170-year-old champagne bottles from the Baltic Sea: Revealing tastes from the past

PubMed Central

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

2015-01-01

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. PMID:25897020

Chemical messages in 170-year-old champagne bottles from the Baltic Sea: Revealing tastes from the past.

PubMed

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.

Novel Functional Properties of Drosophila CNS Glutamate Receptors.

PubMed

Li, Yan; Dharkar, Poorva; Han, Tae-Hee; Serpe, Mihaela; Lee, Chi-Hon; Mayer, Mark L

2016-12-07

Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation by its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation. VIDEO ABSTRACT. Published by Elsevier Inc.

The role of high-frequency oscillatory activity in reward processing and learning.

PubMed

Marco-Pallarés, Josep; Münte, Thomas F; Rodríguez-Fornells, Antoni

2015-02-01

Oscillatory activity has been proposed as a key mechanism in the integration of brain activity of distant structures. Particularly, high frequency brain oscillatory activity in the beta and gamma range has received increasing interest in the domains of attention and memory. In addition, a number of recent studies have revealed an increase of beta-gamma activity (20-35 Hz) after unexpected or relevant positive reward outcomes. In the present manuscript we review the literature on this phenomenon and we propose that this activity is a brain signature elicited by unexpected positive outcomes in order to transmit a fast motivational value signal to the reward network. In addition, we hypothesize that beta-gamma oscillatory activity indexes the interaction between attentional and emotional systems, and that it directly reflects the appearance of unexpected positive rewards in learning-related contexts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Unexpected molecular weight effect in polymer nanocomposites

DOE PAGES

Cheng, Shiwang; Holt, Adam P.; Wang, Huiqun; ...

2016-01-22

Here, the properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp constrast to theoretical predictions. Further analyses reveal amore » reduction in mass density of the interfacial layer with increasing MW, which can explain these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties.« less

Structural imaging biomarkers of sudden unexpected death in epilepsy

PubMed Central

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

2015-01-01

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. PMID:26264515

Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface

PubMed Central

Juranic Lisnic, Vanda; Babic Cac, Marina; Lisnic, Berislav; Trsan, Tihana; Mefferd, Adam; Das Mukhopadhyay, Chitrangada; Cook, Charles H.; Jonjic, Stipan; Trgovcich, Joanne

2013-01-01

Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases. PMID:24086132

A potential target for organophosphate insecticides leading to spermatotoxicity.

PubMed

Suzuki, Himiko; Tomizawa, Motohiro; Ito, Yuki; Abe, Keisuke; Noro, Yuki; Kamijima, Michihiro

2013-10-16

Organophosphate (OP) insecticides as an anticholinesterase also act on the diverse serine hydrolase targets, thereby revealing secondary or unexpected toxic effects including male reproductive toxicity. The present investigation detects a possible target molecule(s) for OP-induced spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) from a chemical standpoint. The activity-based protein profiling (ABPP) approach with a phosphonofluoridate fluorescent probe pinpointed the molecular target for fenitrothion (FNT, a major OP insecticide) oxon (bioactive metabolite of FNT) in the mouse testicular membrane proteome, i.e., FNT oxon phosphorylates the fatty acid amide hydrolase (FAAH), which plays pivotal roles in spermatogenesis and sperm motility acquirement. Subsequently, mice were treated orally with vehicle or FNT for 10 days, and FAAH activity in testis or epididymis cauda was markedly reduced by the subacute exposure. ABPP analysis revealed that FAAH was selectively inhibited among the FNT-treated testicular membrane proteome. Accordingly, FAAH is a potential target for OP-elicited spermatotoxicity.

Efficient use of single molecule time traces to resolve kinetic rates, models and uncertainties

NASA Astrophysics Data System (ADS)

Schmid, Sonja; Hugel, Thorsten

2018-03-01

Single molecule time traces reveal the time evolution of unsynchronized kinetic systems. Especially single molecule Förster resonance energy transfer (smFRET) provides access to enzymatically important time scales, combined with molecular distance resolution and minimal interference with the sample. Yet the kinetic analysis of smFRET time traces is complicated by experimental shortcomings—such as photo-bleaching and noise. Here we recapitulate the fundamental limits of single molecule fluorescence that render the classic, dwell-time based kinetic analysis unsuitable. In contrast, our Single Molecule Analysis of Complex Kinetic Sequences (SMACKS) considers every data point and combines the information of many short traces in one global kinetic rate model. We demonstrate the potential of SMACKS by resolving the small kinetic effects caused by different ionic strengths in the chaperone protein Hsp90. These results show an unexpected interrelation between conformational dynamics and ATPase activity in Hsp90.

A versatile pipeline for the multi-scale digital reconstruction and quantitative analysis of 3D tissue architecture

PubMed Central

Morales-Navarrete, Hernán; Segovia-Miranda, Fabián; Klukowski, Piotr; Meyer, Kirstin; Nonaka, Hidenori; Marsico, Giovanni; Chernykh, Mikhail; Kalaidzidis, Alexander; Zerial, Marino; Kalaidzidis, Yannis

2015-01-01

A prerequisite for the systems biology analysis of tissues is an accurate digital three-dimensional reconstruction of tissue structure based on images of markers covering multiple scales. Here, we designed a flexible pipeline for the multi-scale reconstruction and quantitative morphological analysis of tissue architecture from microscopy images. Our pipeline includes newly developed algorithms that address specific challenges of thick dense tissue reconstruction. Our implementation allows for a flexible workflow, scalable to high-throughput analysis and applicable to various mammalian tissues. We applied it to the analysis of liver tissue and extracted quantitative parameters of sinusoids, bile canaliculi and cell shapes, recognizing different liver cell types with high accuracy. Using our platform, we uncovered an unexpected zonation pattern of hepatocytes with different size, nuclei and DNA content, thus revealing new features of liver tissue organization. The pipeline also proved effective to analyse lung and kidney tissue, demonstrating its generality and robustness. DOI: http://dx.doi.org/10.7554/eLife.11214.001 PMID:26673893

Evidence, Emotion and Eminence: A Qualitative and Evaluative Analysis of Doctors' Skills in Macroallocation.

PubMed

Gallagher, Siun; Little, Miles; Hooker, Claire

2018-03-24

In this analysis of the ethical dimensions of doctors' participation in macroallocation we set out to understand the skills they use, how they are acquired, and how they influence performance of the role. Using the principles of grounded moral analysis, we conducted a semi-structured interview study with Australian doctors engaged in macroallocation. We found that they performed expertise as argument, bringing together phronetic and rhetorical skills founded on communication, strategic thinking, finance, and health data. They had made significant, purposeful efforts to gain skills for the role. Our findings challenge common assumptions about doctors' preferences in argumentation, and reveal an unexpected commitment to practical reason. Using the ethics of Paul Ricoeur in our analysis enabled us to identify the moral meaning of doctors' skills and learning. We concluded that Ricoeur's ethics offers an empirically grounded matrix for ethical analysis of the doctor's role in macroallocation that may help to establish norms for procedure.

Physicians’ Perspectives on the Uncertainties and Implications of Chromosomal Microarray Testing of Children and Families

PubMed Central

Reiff, Marian; Ross, Kathryn; Mulchandani, Surabhi; Propert, Kathleen Joy; Pyeritz, Reed E.; Spinner, Nancy B.; Bernhardt, Barbara A.

2012-01-01

Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This paper explores clinicians’ perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using non-parametric statistical tests. Clinicians’ comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late-onset disease, in a hypothetical case. Many non-genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings. PMID:22989118

Pirate Stealth or Inattentional Blindness? The Effects of Target Relevance and Sustained Attention on Security Monitoring for Experienced and Naïve Operators

PubMed Central

Näsholm, Erika; Rohlfing, Sarah; Sauer, James D.

2014-01-01

Closed Circuit Television (CCTV) operators are responsible for maintaining security in various applied settings. However, research has largely ignored human factors that may contribute to CCTV operator error. One important source of error is inattentional blindness – the failure to detect unexpected but clearly visible stimuli when attending to a scene. We compared inattentional blindness rates for experienced (84 infantry personnel) and naïve (87 civilians) operators in a CCTV monitoring task. The task-relevance of the unexpected stimulus and the length of the monitoring period were manipulated between participants. Inattentional blindness rates were measured using typical post-event questionnaires, and participants' real-time descriptions of the monitored event. Based on the post-event measure, 66% of the participants failed to detect salient, ongoing stimuli appearing in the spatial field of their attentional focus. The unexpected task-irrelevant stimulus was significantly more likely to go undetected (79%) than the unexpected task-relevant stimulus (55%). Prior task experience did not inoculate operators against inattentional blindness effects. Participants' real-time descriptions revealed similar patterns, ruling out inattentional amnesia accounts. PMID:24465932

High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

PubMed

Czerniecki, Stefan M; Cruz, Nelly M; Harder, Jennifer L; Menon, Rajasree; Annis, James; Otto, Edgar A; Gulieva, Ramila E; Islas, Laura V; Kim, Yong Kyun; Tran, Linh M; Martins, Timothy J; Pippin, Jeffrey W; Fu, Hongxia; Kretzler, Matthias; Shankland, Stuart J; Himmelfarb, Jonathan; Moon, Randall T; Paragas, Neal; Freedman, Benjamin S

2018-05-15

Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening. Copyright © 2018 Elsevier Inc. All rights reserved.

Body-packing as cause of unexpected sudden death.

PubMed

Heinemann, A; Miyaishi, S; Iwersen, S; Schmoldt, A; Püschel, K

1998-03-02

Four fatalities related to smuggling of drugs by body-packing were investigated. The victims were examined at the Institute of Forensic Medicine of Hamburg University between 1983 and 1995, two of them due to "sudden" unknown cause of death. All victims were male. Two of them were found already dead in a backyard and in a hotel, two other were emergency cases and died at a hospital. Smuggled substances included cocaine (two cases), heroin and amphetamine/caffeine. In all cases, the cause of death was intoxication caused by torn packages which were detected at autopsy. The maximum weight of the packet's contents was 630 g divided in 90 packages. Only one victim was apparently an intravenous drug-abuser. Hair analysis was performed in three cases and revealed in one case a difference between a concealed and a habitually consumed drug. Toxicological analysis revealed that the substances were quite pure and provided evidence that rather long survival was possible following intoxication in three cases, in two cases supported by hospital treatment in the final stage. The procedural regimen in cases of suspected body-packing is discussed.

Proteomic Investigation of Aphid Honeydew Reveals an Unexpected Diversity of Proteins

PubMed Central

Haubruge, Eric; Hance, Thierry; Thonart, Philippe; De Pauw, Edwin; Francis, Frédéric

2013-01-01

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. PMID:24086359

Mathematics Placement Test: Typical Results with Unexpected Outcomes

ERIC Educational Resources Information Center

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…

Getting the Words Out: Case Studies in Facilitated Communication Training.

ERIC Educational Resources Information Center

Crossley, Rosemary

1992-01-01

Case studies are presented of three individuals with severe communication impairments who had been judged to be intellectually impaired but revealed unexpected achievements after training in nonspeech communication. The communication training used facilitation to circumvent hand function impairments. (JDD)

Building Community in School.

ERIC Educational Resources Information Center

Schaps, Eric; And Others

1996-01-01

Evaluation studies of the Child Development Project revealed unexpected findings concerning students' sense of classroom community. Teachers should systematically build relationships with students, involve them in planning and problem solving, help them learn classmates' strengths and interests, downplay competition, and involve all children in…

Facial attractiveness, symmetry, and physical fitness in young women.

PubMed

Hönekopp, Johannes; Bartholomé, Tobias; Jansen, Gregor

2004-06-01

This study explores the evolutionary-based hypothesis that facial attractiveness (a guiding force in mate selection) is a cue for physical fitness (presumably an important contributor to mate value in ancestral times). Since fluctuating asymmetry, a measure of developmental stability, is known to be a valid cue for fitness in several biological domains, we scrutinized facial asymmetry as a potential mediator between attractiveness and fitness. In our sample of young women, facial beauty indeed indicated physical fitness. The relationships that pertained to asymmetry were in the expected direction. However, a closer analysis revealed that facial asymmetry did not mediate the relationship between fitness and attractiveness. Unexpected problems regarding the measurement of facial asymmetry are discussed.

Identifying relationships between unrelated pharmaceutical target proteins on the basis of shared active compounds.

PubMed

Miljković, Filip; Kunimoto, Ryo; Bajorath, Jürgen

2017-08-01

Computational exploration of small-molecule-based relationships between target proteins from different families. Target annotations of drugs and other bioactive compounds were systematically analyzed on the basis of high-confidence activity data. A total of 286 novel chemical links were established between distantly related or unrelated target proteins. These relationships involved a total of 1859 bioactive compounds including 147 drugs and 141 targets. Computational analysis of large amounts of compounds and activity data has revealed unexpected relationships between diverse target proteins on the basis of compounds they share. These relationships are relevant for drug discovery efforts. Target pairs that we have identified and associated compound information are made freely available.

The Mediating Role of Perceived Descriptive and Injunctive Norms in the Effects of Media Messages on Youth Smoking.

PubMed

Nan, Xiaoli; Zhao, Xiaoquan

2016-01-01

This research advances and tests a normative mediation model of media effects on youth smoking. The model predicts that exposure to various types of smoking-related media messages, including anti-smoking ads, cigarette ads, and smoking scenes in movies and television shows, exerts indirect effects on youth smoking intentions through the mediation of perceived descriptive and injunctive norms. Analysis of the data from the 3rd Legacy Media Tracking Survey offers general support for the proposed model with some unexpected findings, revealing a complex picture of media influence on youth smoking via normative and non-normative mechanisms. Theoretical and practical implications of the findings are discussed.

The event-related potential effects of cognitive conflict in a Chinese character-generation task.

PubMed

Qiu, Jiang; Zhang, Qinglin; Li, Hong; Luo, Yuejia; Yin, Qinging; Chen, Antao; Yuan, Hong

2007-06-11

High-density event-related potentials were recorded to examine the electrophysiologic correlates of the evaluation of possible answers provided during a Chinese character-generation task. We examined three conditions: the character given was what participants initially generated (Consistent answer), the character given was correct (Unexpected Correct answer), or it was incorrect (Unexpected Incorrect answer). Results showed that Unexpected Correct and Incorrect answers elicited a more negative event-related potential deflection (N320) than did Consistent answers between 300 and 400 ms. Dipole source analysis of difference waves (Unexpected Correct or Incorrect minus Consistent answers) localized the generator of the N320 in the anterior cingulate cortex. The N320 therefore likely reflects the cognitive change or conflict between old and new ways of thinking while identifying and judging characters.

The Wreck of the Pettu as an Example for Nineteenth Century Rural Shipbuilding in South-Western Finland

NASA Astrophysics Data System (ADS)

Auer, Jens; Ditta, Massimiliano

2016-08-01

Although the design and construction of wooden merchant vessels in the nineteenth century is generally considered to be well understood, the excavation and subsequent analysis of the wreck of the wooden Finnish topsail schooner Pettu (1865) revealed a number of unexpected features, which prompted the authors to take a closer look at the ship. In the following study, it will be attempted to gain an insight into the society that produced and used the merchant vessel through a detailed analysis of its construction and an investigation into the concept behind its design. The wreck of the Pettu, which, considering its loss in 1893, is barely covered by the 100 year rule in Danish heritage legislation, is a good example for the archaeological potential of even relatively `modern' wreck sites, adding to their significance.

Visual Prediction Error Spreads Across Object Features in Human Visual Cortex

PubMed Central

Summerfield, Christopher; Egner, Tobias

2016-01-01

Visual cognition is thought to rely heavily on contextual expectations. Accordingly, previous studies have revealed distinct neural signatures for expected versus unexpected stimuli in visual cortex. However, it is presently unknown how the brain combines multiple concurrent stimulus expectations such as those we have for different features of a familiar object. To understand how an unexpected object feature affects the simultaneous processing of other expected feature(s), we combined human fMRI with a task that independently manipulated expectations for color and motion features of moving-dot stimuli. Behavioral data and neural signals from visual cortex were then interrogated to adjudicate between three possible ways in which prediction error (surprise) in the processing of one feature might affect the concurrent processing of another, expected feature: (1) feature processing may be independent; (2) surprise might “spread” from the unexpected to the expected feature, rendering the entire object unexpected; or (3) pairing a surprising feature with an expected feature might promote the inference that the two features are not in fact part of the same object. To formalize these rival hypotheses, we implemented them in a simple computational model of multifeature expectations. Across a range of analyses, behavior and visual neural signals consistently supported a model that assumes a mixing of prediction error signals across features: surprise in one object feature spreads to its other feature(s), thus rendering the entire object unexpected. These results reveal neurocomputational principles of multifeature expectations and indicate that objects are the unit of selection for predictive vision. SIGNIFICANCE STATEMENT We address a key question in predictive visual cognition: how does the brain combine multiple concurrent expectations for different features of a single object such as its color and motion trajectory? By combining a behavioral protocol that independently varies expectation of (and attention to) multiple object features with computational modeling and fMRI, we demonstrate that behavior and fMRI activity patterns in visual cortex are best accounted for by a model in which prediction error in one object feature spreads to other object features. These results demonstrate how predictive vision forms object-level expectations out of multiple independent features. PMID:27810936

Assessing pathogenicity for novel mutation/sequence variants: the value of healthy older individuals.

PubMed

Zatz, Mayana; Pavanello, Rita de Cassia M; Lourenço, Naila Cristina V; Cerqueira, Antonia; Lazar, Monize; Vainzof, Mariz

2012-12-01

Improvement in DNA technology is increasingly revealing unexpected/unknown mutations in healthy persons and generating anxiety due to their still unknown health consequences. We report a 44-year-old healthy father of a 10-year-old daughter with bilateral coloboma and hearing loss, but without muscle weakness, in whom a whole-genome CGH revealed a deletion of exons 38-44 in the dystrophin gene. This mutation was inherited from her asymptomatic father, who was further clinically and molecularly evaluated for prognosis and genetic counseling (GC). This deletion was never identified by us in 982 Duchenne/Becker patients. To assess whether the present case represents a rare case of non-penetrance, and aiming to obtain more information for prognosis and GC, we suggested that healthy older relatives submit their DNA for analysis, to which several complied. Mutation analysis revealed that his mother, brother, and 56-year-old maternal uncle also carry the 38-44 deletion, suggesting it an unlikely cause of muscle weakness. Genome sequencing will disclose mutations and variants whose health impact are still unknown, raising important problems in interpreting results, defining prognosis, and discussing GC. We suggest that, in addition to family history, keeping the DNA of older relatives could be very informative, in particular for those interested in having their genome sequenced.

Noncanoncial signal recognition particle RNAs in a major eukaryotic phylum revealed by purification of SRP from the human pathogen Cryptococcus neoformans

PubMed Central

Dumesic, Phillip A.; Rosenblad, Magnus A.; Samuelsson, Tore; Nguyen, Tiffany; Moresco, James J.; Yates, John R.; Madhani, Hiten D.

2015-01-01

Despite conservation of the signal recognition particle (SRP) from bacteria to man, computational approaches have failed to identify SRP components from genomes of many lower eukaryotes, raising the possibility that they have been lost or altered in those lineages. We report purification and analysis of SRP in the human pathogen Cryptococcus neoformans, providing the first description of SRP in basidiomycetous yeast. The C. neoformans SRP RNA displays a predicted structure in which the universally conserved helix 8 contains an unprecedented stem-loop insertion. Guided by this sequence, we computationally identified 152 SRP RNAs throughout the phylum Basidiomycota. This analysis revealed additional helix 8 alterations including single and double stem-loop insertions as well as loop diminutions affecting RNA structural elements that are otherwise conserved from bacteria to man. Strikingly, these SRP RNA features in Basidiomycota are accompanied by phylum-specific alterations in the RNA-binding domain of Srp54, the SRP protein subunit that directly interacts with helix 8. Our findings reveal unexpected fungal SRP diversity and suggest coevolution of the two most conserved SRP features—SRP RNA helix 8 and Srp54—in basidiomycetes. Because members of this phylum include important human and plant pathogens, these noncanonical features provide new targets for antifungal compound development. PMID:26275773

Using Qualitative Research to Document Variations in Student Experience

ERIC Educational Resources Information Center

Friedensen, Rachel E.; McCrae, Byron P.; Kimball, Ezekiel

2017-01-01

This chapter describes a qualitative study focused on the experiences of students with disabilities within the postsecondary learning environment. Reporting unexpected findings related to athletics, it makes the case that qualitative methods are well-suited for revealing information about minoritized student populations.

The detection of faked identity using unexpected questions and mouse dynamics.

PubMed

Monaro, Merylin; Gamberini, Luciano; Sartori, Giuseppe

2017-01-01

The detection of faked identities is a major problem in security. Current memory-detection techniques cannot be used as they require prior knowledge of the respondent's true identity. Here, we report a novel technique for detecting faked identities based on the use of unexpected questions that may be used to check the respondent identity without any prior autobiographical information. While truth-tellers respond automatically to unexpected questions, liars have to "build" and verify their responses. This lack of automaticity is reflected in the mouse movements used to record the responses as well as in the number of errors. Responses to unexpected questions are compared to responses to expected and control questions (i.e., questions to which a liar also must respond truthfully). Parameters that encode mouse movement were analyzed using machine learning classifiers and the results indicate that the mouse trajectories and errors on unexpected questions efficiently distinguish liars from truth-tellers. Furthermore, we showed that liars may be identified also when they are responding truthfully. Unexpected questions combined with the analysis of mouse movement may efficiently spot participants with faked identities without the need for any prior information on the examinee.

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

PubMed

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.

Genealogy of wine grape cultivars: "Pinot" is related to "Syrah".

PubMed

Vouillamoz, J F; Grando, M S

2006-08-01

Since the domestication of wild grapes ca 6000 years ago, numerous cultivars have been generated by spontaneous or deliberate crosses, and up to 10 000 are still in existence today. Just as in human paternity analysis, DNA typing can reveal unexpected parentage of grape cultivars. In this study, we have analysed 89 grape cultivars with 60 microsatellite markers in order to accurately calculate the identity-by-descent (IBD) and relatedness (r) coefficients among six putatively related cultivars from France ("Pinot", "Syrah" and "Dureza") and northern Italy ("Teroldego", "Lagrein" and "Marzemino"). Using a recently developed likelihood-based approach to analyse kinship in grapes, we provide the first evidence of a genetic link between grapes across the Alps: "Dureza" and "Teroldego" turn out to be full-siblings (FS). For the first time in grapevine genetics we were able to detect FS without knowing one of the parents and identify unexpected second-degree relatives. We reconstructed the most likely pedigree that revealed a third-degree relationship between the worldwide-cultivated "Pinot" from Burgundy and "Syrah" from the Rhone Valley. Our finding was totally unsuspected by classical ampelography and it challenges the commonly assumed independent origins of these grape cultivars. Our results and this new approach in grape genetics will (a) help grape breeders to avoid choosing closely related varieties for new crosses, (b) provide pedigrees of cultivars in order to detect inheritance of disease-resistance genes and (c) open the way for future discoveries of first- and second-degree relationships between grape cultivars in order to better understand viticultural migrations.

Phylogenomic analysis of Copepoda (Arthropoda, Crustacea) reveals unexpected similarities with earlier proposed morphological phylogenies.

PubMed

Eyun, Seong-Il

2017-01-19

Copepods play a critical role in marine ecosystems but have been poorly investigated in phylogenetic studies. Morphological evidence supports the monophyly of copepods, whereas interordinal relationships continue to be debated. In particular, the phylogenetic position of the order Harpacticoida is still ambiguous and inconsistent among studies. Until now, a small number of molecular studies have been done using only a limited number or even partial genes and thus there is so far no consensus at the order-level. This study attempted to resolve phylogenetic relationships among and within four major copepod orders including Harpacticoida and the phylogenetic position of Copepoda among five other crustacean groups (Anostraca, Cladocera, Sessilia, Amphipoda, and Decapoda) using 24 nuclear protein-coding genes. Phylogenomics has confirmed the monophyly of Copepoda and Podoplea. However, this study reveals surprising differences with the majority of the copepod phylogenies and unexpected similarities with postembryonic characters and earlier proposed morphological phylogenies; More precisely, Cyclopoida is more closely related to Siphonostomatoida than to Harpacticoida which is likely the most basally-branching group of Podoplea. Divergence time estimation suggests that the origin of Harpacticoida can be traced back to the Devonian, corresponding well with recently discovered fossil evidence. Copepoda has a close affinity to the clade of Malacostraca and Thecostraca but not to Branchiopoda. This result supports the hypothesis of the newly proposed clades, Communostraca, Multicrustacea, and Allotriocarida but further challenges the validity of Hexanauplia and Vericrustacea. The first phylogenomic study of Copepoda provides new insights into taxonomic relationships and represents a valuable resource that improves our understanding of copepod evolution and their wide range of ecological adaptations.

Overcoming confounded controls in the analysis of gene expression data from microarray experiments.

PubMed

Bhattacharya, Soumyaroop; Long, Dang; Lyons-Weiler, James

2003-01-01

A potential limitation of data from microarray experiments exists when improper control samples are used. In cancer research, comparisons of tumour expression profiles to those from normal samples is challenging due to tissue heterogeneity (mixed cell populations). A specific example exists in a published colon cancer dataset, in which tissue heterogeneity was reported among the normal samples. In this paper, we show how to overcome or avoid the problem of using normal samples that do not derive from the same tissue of origin as the tumour. We advocate an exploratory unsupervised bootstrap analysis that can reveal unexpected and undesired, but strongly supported, clusters of samples that reflect tissue differences instead of tumour versus normal differences. All of the algorithms used in the analysis, including the maximum difference subset algorithm, unsupervised bootstrap analysis, pooled variance t-test for finding differentially expressed genes and the jackknife to reduce false positives, are incorporated into our online Gene Expression Data Analyzer ( http:// bioinformatics.upmc.edu/GE2/GEDA.html ).

Striatal and midbrain connectivity with the hippocampus selectively boosts memory for contextual novelty

PubMed Central

Kafkas, Alexandros; Montaldi, Daniela

2015-01-01

The role of contextual expectation in processing familiar and novel stimuli was investigated in a series of experiments combining eye tracking, functional magnetic resonance imaging, and behavioral methods. An experimental paradigm emphasizing either familiarity or novelty detection at retrieval was used. The detection of unexpected familiar and novel stimuli, which were characterized by lower probability, engaged activity in midbrain and striatal structures. Specifically, detecting unexpected novel stimuli, relative to expected novel stimuli, produced greater activity in the substantia nigra/ventral tegmental area (SN/VTA), whereas the detection of unexpected familiar, relative to expected, familiar stimuli, elicited activity in the striatum/globus pallidus (GP). An effective connectivity analysis showed greater functional coupling between these two seed areas (GP and SN/VTA) and the hippocampus, for unexpected than for expected stimuli. Within this network of midbrain/striatal–hippocampal interactions two pathways are apparent; the direct SN–hippocampal pathway sensitive to unexpected novelty and the perirhinal–GP–hippocampal pathway sensitive to unexpected familiarity. In addition, increased eye fixations and pupil dilations also accompanied the detection of unexpected relative to expected familiar and novel stimuli, reflecting autonomic activity triggered by the functioning of these two pathways. Finally, subsequent memory for unexpected, relative to expected, familiar, and novel stimuli was characterized by enhanced recollection, but not familiarity, accuracy. Taken together, these findings suggest that a hippocampal–midbrain network, characterized by two distinct pathways, mediates encoding facilitation and most critically, that this facilitation is driven by contextual novelty, rather than by the absolute novelty of a stimulus. This contextually sensitive neural mechanism appears to elicit increased exploratory behavior, leading subsequently to greater recollection of the unexpected stimulus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25708843

Confronting the unexpected: temporal, situational, and attributive dimensions of distressing symptom experience for breast cancer survivors.

PubMed

Rosedale, Mary; Fu, Mei R

2010-01-01

To describe women's unexpected and distressing symptom experiences after breast cancer treatment. Qualitative and descriptive. Depending upon their preference, participants were interviewed in their homes or in a private office space in a nearby library. Purposive sample of 13 women 1-18 years after breast cancer treatment. Secondary analysis of phenomenologic data (constant comparative method). Breast cancer symptom distress, ongoing symptoms, and unexpected experiences. Women described experiences of unexpected and distressing symptoms in the years following breast cancer treatment. Symptoms included pain, loss of energy, impaired limb movement, cognitive disturbance, changed sexual experience, and lymphedema. Four central themes were derived: living with lingering symptoms, confronting unexpected situations, losing precancer being, and feeling like a has-been. Distress intensified when women expected symptoms to disappear but symptoms persisted instead. Increased distress also was associated with sudden and unexpected situations or when symptoms elicited feelings of loss about precancer being and feelings of being a has been. Findings suggest that symptom distress has temporal, situational, and attributive dimensions. Breast cancer survivors' perceptions of ongoing and unexpected symptoms have important influences on quality of life. Understanding temporal, situational, and attributive dimensions of symptom distress empowers nurses and healthcare professionals to help breast cancer survivors prepare for subsequent ongoing or unexpected experiences in the years after breast cancer treatment. Follow-up care for breast cancer survivors should foster dialogue about ways that symptoms might emerge and that unexpected situations might occur. Prospective studies are needed to examine symptom distress in terms of temporal, situational, and attributive dimensions and explore the relationship between symptom distress and psychological distress after breast cancer treatment.

Multiple effects of sentential constraint on word processing

PubMed Central

Federmeier, Kara D.; Wlotko, Edward W.; De Ochoa-Dewald, Esmeralda; Kutas, Marta

2009-01-01

Behavioral and electrophysiological studies have uncovered different patterns of constraint effects on the processing of words in sentences. Whereas response time measures have indicated a reduced scope of facilitation from strongly constraining contexts, event-related brain potential (ERP) measures have instead revealed enhanced facilitation for semantically related endings in such sentences. Given this disparity, and the concomitant possibility of functionally separable stages of context effects, the current study jointly examined expectancy (cloze probability) and constraint effects on the ERP response to words. Expected and unexpected (but plausible) words completed strongly and weakly constraining sentences; unexpected items were matched for contextual fit across the two levels of constraint and were semantically unrelated to the most expected endings. N400 amplitudes were graded by expectancy but unaffected by constraint and seemed to index the benefit of contextual information. However, a later effect, in the form of increased frontal positivity from 500 to 900 ms post-stimulus-onset, indicated a possible cost associated with the processing of unexpected words in strongly constraining contexts. PMID:16901469

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

PubMed Central

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

The Classical Vacuum.

ERIC Educational Resources Information Center

Boyer, Timothy H.

1985-01-01

The classical vacuum of physics is not empty, but contains a distinctive pattern of electromagnetic fields. Discovery of the vacuum, thermal spectrum, classical electron theory, zero-point spectrum, and effects of acceleration are discussed. Connection between thermal radiation and the classical vacuum reveals unexpected unity in the laws of…

Polymorphic haplotypes and recombination rates at the LDL receptor gene locus in subjects with and without familial hypercholesterolemia who are from different populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miserez, A.R.; Chiodetti, N.; Keller, U.

1993-04-01

RFLPs at the low-density lipoprotein (LDL) receptor locus for TaqI, StuI, HincII, AvaII, ApaLI (5[prime] and 3[prime]), PvuII, and NcoI were studied in Swiss and German families with familial hypercholesterolemia (FH). A total of 1,104 LDL receptor alleles were analyzed using Southern blotting and new PCR-based techniques for detection of the TaqI, StuI, HincII, AvaII, NcoI RFLPs. Two hundred fifty-six independent haplotypes from 368 individuals of 61 unrelated Swiss families, as well as 114 independent haplotypes from 184 subjects of 25 unrelated German families, were constructed. In 76 families, clinical diagnosis of FH was confirmed by cosegregation analysis. Of themore » 43 unique haplotypes consisting of seven RFLPs detected in the Swiss and Germans, only 9 were common in both population samples. Analysis of linkage disequilibrium revealed nonrandom associations between several of the investigated RFLPs. ApaLI (5[prime]), NcoI, PvuII, TaqI, and AvaII or HincII were particularly informative. Relative frequencies, heterozygosity indexes, and PICs of the RFLPs from the Swiss and Germans were compared with values calculated from reported haplotype data for Italians, Icelanders, North American Caucasians, South African Caucasians, and Japanese. Pairwise comparisons of population samples by common RFLPs demonstrated unexpected differences even between geographically adjacent populations (e.g., the Swiss and Germans). Furthermore, genetic distances from the Germans to the other Caucasians were larger than to the Japanese. An unexpected lack of correlation between linkage disequilibria and physical distances was detected for the German and Japanese data, possibly because of nonuniform recombination with excessively high rates between exon 13 and intron 15. Hence, the present study revealed a striking variety of polymorphic haplotypes and heterogeneity of RFLP frequencies and recombination rates among the seven population samples. 60 refs., 2 figs., 8 tabs.« less

Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome.

PubMed

Mitsumoto, H; Schwartzman, M J; Estes, M L; Chou, S M; La Franchise, E F; De Camilli, P; Solimena, M

1991-04-01

Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.

Kinase inhibitor profiling reveals unexpected opportunities to inhibit disease-associated mutant kinases

PubMed Central

Duong-Ly, Krisna C.; Devarajan, Karthik; Liang, Shuguang; Horiuchi, Kurumi Y.; Wang, Yuren; Ma, Haiching; Peterson, Jeffrey R.

2016-01-01

Summary Small-molecule kinase inhibitors have typically been designed to inhibit wild-type kinases rather than the mutant forms that frequently arise in diseases such as cancer. Mutations can have serious clinical implications by increasing kinase catalytic activity or conferring therapeutic resistance. To identify opportunities to repurpose inhibitors against disease-associated mutant kinases, we conducted a large-scale functional screen of 183 known kinase inhibitors against 76 recombinant, mutant kinases. The results revealed lead compounds with activity against clinically important mutant kinases including ALK, LRRK2, RET, and EGFR as well as unexpected opportunities for repurposing FDA-approved kinase inhibitors as leads for additional indications. Furthermore, using T674I PDGFRα as an example, we show how single-dose screening data can provide predictive structure-activity data to guide subsequent inhibitor optimization. This study provides a resource for the development of inhibitors against numerous disease-associated mutant kinases and illustrates the potential of unbiased profiling as an approach to compound-centric inhibitor development. PMID:26776524

The influence of nondisclosure on the mental health of urban African-American adolescents exposed to community violence.

PubMed

Dinizulu, Sonya Mathies; Grant, Kathryn E; McIntosh, Jeanne M

2014-01-01

African-American youth residing in urban poverty have been shown to be at increased risk for exposure to violence and internalizing symptoms, but there has been little investigation of moderating processes that might attenuate or exacerbate this association. The current study examined nondisclosure as a possible moderator of the association between community violence and internalizing symptoms with a sample of 152 low-income urban African-American early adolescents using hierarchical regression analyses. Results revealed that nondisclosure for relationship reasons (e.g., adults could not be trusted to provide needed support) moderated the association between exposure to community violence and internalizing symptoms. Unexpectedly, however, results of simple effects analyses revealed a stronger association between exposure to violence and internalizing symptoms for youth who disclosed more to adults. Although unexpected, this pattern builds upon prior research indicating that adult-child relationships are compromised within the context of urban poverty and that protective factors may lose their power under conditions of extreme stress.

Structural and Functional Survey of Environmental Aminoglycoside Acetyltransferases Reveals Functionality of Resistance Enzymes.

PubMed

Xu, Zhiyu; Stogios, Peter J; Quaile, Andrew T; Forsberg, Kevin J; Patel, Sanket; Skarina, Tatiana; Houliston, Scott; Arrowsmith, Cheryl; Dantas, Gautam; Savchenko, Alexei

2017-09-08

Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al. Nature 2014 , 509 , 612 ). These enzymes are new members of the Gcn5-Related-N-Acetyltransferase superfamily and confer resistance to the aminoglycosides gentamicin C, sisomicin, and tobramycin. Moreover, the meta-AAC0020 enzyme demonstrated activity comparable with an AAC(3)-I enzyme that serves as a model AAC enzyme identified in a clinical bacterial isolate. The crystal structure of meta-AAC0020 in complex with sisomicin confirmed an unexpected AAC(6') regiospecificity of this enzyme and revealed a drug binding mechanism distinct from previously characterized AAC(6') enzymes. Together, our data highlights the presence of highly active antibiotic-modifying enzymes in the environmental microbiome and reveals unexpected diversity in substrate specificity. These observations of additional AAC enzymes must be considered in the search for novel aminoglycosides less prone to resistance.

The Measurement of Stress in Nonvisual Travel.

ERIC Educational Resources Information Center

Ponchillia, Paul E.; And Others

1984-01-01

Measurement of stress in nonvisual travel was attempted with both an electromyograph and a galvonic skin response unit in four travel situations. Results revealed significantly greater stress response when unexpected contact with objects was made than with expected contacts and street crossings. Instructors' intervention also increased stress.…

Leveraging Failure in Design Research

ERIC Educational Resources Information Center

Lobato, Joanne; Walters, C. David; Hohensee, Charles; Gruver, John; Diamond, Jaime Marie

2015-01-01

Even in the resource-rich, more ideal conditions of many design-based classroom interventions, unexpected events can lead to disappointing results in student learning. However, if later iterations in a design research study are more successful, the previous failures can provide opportunities for comparisons to reveal subtle differences in…

Novel and Unexpected Microbial Diversity in Acid Mine Drainage in Svalbard (78° N), Revealed by Culture-Independent Approaches

PubMed Central

García-Moyano, Antonio; Austnes, Andreas Erling; Lanzén, Anders; González-Toril, Elena; Aguilera, Ángeles; Øvreås, Lise

2015-01-01

Svalbard, situated in the high Arctic, is an important past and present coal mining area. Dozens of abandoned waste rock piles can be found in the proximity of Longyearbyen. This environment offers a unique opportunity for studying the biological control over the weathering of sulphide rocks at low temperatures. Although the extension and impact of acid mine drainage (AMD) in this area is known, the native microbial communities involved in this process are still scarcely studied and uncharacterized. Several abandoned mining areas were explored in the search for active AMD and a culture-independent approach was applied with samples from two different runoffs for the identification and quantification of the native microbial communities. The results obtained revealed two distinct microbial communities. One of the runoffs was more extreme with regards to pH and higher concentration of soluble iron and heavy metals. These conditions favored the development of algal-dominated microbial mats. Typical AMD microorganisms related to known iron-oxidizing bacteria (Acidithiobacillus ferrivorans, Acidobacteria and Actinobacteria) dominated the bacterial community although some unexpected populations related to Chloroflexi were also significant. No microbial mats were found in the second area. The geochemistry here showed less extreme drainage, most likely in direct contact with the ore under the waste pile. Large deposits of secondary minerals were found and the presence of iron stalks was revealed by microscopy analysis. Although typical AMD microorganisms were also detected here, the microbial community was dominated by other populations, some of them new to this type of system (Saccharibacteria, Gallionellaceae). These were absent or lowered in numbers the farther from the spring source and they could represent native populations involved in the oxidation of sulphide rocks within the waste rock pile. This environment appears thus as a highly interesting field of potential novelty in terms of both phylogenetic/taxonomic and functional diversity. PMID:27682111

A systematic analysis of the Braitenberg vehicle 2b for point-like stimulus sources.

PubMed

Rañó, Iñaki

2012-09-01

Braitenberg vehicles have been used experimentally for decades in robotics with limited empirical understanding. This paper presents the first mathematical model of the vehicle 2b, displaying so-called aggression behaviour, and analyses the possible trajectories for point-like smooth stimulus sources. This sensory-motor steering control mechanism is used to implement biologically grounded target approach, target-seeking or obstacle-avoidance behaviour. However, the analysis of the resulting model reveals that complex and unexpected trajectories can result even for point-like stimuli. We also prove how the implementation of the controller and the vehicle morphology interact to affect the behaviour of the vehicle. This work provides a better understanding of Braitenberg vehicle 2b, explains experimental results and paves the way for a formally grounded application on robotics as well as for a new way of understanding target seeking in biology.

Conserved linear dynamics of single-molecule Brownian motion.

PubMed

Serag, Maged F; Habuchi, Satoshi

2017-06-06

Macromolecular diffusion in homogeneous fluid at length scales greater than the size of the molecule is regarded as a random process. The mean-squared displacement (MSD) of molecules in this regime increases linearly with time. Here we show that non-random motion of DNA molecules in this regime that is undetectable by the MSD analysis can be quantified by characterizing the molecular motion relative to a latticed frame of reference. Our lattice occupancy analysis reveals unexpected sub-modes of motion of DNA that deviate from expected random motion in the linear, diffusive regime. We demonstrate that a subtle interplay between these sub-modes causes the overall diffusive motion of DNA to appear to conform to the linear regime. Our results show that apparently random motion of macromolecules could be governed by non-random dynamics that are detectable only by their relative motion. Our analytical approach should advance broad understanding of diffusion processes of fundamental relevance.

Conserved linear dynamics of single-molecule Brownian motion

PubMed Central

Serag, Maged F.; Habuchi, Satoshi

2017-01-01

Macromolecular diffusion in homogeneous fluid at length scales greater than the size of the molecule is regarded as a random process. The mean-squared displacement (MSD) of molecules in this regime increases linearly with time. Here we show that non-random motion of DNA molecules in this regime that is undetectable by the MSD analysis can be quantified by characterizing the molecular motion relative to a latticed frame of reference. Our lattice occupancy analysis reveals unexpected sub-modes of motion of DNA that deviate from expected random motion in the linear, diffusive regime. We demonstrate that a subtle interplay between these sub-modes causes the overall diffusive motion of DNA to appear to conform to the linear regime. Our results show that apparently random motion of macromolecules could be governed by non-random dynamics that are detectable only by their relative motion. Our analytical approach should advance broad understanding of diffusion processes of fundamental relevance. PMID:28585925

Conserved linear dynamics of single-molecule Brownian motion

NASA Astrophysics Data System (ADS)

Serag, Maged F.; Habuchi, Satoshi

2017-06-01

Macromolecular diffusion in homogeneous fluid at length scales greater than the size of the molecule is regarded as a random process. The mean-squared displacement (MSD) of molecules in this regime increases linearly with time. Here we show that non-random motion of DNA molecules in this regime that is undetectable by the MSD analysis can be quantified by characterizing the molecular motion relative to a latticed frame of reference. Our lattice occupancy analysis reveals unexpected sub-modes of motion of DNA that deviate from expected random motion in the linear, diffusive regime. We demonstrate that a subtle interplay between these sub-modes causes the overall diffusive motion of DNA to appear to conform to the linear regime. Our results show that apparently random motion of macromolecules could be governed by non-random dynamics that are detectable only by their relative motion. Our analytical approach should advance broad understanding of diffusion processes of fundamental relevance.

Flow Structures within a Helicopter Rotor Hub Wake

NASA Astrophysics Data System (ADS)

Elbing, Brian; Reich, David; Schmitz, Sven

2015-11-01

A scaled model of a notional helicopter rotor hub was tested in the 48'' Garfield Thomas Water Tunnel at the Applied Research Laboratory Penn State. The measurement suite included total hub drag and wake velocity measurements (LDV, PIV, stereo-PIV) at three downstream locations. The main objective was to understand the spatiotemporal evolution of the unsteady wake between the rotor hub and the nominal location of the empennage (tail). Initial analysis of the data revealed prominent two- and four-per-revolution fluid structures linked to geometric hub features persisting into the wake far-field. In addition, a six-per-revolution fluid structure was observed in the far-field, which is unexpected due to the lack of any hub feature with the corresponding symmetry. This suggests a nonlinear interaction is occurring within the wake to generate these structures. This presentation will provide an overview of the experimental data and analysis with particular emphasis on these six-per-revolution structures.

Psychometric properties of the Social Skills Questionnaire: Portuguese adaptation of the student form (grades 7 to 12).

PubMed

Mota, Catarina Pinheiro; Matos, Paula Mena; Lemos, Marina Serra

2011-05-01

The present study aims to analyze the psychometric properties of the student form (Grades 7 to 12) of the Social Skills Questionnaire authored by Gresham and Elliott (1990), on a sample of Portuguese adolescents. Participants included 573 students, both female and male, aged 14 to 19. Reliability was assessed through Cronbach's alpha and was .87 for the total scale, ranging from.58 to .72 for the subscales. A confirmatory factor analysis revealed that the main adjustment indices presented unexpected values. A principal components analysis indicated that several items of the cooperation subscale correlated with other factors. Adequate adjustment indices were found when cooperation was removed from the model. Semantic dualities due to cultural factors and difficulties assuming the cooperation dimension as an independent dimension might explain the results observed. The reorganization of the SSQ offers a reliable and valid instrument for research within the Portuguese population.

Formation of iron complexs from trifluoroacetic acid based liquid chromatography mobile phases as interference ions in liquid chromatography/electrospray ionization mass spectrometric analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shukla, Anil K.; Zhang, Rui; Orton, Daniel J.

Two unexpected singly charged ions at m/z 1103 and 944 have been observed in mass spectra obtained from electrospray ionization-mass spectrometric analysis of liquid chromatography effluents with mobile phases containing trifluoroacetic acid. Accurate mass measurement and tandem mass spectrometry studies revealed that these two ions are not due to any contamination from solvents and chemicals used for mobile and stationary phases or from the laboratory atmospheric environment. Instead these ions are clusters of trifluoroacetic acid formed in association with acetonitrile, water and iron from the stainless steel union used to connect the column with the electrospray tip and to applymore » high voltage; the molecular formulae are Fe+((OH)(H2O)2)9(CF3COOH)5 and Fe+((OH)(H2O)2)6 (CF3COOH)5.« less

Effects of Unexpected Chords and of Performer's Expression on Brain Responses and Electrodermal Activity

PubMed Central

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

2008-01-01

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. PMID:18612459

Differential diagnosis of left ventricular hypertrophy: usefulness of multimodality imaging and tissue characterization with cardiac magnetic resonance.

PubMed

Izgi, Cemil; Vassiliou, Vassilis; Baksi, A John; Prasad, Sanjay K

2016-11-01

Differential diagnosis of asymmetrical left ventricular hypertrophy may be challenging, particularly in patients with history of hypertension. A middle-aged man underwent an echocardiographic examination during workup for hypertension, which unexpectedly showed significant asymmetrical septal hypertrophy and raised suspicion for hypertrophic cardiomyopathy. Cardiovascular magnetic resonance confirmed the asymmetrical hypertrophy. No myocardial late gadolinium contrast enhancement was seen. However, precontrast T1 mapping revealed a low native myocardial T1 value. This was highly suggestive of Anderson-Fabry disease, which was subsequently proved with very low alpha galactosidase enzyme levels and mutation analysis. The case illustrates clinical usefulness of multimodality imaging and the novel tissue characterization techniques for assessment of left ventricular hypertrophy. © 2016, Wiley Periodicals, Inc.

More than just water channels: unexpected cellular roles of aquaporins.

PubMed

Verkman, A S

2005-08-01

Aquaporins (AQPs) are membrane proteins that transport water and, in some cases, also small solutes such as glycerol. AQPs are expressed in many fluid-transporting tissues, such as kidney tubules and glandular epithelia, as well as in non-fluid-transporting tissues, such as epidermis, adipose tissue and astroglia. Their classical role in facilitating trans-epithelial fluid transport is well understood, as in the urinary concentrating mechanism and gland fluid secretion. AQPs are also involved in swelling of tissues under stress, as in the injured cornea and the brain in stroke, tumor and infection. Recent analysis of AQP-knockout mice has revealed unexpected cellular roles of AQPs. AQPs facilitate cell migration, as manifested by reduced tumor angiogenesis in AQP1-knockout mice, by a mechanism that might involve facilitated water transport in lamellipodia of migrating cells. AQPs that transport both glycerol and water regulate glycerol content in epidermis and fat, and consequently skin hydration/biosynthesis and fat metabolism. AQPs might also be involved in neural signal transduction, cell volume regulation and organellar physiology. The many roles of AQPs could be exploited for clinical benefit; for example, treatments that modulate AQP expression/function could be used as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer.

MULTILOCUS SEQUENCE TYPING OF BRUCELLA ISOLATES FROM THAILAND.

PubMed

Chawjiraphan, Wireeya; Sonthayanon, Piengchan; Chanket, Phanita; Benjathummarak, Surachet; Kerdsin, Anusak; Kalambhaheti, Thareerat

2016-11-01

Although brucellosis outbreaks in Thailand are rare, they cause abortions and infertility in animals, resulting in significant economic loss. Because Brucella spp display > 90% DNA homology, multilocus sequence typing (MLST) was employed to categorize local Brucella isolates into sequence types (STs) and to determine their genetic relatedness. Brucella samples were isolated from vaginal secretion of cows and goats, and from blood cultures of infected individuals. Brucella species were determined by multiplex PCR of eight loci, in addition to MLST based on partial DNA sequences of nine house-keeping genes. MLST analysis of 36 isolates revealed 78 distinct novel allele types and 34 novel STs, while two isolates possessed the known ST8. Sequence alignments identified polymorphic sites in each allele, ranging from 2-6%, while overall genetic diversity was 3.6%. MLST analysis of the 36 Brucella isolates classified them into three species, namely, B. melitensis, B. abortus and B. suis, in agreement with multiplex PCR results. Genetic relatedness among ST members of B. melitensis and B. abortus determined by eBURST program revealed ST2 as founder of B. abortus isolates and ST8 the founder of B. melitensis isolates. ST 36, 41 and 50 of Thai Brucella isolates were identified as single locus variants of clonal cluster (CC) 8, while the majority of STs were diverse. The genetic diversity and relatedness identified using MLST revealed hitherto unexpected diversity among Thai Brucella isolates. Genetic classification of isolates could reveal the route of brucellosis transmission among humans and farm animals and also reveal their relationship with other isolates in the region and other parts of the world.

Revealing misassembled segments in the bovine reference genome by high resolution linkage disequilibrium scan

USDA-ARS?s Scientific Manuscript database

Misassembly signatures, created by shuffling the order of sequences while assembling a genome, can be easily seen by analyzing the unexpected behaviour of the linkage disequilibrium (LD) decay. A heuristic process was proposed to identify those misassembly signatures and presented the ones found in ...

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

EPA Science Inventory

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...

Quinone 1 e – and 2 e – /2 H + Reduction Potentials: Identification and Analysis of Deviations from Systematic Scaling Relationships

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huynh, Mioy T.; Anson, Colin W.; Cavell, Andrew C.

Quinones participate in diverse electron transfer and proton-coupled electron transfer processes in chemistry and biology. An experimental study of common quinones reveals a non-linear correlation between the 1 e – and 2 e –/2 H + reduction potentials. This unexpected observation prompted a computational study of 128 different quinones, probing their 1 e – reduction potentials, pKa values, and 2 e –/2 H + reduction potentials. The density functional theory calculations reveal an approximately linear correlation between these three properties and an effective Hammett constant associated with the quinone substituent(s). However, deviations from this linear scaling relationship are evident formore » quinones that feature halogen substituents, charged substituents, intramolecular hydrogen bonding in the hydroquinone, and/or sterically bulky substituents. These results, particularly the different substituent effects on the 1 e – versus 2 e – /2 H + reduction potentials, have important implications for designing quinones with tailored redox properties.« less

Genetic Dosage Compensation in a Family with Velo-cardio-facial/DiGeorge/22q11.2 Deletion Syndrome

PubMed Central

Alkalay, Avishai A.; Guo, Tingwei; Montagna, Cristina; Digilio, M. Cristina; Marino, Bruno; Dallapiccola, Bruno; Morrow, Bernice

2014-01-01

Cytogenetic studies of a male child carrying the 22q11.2 deletion common in patients with velo-cardio-facial/DiGeorge syndrome revealed an unexpected rearrangement of the 22q11.2 region in his normal appearing mother. The mother carries a 3 Mb deletion on one copy and a reciprocal, similar sized duplication on the other copy of chromosome 22q11.2 as revealed by fluorescence in situ hybridization and array comparative genome hybridization analysis. The most parsimonious mechanism for the rearrangement is a mitotic non-allelic homologous recombination event in a cell in the early embryo soon after fertilization. The normal phenotype of the mother can be explained by the theory of genetic dosage compensation. This is the second documented case of such an event for this or any genomic disorder. This finding helps to reinforce this phenomenon in a human model, and has significant implications for genetic counseling of future children. PMID:21337693

Diverse set of Turing nanopatterns coat corneae across insect lineages

PubMed Central

Blagodatski, Artem; Sergeev, Anton; Kryuchkov, Mikhail; Lopatina, Yuliya; Katanaev, Vladimir L.

2015-01-01

Nipple-like nanostructures covering the corneal surfaces of moths, butterflies, and Drosophila have been studied by electron and atomic force microscopy, and their antireflective properties have been described. In contrast, corneal nanostructures of the majority of other insect orders have either been unexamined or examined by methods that did not allow precise morphological characterization. Here we provide a comprehensive analysis of corneal surfaces in 23 insect orders, revealing a rich diversity of insect corneal nanocoatings. These nanocoatings are categorized into four major morphological patterns and various transitions between them, many, to our knowledge, never described before. Remarkably, this unexpectedly diverse range of the corneal nanostructures replicates the complete set of Turing patterns, thus likely being a result of processes similar to those modeled by Alan Turing in his famous reaction−diffusion system. These findings reveal a beautiful diversity of insect corneal nanostructures and shed light on their molecular origin and evolutionary diversification. They may also be the first-ever biological example of Turing nanopatterns. PMID:26307762

Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse, human glioblastomas in the mouse brain in vivo

PubMed Central

Marin-Valencia, Isaac; Yang, Chendong; Mashimo, Tomoyuki; Cho, Steve; Baek, Hyeonman; Yang, Xiao-Li; Rajagopalan, Kartik N.; Maddie, Melissa; Vemireddy, Vamsidhara; Zhao, Zhenze; Cai, Ling; Good, Levi; Tu, Benjamin P.; Hatanpaa, Kimmo J.; Mickey, Bruce E.; Matés, José M.; Pascual, Juan M.; Maher, Elizabeth A.; Malloy, Craig R.; DeBerardinis, Ralph J.; Bachoo, Robert M.

2012-01-01

SUMMARY Dysregulated metabolism is a hallmark of cancer cell lines, but little is known about the fate of glucose and other nutrients in tumors growing in their native microenvironment. To study tumor metabolism in vivo, we used an orthotopic mouse model of primary human glioblastoma (GBM). We infused 13C-labeled nutrients into mice bearing three independent GBM lines, each with a distinct set of mutations. All three lines displayed glycolysis, as expected for aggressive tumors. They also displayed unexpected metabolic complexity, oxidizing glucose via pyruvate dehydrogenase and the citric acid cycle, and using glucose to supply anaplerosis and other biosynthetic activities. Comparing the tumors to surrounding brain revealed obvious metabolic differences, notably the accumulation of a large glutamine pool within the tumors. Many of these same activities were conserved in cells cultured ex vivo from the tumors. Thus GBM cells utilize mitochondrial glucose oxidation during aggressive tumor growth in vivo. PMID:22682223

Visualization of in vivo metabolic flows reveals accelerated utilization of glucose and lactate in penumbra of ischemic heart

PubMed Central

Sugiura, Yuki; Katsumata, Yoshinori; Sano, Motoaki; Honda, Kurara; Kajimura, Mayumi; Fukuda, Keiichi; Suematsu, Makoto

2016-01-01

Acute ischemia produces dynamic changes in labile metabolites. To capture snapshots of such acute metabolic changes, we utilized focused microwave treatment to fix metabolic flow in vivo in hearts of mice 10 min after ligation of the left anterior descending artery. The left ventricle was subdivided into short-axis serial slices and the metabolites were analyzed by capillary electrophoresis mass spectrometry and matrix-assisted laser desorption/ionization imaging mass spectrometry. These techniques allowed us to determine the fate of exogenously administered 13C6-glucose and 13C3-lactate. The penumbra regions, which are adjacent to the ischemic core, exhibited the greatest adenine nucleotide energy charge and an adenosine overflow extending from the ischemic core, which can cause ischemic hyperemia. Imaging analysis of metabolic pathway flows revealed that the penumbra executes accelerated glucose oxidation, with remaining lactate utilization for tricarboxylic acid cycle for energy compensation, suggesting unexpected metabolic interplays of the penumbra with the ischemic core and normoxic regions. PMID:27581923

Genome-wide Analysis Reveals SR Protein Cooperation and Competition in Regulated Splicing

PubMed Central

Pandit, Shatakshi; Zhou, Yu; Shiue, Lily; Coutinho-Mansfield, Gabriela; Li, Hairi; Qiu, Jinsong; Huang, Jie; Yeo, Gene W.; Ares, Manuel; Fu, Xiang-Dong

2013-01-01

Summary SR proteins are well-characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers (ESEs). However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell. Here, we report global analyses of two prototypical SR proteins SRSF1 (SF2/ASF) and SRSF2 (SC35) using splicing-sensitive arrays and CLIP-seq on mouse embryo fibroblasts (MEFs). Unexpectedly, we find that these SR proteins promote both inclusion and skipping of exons in vivo, but their binding patterns do not explain such opposite responses. Further analyses reveal that loss of one SR protein is accompanied by coordinated loss or compensatory gain in the interaction of other SR proteins at the affected exons. Therefore, specific effects on regulated splicing by one SR protein actually depend on a complex set of relationships with multiple other SR proteins in mammalian genomes. PMID:23562324

Bacterial community compositions of coking wastewater treatment plants in steel industry revealed by Illumina high-throughput sequencing.

PubMed

Ma, Qiao; Qu, Yuanyuan; Shen, Wenli; Zhang, Zhaojing; Wang, Jingwei; Liu, Ziyan; Li, Duanxing; Li, Huijie; Zhou, Jiti

2015-03-01

In this study, Illumina high-throughput sequencing was used to reveal the community structures of nine coking wastewater treatment plants (CWWTPs) in China for the first time. The sludge systems exhibited a similar community composition at each taxonomic level. Compared to previous studies, some of the core genera in municipal wastewater treatment plants such as Zoogloea, Prosthecobacter and Gp6 were detected as minor species. Thiobacillus (20.83%), Comamonas (6.58%), Thauera (4.02%), Azoarcus (7.78%) and Rhodoplanes (1.42%) were the dominant genera shared by at least six CWWTPs. The percentages of autotrophic ammonia-oxidizing bacteria and nitrite-oxidizing bacteria were unexpectedly low, which were verified by both real-time PCR and fluorescence in situ hybridization analyses. Hierarchical clustering and canonical correspondence analysis indicated that operation mode, flow rate and temperature might be the key factors in community formation. This study provides new insights into our understanding of microbial community compositions and structures of CWWTPs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural insights into xenobiotic and inhibitor binding to human aldehyde oxidase.

PubMed

Coelho, Catarina; Foti, Alessandro; Hartmann, Tobias; Santos-Silva, Teresa; Leimkühler, Silke; Romão, Maria João

2015-10-01

Aldehyde oxidase (AOX) is a xanthine oxidase (XO)-related enzyme with emerging importance due to its role in the metabolism of drugs and xenobiotics. We report the first crystal structures of human AOX1, substrate free (2.6-Å resolution) and in complex with the substrate phthalazine and the inhibitor thioridazine (2.7-Å resolution). Analysis of the protein active site combined with steady-state kinetic studies highlight the unique features, including binding and substrate orientation at the active site, that characterize human AOX1 as an important drug-metabolizing enzyme. Structural analysis of the complex with the noncompetitive inhibitor thioridazine revealed a new, unexpected and fully occupied inhibitor-binding site that is structurally conserved among mammalian AOXs and XO. The new structural insights into the catalytic and inhibition mechanisms of human AOX that we now report will be of great value for the rational analysis of clinical drug interactions involving inhibition of AOX1 and for the prediction and design of AOX-stable putative drugs.

Lactobacillus reuteri 100-23 modulates urea hydrolysis in the murine stomach.

PubMed

Wilson, Charlotte M; Loach, Diane; Lawley, Blair; Bell, Tracey; Sims, Ian M; O'Toole, Paul W; Zomer, Aldert; Tannock, Gerald W

2014-10-01

Comparisons of in vivo (mouse stomach) and in vitro (laboratory culture) transcriptomes of Lactobacillus reuteri strain 100-23 were made by microarray analysis. These comparisons revealed the upregulation of genes associated with acid tolerance, including urease production, in the mouse stomach. Inactivation of the ureC gene reduced the acid tolerance of strain 100-23 in vitro, and the mutant was outcompeted by the wild type in the gut of ex-Lactobacillus-free mice. Urine analysis showed that stable isotope-labeled urea, administered by gavage, was metabolized to a greater extent in Lactobacillus-free mice than animals colonized by strain 100-23. This surprising observation was associated with higher levels of urease activity and fecal-type bacteria in the stomach digesta of Lactobacillus-free mice. Despite the modulation of urea hydrolysis in the stomach, recycling of urea nitrogen in the murine host was not affected since the essential amino acid isoleucine, labeled with a stable isotope, was detected in the livers of both Lactobacillus-free and 100-23-colonized animals. Therefore, our experiments reveal a new and unexpected impact of Lactobacillus colonization on urea hydrolysis in the murine gut. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Lactobacillus reuteri 100-23 Modulates Urea Hydrolysis in the Murine Stomach

PubMed Central

Wilson, Charlotte M.; Loach, Diane; Lawley, Blair; Bell, Tracey; Sims, Ian M.; O'Toole, Paul W.; Zomer, Aldert

2014-01-01

Comparisons of in vivo (mouse stomach) and in vitro (laboratory culture) transcriptomes of Lactobacillus reuteri strain 100-23 were made by microarray analysis. These comparisons revealed the upregulation of genes associated with acid tolerance, including urease production, in the mouse stomach. Inactivation of the ureC gene reduced the acid tolerance of strain 100-23 in vitro, and the mutant was outcompeted by the wild type in the gut of ex-Lactobacillus-free mice. Urine analysis showed that stable isotope-labeled urea, administered by gavage, was metabolized to a greater extent in Lactobacillus-free mice than animals colonized by strain 100-23. This surprising observation was associated with higher levels of urease activity and fecal-type bacteria in the stomach digesta of Lactobacillus-free mice. Despite the modulation of urea hydrolysis in the stomach, recycling of urea nitrogen in the murine host was not affected since the essential amino acid isoleucine, labeled with a stable isotope, was detected in the livers of both Lactobacillus-free and 100-23-colonized animals. Therefore, our experiments reveal a new and unexpected impact of Lactobacillus colonization on urea hydrolysis in the murine gut. PMID:25063664

Single nucleotide polymorphism analysis reveals heterogeneity within a seedling tree population of a polyembryonic mango cultivar.

PubMed

Winterhagen, Patrick; Wünsche, Jens-Norbert

2016-05-01

Within a polyembryonic mango seedling tree population, the genetic background of individuals should be identical because vigorous plants for cultivation are expected to develop from nucellar embryos representing maternal clones. Due to the fact that the mango cultivar 'Hôi' is assigned to the polyembryonic ecotype, an intra-cultivar variability of ethylene receptor genes was unexpected. Ethylene receptors in plants are conserved, but the number of receptors or receptor isoforms is variable regarding different plant species. However, it is shown here that the ethylene receptor MiETR1 is present in various isoforms within the mango cultivar 'Hôi'. The investigation of single nucleotide polymorphisms revealed that different MiETR1 isoforms can not be discriminated simply by individual single nucleotide exchanges but by the specific arrangement of single nucleotide polymorphisms at certain positions in the exons of MiETR1. Furthermore, an MiETR1 isoform devoid of introns in the genomic sequence was identified. The investigation demonstrates some limitations of high resolution melting and ScreenClust analysis and points out the necessity of sequencing to identify individual isoforms and to determine the variability within the tree population.

Genomic Diversification in Strains of Rickettsia felis Isolated from Different Arthropods

PubMed Central

Gillespie, Joseph J.; Driscoll, Timothy P.; Verhoeve, Victoria I.; Utsuki, Tadanobu; Husseneder, Claudia; Chouljenko, Vladimir N.; Azad, Abdu F.; Macaluso, Kevin R.

2015-01-01

Rickettsia felis (Alphaproteobacteria: Rickettsiales) is the causative agent of an emerging flea-borne rickettsiosis with worldwide occurrence. Originally described from the cat flea, Ctenocephalides felis, recent reports have identified R. felis from other flea species, as well as other insects and ticks. This diverse host range for R. felis may indicate an underlying genetic variability associated with host-specific strains. Accordingly, to determine a potential genetic basis for host specialization, we sequenced the genome of R. felis str. LSU-Lb, which is an obligate mutualist of the parthenogenic booklouse Liposcelis bostrychophila (Insecta: Psocoptera). We also sequenced the genome of R. felis str. LSU, the second genome sequence for cat flea-associated strains (cf. R. felis str. URRWXCal2), which are presumably facultative parasites of fleas. Phylogenomics analysis revealed R. felis str. LSU-Lb diverged from the flea-associated strains. Unexpectedly, R. felis str. LSU was found to be divergent from R. felis str. URRWXCal2, despite sharing similar hosts. Although all three R. felis genomes contain the pRF plasmid, R. felis str. LSU-Lb carries an additional unique plasmid, pLbaR (plasmid of L. bostrychophila associated Rickettsia), nearly half of which encodes a unique 23-gene integrative conjugative element. Remarkably, pLbaR also encodes a repeats-in-toxin-like type I secretion system and associated toxin, heretofore unknown from other Rickettsiales genomes, which likely originated from lateral gene transfer with another obligate intracellular parasite of arthropods, Cardinium (Bacteroidetes). Collectively, our study reveals unexpected genomic diversity across three R. felis strains and identifies several diversifying factors that differentiate facultative parasites of fleas from obligate mutualists of booklice. PMID:25477419

Special ways of knowing in science: expansive learning opportunities with bilingual children with learning disabilities

NASA Astrophysics Data System (ADS)

Martínez-Álvarez, Patricia

2017-09-01

The field of bilingual special education is currently plagued with contradictions resulting in a serious underrepresentation of emergent bilinguals with learning disabilities in professional science fields. This underrepresentation is due in large part to the fact that educational systems around the world are inadequately prepared to address the educational needs of these children; this inadequacy is rooted in a lack of understanding of the linguistic and cultural factors impacting learning. Accepting such a premise and assuming that children learn in unexpected ways when instructional practices attend to culture and language, this study documents a place-based learning experience integrating geoscience and literacy in a fourth-grade dual language classroom. Data sources include transcribed audio-taped conversations from learning experience sessions and interviews that took place as six focus children, who had been identified as having specific learning disabilities, read published science texts (i.e. texts unaltered linguistically or conceptually to meet the needs of the readers). My analysis revealed that participants generated responses that were often unexpected if solely analyzed from those Western scientific perspectives traditionally valued in school contexts. However, these responses were also full of purposeful and rich understandings that revealed opportunities for expansive learning. Adopting a cultural historical activity theory perspective, instructional tools such as texts, visuals, and questions were found to act as mediators impacting the learning in both activity systems: (a) teacher- researcher learning from children, and (b) children learning from teachers. I conclude by suggesting that there is a need to understand students' ways of knowing to their full complexity, and to deliberately recognize teachers as learners, researchers, and means to expansive learning patterns that span beyond traditional learning boundaries.

Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics.

PubMed

Harris, Kenneth D; Hochgerner, Hannah; Skene, Nathan G; Magno, Lorenza; Katona, Linda; Bengtsson Gonzales, Carolina; Somogyi, Peter; Kessaris, Nicoletta; Linnarsson, Sten; Hjerling-Leffler, Jens

2018-06-18

Understanding any brain circuit will require a categorization of its constituent neurons. In hippocampal area CA1, at least 23 classes of GABAergic neuron have been proposed to date. However, this list may be incomplete; additionally, it is unclear whether discrete classes are sufficient to describe the diversity of cortical inhibitory neurons or whether continuous modes of variability are also required. We studied the transcriptomes of 3,663 CA1 inhibitory cells, revealing 10 major GABAergic groups that divided into 49 fine-scale clusters. All previously described and several novel cell classes were identified, with three previously described classes unexpectedly found to be identical. A division into discrete classes, however, was not sufficient to describe the diversity of these cells, as continuous variation also occurred between and within classes. Latent factor analysis revealed that a single continuous variable could predict the expression levels of several genes, which correlated similarly with it across multiple cell types. Analysis of the genes correlating with this variable suggested it reflects a range from metabolically highly active faster-spiking cells that proximally target pyramidal cells to slower-spiking cells targeting distal dendrites or interneurons. These results elucidate the complexity of inhibitory neurons in one of the simplest cortical structures and show that characterizing these cells requires continuous modes of variation as well as discrete cell classes.

Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy

PubMed Central

Kuzmanov, Uros; Guo, Hongbo; Buchsbaum, Diana; Cosme, Jake; Abbasi, Cynthia; Isserlin, Ruth; Sharma, Parveen; Gramolini, Anthony O.; Emili, Andrew

2016-01-01

Phospholamban (PLN) plays a central role in Ca2+ homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase 2A (SERCA2A) Ca2+ pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates. Dysregulated phosphorylation sites were quantified after affinity capture and identification of 3,908 phosphopeptides from fractionated whole-heart homogenates. Global statistical enrichment analysis of the differential phosphoprotein patterns revealed selective perturbation of signaling pathways regulating cardiovascular activity in early stages of DCM. Strikingly, dysregulated signaling through the Notch-1 receptor, recently linked to cardiomyogenesis and embryonic cardiac stem cell development and differentiation but never directly implicated in DCM before, was a prominently perturbed pathway. We verified alterations in Notch-1 downstream components in early symptomatic R9C transgenic mouse cardiomyocytes compared with wild type by immunoblot analysis and confocal immunofluorescence microscopy. These data reveal unexpected connections between stress-regulated cell signaling networks, specific protein kinases, and downstream effectors essential for proper cardiac function. PMID:27742792

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

PubMed

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.

The management of small area burns and unexpected illness after burn in children under five years of age - A costing study in the English healthcare setting.

PubMed

Kandiyali, R; Sarginson, J H; Hollén, L I; Spickett-Jones, F; Young, A E R

2018-02-01

The objective of this economic study was to evaluate the resource use and cost associated with the management of small area burns, including the additional costs associated with unexpected illness after burn in children of less than five years of age. This study was conducted as a secondary analysis of a multi-centre prospective observational cohort study investigating the physiological response to burns in children. 452 children were included in the economic analysis (median age=1.60years, 61.3% boys, median total burn surface area [TBSA]=1.00%) with a mean length of stay of 0.69 days. Of these children, 21.5% re-presented to medical care with an unexpected illness within fourteen days of injury. The cost of managing a burn of less than 10% TBSA in a child less than five years of age was £785. The additional cost associated with the management of illness after burn was £1381. A generalised linear regression model was used to determine the association between an unexpected illness after burn, presenting child characteristics and NHS cost. Our findings may be of value to those planning economic evaluations of novel technologies in burn care. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

[Sudden death of twins: botulism because of contamination by pap vegetables].

PubMed

Fischer, D; Freislederer, A; Jorch, G

2004-01-01

Botulism is caused by the blockage of the neural transmission in the cholinergic synapses by botulinum neurotoxin (BoNT) which is produced by Clostridium botulinum or other Clostridia. The classic form of botulism occurs after the ingestion of food contaminated by BoNT. The course of the infection can be asymptomatic, mild with subtle paralysis ("failure to thrive") oder severe with generalized paralysis ("floppy infant"). Infected infants can also die sudden and unexpectedly. These deaths often are attributed to Sudden Infant Death Syndrome (SIDS), unless a thorough postmortem examination reveals Botulism. The rate of fatal Botulism falsely attributed to SIDS is not known, because it is difficult in most cases to show the causal relationship between contamination, disease and death. We report the sudden and unexpected simultaneous death of twins of 22 months which could be attributed to Botulism. Contamination of food, colonization of the gut by Clostridia and infection with specific pathomorphological changes could be proven. The initial suspicion of infanticide could be excluded. lt could be shown, that Botulism is a potential cause of simultaneous unexpected deaths in twins.

Unexpected inhibition of CO 2 gas hydrate formation in dilute TBAB solutions and the critical role of interfacial water structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Ngoc N.; Nguyen, Anh V.; Nguyen, Khoi T.

Gas hydrates formed under moderated conditions open up novel approaches to tackling issues related to energy supply, gas separation, and CO 2 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 CO 2 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 (TBAmore » +) 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.« less

The crystal structures of EAP domains from Staphylococcus aureus reveal an unexpected homology to bacterial superantigens.

PubMed

Geisbrecht, Brian V; Hamaoka, Brent Y; Perman, Benjamin; Zemla, Adam; Leahy, Daniel J

2005-04-29

The Eap (extracellular adherence protein) of Staphylococcus aureus functions as a secreted virulence factor by mediating interactions between the bacterial cell surface and several extracellular host proteins. Eap proteins from different Staphylococcal strains consist of four to six tandem repeats of a structurally uncharacterized domain (EAP domain). We have determined the three-dimensional structures of three different EAP domains to 1.8, 2.2, and 1.35 A resolution, respectively. These structures reveal a core fold that is comprised of an alpha-helix lying diagonally across a five-stranded, mixed beta-sheet. Comparison of EAP domains with known structures reveals an unexpected homology with the C-terminal domain of bacterial superantigens. Examination of the structure of the superantigen SEC2 bound to the beta-chain of a T-cell receptor suggests a possible ligand-binding site within the EAP domain (Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. (1996) Nature 384, 188-192). These results provide the first structural characterization of EAP domains, relate EAP domains to a large class of bacterial toxins, and will guide the design of future experiments to analyze EAP domain structure/function relationships.

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

PubMed

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.

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

PubMed Central

Leese, Elizabeth; Clench, Malcolm; Morton, Jackie; Gardiner, Philip H.E.; Carolan, Vikki A.

2017-01-01

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. PMID:29051444

Of Feral Faculty and Magisterial Mowglis: The Domestication of Junior Faculty

ERIC Educational Resources Information Center

Reddick, Richard J.

2015-01-01

This chapter presents an assistant professor's scholarly personal narrative at the precipice of promotion, and reveals how the feral child metaphor might aptly describe many junior professors' experiences as they navigate a path toward tenure. This chronicling of mentorship in sometimes unexpected venues may aid new faculty and those invested in…

A whole-plant perspective reveals unexpected impacts of above- and belowground herbivores on plant growth and defense

USDA-ARS?s Scientific Manuscript database

Tradeoffs between plant growth and defense are central to theoretical frameworks used to study the ecology and evolution of plant defense against herbivores. However, these frameworks, as well as the experiments designed to test them, rarely include the remarkable diversity of belowground herbivores...

Talking about "Real Stuff": Explorations of Agency and Romance in an All-Girls' Book Club.

ERIC Educational Resources Information Center

Smith, Sally A.

2000-01-01

Examines six adolescent girls' talk around a young adult novel ("The Beggar's Ride" by T. Nelson). Reveals unexpected reading purposes: adolescent girls' reading for the combined purposes of agency and desire, exploring the fears and potentialities of being female and of the possibilities of autonomy. (SR)

Unexpected Preferential Dehydration of Artemisinin in Ionic Liquids

NASA Astrophysics Data System (ADS)

Sanders, Marc W.; Wright, Lawrence; Tate, Lauren; Fairless, Gayle; Crowhurst, Lorna; Bruce, Neil C.; Walker, Adam J.; Hembury, Guy A.; Shimizu, Seishi

2009-09-01

Thermodynamic measurements (at 298 K) reveal that a crucial step in the extraction process of the key antimalarial drug artemisinin by ionic liquids (ILs), namely, precipitation through the addition of water, is driven by artemisinin dehydration due to the differences in the water's interaction with the bulk ILs, rather than with the artemisinin itself.

Adult Structure and Development of the Human Fronto-Opercular Cerebral Cortex (Broca's Region)

ERIC Educational Resources Information Center

Judas, Milos; Cepanec, Maja

2007-01-01

Broca's area encompasses opercular and triangular part of the inferior frontal gyrus, covered by Brodmann's areas 44 and 45, respectively. Recent neuroimaging studies have revealed that, in addition to classical language functions, Broca's area has novel and unexpected functions, serving as a likely interface of action and perception important for…

Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency.

PubMed

Menzies, Paula; Langs, Lisa; Boermans, Herman; Martin, John; McNally, John

2004-03-01

A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs.

Effect of Prefrontal Cortex Damage on Resolving Lexical Ambiguity in Text

ERIC Educational Resources Information Center

Frattali, Carol; Hanna, Rebecca; McGinty, Anita Shukla; Gerber, Lynn; Wesley, Robert; Grafman, Jordan; Coelho, Carl

2007-01-01

The function of suppression of context-inappropriate meanings during lexical ambiguity resolution was examined in 25 adults with prefrontal cortex damage (PFCD) localized to the left (N = 8), right (N = 6), or bilaterally (N = 11); and 21 matched Controls. Results revealed unexpected inverse patterns of suppression between PFCD and Control groups,…

Chlamydia Pneumoniae Infections and Sudden Unexpected Deaths in Denmark.

ERIC Educational Resources Information Center

Johannsen, Finn

1993-01-01

Blood samples from 38 runners on the Danish national orienteering team revealed no ongoing chlamydia pneumoniae, although 42% had an earlier infection, similar to the incidence in the general population. However, over 2% had an ongoing lyme borreliosis infection, and 18% had an earlier infection, which is a higher incidence than in the general…

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

PubMed

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.

Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis.

PubMed

Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta

2016-09-01

In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded.

Conservation of Transcription Start Sites within Genes across a Bacterial Genus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Wenjun; Price, Morgan N.; Deutschbauer, Adam M.

Transcription start sites (TSSs) lying inside annotated genes, on the same or opposite strand, have been observed in diverse bacteria, but the function of these unexpected transcripts is unclear. Here, we use the metal-reducing bacterium Shewanella oneidensis MR-1 and its relatives to study the evolutionary conservation of unexpected TSSs. Using high-resolution tiling microarrays and 5'-end RNA sequencing, we identified 2,531 TSSs in S. oneidensis MR-1, of which 18% were located inside coding sequences (CDSs). Comparative transcriptome analysis with seven additional Shewanella species revealed that the majority (76%) of the TSSs within the upstream regions of annotated genes (gTSSs) were conserved.more » Thirty percent of the TSSs that were inside genes and on the sense strand (iTSSs) were also conserved. Sequence analysis around these iTSSs showed conserved promoter motifs, suggesting that many iTSS are under purifying selection. Furthermore, conserved iTSSs are enriched for regulatory motifs, suggesting that they are regulated, and they tend to eliminate polar effects, which confirms that they are functional. In contrast, the transcription of antisense TSSs located inside CDSs (aTSSs) was significantly less likely to be conserved (22%). However, aTSSs whose transcription was conserved often have conserved promoter motifs and drive the expression of nearby genes. Overall, our findings demonstrate that some internal TSSs are conserved and drive protein expression despite their unusual locations, but the majority are not conserved and may reflect noisy initiation of transcription rather than a biological function.« less

Crystal structure of a c-kit promoter quadruplex reveals the structural role of metal ions and water molecules in maintaining loop conformation.

PubMed

Wei, Dengguo; Parkinson, Gary N; Reszka, Anthony P; Neidle, Stephen

2012-05-01

We report here the 1.62 Å crystal structure of an intramolecular quadruplex DNA formed from a sequence in the promoter region of the c-kit gene. This is the first reported crystal structure of a promoter quadruplex and the first observation of localized magnesium ions in a quadruplex structure. The structure reveals that potassium and magnesium ions have an unexpected yet significant structural role in stabilizing particular quadruplex loops and grooves that is distinct from but in addition to the role of potassium ions in the ion channel at the centre of all quadruplex structures. The analysis also shows how ions cluster together with structured water molecules to stabilize the quadruplex arrangement. This particular quadruplex has been previously studied by NMR methods, and the present X-ray structure is in accord with the earlier topology assignment. However, as well as the observations of potassium and magnesium ions, the crystal structure has revealed a highly significant difference in the dimensions of the large cleft in the structure, which is a plausible target for small molecules. This difference can be understood by the stabilizing role of structured water networks.

The neural representation of unexpected uncertainty during value-based decision making.

PubMed

Payzan-LeNestour, Elise; Dunne, Simon; Bossaerts, Peter; O'Doherty, John P

2013-07-10

Uncertainty is an inherent property of the environment and a central feature of models of decision-making and learning. Theoretical propositions suggest that one form, unexpected uncertainty, may be used to rapidly adapt to changes in the environment, while being influenced by two other forms: risk and estimation uncertainty. While previous studies have reported neural representations of estimation uncertainty and risk, relatively little is known about unexpected uncertainty. Here, participants performed a decision-making task while undergoing functional magnetic resonance imaging (fMRI), which, in combination with a Bayesian model-based analysis, enabled us to separately examine each form of uncertainty examined. We found representations of unexpected uncertainty in multiple cortical areas, as well as the noradrenergic brainstem nucleus locus coeruleus. Other unique cortical regions were found to encode risk, estimation uncertainty, and learning rate. Collectively, these findings support theoretical models in which several formally separable uncertainty computations determine the speed of learning. Copyright © 2013 Elsevier Inc. All rights reserved.

Magnetization dynamics in dilute Pd1-xFex thin films and patterned microstructures considered for superconducting electronics

NASA Astrophysics Data System (ADS)

Golovchanskiy, I. A.; Bolginov, V. V.; Abramov, N. N.; Stolyarov, V. S.; Ben Hamida, A.; Chichkov, V. I.; Roditchev, D.; Ryazanov, V. V.

2016-10-01

Motivated by recent burst of applications of ferromagnetic layers in superconducting digital and quantum elements, we study the magnetism of thin films and patterned microstructures of Pd0.99Fe0.01. In this diluted ferromagnetic system, a high-sensitivity ferromagnetic resonance (FMR) experiment reveals spectroscopic signatures of re-magnetization and enables the estimation of the saturation magnetization, the anisotropy field, and the Gilbert damping constant. The detailed analysis of FMR spectra links the observed unexpectedly high reduced anisotropy field (0.06-0.14) with the internal anisotropy, points towards a cluster nature of the ferromagnetism, and allows estimating characteristic time scale for magnetization dynamics in Pd-Fe based cryogenic memory elements to ( 3 - 5 ) × 10 - 9 s.

FRET detection of lymphocyte function–associated antigen-1 conformational extension

PubMed Central

Chigaev, Alexandre; Smagley, Yelena; Haynes, Mark K.; Ursu, Oleg; Bologa, Cristian G.; Halip, Liliana; Oprea, Tudor; Waller, Anna; Carter, Mark B.; Zhang, Yinan; Wang, Wei; Buranda, Tione; Sklar, Larry A.

2015-01-01

Lymphocyte function–associated antigen 1 (LFA-1, CD11a/CD18, αLβ2-integrin) and its ligands are essential for adhesion between T-cells and antigen-presenting cells, formation of the immunological synapse, and other immune cell interactions. LFA-1 function is regulated through conformational changes that include the modulation of ligand binding affinity and molecular extension. However, the relationship between molecular conformation and function is unclear. Here fluorescence resonance energy transfer (FRET) with new LFA-1–specific fluorescent probes showed that triggering of the pathway used for T-cell activation induced rapid unquenching of the FRET signal consistent with extension of the molecule. Analysis of the FRET quenching at rest revealed an unexpected result that can be interpreted as a previously unknown LFA-1 conformation. PMID:25378583

Impact of a Child-Based Health Promotion Service-Learning Project on the Growth of Occupational Therapy Students.

PubMed

Lau, Cynthia

2016-01-01

This phenomenological study revealed the lived experiences of occupational therapy students as they embarked on a semester-long volunteer health promotion service-learning project during their entry-level master's program. Data analysis extrapolated themes from student journals, transcriptions of pre- and postinterviews, and field notes. Student roles were exemplified by what students wanted to learn, what they actually learned, and the unexpected benefits they experienced. In particular, issues with teaming, interprofessional development, and time management were discovered. The findings add to the growing literature about the benefits of service learning as a teaching strategy and how it facilitates mindfulness of community service, communication, and clinical reasoning of future therapists. Implications for learning and practice are discussed. Copyright © 2016 by the American Occupational Therapy Association, Inc.

Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase

PubMed Central

Lucas, James E; Siegel, Justin B

2015-01-01

Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses. PMID:25752240

Can we still learn something from the relationship between fertility and mother's employment? Evidence from developing countries.

PubMed

Cáceres-Delpiano, Julio

2012-02-01

In this work, I study the impact of fertility on mothers' employment for a sample of developing countries. Using the event of multiple births as an instrumental variable (IV) for fertility, I find that having children has a negative impact on female employment. In addition, three types of heterogeneity are found. First, the magnitude of the impact depends on the birth at which the increase in fertility takes place. Second, the types of jobs affected by a fertility shock (multiple births) are jobs identified with a higher degree of informality, such as self-employment or unpaid jobs. Finally, the heterogeneity analysis reveals that an unexpected change in fertility is stronger at a higher education level of the mother and in urban areas.

Synthesis, Characterization, and Theoretical Considerations of 1,2-bis(oxyamino)ethane Salts

NASA Technical Reports Server (NTRS)

Crake, Greg; Hawkins, Tom; Hall, Leslie; Tollison, Kerri; Brand, Adam

2003-01-01

The synthesis, characterization, theoretical calculations, and safety studies of energetic salts of 1,2- bis(oxyamino) ethane, (H2N-O-CH2-CH2-O-NH2), were carried out. The salts were characterized by vibrational (infrared, Raman), multinuclear nmr studies (1H, 13C), differential scanning calorimetry (DSC); elemental analysis; and initial safety testing (impact and friction sensitivity) . Theoretical calculations on the neutral, monoprotonated, and doubly protonated species of ethylene bisoxyamine were carried out using xxxx level of theory for the lowest energy structure and these theoretical results compared with the experimentally observed bond distances and vibrational (ir, Raman) frequency values. The single crystal X-ray diffraction study was carried out on the mono-perchlorate salt revealing a high degree of hydrogen bonding with an unexpected structure.

On the topology of chromatin fibres

PubMed Central

Barbi, Maria; Mozziconacci, Julien; Victor, Jean-Marc; Wong, Hua; Lavelle, Christophe

2012-01-01

The ability of cells to pack, use and duplicate DNA remains one of the most fascinating questions in biology. To understand DNA organization and dynamics, it is important to consider the physical and topological constraints acting on it. In the eukaryotic cell nucleus, DNA is organized by proteins acting as spools on which DNA can be wrapped. These proteins can subsequently interact and form a structure called the chromatin fibre. Using a simple geometric model, we propose a general method for computing topological properties (twist, writhe and linking number) of the DNA embedded in those fibres. The relevance of the method is reviewed through the analysis of magnetic tweezers single molecule experiments that revealed unexpected properties of the chromatin fibre. Possible biological implications of these results are discussed. PMID:24098838

Opsin vs opsin: New materials for biotechnological applications

NASA Astrophysics Data System (ADS)

Alfinito, Eleonora; Reggiani, Lino

2014-08-01

The need of new diagnostic methods satisfying, as an early detection, a low invasive procedure and a cost-efficient value, is orienting the technological research toward the use of bio-integrated devices, in particular, bio-sensors. The set of know-why necessary to achieve this goal is wide, from biochemistry to electronics and is summarized in an emerging branch of electronics, called proteotronics. Proteotronics is here applied to state a comparative analysis of the electrical responses coming from type-1 and type-2 opsins. In particular, the procedure is used as an early investigation of a recently discovered family of opsins, the proteorhodopsins activated by blue light, BPRs. The results reveal some interesting and unexpected similarities between proteins of the two families, suggesting the global electrical response are not strictly linked to the class identity.

Unexpected Control Structure Interaction on International Space Station

NASA Technical Reports Server (NTRS)

Gomez, Susan F.; Platonov, Valery; Medina, Elizabeth A.; Borisenko, Alexander; Bogachev, Alexey

2017-01-01

On June 23, 2011, the International Space Station (ISS) was performing a routine 180 degree yaw maneuver in support of a Russian vehicle docking when the on board Russian Segment (RS) software unexpectedly declared two attitude thrusters failed and switched thruster configurations in response to unanticipated ISS dynamic motion. Flight data analysis after the maneuver indicated that higher than predicted structural loads had been induced at various locations on the United States (U.S.) segment of the ISS. Further analysis revealed that the attitude control system was firing thrusters in response to both structural flex and rigid body rates, which resonated the structure and caused high loads and fatigue cycles. It was later determined that the thruster themselves were healthy. The RS software logic, which was intended to react to thruster failures, had instead been heavily influenced by interaction between the control system and structural flex. This paper will discuss the technical aspects of the control structure interaction problem that led to the RS control system firing thrusters in response to structural flex, the factors that led to insufficient preflight analysis of the thruster firings, and the ramifications the event had on the ISS. An immediate consequence included limiting which thrusters could be used for attitude control. This complicated the planning of on-orbit thruster events and necessitated the use of suboptimal thruster configurations that increased propellant usage and caused thruster lifetime usage concerns. In addition to the technical aspects of the problem, the team dynamics and communication shortcomings that led to such an event happening in an environment where extensive analysis is performed in support of human space flight will also be examined. Finally, the technical solution will be presented, which required a multidisciplinary effort between the U.S. and Russian control system engineers and loads and dynamics structural engineers to develop and implement an extensive modification in the RS software logic for ISS attitude control thruster firings.

Out of place, out of mind: Schema-driven false memory effects for object-location bindings.

PubMed

Lew, Adina R; Howe, Mark L

2017-03-01

Events consist of diverse elements, each processed in specialized neocortical networks, with temporal lobe memory systems binding these elements to form coherent event memories. We provide a novel theoretical analysis of an unexplored consequence of the independence of memory systems for elements and their bindings, 1 that raises the paradoxical prediction that schema-driven false memories can act solely on the binding of event elements despite the superior retrieval of individual elements. This is because if 2, or more, schema-relevant elements are bound together in unexpected conjunctions, the unexpected conjunction will increase attention during encoding to both the elements and their bindings, but only the bindings will receive competition with evoked schema-expected bindings. We test our model by examining memory for object-location bindings in recognition (Study 1) and recall (Studies 2 and 3) tasks. After studying schema-relevant objects in unexpected locations (e.g., pan on a stool in a kitchen scene), participants who then viewed these objects in expected locations (e.g., pan on stove) at test were more likely to falsely remember this object-location pairing as correct, compared with participants that viewed a different unexpected object-location pairing (e.g., pan on floor). In recall, participants were more likely to correctly remember individual schema-relevant objects originally viewed in unexpected, as opposed to expected locations, but were then more likely to misplace these items in the original room scene to expected places, relative to control schema-irrelevant objects. Our theoretical analysis and novel paradigm provide a tool for investigating memory distortions acting on binding processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

PubMed

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 .

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa

PubMed Central

Frank, Guido K.W.; Collier, Shaleise; Shott, Megan E.; O’Reilly, Randall C.

2016-01-01

Background Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls. Methods Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. Results Twenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error– and small volume–corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. Limitations This was a cross-sectional study, and the sample size was modest. Conclusion Anorexia nervosa after recovery is associated with heightened prediction error–related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study. PMID:26836623

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa.

PubMed

Frank, Guido K W; Collier, Shaleise; Shott, Megan E; O'Reilly, Randall C

2016-08-01

Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls. Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. Twenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error- and small volume-corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. This was a cross-sectional study, and the sample size was modest. Anorexia nervosa after recovery is associated with heightened prediction error-related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study.

New water soluble heterometallic complex showing unpredicted coordination modes of EDTA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mudsainiyan, R.K., E-mail: mudsainiyanrk@gmail.com; Jassal, A.K.; Chawla, S.K., E-mail: sukhvinder.k.chawla@gmail.com

2015-10-15

A mesoporous 3D polymeric complex (I) having formula ([Zr(IV)O-μ{sup 3}-(EDTA)Fe(III)OH]·H{sub 2}O){sub n} has been crystallized and characterized by various techniques. Single-crystal X-ray diffraction analysis revealed that complex (I) crystallized in chiral monoclinic space group Cc (space group no. 9) with unexpected coordination modes of EDTA and mixture of two transition metal ions. In this complex, the coordination number of Zr(IV) ion is seven where four carboxylate oxygen atoms, two nitrogen atoms, one oxide atom are coordinating with Zr(IV). Fe(III) is four coordinated and its coordination environment is composed of three different carboxylic oxygen atoms from three different EDTA and onemore » oxygen atom of –OH group. The structure consists of 4-c and 16-c (2-nodal) net with new topology and point symbol for net is (3{sup 36}·4{sup 54}·5{sup 30})·(3{sup 6}). TGA study and XRPD pattern showed that the coordination polymer is quite stable even after losing water molecule and –OH ion. Quenching behavior in fluorescence of ligand is observed by complexation with transition metal ions is due to n–π⁎ transition. The SEM micrograph shows the morphology of complex (I) exhibits spherical shape with size ranging from 50 to 280 nm. The minimum N{sub 2} (S{sub BET}=8.7693 m{sup 2}/g) and a maximum amount of H{sub 2} (high surface area=1044.86 m{sup 2}/g (STP)) could be adsorbed at 77 K. From DLS study, zeta potential is calculated i.e. −7.94 shows the negative charges on the surface of complex. Hirshfeld surface analysis and fingerprint plots revealed influence of weak or non bonding interactions in crystal packing of complex. - Graphical abstract: The complex (I) crystallized with unexpected coordination modes of EDTA having 4-c, 16-c net with new topology and point symbol is (3{sup 36}·4{sup 54}·5{sup 30})·(3{sup 6}). TGA study and XRPD pattern proved its stability with high preference of H{sub 2} uptake by complex. - Highlights: • 3D complex having unexpected coordination modes of EDTA with Zr(IV) and Fe(III). • The structure consists of 4-c and 16-c (2-nodal) net with new topology. • Reasonable S{sub BET} (8.7693 m{sup 2}/g) but high H{sub 2} uptake (1044.86 m{sup 2}/g) due to limited pore size. • Quenching behavior due to n–π⁎ transition by complexation with transition metal ions. • From DLS study, zeta potential value is −7.94.« less

Unexpected infant death due to hypoplastic left heart syndrome: a case report.

PubMed

Hayashizaki, Yoshie; Usui, Kiyotaka; Moriya, Takuya; Hashiyada, Masaki; Usui, Akihito; Hosokai, Yoshiyuki; Kawasumi, Yusuke; Saito, Haruo; Funayama, Masato

2011-11-01

A female infant was found unresponsive at home. The mother alleged that she delivered the baby at home 13 days prior to the death. The mother did not have any prenatal examinations during the pregnancy and the infant was not examined by a doctor until death. The autopsy revealed that the cause of death was hypoplastic left heart syndrome (HLHS) and the infant's chest showed bilateral breast enlargement. Forensic pathologists may encounter very rare pathological findings with unexpected infant deaths. Some, like HLHS, are serious congenital heart defects related to the cause of death, and others are unique phenomena unrelated to the cause of death such as breast swelling and discharge called "witch's milk." In this case, we observed both findings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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.

Molecular complexity of successive bacterial epidemics deconvoluted by comparative pathogenomics.

PubMed

Beres, Stephen B; Carroll, Ronan K; Shea, Patrick R; Sitkiewicz, Izabela; Martinez-Gutierrez, Juan Carlos; Low, Donald E; McGeer, Allison; Willey, Barbara M; Green, Karen; Tyrrell, Gregory J; Goldman, Thomas D; Feldgarden, Michael; Birren, Bruce W; Fofanov, Yuriy; Boos, John; Wheaton, William D; Honisch, Christiane; Musser, James M

2010-03-02

Understanding the fine-structure molecular architecture of bacterial epidemics has been a long-sought goal of infectious disease research. We used short-read-length DNA sequencing coupled with mass spectroscopy analysis of SNPs to study the molecular pathogenomics of three successive epidemics of invasive infections involving 344 serotype M3 group A Streptococcus in Ontario, Canada. Sequencing the genome of 95 strains from the three epidemics, coupled with analysis of 280 biallelic SNPs in all 344 strains, revealed an unexpectedly complex population structure composed of a dynamic mixture of distinct clonally related complexes. We discovered that each epidemic is dominated by micro- and macrobursts of multiple emergent clones, some with distinct strain genotype-patient phenotype relationships. On average, strains were differentiated from one another by only 49 SNPs and 11 insertion-deletion events (indels) in the core genome. Ten percent of SNPs are strain specific; that is, each strain has a unique genome sequence. We identified nonrandom temporal-spatial patterns of strain distribution within and between the epidemic peaks. The extensive full-genome data permitted us to identify genes with significantly increased rates of nonsynonymous (amino acid-altering) nucleotide polymorphisms, thereby providing clues about selective forces operative in the host. Comparative expression microarray analysis revealed that closely related strains differentiated by seemingly modest genetic changes can have significantly divergent transcriptomes. We conclude that enhanced understanding of bacterial epidemics requires a deep-sequencing, geographically centric, comparative pathogenomics strategy.

Emotional Disorder in XYY Children: Four Case Reports.

ERIC Educational Resources Information Center

Ratcliffe, Shirley G.; Field, Michael A. S.

1982-01-01

Four boys ages 7 to 9 years, who were identified at birth as having an XYY sex chromosome constitution, were studied in order to examine the thesis that XYY karyotype creates a predisposition to violent or antisocial childhood behavior. Results gave no support to this thesis, but reveal an unexpected shift towards a depression reaction to…

Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency

PubMed Central

2004-01-01

Abstract A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs. PMID:15072198

The State of Play: Gallup Survey of Principals on School Recess

ERIC Educational Resources Information Center

Robert Wood Johnson Foundation, 2010

2010-01-01

When most people talk about how to improve education, they tend to focus only on what happens in the classroom. But the most unexpected opportunity to boost learning lies outside the classroom: on the playground at recess. A new, first-of-its-kind Gallup poll reveals that elementary school principals overwhelmingly believe recess has a positive…

Complex within complex: integrative taxonomy reveals hidden diversity in Cicadetta brevipennis (Hemiptera: Cicadidae) and unexpected relationships with a song divergent relative

USDA-ARS?s Scientific Manuscript database

Multiple sources of data in combination are essential for species delimitation and classification of difficult taxonomic groups. Here we investigate a cicada taxon with unusual cryptic diversity and we attempt to resolve seemingly contradictory data sets. Cicada songs act as species-specific premati...

Competition can lead to unexpected patterns in tropical ant communities

NASA Astrophysics Data System (ADS)

Ellwood, M. D. Farnon; Blüthgen, Nico; Fayle, Tom M.; Foster, William A.; Menzel, Florian

2016-08-01

Ecological communities are structured by competitive, predatory, mutualistic and parasitic interactions combined with chance events. Separating deterministic from stochastic processes is possible, but finding statistical evidence for specific biological interactions is challenging. We attempt to solve this problem for ant communities nesting in epiphytic bird's nest ferns (Asplenium nidus) in Borneo's lowland rainforest. By recording the frequencies with which each and every single ant species occurred together, we were able to test statistically for patterns associated with interspecific competition. We found evidence for competition, but the resulting co-occurrence pattern was the opposite of what we expected. Rather than detecting species segregation-the classical hallmark of competition-we found species aggregation. Moreover, our approach of testing individual pairwise interactions mostly revealed spatially positive rather than negative associations. Significant negative interactions were only detected among large ants, and among species of the subfamily Ponerinae. Remarkably, the results from this study, and from a corroborating analysis of ant communities known to be structured by competition, suggest that competition within the ants leads to species aggregation rather than segregation. We believe this unexpected result is linked with the displacement of species following asymmetric competition. We conclude that analysing co-occurrence frequencies across complete species assemblages, separately for each species, and for each unique pairwise combination of species, represents a subtle yet powerful way of detecting structure and compartmentalisation in ecological communities.

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

PubMed

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.

The role of trauma scoring in developing trauma clinical governance in the Defence Medical Services

PubMed Central

Russell, R. J.; Hodgetts, T. J.; McLeod, J.; Starkey, K.; Mahoney, P.; Harrison, K.; Bell, E.

2011-01-01

This paper discusses mathematical models of expressing severity of injury and probability of survival following trauma and their use in establishing clinical governance of a trauma system. There are five sections: (i) Historical overview of scoring systems—anatomical, physiological and combined systems and the advantages and disadvantages of each. (ii) Definitions used in official statistics—definitions of ‘killed in action’ and other categories and the importance of casualty reporting rates and comparison across conflicts and nationalities. (iii) Current scoring systems and clinical governance—clinical governance of the trauma system in the Defence Medical Services (DMS) by using trauma scoring models to analyse injury and clinical patterns. (iv) Unexpected outcomes—unexpected outcomes focus clinical governance tools. Unexpected survivors signify good practice to be promulgated. Unexpected deaths pick up areas of weakness to be addressed. Seventy-five clinically validated unexpected survivors were identified over 2 years during contemporary combat operations. (v) Future developments—can the trauma scoring methods be improved? Trauma scoring systems use linear approaches and have significant weaknesses. Trauma and its treatment is a complex system. Nonlinear methods need to be investigated to determine whether these will produce a better approach to the analysis of the survival from major trauma. PMID:21149354

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

PubMed

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.

Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xia; Liu, Siwen; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016

2015-11-15

Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteinsmore » and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.« less

A Weighted and Directed Interareal Connectivity Matrix for Macaque Cerebral Cortex

PubMed Central

Markov, N. T.; Ercsey-Ravasz, M. M.; Ribeiro Gomes, A. R.; Lamy, C.; Magrou, L.; Vezoli, J.; Misery, P.; Falchier, A.; Quilodran, R.; Gariel, M. A.; Sallet, J.; Gamanut, R.; Huissoud, C.; Clavagnier, S.; Giroud, P.; Sappey-Marinier, D.; Barone, P.; Dehay, C.; Toroczkai, Z.; Knoblauch, K.; Van Essen, D. C.; Kennedy, H.

2014-01-01

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks. PMID:23010748

Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach

PubMed Central

Nanda, Neha; Dhawan, Devinder K.; Bhatia, Alka; Mahmood, Akhtar; Mahmood, Safrun

2016-01-01

Background Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. Materials & Methods In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats. Results Doxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers. Conclusion These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects. PMID:26998758

Sequence analysis of Jembrana disease virus strains reveals a genetically stable lentivirus.

PubMed

Desport, Moira; Stewart, Meredith E; Mikosza, Andrew S; Sheridan, Carol A; Peterson, Shane E; Chavand, Olivier; Hartaningsih, Nining; Wilcox, Graham E

2007-06-01

Jembrana disease virus (JDV) is a lentivirus associated with an acute disease syndrome with a 20% case fatality rate in Bos javanicus (Bali cattle) in Indonesia, occurring after a short incubation period and with no recurrence of the disease after recovery. Partial regions of gag and pol and the entire env were examined for sequence variation in DNA samples from cases of Jembrana disease obtained from Bali, Sumatra and South Kalimantan in Indonesian Borneo. A high level of nucleotide conservation (97-100%) was observed in gag sequences from samples taken in Bali and Sumatra, indicating that the source of JDV in Sumatra was most likely to have originated from Bali. The pol sequences and, unexpectedly, the env sequences from Bali samples were also well conserved with low nucleotide (96-99%) and amino acid substitutions (95-99%). However, the sample from South Kalimantan (JDV(KAL/01)) contained more divergent sequences, particularly in env (88% identity). Phylogenetic analysis revealed that the JDV(KAL/01)env sequences clustered with the sequence from the Pulukan sample (Bali) from 2001. JDV appears to be remarkably stable genetically and has undergone minor genetic changes over a period of nearly 20 years in Bali despite becoming endemic in the cattle population of the island.

A Splice Defect in the EDA Gene in Dogs with an X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) Phenotype.

PubMed

Waluk, Dominik P; Zur, Gila; Kaufmann, Ronnie; Welle, Monika M; Jagannathan, Vidhya; Drögemüller, Cord; Müller, Eliane J; Leeb, Tosso; Galichet, Arnaud

2016-09-08

X-linked hypohidrotic ectodermal dysplasia (XLHED) caused by variants in the EDA gene represents the most common ectodermal dysplasia in humans. We investigated three male mixed-breed dogs with an ectodermal dysplasia phenotype characterized by marked hypotrichosis and multifocal complete alopecia, almost complete absence of sweat and sebaceous glands, and altered dentition with missing and abnormally shaped teeth. Analysis of SNP chip genotypes and whole genome sequence data from the three affected dogs revealed that the affected dogs shared the same haplotype on a large segment of the X-chromosome, including the EDA gene. Unexpectedly, the whole genome sequence data did not reveal any nonsynonymous EDA variant in the affected dogs. We therefore performed an RNA-seq experiment on skin biopsies to search for changes in the transcriptome. This analysis revealed that the EDA transcript in the affected dogs lacked 103 nucleotides encoded by exon 2. We speculate that this exon skipping is caused by a genetic variant located in one of the large introns flanking this exon, which was missed by whole genome sequencing with the illumina short read technology. The altered EDA transcript splicing most likely causes the observed ectodermal dysplasia in the affected dogs. These dogs thus offer an excellent opportunity to gain insights into the complex splicing processes required for expression of the EDA gene, and other genes with large introns. Copyright © 2016 Waluk et al.

Image-based compound profiling reveals a dual inhibitor of tyrosine kinase and microtubule polymerization.

PubMed

Tanabe, Kenji

2016-04-27

Small-molecule compounds are widely used as biological research tools and therapeutic drugs. Therefore, uncovering novel targets of these compounds should provide insights that are valuable in both basic and clinical studies. I developed a method for image-based compound profiling by quantitating the effects of compounds on signal transduction and vesicle trafficking of epidermal growth factor receptor (EGFR). Using six signal transduction molecules and two markers of vesicle trafficking, 570 image features were obtained and subjected to multivariate analysis. Fourteen compounds that affected EGFR or its pathways were classified into four clusters, based on their phenotypic features. Surprisingly, one EGFR inhibitor (CAS 879127-07-8) was classified into the same cluster as nocodazole, a microtubule depolymerizer. In fact, this compound directly depolymerized microtubules. These results indicate that CAS 879127-07-8 could be used as a chemical probe to investigate both the EGFR pathway and microtubule dynamics. The image-based multivariate analysis developed herein has potential as a powerful tool for discovering unexpected drug properties.

Great majority of recombination events in Arabidopsis are gene conversion events

PubMed Central

Yang, Sihai; Yuan, Yang; Wang, Long; Li, Jing; Wang, Wen; Liu, Haoxuan; Chen, Jian-Qun; Hurst, Laurence D.; Tian, Dacheng

2012-01-01

The evolutionary importance of meiosis may not solely be associated with allelic shuffling caused by crossing-over but also have to do with its more immediate effects such as gene conversion. Although estimates of the crossing-over rate are often well resolved, the gene conversion rate is much less clear. In Arabidopsis, for example, next-generation sequencing approaches suggest that the two rates are about the same, which contrasts with indirect measures, these suggesting an excess of gene conversion. Here, we provide analysis of this problem by sequencing 40 F2 Arabidopsis plants and their parents. Small gene conversion tracts, with biased gene conversion content, represent over 90% (probably nearer 99%) of all recombination events. The rate of alteration of protein sequence caused by gene conversion is over 600 times that caused by mutation. Finally, our analysis reveals recombination hot spots and unexpectedly high recombination rates near centromeres. This may be responsible for the previously unexplained pattern of high genetic diversity near Arabidopsis centromeres. PMID:23213238

Creative Commons licenses and the non-commercial condition: Implications for the re-use of biodiversity information

PubMed Central

Hagedorn, Gregor; Mietchen, Daniel; Morris, Robert A.; Agosti, Donat; Penev, Lyubomir; Berendsohn, Walter G.; Hobern, Donald

2011-01-01

Abstract The Creative Commons (CC) licenses are a suite of copyright-based licenses defining terms for the distribution and re-use of creative works. CC provides licenses for different use cases and includes open content licenses such as the Attribution license (CC BY, used by many Open Access scientific publishers) and the Attribution Share Alike license (CC BY-SA, used by Wikipedia, for example). However, the license suite also contains non-free and non-open licenses like those containing a “non-commercial” (NC) condition. Although many people identify “non-commercial” with “non-profit”, detailed analysis reveals that significant differences exist and that the license may impose some unexpected re-use limitations on works thus licensed. After providing background information on the concepts of Creative Commons licenses in general, this contribution focuses on the NC condition, its advantages, disadvantages and appropriate scope. Specifically, it contributes material towards a risk analysis for potential re-users of NC-licensed works. PMID:22207810

Creative Commons licenses and the non-commercial condition: Implications for the re-use of biodiversity information.

PubMed

Hagedorn, Gregor; Mietchen, Daniel; Morris, Robert A; Agosti, Donat; Penev, Lyubomir; Berendsohn, Walter G; Hobern, Donald

2011-01-01

The Creative Commons (CC) licenses are a suite of copyright-based licenses defining terms for the distribution and re-use of creative works. CC provides licenses for different use cases and includes open content licenses such as the Attribution license (CC BY, used by many Open Access scientific publishers) and the Attribution Share Alike license (CC BY-SA, used by Wikipedia, for example). However, the license suite also contains non-free and non-open licenses like those containing a "non-commercial" (NC) condition. Although many people identify "non-commercial" with "non-profit", detailed analysis reveals that significant differences exist and that the license may impose some unexpected re-use limitations on works thus licensed. After providing background information on the concepts of Creative Commons licenses in general, this contribution focuses on the NC condition, its advantages, disadvantages and appropriate scope. Specifically, it contributes material towards a risk analysis for potential re-users of NC-licensed works.

Cryptozoology Society

NASA Astrophysics Data System (ADS)

Richman, Barbara T.

Reports of Loch Ness monsters, Bigfoot, and the Yeti spring u p from time to time, sparking scientific controversy about the veracity of these observations. Now an organization has been established to help cull, analyze, and disseminate information on the alleged creatures. The International Society of Cryptozoology, formed at a January meeting at the U.S. National Museum of Natural History of the Smithsonian Institution, will serve as the focal point for the investigation, analysis, publication, and discussion of animals of unexpected form or size or of unexpected occurrences in time or space.

Toxicity assessment of ash and dust from handmade gold jewelry manufacturing workshops in Bangladesh.

PubMed

Sikder, Arif M; Hossain, Tanvir; Khan, Manzurul H; Aziz Hasan, M; Fakhruzzaman, M; Turner, Joseph B; Pestov, Dmitry; McCallister, Leigh S; Maudood Elahi, K

2017-06-01

Traditionally, handmade gold jewelry played a very important role in the cultural heritage of Bangladesh. Goldsmiths still are partially using ancient manufacturing process with coal fire, candle flame blowing, and nitric and sulfuric acid treatments. Such process leads to the contamination of workplace with the dust of toxic metals, acidic vapors, and particles of different natures. To evaluate contamination by particulate matter (PM), the passive particle collectors were installed in different manufacturing units for a period of 85 days at Tanti Bazar, Dhaka, Bangladesh. The laser diffraction analysis of the samples collected at the soldering units showed significant amounts of particulates, both PM10 and PM 2.5, and also nanoparticles in both nucleation and accumulation mode. SEM/EDS analysis revealed partially melted micro blebs that contain a very high concentration of Fe along with Cu. The toxic elements were detected with ICP analysis and include higher concentrations of cadmium (Cd), chromium (Cr), lead (Pb), and arsenic (As). It is notable that detection of arsenic contamination was unexpected since raw materials used for jewelry making should not have any arsenic.

A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation.

PubMed

Bleichert, Franziska; Balasov, Maxim; Chesnokov, Igor; Nogales, Eva; Botchan, Michael R; Berger, James M

2013-10-08

In eukaryotes, DNA replication requires the origin recognition complex (ORC), a six-subunit assembly that promotes replisome formation on chromosomal origins. Despite extant homology between certain subunits, the degree of structural and organizational overlap between budding yeast and metazoan ORC has been unclear. Using 3D electron microscopy, we determined the subunit organization of metazoan ORC, revealing that it adopts a global architecture very similar to the budding yeast complex. Bioinformatic analysis extends this conservation to Orc6, a subunit of somewhat enigmatic function. Unexpectedly, a mutation in the Orc6 C-terminus linked to Meier-Gorlin syndrome, a dwarfism disorder, impedes proper recruitment of Orc6 into ORC; biochemical studies reveal that this region of Orc6 associates with a previously uncharacterized domain of Orc3 and is required for ORC function and MCM2-7 loading in vivo. Together, our results suggest that Meier-Gorlin syndrome mutations in Orc6 impair the formation of ORC hexamers, interfering with appropriate ORC functions. DOI:http://dx.doi.org/10.7554/eLife.00882.001.

Knowledge discovery by accuracy maximization

PubMed Central

Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

2014-01-01

Here we describe KODAMA (knowledge discovery by accuracy maximization), an unsupervised and semisupervised learning algorithm that performs feature extraction from noisy and high-dimensional data. Unlike other data mining methods, the peculiarity of KODAMA is that it is driven by an integrated procedure of cross-validation of the results. The discovery of a local manifold’s topology is led by a classifier through a Monte Carlo procedure of maximization of cross-validated predictive accuracy. Briefly, our approach differs from previous methods in that it has an integrated procedure of validation of the results. In this way, the method ensures the highest robustness of the obtained solution. This robustness is demonstrated on experimental datasets of gene expression and metabolomics, where KODAMA compares favorably with other existing feature extraction methods. KODAMA is then applied to an astronomical dataset, revealing unexpected features. Interesting and not easily predictable features are also found in the analysis of the State of the Union speeches by American presidents: KODAMA reveals an abrupt linguistic transition sharply separating all post-Reagan from all pre-Reagan speeches. The transition occurs during Reagan’s presidency and not from its beginning. PMID:24706821

Probing Dominant Negative Behavior of Glucocorticoid Receptor β through a Hybrid Structural and Biochemical Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Min, Jungki; Perera, Lalith; Krahn, Juno M.

ABSTRACT Glucocorticoid receptor β (GRβ) is associated with glucocorticoid resistance via dominant negative regulation of GRα. To better understand how GRβ functions as a dominant negative inhibitor of GRα at a molecular level, we determined the crystal structure of the ligand binding domain of GRβ complexed with the antagonist RU-486. The structure reveals that GRβ binds RU-486 in the same ligand binding pocket as GRα, and the unique C-terminal amino acids of GRβ are mostly disordered. Binding energy analysis suggests that these C-terminal residues of GRβ do not contribute to RU-486 binding. Intriguingly, the GRβ/RU-486 complex binds corepressor peptide withmore » affinity similar to that of a GRα/RU-486 complex, despite the lack of helix 12. Our biophysical and biochemical analyses reveal that in the presence of RU-486, GRβ is found in a conformation that favors corepressor binding, potentially antagonizing GRα function. This study thus presents an unexpected molecular mechanism by which GRβ could repress transcription.« less

Unexpected high 35S concentration revealing strong downward transport of stratospheric air during the monsoon transitional period in East Asia

NASA Astrophysics Data System (ADS)

Lin, Mang; Zhang, Zhisheng; Su, Lin; Su, Binbin; Liu, Lanzhong; Tao, Jun; Fung, Jimmy C. H.; Thiemens, Mark H.

2016-03-01

October is the monsoon transitional period in East Asia (EA) involving a series of synoptic activities that may enhance the downward transport of stratospheric air to the planetary boundary layer (PBL). Here we use cosmogenic 35S in sulfate aerosols (35SO42-) as a tracer for air masses originating from the stratosphere and transported downward to quantify these mixing processes. From 1 year 35SO42- measurements (March 2014 to February 2015) at a background station in EA we find remarkably enhanced 35SO42- concentration (3150 atoms m-3) in October, the highest value ever reported for natural sulfate aerosols. A four-box 1-D model and meteorological analysis reveal that strong downward transport from the free troposphere is a vital process entraining aged stratospheric air masses to the PBL. The aged stratospheric masses are accumulated in the PBL, accelerating the SO2 transformation to SO42-. Implications for the tropospheric O3 budget and the CO2 biogeochemical cycle are discussed.

Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer’s disease

PubMed Central

Berchtold, Nicole C.; Coleman, Paul D.; Cribbs, David H.; Rogers, Joseph; Gillen, Daniel L.; Cotman, Carl W.

2014-01-01

Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer’s disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20–99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD. PMID:23273601

Regulation of Memory Formation by the Transcription Factor XBP1.

PubMed

Martínez, Gabriela; Vidal, René L; Mardones, Pablo; Serrano, Felipe G; Ardiles, Alvaro O; Wirth, Craig; Valdés, Pamela; Thielen, Peter; Schneider, Bernard L; Kerr, Bredford; Valdés, Jose L; Palacios, Adrian G; Inestrosa, Nibaldo C; Glimcher, Laurie H; Hetz, Claudio

2016-02-16

Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells

PubMed Central

Hainer, Sarah J; McCannell, Kurtis N; Yu, Jun; Ee, Ly-Sha; Zhu, Lihua J; Rando, Oliver J; Fazzio, Thomas G

2016-01-01

Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3. We show that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, we find Mbd2 and Mbd3 are interdependent for chromatin association. Further investigation reveals that both proteins are required for normal levels of cytosine methylation and hydroxymethylation in murine embryonic stem cells. Furthermore, Mbd2 and Mbd3 regulate overlapping sets of genes that are also regulated by DNA methylation/hydroxymethylation factors. These findings reveal an interdependent regulatory mechanism mediated by the DNA methylation machinery and its readers. DOI: http://dx.doi.org/10.7554/eLife.21964.001 PMID:27849519

Vanadium Oxide Thin Films Alloyed with Ti, Zr, Nb, and Mo for Uncooled Infrared Imaging Applications

NASA Astrophysics Data System (ADS)

Ozcelik, Adem; Cabarcos, Orlando; Allara, David L.; Horn, Mark W.

2013-05-01

Microbolometer-grade vanadium oxide (VO x ) thin films with 1.3 < x < 2.0 were prepared by pulsed direct-current (DC) sputtering using substrate bias in a controlled oxygen and argon environment. These films were systematically alloyed with Ti, Nb, Mo, and Zr using a second gun and radiofrequency (RF) reactive co-sputtering to probe the effects of the transition metals on the film charge transport characteristics. The results reveal that the temperature coefficient of resistance (TCR) and resistivity are unexpectedly similar for alloyed and unalloyed films up to alloy compositions in the ˜20 at.% range. Analysis of the film structures for the case of the 17% Nb-alloyed film by glancing-angle x-ray diffraction and transmission electron microscopy shows that the microstructure remains even with the addition of high concentrations of alloy metal, demonstrating the robust character of the VO x films to maintain favorable electrical transport properties for bolometer applications. Postdeposition thermal annealing of the alloyed VO x films further reveals improvement of electrical properties compared with unalloyed films, indicating a direction for further improvements in the materials.

Analysis on an illusion unexpected occurred on a moving statue leaving in fact but approaching by environmental judgment

NASA Astrophysics Data System (ADS)

He, Youwu; Li, Zhifang; Qiu, Yishen; Li, Hui

2017-08-01

Earlier this year we visited Sanya, Hainan Province, China. There is a huge statue, the South Sea Avalokitesvara (南海观世音菩萨), at Sanya Nanshan Buddhism Cultural Tourism Resort. When we were gazing at the statue on a leaving car on gradually rising road, an unexpected visual illusion took place in which the statue seemed running after us. In this presentation, an optical model is developed to explain the illusion occurred on a moving object leaving in fact but approaching by environmental judgement. Such an interesting illusion analysis will play a significant role in having students understood the main principles in geometrical optics.

Multilocus dataset reveals demographic histories of two peat mosses in Europe

PubMed Central

Szövényi, Péter; Hock, Zsófia; Schneller, Jakob J; Tóth, Zoltán

2007-01-01

Background Revealing the past and present demographic history of populations is of high importance to evaluate the conservation status of species. Demographic data can be obtained by direct monitoring or by analysing data of historical and recent collections. Although these methods provide the most detailed information they are very time consuming. Another alternative way is to make use of the information accumulated in the species' DNA over its history. Recent development of the coalescent theory makes it possible to reconstruct the demographic history of species using nucleotide polymorphism data. To separate the effect of natural selection and demography, multilocus analysis is needed because these two forces can produce similar patterns of polymorphisms. In this study we investigated the amount and pattern of sequence variability of a Europe wide sample set of two peat moss species (Sphagnum fimbriatum and S. squarrosum) with similar distributions and mating systems but presumably contrasting historical demographies using 3 regions of the nuclear genome (appr. 3000 bps). We aimed to draw inferences concerning demographic, and phylogeographic histories of the species. Results All three nuclear regions supported the presence of an Atlantic and Non-Atlantic clade of S. fimbriatum suggesting glacial survival of the species along the Atlantic coast of Europe. Contrarily, S. squarrosum haplotypes showed three clades but no geographic structure at all. Maximum likelihood, mismatch and Bayesian analyses supported a severe historical bottleneck and a relatively recent demographic expansion of the Non-Atlantic clade of S. fimbriatum, whereas size of S. squarrosum populations has probably decreased in the past. Species wide molecular diversity of the two species was nearly the same with an excess of replacement mutations in S. fimbriatum. Similar levels of molecular diversity, contrasting phylogeographic patterns and excess of replacement 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. PMID:17714592

Analysis of Position Error Headway Protection

DOT National Transportation Integrated Search

1975-07-01

An analysis is developed to determine safe headway on PRT systems that use point-follower control. Periodic measurements of the position error relative to a nominal trajectory provide warning against the hazards of overspeed and unexpected stop. A co...

The Unexpected in Primary Care: A Multicenter Study on the Emergence of Unvoiced Patient Agenda

PubMed Central

Peltenburg, Michael; Fischer, Joachim E.; Bahrs, Ottomar; van Dulmen, Sandra; van den Brink-Muinen, Atie

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 quantify the occurrence rate of emerging agendas in primary care practices and to explain the variation between patients and practices. METHODS This observational cross-sectional study involved 182 primary care practices in 9 European cultural regions. Consecutive primary care consultations were videotaped and rated. Patients completed preconsultation and postconsultation questionnaires assessing their expectations and perceived care. Emerging agenda, determined by using 11-item preconsultation and postconsultation questionnaires, was defined as care perceived by the patient to be in addition to expected care, after adjustment for cultural variations of patient expectations. RESULTS For consultations involving 2,243 patients (mean age, 44.8 years, 58.4% women), every sixth (15.8%) consultation revealed emerging psychosocial agenda. Biomedical agenda emerged in14.5% of the consultations. Rates for unmet expectations were 13.6% and 10.3%, respectively, for psychosocial and biomedical problems. Practices showed considerable heterogeneity of occurrence of emerging agenda (biomedical, median 13%, range 0%–67%; psychosocial, median 14%, range 0%–53%). After controlling for region and patient baseline characteristics, variables significantly related to emerging agenda were patient expectations and biomedical or psychosocial discourse content, but not consultation time or sex of the patient. A large proportion of the variance attributable to physicians remained concealed in a practice dummy variable (explaining up to 8% of the variance). CONCLUSION Unexpected agenda emerges in every sixth to seventh consultation in outpatient primary care visits. PMID:15576537

Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.

PubMed

Cory, Seth A; Van Vranken, Jonathan G; Brignole, Edward J; Patra, Shachin; Winge, Dennis R; Drennan, Catherine L; Rutter, Jared; Barondeau, David P

2017-07-03

In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters. Here we present crystallographic and electron microscopic structures of the SDA complex coupled to enzyme kinetic and cell-based studies to provide structure-function properties of a mitochondrial cysteine desulfurase. Unlike prokaryotic cysteine desulfurases, the SDA structure adopts an unexpected architecture in which a pair of ISD11 subunits form the dimeric core of the SDA complex, which clarifies the critical role of ISD11 in eukaryotic assemblies. The different quaternary structure results in an incompletely formed substrate channel and solvent-exposed pyridoxal 5'-phosphate cofactor and provides a rationale for the allosteric activator function of FXN in eukaryotic systems. The structure also reveals the 4'-phosphopantetheine-conjugated acyl-group of ACP occupies the hydrophobic core of ISD11, explaining the basis of ACP stabilization. The unexpected architecture for the SDA complex provides a framework for understanding interactions with acceptor proteins for sulfur-containing biosynthetic pathways, elucidating mechanistic details of eukaryotic Fe-S cluster biosynthesis, and clarifying how defects in Fe-S cluster assembly lead to diseases such as Friedreich's ataxia. Moreover, our results support a lock-and-key model in which LYR proteins associate with acyl-ACP as a mechanism for fatty acid biosynthesis to coordinate the expression, Fe-S cofactor maturation, and activity of the respiratory complexes.

Scn2a deletion improves survival and brain-heart dynamics in the Kcna1-null mouse model of sudden unexpected death in epilepsy (SUDEP).

PubMed

Mishra, Vikas; Karumuri, Bharat K; Gautier, Nicole M; Liu, Rui; Hutson, Timothy N; Vanhoof-Villalba, Stephanie L; Vlachos, Ioannis; Iasemidis, Leonidas; Glasscock, Edward

2017-06-01

People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings. The human epilepsy gene Kcna1 encodes voltage-gated Kv1.1 potassium channels that act to dampen neuronal excitability whereas Scn2a encodes voltage-gated Nav1.2 sodium channels important for action potential initiation and conduction. SUDEP-prone Kcna1-/- mice with partial genetic ablation of Nav1.2 channels (i.e. Scn2a+/-; Kcna1-/-) exhibited a two-fold increase in survival. Classical analysis of EEG and ECG recordings separately showed significantly decreased seizure durations in Scn2a+/-; Kcna1-/- mice compared with Kcna1-/- mice, without substantial modification of cardiac abnormalities. Novel analysis of the EEG and ECG together revealed a significant reduction in EEG-ECG association in Kcna1-/- mice compared with wild types, which was partially restored in Scn2a+/-; Kcna1-/- mice. The degree of EEG-ECG association was also proportional to the survival rate of mice across genotypes. These results show that Scn2a gene deletion acts as protective genetic modifier of SUDEP and suggest measures of brain-heart association as potential indices of SUDEP susceptibility. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Postmodern Feminism: Cultural Trauma in Construction of Female Identities in Virginia Woolf's "The Waves"

ERIC Educational Resources Information Center

Jamili, Leila Baradaran; Roshanzamir, Ziba

2017-01-01

The present article sheds new light on trauma as a devastating phenomenon respecting the construction of male and female characters' identities and reveals reconstruction of male and female identities in Virginia Woolf's (1882-1941) "The Waves" (1931). Trauma is defined as an unexpected event that leaves the most terrible marks on the…

Sequence tagging reveals unexpected modifications in toxicoproteomics

PubMed Central

Dasari, Surendra; Chambers, Matthew C.; Codreanu, Simona G.; Liebler, Daniel C.; Collins, Ben C.; Pennington, Stephen R.; Gallagher, William M.; Tabb, David L.

2010-01-01

Toxicoproteomic samples are rich in posttranslational modifications (PTMs) of proteins. Identifying these modifications via standard database searching can incur significant performance penalties. Here we describe the latest developments in TagRecon, an algorithm that leverages inferred sequence tags to identify modified peptides in toxicoproteomic data sets. TagRecon identifies known modifications more effectively than the MyriMatch database search engine. TagRecon outperformed state of the art software in recognizing unanticipated modifications from LTQ, Orbitrap, and QTOF data sets. We developed user-friendly software for detecting persistent mass shifts from samples. We follow a three-step strategy for detecting unanticipated PTMs in samples. First, we identify the proteins present in the sample with a standard database search. Next, identified proteins are interrogated for unexpected PTMs with a sequence tag-based search. Finally, additional evidence is gathered for the detected mass shifts with a refinement search. Application of this technology on toxicoproteomic data sets revealed unintended cross-reactions between proteins and sample processing reagents. Twenty five proteins in rat liver showed signs of oxidative stress when exposed to potentially toxic drugs. These results demonstrate the value of mining toxicoproteomic data sets for modifications. PMID:21214251

Transgenic mice reveal unexpected diversity of On-Off direction selective retinal ganglion cell subtypes and brain structures involved in motion processing

PubMed Central

Rivlin-Etzion, Michal; Zhou, Kaili; Wei, Wei; Elstrott, Justin; Nguyen, Phong L.; Barres, Ben; Huberman, Andrew D.; Feller, Marla B.

2011-01-01

On-Off direction selective retinal ganglion cells (DSGCs) encode the axis of visual motion. They respond strongly to an object moving in a preferred direction and weakly to an object moving in the opposite, ‘null’, direction. Historically, On-Off DSGCs were classified into 4 subtypes according to their directional preference (anterior, posterior, superior or inferior). Here, we compare two genetically identified populations of On-Off DSGCs: DRD4-DSGCs and TRHR-DSGCs. We find that although both populations are tuned for posterior motion, they can be distinguished by a variety of physiological and anatomical criteria. First, the directional tuning of TRHR-DSGCs is broader than that of DRD4-DSGCs. Second, whereas both populations project similarly to the dorsal lateral geniculate nucleus, they project differently to the ventral lateral geniculate nucleus and the superior colliculus. Moreover, TRHR-DSGCs, but not DRD4-DSGCs, also project to the zona incerta, a thalamic area not previously known to receive direction-tuned visual information. Our findings reveal unexpected diversity among mouse On-Off DSGC subtypes that uniquely process and convey image motion to the brain. PMID:21677160

Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome.

PubMed

Chang, Dong W; Hayashi, Shinichi; Gharib, Sina A; Vaisar, Tomas; King, S Trevor; Tsuchiya, Mitsuhiro; Ruzinski, John T; Park, David R; Matute-Bello, Gustavo; Wurfel, Mark M; Bumgarner, Roger; Heinecke, Jay W; Martin, Thomas R

2008-10-01

Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.

Opsin vs opsin: New materials for biotechnological applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alfinito, Eleonora, E-mail: eleonora.alfinito@unisalento.it; CNISM, Via della Vasca Navale, 84, 00146 Roma; Reggiani, Lino, E-mail: lino.reggiani@unisalento.it

2014-08-14

The need of new diagnostic methods satisfying, as an early detection, a low invasive procedure and a cost-efficient value, is orienting the technological research toward the use of bio-integrated devices, in particular, bio-sensors. The set of know-why necessary to achieve this goal is wide, from biochemistry to electronics and is summarized in an emerging branch of electronics, called proteotronics. Proteotronics is here applied to state a comparative analysis of the electrical responses coming from type-1 and type-2 opsins. In particular, the procedure is used as an early investigation of a recently discovered family of opsins, the proteorhodopsins activated by bluemore » light, BPRs. The results reveal some interesting and unexpected similarities between proteins of the two families, suggesting the global electrical response are not strictly linked to the class identity.« less

Structure and composition of the neutral upper atmosphere of Mars from the MAVEN NGIMS investigation

PubMed Central

Benna, M.; Elrod, M.; Yelle, R. V.; Bougher, S. W.; Stone, S. W.; Jakosky, B. M.

2015-01-01

Abstract The Mars Atmosphere and Volatile EvolutioN (MAVEN) Neutral Gas and Ion Mass Spectrometer (NGIMS) provides sensitive detections of neutral gas and ambient ion composition. NGIMS measurements of nine atomic and molecular neutral species, and their variation with altitude, latitude, and solar zenith angle are reported over several months of operation of the MAVEN mission. Sampling NGIMS signals from multiple neutral species every several seconds reveals persistent and unexpectedly large amplitude density structures. The scale height temperatures are mapped over the course of the first few months of the mission from high down to midlatitudes. NGIMS measurements near the homopause of 40Ar/N2 ratios agree with those reported by the Sample Analysis at Mars investigation and allow the altitude of the homopause for the most abundant gases to be established. PMID:27667873

Molecular analysis of ependymins from the cerebrospinal fluid of the orders Clupeiformes and Salmoniformes: no indication for the existence of an euteleost infradivision.

PubMed

Müller-Schmid, A; Ganss, B; Gorr, T; Hoffmann, W

1993-06-01

Ependymins represent the predominant protein constituents in the cerebrospinal fluid of many teleost fish and they are synthesized in meningeal fibroblasts. Here, we present the ependymin sequences from the herring (Clupea harengus) and the pike (Esox lucius). A comparison of ependymin homologous sequences from three different orders of teleost fish (Salmoniformes, Cypriniformes, and Clupeiformes) revealed the highest similarity between Clupeiformes and Cypriniformes. This result is unexpected because it does not reflect current systematics, in which Clupeiformes belong to a separate infradivision (Clupeomorpha) than Salmoniformes and Cypriniformes (Euteleostei). Furthermore, in Salmoniformes the evolutionary rate of ependymins seems to be accelerated mainly on the protein level. However, considering these inconstant rates, neither neighbor-joining trees nor DNA parsimony methods gave any indication that a separate euteleost infradivision exists.

The Personal Human Oral Microbiome Obscures the Effects of Treatment on Periodontal Disease

PubMed Central

Schwarzberg, Karen; Le, Rosalin; Bharti, Balambal; Lindsay, Suzanne; Casaburi, Giorgio; Salvatore, Francesco; Saber, Mohamed H.; Alonaizan, Faisal; Slots, Jørgen; Gottlieb, Roberta A.; Caporaso, J. Gregory; Kelley, Scott T.

2014-01-01

Periodontitis is a progressive disease of the periodontium with a complex, polymicrobial etiology. Recent Next-Generation Sequencing (NGS) studies of the microbial diversity associated with periodontitis have revealed strong, community-level differences in bacterial assemblages associated with healthy or diseased periodontal sites. In this study, we used NGS approaches to characterize changes in periodontal pocket bacterial diversity after standard periodontal treatment. Despite consistent changes in the abundance of certain taxa in individuals whose condition improved with treatment, post-treatment samples retained the highest similarity to pre-treatment samples from the same individual. Deeper phylogenetic analysis of periodontal pathogen-containing genera Prevotella and Fusobacterium found both unexpected diversity and differential treatment response among species. Our results highlight how understanding interpersonal variability among microbiomes is necessary for determining how polymicrobial diseases respond to treatment and disturbance. PMID:24489772

Use of an injection port for thermochemolysis-gas chromatography/mass spectrometry: rapid profiling of biomaterials.

PubMed

Shadkami, Farzad; Helleur, Robert

2009-07-31

A simple and direct approach was developed for thermochemolytic analysis of a wide range of biomolecules present in plant materials using an injection port of a gas chromatograph/mass spectrometer (GC/MS) and a novel solids injector consisting of a coiled stainless steel wire placed inside a modified needle syringe. Optimum thermochemolysis (or Thermally Assisted Hydrolysis/Methylation) was achieved by using a suitable methanolic solution of trimethylsulfonium hydroxide (TMSH) or tetramethylammonium hydroxide (TMAH) with an injection port temperature of 350 degrees C. Intact, methylated flavonoids, saccharides, phenolic and fatty acids, lignin dimers and diterpene resin acids were identified. Samples include tea leaves, hemicelluloses, lignin isolates and herbal medicines. Unexpected chromatographic results using TMAH reagent revealed the presence of intact methylated trisaccharides (658 Da) and structurally informative dimer lignin markers.

A benchmark for evaluation of algorithms for identification of cellular correlates of clinical outcomes.

PubMed

Aghaeepour, Nima; Chattopadhyay, Pratip; Chikina, Maria; Dhaene, Tom; Van Gassen, Sofie; Kursa, Miron; Lambrecht, Bart N; Malek, Mehrnoush; McLachlan, G J; Qian, Yu; Qiu, Peng; Saeys, Yvan; Stanton, Rick; Tong, Dong; Vens, Celine; Walkowiak, Sławomir; Wang, Kui; Finak, Greg; Gottardo, Raphael; Mosmann, Tim; Nolan, Garry P; Scheuermann, Richard H; Brinkman, Ryan R

2016-01-01

The Flow Cytometry: Critical Assessment of Population Identification Methods (FlowCAP) challenges were established to compare the performance of computational methods for identifying cell populations in multidimensional flow cytometry data. Here we report the results of FlowCAP-IV where algorithms from seven different research groups predicted the time to progression to AIDS among a cohort of 384 HIV+ subjects, using antigen-stimulated peripheral blood mononuclear cell (PBMC) samples analyzed with a 14-color staining panel. Two approaches (FlowReMi.1 and flowDensity-flowType-RchyOptimyx) provided statistically significant predictive value in the blinded test set. Manual validation of submitted results indicated that unbiased analysis of single cell phenotypes could reveal unexpected cell types that correlated with outcomes of interest in high dimensional flow cytometry datasets. © 2015 International Society for Advancement of Cytometry.

Oxidized crystalline (3 × 1)-O surface phases of InAs and InSb studied by high-resolution photoelectron spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuominen, M., E-mail: tmleir@utu.fi, E-mail: pekka.laukkanen@utu.fi; Lång, J.; Dahl, J.

2015-01-05

The pre-oxidized crystalline (3×1)-O structure of InAs(100) has been recently found to significantly improve insulator/InAs junctions for devices, but the atomic structure and formation of this useful oxide layer are not well understood. We report high-resolution photoelectron spectroscopy analysis of (3×1)-O on InAs(100) and InSb(100). The findings reveal that the atomic structure of (3×1)-O consists of In atoms with unexpected negative (between −0.64 and −0.47 eV) and only moderate positive (In{sub 2}O type) core-level shifts; highly oxidized group-V sites; and four different oxygen sites. These fingerprint shifts are compared to those of previously studied oxides of III-V to elucidate oxidation processes.

Toward A Social Policy Analysis Curriculum.

ERIC Educational Resources Information Center

Stimson, John; Stimson, Ardyth

An eight-course curriculum in social policy analysis which follows a policy analysis paradigm is proposed. The undergraduate curriculum concentrates on the ability to appreciate and operate under uncertainty; anticipation of interrelated, unexpected ramifications of new stimuli; understanding of the social construction of problems and their cures;…

Incorporating uncertainty into medical decision making: an approach to unexpected test results.

PubMed

Bianchi, Matt T; Alexander, Brian M; Cash, Sydney S

2009-01-01

The utility of diagnostic tests derives from the ability to translate the population concepts of sensitivity and specificity into information that will be useful for the individual patient: the predictive value of the result. As the array of available diagnostic testing broadens, there is a temptation to de-emphasize history and physical findings and defer to the objective rigor of technology. However, diagnostic test interpretation is not always straightforward. One significant barrier to routine use of probability-based test interpretation is the uncertainty inherent in pretest probability estimation, the critical first step of Bayesian reasoning. The context in which this uncertainty presents the greatest challenge is when test results oppose clinical judgment. It is this situation when decision support would be most helpful. The authors propose a simple graphical approach that incorporates uncertainty in pretest probability and has specific application to the interpretation of unexpected results. This method quantitatively demonstrates how uncertainty in disease probability may be amplified when test results are unexpected (opposing clinical judgment), even for tests with high sensitivity and specificity. The authors provide a simple nomogram for determining whether an unexpected test result suggests that one should "switch diagnostic sides.'' This graphical framework overcomes the limitation of pretest probability uncertainty in Bayesian analysis and guides decision making when it is most challenging: interpretation of unexpected test results.

Comparative metagenomic and metatranscriptomic analyses of microbial communities in acid mine drainage.

PubMed

Chen, Lin-xing; Hu, Min; Huang, Li-nan; Hua, Zheng-shuang; Kuang, Jia-liang; Li, Sheng-jin; Shu, Wen-sheng

2015-07-01

The microbial communities in acid mine drainage have been extensively studied to reveal their roles in acid generation and adaption to this environment. Lacking, however, are integrated community- and organism-wide comparative gene transcriptional analyses that could reveal the response and adaptation mechanisms of these extraordinary microorganisms to different environmental conditions. In this study, comparative metagenomics and metatranscriptomics were performed on microbial assemblages collected from four geochemically distinct acid mine drainage (AMD) sites. Taxonomic analysis uncovered unexpectedly high microbial biodiversity of these extremely acidophilic communities, and the abundant taxa of Acidithiobacillus, Leptospirillum and Acidiphilium exhibited high transcriptional activities. Community-wide comparative analyses clearly showed that the AMD microorganisms adapted to the different environmental conditions via regulating the expression of genes involved in multiple in situ functional activities, including low-pH adaptation, carbon, nitrogen and phosphate assimilation, energy generation, environmental stress resistance, and other functions. Organism-wide comparative analyses of the active taxa revealed environment-dependent gene transcriptional profiles, especially the distinct strategies used by Acidithiobacillus ferrivorans and Leptospirillum ferrodiazotrophum in nutrients assimilation and energy generation for survival under different conditions. Overall, these findings demonstrate that the gene transcriptional profiles of AMD microorganisms are closely related to the site physiochemical characteristics, providing clues into the microbial response and adaptation mechanisms in the oligotrophic, extremely acidic environments.

Bio-mimicking of Proline-Rich Motif Applied to Carbon Nanotube Reveals Unexpected Subtleties Underlying Nanoparticle Functionalization

NASA Astrophysics Data System (ADS)

Zhang, Yuanzhao; Jimenez-Cruz, Camilo A.; Wang, Jian; Zhou, Bo; Yang, Zaixing; Zhou, Ruhong

2014-11-01

Here, we report computational studies of the SH3 protein domain interacting with various single-walled carbon nanotubes (SWCNT) either bare or functionalized by mimicking the proline-rich motif (PRM) ligand (PPPVPPRR) and compare it to the SH3-PRM complex binding. With prolines or a single arginine attached, the SWCNT gained slightly on specificity when compared with the bare control, whereas with multi-arginine systems the specificity dropped dramatically to our surprise. Although the electrostatic interaction provided by arginines is crucial in the recognition between PRM and SH3 domain, our results suggest that attaching multiple arginines to the SWCNT has a detrimental effect on the binding affinity. Detailed analysis of the MD trajectories found two main factors that modulate the specificity of the binding: the existence of competing acidic patches at the surface of SH3 that leads to ``trapping and clamping'' by the arginines, and the rigidity of the SWCNT introducing entropic penalties in the proper binding. Further investigation revealed that the same ``clamping'' phenomenon exits in the PRM-SH3 system, which has not been reported in previous literature. The competing effects between nanoparticle and its functionalization components revealed by our model system should be of value to current and future nanomedicine designs.

Bio-mimicking of Proline-Rich Motif Applied to Carbon Nanotube Reveals Unexpected Subtleties Underlying Nanoparticle Functionalization

PubMed Central

Zhang, Yuanzhao; Jimenez-Cruz, Camilo A.; Wang, Jian; Zhou, Bo; Yang, Zaixing; Zhou, Ruhong

2014-01-01

Here, we report computational studies of the SH3 protein domain interacting with various single-walled carbon nanotubes (SWCNT) either bare or functionalized by mimicking the proline-rich motif (PRM) ligand (PPPVPPRR) and compare it to the SH3-PRM complex binding. With prolines or a single arginine attached, the SWCNT gained slightly on specificity when compared with the bare control, whereas with multi-arginine systems the specificity dropped dramatically to our surprise. Although the electrostatic interaction provided by arginines is crucial in the recognition between PRM and SH3 domain, our results suggest that attaching multiple arginines to the SWCNT has a detrimental effect on the binding affinity. Detailed analysis of the MD trajectories found two main factors that modulate the specificity of the binding: the existence of competing acidic patches at the surface of SH3 that leads to “trapping and clamping” by the arginines, and the rigidity of the SWCNT introducing entropic penalties in the proper binding. Further investigation revealed that the same “clamping” phenomenon exits in the PRM-SH3 system, which has not been reported in previous literature. The competing effects between nanoparticle and its functionalization components revealed by our model system should be of value to current and future nanomedicine designs. PMID:25427563

Principle Component Analysis of AIRS and CrIS Data

NASA Technical Reports Server (NTRS)

Aumann, H. H.; Manning, Evan

2015-01-01

Synthetic Eigen Vectors (EV) used for the statistical analysis of the PC reconstruction residual of large ensembles of data are a novel tool for the analysis of data from hyperspectral infrared sounders like the Atmospheric Infrared Sounder (AIRS) on the EOS Aqua and the Cross-track Infrared Sounder (CrIS) on the SUOMI polar orbiting satellites. Unlike empirical EV, which are derived from the observed spectra, the synthetic EV are derived from a large ensemble of spectra which are calculated assuming that, given a state of the atmosphere, the spectra created by the instrument can be accurately calculated. The synthetic EV are then used to reconstruct the observed spectra. The analysis of the differences between the observed spectra and the reconstructed spectra for Simultaneous Nadir Overpasses of tropical oceans reveals unexpected differences at the more than 200 mK level under relatively clear conditions, particularly in the mid-wave water vapor channels of CrIS. The repeatability of these differences using independently trained SEV and results from different years appears to rule out inconsistencies in the radiative transfer algorithm or the data simulation. The reasons for these discrepancies are under evaluation.

Making a big thing of a small cell--recent advances in single cell analysis.

PubMed

Galler, Kerstin; Bräutigam, Katharina; Große, Christina; Popp, Jürgen; Neugebauer, Ute

2014-03-21

Single cell analysis is an emerging field requiring a high level interdisciplinary collaboration to provide detailed insights into the complex organisation, function and heterogeneity of life. This review is addressed to life science researchers as well as researchers developing novel technologies. It covers all aspects of the characterisation of single cells (with a special focus on mammalian cells) from morphology to genetics and different omics-techniques to physiological, mechanical and electrical methods. In recent years, tremendous advances have been achieved in all fields of single cell analysis: (1) improved spatial and temporal resolution of imaging techniques to enable the tracking of single molecule dynamics within single cells; (2) increased throughput to reveal unexpected heterogeneity between different individual cells raising the question what characterizes a cell type and what is just natural biological variation; and (3) emerging multimodal approaches trying to bring together information from complementary techniques paving the way for a deeper understanding of the complexity of biological processes. This review also covers the first successful translations of single cell analysis methods to diagnostic applications in the field of tumour research (especially circulating tumour cells), regenerative medicine, drug discovery and immunology.

A Missense Variant in KCNJ10 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA1).

PubMed

Mauri, Nico; Kleiter, Miriam; Leschnik, Michael; Högler, Sandra; Dietschi, Elisabeth; Wiedmer, Michaela; Dietrich, Joëlle; Henke, Diana; Steffen, Frank; Schuller, Simone; Gurtner, Corinne; Stokar-Regenscheit, Nadine; O'Toole, Donal; Bilzer, Thomas; Herden, Christiane; Oevermann, Anna; Jagannathan, Vidhya; Leeb, Tosso

2017-02-09

Spongy degeneration with cerebellar ataxia (SDCA) is a severe neurodegenerative disease with monogenic autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. We performed a genetic investigation in six families and seven isolated cases of Malinois dogs with signs of cerebellar dysfunction. Linkage analysis revealed an unexpected genetic heterogeneity within the studied cases. The affected dogs from four families and one isolated case shared a ∼1.4 Mb common homozygous haplotype segment on chromosome 38. Whole genome sequence analysis of three affected and 140 control dogs revealed a missense variant in the KCNJ10 gene encoding a potassium channel (c.986T>C; p.Leu329Pro). Pathogenic variants in KCNJ10 were reported previously in humans, mice, and dogs with neurological phenotypes. Therefore, we consider KCNJ10 :c.986T>C the most likely candidate causative variant for one subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia 1 (SDCA1). However, our study also comprised samples from 12 Malinois dogs with cerebellar dysfunction which were not homozygous for this variant, suggesting a different genetic basis in these dogs. A retrospective detailed clinical and histopathological analysis revealed subtle neuropathological differences with respect to SDCA1-affected dogs. Thus, our study highlights the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population. These dogs represent an animal model for the human EAST syndrome. Copyright © 2017 Mauri et al.

Incidence, Risk Factors, and Analysis of Survival of Unexpected N2 Disease in Stage I Non-Small Cell Lung Cancer.

PubMed

Fiorelli, Alfonso; Sagan, Dariusz; Mackiewicz, Lukasz; Cagini, Lucio; Scarnecchia, Elisa; Chiodini, Paolo; Caronia, Francesco Paolo; Puma, Francesco; Santini, Mario; Ragusa, Mark

2015-10-01

To evaluate the incidence, predictors, and survival of unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer. This is a retrospective observational multicenter study on all consecutive patients operated for clinical stage I non-small cell lung cancer from January 2006 to December 2012. Medical records were reviewed to investigate the incidence and risk factors for unexpected pN2 disease. Then, the survival of patients with unexpected pN2 disease was statistically compared with that of patients with clinical N2 disease operated after induction therapy in the same period. Our study population counted 901 patients. An incidence of 12% (108/901) unexpected pN2 disease was found. Among 3,389 lymph nodes sampled, 124 distinct metastases were found. Of the 108 patients, 92 (85%) had metastases in single N2 station and 16 (15%) patients had disease in multiple N2 stations; 47 (44%) had pN2 disease without pN1 involvement (skip metastases) and 61/108 (56%) had also pN1 metastases. Factors associated with unexpected pN2 disease were central tumor location (p < 0.003), cT2a (p < 0.0001) and pT2a stage (p < 0.0001), pN1 disease (p = 0.004), and a standard uptake value > 4.0 (0.007). Patients with pN2 disease compared with patients with cN2 disease presented a better median overall survival (56 versus 20 months; p = 0.001) and disease-free survival (46 versus 11 months; p < 0.0001). The preoperative effort to discover unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer is not justified, considering their good survival. Thus, preoperative invasive mediastinal procedures in such cases are not indicated. Georg Thieme Verlag KG Stuttgart · New York.

"I Would Rather Be Size 10 Than Have Straight A's": A Focus Study Group of Adolescent Girls' Wish To Be Thinner.

ERIC Educational Resources Information Center

Tiggemann, Marika; Gardiner, Maria; Slater, Amy

2000-01-01

Investigates the body concerns of adolescent girls (N=67), together with the underlying motivations for wishes to be thinner. Results of focus group studies reveal that sociocultural influences exerted the strongest pressures to be thin. The girls displayed an unexpected sophistication in their conceptualization of the role of both media effects…

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

Treesearch

Aimee H. Fullerton; Christian E. Torgersen; Joshua J. Lawler; Russell N. Faux; Ashley Steel; Timothy J. Beechie; Joseph L. Ebersole; Scott G. Leibowitz

2015-01-01

Prevailing theory suggests that stream temperature warms asymptotically in a downstream direction, beginning at the temperature of the source in the headwaters and levelling off downstream as it converges to matchmeteorological conditions.However, there have been few empirical examples of longitudinal patterns of temperature in large rivers due to a paucity of data. We...

Genetic Linkage Mapping of Genomic Regions Conferring Tolerance to High Aluminum in Slash Pine

Treesearch

Thomas L. Kubisiak; C. Dana Nelson; J. Nowak; A.L. Friend

2000-01-01

Reports of reduced growth and vigor of forest trees in Europe and North America have been accumulating in recent years. In eastern North America, increased mortality and reduced radial growth rates have been noted for red spruce, frasier fir, and sugar maple. USDA Forest Service inventory data from permanent survey plots has revealed an unexpected reduction of radial...

Preservation of the Acetabular Cup During Revision Total Hip Arthroplasty Using a Novel Mini-navigation Tool: A Case Report.

PubMed

Vincent, John; Alshaygy, Ibrahim; Muir, Jeffrey M; Kuzyk, Paul

2018-01-01

While intraoperative navigation systems have been shown to improve outcomes in primary total hip arthroplasty (THA), their use in the context of revision has been largely overlooked. This case report presents the first documented use of an imageless navigation tool in the context of revision THA, and an unexpected benefit to the surgical procedure as a result. An 84-year-old female patient presented following five episodes of dislocation of the left hip and with pain in the left buttock, groin, and posterior aspect of her hip. Relevant surgical history included primary hip arthroplasty in 1999 and the first revision in 2014. Preoperative analysis revealed a constrained liner that had become disengaged and migrated inferiorly, lodging at the distal aspect of the femoral neck. Acetabular protrusion was also noted. The pre-operative plan included the replacement of the fragmented liner and likely of the acetabular cup due to hardware failure. Intraoperative assessment, however, revealed that the cup was in good condition and would be difficult to remove due to substantial bony ingrowth. With the assistance of imageless navigation, the orientation of the acetabular cup was determined and a new constrained liner was cemented into the preexisting acetabular component at an altered orientation, correcting anteversion by 7°. In revision hip arthroplasty cases, image-based navigation is limited by the presence of existing implants and corresponding metal artefact. This case demonstrates the successful use of an imageless navigation tool for revision surgery. Use of navigation led to the unexpected intraoperative discovery that the acetabular cup was in an acceptable state, and allowed the surgical team to correct the position of the cup using a constrained liner, thus preserving the cup. This significantly benefitted patient outcome, due to the risks associated with the removal of a firmly fixated acetabular cup. While more extensive research is required, this case demonstrates that imageless navigation may be an indispensable tool for revision surgery.

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

PubMed Central

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

Microevolution Analysis of Bacillus coahuilensis Unveils Differences in Phosphorus Acquisition Strategies and Their Regulation.

PubMed

Gómez-Lunar, Zulema; Hernández-González, Ismael; Rodríguez-Torres, María-Dolores; Souza, Valeria; Olmedo-Álvarez, Gabriela

2016-01-01

Bacterial genomes undergo numerous events of gene losses and gains that generate genome variability among strains of the same species (microevolution). Our aim was to compare the genomes and relevant phenotypes of three Bacillus coahuilensis strains from two oligotrophic hydrological systems in the Cuatro Ciénegas Basin (México), to unveil the environmental challenges that this species cope with, and the microevolutionary differences in these genotypes. Since the strains were isolated from a low P environment, we placed emphasis on the search of different phosphorus acquisition strategies. The three B. coahuilensis strains exhibited similar numbers of coding DNA sequences, of which 82% (2,893) constituted the core genome, and 18% corresponded to accessory genes. Most of the genes in this last group were associated with mobile genetic elements (MGEs) or were annotated as hypothetical proteins. Ten percent of the pangenome consisted of strain-specific genes. Alignment of the three B. coahuilensis genomes indicated a high level of synteny and revealed the presence of several genomic islands. Unexpectedly, one of these islands contained genes that encode the 2-keto-3-deoxymannooctulosonic acid (Kdo) biosynthesis enzymes, a feature associated to cell walls of Gram-negative bacteria. Some microevolutionary changes were clearly associated with MGEs. Our analysis revealed inconsistencies between phenotype and genotype, which we suggest result from the impossibility to map regulatory features to genome analysis. Experimental results revealed variability in the types and numbers of auxotrophies between the strains that could not consistently be explained by in silico metabolic models. Several intraspecific differences in preferences for carbohydrate and phosphorus utilization were observed. Regarding phosphorus recycling, scavenging, and storage, variations were found between the three genomes. The three strains exhibited differences regarding alkaline phosphatase that revealed that in addition to gene gain and loss, regulation adjustment of gene expression also has contributed to the intraspecific diversity of B. coahuilensis.

Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour.

PubMed

Godenschwege, Tanja A; Reisch, Dietmar; Diegelmann, Sören; Eberle, Kai; Funk, Natalja; Heisenberg, Martin; Hoppe, Viviane; Hoppe, Jürgen; Klagges, Bert R E; Martin, Jean-René; Nikitina, Ekaterina A; Putz, Gabi; Reifegerste, Rita; Reisch, Natascha; Rister, Jens; Schaupp, Michael; Scholz, Henrike; Schwärzel, Martin; Werner, Ursula; Zars, Troy D; Buchner, Sigrid; Buchner, Erich

2004-08-01

Vertebrate synapsins are abundant synaptic vesicle phosphoproteins that have been proposed to fine-regulate neurotransmitter release by phosphorylation-dependent control of synaptic vesicle motility. However, the consequences of a total lack of all synapsin isoforms due to a knock-out of all three mouse synapsin genes have not yet been investigated. In Drosophila a single synapsin gene encodes several isoforms and is expressed in most synaptic terminals. Thus the targeted deletion of the synapsin gene of Drosophila eliminates the possibility of functional knock-out complementation by other isoforms. Unexpectedly, synapsin null mutant flies show no obvious defects in brain morphology, and no striking qualitative changes in behaviour are observed. Ultrastructural analysis of an identified 'model' synapse of the larval nerve muscle preparation revealed no difference between wild-type and mutant, and spontaneous or evoked excitatory junction potentials at this synapse were normal up to a stimulus frequency of 5 Hz. However, when several behavioural responses were analysed quantitatively, specific differences between mutant and wild-type flies are noted. Adult locomotor activity, optomotor responses at high pattern velocities, wing beat frequency, and visual pattern preference are modified. Synapsin mutant flies show faster habituation of an olfactory jump response, enhanced ethanol tolerance, and significant defects in learning and memory as measured using three different paradigms. Larval behavioural defects are described in a separate paper. We conclude that Drosophila synapsins play a significant role in nervous system function, which is subtle at the cellular level but manifests itself in complex behaviour.

Anterior insula coordinates hierarchical processing of tactile mismatch responses

PubMed Central

Allen, Micah; Fardo, Francesca; Dietz, Martin J.; Hillebrandt, Hauke; Friston, Karl J.; Rees, Geraint; Roepstorff, Andreas

2016-01-01

The body underlies our sense of self, emotion, and agency. Signals arising from the skin convey warmth, social touch, and the physical characteristics of external stimuli. Surprising or unexpected tactile sensations can herald events of motivational salience, including imminent threats (e.g., an insect bite) and hedonic rewards (e.g., a caressing touch). Awareness of such events is thought to depend upon the hierarchical integration of body-related mismatch responses by the anterior insula. To investigate this possibility, we measured brain activity using functional magnetic resonance imaging, while healthy participants performed a roving tactile oddball task. Mass-univariate analysis demonstrated robust activations in limbic, somatosensory, and prefrontal cortical areas previously implicated in tactile deviancy, body awareness, and cognitive control. Dynamic Causal Modelling revealed that unexpected stimuli increased the strength of forward connections along a caudal to rostral hierarchy—projecting from thalamic and somatosensory regions towards insula, cingulate and prefrontal cortices. Within this ascending flow of sensory information, the AIC was the only region to show increased backwards connectivity to the somatosensory cortex, augmenting a reciprocal exchange of neuronal signals. Further, participants who rated stimulus changes as easier to detect showed stronger modulation of descending PFC to AIC connections by deviance. These results suggest that the AIC coordinates hierarchical processing of tactile prediction error. They are interpreted in support of an embodied predictive coding model where AIC mediated body awareness is involved in anchoring a global neuronal workspace. PMID:26584870

Transcriptome-Wide Identification of RNA Targets of Arabidopsis SERINE/ARGININE-RICH45 Uncovers the Unexpected Roles of This RNA Binding Protein in RNA Processing[OPEN

PubMed Central

Wang, Yajun; Hamilton, Michael; Ben-Hur, Asa; Reddy, Anireddy S.N.

2015-01-01

Plant SR45 and its metazoan ortholog RNPS1 are serine/arginine-rich (SR)-like RNA binding proteins that function in splicing/postsplicing events and regulate diverse processes in eukaryotes. Interactions of SR45 with both RNAs and proteins are crucial for regulating RNA processing. However, in vivo RNA targets of SR45 are currently unclear. Using RNA immunoprecipitation followed by high-throughput sequencing, we identified over 4000 Arabidopsis thaliana RNAs that directly or indirectly associate with SR45, designated as SR45-associated RNAs (SARs). Comprehensive analyses of these SARs revealed several roles for SR45. First, SR45 associates with and regulates the expression of 30% of abscisic acid (ABA) signaling genes at the postsplicing level. Second, although most SARs are derived from intron-containing genes, surprisingly, 340 SARs are derived from intronless genes. Expression analysis of the SARs suggests that SR45 differentially regulates intronless and intron-containing SARs. Finally, we identified four overrepresented RNA motifs in SARs that likely mediate SR45’s recognition of its targets. Therefore, SR45 plays an unexpected role in mRNA processing of intronless genes, and numerous ABA signaling genes are targeted for regulation at the posttranscriptional level. The diverse molecular functions of SR45 uncovered in this study are likely applicable to other species in view of its conservation across eukaryotes. PMID:26603559

H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements

PubMed Central

Zink, Lisa-Maria; Delbarre, Erwan; Eberl, H. Christian; Keilhauer, Eva C.; Bönisch, Clemens; Pünzeler, Sebastian; Bartkuhn, Marek; Collas, Philippe; Mann, Matthias

2017-01-01

Abstract Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted manner. Here, we identify the binding partners of the primate-specific and H3.3-related histone variant H3.Y using several quantitative mass spectrometry approaches, and biochemical and cell biological assays. We find the HIRA, but not the DAXX/ATRX, complex to recognize H3.Y, explaining its presence in transcriptionally active euchromatic regions. Accordingly, H3.Y nucleosomes are enriched in the transcription-promoting FACT complex and depleted of repressive post-translational histone modifications. H3.Y mutational gain-of-function screens reveal an unexpected combinatorial amino acid sequence requirement for histone H3.3 interaction with DAXX but not HIRA, and for H3.3 recruitment to PML nuclear bodies. We demonstrate the importance and necessity of specific H3.3 core and C-terminal amino acids in discriminating between distinct chaperone complexes. Further, chromatin immunoprecipitation sequencing experiments reveal that in contrast to euchromatic HIRA-dependent deposition sites, human DAXX/ATRX-dependent regions of histone H3 variant incorporation are enriched in heterochromatic H3K9me3 and simple repeat sequences. These data demonstrate that H3.Y's unique amino acids allow a functional distinction between HIRA and DAXX binding and its consequent deposition into open chromatin. PMID:28334823

Enigma Variations for Peptides and Their Transporters in Higher Plants

PubMed Central

WATERWORTH, WANDA M.; BRAY, CLIFFORD M.

2006-01-01

• Background. Two families of proteins that transport small peptides, the oligopeptide transporters (OPTs) and the peptide transporters (PTRs), have been recognized in eukaryotes. Higher plants contain a far greater number of genes for these transporters than do other eukaryotes. This may be indicative of the relative importance of (oligo)peptides and their transport to plant growth and metabolism. • Recent progress. Recent studies are now allowing us to assign functions to these transporters and are starting to identify their in-planta substrates, revealing unexpected and important contributions of the transporters to plant growth and developmental processes. This Botanical Briefing appraises recent findings that PTRs and OPTs have key roles to play in the control of plant cell growth and development. Evidence is presented that some of these transporters have functions outside that of nitrogen nutrition and that these carriers can also surprise us with their totally unexpected choice of substrates. PMID:16735405

The architecture of a eukaryotic replisome

DOE PAGES

Sun, Jingchuan; Yuan, Zuanning; Shi, Yi; ...

2015-11-02

At the eukaryotic DNA replication fork, it is widely believed that the Cdc45–Mcm2–7–GINS (CMG) helicase is positioned in front to unwind DNA and that DNA polymerases trail behind the helicase. Here we used single-particle EM to directly image a Saccharomyces cerevisiae replisome. Contrary to expectations, the leading strand Pol ε is positioned ahead of CMG helicase, whereas Ctf4 and the lagging-strand polymerase (Pol) α–primase are behind the helicase. This unexpected architecture indicates that the leading-strand DNA travels a long distance before reaching Pol ε, first threading through the Mcm2–7 ring and then making a U-turn at the bottom and reachingmore » Pol ε at the top of CMG. Lastly, our work reveals an unexpected configuration of the eukaryotic replisome, suggests possible reasons for this architecture and provides a basis for further structural and biochemical replisome studies.« less

[Unexpected cutaneous purpura in an infant].

PubMed

Luo, Yang-Yang; Wei, Zhu; Zeng, Ying-Hong; Zhou, Bin; Tang, Jian-Ping

2016-11-01

A two-month-old boy visited the hospital due to unexpected cutaneous purpura and thrombocytopenia for 2 days. The physical examination revealed a purple mass on the back. The soft tissue color Doppler ultrasound showed rich blood signals in the tissue, and the results of bone marrow puncture indicated an increased number of megakaryocytes. After the treatment with hormone and gamma globulin, the platelet count rapidly increased and maintained at a normal level. Meanwhile, the boy was given oral administration of propranolol. He was followed up for 4 months and the volume of the mass on the back was reduced significantly. He had a definite diagnosis of hemangioma and immune thrombocytopenia. As for the patients with hemangioma complicated by thrombocytopenia, knowledge of Kasabach-Merritt syndrome should be enhanced and there should be a clarification of the association between thrombocytopenia and hemangioma. There should also be an alertness for thrombocytopenia of other causes.

Particle-hole symmetry reveals failed superconductivity in the metallic phase of two-dimensional superconducting films

DOE PAGES

Breznay, Nicholas P.; Kapitulnik, Aharon

2017-09-15

Electrons confined to two dimensions display an unexpected diversity of behaviors as they are cooled to absolute zero. Noninteracting electrons are predicted to eventually “localize” into an insulating ground state, and it has long been supposed that electron correlations stabilize only one other phase: superconductivity. However, many two-dimensional (2D) superconducting materials have shown surprising evidence for metallic behavior, where the electrical resistivity saturates in the zero-temperature limit; the nature of this unexpected metallic state remains under intense scrutiny. We report electrical transport properties for two disordered 2D superconductors, indium oxide and tantalum nitride, and observe a magnetic field–tuned transition frommore » a true superconductor to a metallic phase with saturated resistivity. Lastly, this metallic phase is characterized by a vanishing Hall resistivity, suggesting that it retains particle-hole symmetry from the disrupted superconducting state.« less

Particle-hole symmetry reveals failed superconductivity in the metallic phase of two-dimensional superconducting films

PubMed Central

Breznay, Nicholas P.; Kapitulnik, Aharon

2017-01-01

Electrons confined to two dimensions display an unexpected diversity of behaviors as they are cooled to absolute zero. Noninteracting electrons are predicted to eventually “localize” into an insulating ground state, and it has long been supposed that electron correlations stabilize only one other phase: superconductivity. However, many two-dimensional (2D) superconducting materials have shown surprising evidence for metallic behavior, where the electrical resistivity saturates in the zero-temperature limit; the nature of this unexpected metallic state remains under intense scrutiny. We report electrical transport properties for two disordered 2D superconductors, indium oxide and tantalum nitride, and observe a magnetic field–tuned transition from a true superconductor to a metallic phase with saturated resistivity. This metallic phase is characterized by a vanishing Hall resistivity, suggesting that it retains particle-hole symmetry from the disrupted superconducting state. PMID:28929135

Particle-hole symmetry reveals failed superconductivity in the metallic phase of two-dimensional superconducting films.

PubMed

Breznay, Nicholas P; Kapitulnik, Aharon

2017-09-01

Electrons confined to two dimensions display an unexpected diversity of behaviors as they are cooled to absolute zero. Noninteracting electrons are predicted to eventually "localize" into an insulating ground state, and it has long been supposed that electron correlations stabilize only one other phase: superconductivity. However, many two-dimensional (2D) superconducting materials have shown surprising evidence for metallic behavior, where the electrical resistivity saturates in the zero-temperature limit; the nature of this unexpected metallic state remains under intense scrutiny. We report electrical transport properties for two disordered 2D superconductors, indium oxide and tantalum nitride, and observe a magnetic field-tuned transition from a true superconductor to a metallic phase with saturated resistivity. This metallic phase is characterized by a vanishing Hall resistivity, suggesting that it retains particle-hole symmetry from the disrupted superconducting state.

Medications as causes of intraluminal hyperdensities: what radiologists need to know.

PubMed

Sin, Francesca Nga Yee; Tsang, Jane Pui Ki; Siu, Kwong Lok; Ma, Johnny Ka Fai; Yung, Alfred Wei Tak

2012-07-01

In computed tomography (CT) angiogram or some dedicated CT studies of the abdomen, the use of positive enteric contrast should be avoided as its presence could decrease the sensitivity of the test. There are, however, cases of CT scans with unexpected hyperdense intraluminal contents detected due to the use of certain oral or rectal medications. Reports on medications as causes of intraluminal hyperdensities are sparse in the English literature. We have studied several commonly used medications and revealed that many drugs appear hyperdense in CT scans. The presence of unexpected intraluminal hyperdensities can potentially cause erroneous interpretation of images and in some cases decrease the sensitivity of the test. The hyperdense bowel contents may be mistaken as acute hemorrhage in CT angiogram for detection of GI bleeding. Active GI bleeding, presented as intraluminal extravasation of contrast material, can also be obscured. Certain intra-abdominal pathologies could be masked, for example, in plain CT scan for detection of urinary tract stones or in contrast CT study for suspected bowel ischaemia. It is important for radiologists and clinicians to be aware of this situation in order to prevent misinterpretation of images and to select the most appropriate imaging modality when such unexpected intraluminal hyperdensities are encountered. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Unexpected Complications of Novel Deep Brain Stimulation Treatments: Ethical Issues and Clinical Recommendations

PubMed Central

Cheeran, Binith; Pugh, Jonathan; Pycroft, Laurie; Boccard, Sandra; Prangnell, Simon; Green, Alexander L.; FitzGerald, James; Savulescu, Julian; Aziz, Tipu

2017-01-01

Background Innovative neurosurgical treatments present a number of known risks, the natures and probabilities of which can be adequately communicated to patients via the standard procedures governing obtaining informed consent. However, due to their novelty, these treatments also come with unknown risks, which require an augmented approach to obtaining informed consent. Objective This paper aims to discuss and provide concrete procedural guidance on the ethical issues raised by serious unexpected complications of novel deep brain stimulation treatments. Approach We illustrate our analysis using a case study of the unexpected development of recurrent stereotyped events in patients following the use of deep brain stimulation (DBS) to treat severe chronic pain. Examining these unexpected complications in light of medical ethical principles, we argue that serious complications of novel DBS treatments do not necessarily make it unethical to offer the intervention to eligible patients. However, the difficulty the clinician faces in determining whether the intervention is in the patient's best interests generates reasons to take extra steps to promote the autonomous decision making of these patients. Conclusion and recommendations We conclude with clinical recommendations, including details of an augmented consent process for novel DBS treatment. PMID:28557242

Unexpected Anomaly of GHF (Gradient Heating Furnace) On-Board

NASA Astrophysics Data System (ADS)

Kobayashi, Ryoji

2013-09-01

GHF (Gradient Heating Furnace) is vacuum furnace that enables to raise temperature up to 1600 degree Celsius. GHF consumes large amount of power (about 4 kW), contains pressure vessel and has interface with vacuum line. Therefore, GHF has hazardous function in nature. JAXA performed safety analysis thoroughly, identified all causes and set appropriate safety controls to meet safety requirements. JAXA launched GHF in January of 2011 and operates in Kibo laboratory of ISS (International Space Station). JAXA encountered unexpected anomalies during operations on-board. They did not give safety degradation actually since safety devices inherent to GHF worked, but some of anomalies were unexpected.This paper presents one of the "unexpected" anomaly happened on-board, and how it relates with safety and how it is controlled not to lead to safety accident.It is pretty hard to find out "root cause" for some of anomalies due to limited telemetry information and crew resources. In addition, most of engineers designing GHF have gone. This paper also introduces agency level efforts to struggle to find out causes and to set appropriate countermeasure.Finally, this paper summaries lessons and learned from anomaly JAXA encountered.

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis

PubMed Central

Luzius, Anne; Saggau, Carina; Ruder, Barbara; Bolik, Julia; Schmidt-Arras, Dirk; Linkermann, Andreas; Becker, Christoph; Rosenstiel, Philip; Rose-John, Stefan; Adam, Dieter

2018-01-01

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17ex/ex) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17ex/ex mice with mice that lack the necroptotic core protein RIPK3. Despite the loss of RIPK3, ADAM17ex/ex/RIPK3−/− mice showed the same increased susceptibility as ADAM17ex/ex mice in both acute and chronic models of DSS-induced colitis. Mice of both genotypes revealed comparable results with regard to weight loss, disease activity index and colitis-associated changes of inner organs. Histopathological analyses confirmed similar tissue destruction, loss of barrier integrity, immune cell infiltration, and cell death; serum analyses revealed similar levels of the pro-inflammatory cytokine KC. Resolving these unexpected findings, ADAM17ex/ex mice did not show phosphorylation of RIPK3 and its necroptotic interaction partner MLKL during DSS-induced colitis, although both proteins were clearly expressed. Consistent with these findings, murine embryonic fibroblasts derived from ADAM17ex/ex mice were protected from tumor necrosis factor (TNF)-induced necroptosis and failed to show phosphorylation of MLKL and RIPK3 after induction of necroptosis by TNF, revealing a novel, undescribed role of the protease ADAM17 in necroptosis. PMID:29560122

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis.

PubMed

Fuchslocher Chico, Johaiber; Falk-Paulsen, Maren; Luzius, Anne; Saggau, Carina; Ruder, Barbara; Bolik, Julia; Schmidt-Arras, Dirk; Linkermann, Andreas; Becker, Christoph; Rosenstiel, Philip; Rose-John, Stefan; Adam, Dieter

2018-02-27

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17 ex/ex ) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17 ex/ex mice with mice that lack the necroptotic core protein RIPK3. Despite the loss of RIPK3, ADAM17 ex/ex /RIPK3 -/- mice showed the same increased susceptibility as ADAM17 ex/ex mice in both acute and chronic models of DSS-induced colitis. Mice of both genotypes revealed comparable results with regard to weight loss, disease activity index and colitis-associated changes of inner organs. Histopathological analyses confirmed similar tissue destruction, loss of barrier integrity, immune cell infiltration, and cell death; serum analyses revealed similar levels of the pro-inflammatory cytokine KC. Resolving these unexpected findings, ADAM17 ex/ex mice did not show phosphorylation of RIPK3 and its necroptotic interaction partner MLKL during DSS-induced colitis, although both proteins were clearly expressed. Consistent with these findings, murine embryonic fibroblasts derived from ADAM17 ex/ex mice were protected from tumor necrosis factor (TNF)-induced necroptosis and failed to show phosphorylation of MLKL and RIPK3 after induction of necroptosis by TNF, revealing a novel, undescribed role of the protease ADAM17 in necroptosis.

Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

PubMed Central

Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

2015-01-01

Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness

PubMed Central

Yue, Shuhua; Li, Junjie; Lee, Seung-Young; Lee, Hyeon Jeong; Shao, Tian; Song, Bing; Cheng, Liang; Masterson, Timothy A.; Liu, Xiaoqi; Ratliff, Timothy L.; Cheng, Ji-Xin

2014-01-01

Summary Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism. PMID:24606897

Alexithymia, emotional dysregulation, and recovery from alcoholism: therapeutic response to assessment of mood.

PubMed

Krentzman, Amy R; Higgins, Margaret M; Staller, Karen M; Klatt, Emily S

2015-06-01

This study is a secondary analysis of a randomized controlled trial that tested the effects of a gratitude intervention on well-being in a sample of individuals in outpatient treatment for alcohol use disorder (AUD). Follow-up qualitative interviews unexpectedly revealed that participants found the Positive and Negative Affect Schedule (PANAS) to be helpful to their recovery in the ways that it asked them to identify and rate their emotions. Participant statements were purposively sampled and analyzed using grounded theory methods to produce a conceptual framework illustrating the process of mood identification and its sequelae. Evidence of existing alexithymia and emotional dysregulation, dominance of negative mood, and increasing ability to identify, accept, and regulate mood as part of recovery was found. Findings suggest that emotion regulation is a compelling topic for those in recovery from AUD, and may deserve a more prominent role in treatment. © The Author(s) 2015.

Towards terrain interaction prediction for bioinspired planetary exploration rovers.

PubMed

Yeomans, Brian; Saaj, Chakravathini M

2014-03-01

Deployment of a small legged vehicle to extend the reach of future planetary exploration missions is an attractive possibility but little is known about the behaviour of a walking rover on deformable planetary terrain. This paper applies ideas from the developing study of granular materials together with a detailed characterization of the sinkage process to propose and validate a combined model of terrain interaction based on an understanding of the physics and micro mechanics at the granular level. Whilst the model reflects the complexity of interactions expected from a walking rover, common themes emerge which enable the model to be streamlined to the extent that a simple mathematical representation is possible without resorting to numerical methods. Bespoke testing and analysis tools are described which reveal some unexpected conclusions and point the way towards intelligent control and foot geometry techniques to improve thrust generation.

Using direct calorimetry to test the accuracy of indirect calorimetry in an ectotherm.

PubMed

Walsberg, Glenn E; Hoffman, Ty C M

2006-01-01

We previously demonstrated that the relationship between respiratory gas exchange and metabolic heat production is unexpectedly variable and that conventional approaches to estimating energy expenditure by indirect calorimetry can incorporate large errors. Prior studies, however, comparing direct and indirect calorimetry of animals focused only on endothermic organisms. Given that endothermy and ectothermy represent a fundamental dichotomy of animal energetics, in this analysis we explore how these contrasting physiologies correlate with the relationship between heat production and respiratory gas exchange. Simultaneous indirect and direct calorimetry in an ectotherm, the ball python (Python regius Shaw), revealed that the relationships between gas exchange and heat production were within 1% of those expected when analyses using indirect calorimetry were based on the assumption that the fasting animal catabolized only protein. This accuracy of indirect calorimetry contrasts sharply with our previous conclusions for three species of birds and mammals.

Signal, noise, and variation in neural and sensory-motor latency

PubMed Central

Lee, Joonyeol; Joshua, Mati; Medina, Javier F.; Lisberger, Stephen G.

2016-01-01

Analysis of the neural code for sensory-motor latency in smooth pursuit eye movements reveals general principles of neural variation and the specific origin of motor latency. The trial-by-trial variation in neural latency in MT comprises: a shared component expressed as neuron-neuron latency correlations; and an independent component that is local to each neuron. The independent component arises heavily from fluctuations in the underlying probability of spiking with an unexpectedly small contribution from the stochastic nature of spiking itself. The shared component causes the latency of single neuron responses in MT to be weakly predictive of the behavioral latency of pursuit. Neural latency deeper in the motor system is more strongly predictive of behavioral latency. A model reproduces both the variance of behavioral latency and the neuron-behavior latency correlations in MT if it includes realistic neural latency variation, neuron-neuron latency correlations in MT, and noisy gain control downstream from MT. PMID:26971946

High-throughput discovery of novel developmental phenotypes.

PubMed

Dickinson, Mary E; Flenniken, Ann M; Ji, Xiao; Teboul, Lydia; Wong, Michael D; White, Jacqueline K; Meehan, Terrence F; Weninger, Wolfgang J; Westerberg, Henrik; Adissu, Hibret; Baker, Candice N; Bower, Lynette; Brown, James M; Caddle, L Brianna; Chiani, Francesco; Clary, Dave; Cleak, James; Daly, Mark J; Denegre, James M; Doe, Brendan; Dolan, Mary E; Edie, Sarah M; Fuchs, Helmut; Gailus-Durner, Valerie; Galli, Antonella; Gambadoro, Alessia; Gallegos, Juan; Guo, Shiying; Horner, Neil R; Hsu, Chih-Wei; Johnson, Sara J; Kalaga, Sowmya; Keith, Lance C; Lanoue, Louise; Lawson, Thomas N; Lek, Monkol; Mark, Manuel; Marschall, Susan; Mason, Jeremy; McElwee, Melissa L; Newbigging, Susan; Nutter, Lauryl M J; Peterson, Kevin A; Ramirez-Solis, Ramiro; Rowland, Douglas J; Ryder, Edward; Samocha, Kaitlin E; Seavitt, John R; Selloum, Mohammed; Szoke-Kovacs, Zsombor; Tamura, Masaru; Trainor, Amanda G; Tudose, Ilinca; Wakana, Shigeharu; Warren, Jonathan; Wendling, Olivia; West, David B; Wong, Leeyean; Yoshiki, Atsushi; MacArthur, Daniel G; Tocchini-Valentini, Glauco P; Gao, Xiang; Flicek, Paul; Bradley, Allan; Skarnes, William C; Justice, Monica J; Parkinson, Helen E; Moore, Mark; Wells, Sara; Braun, Robert E; Svenson, Karen L; de Angelis, Martin Hrabe; Herault, Yann; Mohun, Tim; Mallon, Ann-Marie; Henkelman, R Mark; Brown, Steve D M; Adams, David J; Lloyd, K C Kent; McKerlie, Colin; Beaudet, Arthur L; Bućan, Maja; Murray, Stephen A

2016-09-22

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.

Recurrent astrocytoma in a child: a report of cytogenetics and TP53 gene mutation screening.

PubMed Central

Dam, A.; Fock, J. M.; Hayes, V. M.; Molenaar, W. M.; van den Berg, E.

2000-01-01

An 8-year-old girl presented with a cerebral tumor and 3 recurrences within 15 months. The primary tumor was a low-grade astrocytoma, but the recurrences showed progressively malignant phenotypes with increasing mitotic activity and MIB-1 labeling indices. Radiotherapy was given between the first and the second recurrences. Cytogenetic analysis of the first and the second recurrences showed abnormal karyotypes. There seemed to be 2 common breakpoints in these 2 recurrences. TP53 gene mutation screening, using comprehensive denaturing gradient gel electrophoresis, revealed among others a possibly causative mutation of exon 5 in 3 of 4 tumor samples. The meaning of TP53 mutations in low-grade astrocytomas is still unclear, but the highly abnormal karyotypes, which are unusual in these tumors, probably provide genetic evidence for the unexpected aggressive behavior of the tumor in this patient. PMID:11302339

Saccharomyces cerevisiae metabolism in ecological context.

PubMed

Jouhten, Paula; Ponomarova, Olga; Gonzalez, Ramon; Patil, Kiran R

2016-11-01

The architecture and regulation of Saccharomyces cerevisiae metabolic network are among the best studied owing to its widespread use in both basic research and industry. Yet, several recent studies have revealed notable limitations in explaining genotype-metabolic phenotype relations in this yeast, especially when concerning multiple genetic/environmental perturbations. Apparently unexpected genotype-phenotype relations may originate in the evolutionarily shaped cellular operating principles being hidden in common laboratory conditions. Predecessors of laboratory S. cerevisiae strains, the wild and the domesticated yeasts, have been evolutionarily shaped by highly variable environments, very distinct from laboratory conditions, and most interestingly by social life within microbial communities. Here we present a brief review of the genotypic and phenotypic peculiarities of S. cerevisiae in the context of its social lifestyle beyond laboratory environments. Accounting for this ecological context and the origin of the laboratory strains in experimental design and data analysis would be essential in improving the understanding of genotype-environment-phenotype relationships. © FEMS 2016.

The role of life skills promotion in substance abuse prevention: a mediation analysis.

PubMed

Bühler, Anneke; Schröder, Elke; Silbereisen, Rainer K

2008-08-01

Research has shown that life skills programs are the most effective single activity in school-based substance abuse prevention. However, little is known about the processes through which they are effective. This study examines whether an evidence-based prevention program targeting general competence is effective through the promotion of knowledge about life skills and enhanced related behaviors. Based on a sample of 442 fifth graders participating in a quasi-experimental prevention study, as expected, mediation analyses revealed that increased knowledge about life skills paralleled an increase in students' distant attitudes toward alcohol and nicotine use. Unexpectedly, behaviors manifesting enhanced life skills were found not only among program participants who remained experimental/non-smokers or stopped smoking but also among smokers. In general, findings suggest that favorable prevention outcomes may be influenced through building knowledge about general life skills. The notion of uniform mechanisms of effectiveness in prevention programs is discussed.

Seasonal variations of snow depth on Mars.

PubMed

Smith, D E; Zuber, M T; Neumann, G A

2001-12-07

Using topography collected over one martian year from the Mars Orbiter Laser Altimeter on the Mars Global Surveyor (MGS) spacecraft, we have measured temporal changes in the elevation of the martian surface that correlate with the seasonal cycle of carbon dioxide exchange between the surface and atmosphere. The greatest elevation change (1.5 to 2 meters) occurs at high latitudes ( above 80 degrees ), whereas the bulk of the mass exchange occurs at lower latitudes (below 75 degrees N and below 73 degrees S). An unexpected period of sublimation was observed during northern hemisphere autumn, coincident with dust storms in the southern hemisphere. Analysis of MGS Doppler tracking residuals revealed temporal variations in the flattening of Mars that correlate with elevation changes. The combined changes in gravity and elevation constrain the average density of seasonally deposited carbon dioxide to be 910 +/- 230 kilograms per cubic meter, which is considerably denser than terrestrial snow.

Determination of pyrrolizidine alkaloids in tea, herbal drugs and honey.

PubMed

Bodi, Dorina; Ronczka, Stefan; Gottschalk, Christoph; Behr, Nastassja; Skibba, Anne; Wagner, Matthias; Lahrssen-Wiederholt, Monika; Preiss-Weigert, Angelika; These, Anja

2014-01-01

Honey was previously considered to be one of the main food sources of human pyrrolizidine alkaloid (PA) exposure in Europe. However, comprehensive analyses of honey and tea sampled in the Berlin retail market revealed unexpected high PA amounts in teas. This study comprised the analysis of 87 honey as well as 274 tea samples including black, green, rooibos, melissa, peppermint, chamomile, fennel, nettle, and mixed herbal tea or fruit tea. Total PA concentrations in tea ranged from < LOD to 5647 µg kg(-1), while a mean value of about 10 µg kg(-1) was found in honey samples. Additionally, herbal drugs were investigated to identify the source of PA in teas. Results suggest that PA in tea samples are most likely a contamination caused by co-harvesting of PA-producing plants. In some cases such as fennel, anise or caraway, it cannot be excluded that these plants are able to produce PA themselves.

Nickel-catalyzed cross-coupling of photoredox-generated radicals: uncovering a general manifold for stereoconvergence in nickel-catalyzed cross-couplings.

PubMed

Gutierrez, Osvaldo; Tellis, John C; Primer, David N; Molander, Gary A; Kozlowski, Marisa C

2015-04-22

The cross-coupling of sp(3)-hybridized organoboron reagents via photoredox/nickel dual catalysis represents a new paradigm of reactivity for engaging alkylmetallic reagents in transition-metal-catalyzed processes. Reported here is an investigation into the mechanistic details of this important transformation using density functional theory. Calculations bring to light a new reaction pathway involving an alkylnickel(I) complex generated by addition of an alkyl radical to Ni(0) that is likely to operate simultaneously with the previously proposed mechanism. Analysis of the enantioselective variant of the transformation reveals an unexpected manifold for stereoinduction involving dynamic kinetic resolution (DKR) of a Ni(III) intermediate wherein the stereodetermining step is reductive elimination. Furthermore, calculations suggest that the DKR-based stereoinduction manifold may be responsible for stereoselectivity observed in numerous other stereoconvergent Ni-catalyzed cross-couplings and reductive couplings.

High-throughput discovery of novel developmental phenotypes

PubMed Central

Dickinson, Mary E.; Flenniken, Ann M.; Ji, Xiao; Teboul, Lydia; Wong, Michael D.; White, Jacqueline K.; Meehan, Terrence F.; Weninger, Wolfgang J.; Westerberg, Henrik; Adissu, Hibret; Baker, Candice N.; Bower, Lynette; Brown, James M.; Caddle, L. Brianna; Chiani, Francesco; Clary, Dave; Cleak, James; Daly, Mark J.; Denegre, James M.; Doe, Brendan; Dolan, Mary E.; Edie, Sarah M.; Fuchs, Helmut; Gailus-Durner, Valerie; Galli, Antonella; Gambadoro, Alessia; Gallegos, Juan; Guo, Shiying; Horner, Neil R.; Hsu, Chih-wei; Johnson, Sara J.; Kalaga, Sowmya; Keith, Lance C.; Lanoue, Louise; Lawson, Thomas N.; Lek, Monkol; Mark, Manuel; Marschall, Susan; Mason, Jeremy; McElwee, Melissa L.; Newbigging, Susan; Nutter, Lauryl M.J.; Peterson, Kevin A.; Ramirez-Solis, Ramiro; Rowland, Douglas J.; Ryder, Edward; Samocha, Kaitlin E.; Seavitt, John R.; Selloum, Mohammed; Szoke-Kovacs, Zsombor; Tamura, Masaru; Trainor, Amanda G; Tudose, Ilinca; Wakana, Shigeharu; Warren, Jonathan; Wendling, Olivia; West, David B.; Wong, Leeyean; Yoshiki, Atsushi; MacArthur, Daniel G.; Tocchini-Valentini, Glauco P.; Gao, Xiang; Flicek, Paul; Bradley, Allan; Skarnes, William C.; Justice, Monica J.; Parkinson, Helen E.; Moore, Mark; Wells, Sara; Braun, Robert E.; Svenson, Karen L.; de Angelis, Martin Hrabe; Herault, Yann; Mohun, Tim; Mallon, Ann-Marie; Henkelman, R. Mark; Brown, Steve D.M.; Adams, David J.; Lloyd, K.C. Kent; McKerlie, Colin; Beaudet, Arthur L.; Bucan, Maja; Murray, Stephen A.

2016-01-01

Approximately one third of all mammalian genes are essential for life. Phenotypes resulting from mouse knockouts of these genes have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5000 knockout mouse lines, we have identified 410 lethal genes during the production of the first 1751 unique gene knockouts. Using a standardised phenotyping platform that incorporates high-resolution 3D imaging, we identified novel phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes identified in our screen, thus providing a novel dataset that facilitates prioritization and validation of mutations identified in clinical sequencing efforts. PMID:27626380

Distinct human antibody response to the biological warfare agent Burkholderia mallei.

PubMed

Varga, John J; Vigil, Adam; DeShazer, David; Waag, David M; Felgner, Philip; Goldberg, Joanna B

2012-10-01

The genetic similarity between Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis) had led to the general assumption that pathogenesis of each bacterium would be similar. In 2000, the first human case of glanders in North America since 1945 was reported in a microbiology laboratory worker. Leveraging the availability of pre-exposure sera for this individual and employing the same well-characterized protein array platform that has been previously used to study a large cohort of melioidosis patients in southeast Asia, we describe the antibody response in a human with glanders. Analysis of 156 peptides present on the array revealed antibodies against 17 peptides with a > 2-fold increase in this infection. Unexpectedly, when the glanders data were compared with a previous data set from B. pseudomallei infections, there were only two highly increased antibodies shared between these two infections. These findings have implications in the diagnosis and treatment of B. mallei and B. pseudomallei infections.

Saccharomyces cerevisiae metabolism in ecological context

PubMed Central

Jouhten, Paula; Ponomarova, Olga; Gonzalez, Ramon

2016-01-01

The architecture and regulation of Saccharomyces cerevisiae metabolic network are among the best studied owing to its widespread use in both basic research and industry. Yet, several recent studies have revealed notable limitations in explaining genotype–metabolic phenotype relations in this yeast, especially when concerning multiple genetic/environmental perturbations. Apparently unexpected genotype–phenotype relations may originate in the evolutionarily shaped cellular operating principles being hidden in common laboratory conditions. Predecessors of laboratory S. cerevisiae strains, the wild and the domesticated yeasts, have been evolutionarily shaped by highly variable environments, very distinct from laboratory conditions, and most interestingly by social life within microbial communities. Here we present a brief review of the genotypic and phenotypic peculiarities of S. cerevisiae in the context of its social lifestyle beyond laboratory environments. Accounting for this ecological context and the origin of the laboratory strains in experimental design and data analysis would be essential in improving the understanding of genotype–environment–phenotype relationships. PMID:27634775

Obtaining gravitational waves from inspiral binary systems using LIGO data

NASA Astrophysics Data System (ADS)

Antelis, Javier M.; Moreno, Claudia

2017-01-01

The discovery of the astrophysical events GW150926 and GW151226 has experimentally confirmed the existence of gravitational waves (GW) and has demonstrated the existence of binary stellar-mass black hole systems. This finding marks the beginning of a new era that will reveal unexpected features of our universe. This work presents a basic insight to the fundamental theory of GW emitted by inspiral binary systems and describes the scientific and technological efforts developed to measure these waves using the interferometer-based detector called LIGO. Subsequently, the work presents a comprehensive data analysis methodology based on the matched filter algorithm, which aims to recovery GW signals emitted by inspiral binary systems of astrophysical sources. This algorithm was evaluated with freely available LIGO data containing injected GW waveforms. Results of the experiments performed to assess detection accuracy showed the recovery of 85% of the injected GW.

Investigation of degradation mechanisms in composite matrices

NASA Technical Reports Server (NTRS)

Giori, C.; Yamauchi, T.

1982-01-01

Degradation mechanisms were investigated for graphite/polysulfone and graphite/epoxy laminates exposed to ultraviolet and high-energy electron radiations in vacuum up to 960 equivalent sun hours and 10 to the ninth power rads respectively. Based on GC and combined GC/MS analysis of volatile by-products evolved during irradiation, several free radical mechanisms of composite degradation were identified. The radiation resistance of different matrices was compared in terms of G values and quantum yields for gas formation. All the composite materials evaluated show high electron radiation stability and relatively low ultraviolet stability as indicated by low G values and high quantum for gas formation. Mechanical property measurements of irradiated samples did not reveal significant changes, with the possible exception of UV exposed polysulfone laminates. Hydrogen and methane were identified as the main by-products of irradiation, along with unexpectedly high levels of CO and CO2.

Concepts and analysis for precision segmented reflector and feed support structures

NASA Technical Reports Server (NTRS)

Miller, Richard K.; Thomson, Mark W.; Hedgepeth, John M.

1990-01-01

Several issues surrounding the design of a large (20-meter diameter) Precision Segmented Reflector are investigated. The concerns include development of a reflector support truss geometry that will permit deployment into the required doubly-curved shape without significant member strains. For deployable and erectable reflector support trusses, the reduction of structural redundancy was analyzed to achieve reduced weight and complexity for the designs. The stiffness and accuracy of such reduced member trusses, however, were found to be affected to a degree that is unexpected. The Precision Segmented Reflector designs were developed with performance requirements that represent the Reflector application. A novel deployable sunshade concept was developed, and a detailed parametric study of various feed support structural concepts was performed. The results of the detailed study reveal what may be the most desirable feed support structure geometry for Precision Segmented Reflector/Large Deployable Reflector applications.

Automated deep-phenotyping of the vertebrate brain

PubMed Central

Allalou, Amin; Wu, Yuelong; Ghannad-Rezaie, Mostafa; Eimon, Peter M; Yanik, Mehmet Fatih

2017-01-01

Here, we describe an automated platform suitable for large-scale deep-phenotyping of zebrafish mutant lines, which uses optical projection tomography to rapidly image brain-specific gene expression patterns in 3D at cellular resolution. Registration algorithms and correlation analysis are then used to compare 3D expression patterns, to automatically detect all statistically significant alterations in mutants, and to map them onto a brain atlas. Automated deep-phenotyping of a mutation in the master transcriptional regulator fezf2 not only detects all known phenotypes but also uncovers important novel neural deficits that were overlooked in previous studies. In the telencephalon, we show for the first time that fezf2 mutant zebrafish have significant patterning deficits, particularly in glutamatergic populations. Our findings reveal unexpected parallels between fezf2 function in zebrafish and mice, where mutations cause deficits in glutamatergic neurons of the telencephalon-derived neocortex. DOI: http://dx.doi.org/10.7554/eLife.23379.001 PMID:28406399

Effect of Ground Layer Patterns with Slits on Conducted Noise Currents from Printed Circuit Board

NASA Astrophysics Data System (ADS)

Maeno, Tsuyoshi; Unou, Takanori; Ichikawa, Kouji; Fujiwara, Osamu

Electromagnetic disturbances for vehicle-mounted radios can be caused by conducted noise currents that flows out from electronic equipment for vehicles to wire-harnesses. In this paper, for reducing the conducted noise currents from electronic equipment for vehicles, we made a simulation and experiment on how ground patterns affect the noise currents from three-layer printed circuit boards (PCBs) with slit-types and plane-type ground patterns. As a result, we could confirm that slits on a ground pattern allow conducted noise currents to flow out from PCBs to wire-harnesses. For the PCBs with plane-type ground and one of three slit-type patterns, on the other hand, both the simulation and examination showed that resonance phenomena occur at unexpected low-frequencies. A circuit analysis revealed that the above phenomena can be caused by the imbalance of a bridge circuit consisting of the trace circuits on the PCB.

Laser-induced atomic assembling of periodic layered nanostructures of silver nanoparticles in fluoro-polymer film matrix

NASA Astrophysics Data System (ADS)

Bagratashvili, V. N.; Rybaltovsky, A. O.; Minaev, N. V.; Timashev, P. S.; Firsov, V. V.; Yusupov, V. I.

2010-05-01

Fluorinated acrylic polymer (FAP) films have been impregnated with silver precursor (Ag(hfac)COD) by supercritical fluid technique and next irradiated with laser (λ = 532 nm). Laser-chemically reduced Ag atoms have been assembled into massifs of Ag nanoparticles (3 - 8 nm) in FAP/Ag(hfac)COD films matrix in the form of periodic layered nanostructures (horizontal to film surface) with unexpectedly short period (90 - 180 nm). The wavelet analysis of TEM images reveals the existence of even shorter-period structures in such films. Photolysis with non-coherent light or pyrolysis of FAP/Ag(hfac)COD film results in formation of Ag nanoparticles massifs but free of any periodic nanoparticle assemblies. Our interpretation of the observed effect of laser formation of short-period nano-sized Ag nanoparticle assemblies is based on self-enhanced interference process in the course of modification of optical properties of film.

Data Analysis Methods for Synthetic Polymer Mass Spectrometry: Autocorrelation

PubMed Central

Wallace, William E.; Guttman, Charles M.

2002-01-01

Autocorrelation is shown to be useful in describing the periodic patterns found in high- resolution mass spectra of synthetic polymers. Examples of this usefulness are described for a simple linear homopolymer to demonstrate the method fundamentals, a condensation polymer to demonstrate its utility in understanding complex spectra with multiple repeating patterns on different mass scales, and a condensation copolymer to demonstrate how it can elegantly and efficiently reveal unexpected phenomena. It is shown that using autocorrelation to determine where the signal devolves into noise can be useful in determining molecular mass distributions of synthetic polymers, a primary focus of the NIST synthetic polymer mass spectrometry effort. The appendices describe some of the effects of transformation from time to mass space when time-of-flight mass separation is used, as well as the effects of non-trivial baselines on the autocorrelation function. PMID:27446716

Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma.

PubMed

Salmasi, Vafi; Schiavi, Adam; Binder, Zev A; Ruzevick, Jacob; Orr, Brent A; Burger, Peter C; Ball, Douglas W; Blitz, Ari M; Koch, Wayne M; Ishii, Masaru; Gallia, Gary L

2015-06-01

Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed an intraoperative hypertensive crisis. A patient with a history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Workup revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade before the second stage. Serum catecholamine levels after this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma. © 2015 Wiley Periodicals, Inc.

Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma

PubMed Central

Salmasi, Vafi; Schiavi, Adam; Binder, Zev A.; Ruzevick, Jacob; Orr, Brent A.; Burger, Peter C.; Ball, Douglas W.; Blitz, Ari M.; Koch, Wayne M.; Ishii, Masaru; Gallia, Gary L.

2015-01-01

Background Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. Methods We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed intraoperative hypertensive crisis. Results A patient with history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Work-up revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade prior to the second stage. Serum catecholamine levels following this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in cathecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. Conclusion Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma. PMID:25352487

A fast and simple LC-MS-based characterization of the flavonoid biosynthesis pathway for few seed(ling)s.

PubMed

Jaegle, Benjamin; Uroic, Miran Kalle; Holtkotte, Xu; Lucas, Christina; Termath, Andreas Ole; Schmalz, Hans-Günther; Bucher, Marcel; Hoecker, Ute; Hülskamp, Martin; Schrader, Andrea

2016-09-01

(Pro)anthocyanidins are synthesized by the flavonoid biosynthesis pathway with multi-layered regulatory control. Methods for the analysis of the flavonoid composition in plants are well established for different purposes. However, they typically compromise either on speed or on depth of analysis. In this work we combined and optimized different protocols to enable the analysis of the flavonoid biosynthesis pathway with as little as possible biological material. We chose core substances of this metabolic pathway that serve as a fingerprint to recognize alterations in the main branches of the pathway. We used a simplified sample preparation, two deuterated internal standards, a short and efficient LC separation, highly sensitive detection with tandem MS in multiple reaction monitoring (MRM) mode and hydrolytic release of the core substances to reduce complexity. The method was optimized for Arabidopsis thaliana seeds and seedlings. We demonstrate that one Col-0 seed/seedling is sufficient to obtain a fingerprint of the core substances of the flavonoid biosynthesis pathway. For comparative analysis of different genotypes, we suggest the use of 10 seed(lings). The analysis of Arabidopsis thaliana mutants affecting steps in the pathway revealed foreseen and unexpected alterations of the pathway. For example, HY5 was found to differentially regulate kaempferol in seeds vs. seedlings. Furthermore, our results suggest that COP1 is a master regulator of flavonoid biosynthesis in seedlings but not of flavonoid deposition in seeds. When sample numbers are high and the plant material is limited, this method effectively facilitates metabolic fingerprinting with one seed(ling), revealing shifts and differences in the pathway. Moreover the combination of extracted non-hydrolysed, extracted hydrolysed and non-extracted hydrolysed samples proved useful to deduce the class of derivative from which the individual flavonoids have been released.

Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response.

PubMed

Bendjilali, Nasrine; MacLeon, Samuel; Kalra, Gurmannat; Willis, Stephen D; Hossian, A K M Nawshad; Avery, Erica; Wojtowicz, Olivia; Hickman, Mark J

2017-01-05

Many cells experience hypoxia, or low oxygen, and respond by dramatically altering gene expression. In the yeast Saccharomyces cerevisiae, genes that respond are required for many oxygen-dependent cellular processes, such as respiration, biosynthesis, and redox regulation. To more fully characterize the global response to hypoxia, we exposed yeast to hypoxic conditions, extracted RNA at different times, and performed RNA sequencing (RNA-seq) analysis. Time-course statistical analysis revealed hundreds of genes that changed expression by up to 550-fold. The genes responded with varying kinetics suggesting that multiple regulatory pathways are involved. We identified most known oxygen-regulated genes and also uncovered new regulated genes. Reverse transcription-quantitative PCR (RT-qPCR) analysis confirmed that the lysine methyltransferase EFM6 and the recombinase DMC1, both conserved in humans, are indeed oxygen-responsive. Looking more broadly, oxygen-regulated genes participate in expected processes like respiration and lipid metabolism, but also in unexpected processes like amino acid and vitamin metabolism. Using principle component analysis, we discovered that the hypoxic response largely occurs during the first 2 hr and then a new steady-state expression state is achieved. Moreover, we show that the oxygen-dependent genes are not part of the previously described environmental stress response (ESR) consisting of genes that respond to diverse types of stress. While hypoxia appears to cause a transient stress, the hypoxic response is mostly characterized by a transition to a new state of gene expression. In summary, our results reveal that hypoxia causes widespread and complex changes in gene expression to prepare the cell to function with little or no oxygen. Copyright © 2017 Bendjilali et al.

When cancer cannot be cured: A qualitative study on relationship changes in couples facing advanced melanoma.

PubMed

Drabe, Natalie; Jenewein, Josef; Weidt, Steffi; Engeli, Lucia; Meier, Caroline; Büchi, Stefan; Schad, Karin; Schönbucher, Verena; Canella, Claudia; Nuñez, David Garcia

2016-12-01

The aim of this qualitative study was to gain a deeper understanding about couples' relationship changes over time (the first six months) after one partner is diagnosed with an incurable advanced melanoma (stage III or IV). In semistructured interviews, eight patients and their partners were asked separately about potential changes in their relationship since diagnosis. The same questions were asked again six months later, but focusing on relationship changes over the preceding six months. Some 32 audiotaped interviews were analyzed applying qualitative content analysis. At baseline (t1), relationship changes were mostly reported in terms of caring, closeness/distance regulation, and communication patterns. While changes in caregiving and distance/closeness regulation remained main issues at six months follow-up (t2), greater appreciation of the relationship and limitations in terms of planning spare time also emerged as major issues. Unexpectedly, 50% of patients and partners reported actively hiding their negative emotions and sorrows from their counterparts to spare them worry. Furthermore, qualitative content analysis revealed relationship changes even in those patients and partners who primarily reported no changes over the course of the disease. Our findings revealed a differentiated and complex picture about relationship changes over time, which also might aid in the development of support programs for couples dealing with advanced cancer, focusing on the aspects of caring, closeness/distance regulation, and communication patterns.

Always expect the unexpected: lung abscess due to pseudomonas aeruginosa mimicking pulmonary aspergilloma in acute B-cell leukemia.

PubMed

Dieks, J-K; von Bueren, A O; Schaefer, I-M; Menke, J; Lex, C; Krause, U; Zenker, D; Kühnle, I; Kramm, C M

2013-11-01

We report on a case of Pseudomonas aeruginosa sepsis and consecutive lung abscess in a 13-year-old patient with acute B-cell leukemia. At first, radiographic findings strongly suggested presence of pulmonary aspergilloma and only microbiological testing of the surgically enucleated mass revealed the correct underlying pathogen and confirmed final diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

Initial-state colour dipole emission associated with QCD Pomeron exchange

NASA Astrophysics Data System (ADS)

Bialas, A.; Peschanski, R.

1995-02-01

The initial-state radiation of soft colour dipoles produced together with a single QCD Pomeron exchange (BFKL) in onium-onium scattering is calculated in the framework of Mueller's approach. The resulting dipole production grows with increasing energy and reveals an unexpected feature of a power-law tail at appreciably large transverse distances from the collision axis, this phenomenon being related to the scale-invariant structure of dipole-dipole correlations.

Colors of the Daytime Overcast Sky

DTIC Science & Technology

2005-09-20

sunlight) spectra beneath overcast skies reveal an unexpectedly wide gamut of pastel colors. Analyses of these spectra indicate that at visible wavelengths...care, however, we also were able to acquire some data in drizzle, light rain, and snow. What kinds of chromaticity gamuts do such overcasts produce...noteworthy in Fig. 1. First, its chromaticity gamut for clear daylight is much less than for its two stratus and stratocumu- lus overcasts. Using the

Newborn infant with maternal anti-SSA antibody-induced complete heart block accompanying cardiomyopathy.

PubMed

Iida, Midori; Inamura, Noboru; Takeuchi, Makoto

2006-01-01

Newborn case of maternal anti-SSA antibody-induced congenital complete heart block (CCHB) accompanying cardiomyopathy is presented. Unexpectedly, she died of ventricular tachycardia, not bradycardia, 6 days after birth. Autopsy revealed left ventricular cardiomyopathy with endocardial fibroelastosis. Thus, when evaluating fetal cardiac performance in cases of maternal anti-SSA antibody-induced CCHB, it is necessary to pay attention to myocardial attributes such as endocardial hyperplasia.

Chronicle of a Neuronal Death Foretold: Preventing Aging by Keeping MGRN1 at the Nucleus.

PubMed

Ortolano, Natalya A; Gama, Vivian

2017-05-04

In this issue of Molecular Cell, Benvegnù et al. (2017) report an unexpected phenomenon by which the E3 ligase mahogunin ring finger-1 (MGRN1) translocates to the nucleus in an age-dependent manner, revealing an intriguing mechanism that allows for an adaptive neuronal response to proteotoxic stress, often seen with aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Dualities of fields and strings

NASA Astrophysics Data System (ADS)

Polchinski, Joseph

2017-08-01

Duality, the equivalence between seemingly distinct quantum systems, is a curious property that has been known for at least three quarters of a century. In the past two decades it has played a central role in mapping out the structure of theoretical physics. I discuss the unexpected connections that have been revealed among quantum field theories and string theories. Written for a special issue of Studies in History and Philosophy of Modern Physics.

Long-term stream discharge and chemistry observations reveal unexpected ecosystem dynamics: Coweeta Watershed 7 clearcut manipulation

NASA Astrophysics Data System (ADS)

Jackson, C. R.; Webster, J. R.; Knoepp, J. D.; Elliott, K.; Emanuel, R. E.; Miniat, C.

2017-12-01

In the 1970s, the Coweeta Hydrologic Laboratory Watershed 7 was clearcut from ridge to ridge to observe how far the perturbation would move the ecosystem and how quickly the ecosystem would return to its pre-disturbance state. Nearly 40 years of observations of streamflow and DIN export demonstrate that this view of ecosystem resistance and resilience was too simplistic. Forest disturbance triggered a chain of ecological dynamics that are still evolving. For the first 12 years following watershed road building, forest harvest, and forest regeneration, streamflows and DIN concentrations temporarily increased and then appeared to return to pre-harvest behavior. Thereupon the ecosystem trajectory diverged from expectations. Unexpected successional changes in forest composition interacted with drought cycles, climate change effects, and forest changes due to pests and diseases to push the biogeochemical system into an alternate state featuring persistently high DIN concentrations and hydrological rather than biological control of DIN exports. Thirty years after harvest, these forest changes also increased evapotranspiration and reduced water yields. These ecosystem dynamics were only revealed because of long-term monitoring, and they inspired new research to elucidate mechanisms behind these dynamics. We conclude that long-term approaches are critical for understanding ecosystem dynamics and responses to disturbances.

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

PubMed

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.

Risk factors and consequences of unexpected trapping for ruptured anterior communicating artery aneurysms

PubMed Central

Fukuda, Hitoshi; Iwasaki, Koichi; Murao, Kenichi; Yamagata, Sen; Lo, Benjamin W.Y.; Macdonald, R. Loch

2014-01-01

Background: While clipping cerebral aneurysms at the neck is optimal, in some cases this is not possible and other strategies are necessary. The purpose of this study was to describe the incidence, risk factors, and outcomes for inability to clip reconstruct ruptured anterior communicating artery (ACoA) aneurysms. Methods: Of the 70 cases of ruptured ACoA aneurysms between January 2006 and December 2013, our institutional experience revealed four cases of small ACoA aneurysms that had been considered clippable prior to operation but required trapping. When a unilateral A2 segment of anterior cerebral artery (ACA) was compromised by trapping, revascularization was performed by bypass surgery. Clinical presentation, angiographic characteristics, operative approach, intraoperative findings, and treatment outcomes were assessed. Results: Very small aneurysm under 3 mm was a risk factor for unexpected trapping. The reason for unexpected trapping was laceration of the aneurysmal neck in two cases, and lack of clippaple component due to disintegration of entire aneurysmal wall at the time of rupture in the others. Aneurysms with bilateral A1 were treated with sole trapping through pterional approach in two cases. The other two cases had hypoplastic unilateral A1 segment of ACA and were treated with combination of aneurysm trapping and revascularization of A2 segment of ACA through interhemispheric approach. No patients had new cerebral infarctions of cortical ACA territory from surgery. Cognitive dysfunction was observed in three cases, but all patients became independent at 12-month follow up. Conclusions: Unexpected trapping was performed when ruptured ACoA aneurysms were unclippable. Trapping with or without bypass can result in reasonable outcomes, with acceptable risk of cognitive dysfunction. PMID:25101201

Systematic Association of Genes to Phenotypes by Genome and Literature Mining

PubMed Central

Jensen, Lars J; Perez-Iratxeta, Carolina; Kaczanowski, Szymon; Hooper, Sean D; Andrade, Miguel A

2005-01-01

One of the major challenges of functional genomics is to unravel the connection between genotype and phenotype. So far no global analysis has attempted to explore those connections in the light of the large phenotypic variability seen in nature. Here, we use an unsupervised, systematic approach for associating genes and phenotypic characteristics that combines literature mining with comparative genome analysis. We first mine the MEDLINE literature database for terms that reflect phenotypic similarities of species. Subsequently we predict the likely genomic determinants: genes specifically present in the respective genomes. In a global analysis involving 92 prokaryotic genomes we retrieve 323 clusters containing a total of 2,700 significant gene–phenotype associations. Some clusters contain mostly known relationships, such as genes involved in motility or plant degradation, often with additional hypothetical proteins associated with those phenotypes. Other clusters comprise unexpected associations; for example, a group of terms related to food and spoilage is linked to genes predicted to be involved in bacterial food poisoning. Among the clusters, we observe an enrichment of pathogenicity-related associations, suggesting that the approach reveals many novel genes likely to play a role in infectious diseases. PMID:15799710

Natural progression of blood-induced joint damage in patients with haemophilia: clinical relevance and reproducibility of three-dimensional gait analysis.

PubMed

Lobet, S; Detrembleur, C; Francq, B; Hermans, C

2010-09-01

A major complication in haemophilia is the destruction of joint cartilage because of recurrent intraarticular and intramuscular bleeds. Therefore, joint assessment is critical to quantify the extent of joint damage, which has traditionally been evaluated using both radiological and clinical joint scores. Our study aimed to evaluate the natural progression of haemophilic arthopathy using three-dimensional gait analysis (3DGA) and to assess the reproducibility of this technique. We hypothesized that the musculoskeletal function was relatively stable in patients with haemophilia. Eighteen adults with established haemophilic arthropathies were evaluated twice by 3DGA (mean follow-up: 18 +/- 5 weeks). Unexpectedly, our findings revealed infraclinical deterioration of gait pattern, characterized by a 3.2% decrease in the recovery index, which is indicative of the subject's ability to save energy while walking. A tendency towards modification of segmental joint function was also observed. Gait analysis was sufficiently reproducible with regards to spatiotemporal parameters as well as kinetic, mechanical and energetic gait variables. The kinematic variables were reproducible in both the sagittal and frontal planes. In conclusion, 3DGA is a reproducible tool to assess abnormal gait patterns and monitor natural disease progression in haemophilic patients.

Publish unexpected results that conflict with assumptions

USDA-ARS?s Scientific Manuscript database

Some widely held scientific assumptions have been discredited, whereas others are just inappropriate for many applications. Sometimes, a widely-held analysis procedure takes on a life of its own, forgetting the original purpose of the analysis. The peer-reviewed system makes it difficult to get a pa...

Intracellular route and biological activity of exogenously delivered Rep proteins from the adeno-associated virus type 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Awedikian, Rafi; Francois, Achille; Guilbaud, Mickael

2005-05-10

The two large Rep proteins, Rep78 and Rep68, from the adeno-associated virus type 2 (AAV-2) are required for AAV-2 DNA replication, site-specific integration, and for the regulation of viral gene expression. The study of their activities is dependent on the ability to deliver these proteins to the cells in a time and dose-dependent manner. We evaluated the ability of a protein transduction domain (PTD) derived from the human immunodeficiency virus 1 (HIV-1) TAT protein to drive the cellular internalization of exogenously delivered PTD-fused Rep68 proteins. This analysis unexpectedly revealed that recombinant Rep68 alone, in the absence of any PTD, couldmore » be endocytosed by the cells. Rep68 as the chimeric TAT-Rep68 proteins were internalized through endocytosis in clathrin-coated vesicles and retained in late endosomes/lysosomes with no detectable nuclear localization. In the presence of adenovirus, the Rep proteins could translocate into the nucleus where they displayed a biological activity. These findings support recent reports on the mechanism of entry of TAT-fused proteins and also revealed a new property of Rep68.« less

Different Planctomycetes diversity patterns in latitudinal surface seawater of the open sea and in sediment.

PubMed

Shu, Qinglong; Jiao, Nianzhi

2008-04-01

The 16S rRNA gene approach was applied to investigate the diversity of Planctomycetes in latitudinal surface seawater of the Western Pacific Ocean. The results revealed that the Pirellula-Rhodopirellula-Blastopirellula clade dominated the Planctomycetes community at all surface seawater sites while the minority genera Gemmata and Planctomyces were only found at sites H5 and H2 respectively. Although the clone frequency of the PRB clade seemed stable (between 83.3% and 94.1%) for all surface seawater sites, the retrieved Pirellula-Rhodopirellula-Blastopirellula clade presented unexpected diversity. Interestingly, low latitude seawater appeared to have higher diversity than mid-latitudes. integral-LIBSHUFF software analysis revealed significantly different diversity patterns between in latitudinal surface seawater and in the sediment of South China Sea station M2896. Our data suggested that different hydrological and geographic features contributed to the shift of Planctomycetes diversity in marine environments. This is, to our knowledge, the first systematic assessment of Planctomycetes in latitudinal surface seawater of the open sea and the first comparison of diversity pattern between surface seawater and sediments and has broadened our understanding of Planctomycetes diversity in marine environments.

The Influence of Task-Irrelevant Music on Language Processing: Syntactic and Semantic Structures

PubMed Central

Hoch, Lisianne; Poulin-Charronnat, Benedicte; Tillmann, Barbara

2011-01-01

Recent research has suggested that music and language processing share neural resources, leading to new hypotheses about interference in the simultaneous processing of these two structures. The present study investigated the effect of a musical chord's tonal function on syntactic processing (Experiment 1) and semantic processing (Experiment 2) using a cross-modal paradigm and controlling for acoustic differences. Participants read sentences and performed a lexical decision task on the last word, which was, syntactically or semantically, expected or unexpected. The simultaneously presented (task-irrelevant) musical sequences ended on either an expected tonic or a less-expected subdominant chord. Experiment 1 revealed interactive effects between music-syntactic and linguistic-syntactic processing. Experiment 2 showed only main effects of both music-syntactic and linguistic-semantic expectations. An additional analysis over the two experiments revealed that linguistic violations interacted with musical violations, though not differently as a function of the type of linguistic violations. The present findings were discussed in light of currently available data on the processing of music as well as of syntax and semantics in language, leading to the hypothesis that resources might be shared for structural integration processes and sequencing. PMID:21713122

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

PubMed

Di Gregorio, E; Riberi, E; Belligni, E F; Biamino, E; Spielmann, M; Ala, U; Calcia, A; Bagnasco, I; Carli, D; Gai, G; Giordano, M; Guala, A; Keller, R; Mandrile, G; Arduino, C; Maffè, A; Naretto, V G; Sirchia, F; Sorasio, L; Ungari, S; Zonta, A; Zacchetti, G; Talarico, F; Pappi, P; Cavalieri, S; Giorgio, E; Mancini, C; Ferrero, M; Brussino, A; Savin, E; Gandione, M; Pelle, A; Giachino, D F; De Marchi, M; Restagno, G; Provero, P; Cirillo Silengo, M; Grosso, E; Buxbaum, J D; Pasini, B; De Rubeis, S; Brusco, A; Ferrero, G B

2017-10-01

Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). Identification of genomic disorders in DD/ID. We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reading Instruments: Objects, Texts and Museums

NASA Astrophysics Data System (ADS)

Anderson, Katharine; Frappier, Mélanie; Neswald, Elizabeth; Trim, Henry

2013-05-01

Science educators, historians of science and their students often share a curiosity about historical instruments as a tangible link between past and present practices in the sciences. We less often integrate instruments into our research and pedagogy, considering artefact study as the domain of museum specialists. We argue here that scholars and teachers new to material culture can readily use artefacts to reveal rich and complex networks of narratives. We illustrate this point by describing our own lay encounter with an artefact turned over for our analysis during a week-long workshop at the Canada Science and Technology Museum. The text explains how elements as disparate as the military appearance of the instrument, the crest stamped on its body, the manipulation of its telescopes, or a luggage tag revealed the object's scientific and political significance in different national contexts. In this way, the presence of the instrument in the classroom vividly conveyed the nature of geophysics as a field practice and an international science, and illuminated relationships between pure and applied science for early twentieth century geologists. We conclude that artefact study can be an unexpectedly powerful and accessible tool in the study of science, making visible the connections between past and present, laboratory and field, texts and instruments.

9-cis-retinoic acid represses estrogen-induced expression of the very low density apolipoprotein II gene.

PubMed

Schippers, I J; Kloppenburg, M; Snippe, L; Ab, G

1994-11-01

The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9-cis-retinoic acid (9-cis-RA) in the activation of the apoVLDLII promoter. We first concentrated on a potential RXR recognition site, which deviates at only one position from a perfect direct A/GGGTCA repeat spaced by one nucleotide (DR-1) and was earlier identified as a common HNF-4/COUP-TF recognition site. However, band shift analysis revealed that this imperfect DR-1 motif does not interact with RXR alpha-homodimers. In accordance with this observation we found that this regulatory element does not mediate transactivation through RXR alpha in the presence of 9-cis-RA. However, our experiments revealed another, unexpected, effect of 9-cis-RA. Instead of stimulating, 9-cis-RA attenuated estrogen-induced expression of transfected estrogen-responsive VLDL-CAT reporter plasmids. This repression appeared to take place through the main estrogen response element (ERE) of the gene. Importantly, 9-cis-RA also strongly repressed the estrogen-induced expression of the endogenous apoVLDLII gene in cultured chicken hepatoma cells.

Molecular signatures of fossil leaves provide unexpected new evidence for extinct plant relationships.

PubMed

Vajda, Vivi; Pucetaite, Milda; McLoughlin, Stephen; Engdahl, Anders; Heimdal, Jimmy; Uvdal, Per

2017-08-01

Gene sequences form the primary basis for understanding the relationships among extant plant groups, but genetic data are unavailable from fossils to evaluate the affinities of extinct taxa. Here we show that geothermally resistant fossil cuticles of seed-bearing plants, analysed with Fourier transform infrared (FTIR) spectroscopy and hierarchical cluster analysis (HCA), retain biomolecular suites that consistently distinguish major taxa even after experiencing different diagenetic histories. Our results reveal that similarities between the cuticular biochemical signatures of major plant groups (extant and fossil) are mostly consistent with recent phylogenetic hypotheses based on molecular and morphological data. Our novel chemotaxonomic data also support the hypothesis that the extinct Nilssoniales and Bennettitales are closely allied, but only distantly related to Cycadales. The chemical signature of the cuticle of Czekanowskia (Leptostrobales) is strongly similar to that of Ginkgo leaves and supports a close evolutionary relationship between these groups. Finally, our results also reveal that the extinct putative araucariacean, Allocladus, when analysed through HCA, is grouped closer to Ginkgoales than to conifers. Thus, in the absence of modern relatives yielding molecular information, FTIR spectroscopy provides valuable proxy biochemical data complementing morphological characters to distinguish fossil taxa and to help elucidate extinct plant relationships.

Nanocolloids in Natural Water: Isolation, Characterization, and Toxicity.

PubMed

Ouyang, Shaohu; Hu, Xiangang; Zhou, Qixing; Li, Xiaokang; Miao, Xinyu; Zhou, Ruiren

2018-04-17

Nanocolloids are widespread in natural water systems, but their characterization and ecological risks are largely unknown. Herein, tangential flow ultrafiltration (TFU) was used to separate and concentrate nanocolloids from surface waters. Unexpectedly, nanocolloids were present in high concentrations ranging from 3.7 to 7.2 mg/L in the surface waters of the Harihe River in Tianjin City, China. Most of the nanocolloids were 10-40 nm in size, contained various trace metals and polycyclic aromatic hydrocarbons, and exhibited fluorescence properties. Envelopment effects and aggregation of Chlorella vulgaris in the presence of nanocolloids were observed. Nanocolloids entered cells and nanocolloid-exposed cells exhibited stronger plasmolysis, chloroplast damage and more starch grains than the control cells. Moreover, nanocolloids inhibited the cell growth, promoted reactive oxygen species (ROS), reduce the chlorophyll a content and increased the cell permeability. The genotoxicity of nanocolloids was also observed. The metabolomics analysis revealed a significant ( p < 0.05) downregulation of amino acids and upregulation of fatty acids contributing to ROS increase, chlorophyll a decrease and plasmolysis. The present work reveals that nanocolloids, which are different from specific, engineered nanoparticles (e.g., Ag nanoparticles), are present at high concentrations, exhibit an obvious toxicity in environments, and deserve more attention in the future.

Intestinal absorption of the acetamiprid neonicotinoid by Caco-2 cells: transepithelial transport, cellular uptake and efflux.

PubMed

Brunet, Jean-Luc; Maresca, Marc; Fantini, Jacques; Belzunces, Luc P

2008-01-01

The human intestinal absorption of acetamiprid (AAP) using the Caco-2 cell line reveals that AAP flux was active in a bidirectional mode with an apparent permeability coefficient of 26 x 10(-6) cm x s(-1) at 37 degrees C. Apical uptake was concentration-dependent and unsaturated for AAP concentrations up to 200 micro M. AAP cell preloading demonstrated the involvement of active transport mechanisms. Arrhenius plot analysis revealed an unusual profile with two apparent activation energies suggesting two transport processes. Uptake Vi studies indicated the involvement of a sodium-dependent transporter, the presence of a common transporter of AAP and nicotine and the involvement of Ti-sensitive ATP-dependent efflux transporters. Apical efflux investigations showed the involvement of inward active transporter(s). Whereas vincristine had no effect on intracellular accumulation, taxol and daunorubicin treatments unexpectedly led to 10% and 23% reductions respectively, suggesting that the latter shared a common inward transporter with AAP. All these results suggest full and express AAP absorption in vivo with transport involving both inward and outward, passive and active mechanisms. Thus, AAP or its metabolites could be representative of a risk for human health after its ingestion in food.

Linking performance decline to choking: players' perceptions in basketball.

PubMed

Fryer, Ashley Marie; Tenenbaum, Gershon; Chow, Graig M

2018-02-01

This study was aimed at examining how basketball players view unexpected performance errors in basketball, and under what conditions they perceive them as choking. Fifty-three basketball players were randomly assigned into 2 groups (game half) to evaluate the linkage between performance decline and choking as a function of game-time, score gap and game half. Within each group, players viewed 8 scenario clips, which featured a different player conducting an error, and subsequently rated the extent of performance decline, the instance of choking and the salience of various performance attributions regarding the error. The analysis revealed that choking was most salient in the 2nd half of the game, but an error was perceived as choking more saliently in the beginning of the 2nd half. This trend was also shown for players' perception of performance decline. Players' ratings of the attributions assigned to errors, however, revealed that during the end of the 2nd half, time pressure and lack of concentration were the causes of errors. Overall, the results provide evidence towards a conceptual framework linking performance decline to the perception of choking, and that errors conducted by players are perceived as choking when there is not a salient reason to suggest its occurrence.

A second trigeminal CGRP receptor: function and expression of the AMY1 receptor

PubMed Central

Walker, Christopher S; Eftekhari, Sajedeh; Bower, Rebekah L; Wilderman, Andrea; Insel, Paul A; Edvinsson, Lars; Waldvogel, Henry J; Jamaluddin, Muhammad A; Russo, Andrew F; Hay, Debbie L

2015-01-01

Objective The trigeminovascular system plays a central role in migraine, a condition in need of new treatments. The neuropeptide, calcitonin gene-related peptide (CGRP), is proposed as causative in migraine and is the subject of intensive drug discovery efforts. This study explores the expression and functionality of two CGRP receptor candidates in the sensory trigeminal system. Methods Receptor expression was determined using Taqman G protein-coupled receptor arrays and immunohistochemistry in trigeminal ganglia (TG) and the spinal trigeminal complex of the brainstem in rat and human. Receptor pharmacology was quantified using sensitive signaling assays in primary rat TG neurons. Results mRNA and histological expression analysis in rat and human samples revealed the presence of two CGRP-responsive receptors (AMY1: calcitonin receptor/receptor activity-modifying protein 1 [RAMP1]) and the CGRP receptor (calcitonin receptor-like receptor/RAMP1). In support of this finding, quantification of agonist and antagonist potencies revealed a dual population of functional CGRP-responsive receptors in primary rat TG neurons. Interpretation The unexpected presence of a functional non-canonical CGRP receptor (AMY1) at neural sites important for craniofacial pain has important implications for targeting the CGRP axis in migraine. PMID:26125036

Blackbody emission from laser breakdown in high-pressure gases.

PubMed

Bataller, A; Plateau, G R; Kappus, B; Putterman, S

2014-08-15

Laser induced breakdown of pressurized gases is used to generate plasmas under conditions where the atomic density and temperature are similar to those found in sonoluminescing bubbles. Calibrated streak spectroscopy reveals that a blackbody persists well after the exciting femtosecond laser pulse has turned off. Deviation from Saha's equation of state and an accompanying large reduction in ionization potential are observed at unexpectedly low atomic densities-in parallel with sonoluminescence. In laser breakdown, energy input proceeds via excitation of electrons whereas in sonoluminescence it is initiated via the atoms. The similar responses indicate that these systems are revealing the thermodynamics and transport of a strongly coupled plasma.

Blackbody Emission from Laser Breakdown in High-Pressure Gases

NASA Astrophysics Data System (ADS)

Bataller, A.; Plateau, G. R.; Kappus, B.; Putterman, S.

2014-08-01

Laser induced breakdown of pressurized gases is used to generate plasmas under conditions where the atomic density and temperature are similar to those found in sonoluminescing bubbles. Calibrated streak spectroscopy reveals that a blackbody persists well after the exciting femtosecond laser pulse has turned off. Deviation from Saha's equation of state and an accompanying large reduction in ionization potential are observed at unexpectedly low atomic densities—in parallel with sonoluminescence. In laser breakdown, energy input proceeds via excitation of electrons whereas in sonoluminescence it is initiated via the atoms. The similar responses indicate that these systems are revealing the thermodynamics and transport of a strongly coupled plasma.

A Network Analysis of Countries’ Export Flows: Firm Grounds for the Building Blocks of the Economy

PubMed Central

Caldarelli, Guido; Cristelli, Matthieu; Gabrielli, Andrea; Pietronero, Luciano; Scala, Antonio; Tacchella, Andrea

2012-01-01

In this paper we analyze the bipartite network of countries and products from UN data on country production. We define the country-country and product-product projected networks and introduce a novel method of filtering information based on elements’ similarity. As a result we find that country clustering reveals unexpected socio-geographic links among the most competing countries. On the same footings the products clustering can be efficiently used for a bottom-up classification of produced goods. Furthermore we mathematically reformulate the “reflections method” introduced by Hidalgo and Hausmann as a fixpoint problem; such formulation highlights some conceptual weaknesses of the approach. To overcome such an issue, we introduce an alternative methodology (based on biased Markov chains) that allows to rank countries in a conceptually consistent way. Our analysis uncovers a strong non-linear interaction between the diversification of a country and the ubiquity of its products, thus suggesting the possible need of moving towards more efficient and direct non-linear fixpoint algorithms to rank countries and products in the global market. PMID:23094044

Sociocultural influences on science and on science identities

NASA Astrophysics Data System (ADS)

Guerra, Andreia; Rezende, Flavia

2017-06-01

Angela Chapman and Allan Feldman (2016) conducted a study that aimed to exam how a group of diverse urban high school students were affected by the participation in a contextually based authentic science experience. The analysis of all data led the authors to conclude that the experience of authentic science positively influenced the science identity of students and promoted a shift in perceptions from stereotypical to more diverse views of scientists. For the purpose of this forum paper, we concentrated on the unexpected results of Hispanic students in the IAS instrument. In the authors' interpretation, Hispanic students were classified as non science identities because they do not feel recognized as a particular kind of student in that school, being possibly more marginalized than other students. We tried to expand the discussion bringing the contribution of a sociocultural approach of science construction and of science identity to enrich some of the issues involved. Our concise analysis does not allow conclusions about the Hispanic students' results, but we believe it helped to understand sociocultural problems involved in their science identity and to reveal the inequality in science production as one of these problems.

Isomerization, Perturbations, Calculations and the S_{1} State of C_{2}H_{2}

NASA Astrophysics Data System (ADS)

Baraban, J. H.; Changala, P. B.; Berk, J. R. P.; Field, R. W.; Stanton, J. F.; Merer, A. J.

2013-06-01

Preliminary analysis of the energy region of the cis-trans isomerization transition state on the S_{1} surface of C_{2}H_{2} has revealed novel patterns and surprising perturbations, including unusually large (and high-order) anharmonicities, as well as K-staggerings of several vibrational levels. These effects complicate the analysis considerably, and require new models and calculations to account for and predict features of the observed spectra. The ˜{A}-˜{X} spectrum of acetylene has been studied both experimentally and theoretically for almost a century, and this cycle of unexpected phenomena eliciting innovative responses is found throughout its history. Especially in the last ten years, progress in understanding the S_{1} state rovibrational level structure and cis-trans isomerization has been accelerated by combining the information available from both ab initio computation and spectroscopic observations. The resulting dialogue has then frequently suggested fruitful avenues for further experiments and calculations. Current challenges and recent results in understanding the cis-trans isomerization transition state region will be discussed in this context.

Evolution of the Drosophila melanogaster-sigma virus system in natural populations from Languedoc (southern France).

PubMed

Fleuriet, A; Periquet, G

1993-01-01

An analysis of natural populations of Drosophila melanogaster in a southern French region (Languedoc) was started in 1983, concerning two non Mendelian systems: the P-M system of transposable elements and the sigma virus. This virus is not contagious, but only transmitted through gametes; it is usually present in a minority of individuals in natural populations. The first data collected revealed unexpectedly clear and fast-evolving phenomena; they also gave evidence of some interesting correlations between the two systems. This paper presents all the results gathered from 1983 to 1991 in the Drosophila-sigma system. Striking correlations were observed for three interconnected parameters: frequency of infected flies, frequency of an allele of the fly giving resistance to the virus, and adaptation of the virus to this allele. This adaptation consisted of a qualitative step (change of viral type) followed by quantitative variation (better adaptation to the allele). This analysis also showed, firstly, that the evolution of natural populations differs completely in Languedoc from the rest of France; secondly, that three geographical zones where selective forces worked differently persisted over time in Languedoc.

Unexpected identification of a recurrent mutation in the DLX3 gene causing amelogenesis imperfecta.

PubMed

Kim, Y-J; Seymen, F; Koruyucu, M; Kasimoglu, Y; Gencay, K; Shin, T J; Hyun, H-K; Lee, Z H; Kim, J-W

2016-05-01

To identify the molecular genetic aetiology of a family with autosomal dominant amelogenesis imperfecta (AI). DNA samples were collected from a six-generation family, and the candidate gene approach was used to screen for the enamelin (ENAM) gene. Whole-exome sequencing and linkage analysis with SNP array data identified linked regions, and candidate gene screening was performed. Mutational analysis revealed a mutation (c.561_562delCT and p.Tyr188Glnfs*13) in the DLX3 gene. After finding a recurrent DLX3 mutation, the clinical phenotype of the family members was re-examined. The proband's mother had pulp elongation in the third molars. The proband had not hair phenotype, but her cousin had curly hair at birth. In this study, we identified a recurrent 2-bp deletional DLX3 mutation in a new family. The clinical phenotype was the mildest one associated with the DLX3 mutations. These results will advance the understanding of the functional role of DLX3 in developmental processes. © 2016 The Authors. Oral Diseases Published by John Wiley & Sons Ltd.

Nonlinear Parametric Excitation Effect Induces Stability Transitions in Swimming Direction of Flexible Superparamagnetic Microswimmers.

PubMed

Harduf, Yuval; Jin, Dongdong; Or, Yizhar; Zhang, Li

2018-04-05

Microscopic artificial swimmers have recently become highly attractive due to their promising potential for biomedical microrobotic applications. Previous pioneering work has demonstrated the motion of a robotic microswimmer with a flexible chain of superparamagnetic beads, which is actuated by applying an oscillating external magnetic field. Interestingly, they have shown that the microswimmer's orientation undergoes a 90°-transition when the magnetic field's oscillation amplitude is increased above a critical value. This unexpected transition can cause severe problems in steering and manipulation of flexible magnetic microrobotic swimmers. Thus, theoretical understanding and analysis of the physical origins of this effect are of crucial importance. In this work, we investigate this transition both theoretically and experimentally by using numerical simulations and presenting a novel flexible microswimmer with an anisotropic superparamagnetic head. We prove that this effect depends on both frequency and amplitude of the oscillating magnetic field, and demonstrate existence of an optimal amplitude achieving maximal swimming speed. Asymptotic analysis of a minimal two-link model reveals that the changes in the swimmer's direction represent stability transitions, which are induced by a nonlinear parametric excitation.

Detailed Wave Function Analysis for Multireference Methods: Implementation in the Molcas Program Package and Applications to Tetracene.

PubMed

Plasser, Felix; Mewes, Stefanie A; Dreuw, Andreas; González, Leticia

2017-11-14

High-level multireference computations on electronically excited and charged states of tetracene are performed, and the results are analyzed using an extensive wave function analysis toolbox that has been newly implemented in the Molcas program package. Aside from verifying the strong effect of dynamic correlation, this study reveals an unexpected critical influence of the atomic orbital basis set. It is shown that different polarized double-ζ basis sets produce significantly different results for energies, densities, and overall wave functions, with the best performance obtained for the atomic natural orbital (ANO) basis set by Pierloot et al. Strikingly, the ANO basis set not only reproduces the energies but also performs exceptionally well in terms of describing the diffuseness of the different states and of their attachment/detachment densities. This study, thus, not only underlines the fact that diffuse basis functions are needed for an accurate description of the electronic wave functions but also shows that, at least for the present example, it is enough to include them implicitly in the contraction scheme.

Reduction-resistant and reduction-catalytic double-crown nickel nanoclusters

NASA Astrophysics Data System (ADS)

Zhu, Min; Zhou, Zhou, Shiming; Yao, Chuanhao; Liao, Lingwen; Wu, Zhikun

2014-11-01

In this work, an attempt to synthesize zero-valent Ni nanoclusters using the Brust method resulted in an unexpected material, Ni6(SCH2CH2Ph)12, which is a nanoscale Ni(ii)-phenylethanethiolate complex and a hexameric, double-crown-like structure, as determined by a series of characterizations, including mass spectrometry (MS), thermal gravimetric analysis (TGA), single-crystal X-ray diffraction (XRD), and X-ray photoelectron spectrometry (XPS). An interesting finding is that this complex is resistant to aqueous BH4-. Investigations into other metal-phenylethanethiolate and Ni-thiolate complexes reveal that this property is not universal and appears only in complexes with a double-crown-like structure, indicating the correlation between this interesting property and the complexes' special structure. Another interesting finding is that the reduction-resistant Ni6(SCH2CH2Ph)12 exhibits remarkably higher catalytic activity than a well-known catalyst, Au25(SCH2CH2Ph)18, toward the reduction of 4-nitrophenol at low temperature (e.g., 0 °C). This work will help stimulate more research on the properties and applications of less noble metal nanoclusters.In this work, an attempt to synthesize zero-valent Ni nanoclusters using the Brust method resulted in an unexpected material, Ni6(SCH2CH2Ph)12, which is a nanoscale Ni(ii)-phenylethanethiolate complex and a hexameric, double-crown-like structure, as determined by a series of characterizations, including mass spectrometry (MS), thermal gravimetric analysis (TGA), single-crystal X-ray diffraction (XRD), and X-ray photoelectron spectrometry (XPS). An interesting finding is that this complex is resistant to aqueous BH4-. Investigations into other metal-phenylethanethiolate and Ni-thiolate complexes reveal that this property is not universal and appears only in complexes with a double-crown-like structure, indicating the correlation between this interesting property and the complexes' special structure. Another interesting finding is that the reduction-resistant Ni6(SCH2CH2Ph)12 exhibits remarkably higher catalytic activity than a well-known catalyst, Au25(SCH2CH2Ph)18, toward the reduction of 4-nitrophenol at low temperature (e.g., 0 °C). This work will help stimulate more research on the properties and applications of less noble metal nanoclusters. Electronic supplementary information (ESI) available: Experimental section, detailed structural data, MS analyses of M-SCH2CH2Ph complexes, stability study of Ni6 and TGA analysis of Au25(SCH2CH2Ph)18. See DOI: 10.1039/c4nr04981k

Analytic Steering: Inserting Context into the Information Dialog

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bohn, Shawn J.; Calapristi, Augustin J.; Brown, Shyretha D.

2011-10-23

An analyst’s intrinsic domain knowledge is a primary asset in almost any analysis task. Unstructured text analysis systems that apply un-supervised content analysis approaches can be more effective if they can leverage this domain knowledge in a manner that augments the information discovery process without obfuscating new or unexpected content. Current unsupervised approaches rely upon the prowess of the analyst to submit the right queries or observe generalized document and term relationships from ranked or visual results. We propose a new approach which allows the user to control or steer the analytic view within the unsupervised space. This process ismore » controlled through the data characterization process via user supplied context in the form of a collection of key terms. We show that steering with an appropriate choice of key terms can provide better relevance to the analytic domain and still enable the analyst to uncover un-expected relationships; this paper discusses cases where various analytic steering approaches can provide enhanced analysis results and cases where analytic steering can have a negative impact on the analysis process.« less

Computerized video-enhanced high temporal resolution of erythrocytes sedimentation rate (ESR-graphy) reveals complex dynamic and self-organizing properties of whole blood

NASA Astrophysics Data System (ADS)

Voeikov, Vladimir L.; Kondakov, Sergey E.; Buravleva, Ekaterina; Kaganovsky, Isaak; Reznikov, Mikhail

2000-05-01

An automatic device for high-temporal resolution of the process of red blood sedimentation was designed. The position of the boundary between red blood and plasma may be registered each 30 sec in several pipettes simultaneously with +/- 10 mkm precision. Fractional rates of the boundary movement are deduced with high accuracy. Data are processed by a PC and presented as velocity-time curves (ESR-grams) and the curves describing time evolution of the boundary position. Several unexpected phenomena in the process of red blood sedimentation have been revealed. Upward fast movements of the boundary up to 1 mm were noted. In patients' blood sets of 5 - 10 milliHz oscillations of sedimentation rate were usually developing at early stages of blood sedimentation. In non-diluted healthy donors' blood high amplitude periodic oscillations were either absent, or were emerging only after blood resided in pipettes for several hours. When blood was diluted to a certain degree with physiological saline or with own plasma long-term low frequency (1 - 3 milliHz) rate oscillations regularly appeared. Non-trivial dependence of patterns of ESR-grams on diluting of blood with own plasma or saline was observed. Thus, non-linear dynamic behavior of living blood has been revealed due to application of the principles of the system of technical vision for the detailed analysis of red blood sedimentation kinetics.

Unexpected Results are Usually Wrong, but Often Interesting

NASA Astrophysics Data System (ADS)

Huber, M.

2014-12-01

In climate modeling, an unexpected result is usually wrong, arising from some sort of mistake. Despite the fact that we all bemoan uncertainty in climate, the field is underlain by a robust, successful body of theory and any properly conducted modeling experiment is posed and conducted within that context. Consequently, if results from a complex climate model disagree with theory or from expectations from simpler models, much skepticism is in order. But, this exposes the fundamental tension of using complex, sophisticated models. If simple models and theory were perfect there would be no reason for complex models--the entire point of sophisticated models is to see if unexpected phenomena arise as emergent properties of the system. In this talk, I will step through some paleoclimate examples, drawn from my own work, of unexpected results that emerge from complex climate models arising from mistakes of two kinds. The first kind of mistake, is what I call a 'smart mistake'; it is an intentional incorporation of assumptions, boundary conditions, or physics that is in violation of theoretical or observational constraints. The second mistake, a 'dumb mistake', is just that, an unintentional violation. Analysis of such mistaken simulations provides some potentially novel and certainly interesting insights into what is possible and right in paleoclimate modeling by forcing the reexamination of well-held assumptions and theories.

Community structure analysis of rejection sensitive personality profiles: A common neural response to social evaluative threat?

PubMed

Kortink, Elise D; Weeda, Wouter D; Crowley, Michael J; Gunther Moor, Bregtje; van der Molen, Melle J W

2018-06-01

Monitoring social threat is essential for maintaining healthy social relationships, and recent studies suggest a neural alarm system that governs our response to social rejection. Frontal-midline theta (4-8 Hz) oscillatory power might act as a neural correlate of this system by being sensitive to unexpected social rejection. Here, we examined whether frontal-midline theta is modulated by individual differences in personality constructs sensitive to social disconnection. In addition, we examined the sensitivity of feedback-related brain potentials (i.e., the feedback-related negativity and P3) to social feedback. Sixty-five undergraduate female participants (mean age = 19.69 years) participated in the Social Judgment Paradigm, a fictitious peer-evaluation task in which participants provided expectancies about being liked/disliked by peer strangers. Thereafter, they received feedback signaling social acceptance/rejection. A community structure analysis was employed to delineate personality profiles in our data. Results provided evidence of two subgroups: one group scored high on attachment-related anxiety and fear of negative evaluation, whereas the other group scored high on attachment-related avoidance and low on fear of negative evaluation. In both groups, unexpected rejection feedback yielded a significant increase in theta power. The feedback-related negativity was sensitive to unexpected feedback, regardless of valence, and was largest for unexpected rejection feedback. The feedback-related P3 was significantly enhanced in response to expected social acceptance feedback. Together, these findings confirm the sensitivity of frontal midline theta oscillations to the processing of social threat, and suggest that this alleged neural alarm system behaves similarly in individuals that differ in personality constructs relevant to social evaluation.

Plants and climate change: complexities and surprises

PubMed Central

Parmesan, Camille; Hanley, Mick E.

2015-01-01

Background Anthropogenic climate change (ACC) will influence all aspects of plant biology over coming decades. Many changes in wild species have already been well-documented as a result of increased atmospheric CO2 concentrations, warming climate and changing precipitation regimes. A wealth of available data has allowed the use of meta-analyses to examine plant–climate interactions on more sophisticated levels than before. These analyses have revealed major differences in plant response among groups, e.g. with respect to functional traits, taxonomy, life-history and provenance. Interestingly, these meta-analyses have also exposed unexpected mismatches between theory, experimental, and observational studies. Scope We reviewed the literature on species’ responses to ACC, finding ∼42 % of 4000 species studied globally are plants (primarily terrestrial). We review impacts on phenology, distributions, ecophysiology, regeneration biology, plant–plant and plant–herbivore interactions, and the roles of plasticity and evolution. We focused on apparent deviations from expectation, and highlighted cases where more sophisticated analyses revealed that unexpected changes were, in fact, responses to ACC. Conclusions We found that conventionally expected responses are generally well-understood, and that it is the aberrant responses that are now yielding greater insight into current and possible future impacts of ACC. We argue that inconclusive, unexpected, or counter-intuitive results should be embraced in order to understand apparent disconnects between theory, prediction, and observation. We highlight prime examples from the collection of papers in this Special Issue, as well as general literature. We found use of plant functional groupings/traits had mixed success, but that some underutilized approaches, such as Grime's C/S/R strategies, when incorporated, have improved understanding of observed responses. Despite inherent difficulties, we highlight the need for ecologists to conduct community-level experiments in systems that replicate multiple aspects of ACC. Specifically, we call for development of coordinating experiments across networks of field sites, both natural and man-made. PMID:26555281

Economic and workflow analysis of a blood bank automated system.

PubMed

Shin, Kyung-Hwa; Kim, Hyung Hoi; Chang, Chulhun L; Lee, Eun Yup

2013-07-01

This study compared the estimated costs and times required for ABO/Rh(D) typing and unexpected antibody screening using an automated system and manual methods. The total cost included direct and labor costs. Labor costs were calculated on the basis of the average operator salaries and unit values (minutes), which was the hands-on time required to test one sample. To estimate unit values, workflows were recorded on video, and the time required for each process was analyzed separately. The unit values of ABO/Rh(D) typing using the manual method were 5.65 and 8.1 min during regular and unsocial working hours, respectively. The unit value was less than 3.5 min when several samples were tested simultaneously. The unit value for unexpected antibody screening was 2.6 min. The unit values using the automated method for ABO/Rh(D) typing, unexpected antibody screening, and both simultaneously were all 1.5 min. The total cost of ABO/Rh(D) typing of only one sample using the automated analyzer was lower than that of testing only one sample using the manual technique but higher than that of testing several samples simultaneously. The total cost of unexpected antibody screening using an automated analyzer was less than that using the manual method. ABO/Rh(D) typing using an automated analyzer incurs a lower unit value and cost than that using the manual technique when only one sample is tested at a time. Unexpected antibody screening using an automated analyzer always incurs a lower unit value and cost than that using the manual technique.

Saturation Mutagenesis of 5S rRNA in Saccharomyces cerevisiae

PubMed Central

Smith, Maria W.; Meskauskas, Arturas; Wang, Pinger; Sergiev, Petr V.; Dinman, Jonathan D.

2001-01-01

rRNAs are the central players in the reactions catalyzed by ribosomes, and the individual rRNAs are actively involved in different ribosome functions. Our previous demonstration that yeast 5S rRNA mutants (called mof9) can impact translational reading frame maintenance showed an unexpected function for this ubiquitous biomolecule. At the time, however, the highly repetitive nature of the genes encoding rRNAs precluded more detailed genetic and molecular analyses. A new genetic system allows all 5S rRNAs in the cell to be transcribed from a small, easily manipulated plasmid. The system is also amenable for the study of the other rRNAs, and provides an ideal genetic platform for detailed structural and functional studies. Saturation mutagenesis reveals regions of 5S rRNA that are required for cell viability, translational accuracy, and virus propagation. Unexpectedly, very few lethal alleles were identified, demonstrating the resilience of this molecule. Superimposition of genetic phenotypes on a physical map of 5S rRNA reveals the existence of phenotypic clusters of mutants, suggesting that specific regions of 5S rRNA are important for specific functions. Mapping these mutants onto the Haloarcula marismortui large subunit reveals that these clusters occur at important points of physical interaction between 5S rRNA and the different functional centers of the ribosome. Our analyses lead us to propose that one of the major functions of 5S rRNA may be to enhance translational fidelity by acting as a physical transducer of information between all of the different functional centers of the ribosome. PMID:11713264

Salt appetite is not increased in summer heat.

PubMed

Leshem, Micah

2017-01-01

We tested the hypothesis that salt appetite increases in summer heat due to increased sodium loss due to increased drinking and perspiration. A test battery in the same sample of healthy young people tested in summer and winter revealed no seasonal differences in salt appetite (or fluid intake) despite a 10 °C rise in mean environmental temperature. Unexpectedly, sweet preference is reduced in summer. Copyright © 2016 Elsevier Ltd. All rights reserved.

What New Parents "Really" Want to Know. A Principal Responds When a Parent Survey Reveals Some Unexpected Concerns

ERIC Educational Resources Information Center

Young, Anne

2005-01-01

Part of Clark Elementary School was built in 1911 as a rural school housing grades 1-12 that also served as the community center. In l984, when I first taught there, it was a school with 225 students where the staff knew not only the students, but their immediate families, extended families, and even long-deceased relatives who had attended Clark…

43 CFR 3931.30 - Suspension of operations and production.

Code of Federal Regulations, 2012 CFR

2012-10-01

... environmental studies or analysis; (2) To ensure that necessary environmental remediation or cleanup is being... environmental remediation or cleanup is being performed as a result of unwarranted or unexpected actions. (c...

43 CFR 3931.30 - Suspension of operations and production.

Code of Federal Regulations, 2013 CFR

2013-10-01

... environmental studies or analysis; (2) To ensure that necessary environmental remediation or cleanup is being... environmental remediation or cleanup is being performed as a result of unwarranted or unexpected actions. (c...

43 CFR 3931.30 - Suspension of operations and production.

Code of Federal Regulations, 2011 CFR

2011-10-01

... environmental studies or analysis; (2) To ensure that necessary environmental remediation or cleanup is being... environmental remediation or cleanup is being performed as a result of unwarranted or unexpected actions. (c...

43 CFR 3931.30 - Suspension of operations and production.

Code of Federal Regulations, 2014 CFR

2014-10-01

... environmental studies or analysis; (2) To ensure that necessary environmental remediation or cleanup is being... environmental remediation or cleanup is being performed as a result of unwarranted or unexpected actions. (c...

Testing the validity of a continuous false belief task in 3- to 7-year-old children.

PubMed

Mahy, Caitlin E V; Bernstein, Daniel M; Gerrard, Lindsey D; Atance, Cristina M

2017-08-01

In two studies, we examined young children's performance on the paper-and-pencil version of the Sandbox task, a continuous measure of false belief, and its relations with other false belief and inhibition tasks. In Study 1, 96 children aged 3 to 7years completed three false belief tasks (Sandbox, Unexpected Contents, and Appearance/Reality) and two inhibition tasks (Head-Shoulders-Knees-Toes and Grass/Snow). Results revealed that false belief bias-a measure of egocentrism-on the Sandbox task correlated with age but not with the Unexpected Contents or Appearance/Reality task or with measures of inhibition after controlling for age. In Study 2, 90 3- to 7-year-olds completed five false belief tasks (Sandbox, Unexpected Contents, Appearance/Reality, Change of Location, and a second-order false belief task), two inhibition tasks (Simon Says and Grass/Snow), and a receptive vocabulary task (Peabody Picture Vocabulary Test). Results showed that false belief bias on the Sandbox task correlated negatively with age and with the Change of Location task but not with the other false belief or inhibition tasks after controlling for age and receptive vocabulary. The Sandbox task shows promise as an age-sensitive measure of false belief performance during early childhood and shows convergent and discriminant validity. Copyright © 2017 Elsevier Inc. All rights reserved.

The importance of working memory for school achievement in primary school children with intellectual or learning disabilities.

PubMed

Maehler, Claudia; Schuchardt, Kirsten

2016-11-01

Given the well-known relation between intelligence and school achievement we expect children with normal intelligence to perform well at school and those with intelligence deficits to meet learning problems. But, contrary to these expectations, some children do not perform according to these predictions: children with normal intelligence but sub-average school achievement and children with lower intelligence but average success at school. Yet, it is an open question how the unexpected failure or success can be explained. This study examined the role of working memory sensu Baddeley (1986) for school achievement, especially for unexpected failure or success. An extensive working memory battery with a total of 14 tasks for the phonological loop, the visual-spatial sketchpad and central executive skills was presented in individual sessions to four groups of children differing in IQ (normal vs. low) and school success (good vs. poor). Results reveal that children with sub-average school achievement showed deficits in working memory functioning, irrespective of intelligence. By contrast, children with regular school achievement did not show deficits in working memory, again irrespective of intelligence. Therefore working memory should be considered an important predictor of academic success that can lead both to unexpected overachievement and failure at school. Individual working memory competencies should be taken into account with regard to diagnosis and intervention for children with learning problems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Morphologic changes in the mesolimbic pathway in Parkinson's disease motor subtypes.

PubMed

Nyberg, Eric M; Tanabe, Jody; Honce, Justin M; Krmpotich, Theodore; Shelton, Erika; Hedeman, Jessica; Berman, Brian D

2015-05-01

Parkinson's disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy. Cortical atrophy patterns may further help distinguish between PD motor subtypes. Comparable differences in subcortical volumes have not been found. Twenty-one cognitively intact and treated PD patients, including 12 tremor dominant (TD) subtype, Nine postural instability gait dominant (PIGD) subtype, and 20 matched healthy control subjects underwent 3.0 T high-resolution structural MRI scanning. Subcortical volumetric analysis was performed using FreeSurfer and shape analysis was performed with FIRST to assess for differences between PD patients and controls and between PD subtypes. No significant differences in subcortical volumes were found between motor PD subtypes, but comparing grouped PD patients with controls revealed a significant increase in hippocampal volume in PD patients (p = 0.03). A significant shape difference was detected in the right nucleus accumbens (NAcc) between PD and controls and between motor subtypes. Shape differences were driven by positive deviations in the TD subtype. Correlation analysis revealed a trend between hippocampal volume and decreasing MDS-UPDRS (p = 0.06). While no significant differences in subcortical volumes between PD motor subtypes were found, increased hippocampal volumes were observed in PD patients compared to controls. Right NAcc shape differences in PD patients were driven by changes in the TD subtype. These unexpected findings may be related to the effects of chronic dopaminergic replacement on the mesolimbic pathway. Further studies are needed to replicate and determine the clinical significance of such morphologic changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Population genomic analysis of elongated skulls reveals extensive female-biased immigration in Early Medieval Bavaria

PubMed Central

Veeramah, Krishna R.; Rott, Andreas; Groß, Melanie; López, Saioa; Kirsanow, Karola; Sell, Christian; Blöcher, Jens; Link, Vivian; Hofmanová, Zuzana; Peters, Joris; Trautmann, Bernd; Gairhos, Anja; Haberstroh, Jochen; Päffgen, Bernd; Hellenthal, Garrett; Haas-Gebhard, Brigitte; Harbeck, Michaela; Burger, Joachim

2018-01-01

Modern European genetic structure demonstrates strong correlations with geography, while genetic analysis of prehistoric humans has indicated at least two major waves of immigration from outside the continent during periods of cultural change. However, population-level genome data that could shed light on the demographic processes occurring during the intervening periods have been absent. Therefore, we generated genomic data from 41 individuals dating mostly to the late 5th/early 6th century AD from present-day Bavaria in southern Germany, including 11 whole genomes (mean depth 5.56×). In addition we developed a capture array to sequence neutral regions spanning a total of 5 Mb and 486 functional polymorphic sites to high depth (mean 72×) in all individuals. Our data indicate that while men generally had ancestry that closely resembles modern northern and central Europeans, women exhibit a very high genetic heterogeneity; this includes signals of genetic ancestry ranging from western Europe to East Asia. Particularly striking are women with artificial skull deformations; the analysis of their collective genetic ancestry suggests an origin in southeastern Europe. In addition, functional variants indicate that they also differed in visible characteristics. This example of female-biased migration indicates that complex demographic processes during the Early Medieval period may have contributed in an unexpected way to shape the modern European genetic landscape. Examination of the panel of functional loci also revealed that many alleles associated with recent positive selection were already at modern-like frequencies in European populations ∼1,500 years ago. PMID:29531040

Significant Natural Product Biosynthetic Potential of Actinorhizal Symbionts of the Genus Frankia, as Revealed by Comparative Genomic and Proteomic Analyses▿

PubMed Central

Udwary, Daniel W.; Gontang, Erin A.; Jones, Adam C.; Jones, Carla S.; Schultz, Andrew W.; Winter, Jaclyn M.; Yang, Jane Y.; Beauchemin, Nicholas; Capson, Todd L.; Clark, Benjamin R.; Esquenazi, Eduardo; Eustáquio, Alessandra S.; Freel, Kelle; Gerwick, Lena; Gerwick, William H.; Gonzalez, David; Liu, Wei-Ting; Malloy, Karla L.; Maloney, Katherine N.; Nett, Markus; Nunnery, Joshawna K.; Penn, Kevin; Prieto-Davo, Alejandra; Simmons, Thomas L.; Weitz, Sara; Wilson, Micheal C.; Tisa, Louis S.; Dorrestein, Pieter C.; Moore, Bradley S.

2011-01-01

Bacteria of the genus Frankia are mycelium-forming actinomycetes that are found as nitrogen-fixing facultative symbionts of actinorhizal plants. Although soil-dwelling actinomycetes are well-known producers of bioactive compounds, the genus Frankia has largely gone uninvestigated for this potential. Bioinformatic analysis of the genome sequences of Frankia strains ACN14a, CcI3, and EAN1pec revealed an unexpected number of secondary metabolic biosynthesis gene clusters. Our analysis led to the identification of at least 65 biosynthetic gene clusters, the vast majority of which appear to be unique and for which products have not been observed or characterized. More than 25 secondary metabolite structures or structure fragments were predicted, and these are expected to include cyclic peptides, siderophores, pigments, signaling molecules, and specialized lipids. Outside the hopanoid gene locus, no cluster could be convincingly demonstrated to be responsible for the few secondary metabolites previously isolated from other Frankia strains. Few clusters were shared among the three species, demonstrating species-specific biosynthetic diversity. Proteomic analysis of Frankia sp. strains CcI3 and EAN1pec showed that significant and diverse secondary metabolic activity was expressed in laboratory cultures. In addition, several prominent signals in the mass range of peptide natural products were observed in Frankia sp. CcI3 by intact-cell matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). This work supports the value of bioinformatic investigation in natural products biosynthesis using genomic information and presents a clear roadmap for natural products discovery in the Frankia genus. PMID:21498757

The role of the right temporoparietal junction in attention and social interaction as revealed by ALE meta-analysis

PubMed Central

Rottschy, C.; Oberwelland, E.; Bzdok, D.; Fox, P. T.; Eickhoff, S. B.; Fink, G. R.; Konrad, K.

2016-01-01

The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others’ (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region. PMID:24915964

Information spreading by a combination of MEG source estimation and multivariate pattern classification.

PubMed

Sato, Masashi; Yamashita, Okito; Sato, Masa-Aki; Miyawaki, Yoichi

2018-01-01

To understand information representation in human brain activity, it is important to investigate its fine spatial patterns at high temporal resolution. One possible approach is to use source estimation of magnetoencephalography (MEG) signals. Previous studies have mainly quantified accuracy of this technique according to positional deviations and dispersion of estimated sources, but it remains unclear how accurately MEG source estimation restores information content represented by spatial patterns of brain activity. In this study, using simulated MEG signals representing artificial experimental conditions, we performed MEG source estimation and multivariate pattern analysis to examine whether MEG source estimation can restore information content represented by patterns of cortical current in source brain areas. Classification analysis revealed that the corresponding artificial experimental conditions were predicted accurately from patterns of cortical current estimated in the source brain areas. However, accurate predictions were also possible from brain areas whose original sources were not defined. Searchlight decoding further revealed that this unexpected prediction was possible across wide brain areas beyond the original source locations, indicating that information contained in the original sources can spread through MEG source estimation. This phenomenon of "information spreading" may easily lead to false-positive interpretations when MEG source estimation and classification analysis are combined to identify brain areas that represent target information. Real MEG data analyses also showed that presented stimuli were able to be predicted in the higher visual cortex at the same latency as in the primary visual cortex, also suggesting that information spreading took place. These results indicate that careful inspection is necessary to avoid false-positive interpretations when MEG source estimation and multivariate pattern analysis are combined.

Information spreading by a combination of MEG source estimation and multivariate pattern classification

PubMed Central

Sato, Masashi; Yamashita, Okito; Sato, Masa-aki

2018-01-01

To understand information representation in human brain activity, it is important to investigate its fine spatial patterns at high temporal resolution. One possible approach is to use source estimation of magnetoencephalography (MEG) signals. Previous studies have mainly quantified accuracy of this technique according to positional deviations and dispersion of estimated sources, but it remains unclear how accurately MEG source estimation restores information content represented by spatial patterns of brain activity. In this study, using simulated MEG signals representing artificial experimental conditions, we performed MEG source estimation and multivariate pattern analysis to examine whether MEG source estimation can restore information content represented by patterns of cortical current in source brain areas. Classification analysis revealed that the corresponding artificial experimental conditions were predicted accurately from patterns of cortical current estimated in the source brain areas. However, accurate predictions were also possible from brain areas whose original sources were not defined. Searchlight decoding further revealed that this unexpected prediction was possible across wide brain areas beyond the original source locations, indicating that information contained in the original sources can spread through MEG source estimation. This phenomenon of “information spreading” may easily lead to false-positive interpretations when MEG source estimation and classification analysis are combined to identify brain areas that represent target information. Real MEG data analyses also showed that presented stimuli were able to be predicted in the higher visual cortex at the same latency as in the primary visual cortex, also suggesting that information spreading took place. These results indicate that careful inspection is necessary to avoid false-positive interpretations when MEG source estimation and multivariate pattern analysis are combined. PMID:29912968

Process improvement methodologies uncover unexpected gaps in stroke care.

PubMed

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.

Breast Cancer Survivors’ Experiences of Lymphedema-Related Symptoms

PubMed Central

Fu, Mei Rosemary; Rosedale, Mary

2009-01-01

The purpose of this study was to explore and describe breast cancer survivors’ lymphedema-related symptom experiences. As a serious chronic condition from breast cancer treatment, lymphedema, or persistent swelling, is caused by chronic accumulation of lymph fluid in the interstitial spaces of the affected limb or surrounding areas. While significant prevalence of ongoing multiple symptoms have been reported, little is known about how survivors with lymphedema perceive and respond to lymphedema-related symptoms in their daily lives. This study employed a descriptive phenomenological method. Thirty-four participants were recruited in the US. Three in-depth interviews were conducted with each participant; a total of 102 interviews were completed, audio-taped, and transcribed. Interview transcripts and field notes were the data sources for this analysis, which was part of three larger studies. Data were analyzed to identify the essential themes within and across cases. Four essential themes were revealed: living with perpetual discomfort; confronting the unexpected; losing pre-lymphedema being; and feeling handicapped. Participants experienced multiple symptoms on a daily basis. Distress was heightened when women expected symptoms to disappear but instead they remained as a “perpetual discomfort.” Moreover, distress was intensified when symptoms evoked unexpected situations or when symptoms elicited emotional responses powerful enough to change perceived personal identity. Findings suggest that symptom distress may encompass temporal, situational and attributive dimensions. Prospective studies are needed to examine lymphedema-related symptom distress in terms of these dimensions so that more specific interventions can be developed to target distress occurring in each dimension. PMID:19819668

Diversity of Bacteria at Healthy Human Conjunctiva

PubMed Central

Dong, Qunfeng; Brulc, Jennifer M.; Iovieno, Alfonso; Bates, Brandon; Garoutte, Aaron; Miller, Darlene; Revanna, Kashi V.; Gao, Xiang; Antonopoulos, Dionysios A.; Slepak, Vladlen Z.

2011-01-01

Purpose. Ocular surface (OS) microbiota contributes to infectious and autoimmune diseases of the eye. Comprehensive analysis of microbial diversity at the OS has been impossible because of the limitations of conventional cultivation techniques. This pilot study aimed to explore true diversity of human OS microbiota using DNA sequencing-based detection and identification of bacteria. Methods. Composition of the bacterial community was characterized using deep sequencing of the 16S rRNA gene amplicon libraries generated from total conjunctival swab DNA. The DNA sequences were classified and the diversity parameters measured using bioinformatics software ESPRIT and MOTHUR and tools available through the Ribosomal Database Project-II (RDP-II). Results. Deep sequencing of conjunctival rDNA from four subjects yielded a total of 115,003 quality DNA reads, corresponding to 221 species-level phylotypes per subject. The combined bacterial community classified into 5 phyla and 59 distinct genera. However, 31% of all DNA reads belonged to unclassified or novel bacteria. The intersubject variability of individual OS microbiomes was very significant. Regardless, 12 genera—Pseudomonas, Propionibacterium, Bradyrhizobium, Corynebacterium, Acinetobacter, Brevundimonas, Staphylococci, Aquabacterium, Sphingomonas, Streptococcus, Streptophyta, and Methylobacterium—were ubiquitous among the analyzed cohort and represented the putative “core” of conjunctival microbiota. The other 47 genera accounted for <4% of the classified portion of this microbiome. Unexpectedly, healthy conjunctiva contained many genera that are commonly identified as ocular surface pathogens. Conclusions. The first DNA sequencing-based survey of bacterial population at the conjunctiva have revealed an unexpectedly diverse microbial community. All analyzed samples contained ubiquitous (core) genera that included commensal, environmental, and opportunistic pathogenic bacteria. PMID:21571682

Murine Sialidase Neu3 facilitates GM2 degradation and bypass in mouse model of Tay-Sachs disease.

PubMed

Seyrantepe, Volkan; Demir, Secil Akyildiz; Timur, Zehra Kevser; Von Gerichten, Johanna; Marsching, Christian; Erdemli, Esra; Oztas, Emin; Takahashi, Kohta; Yamaguchi, Kazunori; Ates, Nurselin; Dönmez Demir, Buket; Dalkara, Turgay; Erich, Katrin; Hopf, Carsten; Sandhoff, Roger; Miyagi, Taeko

2018-01-01

Tay-Sachs disease is a severe lysosomal storage disorder caused by mutations in Hexa, the gene that encodes for the α subunit of lysosomal β-hexosaminidase A (HEXA), which converts GM2 to GM3 ganglioside. Unexpectedly, Hexa -/- mice have a normal lifespan and show no obvious neurological impairment until at least one year of age. These mice catabolize stored GM2 ganglioside using sialidase(s) to remove sialic acid and form the glycolipid GA2, which is further processed by β-hexosaminidase B. Therefore, the presence of the sialidase (s) allows the consequences of the Hexa defect to be bypassed. To determine if the sialidase NEU3 contributes to GM2 ganglioside degradation, we generated a mouse model with combined deficiencies of HEXA and NEU3. The Hexa -/- Neu3 -/- mice were healthy at birth, but died at 1.5 to 4.5months of age. Thin-layer chromatography and mass spectrometric analysis of the brains of Hexa -/- Neu3 -/- mice revealed the abnormal accumulation of GM2 ganglioside. Histological and immunohistochemical analysis demonstrated cytoplasmic vacuolation in the neurons. Electron microscopic examination of the brain, kidneys and testes revealed pleomorphic inclusions of many small vesicles and complex lamellar structures. The Hexa -/- Neu3 -/- mice exhibited progressive neurodegeneration with neuronal loss, Purkinje cell depletion, and astrogliosis. Slow movement, ataxia, and tremors were the prominent neurological abnormalities observed in these mice. Furthermore, radiographs revealed abnormalities in the skeletal bones of the Hexa -/- Neu3 -/- mice. Thus, the Hexa -/- Neu3 -/- mice mimic the neuropathological and clinical abnormalities of the classical early-onset Tay-Sachs patients, and provide a suitable model for the future pre-clinical testing of potential treatments for this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

[Analysis of nursing students' attitude toward bioethics (3). Attitude toward induced abortion].

PubMed

Nakayama, O; Ishizaka, K; Mizutani, N

1986-04-01

Nursing students were found to be somewhat hesitant and indecisive about induced abortion in general. They are in favor of some cases of abortion but feel that it should be avoided if possible. They agree to abortion in cases of a mother's health being in danger and possible deformity of the child, but are opposed to it for such selfish reasons as parents' sex preference of their child and motherhood's interference with parents' study or career. They are most undecided about abortion because of financial difficulties since each case would be different. Quantitative analysis via computer was made of the results of a questionnaire given to 112 nursing students. The students were encouraged to give their candid opinion in exchange for their complete anonymity. They were asked to respond to the following reasons for having induced abortion by circling agree, somewhat agree, somewhat opposed, or opposed: 1) unexpected pregnancy at financially difficult times, 2) unwanted sex of fetus revealed by amniocentesis, 3) unwanted pregnancy with a possible hereditary disease 4) some disability of the child revealed by the fetal examination, 5) pregnancy due to rape, 6) pregnancy due to wife's adultery, 7) maternal health risk, 8) unwanted pregnancy, 9) teenage pregnancy (junior high age), 10) German measles contracted during the 1st trimester, 11) untimely pregnancy interfering with a woman's career or college studies, and 12) women's freedom of choice. Problems such as 2), 3), and 4) arose only because of advancement in medical technology, i.e., amniocentesis. Induced abortion because of unwanted sex of the fetus revealed by amniocentesis was the most clear-cut case of disapproval by nursing students.

A Comparative Study of Definitions on Limit and Continuity of Functions

ERIC Educational Resources Information Center

Shipman, Barbara A.

2012-01-01

Differences in definitions of limit and continuity of functions as treated in courses on calculus and in rigorous undergraduate analysis yield contradictory outcomes and unexpected language. There are results about limits in calculus that are false by the definitions of analysis, functions not continuous by one definition and continuous by…

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

PubMed

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.

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

PubMed

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.

Does working memory capacity predict cross-modally induced failures of awareness?

PubMed

Kreitz, Carina; Furley, Philip; Simons, Daniel J; Memmert, Daniel

2016-01-01

People often fail to notice unexpected stimuli when they are focusing attention on another task. Most studies of this phenomenon address visual failures induced by visual attention tasks (inattentional blindness). Yet, such failures also occur within audition (inattentional deafness), and people can even miss unexpected events in one sensory modality when focusing attention on tasks in another modality. Such cross-modal failures are revealing because they suggest the existence of a common, central resource limitation. And, such central limits might be predicted from individual differences in cognitive capacity. We replicated earlier evidence, establishing substantial rates of inattentional deafness during a visual task and inattentional blindness during an auditory task. However, neither individual working memory capacity nor the ability to perform the primary task predicted noticing in either modality. Thus, individual differences in cognitive capacity did not predict failures of awareness even though the failures presumably resulted from central resource limitations. Copyright © 2015 Elsevier Inc. All rights reserved.

The C-terminal residue of phage Vp16 PDF, the smallest peptide deformylase, acts as an offset element locking the active conformation.

PubMed

Grzela, Renata; Nusbaum, Julien; Fieulaine, Sonia; Lavecchia, Francesco; Bienvenut, Willy V; Dian, Cyril; Meinnel, Thierry; Giglione, Carmela

2017-09-08

Prokaryotic proteins must be deformylated before the removal of their first methionine. Peptide deformylase (PDF) is indispensable and guarantees this mechanism. Recent metagenomics studies revealed new idiosyncratic PDF forms as the most abundant family of viral sequences. Little is known regarding these viral PDFs, including the capacity of the corresponding encoded proteins to ensure deformylase activity. We provide here the first evidence that viral PDFs, including the shortest PDF identified to date, Vp16 PDF, display deformylase activity in vivo, despite the absence of the key ribosome-interacting C-terminal region. Moreover, characterization of phage Vp16 PDF underscores unexpected structural and molecular features with the C-terminal Isoleucine residue significantly contributing to deformylase activity both in vitro and in vivo. This residue fully compensates for the absence of the usual long C-domain. Taken together, these data elucidate an unexpected mechanism of enzyme natural evolution and adaptation within viral sequences.

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

NASA Astrophysics Data System (ADS)

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.

Boundaries for martensitic transition of 7Li under pressure

DOE PAGES

Schaeffer, Anne Marie; Cai, Weizhao; Olejnik, Ella; ...

2015-08-14

We report that physical properties of lithium under extreme pressures continuously reveal unexpected features. These include a sequence of structural transitions to lower symmetry phases, metal-insulator-metal transition, superconductivity with one of the highest elemental transition temperatures, and a maximum followed by a minimum in its melting line. The instability of the bcc structure of lithium is well established by the presence of a temperature-driven martensitic phase transition. The boundaries of this phase, however, have not been previously explored above 3 GPa. All higher pressure phase boundaries are either extrapolations or inferred based on indirect evidence. Here we explore the pressuremore » dependence of the martensitic transition of lithium up to 7 GPa using a combination of neutron and X-ray scattering. We find a rather unexpected deviation from the extrapolated boundaries of the hR3 phase of lithium. Furthermore, there is evidence that, above ~3 GPa, once in fcc phase, lithium does not undergo a martensitic transition.« less

An unexpected N-terminal loop in PD-1 dominates binding by nivolumab

PubMed Central

Tan, Shuguang; Zhang, Hao; Chai, Yan; Song, Hao; Tong, Zhou; Wang, Qihui; Qi, Jianxun; Wong, Gary; Zhu, Xiaodong; Liu, William J.; Gao, Shan; Wang, Zhongfu; Shi, Yi; Yang, Fuquan; Gao, George F.; Yan, Jinghua

2017-01-01

Cancer immunotherapy by targeting of immune checkpoint molecules has been a research ‘hot-spot' in recent years. Nivolumab, a human monoclonal antibody targeting PD-1, has been widely used clinically since 2014. However, the binding mechanism of nivolumab to PD-1 has not yet been shown, despite a recent report describing the complex structure of pembrolizumab/PD-1. It has previously been speculated that PD-1 glycosylation is involved in nivolumab recognition. Here we report the complex structure of nivolumab with PD-1 and evaluate the effects of PD-1 N-glycosylation on the interactions with nivolumab. Structural and functional analyses unexpectedly reveal an N-terminal loop outside the IgV domain of PD-1. This loop is not involved in recognition of PD-L1 but dominates binding to nivolumab, whereas N-glycosylation is not involved in binding at all. Nivolumab binds to a completely different area than pembrolizumab. These results provide the basis for the design of future inhibitory molecules targeting PD-1. PMID:28165004

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

Phospho-ubiquitin: upending the PINK–Parkin–ubiquitin cascade

PubMed Central

Matsuda, Noriyuki

2016-01-01

Mitochondria with decreased membrane potential are characterized by defects in protein import into the matrix and impairments in high-efficiency synthesis of ATP. These low-quality mitochondria are marked with ubiquitin for selective degradation. Key factors in this mechanism are PTEN-induced putative kinase 1 (PINK1, a mitochondrial kinase) and Parkin (a ubiquitin ligase), disruption of which has been implicated in predisposition to Parkinson’s disease. Previously, the clearance of damaged mitochondria had been thought to be the end result of a simple cascading reaction of PINK1–Parkin–ubiquitin. However, in the past year, several research groups including ours unexpectedly revealed that Parkin regulation is mediated by PINK1-dependent phosphorylation of ubiquitin. These results overturned the simple hierarchy that posited PINK1 and ubiquitin as the upstream and downstream factors of Parkin, respectively. Although ubiquitylation is well-known as a post-translational modification, it has recently become clear that ubiquitin itself can be modified, and that this modification unexpectedly converts ubiquitin to a factor that functions in retrograde signalling. PMID:26839319

Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smetanina, Mariya A., E-mail: maria.smetanina@gmail.com; Laboratory of Gene Expression Control, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 10, Novosibirsk 630090; Group of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 8, Novosibirsk 630090

2'-3-dimethyl-4-aminoazobenzene (ortho-aminoazotoluene, OAT) is an azo dye and a rodent carcinogen that has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (class 2B) human carcinogen. Its mechanism of action remains unclear. We examined the role of the xenobiotic receptor Constitutive Androstane Receptor (CAR, NR1I3) as a mediator of the effects of OAT. We found that OAT increases mouse CAR (mCAR) transactivation in a dose-dependent manner. This effect is specific because another closely related azo dye, 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB), did not activate mCAR. Real-time Q-PCR analysis in wild-type C57BL/6 mice revealed that OAT induces the hepaticmore » mRNA expression of the following CAR target genes: Cyp2b10, Cyp2c29, Cyp3a11, Ugt1a1, Mrp4, Mrp2 and c-Myc. CAR-null (Car{sup -/-}) mice showed no increased expression of these genes following OAT treatment, demonstrating that CAR is required for their OAT dependent induction. The OAT-induced CAR-dependent increase of Cyp2b10 and c-Myc expression was confirmed by Western blotting. Immunohistochemistry analysis of wild-type and Car{sup -/-} livers showed that OAT did not acutely induce hepatocyte proliferation, but at much later time points showed an unexpected CAR-dependent proliferative response. These studies demonstrate that mCAR is an OAT xenosensor, and indicate that at least some of the biological effects of this compound are mediated by this nuclear receptor. - Highlights: > The azo dye and mouse carcinogen OAT is a very effective mCAR activator. > OAT increases mCAR transactivation in a dose-dependent manner. > OAT CAR-dependently increases the expression of a specific subset of CAR target genes. > OAT induces an unexpectedly deferred, but CAR-dependent hepatocyte proliferation.« less

In vivo and in vitro evidence of somatostatin receptors expression in a dedifferentiated retroperitoneal liposarcoma.

PubMed

Imperiale, Alessio; Chenard, Marie-Pierre; Rohr, Serge; Barlier, Anne; Goichot, Bernard

2014-10-01

A 62-year-old patient presented with mildly elevated catecholamines and an abdominal painless mass. Abdominal CT revealed an 18 × 12 cm tumor in the right retroperitoneum with intense contrast enhancement. Somatostatin receptor scintigraphy (SRS) showed pathologic uptake by the lesion. Given the suspicion of paraganglioma, the patient was referred to surgery for tumor removal. Surprisingly, the histopathological examination revealed a dedifferentiated liposarcoma. Somatostatin receptors of type 2 were identified and quantified by reverse transcription polymerase chain reaction. The unexpected presentation of our patient draws clinicians' attention when performing diagnostic procedure for retroperitoneal lesions, even though hormone secretion and positive SRS strongly suggest paraganglioma.

SPQR - Spectroscopy: Prospects, Questions & Results

NASA Astrophysics Data System (ADS)

Pennington, M. R.

2014-06-01

Tremendous progress has been made in mapping out the spectrum of hadrons over the past decade with plans to make further advances in the decade ahead. Baryons and mesons, both expected and unexpected, have been found, the results of precision experiments often with polarized beams, polarized targets and sometimes polarization of the final states. All these hadrons generate poles in the complex energy plane that are consequences of the strong coupling regime of QCD. They reveal how this works.

What happens to your brain on the way to Mars.

PubMed

Parihar, Vipan K; Allen, Barrett; Tran, Katherine K; Macaraeg, Trisha G; Chu, Esther M; Kwok, Stephanie F; Chmielewski, Nicole N; Craver, Brianna M; Baulch, Janet E; Acharya, Munjal M; Cucinotta, Francis A; Limoli, Charles L

2015-05-01

As NASA prepares for the first manned spaceflight to Mars, questions have surfaced concerning the potential for increased risks associated with exposure to the spectrum of highly energetic nuclei that comprise galactic cosmic rays. Animal models have revealed an unexpected sensitivity of mature neurons in the brain to charged particles found in space. Astronaut autonomy during long-term space travel is particularly critical as is the need to properly manage planned and unanticipated events, activities that could be compromised by accumulating particle traversals through the brain. Using mice subjected to space-relevant fluences of charged particles, we show significant cortical- and hippocampal-based performance decrements 6 weeks after acute exposure. Animals manifesting cognitive decrements exhibited marked and persistent radiation-induced reductions in dendritic complexity and spine density along medial prefrontal cortical neurons known to mediate neurotransmission specifically interrogated by our behavioral tasks. Significant increases in postsynaptic density protein 95 (PSD-95) revealed major radiation-induced alterations in synaptic integrity. Impaired behavioral performance of individual animals correlated significantly with reduced spine density and trended with increased synaptic puncta, thereby providing quantitative measures of risk for developing cognitive decrements. Our data indicate an unexpected and unique susceptibility of the central nervous system to space radiation exposure, and argue that the underlying radiation sensitivity of delicate neuronal structure may well predispose astronauts to unintended mission-critical performance decrements and/or longer-term neurocognitive sequelae.

Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme

PubMed Central

Kim, Tae-Hee; Kim, Byeong-Moo; Mao, Junhao; Rowan, Sheldon; Shivdasani, Ramesh A.

2011-01-01

The digestive tract epithelium and its adjoining mesenchyme undergo coordinated patterning and growth during development. The signals they exchange in the process are not fully characterized but include ligands of the Hedgehog (Hh) family, which originate in the epithelium and are necessary for mesenchymal cells to expand in number and drive elongation of the developing gut tube. The Notch signaling pathway has known requirements in fetal and adult intestinal epithelial progenitors. We detected Notch pathway activity in the embryonic gut mesenchyme and used conditional knockout mice to study its function. Selective disruption of the Notch effector gene RBP-Jκ (Rbpj) in the mesenchyme caused progressive loss of subepithelial fibroblasts and abbreviated gut length, revealing an unexpected requirement in this compartment. Surprisingly, constitutive Notch activity also induced rapid mesenchymal cell loss and impaired organogenesis, probably resulting from increased cell death and suggesting the need for a delicate balance in Notch signaling. Because digestive tract anomalies in mouse embryos with excess Notch activity phenocopy the absence of Hh signaling, we postulated that endodermal Hh restrains mesenchymal Notch pathway activity. Indeed, Hh-deficient embryos showed Notch overactivity in their defective gut mesenchyme and exposure to recombinant sonic hedgehog could override Notch-induced death of cultured fetal gut mesenchymal cells. These results reveal unexpected interactions between prominent signals in gastrointestinal development and provide a coherent explanation for Hh requirements in mesenchymal cell survival and organ growth. PMID:21750033

Sudden death from systemic sarcoidosis: a case of legal medicine.

PubMed

Zoja, R; Andreola, S; Gentile, G; Rancati, A

2012-03-01

The sarcoid condition of vital organs such as heart, lungs, liver and brain, may constitute, though rarely, a dangerous situation for survival. In forensic pathology, sudden death related to such disease represents an unusual event occurring in subjects who die unexpectedly in spite of their previous good health, and whose autopsy reveals, mainly, the involvement of heart or the central nervous system (CNS). The Authors describe a case of sudden death due to systemic sarcoidosis with atypical presentation in a young South American nulliparous woman showing, as the only symptom, occasional episodes of spotting during the last two months of her life. The only noteworthy finding from the autopsy resulted in secondary obstructive hydrocephalus. The subsequent forensic toxicological examination was negative, whereas the histopathological examination, conducted by means of post-fixation techniques and standard coloring methods on the viscera removed during autopsy, revealed useful data to determine the cause of death, consisting of a diffuse inflammatory reaction with giant cells and epithelioid cells of sarcoid type localized in the CNS and in the genitourinary apparatus. The case presented, ranking among deaths occurred unexpectedly, is a useful opportunity both for clinical remarks, given its inherent diagnostic difficulties, especially in the presence of atypical symptoms, and for legal medicine ones, given the inclusion of sarcoidosis in cases of sudden death that can give rise to criminal investigations.

Analysis of folded pulse forming line operation.

PubMed

Domonkos, M T; Watrous, J; Parker, J V; Cavazos, T; Slenes, K; Heidger, S; Brown, D; Wilson, D

2014-09-01

A compact pulse forming line (CPFL) concept based on a folded transmission line and high-breakdown strength dielectric was explored through an effort combining proof-of-principle experiments with electromagnetic modeling. A small-scale folded CPFL was fabricated using surface-mount ceramic multilayer capacitors. The line consisted of 150 capacitors close-packed in parallel and delivered a 300 ns flat-top pulse. The concept was carried to a 10 kV class device using a polymer-ceramic nanocomposite dielectric with a permittivity of 37.6. The line was designed for a 161 ns FWHM length pulse into a matched load. The line delivered a 110 ns FWHM pulse, and the pulse peak amplitude exceeded the matched load ideal. Transient electromagnetic analysis using the particle-in-cell code ICEPIC was conducted to examine the nature of the unexpected pulse shortening and distortion. Two-dimensional analysis failed to capture the anomalous behavior. Three-dimensional analysis replicated the pulse shape and revealed that the bends were largely responsible for the pulse shortening. The bends not only create the expected reflection of the incident TEM wave but also produce a non-zero component of the Poynting vector perpendicular to the propagation direction of the dominant electromagnetic wave, resulting in power flow largely external to the PFL. This analysis explains both the pulse shortening and the amplitude of the pulse.

Analysis of folded pulse forming line operation

NASA Astrophysics Data System (ADS)

Domonkos, M. T.; Watrous, J.; Parker, J. V.; Cavazos, T.; Slenes, K.; Heidger, S.; Brown, D.; Wilson, D.

2014-09-01

A compact pulse forming line (CPFL) concept based on a folded transmission line and high-breakdown strength dielectric was explored through an effort combining proof-of-principle experiments with electromagnetic modeling. A small-scale folded CPFL was fabricated using surface-mount ceramic multilayer capacitors. The line consisted of 150 capacitors close-packed in parallel and delivered a 300 ns flat-top pulse. The concept was carried to a 10 kV class device using a polymer-ceramic nanocomposite dielectric with a permittivity of 37.6. The line was designed for a 161 ns FWHM length pulse into a matched load. The line delivered a 110 ns FWHM pulse, and the pulse peak amplitude exceeded the matched load ideal. Transient electromagnetic analysis using the particle-in-cell code ICEPIC was conducted to examine the nature of the unexpected pulse shortening and distortion. Two-dimensional analysis failed to capture the anomalous behavior. Three-dimensional analysis replicated the pulse shape and revealed that the bends were largely responsible for the pulse shortening. The bends not only create the expected reflection of the incident TEM wave but also produce a non-zero component of the Poynting vector perpendicular to the propagation direction of the dominant electromagnetic wave, resulting in power flow largely external to the PFL. This analysis explains both the pulse shortening and the amplitude of the pulse.

The Bacterial Response Regulator ArcA Uses a Diverse Binding Site Architecture to Regulate Carbon Oxidation Globally

PubMed Central

Park, Dan M.; Akhtar, Md. Sohail; Ansari, Aseem Z.; Landick, Robert; Kiley, Patricia J.

2013-01-01

Despite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by mapping the regulon of the response regulator ArcA from Escherichia coli, which responds to the quinone/quinol redox couple via its membrane-bound sensor kinase, ArcB. Our genome-wide analysis reveals that ArcA reprograms metabolism under anaerobic conditions such that carbon oxidation pathways that recycle redox carriers via respiration are transcriptionally repressed by ArcA. We propose that this strategy favors use of catabolic pathways that recycle redox carriers via fermentation akin to lactate production in mammalian cells. Unexpectedly, bioinformatic analysis of the sequences bound by ArcA in ChIP-seq revealed that most ArcA binding sites contain additional direct repeat elements beyond the two required for binding an ArcA dimer. DNase I footprinting assays suggest that non-canonical arrangements of cis-regulatory modules dictate both the length and concentration-sensitive occupancy of DNA sites. We propose that this plasticity in ArcA binding site architecture provides both an efficient means of encoding binding sites for ArcA, σ70-RNAP and perhaps other transcription factors within the same narrow sequence space and an effective mechanism for global control of carbon metabolism to maintain redox homeostasis. PMID:24146625

Changing Abundance of Magnetofossil Morphologies in Pelagic Red Clay Around Minamitorishima, Western North Pacific

NASA Astrophysics Data System (ADS)

Usui, Yoichi; Yamazaki, Toshitsugu; Saitoh, Masafumi

2017-12-01

Recent investigations have discovered an unexpected abundance of magnetofossils in oxic pelagic red clays. These have potential to serve as paleoenvironmental tracers in otherwise nonfossiliferous sediments. Here, we report on variations in the abundance and morphology of magnetofossils in red clay from the western North Pacific. Magnetic measurements revealed that magnetofossils dominate the magnetic mineral assemblage of the sediments. An endmember analysis of isothermal remanent magnetization acquisition curves, supplemented by an analysis of S ratios, indicates that the magnetic assemblage can be unmixed into three endmembers, two corresponding to magnetofossils and one to terrigenous magnetic minerals. Direct counting of magnetofossil morphologies under a transmission electron microscope shows that the two magnetofossil endmembers differentiate equant magnetofossils and bullet-shaped magnetofossils, respectively. The stratigraphic variation of the endmember contributions revealed that the equant magnetofossils are dominant for the most part, while an interval at around 7 m in core depth shows higher abundance of the bullet-shaped magnetofossils. This may reflect enhanced organic carbon flux to the sediments. The organic carbon content is low throughout the sediments, and it does not show any change corresponding to the increase of bullet-shaped magnetofossils, pointing at extensive remineralization of the organic carbon. On the basis of lithostratigraphic correlation to nearby drilling sites, we tentatively estimate the age of the bullet-shaped magnetofossil increase as sometime between ˜75 and 25 Ma. These results suggest that environmental information can be obtained from magnetofossils in pelagic red clay.

Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores

PubMed Central

Ryzhov, Sergey; Tikhomirov, Oleg; Duarte, Christine W.; Congdon, Clare Bates; Lessard, Craig R.; McFarland, Samuel; Rochette-Egly, Cecile; Tran, Truc-Linh; Galindo, Cristi L.; Favreau-Lessard, Amanda J.; Sawyer, Douglas B.

2016-01-01

To determine whether hepatic depletion of vitamin A (VA) stores has an effect on the postnatal heart, studies were carried out with mice lacking liver retinyl ester stores fed either a VA-sufficient (LRVAS) or VA-deficient (LRVAD) diet (to deplete circulating retinol and extrahepatic stores of retinyl esters). There were no observable differences in the weights or gross morphology of hearts from LRVAS or LRVAD mice relative to sex-matched, age-matched, and genetically matched wild-type (WT) controls fed the VAS diet (WTVAS), but changes in the transcription of functionally relevant genes were consistent with a state of VAD in LRVAS and LRVAD ventricles. In silico analysis revealed that 58/67 differentially expressed transcripts identified in a microarray screen are products of genes that have DNA retinoic acid response elements. Flow cytometric analysis revealed a significant and cell-specific increase in the number of proliferating Sca-1 cardiac progenitor cells in LRVAS animals relative to WTVAS controls. Before myocardial infarction, LRVAS and WTVAS mice had similar cardiac systolic function and structure, as measured by echocardiography, but, unexpectedly, repeat echocardiography demonstrated that LRVAS mice had less adverse remodeling by 1 wk after myocardial infarction. Overall, the results demonstrate that the adult heart is responsive to retinoids, and, most notably, reducing hepatic VA stores (while maintaining circulating levels of VA) impacts ventricular gene expression profiles, progenitor cell numbers, and response to injury. PMID:27084391

Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.

PubMed

Asson-Batres, Mary Ann; Ryzhov, Sergey; Tikhomirov, Oleg; Duarte, Christine W; Congdon, Clare Bates; Lessard, Craig R; McFarland, Samuel; Rochette-Egly, Cecile; Tran, Truc-Linh; Galindo, Cristi L; Favreau-Lessard, Amanda J; Sawyer, Douglas B

2016-06-01

To determine whether hepatic depletion of vitamin A (VA) stores has an effect on the postnatal heart, studies were carried out with mice lacking liver retinyl ester stores fed either a VA-sufficient (LRVAS) or VA-deficient (LRVAD) diet (to deplete circulating retinol and extrahepatic stores of retinyl esters). There were no observable differences in the weights or gross morphology of hearts from LRVAS or LRVAD mice relative to sex-matched, age-matched, and genetically matched wild-type (WT) controls fed the VAS diet (WTVAS), but changes in the transcription of functionally relevant genes were consistent with a state of VAD in LRVAS and LRVAD ventricles. In silico analysis revealed that 58/67 differentially expressed transcripts identified in a microarray screen are products of genes that have DNA retinoic acid response elements. Flow cytometric analysis revealed a significant and cell-specific increase in the number of proliferating Sca-1 cardiac progenitor cells in LRVAS animals relative to WTVAS controls. Before myocardial infarction, LRVAS and WTVAS mice had similar cardiac systolic function and structure, as measured by echocardiography, but, unexpectedly, repeat echocardiography demonstrated that LRVAS mice had less adverse remodeling by 1 wk after myocardial infarction. Overall, the results demonstrate that the adult heart is responsive to retinoids, and, most notably, reducing hepatic VA stores (while maintaining circulating levels of VA) impacts ventricular gene expression profiles, progenitor cell numbers, and response to injury. Copyright © 2016 the American Physiological Society.

Somatic mosaicism containing double mutations in PTCH1 revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome.

PubMed

Ikemoto, Yu; Takayama, Yoshinaga; Fujii, Katsunori; Masuda, Mokuri; Kato, Chise; Hatsuse, Hiromi; Fujitani, Kazuko; Nagao, Kazuaki; Kameyama, Kohzoh; Ikehara, Hajime; Toyoda, Masashi; Umezawa, Akihiro; Miyashita, Toshiyuki

2017-08-01

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterised by developmental defects and tumorigenesis, such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 ( PTCH1 ) gene. In this article, we seek to demonstrate a mosaicism containing double mutations in PTCH1 in an individual with NBCCS. A de novo germline mutation of PTCH1 (c.272delG) was detected in a 31-year-old woman with NBCCS. Gene analysis of two out of four induced pluripotent stem cell (iPSC) clones established from the patient unexpectedly revealed an additional mutation, c.274delT. Deep sequencing confirmed a low-prevalence somatic mutation (5.5%-15.6% depending on the tissue) identical to the one found in iPSC clones. This is the first case of mosaicism unequivocally demonstrated in NBCCS. Furthermore, the mosaicism is unique in that the patient carries one normal and two mutant alleles. Because these mutations are located in close proximity, reversion error is likely to be involved in this event rather than a spontaneous mutation. In addition, this study indicates that gene analysis of iPSC clones can contribute to the detection of mosaicism containing a minor population carrying a second mutation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Deep Sequence Analysis of AgoshRNA Processing Reveals 3' A Addition and Trimming.

PubMed

Harwig, Alex; Herrera-Carrillo, Elena; Jongejan, Aldo; van Kampen, Antonius Hubertus; Berkhout, Ben

2015-07-14

The RNA interference (RNAi) pathway, in which microprocessor and Dicer collaborate to process microRNAs (miRNA), was recently expanded by the description of alternative processing routes. In one of these noncanonical pathways, Dicer action is replaced by the Argonaute2 (Ago2) slicer function. It was recently shown that the stem-length of precursor-miRNA or short hairpin RNA (shRNA) molecules is a major determinant for Dicer versus Ago2 processing. Here we present the results of a deep sequence study on the processing of shRNAs with different stem length and a top G·U wobble base pair (bp). This analysis revealed some unexpected properties of these so-called AgoshRNA molecules that are processed by Ago2 instead of Dicer. First, we confirmed the gradual shift from Dicer to Ago2 processing upon shortening of the hairpin length. Second, hairpins with a stem larger than 19 base pair are inefficiently cleaved by Ago2 and we noticed a shift in the cleavage site. Third, the introduction of a top G·U bp in a regular shRNA can promote Ago2-cleavage, which coincides with a loss of Ago2-loading of the Dicer-cleaved 3' strand. Fourth, the Ago2-processed AgoshRNAs acquire a short 3' tail of 1-3 A-nucleotides (nt) and we present evidence that this product is subsequently trimmed by the poly(A)-specific ribonuclease (PARN).

Deep Sequence Analysis of AgoshRNA Processing Reveals 3' A Addition and Trimming

PubMed Central

Harwig, Alex; Herrera-Carrillo, Elena; Jongejan, Aldo; van Kampen, Antonius Hubertus; Berkhout, Ben

2015-01-01

The RNA interference (RNAi) pathway, in which microprocessor and Dicer collaborate to process microRNAs (miRNA), was recently expanded by the description of alternative processing routes. In one of these noncanonical pathways, Dicer action is replaced by the Argonaute2 (Ago2) slicer function. It was recently shown that the stem-length of precursor-miRNA or short hairpin RNA (shRNA) molecules is a major determinant for Dicer versus Ago2 processing. Here we present the results of a deep sequence study on the processing of shRNAs with different stem length and a top G·U wobble base pair (bp). This analysis revealed some unexpected properties of these so-called AgoshRNA molecules that are processed by Ago2 instead of Dicer. First, we confirmed the gradual shift from Dicer to Ago2 processing upon shortening of the hairpin length. Second, hairpins with a stem larger than 19 base pair are inefficiently cleaved by Ago2 and we noticed a shift in the cleavage site. Third, the introduction of a top G·U bp in a regular shRNA can promote Ago2-cleavage, which coincides with a loss of Ago2-loading of the Dicer-cleaved 3' strand. Fourth, the Ago2-processed AgoshRNAs acquire a short 3' tail of 1–3 A-nucleotides (nt) and we present evidence that this product is subsequently trimmed by the poly(A)-specific ribonuclease (PARN). PMID:26172504

Metatranscriptomic evidence of pervasive and diverse chemolithoautotrophy relevant to C, S, N and Fe cycling in a shallow alluvial aquifer

PubMed Central

Jewell, Talia N M; Karaoz, Ulas; Brodie, Eoin L; Williams, Kenneth H; Beller, Harry R

2016-01-01

Groundwater ecosystems are conventionally thought to be fueled by surface-derived allochthonous organic matter and dominated by heterotrophic microbes living under often-oligotrophic conditions. However, in a 2-month study of nitrate amendment to a perennially suboxic aquifer in Rifle (CO), strain-resolved metatranscriptomic analysis revealed pervasive and diverse chemolithoautotrophic bacterial activity relevant to C, S, N and Fe cycling. Before nitrate injection, anaerobic ammonia-oxidizing (anammox) bacteria accounted for 16% of overall microbial community gene expression, whereas during the nitrate injection, two other groups of chemolithoautotrophic bacteria collectively accounted for 80% of the metatranscriptome: (1) members of the Fe(II)-oxidizing Gallionellaceae family and (2) strains of the S-oxidizing species, Sulfurimonas denitrificans. Notably, the proportion of the metatranscriptome accounted for by these three groups was considerably greater than the proportion of the metagenome coverage that they represented. Transcriptional analysis revealed some unexpected metabolic couplings, in particular, putative nitrate-dependent Fe(II) and S oxidation among nominally microaerophilic Gallionellaceae strains, including expression of periplasmic (NapAB) and membrane-bound (NarGHI) nitrate reductases. The three most active groups of chemolithoautotrophic bacteria in this study had overlapping metabolisms that allowed them to occupy different yet related metabolic niches throughout the study. Overall, these results highlight the important role that chemolithoautotrophy can have in aquifer biogeochemical cycling, a finding that has broad implications for understanding terrestrial carbon cycling and is supported by recent studies of geochemically diverse aquifers. PMID:26943628

Metatranscriptomic evidence of pervasive and diverse chemolithoautotrophy relevant to C, S, N and Fe cycling in a shallow alluvial aquifer

DOE PAGES

Jewell, Talia N. M.; Karaoz, Ulas; Brodie, Eoin L.; ...

2016-03-04

Groundwater ecosystems are conventionally thought to be fueled by surface-derived allochthonous organic matter and dominated by heterotrophic microbes living under often-oligotrophic conditions. However, in a 2-month study of nitrate amendment to a perennially suboxic aquifer in Rifle (CO), strain-resolved metatranscriptomic analysis revealed pervasive and diverse chemolithoautotrophic bacterial activity relevant to C, S, N and Fe cycling. Before nitrate injection, anaerobic ammonia-oxidizing (anammox) bacteria accounted for 16% of overall microbial community gene expression, whereas during the nitrate injection, two other groups of chemolithoautotrophic bacteria collectively accounted for 80% of the metatranscriptome: (1) members of the Fe(II)-oxidizing Gallionellaceae family and (2) strainsmore » of the S-oxidizing species, Sulfurimonas denitrificans. Notably, the proportion of the metatranscriptome accounted for by these three groups was considerably greater than the proportion of the metagenome coverage that they represented. Transcriptional analysis revealed some unexpected metabolic couplings, in particular, putative nitrate-dependent Fe(II) and S oxidation among nominally microaerophilic Gallionellaceae strains, including expression of periplasmic (NapAB) and membrane-bound (NarGHI) nitrate reductases. The three most active groups of chemolithoautotrophic bacteria in this study had overlapping metabolisms that allowed them to occupy different yet related metabolic niches throughout the study. Overall, these results highlight the important role that chemolithoautotrophy can have in aquifer biogeochemical cycling, a finding that has broad implications for understanding terrestrial carbon cycling and is supported by recent studies of geochemically diverse aquifers.« less

Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2′-O methylations

PubMed Central

Laudenbach, Beatrice Theres; Martínez-Montero, Saúl; Cencic, Regina; Habjan, Matthias; Pichlmair, Andreas; Damha, Masad J.; Pelletier, Jerry; Nagar, Bhushan

2017-01-01

IFIT1 (IFN-induced protein with tetratricopeptide repeats-1) is an effector of the host innate immune antiviral response that prevents propagation of virus infection by selectively inhibiting translation of viral mRNA. It relies on its ability to compete with the translation initiation factor eIF4F to specifically recognize foreign capped mRNAs, while remaining inactive against host mRNAs marked by ribose 2′-O methylation at the first cap-proximal nucleotide (N1). We report here several crystal structures of RNA-bound human IFIT1, including a 1.6-Å complex with capped RNA. IFIT1 forms a water-filled, positively charged RNA-binding tunnel with a separate hydrophobic extension that unexpectedly engages the cap in multiple conformations (syn and anti) giving rise to a relatively plastic and nonspecific mode of binding, in stark contrast to eIF4E. Cap-proximal nucleotides encircled by the tunnel provide affinity to compete with eIF4F while allowing IFIT1 to select against N1 methylated mRNA. Gel-shift binding assays confirm that N1 methylation interferes with IFIT1 binding, but in an RNA-dependent manner, whereas translation assays reveal that N1 methylation alone is not sufficient to prevent mRNA recognition at high IFIT1 concentrations. Structural and functional analysis show that 2′-O methylation at N2, another abundant mRNA modification, is also detrimental for RNA binding, thus revealing a potentially synergistic role for it in self- versus nonself-mRNA discernment. Finally, structure-guided mutational analysis confirms the importance of RNA binding for IFIT1 restriction of a human coronavirus mutant lacking viral N1 methylation. Our structural and biochemical analysis sheds new light on the molecular basis for IFIT1 translational inhibition of capped viral RNA. PMID:28251928

Molecular and macro-scale analysis of enzyme-crosslinked silk hydrogels for rational biomaterial design.

PubMed

McGill, Meghan; Coburn, Jeannine M; Partlow, Benjamin P; Mu, Xuan; Kaplan, David L

2017-11-01

Silk fibroin-based hydrogels have exciting applications in tissue engineering and therapeutic molecule delivery; however, their utility is dependent on their diffusive properties. The present study describes a molecular and macro-scale investigation of enzymatically-crosslinked silk fibroin hydrogels, and demonstrates that these systems have tunable crosslink density and diffusivity. We developed a liquid chromatography tandem mass spectroscopy (LC-MS/MS) method to assess the quantity and order of covalent tyrosine crosslinks in the hydrogels. This analysis revealed between 28 and 56% conversion of tyrosine to dityrosine, which was dependent on the silk concentration and reactant concentration. The crosslink density was then correlated with storage modulus, revealing that both crosslinking and protein concentration influenced the mechanical properties of the hydrogels. The diffusive properties of the bulk material were studied by fluorescence recovery after photobleaching (FRAP), which revealed a non-linear relationship between silk concentration and diffusivity. As a result of this work, a model for synthesizing hydrogels with known crosslink densities and diffusive properties has been established, enabling the rational design of silk hydrogels for biomedical applications. Hydrogels from naturally-derived silk polymers offer versitile opportunities in the biomedical field, however, their design has largely been an empirical process. We present a fundamental study of the crosslink density, storage modulus, and diffusion behavior of enzymatically-crosslinked silk hydrogels to better inform scaffold design. These studies revealed unexpected non-linear trends in the crosslink density and diffusivity of silk hydrogels with respect to protein concentration and crosslink reagent concentration. This work demonstrates the tunable diffusivity and crosslinking in silk fibroin hydrogels, and enables the rational design of biomaterials. Further, the characterization methods presented have applications for other materials with dityrosine crosslinks, which are found in nature as post-translational modificaitons, as well as in engineered matrices such as tyramine-substituted hyaluronic acid and recombinant resilin. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

On the globality of motor suppression: unexpected events and their influence on behavior and cognition

PubMed Central

Wessel, Jan R.; Aron, Adam R.

2016-01-01

SUMMARY Unexpected events are part of everyday experience. They come in several varieties – action errors, unexpected action outcomes, and unexpected perceptual events – and they lead to motor slowing and cognitive distraction. While different varieties of unexpected events have been studied largely independently, and many different mechanisms are thought to explain their effects on action and cognition, we suggest a unifying theory. We propose that unexpected events recruit a fronto-basal-ganglia network for stopping. This network includes specific prefrontal cortical nodes and is posited to project to the subthalamic nucleus, with a putative global suppressive effect on basal-ganglia output. We argue that unexpected events interrupt action and impact cognition, partly at least, by recruiting this global suppressive network. This provides a common mechanistic basis for different types of unexpected events, links the literatures on motor inhibition, performance-monitoring, attention, and working memory, and is relevant for understanding clinical symptoms of distractibility and mental inflexibility. PMID:28103476

On the Globality of Motor Suppression: Unexpected Events and Their Influence on Behavior and Cognition.

PubMed

Wessel, Jan R; Aron, Adam R

2017-01-18

Unexpected events are part of everyday experience. They come in several varieties-action errors, unexpected action outcomes, and unexpected perceptual events-and they lead to motor slowing and cognitive distraction. While different varieties of unexpected events have been studied largely independently, and many different mechanisms are thought to explain their effects on action and cognition, we suggest a unifying theory. We propose that unexpected events recruit a fronto-basal-ganglia network for stopping. This network includes specific prefrontal cortical nodes and is posited to project to the subthalamic nucleus, with a putative global suppressive effect on basal-ganglia output. We argue that unexpected events interrupt action and impact cognition, partly at least, by recruiting this global suppressive network. This provides a common mechanistic basis for different types of unexpected events; links the literatures on motor inhibition, performance monitoring, attention, and working memory; and is relevant for understanding clinical symptoms of distractibility and mental inflexibility. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of the Legionella longbeachae Genome and Transcriptome Uncovers Unique Strategies to Cause Legionnaires' Disease

PubMed Central

Rusniok, Christophe; Lomma, Mariella; Dervins-Ravault, Delphine; Newton, Hayley J.; Sansom, Fiona M.; Jarraud, Sophie; Zidane, Nora; Ma, Laurence; Bouchier, Christiane; Etienne, Jerôme; Hartland, Elizabeth L.; Buchrieser, Carmen

2010-01-01

Legionella pneumophila and L. longbeachae are two species of a large genus of bacteria that are ubiquitous in nature. L. pneumophila is mainly found in natural and artificial water circuits while L. longbeachae is mainly present in soil. Under the appropriate conditions both species are human pathogens, capable of causing a severe form of pneumonia termed Legionnaires' disease. Here we report the sequencing and analysis of four L. longbeachae genomes, one complete genome sequence of L. longbeachae strain NSW150 serogroup (Sg) 1, and three draft genome sequences another belonging to Sg1 and two to Sg2. The genome organization and gene content of the four L. longbeachae genomes are highly conserved, indicating strong pressure for niche adaptation. Analysis and comparison of L. longbeachae strain NSW150 with L. pneumophila revealed common but also unexpected features specific to this pathogen. The interaction with host cells shows distinct features from L. pneumophila, as L. longbeachae possesses a unique repertoire of putative Dot/Icm type IV secretion system substrates, eukaryotic-like and eukaryotic domain proteins, and encodes additional secretion systems. However, analysis of the ability of a dotA mutant of L. longbeachae NSW150 to replicate in the Acanthamoeba castellanii and in a mouse lung infection model showed that the Dot/Icm type IV secretion system is also essential for the virulence of L. longbeachae. In contrast to L. pneumophila, L. longbeachae does not encode flagella, thereby providing a possible explanation for differences in mouse susceptibility to infection between the two pathogens. Furthermore, transcriptome analysis revealed that L. longbeachae has a less pronounced biphasic life cycle as compared to L. pneumophila, and genome analysis and electron microscopy suggested that L. longbeachae is encapsulated. These species-specific differences may account for the different environmental niches and disease epidemiology of these two Legionella species. PMID:20174605

Theory of mind for processing unexpected events across contexts.

PubMed

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.

Unexpected weak seasonal climate in the western Mediterranean region during MIS 31, a high-insolation forced interglacial

NASA Astrophysics Data System (ADS)

Oliveira, Dulce; Sánchez Goñi, Maria Fernanda; Naughton, Filipa; Polanco-Martínez, J. M.; Jimenez-Espejo, Francisco J.; Grimalt, Joan O.; Martrat, Belen; Voelker, Antje H. L.; Trigo, Ricardo; Hodell, David; Abrantes, Fátima; Desprat, Stéphanie

2017-04-01

Marine Isotope Stage 31 (MIS 31) is an important analogue for ongoing and projected global warming, yet key questions remain about the regional signature of its extreme orbital forcing and intra-interglacial variability. Based on a new direct land-sea comparison in SW Iberian margin IODP Site U1385 we examine the climatic variability between 1100 and 1050 ka including the ;super interglacial; MIS 31, a period dominated by the 41-ky obliquity periodicity. Pollen and biomarker analyses at centennial-scale-resolution provide new insights into the regional vegetation, precipitation regime and atmospheric and oceanic temperature variability on orbital and suborbital timescales. Our study reveals that atmospheric and SST warmth during MIS 31 was not exceptional in this region highly sensitive to precession. Unexpectedly, this warm stage stands out as a prolonged interval of a temperate and humid climate regime with reduced seasonality, despite the high insolation (precession minima values) forcing. We find that the dominant forcing on the long-term temperate forest development was obliquity, which may have induced a decrease in summer dryness and associated reduction in seasonal precipitation contrast. Moreover, this study provides the first evidence for persistent atmospheric millennial-scale variability during this interval with multiple forest decline events reflecting repeated cooling and drying episodes in SW Iberia. Our direct land-sea comparison shows that the expression of the suborbital cooling events on SW Iberian ecosystems is modulated by the predominance of high or low-latitude forcing depending on the glacial/interglacial baseline climate states. Severe dryness and air-sea cooling is detected under the larger ice volume during glacial MIS 32 and MIS 30. The extreme episodes, which in their climatic imprint are similar to the Heinrich events, are likely related to northern latitude ice-sheet instability and a disruption of the Atlantic Meridional Overturning Circulation (AMOC). In contrast, forest declines during MIS 31 are associated to neither SST cooling nor high-latitude freshwater forcing. Time-series analysis reveals a dominant cyclicity of about 6 ky in the temperate forest record, which points to a potential link with the fourth harmonic of precession and thus low-latitude insolation forcing.

Complex Tectono-Magmatic Interaction along the George V Transform Fault, South-East Indian Ridge, 140°E, and Implications for Mantle Dynamics

NASA Astrophysics Data System (ADS)

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

Aujeszky's disease in red fox (Vulpes vulpes): phylogenetic analysis unravels an unexpected epidemiologic link.

PubMed

Caruso, Claudio; Dondo, Alessandro; Cerutti, Francesco; Masoero, Loretta; Rosamilia, Alfonso; Zoppi, Simona; D'Errico, Valeria; Grattarola, Carla; Acutis, Pier Luigi; Peletto, Simone

2014-07-01

We describe Aujeszky's disease in a female of red fox (Vulpes vulpes). Although wild boar (Sus scrofa) would be the expected source of infection, phylogenetic analysis suggested a domestic rather than a wild source of virus, underscoring the importance of biosecurity measures in pig farms to prevent contact with wild animals.

Automated Sensitivity Analysis of Interplanetary Trajectories

NASA Technical Reports Server (NTRS)

Knittel, Jeremy; Hughes, Kyle; Englander, Jacob; Sarli, Bruno

2017-01-01

This work describes a suite of Python tools known as the Python EMTG Automated Trade Study Application (PEATSA). PEATSA was written to automate the operation of trajectory optimization software, simplify the process of performing sensitivity analysis, and was ultimately found to out-perform a human trajectory designer in unexpected ways. These benefits will be discussed and demonstrated on sample mission designs.

Ambiguous genetic relationships among coconut (Cocos nucifera L.) cultivars: the effects of outcrossing, sample source and size, and method of analysis.

USDA-ARS?s Scientific Manuscript database

A prior analysis of eight coconut cultivars with 15 microsatellite (SSR) markers drew unexpected relationships between two of the out-crossing tall cultivars evaluated: ‘Atlantic Tall’ and ‘Panama Tall’. We further investigated the relationships between these eight cultivars by increasing the number...

Directed evolution reveals unexpected epistatic interactions that alter metabolic regulation and enable anaerobic xylose use by Saccharomyces cerevisiae

DOE PAGES

Sato, Trey K.; Tremaine, Mary; Parreiras, Lucas S.; ...

2016-10-14

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 interactionsmore » 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. Lastly, 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.« less

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

PubMed

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.

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

PubMed Central

Tremaine, Mary; Hebert, Alexander S.; Myers, Kevin S.; Sardi, Maria; Dickinson, Quinn; Reed, Jennifer L.; Zhang, Yaoping; Coon, Joshua J.; Hittinger, Chris Todd; Gasch, Audrey P.; Landick, Robert

2016-01-01

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. PMID:27741250

Molybdenum Trafficking for Nitrogen Fixation†

PubMed Central

Hernandez, Jose A.; George, Simon J.; Rubio, Luis M.

2009-01-01

The molybdenum nitrogenase is responsible for most biological nitrogen fixation, a prokaryotic metabolic process that determines the global biogeochemical cycles of nitrogen and carbon. Here we describe the trafficking of molybdenum for nitrogen fixation in the model diazotrophic bacterium Azotobacter vinelandii. The genes and proteins involved in molybdenum uptake, homeostasis, storage, regulation, and nitrogenase cofactor biosynthesis are reviewed. Molybdenum biochemistry in A. vinelandii reveals unexpected mechanisms and a new role for iron-sulfur clusters in the sequestration and delivery of molybdenum. PMID:19772354

Cancer therapy based on oncogene addiction.

PubMed

McCormick, Frank

2011-05-01

Tumor cells contain multiple mutations, yet they often depend on continued expressed of a single oncoprotein for survival. Targeting these proteins has led to dramatic responses. Unfortunately, patients usually progress, through drug resistance or adaptive resistance through reprogramming of signaling networks. The Ras-MAPK pathway provides examples of these successes and failures, and has revealed unexpected degrees of oncogene addiction and signaling complexity that are likely to be useful lessons for the future of targeted therapy. Copyright © 2011 Wiley-Liss, Inc.

Incidental Detection of Urinary Leakage on FDG PET/CT Imaging for Staging of Gastric Cancer.

PubMed

Kim, Dae-Weung; Kim, Myoung Hyoun; Kim, Chang Guhn

2016-03-01

A 71-year-old woman presented to the emergency department with right flank pain and dysuria. An abdominal CT scan detected a gastric malignancy and hydronephrosis with urinary leakage of the right kidney. Percutaneous nephrostomy was performed on the right kidney. F-FDG PET/CT for staging the gastric malignancy revealed additional urinary leakage of the contralateral kidney. The interest in this case is the incidental detection of unexpected urinary leakage during an oncologic assessment with FDG PET/CT.

Olive ingestion causing a false suspicion of relapsed neuroblastoma: A case of "oliveblastoma?"

PubMed

Flynn, Nick; LeFebvre, Amanda; Messahel, Boo; Hogg, Sarah L

2018-06-19

Measurement of the urine catecholamine metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) are the standard method for detecting disease recurrence in neuroblastoma. We present a case of abnormal concentrations of catecholamine metabolites that prompted investigations for relapsed neuroblastoma. However, further study revealed that the abnormal biochemistry was likely due to ingestion of olives. Olive ingestion should be considered when interpreting urine HVA and VMA results, and excluded if concentrations are unexpectedly abnormal. © 2018 Wiley Periodicals, Inc.

Explanation of the quantum phenomenon of off-resonant cavity-mode emission

NASA Astrophysics Data System (ADS)

Echeverri-Arteaga, Santiago; Vinck-Posada, Herbert; Gómez, Edgar A.

2018-04-01

We theoretically investigate the unexpected occurrence of an extra emission peak that has been experimentally observed in off-resonant studies of cavity QED systems. Our results within the Markovian master equation approach successfully explain why the central peak arises, and how it reveals that the system is suffering a dynamical phase transition induced by the phonon-mediated coupling. Our findings are in qualitative agreement with previous reported experimental results, and the fundamental physics behind this quantum phenomenon is understood.

Cartography and Connectomes Perspective article for Neuron 25th Anniversary Issue

PubMed Central

Van Essen, David C.

2013-01-01

The past 25 years have seen great progress in parcellating the cerebral cortex into a mosaic of many distinct areas in mice, monkeys, and humans. Quantitative studies of inter-areal connectivity have revealed unexpectedly many pathways and a wide range of connection strengths in mouse and macaque cortex. In humans, advances in analyzing ‘structural’ and ‘functional’ connectivity using powerful but indirect noninvasive neuroimaging methods are yielding intriguing insights about brain circuits, their variability across individuals, and their relationship to behavior. PMID:24183027

Wybutosine biosynthesis: Structural and mechanistic overview

PubMed Central

Perche-Letuvée, Phanélie; Molle, Thibaut; Forouhar, Farhad; Mulliez, Etienne; Atta, Mohamed

2014-01-01

Over the last 10 years, significant progress has been made in understanding the genetics, enzymology and structural components of the wybutosine (yW) biosynthetic pathway. These studies have played a key role in expanding our understanding of yW biosynthesis and have revealed unexpected evolutionary ties, which are presently being unraveled. The enzymes catalyzing the 5 steps of this pathway, from genetically encoded guanosine to wybutosine base, provide an ensemble of amazing reaction mechanisms that are to be discussed in this review article. PMID:25629788

Brain function during probabilistic learning in relation to IQ and level of education.

PubMed

van den Bos, Wouter; Crone, Eveline A; Güroğlu, Berna

2012-02-15

Knowing how to adapt your behavior based on feedback lies at the core of successful learning. We investigated the relation between brain function, grey matter volume, educational level and IQ in a Dutch adolescent sample. In total 45 healthy volunteers between ages 13 and 16 were recruited from schools for pre-vocational and pre-university education. For each individual, IQ was estimated using two subtests from the WISC-III-R (similarities and block design). While in the magnetic resonance imaging (MRI) scanner, participants performed a probabilistic learning task. Behavioral comparisons showed that participants with higher IQ used a more adaptive learning strategy after receiving positive feedback. Analysis of neural activation revealed that higher IQ was associated with increased activation in DLPFC and dACC when receiving positive feedback, specifically for rules with low reward probability (i.e., unexpected positive feedback). Furthermore, VBM analyses revealed that IQ correlated positively with grey matter volume within these regions. These results provide support for IQ-related individual differences in the developmental time courses of neural circuitry supporting feedback-based learning. Current findings are interpreted in terms of a prolonged window of flexibility and opportunity for adolescents with higher IQ scores. Copyright © 2011 Elsevier Ltd. All rights reserved.

The transcriptome recipe for the venom cocktail of Tityus bahiensis scorpion.

PubMed

de Oliveira, Ursula Castro; Candido, Denise Maria; Dorce, Valquíria Abrão Coronado; Junqueira-de-Azevedo, Inácio de Loiola Meirelles

2015-03-01

Scorpion venom is a mixture of peptides, including antimicrobial, bradykinin-potentiating and anionic peptides and small to medium proteins, such as ion channel toxins, metalloproteinases and phospholipases that together cause severe clinical manifestation. Tityus bahiensis is the second most medically important scorpion species in Brazil and it is widely distributed in the country with the exception of the North Region. Here we sequenced and analyzed the transcripts from the venom glands of T. bahiensis, aiming at identifying and annotating venom gland expressed genes. A total of 116,027 long reads were generated by pyrosequencing and assembled in 2891 isotigs. An annotation process identified transcripts by similarity to known toxins, revealing that putative venom components represent 7.4% of gene expression. The major toxins identified are potassium and sodium channel toxins, whereas metalloproteinases showed an unexpected high abundance. Phylogenetic analysis of deduced metalloproteinases from T. bahiensis and other scorpions revealed a pattern of ancient and intraspecific gene expansions. Other venom molecules identified include antimicrobial, anionic and bradykinin-potentiating peptides, besides several putative new venom components. This report provides the first attempt to massively identify the venom components of this species and constitutes one of the few transcriptomic efforts on the genus Tityus. Copyright © 2015 Elsevier Ltd. All rights reserved.

DELLA genes restrict inflorescence meristem function independently of plant height.

PubMed

Serrano-Mislata, Antonio; Bencivenga, Stefano; Bush, Max; Schiessl, Katharina; Boden, Scott; Sablowski, Robert

2017-09-01

DELLA proteins associate with transcription factors to control plant growth in response to gibberellin 1 . Semi-dwarf DELLA mutants with improved harvest index and decreased lodging greatly improved global food security during the 'green revolution' in the 1960-1970s 2 . However, DELLA mutants are pleiotropic and the developmental basis for their effects on plant architecture remains poorly understood. Here, we show that DELLA proteins have genetically separable roles in controlling stem growth and the size of the inflorescence meristem, where flowers initiate. Quantitative three-dimensional image analysis, combined with a genome-wide screen for DELLA-bound loci in the inflorescence tip, revealed that DELLAs limit meristem size in Arabidopsis by directly upregulating the cell-cycle inhibitor KRP2 in the underlying rib meristem, without affecting the canonical WUSCHEL-CLAVATA meristem size regulators 3 . Mutation of KRP2 in a DELLA semi-dwarf background restored meristem size, but not stem growth, and accelerated flower production. In barley, secondary mutations in the DELLA gain-of-function mutant Sln1d 4 also uncoupled meristem and inflorescence size from plant height. Our work reveals an unexpected and conserved role for DELLA genes in controlling shoot meristem function and suggests how dissection of pleiotropic DELLA functions could unlock further yield gains in semi-dwarf mutants.

DELLA genes restrict inflorescence meristem function independently of plant height

PubMed Central

Serrano-Mislata, Antonio; Bencivenga, Stefano; Bush, Max; Schiessl, Katharina; Boden, Scott; Sablowski, Robert

2017-01-01

Summary DELLA proteins associate with transcription factors to control plant growth in response to gibberellin 1. Semi-dwarf DELLA mutants with improved harvest index and decreased lodging greatly improved global food security during the “green revolution” in the 1960-70s 2. However, DELLA mutants are pleiotropic and the developmental basis for their effects on plant architecture remains poorly understood. Here, we show that DELLA proteins have genetically separable roles in controlling stem growth and the size of the inflorescence meristem, where flowers initiate. Quantitative 3D image analysis, combined with a genome-wide screen for DELLA-bound loci in the inflorescence tip, revealed that DELLAs limit meristem size in Arabidopsis by directly up-regulating the cell cycle inhibitor KRP2 in the underlying rib meristem, without affecting the canonical WUSCHEL-CLAVATA meristem size regulators3. Mutation of KRP2 in a DELLA semi-dwarf background restored meristem size, but not stem growth, and accelerated flower production. In barley, secondary mutations in the DELLA gain of function mutant Sln1d 4 also uncoupled meristem and inflorescence size from plant height. Our work reveals an unexpected and conserved role for DELLA genes in controlling shoot meristem function and suggests how dissection of pleiotropic DELLA functions could unlock further yield gains in semi-dwarf mutants. PMID:28827519

Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus

PubMed Central

Mulvihill, Eoin D.; Moloney, Nicola M.; Owens, Rebecca A.; Dolan, Stephen K.; Russell, Lauren; Doyle, Sean

2017-01-01

The functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in Aspergillus fumigatus is unknown. Here, we generate and characterize eight gene deletion strains, and of most significance reveal that MirC (AFUA_2G05730) contributes to the maintenance of intracellular siderophore [ferricrocin (FC)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal virulence in the Galleria mellonella animal model system. FC levels were unaffected following deletion of all other genes encoding microsome-associated proteins. MirC does not appear to play a role in either siderophore export from, or uptake into, A. fumigatus. Label-free quantitative proteomic analysis unexpectedly revealed increased abundance of siderophore biosynthetic enzymes. In addition, increased expression of hapX (7.2 and 13.8-fold at 48 and 72 h, respectively; p < 0.001) was observed in ΔmirC compared to wild-type under iron-replete conditions by qRT-PCR. This was complemented by significantly elevated extracellular triacetylfusarinine C (TAFC; p < 0.01) and fusarinine C (FSC; p < 0.05) siderophore secretion. We conclude that MirC plays an important role in FC biosynthesis and contributes to the maintenance of iron homeostasis in A. fumigatus. PMID:28367141

Calbindin-D28k is a more reliable marker of human Purkinje cells than standard Nissl stains: a stereological experiment.

PubMed

Whitney, Elizabeth R; Kemper, Thomas L; Rosene, Douglas L; Bauman, Margaret L; Blatt, Gene J

2008-02-15

In a study of human Purkinje cell (PC) number, a striking mismatch between the number of PCs observed with the Nissl stain and the number of PCs immunopositive for calbindin-D28k (CB) was identified in 2 of the 10 brains examined. In the remaining eight brains this mismatch was not observed. Further, in these eight brains, analysis of CB immunostained sections counterstained with the Nissl stain revealed that more than 99% Nissl stained PCs were also immunopositive for CB. In contrast, in the two discordant brains, only 10-20% of CB immunopositive PCs were also identified with the Nissl stain. Although this finding was unexpected, a historical survey of the literature revealed that Spielmeyer [Spielmeyer W. Histopathologie des nervensystems. Julius Springer: Berlin; 1922. p. 56-79] described human cases with PCs that lacked the expected Nissl staining intensity, an important historical finding and critical issue when studying postmortem human brains. The reason for this failure in Nissl staining is not entirely clear, but it may result from premortem circumstances since it is not accounted for by postmortem delay or processing variables. Regardless of the exact cause, these observations suggest that Nissl staining may not be a reliable marker for PCs and that CB is an excellent alternative marker.

A new primitive Neornithischian dinosaur from the Jurassic of Patagonia with gut contents

NASA Astrophysics Data System (ADS)

Salgado, Leonardo; Canudo, José I.; Garrido, Alberto C.; Moreno-Azanza, Miguel; Martínez, Leandro C. A.; Coria, Rodolfo A.; Gasca, José M.

2017-02-01

We describe a new species of an ornithischian dinosaur, Isaberrysaura mollensis gen. et sp. nov. The specimen, consisting in an almost complete skull and incomplete postcranium was collected from the marine-deltaic deposits of the Los Molles Formation (Toarcian-Bajocian), being the first reported dinosaur for this unit, one of the oldest from Neuquén Basin, and the first neornithischian dinosaur known from the Jurassic of South America. Despite showing a general stegosaurian appearance, the extensive phylogenetic analysis carried out depicts Isaberrysaura mollensis gen. et sp. nov. as a basal ornithopod, suggesting that both Thyreophora and neornithischians could have achieved significant convergent features. The specimen was preserved articulated and with some of its gut content place in the middle-posterior part of the thoracic cavity. Such stomach content was identified as seeds, most of them belonging to the Cycadales group. This finding reveals a possible and unexpected role of this ornithischian species as seed-dispersal agent.

Single-Cell Based Quantitative Assay of Chromosome Transmission Fidelity

PubMed Central

Zhu, Jin; Heinecke, Dominic; Mulla, Wahid A.; Bradford, William D.; Rubinstein, Boris; Box, Andrew; Haug, Jeffrey S.; Li, Rong

2015-01-01

Errors in mitosis are a primary cause of chromosome instability (CIN), generating aneuploid progeny cells. Whereas a variety of factors can influence CIN, under most conditions mitotic errors are rare events that have been difficult to measure accurately. Here we report a green fluorescent protein−based quantitative chromosome transmission fidelity (qCTF) assay in budding yeast that allows sensitive and quantitative detection of CIN and can be easily adapted to high-throughput analysis. Using the qCTF assay, we performed genome-wide quantitative profiling of genes that affect CIN in a dosage-dependent manner and identified genes that elevate CIN when either increased (icCIN) or decreased in copy number (dcCIN). Unexpectedly, qCTF screening also revealed genes whose change in copy number quantitatively suppress CIN, suggesting that the basal error rate of the wild-type genome is not minimized, but rather, may have evolved toward an optimal level that balances both stability and low-level karyotype variation for evolutionary adaptation. PMID:25823586

Single-Cell Based Quantitative Assay of Chromosome Transmission Fidelity.

PubMed

Zhu, Jin; Heinecke, Dominic; Mulla, Wahid A; Bradford, William D; Rubinstein, Boris; Box, Andrew; Haug, Jeffrey S; Li, Rong

2015-03-30

Errors in mitosis are a primary cause of chromosome instability (CIN), generating aneuploid progeny cells. Whereas a variety of factors can influence CIN, under most conditions mitotic errors are rare events that have been difficult to measure accurately. Here we report a green fluorescent protein-based quantitative chromosome transmission fidelity (qCTF) assay in budding yeast that allows sensitive and quantitative detection of CIN and can be easily adapted to high-throughput analysis. Using the qCTF assay, we performed genome-wide quantitative profiling of genes that affect CIN in a dosage-dependent manner and identified genes that elevate CIN when either increased (icCIN) or decreased in copy number (dcCIN). Unexpectedly, qCTF screening also revealed genes whose change in copy number quantitatively suppress CIN, suggesting that the basal error rate of the wild-type genome is not minimized, but rather, may have evolved toward an optimal level that balances both stability and low-level karyotype variation for evolutionary adaptation. Copyright © 2015 Zhu et al.

Complex dynamics of selection and cellular memory in adaptation to a changing environment

NASA Astrophysics Data System (ADS)

Kussell, Edo; Lin, Wei-Hsiang

We study a synthetic evolutionary system in bacteria in which an antibiotic resistance gene is controlled by a stochastic on/off switching promoter. At the population level, this system displays all the basic ingredients for evolutionary selection, including diversity, fitness differences, and heritability. At the single cell level, physiological processes can modulate the ability of selection to act. We expose the stochastic switching strains to pulses of antibiotics of different durations in periodically changing environments using microfluidics. Small populations are tracked over a large number of periods at single cell resolution, allowing the visualization and quantification of selective sweeps and counter-sweeps at the population level, as well as detailed single cell analysis. A simple model is introduced to predict long-term population growth rates from single cell measurements, and reveals unexpected aspects of population dynamics, including cellular memory that acts on a fast timescale to modulate growth rates. This work is supported by NIH Grant No. R01-GM097356.

Regulation and physiological functions of mammalian phospholipase C.

PubMed

Nakamura, Yoshikazu; Fukami, Kiyoko

2017-04-01

Phospholipase C (PLC) is a key enzyme in phosphoinositide metabolism. PLC hydrolyses phosphatidylinositol 4,5-bis-phosphate to generate two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol, that generate diverse cellular responses. PLC is activated by various signalling molecules, including Ca2+, heterometric G proteins, small G proteins, and receptor/non-receptor tyrosine kinases. In addition to their enzymatic activity, some PLC subtypes also function as a guanine nucleotide exchange factor, GTPase-activating protein, and adaptor protein, independent of their lipase activity. There are 13 PLC isozymes in mammals, and they are categorized into six classes based on structure. Generation and analysis of genetically modified mice has revealed the unexpectedly diverse physiological functions of PLC isozymes. Although all PLC isozymes catalyze the same reaction, each PLC isozyme has unique physiological functions. This review focuses on the regulation and physiological functions of PLCs. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Composite operators in cubic field theories and link-overlap fluctuations in spin-glass models

NASA Astrophysics Data System (ADS)

Altieri, Ada; Parisi, Giorgio; Rizzo, Tommaso

2016-01-01

We present a complete characterization of the fluctuations and correlations of the squared overlap in the Edwards-Anderson spin-glass model in zero field. The analysis reveals that the energy-energy correlation (and thus the specific heat) has a different critical behavior than the fluctuations of the link overlap in spite of the fact that the average energy and average link overlap have the same critical properties. More precisely the link-overlap fluctuations are larger than the specific heat according to a computation at first order in the 6 -ɛ expansion. An unexpected outcome is that the link-overlap fluctuations have a subdominant power-law contribution characterized by an anomalous logarithmic prefactor which is absent in the specific heat. In order to compute the ɛ expansion we consider the problem of the renormalization of quadratic composite operators in a generic multicomponent cubic field theory: the results obtained have a range of applicability beyond spin-glass theory.

Induction of Interferon-Stimulated Genes by Simian Virus 40 T Antigens

PubMed Central

Rathi, Abhilasha V.; Cantalupo, Paul G.; Sarkar, Saumendra N.; Pipas, James M.

2010-01-01

Simian virus 40 (SV40) large T antigen (TAg) is a multifunctional oncoprotein essential for productive viral infection and for cellular transformation. We have used microarray analysis to examine the global changes in cellular gene expression induced by wild-type T antigen (TAgwt) and TAg-mutants in mouse embryo fibroblasts (MEFs). The expression profile of approximately 800 cellular genes was altered by TAgwt and a truncated TAg (TAgN136), including many genes that influence cell cycle, DNA-replication, transcription, chromatin structure and DNA repair. Unexpectedly, we found a significant number of immune response genes upregulated by TAgwt including many interferon stimulated genes (ISGs) such as ISG56, OAS, Rsad2, Ifi27 and Mx1. Additionally, we also observed activation of STAT1 by TAgwt. Our genetic studies using several TAg mutants reveal an unexplored function of TAg and indicate that the LXCXE motif and p53 binding are required for the upregulation of ISGs. PMID:20692676

SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

PubMed

Brannan, Kristopher W; Jin, Wenhao; Huelga, Stephanie C; Banks, Charles A S; Gilmore, Joshua M; Florens, Laurence; Washburn, Michael P; Van Nostrand, Eric L; Pratt, Gabriel A; Schwinn, Marie K; Daniels, Danette L; Yeo, Gene W

2016-10-20

RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes. Without relying on sequence or structure information, SONAR identifies 1,923 human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs, revealing unexpected RNA binding activity for disease-relevant proteins and DNA binding proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

Immunization-elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability

PubMed Central

Zhao, Xuelian; Howell, Katie A.; He, Shihua; Brannan, Jennifer M.; Wec, Anna Z.; Davidson, Edgar; Turner, Hannah L.; Chiang, Chi-I; Lei, Lin; Fels, J. Maximilian; Vu, Hong; Shulenin, Sergey; Turonis, Ashley N.; Kuehne, Ana I.; Liu, Guodong; Ta, Mi; Wang, Yimeng; Sundling, Christopher; Xiao, Yongli; Spence, Jennifer S.; Doranz, Benjamin J.; Holtsberg, Frederick W.; Ward, Andrew B.; Chandran, Kartik; Dye, John M.; Qiu, Xiangguo; Li, Yuxing; Aman, M. Javad

2018-01-01

Summary While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N-terminus of the ebolavirus glycoproteins (GP) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets. Analysis of memory B cells from the immunized macaque suggests that elicitation of broadly neutralizing antibodies (bNAbs) for ebolaviruses is possible but difficult, potentially due to the rarity of bNAb clones and their precursors. Unexpectedly, germline-reverted CA45, while exhibiting negligible binding to full-length GP, bound a proteolytically remodeled GP with picomolar affinity, suggesting that engineered ebolavirus vaccines could trigger rare bNAb precursors more robustly. These findings have important implications for developing pan-ebolavirus vaccine and immunotherapeutic cocktails. PMID:28525756

"Dark" Singlet Oxygen and Electron Paramagnetic Resonance Spin Trapping as Convenient Tools to Assess Photolytic Drug Degradation.

PubMed

Persich, Peter; Hostyn, Steven; Joie, Céline; Winderickx, Guy; Pikkemaat, Jeroen; Romijn, Edwin P; Maes, Bert U W

2017-05-01

Forced degradation studies are an important tool for a systematic assessment of decomposition pathways and identification of reactive sites in active pharmaceutical ingredients (APIs). Two methodologies have been combined in order to provide a deeper understanding of singlet oxygen-related degradation pathways of APIs under light irradiation. First, we report that a "dark" singlet oxygen test enables the investigation of drug reactivity toward singlet oxygen independently of photolytic irradiation processes. Second, the photosensitizing properties of the API producing the singlet oxygen was proven and quantified by spin trapping and electron paramagnetic resonance analysis. A combination of these techniques is an interesting addition to the forced degradation portfolio as it can be used for (1) revealing unexpected degradation pathways of APIs due to singlet oxygen, (2) clarifying photolytic drug-drug interactions in fixed-dose combinations, and (3) synthesizing larger quantities of hardly accessible oxidative drug degradants. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A draft map of the mouse pluripotent stem cell spatial proteome

PubMed Central

Christoforou, Andy; Mulvey, Claire M.; Breckels, Lisa M.; Geladaki, Aikaterini; Hurrell, Tracey; Hayward, Penelope C.; Naake, Thomas; Gatto, Laurent; Viner, Rosa; Arias, Alfonso Martinez; Lilley, Kathryn S.

2016-01-01

Knowledge of the subcellular distribution of proteins is vital for understanding cellular mechanisms. Capturing the subcellular proteome in a single experiment has proven challenging, with studies focusing on specific compartments or assigning proteins to subcellular niches with low resolution and/or accuracy. Here we introduce hyperLOPIT, a method that couples extensive fractionation, quantitative high-resolution accurate mass spectrometry with multivariate data analysis. We apply hyperLOPIT to a pluripotent stem cell population whose subcellular proteome has not been extensively studied. We provide localization data on over 5,000 proteins with unprecedented spatial resolution to reveal the organization of organelles, sub-organellar compartments, protein complexes, functional networks and steady-state dynamics of proteins and unexpected subcellular locations. The method paves the way for characterizing the impact of post-transcriptional and post-translational modification on protein location and studies involving proteome-level locational changes on cellular perturbation. An interactive open-source resource is presented that enables exploration of these data. PMID:26754106

Hyperthyroidism as a clinical manifestation of a embryonal carcinoma of the testis.

PubMed

Arrabal-Polo, M A; Jimenez-Pacheco, A; Arrabal-Martin, M; Moreno-Jimenez, J; Gutierrez-Tejero, F; Galisteo-Moya, R; Zuluaga-Gomez, A

2012-01-01

This case report describes a case of hyperthyroidism as manifestation of an embryonal carcinoma, and illustrates the causes that led to it. The case describes a 33-year-old male patient who complained of chest pain, palpitations, mild dyspnoea, and weight loss. Blood analysis reveals high levels of human chorionic gonadotropin (833818 mlU/ml), T3 (16.90 pg/ml), and T4 (7.77 ng/dl), as well as a fall of TSH (0.01 ulU/ml). Physical examination and imaging procedures confirm the occurrence of a left testicular tumour associated with numerous lung, hepatic and retroperitoneal metastases. Treatment with carbimazol and propanolol is established to manage hyperthyroidism, and an urgent orchiectomy is performed; the histologic diagnosis confirms an embryonal carcinoma (organoid type), but the patient died unexpectedly 24 hours later after having suffered sudden dyspnoea, tachypnoea, and tachyarrhythmia. Hyperthyroidism is a rare manifestation of a testicular tumour that should be borne in mind with regard to the patient's symptomatology and HCG levels.

The conformational dynamics of the mitochondrial Hsp70 chaperone.

PubMed

Mapa, Koyeli; Sikor, Martin; Kudryavtsev, Volodymyr; Waegemann, Karin; Kalinin, Stanislav; Seidel, Claus A M; Neupert, Walter; Lamb, Don C; Mokranjac, Dejana

2010-04-09

Heat shock proteins 70 (Hsp70) represent a ubiquitous and conserved family of molecular chaperones involved in a plethora of cellular processes. The dynamics of their ATP hydrolysis-driven and cochaperone-regulated conformational cycle are poorly understood. We used fluorescence spectroscopy to analyze, in real time and at single-molecule resolution, the effects of nucleotides and cochaperones on the conformation of Ssc1, a mitochondrial member of the family. We report that the conformation of its ADP state is unexpectedly heterogeneous, in contrast to a uniform ATP state. Substrates are actively involved in determining the conformation of Ssc1. The J protein Mdj1 does not interact transiently with the chaperone, as generally believed, but rather is released slowly upon ATP hydrolysis. Analysis of the major bacterial Hsp70 revealed important differences between highly homologous members of the family, possibly explaining tuning of Hsp70 chaperones to meet specific functions in different organisms and cellular compartments. 2010 Elsevier Inc. All rights reserved.

Unexpected diagnosis of stage IIA dysgerminoma in streak gonad in a patient with Swyer syndrome: a case report.

PubMed

Yada-Hashimoto, Namiko; Komura, Hiroko; Nagata, Shigenori; Kubo, Chiaki; Fujita, Masami; Kamiura, Shoji

2018-06-01

Patients with Swyer syndrome, which is also known as 46,XY pure gonadal dysgenesis, are at an increased risk of gonadoblastoma and germ cell tumor. Prophylactic gonadectomy is recommended for these patients. We report a case of stage IIA dysgerminoma arising in a streak gonad in a patient with Swyer syndrome, which was not diagnosable preoperatively and intraoperatively. The patient was primarily amenorrheic and identified as female phenotypically. She underwent gonadectomy at 27 years of age. Preoperative image analysis showed a relatively small uterus without adnexal masses. Laparoscopic findings showed bilateral streak gonads. Postoperatively, histopathological examination revealed that the patient had dysgerminoma in her left streak gonad. Preoperative and intraoperative diagnosis of dysgerminoma in normal size ovaries is thought to be difficult. Although it is rare, considering the occurrence of dysgerminoma in streak gonad with extension to the mesosalpinx, prompt prophylactic gonadectomy is strongly recommended for these patients regardless of the size of the ovaries.

An ontology of scientific experiments

PubMed Central

Soldatova, Larisa N; King, Ross D

2006-01-01

The formal description of experiments for efficient analysis, annotation and sharing of results is a fundamental part of the practice of science. Ontologies are required to achieve this objective. A few subject-specific ontologies of experiments currently exist. However, despite the unity of scientific experimentation, no general ontology of experiments exists. We propose the ontology EXPO to meet this need. EXPO links the SUMO (the Suggested Upper Merged Ontology) with subject-specific ontologies of experiments by formalizing the generic concepts of experimental design, methodology and results representation. EXPO is expressed in the W3C standard ontology language OWL-DL. We demonstrate the utility of EXPO and its ability to describe different experimental domains, by applying it to two experiments: one in high-energy physics and the other in phylogenetics. The use of EXPO made the goals and structure of these experiments more explicit, revealed ambiguities, and highlighted an unexpected similarity. We conclude that, EXPO is of general value in describing experiments and a step towards the formalization of science. PMID:17015305

Concurrent bilateral pheochromocytoma and thoracic paraganglioma during pregnancy.

PubMed

Snabboon, Thiti; Plengpanich, Wanee; Houngngam, Natnicha; Buranasupkajorn, Patinut; Plengvidhya, Nattachet; Sereepapong, Wisan; Sunthornyothin, Sarat; Shotelersuk, Vorasuk

2010-04-01

Although hypertension occurring during pregnancies is not uncommon and its prognosis is generally excellent, some of its unusual causes can lead to catastrophic consequences, especially in undiagnosed cases. Here, we report a pregnant woman who presented with hypertension in her early pregnancy. It was subsequently found to be caused by bilateral pheochromocytoma. After removal of both tumors, catecholamine levels unexpectedly and unexplainably remained elevated. At 23 weeks of gestation, the fetus was found dead in utero. After the fetal death, additional studies were performed and revealed a thoracic paraganglioma. To our knowledge, this is the first report of a case of three catecholamine-producing tumors occurring concurrently during a pregnancy. Genetic analysis helped identify this unprecedented condition; the patient harbored a heterozygous missense mutation c.482G>A in exon 3 of the VHL gene, indicating von Hippel-Lindau syndrome. Physicians who care for hypertensive pregnant patients should be aware of this condition as its diagnosis would probably lead to a better outcome.

A new primitive Neornithischian dinosaur from the Jurassic of Patagonia with gut contents

PubMed Central

Salgado, Leonardo; Canudo, José I.; Garrido, Alberto C.; Moreno-Azanza, Miguel; Martínez, Leandro C. A.; Coria, Rodolfo A.; Gasca, José M.

2017-01-01

We describe a new species of an ornithischian dinosaur, Isaberrysaura mollensis gen. et sp. nov. The specimen, consisting in an almost complete skull and incomplete postcranium was collected from the marine-deltaic deposits of the Los Molles Formation (Toarcian-Bajocian), being the first reported dinosaur for this unit, one of the oldest from Neuquén Basin, and the first neornithischian dinosaur known from the Jurassic of South America. Despite showing a general stegosaurian appearance, the extensive phylogenetic analysis carried out depicts Isaberrysaura mollensis gen. et sp. nov. as a basal ornithopod, suggesting that both Thyreophora and neornithischians could have achieved significant convergent features. The specimen was preserved articulated and with some of its gut content place in the middle-posterior part of the thoracic cavity. Such stomach content was identified as seeds, most of them belonging to the Cycadales group. This finding reveals a possible and unexpected role of this ornithischian species as seed-dispersal agent. PMID:28202910

A new primitive Neornithischian dinosaur from the Jurassic of Patagonia with gut contents.

PubMed

Salgado, Leonardo; Canudo, José I; Garrido, Alberto C; Moreno-Azanza, Miguel; Martínez, Leandro C A; Coria, Rodolfo A; Gasca, José M

2017-02-16

We describe a new species of an ornithischian dinosaur, Isaberrysaura mollensis gen. et sp. nov. The specimen, consisting in an almost complete skull and incomplete postcranium was collected from the marine-deltaic deposits of the Los Molles Formation (Toarcian-Bajocian), being the first reported dinosaur for this unit, one of the oldest from Neuquén Basin, and the first neornithischian dinosaur known from the Jurassic of South America. Despite showing a general stegosaurian appearance, the extensive phylogenetic analysis carried out depicts Isaberrysaura mollensis gen. et sp. nov. as a basal ornithopod, suggesting that both Thyreophora and neornithischians could have achieved significant convergent features. The specimen was preserved articulated and with some of its gut content place in the middle-posterior part of the thoracic cavity. Such stomach content was identified as seeds, most of them belonging to the Cycadales group. This finding reveals a possible and unexpected role of this ornithischian species as seed-dispersal agent.

Inferred Cosmic-Ray Spectrum from Fermi Large Area Telescope γ -Ray Observations of Earth’s Limb

DOE PAGES

Ackermann, M.; Ajello, M.; Albert, A.; ...

2014-04-17

Accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA recently reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. Here, we use the Fermi Large Area Telescope observations of the γ -ray emission from Earth’s limb for an indirect measurement of the local spectrum of CR protons in the energy range ~ 90 GeV –more » 6 TeV (derived from a photon energy range 15 GeV–1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68 ± 0.04 and 2.61 ± 0.08 above ~ 200 GeV , respectively.« less

Surface determination through atomically resolved secondary-electron imaging

PubMed Central

Ciston, J.; Brown, H. G.; D'Alfonso, A. J.; Koirala, P.; Ophus, C.; Lin, Y.; Suzuki, Y.; Inada, H.; Zhu, Y.; Allen, L. J.; Marks, L. D.

2015-01-01

Unique determination of the atomic structure of technologically relevant surfaces is often limited by both a need for homogeneous crystals and ambiguity of registration between the surface and bulk. Atomically resolved secondary-electron imaging is extremely sensitive to this registration and is compatible with faceted nanomaterials, but has not been previously utilized for surface structure determination. Here we report a detailed experimental atomic-resolution secondary-electron microscopy analysis of the c(6 × 2) reconstruction on strontium titanate (001) coupled with careful simulation of secondary-electron images, density functional theory calculations and surface monolayer-sensitive aberration-corrected plan-view high-resolution transmission electron microscopy. Our work reveals several unexpected findings, including an amended registry of the surface on the bulk and strontium atoms with unusual seven-fold coordination within a typically high surface coverage of square pyramidal TiO5 units. Dielectric screening is found to play a critical role in attenuating secondary-electron generation processes from valence orbitals. PMID:26082275

Information transmission and signal permutation in active flow networks

NASA Astrophysics Data System (ADS)

Woodhouse, Francis G.; Fawcett, Joanna B.; Dunkel, Jörn

2018-03-01

Recent experiments show that both natural and artificial microswimmers in narrow channel-like geometries will self-organise to form steady, directed flows. This suggests that networks of flowing active matter could function as novel autonomous microfluidic devices. However, little is known about how information propagates through these far-from-equilibrium systems. Through a mathematical analogy with spin-ice vertex models, we investigate here the input–output characteristics of generic incompressible active flow networks (AFNs). Our analysis shows that information transport through an AFN is inherently different from conventional pressure or voltage driven networks. Active flows on hexagonal arrays preserve input information over longer distances than their passive counterparts and are highly sensitive to bulk topological defects, whose presence can be inferred from marginal input–output distributions alone. This sensitivity further allows controlled permutations on parallel inputs, revealing an unexpected link between active matter and group theory that can guide new microfluidic mixing strategies facilitated by active matter and aid the design of generic autonomous information transport networks.

Inferred cosmic-ray spectrum from Fermi large area telescope γ-ray observations of Earth's limb.

PubMed

Ackermann, M; Ajello, M; Albert, A; Allafort, A; Baldini, L; Barbiellini, G; Bastieri, D; Bechtol, K; Bellazzini, R; Blandford, R D; Bloom, E D; Bonamente, E; Bottacini, E; Bouvier, A; Brandt, T J; Brigida, M; Bruel, P; Buehler, R; Buson, S; Caliandro, G A; Cameron, R A; Caraveo, P A; Cecchi, C; Charles, E; Chaves, R C G; Chekhtman, A; Chiang, J; Chiaro, G; Ciprini, S; Claus, R; Cohen-Tanugi, J; Conrad, J; Cutini, S; Dalton, M; D'Ammando, F; de Angelis, A; de Palma, F; Dermer, C D; Digel, S W; Di Venere, L; do Couto e Silva, E; Drell, P S; Drlica-Wagner, A; Favuzzi, C; Fegan, S J; Ferrara, E C; Focke, W B; Franckowiak, A; Fukazawa, Y; Funk, S; Fusco, P; Gargano, F; Gasparrini, D; Germani, S; Giglietto, N; Giordano, F; Giroletti, M; Glanzman, T; Godfrey, G; Gomez-Vargas, G A; Grenier, I A; Grove, J E; Guiriec, S; Gustafsson, M; Hadasch, D; Hanabata, Y; Harding, A K; Hayashida, M; Hayashi, K; Hewitt, J W; Horan, D; Hou, X; Hughes, R E; Inoue, Y; Jackson, M S; Jogler, T; Jóhannesson, G; Johnson, A S; Kamae, T; Kawano, T; Knödlseder, J; Kuss, M; Lande, J; Larsson, S; Latronico, L; Longo, F; Loparco, F; Lovellette, M N; Lubrano, P; Mayer, M; Mazziotta, M N; McEnery, J E; Mehault, J; Michelson, P F; Mitthumsiri, W; Mizuno, T; Moiseev, A A; Monte, C; Monzani, M E; Morselli, A; Moskalenko, I V; Murgia, S; Nemmen, R; Nuss, E; Ohsugi, T; Okumura, A; Orienti, M; Orlando, E; Ormes, J F; Paneque, D; Panetta, J H; Perkins, J S; Pesce-Rollins, M; Piron, F; Pivato, G; Porter, T A; Rainò, S; Rando, R; Razzano, M; Razzaque, S; Reimer, A; Reimer, O; Ritz, S; Roth, M; Schaal, M; Schulz, A; Sgrò, C; Siskind, E J; Spandre, G; Spinelli, P; Strong, A W; Takahashi, H; Takeuchi, Y; Thayer, J G; Thayer, J B; Thompson, D J; Tibaldo, L; Tinivella, M; Torres, D F; Tosti, G; Troja, E; Tronconi, V; Usher, T L; Vandenbroucke, J; Vasileiou, V; Vianello, G; Vitale, V; Werner, M; Winer, B L; Wood, K S; Wood, M; Yang, Z

2014-04-18

Recent accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. We use the Fermi Large Area Telescope observations of the γ-ray emission from Earth's limb for an indirect measurement of the local spectrum of CR protons in the energy range ∼90  GeV-6  TeV (derived from a photon energy range 15 GeV-1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68±0.04 and 2.61±0.08 above ∼200  GeV, respectively.

Structural and Functional Analyses of a Glycoside Hydrolase Family 5 Enzyme with an Unexpected [beta]-Fucosidase Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshida, Shosuke; Park, David S.; Bae, Brian

2012-02-15

We present characterization of PbFucA, a family 5 glycoside hydrolase (GH5) from Prevotella bryantii B{sub 1}4. While GH5 members typically are xylanases, PbFucA shows no activity toward xylan polysaccharides. A screen against a panel of p-nitrophenol coupled sugars identifies PbFucA as a {beta}-D-fucosidase. We also present the 2.2 {angstrom} resolution structure of PbFucA and use structure-based mutational analysis to confirm the role of catalytically essential residues. A comparison of the active sites of PbFucA with those of family 5 and 51 glycosidases reveals that while the essential catalytic framework is identical between these enzymes, the steric contours of the respectivemore » active site clefts are distinct and likely account for substrate discrimination. Our results show that members of this cluster of orthologous group (COG) 5520 have {beta}-D-fucosidase activities, despite showing an overall sequence and structural similarity to GH-5 xylanases.« less

Real-time imaging of Huntingtin aggregates diverting target search and gene transcription

PubMed Central

Li, Li; Liu, Hui; Dong, Peng; Li, Dong; Legant, Wesley R; Grimm, Jonathan B; Lavis, Luke D; Betzig, Eric; Tjian, Robert; Liu, Zhe

2016-01-01

The presumptive altered dynamics of transient molecular interactions in vivo contributing to neurodegenerative diseases have remained elusive. Here, using single-molecule localization microscopy, we show that disease-inducing Huntingtin (mHtt) protein fragments display three distinct dynamic states in living cells – 1) fast diffusion, 2) dynamic clustering and 3) stable aggregation. Large, stable aggregates of mHtt exclude chromatin and form 'sticky' decoy traps that impede target search processes of key regulators involved in neurological disorders. Functional domain mapping based on super-resolution imaging reveals an unexpected role of aromatic amino acids in promoting protein-mHtt aggregate interactions. Genome-wide expression analysis and numerical simulation experiments suggest mHtt aggregates reduce transcription factor target site sampling frequency and impair critical gene expression programs in striatal neurons. Together, our results provide insights into how mHtt dynamically forms aggregates and disrupts the finely-balanced gene control mechanisms in neuronal cells. DOI: http://dx.doi.org/10.7554/eLife.17056.001 PMID:27484239

A novel chimeric prophage vB_LdeS-phiJB from commercial Lactobacillus delbrueckii subsp. bulgaricus.

PubMed

Guo, Tingting; Zhang, Chenchen; Xin, Yongping; Xin, Min; Kong, Jian

2016-05-01

Prophage vB_LdeS-phiJB (phiJB) was induced by mitomycin C and UV radiation from the Lactobacillus delbrueckii subsp. bulgaricus SDMCC050201 isolated from a Chinese yoghurt sample. It has an isometric head and a non-contractile tail with 36,969 bp linear double-stranded DNA genome, which is classified into the group a of Lb. delbrueckii phages. The genome of phiJB is highly modular with functionally related genes clustered together. Unexpectedly, there is no similarity of its DNA replication module to any phages that have been reported, while it consists of open-reading frames homologous to the proteins of Lactobacillus strains. Comparative genomic analysis indicated that its late gene clusters, integration/lysogeny modules and DNA replication module derived from different evolutionary ancestors and integrated into a chimera. Our results revealed a novel chimeric phage of commercial Lb. delbrueckii and will broaden the knowledge of phage diversity in the dairy industry.

Distinct human antibody response to the biological warfare agent Burkholderia mallei

PubMed Central

Varga, John J.; Vigil, Adam; DeShazer, David; Waag, David M.; Felgner, Philip; Goldberg, Joanna B.

2012-01-01

The genetic similarity between Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis) had led to the general assumption that pathogenesis of each bacterium would be similar. In 2000, the first human case of glanders in North America since 1945 was reported in a microbiology laboratory worker. Leveraging the availability of pre-exposure sera for this individual and employing the same well-characterized protein array platform that has been previously used to study a large cohort of melioidosis patients in southeast Asia, we describe the antibody response in a human with glanders. Analysis of 156 peptides present on the array revealed antibodies against 17 peptides with a > 2-fold increase in this infection. Unexpectedly, when the glanders data were compared with a previous data set from B. pseudomallei infections, there were only two highly increased antibodies shared between these two infections. These findings have implications in the diagnosis and treatment of B. mallei and B. pseudomallei infections. PMID:23076276

Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response

PubMed Central

Gish, Stacey R.; Maier, Ezekiel J.; Haynes, Brian C.; Santiago-Tirado, Felipe H.; Srikanta, Deepa L.; Ma, Cynthia Z.; Li, Lucy X.; Williams, Matthew; Crouch, Erika C.; Khader, Shabaana A.

2016-01-01

ABSTRACT Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth: GAT201, RIM101, and SP1. Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes. PMID:27094327

Inferred Cosmic-Ray Spectrum from Fermi-LAT Gamma-Ray Observations of the Earths Limb

NASA Technical Reports Server (NTRS)

Ackermann, M.; Ajello, M.; Albert, A.; Allafort, A.; Baldini, L.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Blandford, R. D.;

Surface determination through atomically resolved secondary-electron imaging

DOE PAGES

Ciston, J.; Brown, H. G.; D’Alfonso, A. J.; ...

2015-06-17

We report that unique determination of the atomic structure of technologically relevant surfaces is often limited by both a need for homogeneous crystals and ambiguity of registration between the surface and bulk. Atomically resolved secondary-electron imaging is extremely sensitive to this registration and is compatible with faceted nanomaterials, but has not been previously utilized for surface structure determination. Here we show a detailed experimental atomic-resolution secondary-electron microscopy analysis of the c(6 x 2) reconstruction on strontium titanate (001) coupled with careful simulation of secondary-electron images, density functional theory calculations and surface monolayer-sensitive aberration-corrected plan-view high-resolution transmission electron microscopy. Our workmore » reveals several unexpected findings, including an amended registry of the surface on the bulk and strontium atoms with unusual seven-fold coordination within a typically high surface coverage of square pyramidal TiO 5 units. Lastly, dielectric screening is found to play a critical role in attenuating secondary-electron generation processes from valence orbitals.« less

Impact of asymmetric martensite and austenite nucleation and growth behavior on the phase stability and hysteresis of freestanding shape-memory nanoparticles

NASA Astrophysics Data System (ADS)

Ko, Won-Seok; Grabowski, Blazej; Neugebauer, Jörg

2018-03-01

Martensitic transformations in nanoscaled shape-memory alloys exhibit characteristic features absent for the bulk counterparts. Detailed understanding is required for applications in micro- and nanoelectromechanical systems, and experimental limitations render atomistic simulation an important complementary approach. Using a recently developed, accurate potential we investigate the phase transformation in freestanding Ni-Ti shape-memory nanoparticles with molecular-dynamics simulations. The results confirm that the decrease in the transformation temperature with decreasing particle size is correlated with an overstabilization of the austenitic surface energy over the martensitic surface energy. However, a detailed atomistic analysis of the nucleation and growth behavior reveals an unexpected difference in the mechanisms determining the austenite finish and martensite start temperature. While the austenite finish temperature is directly affected by a contribution of the surface energy difference, the martensite start temperature is mostly affected by the transformation strain, contrary to general expectations. This insight not only explains the reduced transformation temperature but also the reduced thermal hysteresis in freestanding nanoparticles.

Distinct molecular cues ensure a robust microtubule-dependent nuclear positioning in the Drosophila oocyte

PubMed Central

Tissot, Nicolas; Lepesant, Jean-Antoine; Bernard, Fred; Legent, Kevin; Bosveld, Floris; Martin, Charlotte; Faklaris, Orestis; Bellaïche, Yohanns; Coppey, Maïté; Guichet, Antoine

2017-01-01

Controlling nucleus localization is crucial for a variety of cellular functions. In the Drosophila oocyte, nuclear asymmetric positioning is essential for the reorganization of the microtubule (MT) network that controls the polarized transport of axis determinants. A combination of quantitative three-dimensional live imaging and laser ablation-mediated force analysis reveal that nuclear positioning is ensured with an unexpected level of robustness. We show that the nucleus is pushed to the oocyte antero-dorsal cortex by MTs and that its migration can proceed through distinct tracks. Centrosome-associated MTs favour one migratory route. In addition, the MT-associated protein Mud/NuMA that is asymmetrically localized in an Asp-dependent manner at the nuclear envelope hemisphere where MT nucleation is higher promotes a separate route. Our results demonstrate that centrosomes do not provide an obligatory driving force for nuclear movement, but together with Mud, contribute to the mechanisms that ensure the robustness of asymmetric nuclear positioning. PMID:28447612

Evolution of graphene islands growing on Cu foils

NASA Astrophysics Data System (ADS)

Wofford, Joseph; Nie, Shu; Bartelt, Norman; McCarty, Kevin; Dubon, Oscar

2011-03-01

Using low-energy electron microscopy we investigate, in real time, the growth of graphene monolayers on Cu foils. Graphene islands evolve from an initially compact form into an increasingly ramified, four-lobed shape, reflecting the symmetry of the (100)-textured Cu surface. Diffraction analysis reveals that each lobe is an individual graphene domain, differentiated by a rotation about the film normal, making the islands polycrystalline. An inspection of the morphological evolution of the graphene lobes shows the growth fronts posses an angularly dependent velocity, which is consistent with a growth mode dominated by edge kinetics. The fast growth direction of each lobe tends to align with the 001 in-plane directions of the Cu surface but not with a high symmetry direction of the graphene lattice. Finally, the implications of this unexpected growth mechanism on the formation of high-quality graphene films on Cu foils are evaluated. Supported by BES/USDOE under contracts #DE-AC04-94AL85000 and #DE-AC02-05CH11231.

Mapping and analysis of Caenorhabditis elegans transcription factor sequence specificities

PubMed Central

Narasimhan, Kamesh; Lambert, Samuel A; Yang, Ally WH; Riddell, Jeremy; Mnaimneh, Sanie; Zheng, Hong; Albu, Mihai; Najafabadi, Hamed S; Reece-Hoyes, John S; Fuxman Bass, Juan I; Walhout, Albertha JM; Weirauch, Matthew T; Hughes, Timothy R

2015-01-01

Caenorhabditis elegans is a powerful model for studying gene regulation, as it has a compact genome and a wealth of genomic tools. However, identification of regulatory elements has been limited, as DNA-binding motifs are known for only 71 of the estimated 763 sequence-specific transcription factors (TFs). To address this problem, we performed protein binding microarray experiments on representatives of canonical TF families in C. elegans, obtaining motifs for 129 TFs. Additionally, we predict motifs for many TFs that have DNA-binding domains similar to those already characterized, increasing coverage of binding specificities to 292 C. elegans TFs (∼40%). These data highlight the diversification of binding motifs for the nuclear hormone receptor and C2H2 zinc finger families and reveal unexpected diversity of motifs for T-box and DM families. Motif enrichment in promoters of functionally related genes is consistent with known biology and also identifies putative regulatory roles for unstudied TFs. DOI: http://dx.doi.org/10.7554/eLife.06967.001 PMID:25905672

Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen

PubMed Central

Chang, Y. Paul; Xu, Meng; Machado, Ana Carolina Dantas; Yu, Xian Jessica; Rohs, Remo; Chen, Xiaojiang S.

2013-01-01

SUMMARY The DNA tumor virus Simian virus 40 (SV40) is a model system for studying eukaryotic replication. SV40 large tumor antigen (LTag) is the initiator/helicase that is essential for genome replication. LTag recognizes and assembles at the viral replication origin. We determined the structure of two multidomain LTag subunits bound to origin DNA. The structure reveals that the origin binding domains (OBDs) and Zn and AAA+ domains are involved in origin recognition and assembly. Notably, the OBDs recognize the origin in an unexpected manner. The histidine residues of the AAA+ domains insert into a narrow minor groove region with enhanced negative electrostatic potential. Computational analysis indicates that this region is intrinsically narrow, demonstrating the role of DNA shape readout in origin recognition. Our results provide important insights into the assembly of the LTag initiator/ helicase at the replication origin and suggest that histidine contacts with the minor groove serve as a mechanism of DNA shape readout. PMID:23545501

Live-cell analysis of endogenous GFP-RPB1 uncovers rapid turnover of initiating and promoter-paused RNA Polymerase II.

PubMed

Steurer, Barbara; Janssens, Roel C; Geverts, Bart; Geijer, Marit E; Wienholz, Franziska; Theil, Arjan F; Chang, Jiang; Dealy, Shannon; Pothof, Joris; van Cappellen, Wiggert A; Houtsmuller, Adriaan B; Marteijn, Jurgen A

2018-05-08

Initiation and promoter-proximal pausing are key regulatory steps of RNA Polymerase II (Pol II) transcription. To study the in vivo dynamics of endogenous Pol II during these steps, we generated fully functional GFP-RPB1 knockin cells. GFP-RPB1 photobleaching combined with computational modeling revealed four kinetically distinct Pol II fractions and showed that on average 7% of Pol II are freely diffusing, while 10% are chromatin-bound for 2.4 seconds during initiation, and 23% are promoter-paused for only 42 seconds. This unexpectedly high turnover of Pol II at promoters is most likely caused by premature termination of initiating and promoter-paused Pol II and is in sharp contrast to the 23 minutes that elongating Pol II resides on chromatin. Our live-cell-imaging approach provides insights into Pol II dynamics and suggests that the continuous release and reinitiation of promoter-bound Pol II is an important component of transcriptional regulation. Copyright © 2018 the Author(s). Published by PNAS.

Bad apples, bad cases, and bad barrels: meta-analytic evidence about sources of unethical decisions at work.

PubMed

Kish-Gephart, Jennifer J; Harrison, David A; Treviño, Linda Klebe

2010-01-01

As corporate scandals proliferate, practitioners and researchers alike need a cumulative, quantitative understanding of the antecedents associated with unethical decisions in organizations. In this meta-analysis, the authors draw from over 30 years of research and multiple literatures to examine individual ("bad apple"), moral issue ("bad case"), and organizational environment ("bad barrel") antecedents of unethical choice. Findings provide empirical support for several foundational theories and paint a clearer picture of relationships characterized by mixed results. Structural equation modeling revealed the complexity (multidetermined nature) of unethical choice, as well as a need for research that simultaneously examines different sets of antecedents. Moderator analyses unexpectedly uncovered better prediction of unethical behavior than of intention for several variables. This suggests a need to more strongly consider a new "ethical impulse" perspective in addition to the traditional "ethical calculus" perspective. Results serve as a data-based foundation and guide for future theoretical and empirical development in the domain of behavioral ethics. Copyright 2009 APA, all rights reserved.

Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

PubMed Central

Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.; Brierley, Stuart M.; Basbaum, Allan I.; Bosmans, Frank; King, Glenn F.; Julius, David

2016-01-01

Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nociception and pain has not been explored. We exploit these probes to demonstrate that Nav1.1-expressing fibers are modality-specific nociceptors: their activation elicits robust pain behaviors without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibers also express Nav1.1 and show enhanced toxin sensitivity in a model of irritable bowel syndrome. Altogether, these findings establish an unexpected role for Nav1.1 in regulating the excitability of sensory nerve fibers that underlie mechanical pain. PMID:27281198

His and Hers: Economic Factors and Relationship Quality in Germany

PubMed Central

Hardie, Jessica Halliday; Geist, Claudia; Lucas, Amy

2014-01-01

Research has linked economic factors to relationship quality in the United States, primarily using cross-sectional data. In the current study, 2 waves of the Panel Analysis of Intimate Relationships and Family Dynamics data (n = 2,937) were used to test the gendered association between economic factors and relationship satisfaction among young German couples. In contrast to U.S.-based studies, the findings showed striking gender differences in the association between economic factors and relationship satisfaction for Germans. In cross-sectional models, women’s relationship satisfaction was positively associated with receiving government economic support, and men’s satisfaction was positively associated with poverty status and negatively associated with being a breadwinner. Longitudinal models revealed that changes in poverty status are associated with women’s satisfaction, but men’s satisfaction remains tied to their role as family provider. These unexpected results suggest that men’s satisfaction is positively associated with a more equal division of labor market activity between partners. PMID:25045175

Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts

PubMed Central

Ma, Liang; Chen, Zehua; Huang, Da Wei; Kutty, Geetha; Ishihara, Mayumi; Wang, Honghui; Abouelleil, Amr; Bishop, Lisa; Davey, Emma; Deng, Rebecca; Deng, Xilong; Fan, Lin; Fantoni, Giovanna; Fitzgerald, Michael; Gogineni, Emile; Goldberg, Jonathan M.; Handley, Grace; Hu, Xiaojun; Huber, Charles; Jiao, Xiaoli; Jones, Kristine; Levin, Joshua Z.; Liu, Yueqin; Macdonald, Pendexter; Melnikov, Alexandre; Raley, Castle; Sassi, Monica; Sherman, Brad T.; Song, Xiaohong; Sykes, Sean; Tran, Bao; Walsh, Laura; Xia, Yun; Yang, Jun; Young, Sarah; Zeng, Qiandong; Zheng, Xin; Stephens, Robert; Nusbaum, Chad; Birren, Bruce W.; Azadi, Parastoo; Lempicki, Richard A.; Cuomo, Christina A.; Kovacs, Joseph A.

2016-01-01

Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses. PMID:26899007

An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase

NASA Astrophysics Data System (ADS)

Csizmok, Veronika; Orlicky, Stephen; Cheng, Jing; Song, Jianhui; Bah, Alaji; Delgoshaie, Neda; Lin, Hong; Mittag, Tanja; Sicheri, Frank; Chan, Hue Sun; Tyers, Mike; Forman-Kay, Julie D.

2017-01-01

The ubiquitin ligase SCFCdc4 mediates phosphorylation-dependent elimination of numerous substrates by binding one or more Cdc4 phosphodegrons (CPDs). Methyl-based NMR analysis of the Cdc4 WD40 domain demonstrates that Cyclin E, Sic1 and Ash1 degrons have variable effects on the primary Cdc4WD40 binding pocket. Unexpectedly, a Sic1-derived multi-CPD substrate (pSic1) perturbs methyls around a previously documented allosteric binding site for the chemical inhibitor SCF-I2. NMR cross-saturation experiments confirm direct contact between pSic1 and the allosteric pocket. Phosphopeptide affinity measurements reveal negative allosteric communication between the primary CPD and allosteric pockets. Mathematical modelling indicates that the allosteric pocket may enhance ultrasensitivity by tethering pSic1 to Cdc4. These results suggest negative allosteric interaction between two distinct binding pockets on the Cdc4WD40 domain may facilitate dynamic exchange of multiple CPD sites to confer ultrasensitive dependence on substrate phosphorylation.

Structure of human Cdc45 and implications for CMG helicase function

PubMed Central

Simon, Aline C.; Sannino, Vincenzo; Costanzo, Vincenzo; Pellegrini, Luca

2016-01-01

Cell division cycle protein 45 (Cdc45) is required for DNA synthesis during genome duplication, as a component of the Cdc45-MCM-GINS (CMG) helicase. Despite its essential biological function, its biochemical role in DNA replication has remained elusive. Here we report the 2.1-Å crystal structure of human Cdc45, which confirms its evolutionary link with the bacterial RecJ nuclease and reveals several unexpected features that underpin its function in eukaryotic DNA replication. These include a long-range interaction between N- and C-terminal DHH domains, blocking access to the DNA-binding groove of its RecJ-like fold, and a helical insertion in its N-terminal DHH domain, which appears poised for replisome interactions. In combination with available electron microscopy data, we validate by mutational analysis the mechanism of Cdc45 association with the MCM ring and GINS co-activator, critical for CMG assembly. These findings provide an indispensable molecular basis to rationalize the essential role of Cdc45 in genomic duplication. PMID:27189187

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

PubMed Central

Rajendran, Jayasimman; Tomašić, Nikica; Kotarsky, Heike; Hansson, Eva; Velagapudi, Vidya; Kallijärvi, Jukka; Fellman, Vineta

2016-01-01

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. PMID:27809283

Releasing Ski-Smad4 mediated suppression is essential to license Th17 differentiation

PubMed Central

Zhang, Song; Takaku, Motoki; Zou, Liyun; Gu, Ai-di; Chou, Wei-chun; Zhang, Ge; Wu, Bing; Kong, Qing; Thomas, Seddon Y.; Serody, Jonathan S.; Chen, Xian; Xu, Xiaojiang; Wade, Paul A.; Cook, Donald N.; Ting, Jenny P.; Wan, Yisong Y.

2017-01-01

Th17 cells are critically involved in host defense, inflammation, and autoimmunity1–5. TGF-β is instrumental in Th17 differentiation by cooperating with IL-66,7. Yet, the mechanism of how TGF-β enables Th17 differentiation remains elusive. Here we reveal that TGF-β licenses Th17 differentiation by releasing Ski-Smad4-complex suppressed RORγt expression. We found serendipitously that, unlike wild-type T cells, Smad4-deficient T cells differentiated into Th17 cells in the absence of TGF-β signaling in a RORγt-dependent manner. Ectopic Smad4 expression suppressed the RORγt expression and Th17 differentiation of Smad4-deficient T cells. Unexpectedly however, TGF-β neutralized Smad4 mediated suppression without affecting Smad4 binding to Rorc locus. Proteomic analysis revealed that Smad4 interacted with Ski, a transcriptional repressor degraded upon TGF-β stimulation. Ski controlled the histone acetylation/de-acetylation of Rorc locus and Th17 differentiation via Smad4 because ectopic Ski expression inhibited H3K9Ac of Rorc locus, Rorc expression and Th17 differentiation in a Smad4-dependent manner. Therefore, TGF-β-induced disruption of Ski releases Ski-Smad4 complex imposed suppression of RORγt to license Th17 differentiation. This study reveals a critical mechanism by which TGF-β controls Th17 differentiation and uncovers Ski-Smad4 axis as a potential therapeutic target for treating Th17 related diseases. PMID:29072299

Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Jia; Yang, Yuting; Wan, Ke

Budding yeast Cdc13-Stn1-Ten1 (CST) complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A (RPA)-like complex. Previous genetic and structural studies revealed a close resemblance between Stn1-Ten1 and RPA32-RPA14. However, the relationship between Cdc13 and RPA70, the largest subunit of RPA, has remained unclear. Here, we report the crystal structure of the N-terminal OB (oligonucleotide/oligosaccharide binding) fold of Cdc13. Although Cdc13 has an RPA70-like domain organization, the structures of Cdc13 OB folds are significantly different from their counterparts in RPA70, suggesting that they have distinct evolutionary origins. Furthermore, ourmore » structural and biochemical analyses revealed unexpected dimerization by the N-terminal OB fold and showed that homodimerization is probably a conserved feature of all Cdc13 proteins. We also uncovered the structural basis of the interaction between the Cdc13 N-terminal OB fold and the catalytic subunit of DNA polymerase {alpha} (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Pol1 interaction revealed multiple mechanisms by which dimerization regulates telomere lengths in vivo. Collectively, our findings provide novel insights into the mechanisms and evolution of Cdc13.« less

Unexpectedly low nitrogen acquisition and absence of root architecture adaptation to nitrate supply in a Medicago truncatula highly branched root mutant

PubMed Central

Bourion, Virginie

2014-01-01

To complement N2 fixation through symbiosis, legumes can efficiently acquire soil mineral N through adapted root architecture. However, root architecture adaptation to mineral N availability has been little studied in legumes. Therefore, this study investigated the effect of nitrate availability on root architecture in Medicago truncatula and assessed the N-uptake potential of a new highly branched root mutant, TR185. The effects of varying nitrate supply on both root architecture and N uptake were characterized in the mutant and in the wild type. Surprisingly, the root architecture of the mutant was not modified by variation in nitrate supply. Moreover, despite its highly branched root architecture, TR185 had a permanently N-starved phenotype. A transcriptome analysis was performed to identify genes differentially expressed between the two genotypes. This analysis revealed differential responses related to the nitrate acquisition pathway and confirmed that N starvation occurred in TR185. Changes in amino acid content and expression of genes involved in the phenylpropanoid pathway were associated with differences in root architecture between the mutant and the wild type. PMID:24706718

IUE observations of two late-type stars Bx Mon (M + pec) and TV Gem (M1 Iab)

NASA Technical Reports Server (NTRS)

Michalitsianos, A. G.; Hobbs, R. W.; Kafatos, M.

1981-01-01

The IUE observations of two late type stars BX Mon and TV Gem that reveal the emission properties in the ultraviolet of subluminous companions are discussed. Analysis of the continuum emission observed from BX Mon suggests the companion, is a middle A III star. High excitation emission lines observed between 1200 A and 2000 A that generally do not typify emission observed in either late M type variables or A type stars are also detected. It is suggested that these strong high excitation lines arise in a large volume of gas heated by nonradiation processes that could be the result of tidal interaction and mass exchange in the binary system. In contrast to stars such as BX Mon, the luminous M1 supergiant TV Gem shows unexpected intense UV continuum throughout the sensitivity range of IUE. The UV spectrum of TV Gem is characterized by intense continuum with broad absorption features detected in the short wavelength range. The analysis shows that the companion could be a B9 or A1 III-IV star. Alternate suggestions are presented for explaining the UV continuum in terms of an accretion disk in association with TV Gem.

The Drosophila Pericentrin-like-protein (PLP) cooperates with Cnn to maintain the integrity of the outer PCM

PubMed Central

Richens, Jennifer H.; Barros, Teresa P.; Lucas, Eliana P.; Peel, Nina; Pinto, David Miguel Susano; Wainman, Alan; Raff, Jordan W.

2015-01-01

ABSTRACT Centrosomes comprise a pair of centrioles surrounded by a matrix of pericentriolar material (PCM). In vertebrate cells, Pericentrin plays an important part in mitotic PCM assembly, but the Drosophila Pericentrin-like protein (PLP) appears to have a more minor role in mitotic fly cells. Here we investigate the function of PLP during the rapid mitotic cycles of the early Drosophila embryo. Unexpectedly, we find that PLP is specifically enriched in the outer-most regions of the PCM, where it largely co-localizes with the PCM scaffold protein Cnn. In the absence of PLP the outer PCM appears to be structurally weakened, and it rapidly disperses along the centrosomal microtubules (MTs). As a result, centrosomal MTs are subtly disorganized in embryos lacking PLP, although mitosis is largely unperturbed and these embryos develop and hatch at near-normal rates. Y2H analysis reveals that PLP can potentially form multiple interactions with itself and with the PCM recruiting proteins Asl, Spd-2 and Cnn. A deletion analysis suggests that PLP participates in a complex network of interactions that ultimately help to strengthen the PCM. PMID:26157019

The Drosophila Pericentrin-like-protein (PLP) cooperates with Cnn to maintain the integrity of the outer PCM.

PubMed

Richens, Jennifer H; Barros, Teresa P; Lucas, Eliana P; Peel, Nina; Pinto, David Miguel Susano; Wainman, Alan; Raff, Jordan W

2015-07-08

Centrosomes comprise a pair of centrioles surrounded by a matrix of pericentriolar material (PCM). In vertebrate cells, Pericentrin plays an important part in mitotic PCM assembly, but the Drosophila Pericentrin-like protein (PLP) appears to have a more minor role in mitotic fly cells. Here we investigate the function of PLP during the rapid mitotic cycles of the early Drosophila embryo. Unexpectedly, we find that PLP is specifically enriched in the outer-most regions of the PCM, where it largely co-localizes with the PCM scaffold protein Cnn. In the absence of PLP the outer PCM appears to be structurally weakened, and it rapidly disperses along the centrosomal microtubules (MTs). As a result, centrosomal MTs are subtly disorganized in embryos lacking PLP, although mitosis is largely unperturbed and these embryos develop and hatch at near-normal rates. Y2H analysis reveals that PLP can potentially form multiple interactions with itself and with the PCM recruiting proteins Asl, Spd-2 and Cnn. A deletion analysis suggests that PLP participates in a complex network of interactions that ultimately help to strengthen the PCM. © 2015. Published by The Company of Biologists Ltd.

Production of Multiple Growth Factors by a Newly Established Human Thyroid Carcinoma Cell Line

PubMed Central

Yoshida, Yataro; Ohashi, Kensaku; Sano, Emiko; Kobayashi, Hisataka; Endo, Keigo; Naruto, Masanobu; Nakamura, Toru

1992-01-01

A multiple growth factor‐producing tumor cell line (NIM‐1) was newly established from a patient with thyroid cancer and remarkable neutrophilia. NIM‐1 cells also caused severe neutrophilia in nude mice bearing tumors. NIM‐1‐conditioned medium (NIM‐1CM) contained activities that supported not only granulocyte, macrophage and eosinophil colony formation of human bone marrow cells but also the growth of colony‐stimulating factor (CSF)‐dependent cell lines, NFS60‐KX and TF‐1. Northern blot hybridization analysis revealed the constitutive expression of granulocyte‐CSF (G‐CSF), granulocyte/macrophage‐CSF (GM‐CSF) and interleukin(IL)‐6 mRNAs in NIM‐1 cells. Enzyme‐linked immunosorbent assays (ELISA) using NIM‐1CM also confirmed the production of IL‐la and a small amount of IL‐1β besides G‐CSF, GM‐CSF and IL‐6 in NIM‐1 cells. In addition, unexpected production of IL‐11 in NIM‐1 cells was detected by northern blot hybridization analysis and by bioassay using an IL‐11‐dependent cell line. Therefore, NIM‐1 cell line is shown to produce multiple cytokines including potentially megakaryopoietic growth factors such as GM‐CSF, IL‐6 and IL‐11. PMID:1372885

Adult recurrent pilocytic astrocytoma: Clinical, histopathological and molecular study.

PubMed

Trabelsi, S; Mama, N; Ladib, M; Popov, S; Burford, A; Mokni, M; Tlili, K; Krifa, H; Varella-Garcia, M; Jones, C; Tahar Yacoubi, M; Saad, A; H'mida Ben Brahim, D

2015-12-01

PA is a grade I glial tumor that mostly occurs in children. However, although apparently similar to paediatric PA, adult PA presents a different clinical follow-up that could arise from specific molecular alterations. A variety of genetic alterations have been identified as diagnostic or prognostic glioma molecular markers. We describe a right infratentorial tumor that occurred in a 58-year-old man. Neuroimaging and neuropathological examination suggested PA as an initial diagnosis. The tumor was completely resected. Unexpectedly, two years later, a rapidly growing tumor on the operative site was observed with a second location in the pineal region. Immunohistochemical reactions (IHC), Multiplex ligation probe amplification (MLPA) and fluorescence in situ hybridization (FISH) was performed in both primary and relapse tumor. Neuroimaging and neuropathological examinations suggested an unusual diagnosis for adult patients: a recurrent PA. Both MLPA and FISH analysis contribute to diagnostic confirmation by KIAA1549: BRAF fusion detection. Additional genetic results revealed interesting findings that justified the tumor aggressivity. Molecular analysis of adult PA cases should be routinely combined with histopathological and neuroimaging examination to further refine prognostic diagnoses. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Functional redundancy of division specific penicillin-binding proteins in Bacillus subtilis.

PubMed

Sassine, Jad; Xu, Meizhu; Sidiq, Karzan R; Emmins, Robyn; Errington, Jeff; Daniel, Richard A

2017-10-01

Bacterial cell division involves the dynamic assembly of a diverse set of proteins that coordinate the invagination of the cell membrane and synthesis of cell wall material to create the new cell poles of the separated daughter cells. Penicillin-binding protein PBP 2B is a key cell division protein in Bacillus subtilis proposed to have a specific catalytic role in septal wall synthesis. Unexpectedly, we find that a catalytically inactive mutant of PBP 2B supports cell division, but in this background the normally dispensable PBP 3 becomes essential. Phenotypic analysis of pbpC mutants (encoding PBP 3) shows that PBP 2B has a crucial structural role in assembly of the division complex, independent of catalysis, and that its biochemical activity in septum formation can be provided by PBP 3. Bioinformatic analysis revealed a close sequence relationship between PBP 3 and Staphylococcus aureus PBP 2A, which is responsible for methicillin resistance. These findings suggest that mechanisms for rescuing cell division when the biochemical activity of PBP 2B is perturbed evolved prior to the clinical use of β-lactams. © 2017 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

Unexpectedly low nitrogen acquisition and absence of root architecture adaptation to nitrate supply in a Medicago truncatula highly branched root mutant.

PubMed

Bourion, Virginie; Martin, Chantal; de Larambergue, Henri; Jacquin, Françoise; Aubert, Grégoire; Martin-Magniette, Marie-Laure; Balzergue, Sandrine; Lescure, Geoffroy; Citerne, Sylvie; Lepetit, Marc; Munier-Jolain, Nathalie; Salon, Christophe; Duc, Gérard

2014-06-01

To complement N2 fixation through symbiosis, legumes can efficiently acquire soil mineral N through adapted root architecture. However, root architecture adaptation to mineral N availability has been little studied in legumes. Therefore, this study investigated the effect of nitrate availability on root architecture in Medicago truncatula and assessed the N-uptake potential of a new highly branched root mutant, TR185. The effects of varying nitrate supply on both root architecture and N uptake were characterized in the mutant and in the wild type. Surprisingly, the root architecture of the mutant was not modified by variation in nitrate supply. Moreover, despite its highly branched root architecture, TR185 had a permanently N-starved phenotype. A transcriptome analysis was performed to identify genes differentially expressed between the two genotypes. This analysis revealed differential responses related to the nitrate acquisition pathway and confirmed that N starvation occurred in TR185. Changes in amino acid content and expression of genes involved in the phenylpropanoid pathway were associated with differences in root architecture between the mutant and the wild type. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

ONC201 kills breast cancer cells in vitro by targeting mitochondria.

PubMed

Greer, Yoshimi Endo; Porat-Shliom, Natalie; Nagashima, Kunio; Stuelten, Christina; Crooks, Dan; Koparde, Vishal N; Gilbert, Samuel F; Islam, Celia; Ubaldini, Ashley; Ji, Yun; Gattinoni, Luca; Soheilian, Ferri; Wang, Xiantao; Hafner, Markus; Shetty, Jyoti; Tran, Bao; Jailwala, Parthav; Cam, Maggie; Lang, Martin; Voeller, Donna; Reinhold, William C; Rajapakse, Vinodh; Pommier, Yves; Weigert, Roberto; Linehan, W Marston; Lipkowitz, Stanley

2018-04-06

We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines. ONC201 attenuated cell viability in all cancer cell lines tested. Unexpectedly, ONC201 toxicity was not dependent on either TRAIL receptors nor caspases. Time-lapse live cell imaging revealed that ONC201 induces cell membrane ballooning followed by rupture, distinct from the morphology of cells undergoing apoptosis. Further investigation found that ONC201 induces phosphorylation of AMP-dependent kinase and ATP loss. Cytotoxicity and ATP depletion were significantly enhanced in the absence of glucose, suggesting that ONC201 targets mitochondrial respiration. Further analysis indicated that ONC201 indirectly inhibits mitochondrial respiration. Confocal and electron microscopic analysis demonstrated that ONC201 triggers mitochondrial structural damage and functional impairment. Moreover, ONC201 decreased mitochondrial DNA (mtDNA). RNAseq analysis revealed that ONC201 suppresses expression of multiple mtDNA-encoded genes and nuclear-encoded mitochondrial genes involved in oxidative phosphorylation and other mitochondrial functions. Importantly, fumarate hydratase deficient cancer cells and multiple cancer cell lines with reduced amounts of mtDNA were resistant to ONC201. These results indicate that cells not dependent on mitochondrial respiration are ONC201-resistant. Our data demonstrate that ONC201 kills cancer cells by disrupting mitochondrial function and further suggests that cancer cells that are dependent on glycolysis will be resistant to ONC201.

ONC201 kills breast cancer cells in vitro by targeting mitochondria

PubMed Central

Greer, Yoshimi Endo; Porat-Shliom, Natalie; Nagashima, Kunio; Stuelten, Christina; Crooks, Dan; Koparde, Vishal N.; Gilbert, Samuel F.; Islam, Celia; Ubaldini, Ashley; Ji, Yun; Gattinoni, Luca; Soheilian, Ferri; Wang, Xiantao; Hafner, Markus; Shetty, Jyoti; Tran, Bao; Jailwala, Parthav; Cam, Maggie; Lang, Martin; Voeller, Donna; Reinhold, William C.; Rajapakse, Vinodh; Pommier, Yves; Weigert, Roberto; Linehan, W. Marston; Lipkowitz, Stanley

2018-01-01

We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines. ONC201 attenuated cell viability in all cancer cell lines tested. Unexpectedly, ONC201 toxicity was not dependent on either TRAIL receptors nor caspases. Time-lapse live cell imaging revealed that ONC201 induces cell membrane ballooning followed by rupture, distinct from the morphology of cells undergoing apoptosis. Further investigation found that ONC201 induces phosphorylation of AMP-dependent kinase and ATP loss. Cytotoxicity and ATP depletion were significantly enhanced in the absence of glucose, suggesting that ONC201 targets mitochondrial respiration. Further analysis indicated that ONC201 indirectly inhibits mitochondrial respiration. Confocal and electron microscopic analysis demonstrated that ONC201 triggers mitochondrial structural damage and functional impairment. Moreover, ONC201 decreased mitochondrial DNA (mtDNA). RNAseq analysis revealed that ONC201 suppresses expression of multiple mtDNA-encoded genes and nuclear-encoded mitochondrial genes involved in oxidative phosphorylation and other mitochondrial functions. Importantly, fumarate hydratase deficient cancer cells and multiple cancer cell lines with reduced amounts of mtDNA were resistant to ONC201. These results indicate that cells not dependent on mitochondrial respiration are ONC201-resistant. Our data demonstrate that ONC201 kills cancer cells by disrupting mitochondrial function and further suggests that cancer cells that are dependent on glycolysis will be resistant to ONC201. PMID:29719618

Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

PubMed Central

2013-01-01

Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p < 0.0001). GO term enrichment analysis revealed these genes to be involved in immune and inflammatory response, cell death, and chemotaxis. In a network analysis, these genes were part of insulin signaling, chemokine and cytokine signaling and extracellular matrix pathways. Conclusion Beyond insulin signaling, we find chemokine and cytokine signaling as well as modifiers of extracellular matrix composition to be subject to major changes in the aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

PubMed

Schermer, Bernhard; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Braun, Fabian; Schultze, Joachim L; Roodbergen, Marianne; Hoeijmakers, Jan Hj; Schumacher, Björn; Nürnberg, Peter; Dollé, Martijn Et; Benzing, Thomas; Müller, Roman-Ulrich; Kurschat, Christine E

2013-08-16

Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/Δ) mice showed cluster formation between young WT and Ercc1(-/Δ) as well as old WT and Ercc1(-/Δ) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/Δ) mice (p < 0.0001). GO term enrichment analysis revealed these genes to be involved in immune and inflammatory response, cell death, and chemotaxis. In a network analysis, these genes were part of insulin signaling, chemokine and cytokine signaling and extracellular matrix pathways. Beyond insulin signaling, we find chemokine and cytokine signaling as well as modifiers of extracellular matrix composition to be subject to major changes in the aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1(-/Δ) mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies.

Analysis of Unplanned Intensive Care Unit Admissions in Postoperative Pediatric Patients.

PubMed

Landry, Elizabeth K; Gabriel, Rodney A; Beutler, Sascha; Dutton, Richard P; Urman, Richard D

2017-03-01

Currently, there are only a few retrospective, single-institution studies that have addressed the prevalence and risk factors associated with unplanned admissions to the pediatric intensive care unit (ICU) after surgery. Based on the limited amount of studies, it appears that airway and respiratory complications put a child at increased risk for unplanned ICU admission. A more extensive and diverse analysis of unplanned postoperative admissions to the ICU is needed to address risk factors that have yet to be revealed by the current literature. To establish a rate of unplanned postoperative ICU admissions in pediatric patients using a large, multi-institution data set and to further characterize the associated risk factors. Data from the National Anesthesia Clinical Outcomes Registry were analyzed. We recorded the overall risk of unplanned postoperative ICU admission in patients younger than 18 years and performed univariate and multivariate logistic regression analysis to identify the associated patient, surgical, and anesthetic-related characteristics. Of the 324 818 cases analyzed, 211 reported an unexpected ICU admission. There was an increased likelihood of unplanned postoperative ICU in infants (age <1 year) and children who were classified as American Society of Anesthesiologists physical status classification of III or IV. Likewise, longer case duration and cases requiring general anesthesia were also associated with unplanned ICU admissions. This study establishes a rate of unplanned ICU admission following surgery in the heterogeneous pediatric population. This is the first study to utilize such a large data set encompassing a wide range of practice environments to identify risk factors leading to unplanned postoperative ICU admissions. Our study revealed that patient, surgical, and anesthetic complexity each contributed to an increased number of unplanned ICU admissions in the pediatric population.

Assessing the viability of bacterial species in drinking water by combined cellular and molecular analyses.

PubMed

Kahlisch, Leila; Henne, Karsten; Gröbe, Lothar; Brettar, Ingrid; Höfle, Manfred G

2012-02-01

The question which bacterial species are present in water and if they are viable is essential for drinking water safety but also of general relevance in aquatic ecology. To approach this question we combined propidium iodide/SYTO9 staining ("live/dead staining" indicating membrane integrity), fluorescence-activated cell sorting (FACS) and community fingerprinting for the analysis of a set of tap water samples. Live/dead staining revealed that about half of the bacteria in the tap water had intact membranes. Molecular analysis using 16S rRNA and 16S rRNA gene-based single-strand conformation polymorphism (SSCP) fingerprints and sequencing of drinking water bacteria before and after FACS sorting revealed: (1) the DNA- and RNA-based overall community structure differed substantially, (2) the community retrieved from RNA and DNA reflected different bacterial species, classified as 53 phylotypes (with only two common phylotypes), (3) the percentage of phylotypes with intact membranes or damaged cells were comparable for RNA- and DNA-based analyses, and (4) the retrieved species were primarily of aquatic origin. The pronounced difference between phylotypes obtained from DNA extracts (dominated by Betaproteobacteria, Bacteroidetes, and Actinobacteria) and from RNA extracts (dominated by Alpha-, Beta-, Gammaproteobacteria, Bacteroidetes, and Cyanobacteria) demonstrate the relevance of concomitant RNA and DNA analyses for drinking water studies. Unexpected was that a comparable fraction (about 21%) of phylotypes with membrane-injured cells was observed for DNA- and RNA-based analyses, contradicting the current understanding that RNA-based analyses represent the actively growing fraction of the bacterial community. Overall, we think that this combined approach provides an interesting tool for a concomitant phylogenetic and viability analysis of bacterial species of drinking water.

Morphometrics of Daucus (Apiaceae): A counterpart to a phylogenomic study

USDA-ARS?s Scientific Manuscript database

Molecular phylogenetics of genome-scale data sets (phylogenomics) often produces phylogenetic trees with unprecedented resolution. A companion phylogenomics analysis of Daucus (carrots) using 94 conserved nuclear orthologs supported many of the traditional species but showed unexpected results that ...

A Discovery Experiment: Carbon Dioxide Soap Bubble Dynamics.

ERIC Educational Resources Information Center

Millikan, Roger C.

1978-01-01

The observation of soap bubbles in a beaker of carbon dioxide gas helps students to feel the pleasure that comes from understanding nature, from applying that understanding to real problems, and from making unexpected discoveries that yield to analysis. (Author/BB)

Application of uncertainty and sensitivity analysis to the air quality SHERPA modelling tool

NASA Astrophysics Data System (ADS)

Pisoni, E.; Albrecht, D.; Mara, T. A.; Rosati, R.; Tarantola, S.; Thunis, P.

2018-06-01

Air quality has significantly improved in Europe over the past few decades. Nonetheless we still find high concentrations in measurements mainly in specific regions or cities. This dimensional shift, from EU-wide to hot-spot exceedances, calls for a novel approach to regional air quality management (to complement EU-wide existing policies). The SHERPA (Screening for High Emission Reduction Potentials on Air quality) modelling tool was developed in this context. It provides an additional tool to be used in support to regional/local decision makers responsible for the design of air quality plans. It is therefore important to evaluate the quality of the SHERPA model, and its behavior in the face of various kinds of uncertainty. Uncertainty and sensitivity analysis techniques can be used for this purpose. They both reveal the links between assumptions and forecasts, help in-model simplification and may highlight unexpected relationships between inputs and outputs. Thus, a policy steered SHERPA module - predicting air quality improvement linked to emission reduction scenarios - was evaluated by means of (1) uncertainty analysis (UA) to quantify uncertainty in the model output, and (2) by sensitivity analysis (SA) to identify the most influential input sources of this uncertainty. The results of this study provide relevant information about the key variables driving the SHERPA output uncertainty, and advise policy-makers and modellers where to place their efforts for an improved decision-making process.

Sustained removal of uranium from contaminated groundwater following stimulation of dissimilatory metal reduction.

PubMed

N'Guessan, A Lucie; Vrionis, Helen A; Resch, Charles T; Long, Philip E; Lovley, Derek R

2008-04-15

Previous field studies on in situ bioremediation of uranium-contaminated groundwater in an aquifer in Rifle, Colorado identified two distinct phases following the addition of acetate to stimulate microbial respiration. In phase I, Geobacter species are the predominant organisms, Fe(III) is reduced, and microbial reduction of soluble U(VI) to insoluble U(IV) removes uranium from the groundwater. In phase II, Fe(III) is depleted, sulfate is reduced, and sulfate-reducing bacteria predominate. Long-term monitoring revealed an unexpected third phase during which U(VI) removal continues even after acetate additions are stopped. All three of these phases were successfully reproduced in flow-through sediment columns. When sediments from the third phase were heat sterilized, the capacity for U(VI) removal was lost. In the live sediments U(VI) removed from the groundwater was recovered as U(VI) in the sediments. This contrasts to the recovery of U(IV) in sediments resulting from the reduction of U(VI) to U(IV) during the Fe(III) reduction phase in acetate-amended sediments. Analysis of 16S rRNA gene sequences in the sediments in which U(VI) was being adsorbed indicated that members of the Firmicutes were the predominant organisms whereas no Firmicutes sequences were detected in background sediments which did not have the capacity to sorb U(VI), suggesting that the U(VI) adsorption might be due to the presence of these living organisms or at least their intact cell components. This unexpected enhanced adsorption of U(VI) onto sediments following the stimulation of microbial growth in the subsurface may potentially enhance the cost effectiveness of in situ uranium bioremediation.

Strain-resolved Metatranscriptomic Analysis Reveals Unexpectedly Diverse Heterotrophic and Lithoautotrophic Microbial Metabolism in Naturally Reduced Aquifer Sediments

NASA Astrophysics Data System (ADS)

Beller, H. R.; Jewell, T. N. M.; Karaoz, U.; Bill, M.; Chakraborty, R.; Brodie, E.; Williams, K. H.

2016-12-01

In this study, we sought to better understand how natural organic matter fuels microbial communities in the anoxic subsurface at the Rifle (CO) site. We conducted a 20-day microcosm experiment with naturally reduced zone (NRZ) sediments and collected samples every 5 days for omics (metagenome and metatranscriptome) and geochemical measurements. No electron donors were added other than the NRZ sediment, which is enriched in buried woody plant material. The microcosms were constructed and incubated under anaerobic conditions in serum bottles with a N2 headspace. Biogeochemical measurements indicated that the decomposition of native organic matter occurred in different phases, including mineralization of dissolved organic carbon (DOC) to CO2 during the first week of incubation, followed by a pulse of acetogenesis that dominated carbon flux after 2 weeks. The depletion of DOC over time was strongly correlated with increases in expression of many genes associated with heterotrophy (e.g., amino acid, fatty acid, and carbohydrate metabolism) belonging to a Hydrogenophaga strain that accounted for a relatively large percentage ( 8%) of the metatranscriptome. This Hydrogenophaga strain also expressed genes indicative of chemolithoautotrophy, including CO2 fixation (RubisCO), H2 oxidation, S-compound oxidation, and denitrification. The pulse of acetogenesis appears to have been collectively catalyzed by a number of different organisms and metabolisms, most prominently pyruvate:ferredoxin oxidoreductase. Unexpected genes were identified among the most highly expressed (>98th percentile) transcripts, including acetone carboxylase and cell wall-associated hydrolases, some of which are known to act on peptidoglycan. Many of the most highly expressed hydrolases belonged to a Ca. Bathyarchaeota strain and may have been associated with scavenging of bacterial biomass. Overall, observed metabolism ranged far beyond the expected fermentation of plant-derived organic matter.

Effects of the economic crisis on smoking prevalence and number of smokers in the USA.

PubMed

Gallus, Silvano; Ghislandi, Simone; Muttarak, Raya

2015-01-01

Scanty and controversial information is available on the impact of macroeconomic fluctuations on smoking behaviour. No study has quantified the effects of fiscal crises on smoking prevalence. This study aimed to investigate the effects of the 2007-2008 economic crisis on smoking prevalence and number of smokers in the USA. Using data from the repeated Behavioural Risk Factor Surveillance System (BRFSS) surveys in pre-crisis (2005-2007) and post-crisis (2009-2010) periods on a total of 1,981,607 US adults, we separated the expected (after allowance for the demographic growth of the US population, secular smoking prevalence trends and changes in sociodemographic characteristics) from the unexpected (assumed attributable to the economic crisis) changes in the number of smokers across different employment statuses. Joinpoint regression analysis revealed no significant changes in smoking prevalence trends over the period 2005-2010. The crisis resulted in an increase in the number of smokers in the US by 0.6 million. This is largely due to an unexpected decrease of 1.7 million smokers among employed and an increase of 2.4 million smokers among unemployed individuals, whose smoking prevalence also remains extremely high in the post-crisis period (32.6%). The 2008 financial crisis had a weak effect on smoking prevalence. The pro-cyclical relationship (ie, the crisis results in a lower number of smokers) found among the employed is offset by the counter-cyclical relationship (ie, the crisis results in a higher number of smokers) found among unemployed individuals. Public health interventions should specifically target those in unemployment, particularly in hard times. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Analysis of the Expression of Peptide–Major Histocompatibility Complexes Using High Affinity Soluble Divalent T Cell Receptors

PubMed Central

O'Herrin, Sean M.; Lebowitz, Michael S.; Bieler, Joan G.; al-Ramadi, Basel K.; Utz, Ursula; Bothwell, Alfred L.M.; Schneck, Jonathan P.

1997-01-01

Understanding the regulation of cell surface expression of specific peptide–major histocompatibility complex (MHC) complexes is hindered by the lack of direct quantitative analyses of specific peptide–MHC complexes. We have developed a direct quantitative biochemical approach by engineering soluble divalent T cell receptor analogues (TCR–Ig) that have high affinity for their cognate peptide–MHC ligands. The generality of this approach was demonstrated by specific staining of peptide-pulsed cells with two different TCR–Ig complexes: one specific for the murine alloantigen 2C, and one specific for a viral peptide from human T lymphocyte virus–1 presented by human histocompatibility leukocyte antigens–A2. Further, using 2C TCR– Ig, a more detailed analysis of the interaction with cognate peptide–MHC complexes revealed several interesting findings. Soluble divalent 2C TCR–Ig detected significant changes in the level of specific antigenic–peptide MHC cell surface expression in cells treated with γ-interferon (γ-IFN). Interestingly, the effects of γ-IFN on expression of specific peptide–MHC complexes recognized by 2C TCR–Ig were distinct from its effects on total H-2 Ld expression; thus, lower doses of γ-IFN were required to increase expression of cell surface class I MHC complexes than were required for upregulation of expression of specific peptide–MHC complexes. Analysis of the binding of 2C TCR–Ig for specific peptide–MHC ligands unexpectedly revealed that the affinity of the 2C TCR–Ig for the naturally occurring alloreactive, putatively, negatively selecting, complex, dEV-8–H-2 Kbm3, is very low, weaker than 71 μM. The affinity of the 2C TCR for the other naturally occurring, negatively selecting, alloreactive complex, p2Ca–H-2 Ld, is ∼1000-fold higher. Thus, negatively selecting peptide–MHC complexes do not necessarily have intrinsically high affinity for cognate TCR. These results, uniquely revealed by this analysis, indicate the importance of using high affinity biologically relevant cognates, such as soluble divalent TCR, in furthering our understanding of immune responses. PMID:9334373

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans.

PubMed

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C G; Benavente, Ricardo

2012-10-09

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans.

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans

PubMed Central

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C. G.; Benavente, Ricardo

2012-01-01

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans. PMID:23012415

Automated Sensitivity Analysis of Interplanetary Trajectories for Optimal Mission Design

NASA Technical Reports Server (NTRS)

Knittel, Jeremy; Hughes, Kyle; Englander, Jacob; Sarli, Bruno

2017-01-01

This work describes a suite of Python tools known as the Python EMTG Automated Trade Study Application (PEATSA). PEATSA was written to automate the operation of trajectory optimization software, simplify the process of performing sensitivity analysis, and was ultimately found to out-perform a human trajectory designer in unexpected ways. These benefits will be discussed and demonstrated on sample mission designs.

Plants and climate change: complexities and surprises.

PubMed

Parmesan, Camille; Hanley, Mick E

2015-11-01

Anthropogenic climate change (ACC) will influence all aspects of plant biology over coming decades. Many changes in wild species have already been well-documented as a result of increased atmospheric CO2 concentrations, warming climate and changing precipitation regimes. A wealth of available data has allowed the use of meta-analyses to examine plant-climate interactions on more sophisticated levels than before. These analyses have revealed major differences in plant response among groups, e.g. with respect to functional traits, taxonomy, life-history and provenance. Interestingly, these meta-analyses have also exposed unexpected mismatches between theory, experimental, and observational studies. We reviewed the literature on species' responses to ACC, finding ∼42 % of 4000 species studied globally are plants (primarily terrestrial). We review impacts on phenology, distributions, ecophysiology, regeneration biology, plant-plant and plant-herbivore interactions, and the roles of plasticity and evolution. We focused on apparent deviations from expectation, and highlighted cases where more sophisticated analyses revealed that unexpected changes were, in fact, responses to ACC. We found that conventionally expected responses are generally well-understood, and that it is the aberrant responses that are now yielding greater insight into current and possible future impacts of ACC. We argue that inconclusive, unexpected, or counter-intuitive results should be embraced in order to understand apparent disconnects between theory, prediction, and observation. We highlight prime examples from the collection of papers in this Special Issue, as well as general literature. We found use of plant functional groupings/traits had mixed success, but that some underutilized approaches, such as Grime's C/S/R strategies, when incorporated, have improved understanding of observed responses. Despite inherent difficulties, we highlight the need for ecologists to conduct community-level experiments in systems that replicate multiple aspects of ACC. Specifically, we call for development of coordinating experiments across networks of field sites, both natural and man-made. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-/- and CFTRΔF508/ΔF508 Pigs

PubMed Central

Cho, Hyung-Ju; Joo, Nam Soo; Wine, Jeffrey J.

2011-01-01

Background Cystic fibrosis (CF), caused by reduced CFTR function, includes severe sinonasal disease which may predispose to lung disease. Newly developed CF pigs provide models to study the onset of CF pathophysiology. We asked if glands from pig nasal turbinates have secretory responses similar to those of tracheal glands and if CF nasal glands show reduced fluid secretion. Methodology/Principal Findings Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, being smaller, more numerous (density per airway surface area), more sensitive to carbachol, more sensitive to forskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets (12 CF and 12 controls) in response to agonists was measured using digital imaging of mucus bubbles formed under oil. Secretion rates were significantly reduced in all conditions tested. Fluid secretory rates (Controls vs. CF, in pl/min/gland) were as follows: 3 µM forskolin: 9.2±2.2 vs. 0.6±0.3; 1 µM carbachol: 143.5±35.5 vs. 52.2±10.3; 3 µM forskolin + 0.1 µM carbachol: 25.8±5.8 vs. CF 4.5±0.9. We also compared CFΔF508/ΔF508 with CFTR-/- piglets and found significantly greater forskolin-stimulated secretion rates in the ΔF508 vs. the null piglets (1.4±0.8, n = 4 vs. 0.2±0.1, n = 7). An unexpected age effect was also discovered: the ratio of secretion to 3 µM forskolin vs. 1 µM carbachol was ∼4 times greater in adult than in neonatal nasal glands. Conclusions/Significance These findings reveal differences between nasal and tracheal glands, show defective fluid secretion in nasal glands of CF pigs, reveal some spared function in the ΔF508 vs. null piglets, and show unexpected age-dependent differences. Reduced nasal gland fluid secretion may predispose to sinonasal and lung infections. PMID:21935358

Crystallographic identification of an unexpected by-product in an Ullman's reaction toward biphenyls: 1-(4-hexyloxy-3-hydroxyphenyl)ethanone.

PubMed

Manzano, Veronica E; Baggio, Ricardo; Cukiernik, Fabio D

2015-11-01

The synthesis of 3,3'-diacetoxy-4,4'-bis(hexyloxy)biphenyl following the nickel-modified Ullmann reaction yielded a by-product which was identified successfully by crystallographic analysis as 1-(4-hexyloxy-3-hydroxyphenyl)ethanone, C14H20O3. This unexpected nonbiphenyl by-product exhibited IR, (1)H NMR, (13)C NMR and COSY (correlation spectroscopy) spectra fully consistent with the proposed structure. The compound crystallized in the orthorombic Pbca space group, with two independent formula units in the asymmetric unit (one of which was slightly disordered), and showed a supramolecular architecture in which molecules linked by hydroxy-ethanone O-H···O interactions are organized in columns separated by the aliphatic tails.

Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials

PubMed Central

Autefage, Hélène; Littmann, Elena; Hedegaard, Martin A. B.; Von Erlach, Thomas; O’Donnell, Matthew; Burden, Frank R.; Winkler, David A.; Stevens, Molly M.

2015-01-01

Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells’ global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell–material interactions and suggest alternative research routes for evaluating biomaterials to improve their design. PMID:25831522

Rates of abnormalities and infectious agents in cervical smears from female inmates in Texas: comparison with private and university clinic patients.

PubMed

Logrono, R; Wong, J Y

1999-09-01

Inmates are generally considered a high-risk population for gynecologic neoplasia and sexually transmitted diseases. Cervical smears from prisoners of the Texas Department of Corrections (TDC) were expected initially to have higher rates of cellular abnormalities and infectious agents than do smears from the general population. The cytologic findings from 25,522 TDC gynecologic smears were compared with those of 6883 cases from The University of Texas Medical Branch (UTMB) affiliated physician private clinics, and with 56,178 from the UTMB hospital clinics. The period of study was from September 1995 to February 1998. This study revealed a 5.23% higher rate of abnormalities for TDC gynecologic smears as compared with that for the private clinic smears. However, the TDC rate of abnormalities was unexpectedly 1.08% lower than that for the UTMB clinic smears. These unexpected findings were probably the result of a more selected high-risk population referred to the UTMB clinics. The TDC smears showed also the highest incidence of trichomoniasis.

A Neonate with Susceptibility to Long QT Syndrome Type 6 who Presented with Ventricular Fibrillation and Sudden Unexpected Infant Death.

PubMed

Sauer, Charles W; Marc-Aurele, Krishelle L

2016-07-28

BACKGROUND This is a case of a neonate with susceptibility to long QT syndrome (LQTS) who presented with a sudden unexpected infant death. Experts continue to debate whether universal electrocardiogram (ECG) screening of all newborns is feasible, practical, and cost-effective. CASE REPORT A 19-day-old neonate was found unresponsive by her mother. ECG showed ventricular fibrillation and a combination of a lidocaine drip plus multiple defibrillations converted the rhythm to normal sinus. Unfortunately, MRI brain imaging showed multiple infarcts and EEG showed burst suppression pattern with frequent seizures; life supportive treatment was stopped and the infant died. Genetic testing revealed two mutations in the KCNE2 gene consistent with susceptibility to LQTS type 6. CONCLUSIONS We believe this case is the first to demonstrate both a precipitating electrocardiographic and genetic cause of death for an infant with LQTS, showing a cause-and-effect relationship between LQTS mutation, ventricular arrhythmia, and death. We wonder whether universal ECG newborn screening to prevent LQTS death could have saved this baby.

Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist.

PubMed

Zhang, Chen; Zhang, Tuo; Zou, Juan; Miller, Cassandra Lynn; Gorkhali, Rakshya; Yang, Jeong-Yeh; Schilmiller, Anthony; Wang, Shuo; Huang, Kenneth; Brown, Edward M; Moremen, Kelley W; Hu, Jian; Yang, Jenny J

2016-05-01

Ca(2+)-sensing receptors (CaSRs) modulate calcium and magnesium homeostasis and many (patho)physiological processes by responding to extracellular stimuli, including divalent cations and amino acids. We report the first crystal structure of the extracellular domain (ECD) of human CaSR bound with Mg(2+) and a tryptophan derivative ligand at 2.1 Å. The structure reveals key determinants for cooperative activation by metal ions and aromatic amino acids. The unexpected tryptophan derivative was bound in the hinge region between two globular ECD subdomains, and represents a novel high-affinity co-agonist of CaSR. The dissection of structure-function relations by mutagenesis, biochemical, and functional studies provides insights into the molecular basis of human diseases arising from CaSR mutations. The data also provide a novel paradigm for understanding the mechanism of CaSR-mediated signaling that is likely shared by the other family C GPCR [G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor] members and can facilitate the development of novel CaSR-based therapeutics.

Phospho-ubiquitin: upending the PINK-Parkin-ubiquitin cascade.

PubMed

Matsuda, Noriyuki

2016-04-01

Mitochondria with decreased membrane potential are characterized by defects in protein import into the matrix and impairments in high-efficiency synthesis of ATP. These low-quality mitochondria are marked with ubiquitin for selective degradation. Key factors in this mechanism are PTEN-induced putative kinase 1 (PINK1, a mitochondrial kinase) and Parkin (a ubiquitin ligase), disruption of which has been implicated in predisposition to Parkinson's disease. Previously, the clearance of damaged mitochondria had been thought to be the end result of a simple cascading reaction of PINK1-Parkin-ubiquitin. However, in the past year, several research groups including ours unexpectedly revealed that Parkin regulation is mediated by PINK1-dependent phosphorylation of ubiquitin. These results overturned the simple hierarchy that posited PINK1 and ubiquitin as the upstream and downstream factors of Parkin, respectively. Although ubiquitylation is well-known as a post-translational modification, it has recently become clear that ubiquitin itself can be modified, and that this modification unexpectedly converts ubiquitin to a factor that functions in retrograde signalling. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Sudden unexpected death in infants in the Oxford Record Linkage Area: The mother

PubMed Central

Fedrick, Jean

1974-01-01

Of the 206 cases of sudden unexpected death in infancy (SUD) 170 were linked with the maternity information and birth certificates on the Oxford Record Linkage files. Statistically highly significant correlations were demonstrated with low maternal age, high parity, and low social class, the last two associations being more marked among the mothers of infants who died after the 12th week. Each case of SUD was then matched with three control livebirths for maternal age, parity, civil state of mother, social class, year and hospital of delivery, and as closely as possible for area of residence. A comparison of mothers of cases with those of the controls revealed a highly significant preponderance of women who were born outside the area, and no significant effect with maternal religion, previous pregnancy loss, or ABO blood group. Other pregnancies occurring to the case and control mothers between 1965 and 1971 were also traced. It was shown that the infant dying an SUD was more likely to have been conceived within six months of the birth of his preceding sib. PMID:4854522

Methamphetamine Regulation of Firing Activity of Dopamine Neurons

PubMed Central

Lin, Min; Sambo, Danielle

2016-01-01

Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca2+ homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca2+-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane. SIGNIFICANCE STATEMENT Methamphetamine (METH) competes with dopamine uptake, increases dopamine efflux via the dopamine transporter, and affects the excitability of dopamine neurons. Here, we identified an unexpected property of METH on dopamine neuron firing activity. METH transiently increased the spontaneous spike activity of dopamine neurons followed by a progressive reduction of the spontaneous spike activity. METH broadened the action potentials, increased coefficients of variation of the interspike interval, and decreased the amplitude of afterhyperpolarization, which are consistent with changes in the activity of Ca2+-activated potassium (BK) channels. We found that METH decreased the activity of BK channels by stimulating BK-α subunit trafficking. Thus, METH modulation of dopamine neurotransmission and resulting behavioral responses is, in part, due to METH regulation of BK channel activity. PMID:27707972

Somatic and germline mosaicism for a mutation of the PHEX gene can lead to genetic transmission of X-linked hypophosphatemic rickets that mimics an autosomal dominant trait.

PubMed

Goji, Katsumi; Ozaki, Kayo; Sadewa, Ahmad H; Nishio, Hisahide; Matsuo, Masafumi

2006-02-01

Familial hypophosphatemic rickets is usually transmitted as an X-linked dominant disorder (XLH), although autosomal dominant forms have also been observed. Genetic studies of these disorders have identified mutations in PHEX and FGF23 as the causes of X-linked dominant disorder and autosomal dominant forms, respectively. The objective of the study was to describe the molecular genetic findings in a family affected by hypophosphatemic rickets with presumed autosomal dominant inheritance. We studied a family in which the father and the elder of his two daughters, but not the second daughter, were affected by hypophosphatemic rickets. The pedigree interpretation of the family suggested that genetic transmission of the disorder occurred as an autosomal dominant trait. Direct nucleotide sequencing of FGF23 and PHEX revealed that the elder daughter was heterozygous for an R567X mutation in PHEX, rather than FGF23, suggesting that the genetic transmission occurred as an X-linked dominant trait. Unexpectedly, the father was heterozygous for this mutation. Single-nucleotide primer extension and denaturing HPLC analysis of the father using DNA from single hair roots revealed that he was a somatic mosaic for the mutation. Haplotype analysis confirmed that the father transmitted the genotypes for 18 markers on the X chromosome equally to his two daughters. The fact that the father transmitted the mutation to only one of his two daughters indicated that he was a germline mosaic for the mutation. Somatic and germline mosaicism for an X-linked dominant mutation in PHEX may mimic autosomal dominant inheritance.

A series of no isthmus (noi) alleles of the zebrafish pax2.1 gene reveals multiple signaling events in development of the midbrain-hindbrain boundary.

PubMed

Lun, K; Brand, M

1998-08-01

Generation of cell diversity in the vertebrate central nervous system starts during gastrulation stages in the ectodermal germ layer and involves specialized cell groups, such as the organizer located at the midbrain-hindbrain boundary (MHB). Mutations in the zebrafish no isthmus (noi) gene alter development of the MHB, and affect the pax2.1 gene (formerly pax(zf-b)). Analysis of the structure of pax2.1 reveals at least 12 normal splice variants. The noi alleles can be arranged, by molecular and phenotypic criteria, into a series of five alleles of differing strength, ranging from a null allele to weak alleles. In keeping with a role in development of the MHB organizer, gene expression is already affected in the MHB primordium of the gastrula neural ectoderm in noi mutants. eng3 activation is completely and eng2 activation is strongly dependent on noi function. In contrast, onset of wnt1, fgf8 and her5 expression occurs normally in the null mutants, but is eliminated later on. Our observations suggest that three signaling pathways, involving pax2.1, wnt1 and fgf8, are activated independently in early anterior-posterior patterning of this area. In addition, analysis of the allelic series unexpectedly suggests that noi activity is also required during dorsal-ventral patterning of the MHB in somitogenesis stages, and possibly in a later eng expression phase. We propose that noi/pax2.1 participates in sequential signaling processes as a key integrator of midbrain-hindbrain boundary development.

Microbiota-Induced Changes in Drosophila melanogaster Host Gene Expression and Gut Morphology

PubMed Central

Buchon, Nicolas

2014-01-01

ABSTRACT To elucidate mechanisms underlying the complex relationships between a host and its microbiota, we used the genetically tractable model Drosophila melanogaster. Consistent with previous studies, the microbiota was simple in composition and diversity. However, analysis of single flies revealed high interfly variability that correlated with differences in feeding. To understand the effects of this simple and variable consortium, we compared the transcriptome of guts from conventionally reared flies to that for their axenically reared counterparts. Our analysis of two wild-type fly lines identified 121 up- and 31 downregulated genes. The majority of these genes were associated with immune responses, tissue homeostasis, gut physiology, and metabolism. By comparing the transcriptomes of young and old flies, we identified temporally responsive genes and showed that the overall impact of microbiota was greater in older flies. In addition, comparison of wild-type gene expression with that of an immune-deficient line revealed that 53% of upregulated genes exerted their effects through the immune deficiency (Imd) pathway. The genes included not only classic immune response genes but also those involved in signaling, gene expression, and metabolism, unveiling new and unexpected connections between immunity and other systems. Given these findings, we further characterized the effects of gut-associated microbes on gut morphology and epithelial architecture. The results showed that the microbiota affected gut morphology through their impacts on epithelial renewal rate, cellular spacing, and the composition of different cell types in the epithelium. Thus, while bacteria in the gut are highly variable, the influence of the microbiota at large has far-reaching effects on host physiology. PMID:24865556

Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology.

PubMed

Aitken, R J; Muscio, L; Whiting, S; Connaughton, H S; Fraser, B A; Nixon, B; Smith, N D; De Iuliis, G N

2016-12-01

The need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i) a loss of mitochondrial membrane potential (Δψm) via mechanisms that were not related to opening of the permeability transition pore but associated with a reduction in thiol expression, (ii) a decline in intracellular reduced glutathione, (iii) the stimulation of pro-oxidant activity including the induction of ROS generation from mitochondrial and non-mitochondrial sources, (iv) stimulation of lipid peroxidation, (v) the generation of oxidative DNA damage, and (vi) impaired sperm motility. For most of the polyphenolic compounds examined, the loss of motility was gradual and highly correlated with the induction of lipid peroxidation (r=0.889). The exception was gossypol, which induced a rapid loss of motility due to its inherent alkylating activity; one consequence of which was a marked reduction in carboxymethyl lysine expression on the sperm tail; a post-translational modification that is known to play a key role in the regulation of sperm movement. The only polyphenols that did not appear to have adverse effects on spermatozoa were resveratrol, genistein and THP at doses below 100μM. These compounds could, therefore, have some therapeutic potential in a clinical setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Leveraging electronic health record documentation for Failure Mode and Effects Analysis team identification

PubMed Central

Carson, Matthew B; Lee, Young Ji; Benacka, Corrine; Mutharasan, R. Kannan; Ahmad, Faraz S; Kansal, Preeti; Yancy, Clyde W; Anderson, Allen S; Soulakis, Nicholas D

2017-01-01

Objective: Using Failure Mode and Effects Analysis (FMEA) as an example quality improvement approach, our objective was to evaluate whether secondary use of orders, forms, and notes recorded by the electronic health record (EHR) during daily practice can enhance the accuracy of process maps used to guide improvement. We examined discrepancies between expected and observed activities and individuals involved in a high-risk process and devised diagnostic measures for understanding discrepancies that may be used to inform quality improvement planning. Methods: Inpatient cardiology unit staff developed a process map of discharge from the unit. We matched activities and providers identified on the process map to EHR data. Using four diagnostic measures, we analyzed discrepancies between expectation and observation. Results: EHR data showed that 35% of activities were completed by unexpected providers, including providers from 12 categories not identified as part of the discharge workflow. The EHR also revealed sub-components of process activities not identified on the process map. Additional information from the EHR was used to revise the process map and show differences between expectation and observation. Conclusion: Findings suggest EHR data may reveal gaps in process maps used for quality improvement and identify characteristics about workflow activities that can identify perspectives for inclusion in an FMEA. Organizations with access to EHR data may be able to leverage clinical documentation to enhance process maps used for quality improvement. While focused on FMEA protocols, findings from this study may be applicable to other quality activities that require process maps. PMID:27589944

Evolutionary anomalies among the aminoacyl-tRNA synthetases

NASA Technical Reports Server (NTRS)

Doolittle, R. F.; Handy, J.; Bada, J. L. (Principal Investigator)

1998-01-01

Unexpected relationships among the various aminoacyl-tRNA synthetases continue to be uncovered. The question arises - is this mainly the result of promiscuous exchange, or is the confusion really a reflection of the differential loss of past duplications? Phylogenetic analysis may yet provide the answer.

Water in stars: expected and unexpected

NASA Astrophysics Data System (ADS)

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.

The N400 and the P300 are not all that independent.

PubMed

Arbel, Yael; Spencer, Kevin M; Donchin, Emanuel

2011-06-01

This study assessed whether two ERP components that are elicited by unexpected events interact. The conditions that are known to elicit the N400 and the P300 ERP components were applied separately and in combination to terminal-words in sentences. Each sentence ended with a terminal-word that was highly expected, semantically unexpected, physically deviant, or both semantically unexpected and physically deviant. In addition, we varied the level of semantic relatedness between the unexpected terminal-words and the expected exemplars. Physically deviant words elicited a P300, whereas semantically unexpected words elicited an N400, whose amplitude was sensitive to the level of semantic relatedness. Words that were both semantically unexpected and physically deviant elicited both an N400 with enhanced amplitude, and a P300 with reduced amplitude. These results suggest an interaction between the processes manifested by the two components. Copyright © 2010 Society for Psychophysiological Research.

Microbial seascapes revisited.

PubMed

DeLong, E F

2001-06-01

A remarkable array of new discoveries is emerging from studies of naturally occurring marine microbes. These discoveries originate from novel applications of evolving technologies, ranging from molecular phylogenetics to stable isotope analyses, to advanced microscopic techniques, to genomics. As a consequence, new perspectives on the natural history of marine microbes, the inseparable nature of the geological and biological worlds, and a plethora of unexpected new genotypes, phenotypes and physiologies are now being revealed. As our observations of naturally occurring microbes become increasingly more sophisticated, so will theory, technical applications and predictive capabilities in microbial ecology.

Mineralogy, Three Dimensional Structure, and Oxygen Isotope Ratios of Four Crystalline Particles from Comet 81P/Wild 2

NASA Technical Reports Server (NTRS)

Nakamura, T.; Noguchi, T.; Tsuchiyama, A.; Ushikubo, T.; Kita, N. T.; Valley, J. W.; Zolensky, M. E.; Kakazu, Y.; Sakamoto, K.; Mashio, E.;

Microbial oceanography and the Hawaii Ocean Time-series programme.

PubMed

Karl, David M; Church, Matthew J

2014-10-01

The Hawaii Ocean Time-series (HOT) programme has been tracking microbial and biogeochemical processes in the North Pacific Subtropical Gyre since October 1988. The near-monthly time series observations have revealed previously undocumented phenomena within a temporally dynamic ecosystem that is vulnerable to climate change. Novel microorganisms, genes and unexpected metabolic pathways have been discovered and are being integrated into our evolving ecological paradigms. Continued research, including higher-frequency observations and at-sea experimentation, will help to provide a comprehensive scientific understanding of microbial processes in the largest biome on Earth.

Making molecular balloons in laser-induced explosive boiling of polymer solutions.

PubMed

Leveugle, Elodie; Sellinger, Aaron; Fitz-Gerald, James M; Zhigilei, Leonid V

2007-05-25

The effect of the dynamic molecular rearrangements leading to compositional segregation is revealed in coarse-grained molecular dynamics simulations of short pulse laser interaction with a polymer solution in a volatile matrix. An internal release of matrix vapor at the onset of the explosive boiling of the overheated liquid is capable of pushing polymer molecules to the outskirts of a transient bubble, forming a polymer-rich surface layer enclosing the volatile matrix material. The results explain unexpected "deflated balloon" structures observed in films deposited by the matrix-assisted pulsed laser evaporation technique.

Vegetation and climate variability in tropical and subtropical South America during the late Quaternary

NASA Astrophysics Data System (ADS)

Behling, H.

2013-05-01

Detailed palynological studies from different ecosystems in tropical and subtropical South America reflect interesting vegetation and climate dynamics, in particular during glacial and late glacial times. Records from ecosystems such as the Amazon rainforest, savanna, Caatinga, Atlantic rainforest, Araucaria forest and grasslands provide interesting insight of past climate variability. The influence of events such as Dansgaard-Oeschger, Heinnrich stadials, changes in the thermohaline circulation (THC) will be discussed. In particular the Younger Dryas (YD) period shows at different places distinct vegetational changes, revealing unexpected past climatic conditions.

Inducing changes in arousal and valence: comparison of two mood induction procedures.

PubMed

Jallais, Christophe; Gilet, Anne-Laure

2010-02-01

This research examined the relative effectiveness of two mood induction procedures (MIPs) for inducing four specific moods varying along the dimensions of both valence and arousal. Participants were randomly assigned either to an autobiographical recall or to a music and guided imagery MIP and underwent a happiness, serenity, anger, or sadness mood induction. The findings confirmed the effectiveness of the two MIPs in producing changes on both the valence and arousal dimensions of mood. The results also revealed an unexpected greater efficiency of the autobiographical recall than of the combined procedure.

Unexpected substrate specificity of T4 DNA ligase revealed by in vitro selection

NASA Technical Reports Server (NTRS)

Harada, Kazuo; Orgel, Leslie E.

1993-01-01

We have used in vitro selection techniques to characterize DNA sequences that are ligated efficiently by T4 DNA ligase. We find that the ensemble of selected sequences ligates about 50 times as efficiently as the random mixture of sequences used as the input for selection. Surprisingly many of the selected sequences failed to produce a match at or close to the ligation junction. None of the 20 selected oligomers that we sequenced produced a match two bases upstream from the ligation junction.

Aromatase in the brain: not just for reproduction anymore.

PubMed

Garcia-Segura, L M

2008-06-01

Aromatase, the enzyme that synthesises oestrogens from androgen precursors, is expressed in the brain, where it has been classically associated with the regulation of neuroendocrine events and behaviours linked with reproduction. Recent findings, however, have revealed new unexpected roles for brain aromatase, indicating that the enzyme regulates synaptic activity, synaptic plasticity, neurogenesis and the response of neural tissue to injury, and may contribute to control nonreproductive behaviours, mood and cognition. Therefore, the function of brain aromatase is not restricted to the regulation of reproduction as previously thought.

OPEN PROBLEM: Turbulence transition in pipe flow: some open questions

NASA Astrophysics Data System (ADS)

Eckhardt, Bruno

2008-01-01

The transition to turbulence in pipe flow is a longstanding problem in fluid dynamics. In contrast to many other transitions it is not connected with linear instabilities of the laminar profile and hence follows a different route. Experimental and numerical studies within the last few years have revealed many unexpected connections to the nonlinear dynamics of strange saddles and have considerably improved our understanding of this transition. The text summarizes some of these insights and points to some outstanding problems in areas where valuable contributions from nonlinear dynamics can be expected.

Self-assembly of skyrmion-dressed chiral nematic colloids with tangential anchoring.

PubMed

Pandey, M B; Porenta, T; Brewer, J; Burkart, A; Copar, S; Zumer, S; Smalyukh, Ivan I

2014-06-01

We describe dipolar nematic colloids comprising mutually bound solid microspheres, three-dimensional skyrmions, and point defects in a molecular alignment field of chiral nematic liquid crystals. Nonlinear optical imaging and numerical modeling based on minimization of Landau-de Gennes free energy reveal that the particle-induced skyrmions resemble torons and hopfions, while matching surface boundary conditions at the interfaces of liquid crystal and colloidal spheres. Laser tweezers and videomicroscopy reveal that the skyrmion-colloidal hybrids exhibit purely repulsive elastic pair interactions in the case of parallel dipoles and an unexpected reversal of interaction forces from repulsive to attractive as the center-to-center distance decreases for antiparallel dipoles. The ensuing elastic self-assembly gives rise to colloidal chains of antiparallel dipoles with particles entangled by skyrmions.

Dying Is Unexpectedly Positive.

PubMed

Goranson, Amelia; Ritter, Ryan S; Waytz, Adam; Norton, Michael I; Gray, Kurt

2017-07-01

In people's imagination, dying seems dreadful; however, these perceptions may not reflect reality. In two studies, we compared the affective experience of people facing imminent death with that of people imagining imminent death. Study 1 revealed that blog posts of near-death patients with cancer and amyotrophic lateral sclerosis were more positive and less negative than the simulated blog posts of nonpatients-and also that the patients' blog posts became more positive as death neared. Study 2 revealed that the last words of death-row inmates were more positive and less negative than the simulated last words of noninmates-and also that these last words were less negative than poetry written by death-row inmates. Together, these results suggest that the experience of dying-even because of terminal illness or execution-may be more pleasant than one imagines.

Confocal microscopy of fluid inclusions reveals fluid-pressure histories of sediments and an unexpected origin of gas condensate

NASA Astrophysics Data System (ADS)

Aplin, Andrew C.; Larter, Steve R.; Bigge, M. Ashley; MacLeod, Gordon; Swarbrick, Richard E.; Grunberger, Daniel

2000-11-01

We present two examples of how fluid inclusion data can be used to determine geologic pressure histories and to quantify the compositional evolution of petroleum in oil reservoirs. Volumetric liquid: vapor ratios generated with a confocal laser scanning microscope are used along with pressure-vapor-temperature (P-V-T) modeling software to estimate the composition, P-T phase envelope, and isochore of single petroleum inclusions in the North Sea's Judy and Alwyn fields. In both cases, the gas condensates currently in the reservoirs formed by the emplacement of gas into preexisting oil accumulations. Pressure histories of individual units in each field are also revealed, providing the kind of data needed to determine the permeability and fluid flow histories of sedimentary basins.

Early MAVEN Deep Dip campaign reveals thermosphere and ionosphere variability.

PubMed

Bougher, S; Jakosky, B; Halekas, J; Grebowsky, J; Luhmann, J; Mahaffy, P; Connerney, J; Eparvier, F; Ergun, R; Larson, D; McFadden, J; Mitchell, D; Schneider, N; Zurek, R; Mazelle, C; Andersson, L; Andrews, D; Baird, D; Baker, D N; Bell, J M; Benna, M; Brain, D; Chaffin, M; Chamberlin, P; Chaufray, J-Y; Clarke, J; Collinson, G; Combi, M; Crary, F; Cravens, T; Crismani, M; Curry, S; Curtis, D; Deighan, J; Delory, G; Dewey, R; DiBraccio, G; Dong, C; Dong, Y; Dunn, P; Elrod, M; England, S; Eriksson, A; Espley, J; Evans, S; Fang, X; Fillingim, M; Fortier, K; Fowler, C M; Fox, J; Gröller, H; Guzewich, S; Hara, T; Harada, Y; Holsclaw, G; Jain, S K; Jolitz, R; Leblanc, F; Lee, C O; Lee, Y; Lefevre, F; Lillis, R; Livi, R; Lo, D; Ma, Y; Mayyasi, M; McClintock, W; McEnulty, T; Modolo, R; Montmessin, F; Morooka, M; Nagy, A; Olsen, K; Peterson, W; Rahmati, A; Ruhunusiri, S; Russell, C T; Sakai, S; Sauvaud, J-A; Seki, K; Steckiewicz, M; Stevens, M; Stewart, A I F; Stiepen, A; Stone, S; Tenishev, V; Thiemann, E; Tolson, R; Toublanc, D; Vogt, M; Weber, T; Withers, P; Woods, T; Yelle, R

2015-11-06

The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability. Copyright © 2015, American Association for the Advancement of Science.

Predictive coding in autism spectrum disorder and attention deficit hyperactivity disorder.

PubMed

Gonzalez-Gadea, Maria Luz; Chennu, Srivas; Bekinschtein, Tristan A; Rattazzi, Alexia; Beraudi, Ana; Tripicchio, Paula; Moyano, Beatriz; Soffita, Yamila; Steinberg, Laura; Adolfi, Federico; Sigman, Mariano; Marino, Julian; Manes, Facundo; Ibanez, Agustin

2015-11-01

Predictive coding has been proposed as a framework to understand neural processes in neuropsychiatric disorders. We used this approach to describe mechanisms responsible for attentional abnormalities in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We monitored brain dynamics of 59 children (8-15 yr old) who had ASD or ADHD or who were control participants via high-density electroencephalography. We performed analysis at the scalp and source-space levels while participants listened to standard and deviant tone sequences. Through task instructions, we manipulated top-down expectation by presenting expected and unexpected deviant sequences. Children with ASD showed reduced superior frontal cortex (FC) responses to unexpected events but increased dorsolateral prefrontal cortex (PFC) activation to expected events. In contrast, children with ADHD exhibited reduced cortical responses in superior FC to expected events but strong PFC activation to unexpected events. Moreover, neural abnormalities were associated with specific control mechanisms, namely, inhibitory control in ASD and set-shifting in ADHD. Based on the predictive coding account, top-down expectation abnormalities could be attributed to a disproportionate reliance (precision) allocated to prior beliefs in ASD and to sensory input in ADHD. Copyright © 2015 the American Physiological Society.

Predictive coding in autism spectrum disorder and attention deficit hyperactivity disorder

PubMed Central

Gonzalez-Gadea, Maria Luz; Chennu, Srivas; Bekinschtein, Tristan A.; Rattazzi, Alexia; Beraudi, Ana; Tripicchio, Paula; Moyano, Beatriz; Soffita, Yamila; Steinberg, Laura; Adolfi, Federico; Sigman, Mariano; Marino, Julian; Manes, Facundo

2015-01-01

Predictive coding has been proposed as a framework to understand neural processes in neuropsychiatric disorders. We used this approach to describe mechanisms responsible for attentional abnormalities in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We monitored brain dynamics of 59 children (8–15 yr old) who had ASD or ADHD or who were control participants via high-density electroencephalography. We performed analysis at the scalp and source-space levels while participants listened to standard and deviant tone sequences. Through task instructions, we manipulated top-down expectation by presenting expected and unexpected deviant sequences. Children with ASD showed reduced superior frontal cortex (FC) responses to unexpected events but increased dorsolateral prefrontal cortex (PFC) activation to expected events. In contrast, children with ADHD exhibited reduced cortical responses in superior FC to expected events but strong PFC activation to unexpected events. Moreover, neural abnormalities were associated with specific control mechanisms, namely, inhibitory control in ASD and set-shifting in ADHD. Based on the predictive coding account, top-down expectation abnormalities could be attributed to a disproportionate reliance (precision) allocated to prior beliefs in ASD and to sensory input in ADHD. PMID:26311184

Some See It, Some Don’t: Exploring the Relation between Inattentional Blindness and Personality Factors

PubMed Central

Kreitz, Carina; Schnuerch, Robert; Gibbons, Henning; Memmert, Daniel

2015-01-01

Human awareness is highly limited, which is vividly demonstrated by the phenomenon that unexpected objects go unnoticed when attention is focused elsewhere (inattentional blindness). Typically, some people fail to notice unexpected objects while others detect them instantaneously. Whether this pattern reflects stable individual differences is unclear to date. In particular, hardly anything is known about the influence of personality on the likelihood of inattentional blindness. To fill this empirical gap, we examined the role of multiple personality factors, namely the Big Five, BIS/BAS, absorption, achievement motivation, and schizotypy, in these failures of awareness. In a large-scale sample (N = 554), susceptibility to inattentional blindness was associated with a low level of openness to experience and marginally with a low level of achievement motivation. However, in a multiple regression analysis, only openness emerged as an independent, negative predictor. This suggests that the general tendency to be open to experience extends to the domain of perception. Our results complement earlier work on the possible link between inattentional blindness and personality by demonstrating, for the first time, that failures to consciously perceive unexpected objects reflect individual differences on a fundamental dimension of personality. PMID:26011567

A Step Toward High Reliability: Implementation of a Daily Safety Brief in a Children's Hospital.

PubMed

Saysana, Michele; McCaskey, Marjorie; Cox, Elaine; Thompson, Rachel; Tuttle, Lora K; Haut, Paul R

2017-09-01

Health care is a high-risk industry. To improve communication about daily events and begin the journey toward a high reliability organization, the Riley Hospital for Children at Indiana University Health implemented a daily safety brief. Various departments in our children's hospital were asked to participate in a daily safety brief, reporting daily events and unexpected outcomes within their scope of responsibility. Participants were surveyed before and after implementation of the safety brief about communication and awareness of events in the hospital. The length of the brief and percentage of departments reporting unexpected outcomes were measured. The analysis of the presurvey and the postsurvey showed a statistically significant improvement in the questions related to the awareness of daily events as well as communication and relationships between departments. The monthly mean length of time for the brief was 15 minutes or less. Unexpected outcomes were reported by 50% of the departments for 8 months. A daily safety brief can be successfully implemented in a children's hospital. Communication between departments and awareness of daily events were improved. Implementation of a daily safety brief is a step toward becoming a high reliability organization.

Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination.

PubMed

Jia, Lei; Li, Lin; Gui, Tao; Liu, Siyang; Li, Hanping; Han, Jingwan; Guo, Wei; Liu, Yongjian; Li, Jingyun

2016-09-21

With increasing data on HIV-1, a more relevant molecular model describing mechanism details of HIV-1 genetic recombination usually requires upgrades. Currently an incomplete structural understanding of the copy choice mechanism along with several other issues in the field that lack elucidation led us to perform an analysis of the correlation between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarity to further explore structural mechanisms. Near full length sequences of URFs from Asia, Europe, and Africa (one sequence/patient), and representative sequences of worldwide CRFs were retrieved from the Los Alamos HIV database. Their recombination patterns were analyzed by jpHMM in detail. Then the relationships between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarities were investigated. Pearson correlation test showed that all URF groups and the CRF group exhibit the same breakpoint distribution pattern. Additionally, the Wilcoxon two-sample test indicated a significant and inexplicable limitation of recombination in regions with high pairing probability. These regions have been found to be strongly conserved across distinct biological states (i.e., strong intersubtype similarity), and genetic similarity has been determined to be a very important factor promoting recombination. Thus, the results revealed an unexpected disagreement between intersubtype similarity and breakpoint distribution, which were further confirmed by genetic similarity analysis. Our analysis reveals a critical conflict between results from natural HIV-1 isolates and those from HIV-1-based assay vectors in which genetic similarity has been shown to be a very critical factor promoting recombination. These results indicate the region with high-pairing probabilities may be a more fundamental factor affecting HIV-1 recombination than sequence similarity in natural HIV-1 infections. Our findings will be relevant in furthering the understanding of HIV-1 recombination mechanisms.

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

PubMed

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, p<0.001). Individuals who reported having used edibles had greater odds of experiencing an unexpected high, after controlling for the same set of variables (OR=1.56, p<0.05). People who try new marijuana 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.

Identifying black swans in NextGen: predicting human performance in off-nominal conditions.

PubMed

Wickens, Christopher D; Hooey, Becky L; Gore, Brian F; Sebok, Angelia; Koenicke, Corey S

2009-10-01

The objective is to validate a computational model of visual attention against empirical data--derived from a meta-analysis--of pilots' failure to notice safety-critical unexpected events. Many aircraft accidents have resulted, in part, because of failure to notice nonsalient unexpected events outside of foveal vision, illustrating the phenomenon of change blindness. A model of visual noticing, N-SEEV (noticing-salience, expectancy, effort, and value), was developed to predict these failures. First, 25 studies that reported objective data on miss rate for unexpected events in high-fidelity cockpit simulations were identified, and their miss rate data pooled across five variables (phase of flight, event expectancy, event location, presence of a head-up display, and presence of a highway-in-the-sky display). Second, the parameters of the N-SEEV model were tailored to mimic these dichotomies. The N-SEEV model output predicted variance in the obtained miss rate (r = .73). The individual miss rates of all six dichotomous conditions were predicted within 14%, and four of these were predicted within 7%. The N-SEEV model, developed on the basis of an independent data set, was able to successfully predict variance in this safety-critical measure of pilot response to abnormal circumstances, as collected from the literature. As new technology and procedures are envisioned for the future airspace, it is important to predict if these may compromise safety in terms of pilots' failing to notice unexpected events. Computational models such as N-SEEV support cost-effective means of making such predictions.

Snf2 family gene distribution in higher plant genomes reveals DRD1 expansion and diversification in the tomato genome.

PubMed

Bargsten, Joachim W; Folta, Adam; Mlynárová, Ludmila; Nap, Jan-Peter

2013-01-01

As part of large protein complexes, Snf2 family ATPases are responsible for energy supply during chromatin remodeling, but the precise mechanism of action of many of these proteins is largely unknown. They influence many processes in plants, such as the response to environmental stress. This analysis is the first comprehensive study of Snf2 family ATPases in plants. We here present a comparative analysis of 1159 candidate plant Snf2 genes in 33 complete and annotated plant genomes, including two green algae. The number of Snf2 ATPases shows considerable variation across plant genomes (17-63 genes). The DRD1, Rad5/16 and Snf2 subfamily members occur most often. Detailed analysis of the plant-specific DRD1 subfamily in related plant genomes shows the occurrence of a complex series of evolutionary events. Notably tomato carries unexpected gene expansions of DRD1 gene members. Most of these genes are expressed in tomato, although at low levels and with distinct tissue or organ specificity. In contrast, the Snf2 subfamily genes tend to be expressed constitutively in tomato. The results underpin and extend the Snf2 subfamily classification, which could help to determine the various functional roles of Snf2 ATPases and to target environmental stress tolerance and yield in future breeding.

Prevalence of precore-defective mutant of hepatitis B virus in HBV carriers.

PubMed

Niitsuma, H; Ishii, M; Saito, Y; Miura, M; Kobayashi, K; Ohori, H; Toyota, T

1995-08-01

Two hundred and seventy-three serum specimens from hepatitis B virus (HBV) carriers were examined for the presence of a characteristic one point mutation at nucleotide (nt) 1896 from the EcoRI site of the HBV genome in the precore region (the preC mutant) using restriction fragment length polymorphism (RFLP) analysis. This assay approach could detect preC mutants or wild-type sequences when either form constituted more than 10% of the total sample. Overall, 65.5% (76/116) of HBeAg-positive carriers had only the preC wild-type. All HBeAg-positive asymptomatic carriers (n = 14) had only the preC wild-type. In patients with chronic hepatitis B and in anti-HBe-positive asymptomatic carriers, increased prevalence of the preC mutant was associated with the development of anti-HBe antibodies and normalization of the serum alanine aminotransferase concentration. Furthermore, 27 (29.0%) of 93 HBeAg-negative carriers had unexpectedly preC wild-type sequences only. Direct sequencing of the HBV precore region of HBV specimens from 24 patients revealed no mutation at nt 1896, supporting the specificity of the RFLP analysis. These results suggest that RFLP analysis was accurate for the detection of the preC mutation and that the absence of serum HBeAg cannot be explained solely by the dominance of the preC mutant.

Aging-like Changes in the Transcriptome of Irradiated Microglia

PubMed Central

Li, Matthew D.; Burns, Terry C.; Kumar, Sunny; Morgan, Alexander A.; Sloan, Steven A.; Palmer, Theo D.

2014-01-01

Whole brain irradiation remains important in the management of brain tumors. Although necessary for improving survival outcomes, cranial irradiation also results in cognitive decline in long-term survivors. A chronic inflammatory state characterized by microglial activation has been implicated in radiation-induced brain injury. We here provide the first comprehensive transcriptional profile of irradiated microglia. Fluorescence-activated cell sorting (FACS) was used to isolate CD11b+ microglia from the hippocampi of C57BL/6 and Balb/c mice 1 month after 10Gy cranial irradiation. Affymetrix gene expression profiles were evaluated using linear modeling, rank product analyses. One month after irradiation, a conserved irradiation signature across strains was identified, comprising 448 and 85 differentially up- and down-regulated genes, respectively. Gene set enrichment analysis (GSEA) demonstrated enrichment for inflammation, including M1 macrophage-associated genes, but also an unexpected enrichment for extracellular matrix and blood coagulation-related gene sets, in contrast previously described microglial states. Weighted gene co-expression network analysis (WGCNA) confirmed these findings and further revealed alterations in mitochondrial function. The RNA-seq transcriptome of microglia 24h post-radiation proved similar to the 1-month transcriptome, but additionally featured alterations in apoptotic and lysosomal gene expression. Re-analysis of published aging mouse microglia transcriptome data demonstrated striking similarity to the 1 month irradiated microglia transcriptome, suggesting that shared mechanisms may underlie aging and chronic irradiation-induced cognitive decline. PMID:25690519