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.

Gastrointestinal causes of sudden unexpected death: A review.

PubMed

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

2018-01-01

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

The unexpected memorial.

PubMed

Holloway, Richard L

2018-03-01

In this article, the current author tells the story of an unexpected musical memorial he and his fellow band mates performed as a tribute to a man named Gordon "Gizmo," a husband and father. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

Unexpected angular or rotational deformity after corrective osteotomy

PubMed Central

2014-01-01

Background Codman’s paradox reveals a misunderstanding of geometry in orthopedic practice. Physicians often encounter situations that cannot be understood intuitively during orthopedic interventions such as corrective osteotomy. Occasionally, unexpected angular or rotational deformity occurs during surgery. This study aimed to draw the attention of orthopedic surgeons toward the concepts of orientation and rotation and demonstrate the potential for unexpected deformity after orthopedic interventions. This study focused on three situations: shoulder arthrodesis, femoral varization derotational osteotomy, and femoral derotation osteotomy. Methods First, a shoulder model was generated to calculate unexpected rotational deformity to demonstrate Codman’s paradox. Second, femoral varization derotational osteotomy was simulated using a cylinder model. Third, a reconstructed femoral model was used to calculate unexpected angular or rotational deformity during femoral derotation osteotomy. Results Unexpected external rotation was found after forward elevation and abduction of the shoulder joint. In the varization and derotation model, closed-wedge osteotomy and additional derotation resulted in an unexpected extension and valgus deformity, namely, under-correction of coxa valga. After femoral derotational osteotomy, varization and extension of the distal fragment occurred, although the extension was negligible. Conclusions Surgeons should be aware of unexpected angular deformity after surgical procedure involving bony areas. The degree of deformity differs depending on the context of the surgical procedure. However, this study reveals that notable deformities can be expected during orthopedic procedures such as femoral varization derotational osteotomy. PMID:24886469

Unexpected but Incidental Positive Outcomes Predict Real-World Gambling.

PubMed

Otto, A Ross; Fleming, Stephen M; Glimcher, Paul W

2016-03-01

Positive mood can affect a person's tendency to gamble, possibly because positive mood fosters unrealistic optimism. At the same time, unexpected positive outcomes, often called prediction errors, influence mood. However, a linkage between positive prediction errors-the difference between expected and obtained outcomes-and consequent risk taking has yet to be demonstrated. Using a large data set of New York City lottery gambling and a model inspired by computational accounts of reward learning, we found that people gamble more when incidental outcomes in the environment (e.g., local sporting events and sunshine) are better than expected. When local sports teams performed better than expected, or a sunny day followed a streak of cloudy days, residents gambled more. The observed relationship between prediction errors and gambling was ubiquitous across the city's socioeconomically diverse neighborhoods and was specific to sports and weather events occurring locally in New York City. Our results suggest that unexpected but incidental positive outcomes influence risk taking. © The Author(s) 2016.

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

PubMed

Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

2016-07-01

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia

PubMed Central

Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

2016-01-01

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

Sudden Unexpected Death in Fetal Life Through Early Childhood

PubMed Central

Kinney, Hannah C.; Willinger, Marian

2016-01-01

In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled “Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities.” Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term “SIDS” in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and “omics” approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of “SIDS” as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. PMID:27230764

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

Unexpected source of latex sensitization in a neonatal intensive care unit.

PubMed

Wynn, R J; Boneberg, A; Lakshminrusimha, S

2007-09-01

We report a term infant with gastroschisis who presented with a systemic allergic reaction at a specific time of each day coinciding with infusion from a new preparation of total parenteral nutrition and intravenous lipid emulsion. The source of latex was traced to the rubber stopper of the lipid emulsion. We present this case to highlight the possibility of allergy from this unexpected source in a neonate.

Inferring Gene Family Histories in Yeast Identifies Lineage Specific Expansions

PubMed Central

Ames, Ryan M.; Money, Daniel; Lovell, Simon C.

2014-01-01

The complement of genes found in the genome is a balance between gene gain and gene loss. Knowledge of the specific genes that are gained and lost over evolutionary time allows an understanding of the evolution of biological functions. Here we use new evolutionary models to infer gene family histories across complete yeast genomes; these models allow us to estimate the relative genome-wide rates of gene birth, death, innovation and extinction (loss of an entire family) for the first time. We show that the rates of gene family evolution vary both between gene families and between species. We are also able to identify those families that have experienced rapid lineage specific expansion/contraction and show that these families are enriched for specific functions. Moreover, we find that families with specific functions are repeatedly expanded in multiple species, suggesting the presence of common adaptations and that these family expansions/contractions are not random. Additionally, we identify potential specialisations, unique to specific species, in the functions of lineage specific expanded families. These results suggest that an important mechanism in the evolution of genome content is the presence of lineage-specific gene family changes. PMID:24921666

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities.

PubMed

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B; Papamarkou, Theodore; Huber, Kilian V M; Mutz, Cornelia; Toretsky, Jeffrey A; Bennett, Keiryn L; Olsen, Jesper V; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong synergistic propensity in Ewing sarcoma, revealing its targets in critical Ewing sarcoma signaling routes. Using a multilevel experimental approach including quantitative phosphoproteomics, we analyzed the molecular rationale behind the disease-specific synergistic effect of simultaneous application of PKC412 and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88-101. ©2016 AACR. ©2016 American Association for Cancer Research.

Managing the Unexpected: Complexity as Distributed Sensemaking

NASA Astrophysics Data System (ADS)

Weick, Karl E.

In 1998 the Centers for Disease Control (CDC) published a statement of their strategy entitled "Preventing Emerging Infectious Diseases: A Strategy for the 21st Century." They described their central challenge this way: "because we do not know what new diseases will arise, we must always be prepared for the unexpected" (p. vii). Soon after they published that statement CDC was confronted with an unexpected emerging disease, the West Nile Virus, which they misdiagnosed initially.

3 CFR - Unexpected Urgent Refugee and Migration Needs

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Unexpected Urgent Refugee and Migration Needs... Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the authority vested...) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended, (22 U.S.C. 2601(c)(1...

3 CFR - Unexpected Urgent Refugee and Migration Needs

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Unexpected Urgent Refugee and Migration Needs Presidential Documents Other Presidential Documents Presidential Determination No. 2012-6 of April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the authority vested in me as President by the Constitution...

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

PubMed

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

2016-09-01

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

Method To Identify Specific Inhibiutors Of Imp Dehydrogenase

DOEpatents

Collart, Frank R.; Huberman, Eliezer

2000-11-28

This invention relates to methods to identify specific inhibitors of the purine nucleotide synthesis enzyme, IMP dehydrogenase (IMPDH). IMPDH is an essential enzyme found in all free-living organisms from humans to bacteria and is an important therapeutic target. The invention allows the identification of specific inhibitors of any IMPDH enzyme which can be expressed in a functional form in a recombinant host cell. A variety of eukaryotic or prokaryotic host systems commonly used for the expression of recombinant proteins are suitable for the practice of the invention. The methods are amenable to high throughput systems for the screening of inhibitors generated by combinatorial chemistry or other methods such as antisense molecule production. Utilization of exogenous guanosine as a control component of the methods allows for the identification of inhibitors specific for IMPDH rather than other causes of decreased cell proliferation.

Investigation of Unexpected Reaction Intermediates in the Alkaline Hydrolysis of Methyl 3,5-Dinitrobenzoate

ERIC Educational Resources Information Center

Silva, Clesia C.; Silva, Ricardo O.; Navarro, Daniela M. A. F.; Navarro, Marcelo

2009-01-01

An experimental project aimed at identifying stable reaction intermediates is described. Initially, the studied reaction appears to involve the simple hydrolysis, by aqueous sodium hydroxide, of methyl 3,5-dinitrobenzoate dissolved in dimethyl sulfoxide. On mixing the substrates, however, the reaction mixture unexpectedly turns an intense red in…

Detecting the unexpected: a research framework for ocean acidification.

PubMed

Pfister, Catherine A; Esbaugh, Andrew J; Frieder, Christina A; Baumann, Hannes; Bockmon, Emily E; White, Meredith M; Carter, Brendan R; Benway, Heather M; Blanchette, Carol A; Carrington, Emily; McClintock, James B; McCorkle, Daniel C; McGillis, Wade R; Mooney, T Aran; Ziveri, Patrizia

2014-09-02

The threat that ocean acidification (OA) poses to marine ecosystems is now recognized and U.S. funding agencies have designated specific funding for the study of OA. We present a research framework for studying OA that describes it as a biogeochemical event that impacts individual species and ecosystems in potentially unexpected ways. We draw upon specific lessons learned about ecosystem responses from research on acid rain, carbon dioxide enrichment in terrestrial plant communities, and nitrogen deposition. We further characterize the links between carbon chemistry changes and effects on individuals and ecosystems, and enumerate key hypotheses for testing. Finally, we quantify how U.S. research funding has been distributed among these linkages, concluding that there is an urgent need for research programs designed to anticipate how the effects of OA will reverberate throughout assemblages of species.

Unexpected features of the dark proteome.

PubMed

Perdigão, Nelson; Heinrich, Julian; Stolte, Christian; Sabir, Kenneth S; Buckley, Michael J; Tabor, Bruce; Signal, Beth; Gloss, Brian S; Hammang, Christopher J; Rost, Burkhard; Schafferhans, Andrea; O'Donoghue, Seán I

2015-12-29

We surveyed the "dark" proteome-that is, regions of proteins never observed by experimental structure determination and inaccessible to homology modeling. For 546,000 Swiss-Prot proteins, we found that 44-54% of the proteome in eukaryotes and viruses was dark, compared with only ∼14% in archaea and bacteria. Surprisingly, most of the dark proteome could not be accounted for by conventional explanations, such as intrinsic disorder or transmembrane regions. Nearly half of the dark proteome comprised dark proteins, in which the entire sequence lacked similarity to any known structure. Dark proteins fulfill a wide variety of functions, but a subset showed distinct and largely unexpected features, such as association with secretion, specific tissues, the endoplasmic reticulum, disulfide bonding, and proteolytic cleavage. Dark proteins also had short sequence length, low evolutionary reuse, and few known interactions with other proteins. These results suggest new research directions in structural and computational biology.

77 FR 21389 - Unexpected Urgent Refugee and Migration Needs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

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

Cannabis-related hospitalizations: unexpected serious events identified through hospital databases

PubMed Central

Jouanjus, Emilie; Leymarie, Florence; Tubery, Marie; Lapeyre-Mestre, Maryse

2011-01-01

AIMS Cannabis is the most prevalent illicit drug used worldwide and can be responsible for serious health defects in users. However, the risk related to cannabis consumption is not well established. The present study aimed to assess cannabis-related adverse events leading to hospitalization, and to estimate the corresponding annual risk for consumers. METHODS Participants were patients admitted to the public hospitals in the Toulouse area (France) between January 2004 and December 2007 in relation to the use of cannabis. Reasons for admission and other occurring events were identified through hospital discharge summaries. We described all observed adverse events (AEs) and estimated their regional incidence on the basis of cannabis consumption data. RESULTS We included 200 patients, and identified a total of 619 adverse events (AEs), one of which was lethal. Psychiatric disorders involved 57.7% of patients and accounted for 18.2% of AEs. Most frequent outcomes were central and peripheral nervous system disorders (15.8% of AEs), acute intoxication (12.1%), respiratory system disorders (11.1%) and cardiovascular disorders (9.5%). We estimated that in 2007 the incidence of cannabis-related AEs in the Midi-Pyrenees region ranged from 1.2 per 1000 regular cannabis users (95% confidence interval (CI) 0.7, 1.6) to 3.2 (95% CI 2.5, 3.9). CONCLUSIONS Cannabis use is associated with complications, considered to be serious since they lead to hospitalization. Beyond the well-known and widely investigated psychiatric events, serious cerebro and cardiovascular complications have been identified. These findings contribute to improve the knowledge of cannabis-related adverse events. PMID:21204913

Unexpected features of the dark proteome

PubMed Central

Perdigão, Nelson; Heinrich, Julian; Stolte, Christian; Sabir, Kenneth S.; Buckley, Michael J.; Tabor, Bruce; Signal, Beth; Gloss, Brian S.; Hammang, Christopher J.; Rost, Burkhard; Schafferhans, Andrea

2015-01-01

We surveyed the “dark” proteome–that is, regions of proteins never observed by experimental structure determination and inaccessible to homology modeling. For 546,000 Swiss-Prot proteins, we found that 44–54% of the proteome in eukaryotes and viruses was dark, compared with only ∼14% in archaea and bacteria. Surprisingly, most of the dark proteome could not be accounted for by conventional explanations, such as intrinsic disorder or transmembrane regions. Nearly half of the dark proteome comprised dark proteins, in which the entire sequence lacked similarity to any known structure. Dark proteins fulfill a wide variety of functions, but a subset showed distinct and largely unexpected features, such as association with secretion, specific tissues, the endoplasmic reticulum, disulfide bonding, and proteolytic cleavage. Dark proteins also had short sequence length, low evolutionary reuse, and few known interactions with other proteins. These results suggest new research directions in structural and computational biology. PMID:26578815

[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.

Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

PubMed

Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

2012-01-01

Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site

Esophageal Cancer Metastases to Unexpected Sites: A Systematic Review

PubMed Central

2017-01-01

The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain. On the other hand, unexpected metastasis (UM) spread to uncommon sites has increasingly reported and consequently affected the pathway of diagnosis, staging, and management. Using the PubMed database, a systematic search of the following headings “Esophageal” and “Metastasis” or “Metastases” was performed, 10049 articles were identified, and the articles were included if they demonstrated unexpected ECM. 84% of cases were men with an average age of 60.7 years. EC was located in the lower third in 65%. Two-thirds of the UM originated from the lower esophagus, and the two major histological types were adenocarcinoma 40% and squamous cell carcinoma 60%. Metastases were disseminated toward five main anatomical sites: the head and neck (42%), thoracic (17%), abdomen and pelvis (25%), extremities (9%), and multiple skin and muscle metastases (7%). The EC metastases were found to be synchronous 42% and metachronous 58%, isolated in 53.5% and multiple in 46.5%. The overall survival rate was 10.2 months. Since distant metastases are responsible for most EC-related deaths, understanding of ECM dissemination patterns needs more extensive studies. These critical data are the cornerstone of optimal cancer approach and treatment. PMID:28659974

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

Framework for Identifying Cybersecurity Risks in Manufacturing

DOE PAGES

Hutchins, Margot J.; Bhinge, Raunak; Micali, Maxwell K.; ...

2015-10-21

Increasing connectivity, use of digital computation, and off-site data storage provide potential for dramatic improvements in manufacturing productivity, quality, and cost. However, there are also risks associated with the increased volume and pervasiveness of data that are generated and potentially accessible to competitors or adversaries. Enterprises have experienced cyber attacks that exfiltrate confidential and/or proprietary data, alter information to cause an unexpected or unwanted effect, and destroy capital assets. Manufacturers need tools to incorporate these risks into their existing risk management processes. This article establishes a framework that considers the data flows within a manufacturing enterprise and throughout its supplymore » chain. The framework provides several mechanisms for identifying generic and manufacturing-specific vulnerabilities and is illustrated with details pertinent to an automotive manufacturer. Finally, in addition to providing manufacturers with insights into their potential data risks, this framework addresses an outcome identified by the NIST Cybersecurity Framework.« less

Framework for Identifying Cybersecurity Risks in Manufacturing

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

Hutchins, Margot J.; Bhinge, Raunak; Micali, Maxwell K.

Increasing connectivity, use of digital computation, and off-site data storage provide potential for dramatic improvements in manufacturing productivity, quality, and cost. However, there are also risks associated with the increased volume and pervasiveness of data that are generated and potentially accessible to competitors or adversaries. Enterprises have experienced cyber attacks that exfiltrate confidential and/or proprietary data, alter information to cause an unexpected or unwanted effect, and destroy capital assets. Manufacturers need tools to incorporate these risks into their existing risk management processes. This article establishes a framework that considers the data flows within a manufacturing enterprise and throughout its supplymore » chain. The framework provides several mechanisms for identifying generic and manufacturing-specific vulnerabilities and is illustrated with details pertinent to an automotive manufacturer. Finally, in addition to providing manufacturers with insights into their potential data risks, this framework addresses an outcome identified by the NIST Cybersecurity Framework.« less

Orthographic Processing and Visual Sequential Memory in Unexpectedly Poor Spellers

ERIC Educational Resources Information Center

Holmes, Virginia M.; Malone, Aisling M.; Redenbach, Holly

2008-01-01

Does unexpectedly poor spelling in adults result from inferior visual sequential memory? In one experiment, unexpectedly poor spellers performed significantly worse than better spellers in the immediate reproduction of sequences of visual symbols, but in a second experiment, the effect was not replicated. Poor spellers were also no worse at the…

Leaning in and holding on: team support with unexpected death.

PubMed

Kobler, Kathie

2014-01-01

Integral to the care of medically fragile infants and children is the sobering reality that not all will survive. Supporting children and families through the dying process requires knowledge, skill, compassion, and a willingness to be present to the suffering of others. As healthcare professionals journey with a dying child, they experience an ongoing dual nature of their own grief, shifting between focusing on the loss at hand or avoiding the loss and refocusing their attention elsewhere. This internal conflict may be potentiated with the sudden, unexpected death of a patient, which affords little time for caregivers to process their own experience of the loss. When an unanticipated death occurs, a palpable grief ripples through the entire unit, impacting caregivers, the bereaved parents, and other patients and families. Such an event holds the potential for either team disorganization or growth. This article presents a case study of one unit's response to the unexpected death of a long-term patient, which caused caregivers to lean in to support each other. Using a case study approach, the author identifies strategies to best guide teams when death arrives without warning, and provides ideas for cocreating ritual to honor relationship in the midst of tragedy.

Wilderness Emergency: Surviving the Unexpected.

ERIC Educational Resources Information Center

Fear, Gene

In any unexpected survival experience, one must accept the situation with just what one has at the moment it happens, where it happens, and how it happens. Problem solving must be based on known body enemies that threaten life, their priority of influence, and their severity of threat to life. Solutions will depend on the body's energy supply,…

Identifying Group-Specific Sequences for Microbial Communities Using Long k-mer Sequence Signatures

PubMed Central

Wang, Ying; Fu, Lei; Ren, Jie; Yu, Zhaoxia; Chen, Ting; Sun, Fengzhu

2018-01-01

Comparing metagenomic samples is crucial for understanding microbial communities. For different groups of microbial communities, such as human gut metagenomic samples from patients with a certain disease and healthy controls, identifying group-specific sequences offers essential information for potential biomarker discovery. A sequence that is present, or rich, in one group, but absent, or scarce, in another group is considered “group-specific” in our study. Our main purpose is to discover group-specific sequence regions between control and case groups as disease-associated markers. We developed a long k-mer (k ≥ 30 bps)-based computational pipeline to detect group-specific sequences at strain resolution free from reference sequences, sequence alignments, and metagenome-wide de novo assembly. We called our method MetaGO: Group-specific oligonucleotide analysis for metagenomic samples. An open-source pipeline on Apache Spark was developed with parallel computing. We applied MetaGO to one simulated and three real metagenomic datasets to evaluate the discriminative capability of identified group-specific markers. In the simulated dataset, 99.11% of group-specific logical 40-mers covered 98.89% disease-specific regions from the disease-associated strain. In addition, 97.90% of group-specific numerical 40-mers covered 99.61 and 96.39% of differentially abundant genome and regions between two groups, respectively. For a large-scale metagenomic liver cirrhosis (LC)-associated dataset, we identified 37,647 group-specific 40-mer features. Any one of the features can predict disease status of the training samples with the average of sensitivity and specificity higher than 0.8. The random forests classification using the top 10 group-specific features yielded a higher AUC (from ∼0.8 to ∼0.9) than that of previous studies. All group-specific 40-mers were present in LC patients, but not healthy controls. All the assembled 11 LC-specific sequences can be mapped to two

Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a.

PubMed

Yelin-Bekerman, Laura; Elbaz, Idan; Diber, Alex; Dahary, Dvir; Gibbs-Bar, Liron; Alon, Shahar; Lerer-Goldshtein, Tali; Appelbaum, Lior

2015-10-01

Sleep has been conserved throughout evolution; however, the molecular and neuronal mechanisms of sleep are largely unknown. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep\\wake states, feeding, stress, and reward. To elucidate the mechanism that enables these various functions and to identify sleep regulators, we combined fluorescence cell sorting and RNA-seq in hcrt:EGFP zebrafish. Dozens of Hcrt-neuron-specific transcripts were identified and comprehensive high-resolution imaging revealed gene-specific localization in all or subsets of Hcrt neurons. Clusters of Hcrt-neuron-specific genes are predicted to be regulated by shared transcription factors. These findings show that Hcrt neurons are heterogeneous and that integrative molecular mechanisms orchestrate their diverse functions. The voltage-gated potassium channel Kcnh4a, which is expressed in all Hcrt neurons, was silenced by the CRISPR-mediated gene inactivation system. The mutant kcnh4a (kcnh4a(-/-)) larvae showed reduced sleep time and consolidation, specifically during the night, suggesting that Kcnh4a regulates sleep.

Unexpected Outcomes from Teachers' TV

ERIC Educational Resources Information Center

Tanner, Ruth

2006-01-01

In this article, the author explains why she has unexpectedly become a fan of Teacher's TV. It started when she was asked to show some clips from Teachers' TV as part of a workshop she was leading. She dutifully accepted a CD containing three downloaded programmes about using ICT to teach mathematics and put it into her laptop. Within a few…

Learning from the unexpected in life and DNA self-assembly

PubMed Central

2015-01-01

Summary The greatest lessons in life and science often arise from the unexpected. Thus, rather than viewing these experiences as hindering our progress, they should be embraced and appreciated for their ability to lead to new discoveries. In this perspective, I will discuss the unexpected events that have shaped my career path and the early stages of my independent research program. PMID:26877793

SMM-system: A mining tool to identify specific markers in Salmonella enterica.

PubMed

Yu, Shuijing; Liu, Weibing; Shi, Chunlei; Wang, Dapeng; Dan, Xianlong; Li, Xiao; Shi, Xianming

2011-03-01

This report presents SMM-system, a software package that implements various personalized pre- and post-BLASTN tasks for mining specific markers of microbial pathogens. The main functionalities of SMM-system are summarized as follows: (i) converting multi-FASTA file, (ii) cutting interesting genomic sequence, (iii) automatic high-throughput BLASTN searches, and (iv) screening target sequences. The utility of SMM-system was demonstrated by using it to identify 214 Salmonella enterica-specific protein-coding sequences (CDSs). Eighteen primer pairs were designed based on eighteen S. enterica-specific CDSs, respectively. Seven of these primer pairs were validated with PCR assay, which showed 100% inclusivity for the 101 S. enterica genomes and 100% exclusivity of 30 non-S. enterica genomes. Three specific primer pairs were chosen to develop a multiplex PCR assay, which generated specific amplicons with a size of 180bp (SC1286), 238bp (SC1598) and 405bp (SC4361), respectively. This study demonstrates that SMM-system is a high-throughput specific marker generation tool that can be used to identify genus-, species-, serogroup- and even serovar-specific DNA sequences of microbial pathogens, which has a potential to be applied in food industries, diagnostics and taxonomic studies. SMM-system is freely available and can be downloaded from http://foodsafety.sjtu.edu.cn/SMM-system.html. Copyright © 2011 Elsevier B.V. All rights reserved.

Essential and Unexpected Role of YY1 to Promote Mesodermal Cardiac Differentiation

PubMed Central

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

2013-01-01

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

An Unexpected Influence on a Quadratic

ERIC Educational Resources Information Center

Davis, Jon D.

2013-01-01

Using technology to explore the coefficients of a quadratic equation can lead to an unexpected result. This article describes an investigation that involves sliders and dynamically linked representations. It guides students to notice the effect that the parameter "a" has on the graphical representation of a quadratic function in the form…

3 CFR - Unexpected Urgent Refugee and Migration Needs Relating to Syria

Code of Federal Regulations, 2014 CFR

2014-01-01

... 3 The President 1 2014-01-01 2014-01-01 false Unexpected Urgent Refugee and Migration Needs Relating to Syria Presidential Documents Other Presidential Documents Presidential Determination No. 2013-4 of January 29, 2013 Unexpected Urgent Refugee and Migration Needs Relating to Syria Memorandum for the Secretary of State By the authority vested i...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Libya

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Libya Presidential Documents Other Presidential Documents Presidential Determination No. 2011-8 of March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya Memorandum for the Secretary of State By the authority vested in me...

Unexpected marked seizure improvement in paediatric epilepsy surgery candidates.

PubMed

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

2017-02-01

Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number of years they had had seizures was 3.4 years (range 0.6-6.2 years) and the number of seizures at inclusion was 209 per month (range 6-750 per month). The duration of follow-up was 6.6 years after inclusion into the epilepsy surgery programme (range 4.0-13.0 years). The aetiology of the epilepsy for these patients was heterotopia (n=1), focal cortical dysplasia (n=3), infarction (n=1) and unknown, with normal MRI (n=1). They all had an IQ in the normal range. Two of the remaining 7 children were operated later. Unexpected seizure control may occur during epilepsy surgery evaluation. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Signet-ring cell carcinoma in gastric biopsies: expecting the unexpected.

PubMed

Golembeski, Christopher P; Genta, Robert Maximilian

2013-02-01

This study was designed to establish the relative prevalence of intestinal-type and signet-ring carcinoma in gastric biopsy specimens from ambulatory patients, to determine the percentage of signet-ring carcinomas that could be expected based on the available clinical and endoscopic information, and to estimate the likelihood of missing a tumour. We extracted data of all patients with a diagnosis of primary gastric carcinoma from a national pathology database. We then reviewed clinical information and original slides, classified tumours as intestinal or signet-ring-type, and categorised the latter as 'unexpected' (no alarming symptoms, no mention of suspicious lesions) or 'expected' (clinical or endoscopic information suggestive of tumour). Unexpected signet-ring carcinomas were categorised as 'obvious' or 'challenging' (rare signet-ring cells; immunohistochemical stains used to confirm the nature of the infiltrates). There were 310 109 patients with gastric biopsies; 615 patients had primary gastric carcinoma (359 intestinal and 256 signet-ring-type). Gastric cancer was more common in men (OR 2.54; 95% CI 2.05 to 3.14; p<.0001) for intestinal-type and (OR 1.90; 95% CI 1.48 to 2.42; p<0.0001) for signet-ring cell type). Intestinal-type carcinoma occurred in older patients than signet-ring-type (median age 74 vs 65 years, p<0.001). There were 196 expected and 60 unexpected signet-ring carcinomas; 47 of the 60 unexpected cases were histopathologically obvious. Thus, only 13 signet-ring carcinomas (1 in 25 000 gastric biopsy sets) were truly unexpected. Signet-ring carcinoma is a rare finding in gastric biopsy specimens from ambulatory patients; routine due diligence and the clinical/endoscopic information provided are usually adequate to raise pathologists' index of suspicion.

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

Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.

PubMed

Sack, Laura Magill; Davoli, Teresa; Li, Mamie Z; Li, Yuyang; Xu, Qikai; Naxerova, Kamila; Wooten, Eric C; Bernardi, Ronald J; Martin, Timothy D; Chen, Ting; Leng, Yumei; Liang, Anthony C; Scorsone, Kathleen A; Westbrook, Thomas F; Wong, Kwok-Kin; Elledge, Stephen J

2018-04-05

Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes regulate proliferation, with most performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in somatic copy number changes (SCNAs) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue-type-specific genetic network architectures underlie SCNA and driver selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive insights about the genetic network architecture of aneuploidy in tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-11-01

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

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.

Detection of Unexpected High Correlations between Balance Calibration Loads and Load Residuals

NASA Technical Reports Server (NTRS)

Ulbrich, N.; Volden, T.

2014-01-01

An algorithm was developed for the assessment of strain-gage balance calibration data that makes it possible to systematically investigate potential sources of unexpected high correlations between calibration load residuals and applied calibration loads. The algorithm investigates correlations on a load series by load series basis. The linear correlation coefficient is used to quantify the correlations. It is computed for all possible pairs of calibration load residuals and applied calibration loads that can be constructed for the given balance calibration data set. An unexpected high correlation between a load residual and a load is detected if three conditions are met: (i) the absolute value of the correlation coefficient of a residual/load pair exceeds 0.95; (ii) the maximum of the absolute values of the residuals of a load series exceeds 0.25 % of the load capacity; (iii) the load component of the load series is intentionally applied. Data from a baseline calibration of a six-component force balance is used to illustrate the application of the detection algorithm to a real-world data set. This analysis also showed that the detection algorithm can identify load alignment errors as long as repeat load series are contained in the balance calibration data set that do not suffer from load alignment problems.

Dealing With Unexpected Events on the Flight Deck: A Conceptual Model of Startle and Surprise.

PubMed

Landman, Annemarie; Groen, Eric L; van Paassen, M M René; Bronkhorst, Adelbert W; Mulder, Max

2017-12-01

A conceptual model is proposed in order to explain pilot performance in surprising and startling situations. Today's debate around loss of control following in-flight events and the implementation of upset prevention and recovery training has highlighted the importance of pilots' ability to deal with unexpected events. Unexpected events, such as technical malfunctions or automation surprises, potentially induce a "startle factor" that may significantly impair performance. Literature on surprise, startle, resilience, and decision making is reviewed, and findings are combined into a conceptual model. A number of recent flight incident and accident cases are then used to illustrate elements of the model. Pilot perception and actions are conceptualized as being guided by "frames," or mental knowledge structures that were previously learned. Performance issues in unexpected situations can often be traced back to insufficient adaptation of one's frame to the situation. It is argued that such sensemaking or reframing processes are especially vulnerable to issues caused by startle or acute stress. Interventions should focus on (a) increasing the supply and quality of pilot frames (e.g., though practicing a variety of situations), (b) increasing pilot reframing skills (e.g., through the use of unpredictability in training scenarios), and (c) improving pilot metacognitive skills, so that inappropriate automatic responses to startle and surprise can be avoided. The model can be used to explain pilot behavior in accident cases, to design experiments and training simulations, to teach pilots metacognitive skills, and to identify intervention methods.

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS Prohibitions on...

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

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

PubMed

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

2016-09-06

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

77 FR 42947 - Unexpected Urgent Refugee and Migration Needs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

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

Toward identifying specification requirements for digital bone-anchored prosthesis design incorporating substructure fabrication: a pilot study.

PubMed

Eggbeer, Dominic; Bibb, Richard; Evans, Peter

2006-01-01

This paper is the first in a series that aims to identify the specification requirements for advanced digital technologies that may be used to design and fabricate complex, soft tissue facial prostheses. Following a review of previously reported techniques, appropriate and currently available technologies were selected and applied in a pilot study. This study uses a range of optical surface scanning, computerized tomography, computer-aided design, and rapid prototyping technologies to capture, design, and fabricate a bone-anchored auricular prosthesis, including the retentive components. The techniques are assessed in terms of their effectiveness, and the results are used to identify future research and specification requirements to direct developments. The case study identifies that while digital technologies may be used to design implant-retained facial prostheses, many limitations need to be addressed to make the techniques clinically viable. It also identifies the need to develop a more robust specification that covers areas such as resolution, accuracy, materials, and design, against which potential technologies may be assessed. There is a need to develop a specification against which potential technologies may be assessed for their suitability in soft tissue facial prosthetics. The specification will be developed using further experimental research studies.

Trip-specific training enhances recovery after large postural disturbances for which there is NO expectation.

PubMed

Oludare, Simisola O; Pater, Mackenzie L; Rosenblatt, Noah J; Grabiner, Mark D

2018-03-01

Informed consent usually provides foreknowledge of experimental methods that can potentially increase expectation of stimuli and, therefore, influence the response. We determined the effects of increased expectation and trip-specific training on the recovery response following a treadmill-delivered, trip-specific disturbance. To deliver unexpected disturbances, subjects were deceived during the informed consent process. The primary hypothesis was that the recovery response following an expected postural disturbance would be characterized by trunk kinematics that have been shown to decrease the likelihood of a fall, compared to following an unexpected postural disturbance. We further hypothesized that following an unexpected postural disturbance, the recovery response of the subjects who had completed a trip-specific training protocol would be more biomechanically favorable to recovery compared to those of subjects who had not received the training. Young adults were randomized into Untrained or Trained groups. During the informed consent process, the purpose of the study was explained to subjects in both groups as being to determine the effect of trip-specific training on postural sway while performing an attention-demanding task. Untrained subjects completed two trials during which they minimized their postural sway. During the second trial, an unexpected disturbance was delivered while they performed the attention-demanding task. Trained subjects performed a pre-training postural sway trial, followed by the delivery of a series of expected, training disturbances. Finally, an unexpected disturbance was delivered while they minimized postural sway and performed the attention-demanding task. Expectation significantly improved trunk kinematics (p < .05). In addition, participation in the trip-specific training protocol following the unexpected disturbance the trunk kinematics of the Trained subjects were more biomechanically favorable to recovery than those of

PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors

PubMed Central

Gros, Alena; Robbins, Paul F.; Yao, Xin; Li, Yong F.; Turcotte, Simon; Tran, Eric; Wunderlich, John R.; Mixon, Arnold; Farid, Shawn; Dudley, Mark E.; Hanada, Ken-ichi; Almeida, Jorge R.; Darko, Sam; Douek, Daniel C.; Yang, James C.; Rosenberg, Steven A.

2014-01-01

Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression of metastatic melanoma; however, TILs are a heterogeneous population, and there are no effective markers to specifically identify and select the repertoire of tumor-reactive and mutation-specific CD8+ lymphocytes. The lack of biomarkers limits the ability to study these cells and develop strategies to enhance clinical efficacy and extend this therapy to other malignancies. Here, we evaluated unique phenotypic traits of CD8+ TILs and TCR β chain (TCRβ) clonotypic frequency in melanoma tumors to identify patient-specific repertoires of tumor-reactive CD8+ lymphocytes. In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8+ TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8+ lymphocytes, whereas only a fraction of the tumor-reactive population expressed the costimulatory receptor 4-1BB (also known as CD137). TCRβ deep sequencing revealed oligoclonal expansion of specific TCRβ clonotypes in CD8+PD-1+ compared with CD8+PD-1– TIL populations. Furthermore, the most highly expanded TCRβ clonotypes in the CD8+ and the CD8+PD-1+ populations recognized the autologous tumor and included clonotypes targeting mutated antigens. Thus, in addition to the well-documented negative regulatory role of PD-1 in T cells, our findings demonstrate that PD-1 expression on CD8+ TILs also accurately identifies the repertoire of clonally expanded tumor-reactive cells and reveal a dual importance of PD-1 expression in the tumor microenvironment. PMID:24667641

Robust passive dynamics of the musculoskeletal system compensate for unexpected surface changes during human hopping

PubMed Central

van der Krogt, Marjolein M.; de Graaf, Wendy W.; Farley, Claire T.; Moritz, Chet T.; Richard Casius, L. J.; Bobbert, Maarten F.

2009-01-01

When human hoppers are surprised by a change in surface stiffness, they adapt almost instantly by changing leg stiffness, implying that neural feedback is not necessary. The goal of this simulation study was first to investigate whether leg stiffness can change without neural control adjustment when landing on an unexpected hard or unexpected compliant (soft) surface, and second to determine what underlying mechanisms are responsible for this change in leg stiffness. The muscle stimulation pattern of a forward dynamic musculoskeletal model was optimized to make the model match experimental hopping kinematics on hard and soft surfaces. Next, only surface stiffness was changed to determine how the mechanical interaction of the musculoskeletal model with the unexpected surface affected leg stiffness. It was found that leg stiffness adapted passively to both unexpected surfaces. On the unexpected hard surface, leg stiffness was lower than on the soft surface, resulting in close-to-normal center of mass displacement. This reduction in leg stiffness was a result of reduced joint stiffness caused by lower effective muscle stiffness. Faster flexion of the joints due to the interaction with the hard surface led to larger changes in muscle length, while the prescribed increase in active state and resulting muscle force remained nearly constant in time. Opposite effects were found on the unexpected soft surface, demonstrating the bidirectional stabilizing properties of passive dynamics. These passive adaptations to unexpected surfaces may be critical when negotiating disturbances during locomotion across variable terrain. PMID:19589956

The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARγ in Xenopus tropicalis

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

Zhu, Jingmin

2017-01-01

The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show teratogenicity and, unexpectedly, induce similar malformations in Xenopus tropicalis embryos. In the present study, we exposed X. tropicalis embryos to UVI3003 in seven specific developmental windows and identified changes in gene expression. We further measured the ability of UVI3003 to activate Xenopus RXRα (xRXRα) and PPARγ (xPPARγ) in vitro and in vivo. We found that UVI3003 activated xPPARγ either in Cos7 cells (in vitro) or Xenopus embryos (in vivo). UVI3003 did not significantly activate human or mouse PPARγ in vitro; therefore, the activation of Xenopus PPARγ by UVI3003more » is novel. The ability of UVI3003 to activate xPPARγ explains why UVI3003 and TPT yield similar phenotypes in Xenopus embryos. Our results indicate that activating PPARγ leads to teratogenic effects in Xenopus embryos. More generally, we infer that chemicals known to specifically modulate mammalian nuclear hormone receptors cannot be assumed to have the same activity in non-mammalian species, such as Xenopus. Rather they must be tested for activity and specificity on receptors of the species in question to avoid making inappropriate conclusions. - Highlights: • UVI3003 is a RXRs antagonist and shows teratogenicity to Xenopus embryos. • UVI3003 activated xPPARγ either in Cos7 cells or Xenopus embryos. • UVI3003 did not activate human or mouse PPARγ in Cos7 cells. • Activating PPARγ leads to teratogenic effects in Xenopus embryos.« less

Identifying content for the glaucoma-specific item bank to measure quality-of-life parameters.

PubMed

Khadka, Jyoti; McAlinden, Colm; Craig, Jamie E; Fenwick, Eva K; Lamoureux, Ecosse L; Pesudovs, Konrad

2015-01-01

Patient-reported outcomes (PROs) have become essential clinical trial end points. However, a comprehensive, multidimensional, patient-relevant, and precise glaucoma-specific PRO instrument is not available. Therefore, the purpose of this study was to identify content for a new, glaucoma-specific, quality-of-life (QOL) item bank. Content identification was undertaken in 5 phases: (1) identification of extant items in glaucoma-specific instruments and the qualitative literature; (2) focus groups and interviews with glaucoma patients; (3) item classification and selection; (4) expert review and revision of items; and (5) cognitive interviews with patients. A total of 737 unique items (extant items from PRO instruments, 247; qualitative articles, 14 items; focus groups and semistructured interviews, 476 items) were identified. These items were classified into 10 QOL domains. Four criteria (item redundancy, item inconsistent with domain definition, item content too narrow to have wider applicability, and item clarity) were used to remove and refine the items. After the cognitive interviews, the final minimally representative item set had a total of 342 unique items belonging to 10 domains: activity limitation (88), mobility (20), visual symptoms (19), ocular surface symptoms (22), general symptoms (15), convenience (39), health concerns (45), emotional well-being (49), social issues (23), and economic issues (22). The systematic content identification process identified 10 QOL domains, which were important to patients with glaucoma. The majority of the items were identified from the patient-specific focus groups and semistructured interviews suggesting that the existing PRO instruments do not adequately address QOL issues relevant to individuals with glaucoma.

A brittle star-like robot capable of immediately adapting to unexpected physical damage.

PubMed

Kano, Takeshi; Sato, Eiki; Ono, Tatsuya; Aonuma, Hitoshi; Matsuzaka, Yoshiya; Ishiguro, Akio

2017-12-01

A major challenge in robotic design is enabling robots to immediately adapt to unexpected physical damage. However, conventional robots require considerable time (more than several tens of seconds) for adaptation because the process entails high computational costs. To overcome this problem, we focus on a brittle star-a primitive creature with expendable body parts. Brittle stars, most of which have five flexible arms, occasionally lose some of them and promptly coordinate the remaining arms to escape from predators. We adopted a synthetic approach to elucidate the essential mechanism underlying this resilient locomotion. Specifically, based on behavioural experiments involving brittle stars whose arms were amputated in various ways, we inferred the decentralized control mechanism that self-coordinates the arm motions by constructing a simple mathematical model. We implemented this mechanism in a brittle star-like robot and demonstrated that it adapts to unexpected physical damage within a few seconds by automatically coordinating its undamaged arms similar to brittle stars. Through the above-mentioned process, we found that physical interaction between arms plays an essential role for the resilient inter-arm coordination of brittle stars. This finding will help develop resilient robots that can work in inhospitable environments. Further, it provides insights into the essential mechanism of resilient coordinated motions characteristic of animal locomotion.

A brittle star-like robot capable of immediately adapting to unexpected physical damage

PubMed Central

Sato, Eiki; Ono, Tatsuya; Aonuma, Hitoshi; Matsuzaka, Yoshiya; Ishiguro, Akio

2017-01-01

A major challenge in robotic design is enabling robots to immediately adapt to unexpected physical damage. However, conventional robots require considerable time (more than several tens of seconds) for adaptation because the process entails high computational costs. To overcome this problem, we focus on a brittle star—a primitive creature with expendable body parts. Brittle stars, most of which have five flexible arms, occasionally lose some of them and promptly coordinate the remaining arms to escape from predators. We adopted a synthetic approach to elucidate the essential mechanism underlying this resilient locomotion. Specifically, based on behavioural experiments involving brittle stars whose arms were amputated in various ways, we inferred the decentralized control mechanism that self-coordinates the arm motions by constructing a simple mathematical model. We implemented this mechanism in a brittle star-like robot and demonstrated that it adapts to unexpected physical damage within a few seconds by automatically coordinating its undamaged arms similar to brittle stars. Through the above-mentioned process, we found that physical interaction between arms plays an essential role for the resilient inter-arm coordination of brittle stars. This finding will help develop resilient robots that can work in inhospitable environments. Further, it provides insights into the essential mechanism of resilient coordinated motions characteristic of animal locomotion. PMID:29308250

3 CFR - Unexpected Urgent Refugee and Migration Needs Resulting from Flooding in Pakistan

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... Determination No. 2010-14 of September 3, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from... the Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

3 CFR - Unexpected Urgent Refugee and Migration Needs Resulting from Violence in Kyrgyzstan

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... Determination No. 2010-12 of August 26, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from... the Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

Some Unexpected Results Using Computer Algebra Systems.

ERIC Educational Resources Information Center

Alonso, Felix; Garcia, Alfonsa; Garcia, Francisco; Hoya, Sara; Rodriguez, Gerardo; de la Villa, Agustin

2001-01-01

Shows how teachers can often use unexpected outputs from Computer Algebra Systems (CAS) to reinforce concepts and to show students the importance of thinking about how they use the software and reflecting on their results. Presents different examples where DERIVE, MAPLE, or Mathematica does not work as expected and suggests how to use them as a…

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.

Dealing With Unexpected Events on the Flight Deck: A Conceptual Model of Startle and Surprise

PubMed Central

Landman, Annemarie; Groen, Eric L.; van Paassen, M. M. (René); Bronkhorst, Adelbert W.; Mulder, Max

2017-01-01

Objective: A conceptual model is proposed in order to explain pilot performance in surprising and startling situations. Background: Today’s debate around loss of control following in-flight events and the implementation of upset prevention and recovery training has highlighted the importance of pilots’ ability to deal with unexpected events. Unexpected events, such as technical malfunctions or automation surprises, potentially induce a “startle factor” that may significantly impair performance. Method: Literature on surprise, startle, resilience, and decision making is reviewed, and findings are combined into a conceptual model. A number of recent flight incident and accident cases are then used to illustrate elements of the model. Results: Pilot perception and actions are conceptualized as being guided by “frames,” or mental knowledge structures that were previously learned. Performance issues in unexpected situations can often be traced back to insufficient adaptation of one’s frame to the situation. It is argued that such sensemaking or reframing processes are especially vulnerable to issues caused by startle or acute stress. Conclusion: Interventions should focus on (a) increasing the supply and quality of pilot frames (e.g., though practicing a variety of situations), (b) increasing pilot reframing skills (e.g., through the use of unpredictability in training scenarios), and (c) improving pilot metacognitive skills, so that inappropriate automatic responses to startle and surprise can be avoided. Application: The model can be used to explain pilot behavior in accident cases, to design experiments and training simulations, to teach pilots metacognitive skills, and to identify intervention methods. PMID:28777917

Identifying States along the Hematopoietic Stem Cell Differentiation Hierarchy with Single Cell Specificity via Raman Spectroscopy.

PubMed

Ilin, Yelena; Choi, Ji Sun; Harley, Brendan A C; Kraft, Mary L

2015-11-17

A major challenge for expanding specific types of hematopoietic cells ex vivo for the treatment of blood cell pathologies is identifying the combinations of cellular and matrix cues that direct hematopoietic stem cells (HSC) to self-renew or differentiate into cell populations ex vivo. Microscale screening platforms enable minimizing the number of rare HSCs required to screen the effects of numerous cues on HSC fate decisions. These platforms create a strong demand for label-free methods that accurately identify the fate decisions of individual hematopoietic cells at specific locations on the platform. We demonstrate the capacity to identify discrete cells along the HSC differentiation hierarchy via multivariate analysis of Raman spectra. Notably, cell state identification is accurate for individual cells and independent of the biophysical properties of the functionalized polyacrylamide gels upon which these cells are cultured. We report partial least-squares discriminant analysis (PLS-DA) models of single cell Raman spectra enable identifying four dissimilar hematopoietic cell populations across the HSC lineage specification. Successful discrimination was obtained for a population enriched for long-term repopulating HSCs (LT-HSCs) versus their more differentiated progeny, including closely related short-term repopulating HSCs (ST-HSCs) and fully differentiated lymphoid (B cells) and myeloid (granulocytes) cells. The lineage-specific differentiation states of cells from these four subpopulations were accurately identified independent of the stiffness of the underlying biomaterial substrate, indicating subtle spectral variations that discriminated these populations were not masked by features from the culture substrate. This approach enables identifying the lineage-specific differentiation stages of hematopoietic cells on biomaterial substrates of differing composition and may facilitate correlating hematopoietic cell fate decisions with the extrinsic cues that

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.

Mining the Immune Cell Proteome to Identify Ovarian Cancer-Specific Biomarkers

DTIC Science & Technology

2012-03-01

data and are in the process of identifying gene signatures that can be used as biomarkers for the identification of ovarian cancer-specific biomarkers...groups. The groups showed significant difference in age as well as gestational age, which is expected when considering the disease process . Isolation of...MUC4 in intracellular signaling.32 Oligosaccharides attached to the extracellular domains of mucins have also been shown to interact with different

Comparative Transcriptional Profiling of the Axolotl Limb Identifies a Tripartite Regeneration-Specific Gene Program

PubMed Central

Knapp, Dunja; Schulz, Herbert; Rascon, Cynthia Alexander; Volkmer, Michael; Scholz, Juliane; Nacu, Eugen; Le, Mu; Novozhilov, Sergey; Tazaki, Akira; Protze, Stephanie; Jacob, Tina; Hubner, Norbert; Habermann, Bianca; Tanaka, Elly M.

2013-01-01

Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression – early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation. PMID:23658691

Hydrograph Separations can Identify Contaminant-Specific Pathways for Conservation Targeting in a Tile-Drained Watershed

USDA-ARS?s Scientific Manuscript database

Water quality issues continue to vex agriculture. Understanding contaminant-specific pathways could help clarify effective water quality management strategies in watersheds. Hypothesis: If conducted at nested scales, hydrograph separation techniques can identify contaminant-specific pathways that co...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire Presidential Documents Other Presidential Documents Presidential Determination No. 2011-7 of March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire Memorandum for the Secretary of State By the...

Thalamic regulation of sucrose-seeking during unexpected reward omission

PubMed Central

Do-Monte, Fabricio H.; Minier-Toribio, Angélica; Quiñones-Laracuente, Kelvin; Medina-Colón, Estefanía M.; Quirk, Gregory J.

2017-01-01

SUMMARY The paraventricular nucleus of the thalamus (PVT) is thought to regulate behavioral responses under emotionally arousing conditions. Reward-associated cues activate PVT neurons, however, the specific PVT efferents regulating reward-seeking remain elusive. Using a cued sucrose-seeking task, we manipulated PVT activity under two emotionally distinct conditions: 1) when reward was available during the cue as expected, or 2) when reward was unexpectedly omitted during the cue. Pharmacological inactivation of the anterior PVT (aPVT), but not the posterior PVT, increased sucrose-seeking only when reward was omitted. Consistent with this, photoactivation of aPVT neurons abolished sucrose-seeking, and the firing of aPVT neurons differentiated reward availability. Photoinhibition of aPVT projections to the nucleus accumbens or to the amygdala increased or decreased, respectively, sucrose-seeking only when reward was omitted. Our findings suggest that PVT bidirectionally modulates sucrose-seeking under the negative (frustrative) conditions of reward omission. PMID:28426970

Characteristics of the Unexpected Message Queue of MPI applications

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

Keller, Rainer; Graham, Richard L

2010-01-01

High Performance Computing systems are used on a regular basis to run a myriad of application codes, yet a surprising dearth of information exists with respect to communications characteristics. Even less information is available on the low-level communication libraries, such as the length of MPI Unexpected Message Queues (UMQs) and the length of time such messages spend in these queues. Such information is vital to developing appropriate strategies for handling such data at the library and system level. In this paper we present data on the communication characteristics of three applications GTC, LSMS, and S3D. We present data on themore » size of their UMQ, the time spend searching the UMQ and the length of time such messages spend in these queues. We find that for the particular inputs used, these applications have widely varying characteristics with regard to UMQ length and show patterns for specific applications which persist over various scales.« less

42 CFR 493.861 - Standard; Unexpected antibody detection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Unexpected antibody detection. 493.861 Section 493.861 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... for Laboratories Performing Tests of Moderate Complexity (including the Subcategory), High Complexity...

42 CFR 493.861 - Standard; Unexpected antibody detection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Standard; Unexpected antibody detection. 493.861 Section 493.861 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... for Laboratories Performing Tests of Moderate Complexity (including the Subcategory), High Complexity...

Searching for hidden unexpected features in the SnIa data

NASA Astrophysics Data System (ADS)

Shafieloo, A.; Perivolaropoulos, L.

2010-06-01

It is known that κ2 statistic and likelihood analysis may not be sensitive to the all features of the data. Despite of the fact that by using κ2 statistic we can measure the overall goodness of fit for a model confronted to a data set, some specific features of the data can stay undetectable. For instance, it has been pointed out that there is an unexpected brightness of the SnIa data at z > 1 in the Union compilation. We quantify this statement by constructing a new statistic, called Binned Normalized Difference (BND) statistic, which is applicable directly on the Type Ia Supernova (SnIa) distance moduli. This statistic is designed to pick up systematic brightness trends of SnIa data points with respect to a best fit cosmological model at high redshifts. According to this statistic there are 2.2%, 5.3% and 12.6% consistency between the Gold06, Union08 and Constitution09 data and spatially flat ΛCDM model when the real data is compared with many realizations of the simulated monte carlo datasets. The corresponding realization probability in the context of a (w0,w1) = (-1.4,2) model is more than 30% for all mentioned datasets indicating a much better consistency for this model with respect to the BND statistic. The unexpected high z brightness of SnIa can be interpreted either as a trend towards more deceleration at high z than expected in the context of ΛCDM or as a statistical fluctuation or finally as a systematic effect perhaps due to a mild SnIa evolution at high z.

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

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

Unexpected Relationships and Inbreeding in HapMap Phase III Populations

PubMed Central

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

2012-01-01

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

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2010 CFR

2010-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene production wastes. (a) Effective December 19, 1994, the wastes specified in 40...

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].

The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity.

PubMed

Boglev, Yeliz; Wilanowski, Tomasz; Caddy, Jacinta; Parekh, Vishwas; Auden, Alana; Darido, Charbel; Hislop, Nikki R; Cangkrama, Michael; Ting, Stephen B; Jane, Stephen M

2011-01-15

The Grainy head-like 3 (Grhl3) gene encodes a transcription factor that plays essential roles in epidermal morphogenesis during embryonic development, with deficient mice exhibiting failed skin barrier formation, defective wound repair, and loss of eyelid fusion. Despite sharing significant sequence homology, overlapping expression patterns, and an identical core consensus DNA binding site, the other members of the Grhl family (Grhl1 and -2) fail to compensate for the loss of Grhl3 in these processes. Here, we have employed diverse genetic models, coupled with biochemical studies, to define the inter-relationships of the Grhl factors in epidermal development. We show that Grhl1 and Grhl3 have evolved complete functional independence, as evidenced by a lack of genetic interactions in embryos carrying combinations of targeted alleles of these genes. In contrast, compound heterozygous Grhl2/Grhl3 embryos displayed failed wound repair, and loss of a single Grhl2 allele in Grhl3-null embryos results in fully penetrant eyes open at birth. Expression of Grhl2 from the Grhl3 locus in homozygous knock-in mice corrects the wound repair defect, but these embryos still display a complete failure of skin barrier formation. This functional dissociation is due to unexpected differences in target gene specificity, as both GRHL2 and GRHL3 bind to and regulate expression of the wound repair gene Rho GEF 19, but regulation of the barrier forming gene, Transglutaminase 1 (TGase1), is unique to GRHL3. Our findings define the mechanisms underpinning the unique and cooperative roles of the Grhl genes in epidermal development. Copyright © 2010 Elsevier Inc. All rights reserved.

Homozygous and compound heterozygous mutations in the FBN1 gene: unexpected findings in molecular diagnosis of Marfan syndrome.

PubMed

Arnaud, Pauline; Hanna, Nadine; Aubart, Mélodie; Leheup, Bruno; Dupuis-Girod, Sophie; Naudion, Sophie; Lacombe, Didier; Milleron, Olivier; Odent, Sylvie; Faivre, Laurence; Bal, Laurence; Edouard, Thomas; Collod-Beroud, Gwenaëlle; Langeois, Maud; Spentchian, Myrtille; Gouya, Laurent; Jondeau, Guillaume; Boileau, Catherine

2017-02-01

Marfan syndrome (MFS) is an autosomal-dominant connective tissue disorder usually associated with heterozygous mutations in the gene encoding fibrillin-1 (FBN1). Homozygous and compound heterozygous cases are rare events and have been associated with a clinical severe presentation. Report unexpected findings of homozygosity and compound heterozygosity in the course of molecular diagnosis of heterozygous MFS and compare the findings with published cases. In the context of molecular diagnosis of heterozygous MFS, systematic sequencing of the FBN1 gene was performed in 2500 probands referred nationwide. 1400 probands carried a heterozygous mutation in this gene. Unexpectedly, among them four homozygous cases (0.29%) and five compound heterozygous cases (0.36%) were identified (total: 0.64%). Interestingly, none of these cases carried two premature termination codon mutations in the FBN1 gene. Clinical features for these carriers and their families were gathered and compared. There was a large spectrum of severity of the disease in probands carrying two mutated FBN1 alleles, but none of them presented extremely severe manifestations of MFS in any system compared with carriers of only one mutated FBN1 allele. This observation is not in line with the severe clinical features reported in the literature for four homozygous and three compound heterozygous probands. Homozygotes and compound heterozygotes were unexpectedly identified in the course of molecular diagnosis of MFS. Contrary to previous reports, the presence of two mutated alleles was not associated with severe forms of MFS. Although homozygosity and compound heterozygosity are rarely found in molecular diagnosis, they should not be overlooked, especially among consanguineous families. However, no predictive evaluation of severity should be provided. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hepatic Hemangioendothelioma Presenting as Sudden Unexpected Death in Infancy: A Case Report

PubMed Central

Dempers, Johan; Wadee, Shabbir Ahmed; Boyd, Theonia; Wright, Colleen; OdendaaL, Hein J; Sens, Mary Ann

2014-01-01

The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy, death scene investigation and review of medical history to exclude known causes of death. Death from occult neoplastic disease in infancy is extremely rare but is within the broad differential of SIDS. We report the sudden and unexpected death of a one-month-old infant from a hepatic (infantile) hemangioendothelioma. The physiologic mechanism of death was likely cardiac failure induced by the circulatory demands of this large vascular tumor and respiratory compromise from diaphragmatic thoracic incursion. The clinical progression and pathology of these relatively common tumors of infant livers are extremely variable. This case dramatically illustrates the potential for fatal outcome of this tumor, as well as the need for the autopsy to determine the cause of sudden and unexpected death in an infant PMID:20465426

Signatures from Tissue-specific MPSS Libraries Identify Transcripts Preferentially Expressed in the Mouse Inner Ear

PubMed Central

Peters, Linda M.; Belyantseva, Inna A.; Lagziel, Ayala; Battey, James F.; Friedman, Thomas B.; Morell, Robert J.

2007-01-01

Specialization in cell function and morphology is influenced by the differential expression of mRNAs, many of which are expressed at low abundance and restricted to certain cell types. Detecting such transcripts in cDNA libraries may require sequencing millions of clones. Massively parallel signature sequencing (MPSS) is well-suited for identifying transcripts that are expressed in discrete cell types and in low abundance. We have made MPSS libraries from microdissections of three inner ear tissues. By comparing these MPSS libraries to those of 87 other tissues included in the Mouse Reference Transcriptome (MRT) online resource, we have identified genes that are highly enriched in, or specific to, the inner ear. We show by RT-PCR and in situ hybridization that signatures unique to the inner ear libraries identify transcripts with highly specific cell-type localizations. These transcripts serve to illustrate the utility of a resource that is available to the research community. Utilization of these resources will increase the number of known transcription units and expand our knowledge of the tissue-specific regulation of the transcriptome. PMID:17049805

High-Throughput Screening to Identify Regulators of Meiosis-Specific Gene Expression in Saccharomyces cerevisiae.

PubMed

Kassir, Yona

2017-01-01

Meiosis and gamete formation are processes that are essential for sexual reproduction in all eukaryotic organisms. Multiple intracellular and extracellular signals feed into pathways that converge on transcription factors that induce the expression of meiosis-specific genes. Once triggered the meiosis-specific gene expression program proceeds in a cascade that drives progress through the events of meiosis and gamete formation. Meiosis-specific gene expression is tightly controlled by a balance of positive and negative regulatory factors that respond to a plethora of signaling pathways. The budding yeast Saccharomyces cerevisiae has proven to be an outstanding model for the dissection of gametogenesis owing to the sophisticated genetic manipulations that can be performed with the cells. It is possible to use a variety selection and screening methods to identify genes and their functions. High-throughput screening technology has been developed to allow an array of all viable yeast gene deletion mutants to be screened for phenotypes and for regulators of gene expression. This chapter describes a protocol that has been used to screen a library of homozygous diploid yeast deletion strains to identify regulators of the meiosis-specific IME1 gene.

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

PubMed

Swan, Garrett; Wyble, Brad; Chen, Hui

2017-07-01

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

A computational approach to identify cellular heterogeneity and tissue-specific gene regulatory networks.

PubMed

Jambusaria, Ankit; Klomp, Jeff; Hong, Zhigang; Rafii, Shahin; Dai, Yang; Malik, Asrar B; Rehman, Jalees

2018-06-07

The heterogeneity of cells across tissue types represents a major challenge for studying biological mechanisms as well as for therapeutic targeting of distinct tissues. Computational prediction of tissue-specific gene regulatory networks may provide important insights into the mechanisms underlying the cellular heterogeneity of cells in distinct organs and tissues. Using three pathway analysis techniques, gene set enrichment analysis (GSEA), parametric analysis of gene set enrichment (PGSEA), alongside our novel model (HeteroPath), which assesses heterogeneously upregulated and downregulated genes within the context of pathways, we generated distinct tissue-specific gene regulatory networks. We analyzed gene expression data derived from freshly isolated heart, brain, and lung endothelial cells and populations of neurons in the hippocampus, cingulate cortex, and amygdala. In both datasets, we found that HeteroPath segregated the distinct cellular populations by identifying regulatory pathways that were not identified by GSEA or PGSEA. Using simulated datasets, HeteroPath demonstrated robustness that was comparable to what was seen using existing gene set enrichment methods. Furthermore, we generated tissue-specific gene regulatory networks involved in vascular heterogeneity and neuronal heterogeneity by performing motif enrichment of the heterogeneous genes identified by HeteroPath and linking the enriched motifs to regulatory transcription factors in the ENCODE database. HeteroPath assesses contextual bidirectional gene expression within pathways and thus allows for transcriptomic assessment of cellular heterogeneity. Unraveling tissue-specific heterogeneity of gene expression can lead to a better understanding of the molecular underpinnings of tissue-specific phenotypes.

Encountering unexpected difficult airway: relationship with the intubation difficulty scale

PubMed Central

Koh, Wonuk; Kim, Hajung; Kim, Kyongsun; Ro, Young-Jin

2016-01-01

Background An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. Methods We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. Results For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack-Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. Conclusions Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation. PMID:27274369

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

PubMed

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

2014-07-01

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

A Coupling Analysis Approach to Capture Unexpected Behaviors in Ares 1

NASA Astrophysics Data System (ADS)

Kis, David

Coupling of physics in large-scale complex engineering systems must be correctly accounted for during the systems engineering process. Preliminary corrections ensure no unanticipated behaviors arise during operation. Structural vibration of large segmented solid rocket motors, known as thrust oscillation, is a well-documented problem that can effect solid rocket motors in adverse ways. Within the Ares 1 rocket, unexpected vibrations deemed potentially harmful to future crew were recorded during late stage flight that propagated from the engine chamber to the Orion crew module. This research proposes the use of a coupling strength analysis during the design and development phase to identify potential unanticipated behaviors such as thrust oscillation. Once these behaviors and couplings are identified then a value function, based on research in Value Driven Design, is proposed to evaluate mitigation strategies and their impact on system value. The results from this study showcase a strong coupling interaction from structural displacement back onto the fluid flow of the Ares 1 that was previously deemed inconsequential. These findings show that the use of a coupling strength analysis can aid engineers and managers in identifying unanticipated behaviors and then rank order their importance based on the impact they have on value.

Empirical Methods for Identifying Specific Peptide-protein Interactions for Smart Reagent Development

DTIC Science & Technology

2012-09-01

orientated immobilization of proteins,” Biotechnology Progress, 22(2), 401-405 ( 2006 ). [26] J. M. Kogot, D. A. Sarkes , I. Val-Addo et al...Empirical Methods for Identifying Specific Peptide-protein Interactions for Smart Reagent Development by Joshua M. Kogot, Deborah A. Sarkes ...Peptide-protein Interactions for Smart Reagent Development Joshua M. Kogot, Deborah A. Sarkes , Dimitra N. Stratis-Cullum, and Paul M

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…

Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome

PubMed Central

Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O’Connor, Timothy D.; Abecasis, Gonçalo R.; Wojcik, Genevieve L; Gignoux, Christopher R.; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E.; Bustamante, Carlos; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Qin, Zhaohui S.; Preethi Boorgula, Meher; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Ruczinski, Ingo; Scott, Alan F.; Taub, Margaret A.; Vergara, Candelaria; Levin, Albert M.; Padhukasahasram, Badri; Williams, L. Keoki; Dunston, Georgia M.; Faruque, Mezbah U.; Gietzen, Kimberly; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-Youn A.; Kumar, Rajesh; Schleimer, Robert; De La Vega, Francisco M.; Shringarpure, Suyash S.; Musharoff, Shaila; Burchard, Esteban G.; Eng, Celeste; Hernandez, Ryan D.; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Maul, Pissamai; Maul, Trevor; Watson, Harold; Ilma Araujo, Maria; Riccio Oliveira, Ricardo; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Francisco Herrera-Paz, Edwin; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Marina Vasquez, Olga; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria

2017-01-01

A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an ‘African Diaspora Power Chip’ (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry. PMID:28429804

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa Presidential Documents Other Presidential Documents Presidential Determination No. 2011-12 of August 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa Memorandum for the Secretary of State By...

Comparative genome analysis identifies novel nucleic acid diagnostic targets for use in the specific detection of Haemophilus influenzae.

PubMed

Coughlan, Helena; Reddington, Kate; Tuite, Nina; Boo, Teck Wee; Cormican, Martin; Barrett, Louise; Smith, Terry J; Clancy, Eoin; Barry, Thomas

2015-10-01

Haemophilus influenzae is recognised as an important human pathogen associated with invasive infections, including bloodstream infection and meningitis. Currently used molecular-based diagnostic assays lack specificity in correctly detecting and identifying H. influenzae. As such, there is a need to develop novel diagnostic assays for the specific identification of H. influenzae. Whole genome comparative analysis was performed to identify putative diagnostic targets, which are unique in nucleotide sequence to H. influenzae. From this analysis, we identified 2H. influenzae putative diagnostic targets, phoB and pstA, for use in real-time PCR diagnostic assays. Real-time PCR diagnostic assays using these targets were designed and optimised to specifically detect and identify all 55H. influenzae strains tested. These novel rapid assays can be applied to the specific detection and identification of H. influenzae for use in epidemiological studies and could also enable improved monitoring of invasive disease caused by these bacteria. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2012-08-29

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

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2014 CFR

2014-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2013 CFR

2013-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2012 CFR

2012-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2011 CFR

2011-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

Mumps resurgences in the United States: A historical perspective on unexpected elements.

PubMed

Barskey, Albert E; Glasser, John W; LeBaron, Charles W

2009-10-19

In 2006 the United States experienced the largest nationwide mumps epidemic in 20 years, primarily affecting college dormitory residents. Unexpected elements of the outbreak included very abrupt time course (75% of cases occurred within 90 days), geographic focality (85% of cases occurred in eight rural Midwestern states), rapid upward and downward shift in peak age-specific attack rate (5-9-year olds to 18-24-year olds, then back), and two-dose vaccine failure (63% of case-patients had received two doses). To construct a historical context in which to understand the recent outbreak, we reviewed US mumps surveillance data, vaccination coverage estimates, and relevant peer-reviewed literature for the period 1917-2008. Many of the unexpected features of the 2006 mumps outbreak had been reported several times previously in the US, e.g., the 1986-1987 mumps resurgence had extremely abrupt onset, rural geographic focality, and an upward-then-downward age shift. Evidence suggested recurrent mumps outbreak patterns were attributable to accumulation of susceptibles in dispersed situations where the risk of endemic disease exposure was low and were triggered when this susceptible population was brought together in crowded living conditions. The 2006 epidemic followed this pattern, with two unique variations: it was preceded by a period of very high vaccination rates and very low disease incidence and was characterized by two-dose failure rates among adults vaccinated in childhood. Data from the past 80 years suggest that preventing future mumps epidemics will depend on innovative measures to detect and eliminate build-up of susceptibles among highly vaccinated populations.

Autoantigen-specific B-cell depletion overcomes failed immune tolerance in type 1 diabetes.

PubMed

Henry, Rachel A; Kendall, Peggy L; Thomas, James W

2012-08-01

Eliminating autoantigen-specific B cells is an attractive alternative to global B-cell depletion for autoimmune disease treatment. To identify the potential for targeting a key autoimmune B-cell specificity in type 1 diabetes, insulin-binding B cells were tracked within a polyclonal repertoire using heavy chain B-cell receptor (BCR) transgenic (VH125Tg) mice. Insulin-specific B cells are rare in the periphery of nonautoimmune VH125Tg/C57BL/6 mice and WT/NOD autoimmune mice, whereas they clearly populate 1% of mature B-cell subsets in VH125Tg/NOD mice. Autoantigen upregulates CD86 in anti-insulin B cells, suggesting they are competent to interact with T cells. Endogenous insulin occupies anti-insulin BCR beginning with antigen commitment in bone marrow parenchyma, as identified by a second anti-insulin monoclonal antibody. Administration of this monoclonal antibody selectively eliminates insulin-reactive B cells in vivo and prevents disease in WT/NOD mice. Unexpectedly, developing B cells are less amenable to depletion, despite increased BCR sensitivity. These findings exemplify how a critical type 1 diabetes B-cell specificity escapes immune tolerance checkpoints. Disease liability is corrected by eliminating this B-cell specificity, providing proof of concept for a novel therapeutic approach for autoimmune disease.

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

DTIC Science & Technology

2010-05-01

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

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.

Do Unexpected Panic Attacks Occur Spontaneously?

PubMed Central

Meuret, Alicia E.; Rosenfield, David; Wilhelm, Frank H.; Zhou, Enlu; Conrad, Ansgar; Ritz, Thomas; Roth, Walton T.

2012-01-01

Background Spontaneous or unexpected panic attacks, per definition, occur out-of-the blue, in absence of cues or triggers. Accordingly, physiological arousal or instability should occur at the onset of or during the attack, but not preceding it. To test this hypothesisweexaminedif points of significant autonomic changes preceded the onset of spontaneous panic attacks. Methods Forty-three panic disorder patients underwent repeated 24-hour ambulatory monitoring. Thirteen naturally panic attacks were recorded during 1,960 hours of monitoring. Minute-by-minute epochs beginning 60 minutes before, and continuing to 10 minutes after, the onset of individual attacks were examined for respiration, heart rate, and skin conductance level. Measures were controlled for physical activity and vocalization, and compared to time matched control periods within the same person. Results Significant patterns of instability across a numberof autonomic and respiratory variables were detected as early as 47 minutes before panic onset. The final minutes prior to onset were dominated by respiratory changes, with significant decreases in tidal volume followed by abrupt PCO2 increases. Panic attack onset was characterized by heart rate and tidal volume increases and a drop in PCO2. Symptom report was consistent with these changes. Skin conductance levels were generally elevated in the hour before and duringthe attacks. Changes in the matched control periods were largely absent. Conclusions Significant autonomic irregularities preceded the onset of attacks that were reported as abrupt and unexpected. The findings invite reconsideration of the current diagnostic distinction betweenuncuedand cued panic attacks. PMID:21783179

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.

PubMed

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

2018-03-01

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

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins

PubMed Central

Turkington, Hannah L.; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin

2017-01-01

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

Opening the file drawer: Unexpected insights from a chytrid infection experiment.

PubMed

Byrne, Allison Q; Poorten, Thomas J; Voyles, Jamie; Willis, Craig K R; Rosenblum, Erica Bree

2018-01-01

Infection experiments are critical for understanding wildlife disease dynamics. Although infection experiments are typically designed to reduce complexity, disease outcomes still result from complex interactions between host, pathogen, and environmental factors. Cryptic variation across factors can lead to decreased repeatability of infection experiments within and between research groups and hinder research progress. Furthermore, studies with unexpected results are often relegated to the "file drawer" and potential insights gained from these experimental outcomes are lost. Here, we report unexpected results from an infection experiment studying the response of two differentially-susceptible but related frogs (American Bullfrog Rana catesbeiana and the Mountain yellow-legged frog Rana muscosa) to the amphibian-killing chytrid fungus (Batrachochytrium dendrobatidis, Bd). Despite well-documented differences in susceptibility between species, we found no evidence for antibody-mediated immune response and no Bd-related mortality in either species. Additionally, during the study, the sham-inoculated R. catesbeiana control group became unexpectedly Bd-positive. We used a custom genotyping assay to demonstrate that the aberrantly-infected R. catesbeiana carried a Bd genotype distinct from the inoculation genotype. Thus R. catesbeiana individuals were acquired with low-intensity infections that could not be detected with qPCR. In the Bd-inoculated R. catesbeiana treatment group, the inoculated genotype appeared to out-compete the cryptic infection. Thus, our results provide insight into Bd coinfection dynamics, a phenomenon that is increasingly relevant as different pathogen strains are moved around the globe. Our experiment highlights how unexpected experimental outcomes can serve as both cautionary tales and opportunities to explore unanswered research questions. We use our results as a case study to highlight common sources of anomalous results for infection experiments

Efficacy of ACL injury risk screening methods in identifying high-risk landing patterns during a sport-specific task.

PubMed

Fox, A S; Bonacci, J; McLean, S G; Saunders, N

2017-05-01

Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Satellite-based observations of unexpected coastal changes due to the Saemangeum Dyke construction, Korea.

PubMed

Lee, Yoon-Kyung; Ryu, Joo-Hyung; Choi, Jong-Kuk; Lee, Seok; Woo, Han-Jun

2015-08-15

Spatial and temporal changes around an area of conventional coastal engineering can be easily observed from field surveys because of the clear cause-and-effect observable in the before and after stages of the project. However, it is more difficult to determine environmental changes in the vicinity of tidal flats and coastal areas that are a considerable distance from the project. To identify any unexpected environmental impacts of the construction of Saemangeum Dyke in the area, we examined morphological changes identified by satellite-based observations through a field survey on Gomso Bay tidal flats (15km from Saemangeum Dyke), and changes in the suspended sediment distribution identified by satellite-based observations through a hydrodynamic analysis in the Saemangeum and Gomso coastal area. We argue that hydrodynamic changes due to conventional coastal engineering can affect the sedimentation pattern in the vicinity of tidal flats. We suggest that the environmental impact assessment conducted before a conventional coastal engineering project should include a larger area than is currently considered. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Experiences of Parents with Adolescents Identified as Having a Specific Learning Disability

ERIC Educational Resources Information Center

Seals, Linda J.

2010-01-01

Of the 6.6 million children in the United States who were deemed in 2008 to have a disability that required special instruction, over 39% were classified as specific learning disabled (SLD). This figure translates into a high number of people who are parenting a child identified as having a SLD. Bronfenbrenner's theory of the ecology of human…

COMPETITIVE METAGENOMIC DNA HYBRIDIZATION IDENTIFIES HOST-SPECIFIC MICROBIAL GENETIC MARKERS IN COW FECAL SAMPLES

EPA Science Inventory

Several PCR methods have recently been developed to identify fecal contamination in surface waters. In all cases, researchers have relied on one gene or one microorganism for selection of host specific markers. Here, we describe the application of a genome fragment enrichment met...

COMPETITIVE METAGENOMIC DNA HYBRIDIZATION IDENTIFIES HOST-SPECIFIC GENETIC MARKERS IN CATTLE FECAL SAMPLES - ABSTRACT

EPA Science Inventory

Several PCR methods have recently been developed to identify fecal contamination in surface waters. In all cases, researchers have relied on one gene or one microorganism for selection of host specific markers. Here, we describe the application of a genome fragment enrichment met...

Assessment of General Education: An Unexpected (but Effective) Faculty Development Opportunity

ERIC Educational Resources Information Center

Hawthorne, Joan; Zerr, Ryan; Kelsch, Anne V.

2018-01-01

This chapter describes a collective faculty effort to administer, proctor, score, and interpret student work that created an unexpected opportunity for deep discussions of teaching, learning, and assessment.

Left Ventricular Aneurysm: Sudden Unexpected Deaths in a 29-Year-Old Man.

PubMed

Srettabunjong, Supawon

2018-05-01

Left ventricular aneurysm (LVA) is an abnormal dilated heart structure, either congenital or acquired. LVA is a rare cardiac condition with no symptoms in most cases, thus occasionally diagnosed during investigations of other diseases. Its association with certain cardiac complications and sudden cardiac deaths has been reported. However, its role as a cause of sudden unexpected death is rare. The author reported a sudden cardiac death in a 29-year-old man with LVA. Without a significant coronary artery disease and known etiologies of LVA, such an abnormal heart structure in the present case was considered congenital LVA. As no other possible mechanisms of death could be identified other than LVA with its associated pathologic lesions, mural thrombi, and dilated cardiomegaly, his death was attributable to fatal cardiac arrhythmia (most commonly ventricular tachycardia) secondary to LVA. © 2017 American Academy of Forensic Sciences.

CloudNeo: a cloud pipeline for identifying patient-specific tumor neoantigens.

PubMed

Bais, Preeti; Namburi, Sandeep; Gatti, Daniel M; Zhang, Xinyu; Chuang, Jeffrey H

2017-10-01

We present CloudNeo, a cloud-based computational workflow for identifying patient-specific tumor neoantigens from next generation sequencing data. Tumor-specific mutant peptides can be detected by the immune system through their interactions with the human leukocyte antigen complex, and neoantigen presence has recently been shown to correlate with anti T-cell immunity and efficacy of checkpoint inhibitor therapy. However computing capabilities to identify neoantigens from genomic sequencing data are a limiting factor for understanding their role. This challenge has grown as cancer datasets become increasingly abundant, making them cumbersome to store and analyze on local servers. Our cloud-based pipeline provides scalable computation capabilities for neoantigen identification while eliminating the need to invest in local infrastructure for data transfer, storage or compute. The pipeline is a Common Workflow Language (CWL) implementation of human leukocyte antigen (HLA) typing using Polysolver or HLAminer combined with custom scripts for mutant peptide identification and NetMHCpan for neoantigen prediction. We have demonstrated the efficacy of these pipelines on Amazon cloud instances through the Seven Bridges Genomics implementation of the NCI Cancer Genomics Cloud, which provides graphical interfaces for running and editing, infrastructure for workflow sharing and version tracking, and access to TCGA data. The CWL implementation is at: https://github.com/TheJacksonLaboratory/CloudNeo. For users who have obtained licenses for all internal software, integrated versions in CWL and on the Seven Bridges Cancer Genomics Cloud platform (https://cgc.sbgenomics.com/, recommended version) can be obtained by contacting the authors. jeff.chuang@jax.org. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Meta-Profiles of Gene Expression during Aging: Limited Similarities between Mouse and Human and an Unexpectedly Decreased Inflammatory Signature

PubMed Central

Swindell, William R.; Johnston, Andrew; Sun, Liou; Xing, Xianying; Fisher, Gary J.; Bulyk, Martha L.; Elder, James T.; Gudjonsson, Johann E.

2012-01-01

Background Skin aging is associated with intrinsic processes that compromise the structure of the extracellular matrix while promoting loss of functional and regenerative capacity. These processes are accompanied by a large-scale shift in gene expression, but underlying mechanisms are not understood and conservation of these mechanisms between humans and mice is uncertain. Results We used genome-wide expression profiling to investigate the aging skin transcriptome. In humans, age-related shifts in gene expression were sex-specific. In females, aging increased expression of transcripts associated with T-cells, B-cells and dendritic cells, and decreased expression of genes in regions with elevated Zeb1, AP-2 and YY1 motif density. In males, however, these effects were contrasting or absent. When age-associated gene expression patterns in human skin were compared to those in tail skin from CB6F1 mice, overall human-mouse correspondence was weak. Moreover, inflammatory gene expression patterns were not induced with aging of mouse tail skin, and well-known aging biomarkers were in fact decreased (e.g., Clec7a, Lyz1 and Lyz2). These unexpected patterns and weak human-mouse correspondence may be due to decreased abundance of antigen presenting cells in mouse tail skin with age. Conclusions Aging is generally associated with a pro-inflammatory state, but we have identified an exception to this pattern with aging of CB6F1 mouse tail skin. Aging therefore does not uniformly heighten inflammatory status across all mouse tissues. Furthermore, we identified both intercellular and intracellular mechanisms of transcriptome aging, including those that are sex- and species-specific. PMID:22413003

Sudden unexpected death related to enterovirus myocarditis: histopathology, immunohistochemistry and molecular pathology diagnosis at post-mortem

PubMed Central

2012-01-01

Background Viral myocarditis is a major cause of sudden unexpected death in children and young adults. Until recently, coxsackievirus B3 (CVB3) has been the most commonly implicated virus in myocarditis. At present, no standard diagnosis is generally accepted due to the insensitivity of traditional diagnostic tests. This has prompted health professionals to seek new diagnostic approaches, which resulted in the emergence of new molecular pathological tests and a more detailed immunohistochemical and histopathological analysis. When supplemented with immunohistochemistry and molecular pathology, conventional histopathology may provide important clues regarding myocarditis underlying etiology. Methods This study is based on post-mortem samples from sudden unexpected death victims and controls who were investigated prospectively. Immunohistochemical investigations for the detection of the enteroviral capsid protein VP1 and the characterization and quantification of myocardial inflammatory reactions as well as molecular pathological methods for enteroviral genome detection were performed. Results Overall, 48 sudden unexpected death victims were enrolled. As for controls, 37 cases of unnatural traffic accident victims were studied. Enterovirus was detected in 6 sudden unexpected death cases (12.5 %). The control samples were completely enterovirus negative. Furthermore, the enteroviral capsid protein VP1 in the myocardium was detected in enterovirus-positive cases revealed by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Unlike control samples, immunohistochemical investigations showed a significant presence of T and B lymphocytes in sudden unexpected death victims. Conclusions Our findings demonstrate clearly a higher prevalence of viral myocarditis in cases of sudden unexpected death compared to control subjects, suggesting that coxsackie B enterovirus may contribute to myocarditis pathogenesis significantly. PMID:22966951

Invertebrate-Based Water Quality Impairments and Associated Stressors Identified through the US Clean Water Act

NASA Astrophysics Data System (ADS)

Govenor, Heather; Krometis, Leigh Anne H.; Hession, W. Cully

2017-10-01

Macroinvertebrate community assessment is used in most US states to evaluate stream health under the Clean Water Act. While water quality assessment and impairment determinations are reported to the US Environmental Protection Agency, there is no national summary of biological assessment findings. The objective of this work was to determine the national extent of invertebrate-based impairments and to identify pollutants primarily responsible for those impairments. Evaluation of state data in the US Environmental Protection Agency's Assessment and Total Maximum Daily Load Tracking and Implementation System database revealed considerable differences in reporting approaches and terminologies including differences in if and how states report specific biological assessment findings. Only 15% of waters impaired for aquatic life could be identified as having impairments determined by biological assessments (e.g., invertebrates, fish, periphyton); approximately one-third of these were associated with macroinvertebrate bioassessment. Nearly 650 invertebrate-impaired waters were identified nationwide, and sediment was the most common pollutant in bedded (63%) and suspended (9%) forms. This finding is not unexpected, given previous work on the negative impacts of sediment on aquatic life, and highlights the need to more specifically identify the mechanisms driving sediment impairments in order to design effective remediation plans. It also reinforces the importance of efforts to derive sediment-specific biological indices and numerical sediment quality guidelines. Standardization of state reporting approaches and terminology would significantly increase the potential application of water quality assessment data, reveal national trends, and encourage sharing of best practices to facilitate the attainment of water quality goals.

Research Priorities in Sudden Unexpected Infant Death: An International Consensus.

PubMed

Hauck, Fern R; McEntire, Betty L; Raven, Leanne K; Bates, Francine L; Lyus, Lucy A; Willett, Alexis M; Blair, Peter S

2017-07-27

Despite the success of safe sleep campaigns and the progress in understanding risk factors, the rate of reduction in the cases of sudden infant death syndrome has now slowed and it remains a leading cause of postneonatal mortality in many developed countries. Strategic action is needed to tackle this problem and it is now vital to identify how the sudden infant death research community may best target its efforts. The Global Action and Prioritization of Sudden Infant Death Project was an international consensus process that aimed to define and direct future research by investigating the priorities of expert and lay members of the sudden unexpected infant death (SUID) community across countries. The aim was to identify which areas of research should be prioritized to reduce the number of SUID deaths globally. Scientific researchers, clinicians, counselors, educators, and SUID parents from 25 countries took part across 2 online surveys to identify potential research priorities. Workshops subsequently took place in the United Kingdom, United States, and Australia to reach consensus and 10 priority areas for research were established. Three main themes among the priorities emerged: (1) a better understanding of mechanisms underlying SUID, (2) ensuring best practice in data collection, management and sharing, and (3) a better understanding of target populations and more effective communication of risk. SUID is a global problem and this project provides the international SUID community with a list of shared research priorities to more effectively work toward explaining and reducing the number of sudden infant deaths. Copyright © 2017 by the American Academy of Pediatrics.

A parameter control method in reinforcement learning to rapidly follow unexpected environmental changes.

PubMed

Murakoshi, Kazushi; Mizuno, Junya

2004-11-01

In order to rapidly follow unexpected environmental changes, we propose a parameter control method in reinforcement learning that changes each of learning parameters in appropriate directions. We determine each appropriate direction on the basis of relationships between behaviors and neuromodulators by considering an emergency as a key word. Computer experiments show that the agents using our proposed method could rapidly respond to unexpected environmental changes, not depending on either two reinforcement learning algorithms (Q-learning and actor-critic (AC) architecture) or two learning problems (discontinuous and continuous state-action problems).

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

PubMed

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

2017-08-01

Sudden unexpected death during sleep (SUDS) is the most common cause of death in patients with familial dysautonomia (FD), an autosomal recessive disease characterized by sensory and autonomic dysfunction. It remains unknown what causes SUDS in these patients and who is at highest risk. We tested the hypothesis that SUDS in FD is linked to sleep-disordered breathing. We retrospectively identified patients with FD who died suddenly and unexpectedly during sleep and had undergone polysomnography within the 18-month period before death. For each case, we sampled one age-matched surviving subject with FD that had also undergone polysomnography within the 18-month period before study. Data on polysomnography, EKG, ambulatory blood pressure monitoring, arterial blood gases, blood count, and metabolic panel were analyzed. Thirty-two deceased cases and 31 surviving controls were included. Autopsy was available in six cases. Compared with controls, participants with SUDS were more likely to be receiving treatment with fludrocortisone (odds ratio [OR]; 95% confidence interval) (OR 29.7; 4.1-213.4), have untreated obstructive sleep apnea (OR 17.4; 1.5-193), and plasma potassium levels <4 mEq/L (OR 19.5; 2.36-161) but less likely to use noninvasive ventilation at night (OR 0.19; 0.06-0.61). Initiation of noninvasive ventilation when required and discontinuation of fludrocortisone treatment may reduce the high incidence rate of SUDS in patients with FD. Our findings contribute to the understanding of the link between autonomic, cardiovascular, and respiratory risk factors in SUDS. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Long-range DHPS mutations unexpectedly increase Mycobacterium chimaera susceptibility to sulfonamides.

PubMed

Gotthard, Guillaume; Muhammed Ameen, Sirwan; Drancourt, Michel; Chabriere, Eric

2013-12-01

The two closely related mycobacteria, Mycobacterium intracellulare and Mycobacterium chimaera, exhibit a more than two-fold difference in their in vitro susceptibility to sulfonamides. Sulfonamides are antibiotics targeting the 6-hydroxymethyl-7,8-dihydropteroate synthase (DHPS) enzyme involved in the folate synthesis pathway. Comparing the DHPS gene sequence in six M. intracellulare and M. chimaera types trains and clinical isolates yielded only four amino acid changes. In silico structural modelling surprisingly indicated that these amino acids are not located in the active site of DHPS and do not interact directly with sulfonamides. Unexpectedly, these amino acids in distal positions may play a key role in the increased sulfonamide susceptibility observed in M. chimaera compared with M. intracellulare. This example illustrates how three-dimensional models could help to identify distal mutations capable of modulating enzymatic activity. Copyright © 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Clinical, pathological and sonographic characteristics of unexpected gallbladder carcinoma

PubMed Central

Wang, Jin-Huan; Liu, Bo-Ji; Xu, Hui-Xiong; Sun, Li-Ping; Li, Dan-Dan; Guo, Le-Hang; Liu, Lin-Na; Xu, Xiao-Hong

2015-01-01

Objectives: To investigate the clinical, pathological, and sonographic characteristics of unexpected gallbladder carcinoma (UGC). Methods: Of 5424 patients who had undergone cholecystectomy from December 2006 to October 2013, 54 patients with primary gallbladder carcinomas confirmed by pathological diagnosis were identified. The patients were divided into two groups: diagnosed before operation (n=34) and UGC groups (n=20), of whom the clinical, pathological, and sonographic characteristics were compared. Results: No significant differences in age, gender, location of lesion, histological type, length of the gallbladder, existence of biliary sludge, and intestinal gas interference between the two groups were found (all P>0.05). The clinical symptoms, laboratory abnormalities, tumor markers, coexisting gallbladder stones, lesion size, lesion type, degree of differentiation, and tumor staging showed statistically significant differences between the two groups (all P<0.05). On ultrasound, the width of the gallbladder, gallbladder wall thickness, vascularity on color Doppler ultrasound, and bile volume in the gallbladder showed significant differences (all P<0.05). Conclusions: UGCs are commonly found at an early stage, often well-differentiated, wall thickened, and are generally accompanied with cholelithiasis. UGCs should be taken into consideration in cases with cholelithiasis or small gallbladder on ultrasound. PMID:26379911

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.

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks for...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... 8, 2010 Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks... section 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended, (22 U.S.C...

Human Neoplasms Elicit Multiple Specific Immune Responses in the Autologous Host

NASA Astrophysics Data System (ADS)

Sahin, Ugur; Tureci, Ozlem; Schmitt, Holger; Cochlovius, Bjorn; Johannes, Thomas; Schmits, Rudolf; Stenner, Frank; Luo, Guorong; Schobert, Ingrid; Pfreundschuh, Michael

1995-12-01

Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

Comparative Analysis of Four Calypogeia Species Revealed Unexpected Change in Evolutionarily-Stable Liverwort Mitogenomes

PubMed Central

Ślipiko, Monika; Buczkowska-Chmielewska, Katarzyna; Bączkiewicz, Alina; Szczecińska, Monika; Sawicki, Jakub

2017-01-01

Liverwort mitogenomes are considered to be evolutionarily stable. A comparative analysis of four Calypogeia species revealed differences compared to previously sequenced liverwort mitogenomes. Such differences involve unexpected structural changes in the two genes, cox1 and atp1, which have lost three and two introns, respectively. The group I introns in the cox1 gene are proposed to have been lost by two-step localized retroprocessing, whereas one-step retroprocessing could be responsible for the disappearance of the group II introns in the atp1 gene. These cases represent the first identified losses of introns in mitogenomes of leafy liverworts (Jungermanniopsida) contrasting the stability of mitochondrial gene order with certain changes in the gene content and intron set in liverworts. PMID:29257096

Sudden Unexpected Death in Epilepsy Among Patients With Benign Childhood Epilepsy With Centrotemporal Spikes.

PubMed

Doumlele, Kyra; Friedman, Daniel; Buchhalter, Jeffrey; Donner, Elizabeth J; Louik, Jay; Devinsky, Orrin

2017-06-01

Children with benign epilepsy with centrotemporal spikes (BECTS) have traditionally been considered to have a uniformly good prognosis. However, benign may be a misnomer because BECTS is linked to cognitive deficits, a more severe phenotype with intractable seizures, and the potential for sudden unexpected death in epilepsy (SUDEP). To determine if cases of BECTS are present in the North American SUDEP Registry (NASR). The NASR is a clinical and biospecimen repository established in 2011 to promote SUDEP research. The NASR database, which includes medical records, results of electroencephalographic tests, and interviews with family members of patients with epilepsy who died suddenly without other identifiable causes of death, was queried from June 3, 2011, to June 3, 2016, for cases of BECTS. The patients with epilepsy had died suddenly without other identifiable causes of death (eg, drowning, trauma, exposure to toxic substances, or suicide); SUDEP classification was determined by the consensus of 2 epileptologists. Cases of SUDEP among children who received a diagnosis of BECTS among patients reported in the NASR. Three boys (median age at death, 12 years; range, 9-13 years) who received a diagnosis of BECTS by their pediatric epileptologist or neurologists were identified among 189 cases reported in the NASR. The median age of epilepsy onset was 5 years (range, 3-11 years), and the median duration of epilepsy was 4 years (range, 1-10 years). Two deaths were definite SUDEP, and 1 was probable SUDEP. Independent review of clinical and electroencephalographic data supported the diagnosis of BECTS in all 3 patients. None of the patients was prescribed antiseizure drugs, either owing to physician recommendation or mutual decision by the physician and parents. All 3 patients were found dead in circumstances typical of SUDEP. The 3 patients spanned the spectrum of BECTS severity: 1 had only a few seizures, 1 had more than 30 focal motor seizures, and 1 had 4 witnessed

Unexpected arousal modulates the influence of sensory noise on confidence

PubMed Central

Allen, Micah; Frank, Darya; Schwarzkopf, D Samuel; Fardo, Francesca; Winston, Joel S; Hauser, Tobias U; Rees, Geraint

2016-01-01

Human perception is invariably accompanied by a graded feeling of confidence that guides metacognitive awareness and decision-making. It is often assumed that this arises solely from the feed-forward encoding of the strength or precision of sensory inputs. In contrast, interoceptive inference models suggest that confidence reflects a weighted integration of sensory precision and expectations about internal states, such as arousal. Here we test this hypothesis using a novel psychophysical paradigm, in which unseen disgust-cues induced unexpected, unconscious arousal just before participants discriminated motion signals of variable precision. Across measures of perceptual bias, uncertainty, and physiological arousal we found that arousing disgust cues modulated the encoding of sensory noise. Furthermore, the degree to which trial-by-trial pupil fluctuations encoded this nonlinear interaction correlated with trial level confidence. Our results suggest that unexpected arousal regulates perceptual precision, such that subjective confidence reflects the integration of both external sensory and internal, embodied states. DOI: http://dx.doi.org/10.7554/eLife.18103.001 PMID:27776633

Correction: Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

DOE PAGES

Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; ...

2015-07-20

One central question is how specificity in cellular responses to the eukaryotic second messenger Ca 2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca 2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca 2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca 2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruplemore » mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca 2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca 2+-dependent and Ca 2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca 2+-signaling on a cellular, genetic, and biochemical level.« less

Correction: Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

DOE PAGES

Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; ...

2015-07-29

A central question is how specificity in cellular responses to the eukaryotic second messenger Ca 2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca 2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca 2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca 2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruplemore » mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca 2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca 2+-dependent and Ca 2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca 2+-signaling on a cellular, genetic, and biochemical level.« less

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire Presidential Documents Other Presidential Documents Presidential Determination No. 2011-11 of June 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire Memorandum for the Secretary of...

Unexpected carboxylate like CO adsorption at the Sr3Ru2O7 (001) surface

NASA Astrophysics Data System (ADS)

Hieckel, Marcel; Mittendorfer, Florian; Redinger, Josef; Stoeger, Bernhard; Wang, Zhiming; Schmid, Michael; Diebold, Ulrike

2014-03-01

Oxide perovskite materials have attracted enormous attention because of a variety of intriguing physical properties ranging from catalysis to multiferroicity. We present a combined experimental and ab-initio (DFT) study with the Vienna Ab initio Simulation Package (VASP) on the adsorption of CO at the Sr3Ru2O7 (001) surface. We identify both a physisorbed and a chemisorbed CO configuraton. Unexpectedly, in the latter case adsorption occurs in a carboxylate (COO) like state. Both configurations have been confirmed by detailed STM experiments and simulations. In addition we find only a small barrier for the carboxylate formation on the surface. Work supported by the Austrian FWF, SFB F45 (FOXSI).

An unexpected tetanus case.

PubMed

Ergonul, Onder; Egeli, Demet; Kahyaoglu, Bulent; Bahar, Mois; Etienne, Mill; Bleck, Thomas

2016-06-01

1 million cases of tetanus are estimated to occur worldwide each year, with more than 200 000 deaths. Tetanus is a life-threatening but preventable disease caused by a toxin produced by Clostridium tetani-a Gram-positive bacillus found in high concentrations in soil and animal excrement. Tetanus is almost completely preventable by active immunisation, but very rarely unexpected cases can occur in individuals who have been previously vaccinated. We report a case of generalised tetanus in a 22-year-old woman that arose despite the protective antitoxin antibody in her serum. The patient received all her vaccinations in the USA; her last vaccination was 6 years ago. The case was unusual because the patient had received all standard vaccinations, had no defined port of entry at disease onset, and had symptoms lasting for 6 months. Tetanus can present with unusual clinical forms; therefore, the diagnosis and management of this rare but difficult disease should be updated. In this Grand Round, we review the clinical features, epidemiology, treatment, and prognosis of C tetani infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation.

PubMed

Godec, Jernej; Tan, Yan; Liberzon, Arthur; Tamayo, Pablo; Bhattacharya, Sanchita; Butte, Atul J; Mesirov, Jill P; Haining, W Nicholas

2016-01-19

Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Reading Questions in Large-Lecture Courses: Limitations and Unexpected Outcomes

ERIC Educational Resources Information Center

Offerdahl, Erika; Baldwin, Thomas; Elfring, Lisa; Vierling, Elizabeth; Ziegler, Miriam

2008-01-01

As an alternative to reading quizzes, a team of biochemistry instructors implemented student reading questions (Henderson and Rosenthal 2006) as a new instructional strategy within their large-enrollment biochemistry courses. Unexpected positive outcomes of this instructional method were realized, as well as limitations of the method within this…

A microscopy-based screen employing multiplex genome sequencing identifies cargo-specific requirements for dynein velocity

PubMed Central

Tan, Kaeling; Roberts, Anthony J.; Chonofsky, Mark; Egan, Martin J.; Reck-Peterson, Samara L.

2014-01-01

The timely delivery of membranous organelles and macromolecules to specific locations within the majority of eukaryotic cells depends on microtubule-based transport. Here we describe a screening method to identify mutations that have a critical effect on intracellular transport and its regulation using mutagenesis, multicolor-fluorescence microscopy, and multiplex genome sequencing. This screen exploits the filamentous fungus Aspergillus nidulans, which has many of the advantages of yeast molecular genetics but uses long-range microtubule-based transport in a manner more similar to metazoan cells. Using this method, we identified seven mutants that represent novel alleles of components of the intracellular transport machinery: specifically, kinesin-1, cytoplasmic dynein, and the dynein regulators Lis1 and dynactin. The two dynein mutations identified in our screen map to dynein's AAA+ catalytic core. Single-molecule studies reveal that both mutations reduce dynein's velocity in vitro. In vivo these mutants severely impair the distribution and velocity of endosomes, a known dynein cargo. In contrast, another dynein cargo, the nucleus, is positioned normally in these mutants. These results reveal that different dynein functions have distinct stringencies for motor performance. PMID:24403603

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.

Phenotypic Screening Identifies Protein Synthesis Inhibitors as H-Ras-Nanocluster-Increasing Tumor Growth Inducers.

PubMed

Najumudeen, Arafath K; Posada, Itziar M D; Lectez, Benoit; Zhou, Yong; Landor, Sebastian K-J; Fallarero, Adyary; Vuorela, Pia; Hancock, John; Abankwa, Daniel

2015-12-15

Ras isoforms H-, N-, and K-ras are each mutated in specific cancer types at varying frequencies and have different activities in cell fate control. On the plasma membrane, Ras proteins are laterally segregated into isoform-specific nanoscale signaling hubs, termed nanoclusters. As Ras nanoclusters are required for Ras signaling, chemical modulators of nanoclusters represent ideal candidates for the specific modulation of Ras activity in cancer drug development. We therefore conducted a chemical screen with commercial and in-house natural product libraries using a cell-based H-ras-nanoclustering FRET assay. Next to established Ras inhibitors, such as a statin and farnesyl-transferase inhibitor, we surprisingly identified five protein synthesis inhibitors as positive regulators. Using commonly employed cycloheximide as a representative compound, we show that protein synthesis inhibition increased nanoclustering and effector recruitment specifically of active H-ras but not of K-ras. Consistent with these data, cycloheximide treatment activated both Erk and Akt kinases and specifically promoted H-rasG12V-induced, but not K-rasG12V-induced, PC12 cell differentiation. Intriguingly, cycloheximide increased the number of mammospheres, which are enriched for cancer stem cells. Depletion of H-ras in combination with cycloheximide significantly reduced mammosphere formation, suggesting an exquisite synthetic lethality. The potential of cycloheximide to promote tumor cell growth was also reflected in its ability to increase breast cancer cell tumors grown in ovo. These results illustrate the possibility of identifying Ras-isoform-specific modulators using nanocluster-directed screening. They also suggest an unexpected feedback from protein synthesis inhibition to Ras signaling, which might present a vulnerability in certain tumor cell types.

Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.

PubMed

Serafimidis, Ioannis; Rodriguez-Aznar, Eva; Lesche, Mathias; Yoshioka, Kazuaki; Takuwa, Yoh; Dahl, Andreas; Pan, Duojia; Gavalas, Anthony

2017-03-01

During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. S1pr2 signalling promotes progenitor survival as well as acinar and endocrine specification. S1pr2-mediated stabilisation of the yes-associated protein (YAP) is essential for endocrine specification, thus linking a regulator of progenitor growth with specification. YAP stabilisation and endocrine cell specification rely on Gαi subunits, revealing an unexpected specificity of selected GPCR intracellular signalling components. Finally, we found that S1pr2 signalling posttranscriptionally attenuates Notch signalling levels, thus regulating lineage allocation. Both S1pr2-mediated YAP stabilisation and Notch attenuation are necessary for the specification of the endocrine lineage. These findings identify S1p signalling as a novel key pathway coordinating cell survival, lineage allocation, and specification and linking these processes by regulating YAP levels and Notch signalling. Understanding lineage allocation and specification in the pancreas will shed light in the origins of pancreatic diseases and may suggest novel therapeutic approaches.

Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling

PubMed Central

Serafimidis, Ioannis; Rodriguez-Aznar, Eva; Lesche, Mathias; Yoshioka, Kazuaki; Takuwa, Yoh; Dahl, Andreas; Pan, Duojia; Gavalas, Anthony

2017-01-01

During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. S1pr2 signalling promotes progenitor survival as well as acinar and endocrine specification. S1pr2-mediated stabilisation of the yes-associated protein (YAP) is essential for endocrine specification, thus linking a regulator of progenitor growth with specification. YAP stabilisation and endocrine cell specification rely on Gαi subunits, revealing an unexpected specificity of selected GPCR intracellular signalling components. Finally, we found that S1pr2 signalling posttranscriptionally attenuates Notch signalling levels, thus regulating lineage allocation. Both S1pr2-mediated YAP stabilisation and Notch attenuation are necessary for the specification of the endocrine lineage. These findings identify S1p signalling as a novel key pathway coordinating cell survival, lineage allocation, and specification and linking these processes by regulating YAP levels and Notch signalling. Understanding lineage allocation and specification in the pancreas will shed light in the origins of pancreatic diseases and may suggest novel therapeutic approaches. PMID:28248965

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...

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

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

ERIC Educational Resources Information Center

Mason, John

2015-01-01

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

Novel hydrated graphene ribbon unexpectedly promotes aged seed germination and root differentiation

NASA Astrophysics Data System (ADS)

Hu, Xiangang; Zhou, Qixing

2014-01-01

It is well known that graphene (G) induces nanotoxicity towards living organisms. Here, a novel and biocompatible hydrated graphene ribbon (HGR) unexpectedly promoted aged (two years) seed germination. HGR formed at the normal temperature and pressure (120 days hydration), presented 17.1% oxygen, 0.9% nitrogen groups, disorder-layer structure, with 0.38 nm thickness ribbon morphology. Interestingly, there were bulges around the edges of HGR. Compared to G and graphene oxide (GO), HGR increased seed germination by 15% root differentiation between 52 and 59% and enhanced resistance to oxidative stress. The metabonomics analysis discovered that HGR upregulated carbohydrate, amino acid, and fatty acids metabolism that determined secondary metabolism, nitrogen sequestration, cell membrane integrity, permeability, and oxidation resistance. Hexadecanoic acid as a biomarker promoted root differentiation and increased the germination rate. Our discovery is a novel HGR that promotes aged seed germination, illustrates metabolic specificity among graphene-based materials, and inspires innovative concepts in the regulation of seed development.

An HTS-compatible 3D colony formation assay to identify tumor-specific chemotherapeutics.

PubMed

Horman, Shane R; To, Jeremy; Orth, Anthony P

2013-12-01

There has been increasing interest in the development of cellular behavior models that take advantage of three-dimensional (3D) cell culture. To enable assessment of differential perturbagen impacts on cell growth in 2D and 3D, we have miniaturized and adapted for high-throughput screening (HTS) the soft agar colony formation assay, employing a laser-scanning cytometer to image and quantify multiple cell types simultaneously. The assay is HTS compatible, providing high-quality, image-based, replicable data for multiple, co-cultured cell types. As proof of concept, we subjected colorectal carcinoma colonies in 3D soft agar to a mini screen of 1528 natural product compounds. Hit compounds from the primary screen were rescreened in an HTS 3D co-culture matrix containing colon stromal cells and cancer cells. By combining tumor cells and normal, nontransformed colon epithelial cells in one primary screening assay, we were able to obtain differential IC50 data, thereby distinguishing tumor-specific compounds from general cytotoxic compounds. Moreover, we were able to identify compounds that antagonized tumor colony formation in 3D only, highlighting the importance of this assay in identifying agents that interfere with 3D tumor structural growth. This screening platform provides a fast, simple, and robust method for identification of tumor-specific agents in a biologically relevant microenvironment.

A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity.

PubMed

Das, Bhaskar C; McCartin, Kellie; Liu, Ting-Chun; Peterson, Randall T; Evans, Todd

2010-04-02

Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model. We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80-92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested. Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity.

Discovery of unexpected pain in intubated and sedated patients.

PubMed

Clukey, Lory; Weyant, Ruth A; Roberts, Melanie; Henderson, Ann

2014-05-01

The perceptions of patients who are restrained and sedated while being treated with mechanical ventilation in the intensive care unit are not well understood. The effectiveness of sedation used to aid in recovery and enhance comfort during intubation is unknown. To explore the perceptions of patients who were intubated and receiving pain medication while sedated and restrained in the intensive care unit, in particular, their experience and their memories of the experience. In a phenomenological study, 14 patients who were intubated and receiving pain medication while sedated and restrained were interviewed at the bedside. A semistructured interview guide was used. Data were analyzed by using an inductive method consistent with qualitative research. Three major themes were identified from the data: lack of memory of being restrained; a perception of being intubated as horrific; nursing behaviors that were helpful and comforting. An unexpected discovery was that sedation may be interfering with pain assessment and management. Being intubated can be painful and traumatic despite administration of sedatives and analgesics. Sedation may mask uncontrolled pain for intubated patients and prevent them from communicating this condition to a nurse. Nurses may need to evaluate current interventions in order to provide maximum comfort and promote optimal positive outcomes for intensive care patients who are intubated.

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

Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

PubMed Central

Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; Nguyen, Desiree; Yong, Taiming; Yang, Paul G; Poretsky, Elly; Belknap, Thomas F; Waadt, Rainer; Alemán, Fernando; Schroeder, Julian I

2015-01-01

A central question is how specificity in cellular responses to the eukaryotic second messenger Ca2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruple mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca2+-dependent and Ca2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca2+-signaling on a cellular, genetic, and biochemical level. DOI: http://dx.doi.org/10.7554/eLife.03599.001 PMID:26192964

Unexpected case of pneumomediastinum and subcutaneous emphysema: primary or secondary aetiology?

PubMed

Cheng, Amanda J L; Sadler, Timothy J

2018-04-19

A 77-year-old man was admitted with a relapse of antineutrophil cytoplasmic antibody-positive vasculitis with pulmonary involvement and acute kidney injury. There was a background of pulmonary fibrosis (non-specific interstitial pneumonia type pattern) and superadded pulmonary haemorrhage, acute pulmonary oedema and sepsis. The patient was intubated for 4 days and remained dependent on high flow oxygen and continuous positive airway pressure after extubation. A chest radiograph performed 2 weeks after extubation demonstrated unexpected, extensive pneumomediastinum and subcutaneous emphysema. This was confirmed on CT which raised the possibility of a tracheal defect at the level of the prior endotracheal tube cuff position. Tracheal injury was considered clinically unlikely due to the considerable interval since extubation and a short, uneventful intubation period. The cardiothoracic team recommended a diagnostic bronchoscopy but this was felt too high risk by the clinical team. The cause of pneumomediastinum and subcutaneous emphysema remained indeterminate. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sudden unexpected death in infancy: place and time of death.

PubMed

Glasgow, J F T; Thompson, A J; Ingram, P J

2006-01-01

In recent years, many babies who die of Sudden Unexpected Death in Infancy (SUDI) in Northern Ireland are found dead in bed--i.e. co-sleeping--with an adult. In order to assess its frequency autopsy reports between April 1996 and August 2001 were reviewed and linked to temporal factors. The day and month of death, and the place where the baby was found were compared to a reference population of infant deaths between one week of age and the second birthday. Although the rate of SUDI was lower than the UK average, 43 cases of SUDI were identified, and two additional deaths with virtually identical autopsy findings that were attributed to asphyxia caused by suffocation due to overlaying. Thirty-two of the 45 (71%) were less than four months of age. In 30 of the 45 cases (67%) the history stated that the baby was bed sharing with others; 19 died sleeping in an adult bed, and 11 on a sofa or armchair. In 16 of the 30 (53%) there were at least two other people sharing the sleeping surface, and in one case, three. SUDI was twice as frequent at weekends (found dead Saturday-Monday mornings) compared to weekdays (p<0.02), and significantly more common compared to reference deaths (p<0.002). Co-sleeping deaths were also more frequent at weekends. Almost half of all SUDI (49%) occurred in the summer months--more than twice the frequency of reference deaths. While sharing a place of sleep per se may not increase the risk of death, our findings may be linked to factors such as habitual smoking, consumption of alcohol or illicit drugs as reported in case-control studies. In advising parents on safer childcare practices, health professionals must be knowledgeable of current research and when, for example, giving advice on co-sleeping this needs to be person-specific cognisant of the risks within a household. New and better means of targeting such information needs to be researched if those with higher risk life-styles are to be positively influenced.

Galline Ex-FABP is an Antibacterial Siderocalin and a Lysophosphatidic Acid Sensor Functioning through Dual Ligand Specificities

PubMed Central

Correnti, Colin; Clifton, Matthew C.; Abergel, Rebecca J.; Allred, Ben; Hoette, Trisha M.; Ruiz, Mario; Cancedda, Ranieri; Raymond, Kenneth N.; Descalzi, Fiorella; Strong, Roland K.

2011-01-01

SUMMARY Galline Ex-FABP was identified as another candidate antibacterial, catecholate siderophore binding lipocalin (siderocalin) based on structural parallels with the family archetype, mammalian Siderocalin. Binding assays show that Ex-FABP retains iron in a siderophore-dependent manner in both hypertrophic and dedifferentiated chondrocytes, where Ex-FABP expression is induced after treatment with proinflammatory agents, and specifically binds ferric complexes of enterobactin, parabactin, bacillibactin and, unexpectedly, monoglucosylated enterobactin, which does not bind to Siderocalin. Growth arrest assays functionally confirm the bacteriostatic effect of Ex-FABP in vitro under iron-limiting conditions. The 1.8Å crystal structure of Ex-FABP explains the expanded specificity, but also surprisingly reveals an extended, multi-chambered cavity extending through the protein and encompassing two separate ligand specificities, one for bacterial siderophores (as in Siderocalin) at one end and one specifically binding co-purified lysophosphatidic acid, a potent cell signaling molecule, at the other end, suggesting Ex-FABP employs dual functionalities to explain its diverse endogenous activities. PMID:22153502

Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

PubMed

Tang, Yew Chung; Ho, Szu-Chi; Tan, Elisabeth; Ng, Alvin Wei Tian; McPherson, John R; Goh, Germaine Yen Lin; Teh, Bin Tean; Bard, Frederic; Rozen, Steven G

2018-03-22

-SSL patterns of activity in a large proportion of PTEN-deficient breast cancer cell lines and are potential specific vulnerabilities in PTEN-deficient breast cancer. Furthermore, the NUAK1 PTEN-SSL vulnerability identified by RNA interference techniques can be recapitulated and exploited using the small molecule kinase inhibitor HTH-01-015. Thus, NUAK1 inhibition may be an effective strategy for precision treatment of PTEN-deficient breast tumors.

Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta

PubMed Central

Johnson, Michelle D; Dopierala, Justyna

2018-01-01

ABSTRACT DNA methylation is an important regulator of gene function. Fetal sex is associated with the risk of several specific pregnancy complications related to placental function. However, the association between fetal sex and placental DNA methylation remains poorly understood. We carried out whole-genome oxidative bisulfite sequencing in the placentas of two healthy female and two healthy male pregnancies generating an average genome depth of coverage of 25x. Most highly ranked differentially methylated regions (DMRs) were located on the X chromosome but we identified a 225 kb sex-specific DMR in the body of the CUB and Sushi Multiple Domains 1 (CSMD1) gene on chromosome 8. The sex-specific differential methylation pattern observed in this region was validated in additional placentas using in-solution target capture. In a new RNA-seq data set from 64 female and 67 male placentas, CSMD1 mRNA was 1.8-fold higher in male than in female placentas (P value = 8.5 × 10−7, Mann-Whitney test). Exon-level quantification of CSMD1 mRNA from these 131 placentas suggested a likely placenta-specific CSMD1 isoform not detected in the 21 somatic tissues analyzed. We show that the gene body of an autosomal gene, CSMD1, is differentially methylated in a sex- and placental-specific manner, displaying sex-specific differences in placental transcript abundance. PMID:29376485

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.

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

The relationship between specific cognitive impairment and behaviour in Prader-Willi syndrome.

PubMed

Woodcock, K A; Oliver, C; Humphreys, G W

2011-02-01

Individuals with Prader-Willi syndrome (PWS) have been shown to demonstrate a particular cognitive deficit in attention switching and high levels of preference for routine and temper outbursts. This study assesses whether a specific pathway between a cognitive deficit and behaviour via environmental interaction can exist in individuals with PWS. Four individuals with PWS participated in a series of three single-case experiments including laboratory-based and natural environment designs. Cognitive (computer-based) challenges placed varying demands on attention switching or controlled for the cognitive demands of the tasks while placing no demands on switching. Unexpected changes to routines or expectations were presented in controlled games, or imposed on participants' natural environments and compared with control conditions during which no unexpected changes occurred. Behaviour was observed and heart rate was measured. Participants showed significantly increased temper outburst related behaviours during cognitive challenges that placed demands on attention switching, relative to the control cognitive challenges. Participants showed significantly increased temper outburst related behaviours when unexpected changes occurred in an experimental or the natural environment compared with when no changes occurred. Difficult behaviours that could be triggered reliably in an individual by a specific cognitive demand could also be triggered via manipulation of the environment. Results suggest that a directional relationship between a specific cognitive deficit and behaviour, via environmental interaction, can exist in individuals with PWS. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

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

An unexpected epoxidation of benzil derivatives in their reaction with a germene.

PubMed

El Kettani, Sakina Ech-Cherif; Lazraq, Mohamed; Ouhsaine, Fatima; Gornitzka, Heinz; Ranaivonjatovo, Henri; Escudié, Jean

2008-11-07

The germene Mes(2)Ge=CR(2) (Mes = 2,4,6-trimethylphenyl, CR(2) = fluorenylidene) reacts with various benzil derivatives to lead to germanium-containing bicyclic epoxides by an unexpected new type of epoxidation reaction.

Unexpected development of artistic talents

PubMed Central

Gordon, N

2005-01-01

The development of exceptional and unexpected artistic skills at any age must be a matter of curiosity. This can occur among young children with severe learning difficulties, especially if they are autistic. Some examples of these so called idiot-savants are given, and the way in which their brains may function. It is also true that elderly people who suffer from frontotemporal dementia can find that they are able to express themselves in remarkable art forms. This can occur in other types of dementia, but then more often it is the changes that result in the paintings of established artists, for example in the paintings of de Kooning. Possible links between these two phenomenon are discussed, and it is suggested that in both instances it may be that if the brain is relieved of a number of functions it can concentrate on the remaining ones. Ways in which this may operate in both groups are reviewed. PMID:16344297

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

Recent advances in cross-cultural measurement in psychiatric epidemiology: utilizing 'what matters most' to identify culture-specific aspects of stigma.

PubMed

Yang, Lawrence Hsin; Thornicroft, Graham; Alvarado, Ruben; Vega, Eduardo; Link, Bruce George

2014-04-01

While stigma measurement across cultures has assumed growing importance in psychiatric epidemiology, it is unknown to what extent concepts arising from culture have been incorporated. We utilize a formulation of culture-as the everyday interactions that 'matter most' to individuals within a cultural group-to identify culturally-specific stigma dynamics relevant to measurement. A systematic literature review from January 1990 to September 2012 was conducted using PsycINFO, Medline and Google Scholar to identify articles studying: (i) mental health stigma-related concepts; (ii) ≥ 1 non-Western European cultural group. From 5292 abstracts, 196 empirical articles were located. The vast majority of studies (77%) utilized adaptations of existing Western-developed stigma measures to new cultural groups. Extremely few studies (2.0%) featured quantitative stigma measures derived within a non-Western European cultural group. A sizeable amount (16.8%) of studies employed qualitative methods to identify culture-specific stigma processes. The 'what matters most' perspective identified cultural ideals of the everyday activities that comprise 'personhood' of 'preserving lineage' among specific Asian groups, 'fighting hard to overcome problems and taking advantage of immigration opportunities' among specific Latino-American groups, and 'establishing trust among religious institutions due to institutional discrimination' among African-American groups. These essential cultural interactions shaped culture-specific stigma manifestations. Mixed method studies (3.6%) corroborated these qualitative results. Quantitatively-derived, culturally-specific stigma measures were lacking. Further, the vast majority of qualitative studies on stigma were conducted without using stigma-specific frameworks. We propose the 'what matters most' approach to address this key issue in future research.

Complex and unexpected dynamics in simple genetic regulatory networks

NASA Astrophysics Data System (ADS)

Borg, Yanika; Ullner, Ekkehard; Alagha, Afnan; Alsaedi, Ahmed; Nesbeth, Darren; Zaikin, Alexey

2014-03-01

One aim of synthetic biology is to construct increasingly complex genetic networks from interconnected simpler ones to address challenges in medicine and biotechnology. However, as systems increase in size and complexity, emergent properties lead to unexpected and complex dynamics due to nonlinear and nonequilibrium properties from component interactions. We focus on four different studies of biological systems which exhibit complex and unexpected dynamics. Using simple synthetic genetic networks, small and large populations of phase-coupled quorum sensing repressilators, Goodwin oscillators, and bistable switches, we review how coupled and stochastic components can result in clustering, chaos, noise-induced coherence and speed-dependent decision making. A system of repressilators exhibits oscillations, limit cycles, steady states or chaos depending on the nature and strength of the coupling mechanism. In large repressilator networks, rich dynamics can also be exhibited, such as clustering and chaos. In populations of Goodwin oscillators, noise can induce coherent oscillations. In bistable systems, the speed with which incoming external signals reach steady state can bias the network towards particular attractors. These studies showcase the range of dynamical behavior that simple synthetic genetic networks can exhibit. In addition, they demonstrate the ability of mathematical modeling to analyze nonlinearity and inhomogeneity within these systems.

Large and unexpected runup events and their relation to the incident wave field

NASA Astrophysics Data System (ADS)

Li, C.; Ozkan-Haller, H. T.; Garcia-Medina, G.; Holman, R. A.; Ruggiero, P.

2016-12-01

Unusually large runup events are important for the prediction of dune erosion, inundation and coastal flooding during storms and lie at the tail of swash maxima probability distributions. We also distinguish a unique type of large runup event that is sudden and unexpected even if the landward reach of the runup is not a statistical extreme. These unusual runup events are anecdotally reported to be more prevalent on dissipative beaches and are the leading cause of death by drowning along the U.S. Pacific Northwest (northern California, Oregon, and Washington). Herein we examine the environmental conditions that are conducive to large and unexpected runup events and begin to forecast their potential occurrence, validating these predictions with ongoing observations. We explore and compare the statistics of large runup events on two beach types, a dissipative beach at Agate Beach, OR, and the intermediate/reflective site at Duck, NC. Video-based runup observations along with incident wave information from offshore instrumentation are used to assess how frequently large or unexpected runup events occur, how the statistics of these runup events relate to the incident wave characteristics (e.g. height, period, narrow-bandedness), and whether or not these events are indeed more prevalent on dissipative beaches.

Incorporating deep learning with convolutional neural networks and position specific scoring matrices for identifying electron transport proteins.

PubMed

Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

2017-09-05

In several years, deep learning is a modern machine learning technique using in a variety of fields with state-of-the-art performance. Therefore, utilization of deep learning to enhance performance is also an important solution for current bioinformatics field. In this study, we try to use deep learning via convolutional neural networks and position specific scoring matrices to identify electron transport proteins, which is an important molecular function in transmembrane proteins. Our deep learning method can approach a precise model for identifying of electron transport proteins with achieved sensitivity of 80.3%, specificity of 94.4%, and accuracy of 92.3%, with MCC of 0.71 for independent dataset. The proposed technique can serve as a powerful tool for identifying electron transport proteins and can help biologists understand the function of the electron transport proteins. Moreover, this study provides a basis for further research that can enrich a field of applying deep learning in bioinformatics. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cosmogenic radionuclides on LDEF: An unexpected Be-10 result

NASA Technical Reports Server (NTRS)

Gregory, J. C.; Albrecht, A.; Herzog, G.; Klein, J.; Middleton, R.; Dezfouly-Arjomandy, B.; Harmon, B. A.

1993-01-01

Following the discovery of the atmospheric derived cosmogenic radionuclide Be-7 on the Long Duration Exposure Facility (LDEF), a search began for other known nuclides produced by similar mechanisms. None of the others have the narrow gamma-ray line emission of Be-7 decay which enabled its rapid detection and quantification. A search for Be-10 atoms on LDEF clamp plates using accelerator mass spectrometry is described. An unexpected result was obtained.

Real-space analysis of radiation-induced specific changes with independent component analysis

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

Borek, Dominika; Bromberg, Raquel; Hattne, Johan

A method of analysis is presented that allows for the separation of specific radiation-induced changes into distinct components in real space. The method relies on independent component analysis (ICA) and can be effectively applied to electron density maps and other types of maps, provided that they can be represented as sets of numbers on a grid. Here, for glucose isomerase crystals, ICA was used in a proof-of-concept analysis to separate temperature-dependent and temperature-independent components of specific radiation-induced changes for data sets acquired from multiple crystals across multiple temperatures. ICA identified two components, with the temperature-independent component being responsible for themore » majority of specific radiation-induced changes at temperatures below 130 K. The patterns of specific temperature-independent radiation-induced changes suggest a contribution from the tunnelling of electron holes as a possible explanation. In the second case, where a group of 22 data sets was collected on a single thaumatin crystal, ICA was used in another type of analysis to separate specific radiation-induced effects happening on different exposure-level scales. Here, ICA identified two components of specific radiation-induced changes that likely result from radiation-induced chemical reactions progressing with different rates at different locations in the structure. In addition, ICA unexpectedly identified the radiation-damage state corresponding to reduced disulfide bridges rather than the zero-dose extrapolated state as the highest contrast structure. The application of ICA to the analysis of specific radiation-induced changes in real space and the data pre-processing for ICA that relies on singular value decomposition, which was used previously in data space to validate a two-component physical model of X-ray radiation-induced changes, are discussed in detail. This work lays a foundation for a better understanding of protein-specific radiation

Psychological impact of unexpected explicit recall of events occurring during surgery performed under sedation, regional anaesthesia, and general anaesthesia: data from the Anesthesia Awareness Registry.

PubMed

Kent, C D; Mashour, G A; Metzger, N A; Posner, K L; Domino, K B

2013-03-01

Anaesthetic awareness is a recognized complication of general anaesthesia (GA) and is associated with post-traumatic stress disorder (PTSD). Although complete amnesia for intraprocedural events during sedation and regional anaesthesia (RA) may occur, explicit recall is expected by anaesthesia providers. Consequently, the possibility that there could be psychological consequences associated with unexpected explicit recall of events during sedation and RA has not been investigated. This study investigated the psychological sequelae of unexpected explicit recall of events during sedation/RA that was reported to the Anesthesia Awareness Registry. The Registry recruited subjects who self-identified as having had anaesthetic awareness. Inclusion criteria were a patient-reported awareness experience in 1990 or later and availability of medical records. The sensations experienced by the subjects during their procedure and the acute and persistent psychological sequelae attributed to this explicit recall were assessed for patients receiving sedation/RA and those receiving GA. Among the patients fulfilling the inclusion criteria, medical record review identified 27 sedation/RA and 50 GA cases. Most patients experienced distress (78% of sedation/RA vs 94% of GA). Approximately 40% of patients with sedation/RA had persistent psychological sequelae, similar to GA patients. Some sedation/RA patients reported an adverse impact on their job performance (15%), family relationships (11%), and friendships (11%), and 15% reported being diagnosed with PTSD. Patients who self-reported to the Registry unexpected explicit recall of events during sedation/RA experienced distress and persistent psychological sequelae comparable with those who had reported anaesthetic awareness during GA. Further study is warranted to determine if patients reporting distress with explicit recall after sedation/RA require psychiatric follow-up.

A Bottom-Up Proteomic Approach to Identify Substrate Specificity of Outer-Membrane Protease OmpT.

PubMed

Wood, Sarah E; Sinsinbar, Gaurav; Gudlur, Sushanth; Nallani, Madhavan; Huang, Che-Fan; Liedberg, Bo; Mrksich, Milan

2017-12-22

Identifying peptide substrates that are efficiently cleaved by proteases gives insights into substrate recognition and specificity, guides development of inhibitors, and improves assay sensitivity. Peptide arrays and SAMDI mass spectrometry were used to identify a tetrapeptide substrate exhibiting high activity for the bacterial outer-membrane protease (OmpT). Analysis of protease activity for the preferred residues at the cleavage site (P1, P1') and nearest-neighbor positions (P2, P2') and their positional interdependence revealed FRRV as the optimal peptide with the highest OmpT activity. Substituting FRRV into a fragment of LL37, a natural substrate of OmpT, led to a greater than 400-fold improvement in OmpT catalytic efficiency, with a k cat /K m value of 6.1×10 6  L mol -1  s -1 . Wild-type and mutant OmpT displayed significant differences in their substrate specificities, demonstrating that even modest mutants may not be suitable substitutes for the native enzyme. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2016-03-01

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

[Identifying children at risk for cardiorespiratory arrest].

PubMed

Carrillo Alvarez, A; Martínez Gutiérrez, A; Salvat Germán, F

2004-08-01

Cardiorespiratory arrest in children with severe disease does not usually present suddenly or unexpectedly but is often the result of a progressive deterioration of respiratory and/or circulatory function. Before failure of these functions occurs, there is a series of clinical signs that serve as a warning. Health professionals should not only evaluate clinical signs of respiratory and/or circulatory insufficiency but should also be able to identify these warning signs as early as possible, preferably in the compensation phase, given that the possibility that this process can be reversed by therapeutic measures decreases as the process progresses.

The cognitive nuances of surprising events: exposure to unexpected stimuli elicits firing variations in neurons of the dorsal CA1 hippocampus.

PubMed

Valenti, Ornella; Mikus, Nace; Klausberger, Thomas

2018-05-22

The ability to recognize novel situations is among the most fascinating and vital of the brain functions. A hypothesis posits that encoding of novelty is prompted by failures in expectancy, according to computation matching incoming information with stored events. Thus, unexpected changes in context are detected within the hippocampus and transferred to downstream structures, eliciting the arousal of the dopamine system. Nevertheless, the precise locus of detection is a matter of debate. The dorsal CA1 hippocampus (dCA1) appears as an ideal candidate for operating a mismatch computation and discriminating the occurrence of diverse stimuli within the same environment. In this study, we sought to determine dCA1 neuronal firing during the experience of novel stimuli embedded in familiar contexts. We performed population recordings while head-fixed mice navigated virtual environments. Three stimuli were employed, namely a novel pattern of visual cues, an odor, and a reward with enhanced valence. The encounter of unexpected events elicited profound variations in dCA1 that were assessed both as opposite rate directions and altered network connectivity. When experienced in sequence, novel stimuli elicited specific responses that often exhibited cross-sensitization. Short-latency, event-triggered responses were in accordance with the detection of novelty being computed within dCA1. We postulate that firing variations trigger neuronal disinhibition, and constitute a fundamental mechanism in the processing of unexpected events and in learning. Elucidating the mechanisms underlying detection and computation of novelty might help in understanding hippocampal-dependent cognitive dysfunctions associated with neuropathologies and psychiatric conditions.

Critical properties of unlimited gliding: Unexpected flocking behavior driven by the exchange of information

NASA Astrophysics Data System (ADS)

Bigus-Kwiatkowska, Marta; Fronczak, Agata; Fronczak, Piotr

2018-03-01

Inspired by albatrosses that use thermal lifts to fly across oceans we develop a simple model of gliders that serves us to study theoretical limitations of unlimited exploration of the Earth. Our studies, grounded in physical theory of continuous percolation and biased random walks, allow us to identify a variety of percolation transitions, which are understood as providing potentially unlimited movement through a space in a specified direction. We discover an unexpected phenomenon of self-organization of gliders in clusters, which resembles the flock organization of birds. This self-organization is intriguing, as it occurs thanks to exchange of information only and without any particular rules that could favor the clustering of the gliders (in contrast to the causes well known in literature, like, for example, attractive forces used in the Vicsek-type models or fitness functions used in evolutionary computation).

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

USGS Publications Warehouse

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

2014-01-01

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

Sudden unexpected infant death: differentiating natural from abusive causes in the emergency department.

PubMed

Bechtel, Kirsten

2012-10-01

Sudden unexpected infant deaths (SUIDs) are deaths in infants younger than 12 months that occur suddenly, unexpectedly, and without obvious cause in the emergency department (ED). Sudden infant death syndrome, the leading cause of SUID in the United States, is much more common, but fatal child abuse and neglect have been sometimes mistaken for sudden infant death syndrome. The distinction between these 2 entities can only be made after a thorough investigation of the scene, interview of caregivers, and a complete forensic autopsy. Development of ED guidelines for the reporting and evaluation of SUID, in collaboration with the local medical examiner and child death review teams, will enable ED practitioners to collect important information in a compassionate manner that will be valuable to the investigating personnel.

Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity.

PubMed

Zander, Ryan A; Vijay, Rahul; Pack, Angela D; Guthmiller, Jenna J; Graham, Amy C; Lindner, Scott E; Vaughan, Ashley M; Kappe, Stefan H I; Butler, Noah S

2017-11-14

Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist. Unexpectedly, Th1-like memory cells exhibit phenotypic and functional features of Tfh cells during recall and provide potent B cell help and protection following transfer, characteristics that are enhanced following ligation of the T cell co-stimulatory receptor OX40. Our findings delineate critical functional attributes of Plasmodium-specific memory CD4 T cells and identify a host-specific factor that can be targeted to improve resolution of acute malaria and provide durable, long-term protection against Plasmodium parasite re-exposure. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

PubMed

Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

2016-09-07

Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unexpected trend in the compositional maturity of second-cycle sand

USGS Publications Warehouse

Solano-Acosta, W.; Dutta, P.K.

2005-01-01

It is generally accepted that recycling of sandstone generates relatively more mature sand than its parent sandstone. Such maturity is accomplished mainly through chemical weathering as the chemically unstable minerals are eliminated. Because chemical weathering is ubiquitous on the Earth's surface, maturity due to recycling is expected in most geological settings. However, contrary to one's expectation, second-cycle Holocene sand, exclusively derived from sandy facies of the first-cycle Pennsylvanian-Permian Cutler Formation, is actually less mature than its first-cycle parent near Gateway, Colorado. Both the Cutler sandstone and Holocene sand were the products of similar geological processes that controlled their respective composition. In spite of such similarities, a significant difference in composition is observed. We propose that the unexpected immaturity in second-cycle Holocene sand may be due to mechanical disintegration of coarse-grained feldspar and feldspar-rich rock fragments into relatively smaller fractions. Results presented in this paper are the first quantitative estimation of recycling of parent sandstone into daughter sand, and the first observed reverse maturity trend in second-cycle sand. These unexpected results suggest the need for further research to quantitatively understand the recycling process. ?? 2005 Elsevier B.V. All rights reserved.

Identifying children with specific reading disabilities from listening and reading discrepancy scores.

PubMed

Spring, C; French, L

1990-01-01

A method of identifying children with specific reading disabilities by identifying discrepancies between their reading and listening comprehension scores was validated with disabled and nondisabled readers in Grades 4, 5, and 6. The method is based on a modification of the reading comprehension subtest of the Peabody Individual Achievement Test (Dunn & Markwardt, 1970). In this modification, even-numbered sentences are read by subjects, and odd-numbered sentences are read by the test administrator as subjects listen. The features of this test that reduce demands on working memory, thereby making it suitable for the detection of a discrepancy between reading and listening comprehension in readers with disabilities, are discussed. A significant group-by-modality interaction was obtained. Children with reading disabilities scored significantly lower on reading than on listening comprehension, while nondisabled readers scored slightly higher, but not significantly so, on reading than on listening comprehension. The appropriateness of this method as a substitute for the traditional method, which is based on the detection of a discrepancy between intelligence and reading and which has recently been proscribed in certain school districts, is discussed. Issues concerning the listening comprehension skills of disabled readers are also discussed.

Male specific genes from dioecious white campion identified by fluorescent differential display.

PubMed

Scutt, Charles P; Jenkins, Tom; Furuya, Masaki; Gilmartin, Philip M

2002-05-01

Fluorescent differential display (FDD) has been used to screen for cDNAs that are differentially up-regulated in male flowers of the dioecious plant Silene latifolia in which an X/Y chromosome system of sex determination operates. To adapt FDD to the cloning of large numbers of differential cDNAs, a novel method of confirming the differential expression of these has been devised. FDD gels were Southern electro-blotted and probed with mixtures of individual cDNA clones derived from different FDD product ligation reactions. These Southern blots were then stripped and re-probed with further mixtures of individual cloned FDD products to identify the maximum number of recombinant clones carrying the true differential amplification products. Of 135 differential bands identified by FDD, 56 differential amplification products were confirmed; these represent 23 unique differentially expressed genes as determined by virtual Northern analysis and two genes expressed at or below the level of detection by virtual Northern analysis. These two low expressed genes show bands of hybridization on genomic Southern blots that are specific to male plants, indicating that they are derived from, or closely related to, Y chromosome genes.

Sensitivity and specificity of administrative mortality data for identifying prescription opioid–related deaths

PubMed Central

Gladstone, Emilie; Smolina, Kate; Morgan, Steven G.; Fernandes, Kimberly A.; Martins, Diana; Gomes, Tara

2016-01-01

Background: Comprehensive systems for surveilling prescription opioid–related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid–related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid–related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. Methods: We identified all prescription opioid–related deaths from Ontario coroners’ data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid–related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid–related deaths. Results: Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. Interpretation: In the absence of specific systems for monitoring prescription opioid–related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid–related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. PMID:26622006

Sensitivity and specificity of administrative mortality data for identifying prescription opioid-related deaths.

PubMed

Gladstone, Emilie; Smolina, Kate; Morgan, Steven G; Fernandes, Kimberly A; Martins, Diana; Gomes, Tara

2016-03-01

Comprehensive systems for surveilling prescription opioid-related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid-related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid-related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. We identified all prescription opioid-related deaths from Ontario coroners' data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid-related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid-related deaths. Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. In the absence of specific systems for monitoring prescription opioid-related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid-related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. © 2016 Canadian Medical Association or its licensors.

Coupling genetics and proteomics to identify aphid proteins associated with vector-specific transmission of polerovirus (luteoviridae).

PubMed

Yang, Xiaolong; Thannhauser, T W; Burrows, Mary; Cox-Foster, Diana; Gildow, Fred E; Gray, Stewart M

2008-01-01

Cereal yellow dwarf virus-RPV (CYDV-RPV) is transmitted specifically by the aphids Rhopalosiphum padi and Schizaphis graminum in a circulative nonpropagative manner. The high level of vector specificity results from the vector aphids having the functional components of the receptor-mediated endocytotic pathways to allow virus to transverse the gut and salivary tissues. Studies of F(2) progeny from crosses of vector and nonvector genotypes of S. graminum showed that virus transmission efficiency is a heritable trait regulated by multiple genes acting in an additive fashion and that gut- and salivary gland-associated factors are not genetically linked. Utilizing two-dimensional difference gel electrophoresis to compare the proteomes of vector and nonvector parental and F(2) genotypes, four aphid proteins (S4, S8, S29, and S405) were specifically associated with the ability of S. graminum to transmit CYDV-RPV. The four proteins were coimmunoprecipitated with purified RPV, indicating that the aphid proteins are capable of binding to virus. Analysis by mass spectrometry identified S4 as a luciferase and S29 as a cyclophilin, both of which have been implicated in macromolecular transport. Proteins S8 and S405 were not identified from available databases. Study of this unique genetic system coupled with proteomic analysis indicated that these four virus-binding aphid proteins were specifically inherited and conserved in different generations of vector genotypes and suggests that they play a major role in regulating polerovirus transmission.

Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-08-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Final 3. DATES COVERED (From - To) 15May2012 - 31Aug2016 Identifying Military and Combat-Specific Risk Factors for Child Adjustment...deployment and has a child between the age of 3 and 7 and comparison groups of civilain single parent families (N=200) and civilian dual parent

Sudden Unexpected Death in Epilepsy: A Retrospective Autopsy Study of 112 Epileptic Patients.

PubMed

Esen Melez, İpek; Arslan, Murat Nihat; Melez, Deniz Oğuzhan; Şanli, Ahmet Necati; Koç, Sermet

2017-09-01

Sudden unexpected deaths comprise the most important and worthy investigation case profiles in both neurology and forensic medicine. Epilepsy, which is one of the neuropathological causes of sudden unexpected deaths, is an important disorder having mysterious aspects. The aim of this study is to make common the points of view between neurology and forensic medicine experts and to discuss the features of the findings together with the related clinical hypotheses, leading to the differential diagnosis of sudden unexpected death in epilepsy (SUDEP) by presenting autopsy findings and available medical data of patients who had a prior diagnosis of epilepsy. In Istanbul, the cases of 20334 autopsied patients who were referred to The Ministry of Justice Council of Forensic Medicine between 2007 and 2011 were identified from the complete forensic autopsy data of the city and were retrospectively reviewed. Patients who had a prior diagnosis of epilepsy were included. Both descriptive and inferential statistical analyses were performed through the parameters of demographical data, physical properties, incident features, macroscopic-microscopic autopsy findings, and cause of death initially for all cases and then separately for SUDEP cases. Among the 20334 patients, 112 were determined to have a prior diagnosis of epilepsy. A possible macroscopic and/or microscopic epileptic focus was present in 23 (20.5%) of these 112 cases. The cause of death was determined to be SUDEP in 40 (35.7%) cases, while it could not be determined in 28 (25%) cases. Among patients whose death cause was considered as SUDEP, the male-to-female ratio was 1.1:1, while the mean age was 31.5±13.9 years in males and 29.6±12.9 years in females. The presence of hypertrophy and myocardial scar tissue findings in the microscopic examination were significantly more frequent among patients determined to have died from cardiovascular diseases compared to patients in the SUDEP group (p=0.001 for each finding

Sudden unexpected death in epilepsy.

PubMed

Shorvon, Simon; Tomson, Torbjorn

2011-12-10

Sudden unexpected death in epilepsy (SUDEP) refers to the sudden death of a seemingly healthy individual with epilepsy, usually occurring during, or immediately after, a tonic-clonic seizure. The frequency of SUDEP varies depending on the severity of the epilepsy, but overall the risk of sudden death is more than 20 times higher than that in the general population. Several different mechanisms probably exist, and most research has focused on seizure-related respiratory depression, cardiac arrhythmia, cerebral depression, and autonomic dysfunction. Data from a pooled analysis of risk factors indicate that the higher the frequency of tonic-clonic seizures, the higher the risk of SUDEP; furthermore, risk of SUDEP is also elevated in male patients, patients with long-duration epilepsy, and those on antiepileptic polytherapy. SUDEP usually occurs when the seizures are not witnessed and often at night. In this Seminar, we provide advice to clinicians on ways to minimise the risk of SUDEP, information to pass on to patients, and medicolegal aspects of these deaths. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

De Gregorio, Michael; Santos, Veronica J

2013-04-05

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

Targeting IL-2: an unexpected effect in treating immunological diseases.

PubMed

Ye, Congxiu; Brand, David; Zheng, Song G

2018-01-01

Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.

Identifying Military and Combat Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-06-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Annual 3. DATES COVERED (From - To) 15 May - 2013 - 14 May 2014. Identifying Military and Combat-Specific Risk Factors for Child ...parents (N=200) whose spouse/partner is currently in a “low perceived risk” deployment and has a child between the age of 3 and 7 and comparison

Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154.

PubMed

Kunnath-Velayudhan, Shajo; Goldberg, Michael F; Saini, Neeraj K; Johndrow, Christopher T; Ng, Tony W; Johnson, Alison J; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A

2017-10-01

Analysis of Ag-specific CD4 + T cells in mycobacterial infections at the transcriptome level is informative but technically challenging. Although several methods exist for identifying Ag-specific T cells, including intracellular cytokine staining, cell surface cytokine-capture assays, and staining with peptide:MHC class II multimers, all of these have significant technical constraints that limit their usefulness. Measurement of activation-induced expression of CD154 has been reported to detect live Ag-specific CD4 + T cells, but this approach remains underexplored and, to our knowledge, has not previously been applied in mycobacteria-infected animals. In this article, we show that CD154 expression identifies adoptively transferred or endogenous Ag-specific CD4 + T cells induced by Mycobacterium bovis bacillus Calmette-Guérin vaccination. We confirmed that Ag-specific cytokine production was positively correlated with CD154 expression by CD4 + T cells from bacillus Calmette-Guérin-vaccinated mice and show that high-quality microarrays can be performed from RNA isolated from CD154 + cells purified by cell sorting. Analysis of microarray data demonstrated that the transcriptome of CD4 + CD154 + cells was distinct from that of CD154 - cells and showed major enrichment of transcripts encoding multiple cytokines and pathways of cellular activation. One notable finding was the identification of a previously unrecognized subset of mycobacteria-specific CD4 + T cells that is characterized by the production of IL-3. Our results support the use of CD154 expression as a practical and reliable method to isolate live Ag-specific CD4 + T cells for transcriptomic analysis and potentially for a range of other studies in infected or previously immunized hosts. Copyright © 2017 by The American Association of Immunologists, Inc.

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.

Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations

PubMed Central

Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.

2015-01-01

Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087

Teach Students to Dig for Understanding Using an Unexpected Technological Shovel

ERIC Educational Resources Information Center

Lake, Susan E. L.

2004-01-01

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

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

ERIC Educational Resources Information Center

Kroskrity, Paul V.

2011-01-01

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

Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study.

PubMed

Kommajosyula, Srinivasa P; Randall, Marcus E; Brozoski, Thomas J; Odintsov, Boris M; Faingold, Carl L

2017-09-01

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to

A novel archaeal group in the phylum Crenarchaeota found unexpectedly in an eukaryotic survey in the Cariaco Basin.

PubMed

Jeon, Sun-Ok; Ahn, Tae-Seok; Hong, Sun-Hee

2008-02-01

Archaea have been found in many more diverse habitats than previously believed due in part to modern molecular approaches to discovering microbial diversity. We report here an unexpected expansion of the habitat diversity of the Archaea in the Cariaco Basin we found using a primer set designed for 18S eukaryotic rDNA sequence analysis. The results presented here expand the originally identified 9 archaeal clones reported in this environment using bacterial/archaeal primers to 152 archaeal clones: 67 (18 OTU) of these clones were found at a depth of 900 m of station A while 71 (9 OTU) of them were at a depth of between 300 approximately 335 m of station B&C depending upon which location the samples were taken. We used three phylogenetic analysis methods and detected 20 phylotypes belonging to a single previously unreported group distantly related to the Crenarchaeota. Also, we determined that the original nine sequences did not fall into any of the known phyla of the Archaea suggesting that they may represent a novel group within the Kingdom Archaea. Thus, from these two studies, we suggest that Archaea in the Cariaco Basin could be unique; however, further studies using archaeal-specific primers and the design of new primers as well as the systematic use of several different primer combinations may improve the chances of understanding the archeal diversity in the Cariaco Basin.

Unexpected extent of immunochemical cross-reactions between rabbit and human serum proteins

PubMed Central

Johnson, P. K.; Yoder, J. M.

1970-01-01

Precipitin experiments indicated an unexpected extent of immunochemical cross-reactions between rabbit and human serum proteins. Commerical goat or horse antisera to human or rabbit serum were used. Two of the proteins involved in the cross-reactions were lipoproteins. Imagesp294-ap296-a PMID:4991121

Unexpected acoustic stimulation during action preparation reveals gradual re-specification of movement direction.

PubMed

Marinovic, Welber; Tresilian, James; Chapple, Jack L; Riek, Stephan; Carroll, Timothy J

2017-04-21

A loud acoustic stimulus (LAS) is often used as a tool to investigate motor preparation in simple reaction time (RT) tasks, where all movement parameters are known in advance. In this report, we used a LAS to examine direction specification in simple and choice RT tasks. This allowed us to investigate how the specification of movement direction unfolds during the preparation period. In two experiments, participants responded to the appearance of an imperative stimulus (IS) with a ballistic wrist force directed toward one of two targets. In probe trials, a LAS (120dBa) was delivered around the time of IS presentation. In Experiment 1, RTs in the simple RT task were faster when the LAS was presented, but the effect on the movement kinematics was negligible. In the Choice RT task, however, movement direction variability increased when the LAS was presented. In Experiment 2, when we primed movements toward one direction, our analyses revealed that the longer participants took to start a movement, the more accurate their responses became. Our results show not only that movement direction reprogramming occurs quickly and continuously, but also that LAS can be a valuable tool to obtain meaningful readouts of the motor system's preparatory state. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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 .

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... August 26, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from Violence in Kyrgyzstan... humanitarian needs resulting from recent violence in Kyrgyzstan. You are authorized and directed to publish...

The Burden of Loss: Unexpected death of a loved one and psychiatric disorders across the life course in a national study

PubMed Central

Keyes, Katherine M.; Pratt, Charissa; Galea, Sandro; McLaughlin, Katie A.; Koenen, Karestan C.; Shear, M. Katherine

2014-01-01

Background Unexpected death of a loved one is common and associated with subsequent elevations in symptoms of multiple forms of psychopathology. Determining whether this experience predicts novel onset of psychiatric disorders and whether these associations vary across the life course has important clinical implications. Aims To examine associations of a loved one’s unexpected death with first onset of common anxiety, mood, and substance disorders in a population-based sample. Methods Relation between unexpected death and first onset of lifetime DSM-IV disorders estimated using a structured interview of adults in the US general population (analytic sample size=27,534). Models controlled for prior occurrence of any disorder, other traumatic event experiences, and demographics. Results Unexpected death was the most common traumatic experience and most likely to be rated as the respondent’s worst, regardless of other traumatic experiences. Increased incidence after unexpected death was observed at every point across the life course for major depressive episodes, panic disorder, and post-traumatic stress disorder. Increased incidence was clustered in later adult age groups for manic episodes, phobias, alcohol disorders, and generalized anxiety disorder. Conclusions The bereavement period is associated with elevated risk for the onset of multiple psychiatric disorders, consistently across the life course and coincident with the experience of the loved one’s death. Novel associations between unexpected death and onset of several disorders, including mania, confirm multiple case reports and small studies, and suggest an important emerging area for clinical research and practice. PMID:24832609

Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

PubMed

Ahn, Woo-Young; Vassileva, Jasmin

2016-04-01

Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence

PubMed Central

Ahn, Woo-Young; Vassileva, Jasmin

2016-01-01

Background Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. Methods The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. Results The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. Conclusions These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. PMID:26905209

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

PubMed

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

2004-12-15

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

Identifying context-specific competencies required by community Australian Football sports trainers.

PubMed

Donaldson, Alex; Finch, Caroline F

2012-08-01

First-aid is a recommended injury prevention and risk management strategy in community sport; however, little is known about the sport-specific competencies required by first-aid providers. To achieve expert consensus on the competencies required by community Australian Football (community-AF) sports trainers. A three-round online Delphi process. Community-AF. 16 Australian sports first-aid and community-AF experts. Rating of competencies as either 'essential', 'expected', 'ideal' or 'not required'. Results After Round 3, 47 of the 77 (61%) competencies were endorsed as 'essential' or 'expected' for a sports trainer to effectively perform the activities required to the standards expected at a community-AF club by ≥75% of experts. These competencies covered: the role of the sports trainer; the responsibilities of the sports trainer; emergency management; injury and illness assessment and immediate management; taping; and injury prevention and risk management. Four competencies (5%) were endorsed as 'ideal' or 'not required' by ≥85% of experts and were excluded from further consideration. The 26 competencies where consensus was not reached were retained as second-tier, optional competencies. Sports trainers are important members of on-field first-aid teams, providing support to both injured players and other sports medicine professionals. The competencies identified in this study provide the basis of a proposed two-tiered community-AF-specific sports trainer education structure that can be implemented by the peak sports body. This includes six mandatory modules, relating to the 'required' competencies, and a further six optional modules covering competencies on which consensus was not reached.

MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

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

Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.

2004-10-28

We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

How Incidental Sequence Learning Creates Reportable Knowledge: The Role of Unexpected Events

ERIC Educational Resources Information Center

Runger, Dennis; Frensch, Peter A.

2008-01-01

Research on incidental sequence learning typically is concerned with the characteristics of implicit or nonconscious learning. In this article, the authors aim to elucidate the cognitive mechanisms that contribute to the generation of explicit, reportable sequence knowledge. According to the unexpected-event hypothesis (P. A. Frensch, H. Haider,…

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

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

Genome-wide meta-analysis identifies novel gender specific loci associated with thyroid antibodies level in Croatians.

PubMed

Matana, Antonela; Popović, Marijana; Boutin, Thibaud; Torlak, Vesela; Brdar, Dubravka; Gunjača, Ivana; Kolčić, Ivana; Boraska Perica, Vesna; Punda, Ante; Polašek, Ozren; Hayward, Caroline; Barbalić, Maja; Zemunik, Tatijana

2018-04-18

Autoimmune thyroid diseases (AITD) are multifactorial endocrine diseases most frequently accompanied by Tg and TPO autoantibodies. Both antibodies have a higher prevalence in females and act under a strong genetic influence. To identify novel variants underlying thyroid antibody levels, we performed GWAS meta-analysis on the plasma levels of TgAb and TPOAb in three Croatian cohorts, as well as gender specific GWAS and a bivariate analysis. No significant association was detected with the level of TgAb and TPOAb in the meta-analysis of GWAS or bivariate results for all individuals. The bivariate analysis in females only revealed a genome-wide significant association for the locus near GRIN3A (rs4457391, P = 7.76 × 10 -9 ). The same locus had borderline association with TPOAb levels in females (rs1935377, P = 8.58 × 10 -8 ). In conclusion, we identified a novel gender specific locus associated with TgAb and TPOAb levels. Our findings provide a novel insight into genetic and gender differences associated with thyroid antibodies. Copyright © 2018 Elsevier Inc. All rights reserved.

Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity

PubMed Central

Jacques-Fricke, Bridget T.; Gammill, Laura S.

2014-01-01

Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases active in neural crest precursors are unknown. Moreover, the regulation of methylation during the dynamic process of neural crest migration is unclear. Here we show that the lysine methyltransferase NSD3 is abundantly and specifically expressed in premigratory and migratory neural crest cells. NSD3 expression commences before up-regulation of neural crest genes, and NSD3 is necessary for expression of the neural plate border gene Msx1, as well as the key neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3, but not gene expression generally. Nevertheless, only Sox10 histone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3-dependent neural crest gene regulation. In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3-related methyltransferase activity in neural crest migration. These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration. PMID:25318671

GSHSite: Exploiting an Iteratively Statistical Method to Identify S-Glutathionylation Sites with Substrate Specificity

PubMed Central

Chen, Yi-Ju; Lu, Cheng-Tsung; Huang, Kai-Yao; Wu, Hsin-Yi; Chen, Yu-Ju; Lee, Tzong-Yi

2015-01-01

S-glutathionylation, the covalent attachment of a glutathione (GSH) to the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM) that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-glutathionylation remains unknown. Based on a total of 1783 experimentally identified S-glutathionylation sites from mouse macrophages, this work presents an informatics investigation on S-glutathionylation sites including structural factors such as the flanking amino acids composition and the accessible surface area (ASA). TwoSampleLogo presents that positively charged amino acids flanking the S-glutathionylated cysteine may influence the formation of S-glutathionylation in closed three-dimensional environment. A statistical method is further applied to iteratively detect the conserved substrate motifs with statistical significance. Support vector machine (SVM) is then applied to generate predictive model considering the substrate motifs. According to five-fold cross-validation, the SVMs trained with substrate motifs could achieve an enhanced sensitivity, specificity, and accuracy, and provides a promising performance in an independent test set. The effectiveness of the proposed method is demonstrated by the correct identification of previously reported S-glutathionylation sites of mouse thioredoxin (TXN) and human protein tyrosine phosphatase 1b (PTP1B). Finally, the constructed models are adopted to implement an effective web-based tool, named GSHSite (http://csb.cse.yzu.edu.tw/GSHSite/), for identifying uncharacterized GSH substrate sites on the protein sequences. PMID:25849935

Use of mass spectrometry fingerprinting to identify urinary metabolites after consumption of specific foods.

PubMed

Lloyd, Amanda J; Favé, Gaëlle; Beckmann, Manfred; Lin, Wanchang; Tailliart, Kathleen; Xie, Long; Mathers, John C; Draper, John

2011-10-01

The lack of robust biological markers of dietary exposure hinders the quantitative understanding of causal relations between diet and health. We aimed to develop an efficient procedure to discover metabolites in urine that may have future potential as biomarkers of acute exposure to foods of high public health importance. Twenty-four participants were provided with a test breakfast in which the cereal component of a standardized breakfast was replaced by 1 of 4 foods of high public health importance; 1.5-, 3-, and 4.5-h postprandial urine samples were collected. Flow infusion electrospray-ionization mass spectrometry followed by supervised multivariate data analysis was used to discover signals resulting from consumption of each test food. Fasted-state urine samples provided a universal comparator for food biomarker lead discovery in postprandial urine. The filtering of data features associated with consumption of the common components of the standardized breakfast improved discrimination models and readily identified metabolites that showed consumption of specific test foods. A combination of trimethylamine-N-oxide and 1-methylhistidine was associated with salmon consumption. Novel ascorbate derivatives were discovered in urine after consumption of either broccoli or raspberries. Sulphonated caffeic acid and sulphonated methyl-epicatechin concentrations increased dramatically after consumption of raspberries. This biomarker lead discovery strategy can identify urinary metabolites associated with acute exposure to individual foods. Future studies are required to validate the specificity and utility of potential biomarkers in an epidemiologic context.

Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing

PubMed Central

Dijamco, Cheri; Kiefer, Amy K.; Eriksson, Nicholas; Moiseff, Bianca; Tung, Joyce Y.; Mountain, Joanna L.

2013-01-01

appreciated learning their BRCA mutation status. Conclusions. Direct access to BRCA mutation tests, considered a model for high-risk actionable genetic tests of proven clinical utility, provided clear benefits to participants. The unexpected information demonstrated a cascade effect as relatives of newly identified carriers also sought testing and more mutation carriers were identified. Given the absence of evidence for serious emotional distress or inappropriate actions in this subset of mutation-positive customers who agreed to be interviewed for this study, broader screening of Ashkenazi Jewish women for these three BRCA mutations should be considered. PMID:23638402

The role of post-mortem investigations in determining the cause of sudden unexpected death in infancy.

PubMed

Weber, M A; Ashworth, M T; Risdon, R A; Hartley, J C; Malone, M; Sebire, N J

2008-12-01

Several autopsy protocols have been suggested for investigating sudden unexpected deaths in infancy (SUDI). The aim of this study is to provide data on the utility of such post-mortem investigations from a large paediatric autopsy series to inform future policy. Retrospective analysis of >1500 consecutive post-mortem examinations carried out by specialist paediatric pathologists at a single centre during a 10-year period according to a common autopsy protocol that included the use of detailed ancillary investigations. SUDI was defined as the sudden unexpected death of an infant aged from 7 to 365 days. All data capture and cause of death classification were carried out according to defined criteria. Of 1516 paediatric post-mortem examinations, 546 presented as SUDI. In 202 infants (37%), death was explained by the autopsy findings. The other 344 cases (63%) remained unexplained. Of the explained deaths, over half (58%) were infective, most commonly due to pneumonia (22%). The component of the post-mortem examination that primarily determined the final cause of death was histological examination in 92 infants (46%), macroscopic examination in 61 (30%), microbiological investigations in 38 (19%) and clinical history in 10 (5%). This constitutes the largest single-institution autopsy study of SUDI. Ten years on from the Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) SUDI studies, the ascertainment of a cause of death at autopsy has improved. However, with almost two thirds of SUDI remaining unexplained, alternative and/or additional diagnostic techniques are required to improve detection rates of identifiable causes of death at autopsy.

Cuphea wrightii thioesterases have unexpected broad specificities on saturated fatty acids.

PubMed

Leonard, J M; Slabaugh, M B; Knapp, S J

1997-07-01

Cuphea wrightii A. Gray is an herbaceous annual that accumulates 30% caprate (10:0) and 54% laurate (12:0) in seed storage lipids. We investigated the role of acyl-acyl carrier protein (ACP) thioesterases (TE) in acyl chain-length regulation in C. wrightii. Two embryo-derived cDNAs, encoding the TEs Cw FatB1 and Cw FatB2, were isolated. Both proteins were detected in developing embryos and mature seeds but not in other tissues, suggesting involvement in seed oil synthesis. Although expected to be 10:0/12:0-ACP-specific, these genes produced a broad range of fatty acids (12:0, 14:0, and 16:0) in transgenic Arabidopsis with the greatest accumulation at 14:0. Cw FatB2 transformants also accumulated small amounts of 10:0. Because C. wrightii accumulates only ca. 5% 14:0 and ca. 2% 16:0, we tested the possibility that gene dosage effects might significantly alter the overall kinetics of the pathway. Phenotypic comparisons of progeny segregating for the transgenes individually and in a hybrid population demonstrated that increased enzyme pools in vivo had a minor effect on diverting fatty acid production to shorter chains. We propose that Cw FatB1 and Cw FatB2 may be necessary but not sufficient determinants of the C. wrightii phenotype.

Using Simulations to Investigate the Longitudinal Stability of Alternative Schemes for Classifying and Identifying Children with Reading Disabilities

ERIC Educational Resources Information Center

Schatschneider, Christopher; Wagner, Richard K.; Hart, Sara A.; Tighe, Elizabeth L.

2016-01-01

The present study employed data simulation techniques to investigate the 1-year stability of alternative classification schemes for identifying children with reading disabilities. Classification schemes investigated include low performance, unexpected low performance, dual-discrepancy, and a rudimentary form of constellation model of reading…

Functional Peptidomics: Stimulus- and Time-of-Day-Specific Peptide Release in the Mammalian Circadian Clock.

PubMed

Atkins, Norman; Ren, Shifang; Hatcher, Nathan; Burgoon, Penny W; Mitchell, Jennifer W; Sweedler, Jonathan V; Gillette, Martha U

2018-06-20

Daily oscillations of brain and body states are under complex temporal modulation by environmental light and the hypothalamic suprachiasmatic nucleus (SCN), the master circadian clock. To better understand mediators of differential temporal modulation, we characterize neuropeptide releasate profiles by nonselective capture of secreted neuropeptides in an optic nerve horizontal SCN brain slice model. Releasates are collected following electrophysiological stimulation of the optic nerve/retinohypothalamic tract under conditions that alter the phase of the SCN activity state. Secreted neuropeptides are identified by intact mass via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found time-of-day-specific suites of peptides released downstream of optic nerve stimulation. Peptide release was modified differentially with respect to time-of-day by stimulus parameters and by inhibitors of glutamatergic or PACAPergic neurotransmission. The results suggest that SCN physiology is modulated by differential peptide release of both known and unexpected peptides that communicate time-of-day-specific photic signals via previously unreported neuropeptide signatures.

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

ERIC Educational Resources Information Center

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

2015-01-01

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

Illnesses and Other Causes of Unexpected Absences from Work During Residency Training.

ERIC Educational Resources Information Center

Parker, Ruth M.; And Others

1987-01-01

Unexpected absences from work among residents cause scheduling difficulties and stress among residents. University of Rochester internal medicine and pediatric residents recorded the days they had been absent from work and provided their opinions regarding the stress these absences caused and the effectiveness for the sick-call system. (Author/MLW)

[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.

Unravelling the mysteries of sudden unexpected death in epilepsy.

PubMed

Hampel, K G; Rocamora Zuñiga, R; Quesada, C M

2017-04-18

Sudden unexpected death in epilepsy (SUDEP) is the most frequent cause of premature death in epileptic patients. Most SUDEP events occur at night and frequently go unnoticed; the exact pathophysiological mechanisms of this phenomenon therefore remain undetermined. Nevertheless, most cases of SUDEP are attributed to an infrequent yet extremely severe complication of epileptic seizures. We conducted a systematic literature search on PubMed. Our review article summarises scientific evidence on the classification, pathophysiological mechanisms, risk factors, biomarkers, and prevention of SUDEP. Likewise, we propose new lines of research and critically analyse findings that are relevant to clinical practice. Current knowledge suggests that SUDEP is a heterogeneous phenomenon caused by multiple factors. In most cases, however, SUDEP is thought to be due to postictal cardiorespiratory failure triggered by generalised tonic-clonic seizures and ultimately leading to cardiac arrest. The underlying pathophysiological mechanism involves multiple factors, ranging from genetic predisposition to environmental factors. Risk of SUDEP is higher in young adults with uncontrolled generalised tonic-clonic seizures. However, patients apparently at lower risk may also experience SUDEP. Current research focuses on identifying genetic and neuroimaging biomarkers that may help determine which patients are at high risk for SUDEP. Antiepileptic treatment is the only preventive measure proven effective to date. Night-time monitoring together with early resuscitation may reduce the risk of SUDEP. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Coupling Genetics and Proteomics To Identify Aphid Proteins Associated with Vector-Specific Transmission of Polerovirus (Luteoviridae)▿

PubMed Central

Yang, Xiaolong; Thannhauser, T. W.; Burrows, Mary; Cox-Foster, Diana; Gildow, Fred E.; Gray, Stewart M.

2008-01-01

Cereal yellow dwarf virus-RPV (CYDV-RPV) is transmitted specifically by the aphids Rhopalosiphum padi and Schizaphis graminum in a circulative nonpropagative manner. The high level of vector specificity results from the vector aphids having the functional components of the receptor-mediated endocytotic pathways to allow virus to transverse the gut and salivary tissues. Studies of F2 progeny from crosses of vector and nonvector genotypes of S. graminum showed that virus transmission efficiency is a heritable trait regulated by multiple genes acting in an additive fashion and that gut- and salivary gland-associated factors are not genetically linked. Utilizing two-dimensional difference gel electrophoresis to compare the proteomes of vector and nonvector parental and F2 genotypes, four aphid proteins (S4, S8, S29, and S405) were specifically associated with the ability of S. graminum to transmit CYDV-RPV. The four proteins were coimmunoprecipitated with purified RPV, indicating that the aphid proteins are capable of binding to virus. Analysis by mass spectrometry identified S4 as a luciferase and S29 as a cyclophilin, both of which have been implicated in macromolecular transport. Proteins S8 and S405 were not identified from available databases. Study of this unique genetic system coupled with proteomic analysis indicated that these four virus-binding aphid proteins were specifically inherited and conserved in different generations of vector genotypes and suggests that they play a major role in regulating polerovirus transmission. PMID:17959668

Unexpected Decrease in Moment of Inertia Between N = 98-100 in 162,164Gd

NASA Astrophysics Data System (ADS)

Jones, E. F.; Hamilton, J. H.; Gore, P. M.; Ramayya, A. V.; Hwang, J. K.; Delima, A. P.; Zhu, S. J.; Beyer, C. J.; Luo, Y. X.; Kormicki, J.; Zhang, X. Q.; Ma, W. C.; Rasmussen, J. O.; Lee, I. Y.; Wu, S. C.; Folden, C. M.; Fallon, P.; Zielinski, P.; Gregorich, K. E.; Macchiavelli, A. O.; Ginter, T. N.; Stoyer, M.; Cole, J. D.; Janssens, R. V. F.; Ahmad, I.; Daniel, A. V.; Ter-Akopian, G. M.; Oganessian, Yu. Ts.; Donangelo, R.; Asztalos, S. J.

2003-10-01

From γ-γ-γ coincidence studies of the prompt γ-rays emitted in the spontaneous fission (SF) of 252Cf with Gammasphere, the yrast energy levels in neutron-rich 162,164Gd were identified for the first time from 2+ to 16+ and from 2+ to 14+, respectively. The 2+ level energies are 71.6 and 73.3 keV in 162,164Gd, respectively. The transition energies from every level in 164Gd are higher than those from the same levels in 162Gd. There is a systematic decrease at every level of the moment of inertia (MOI) and similarly β2 deformation in N = 100 164Gd compared to N = 98 162Gd. The minimum in E(2+) and maxima in MOI and β2 occur at N = 98. This behavior is unexpected compared to the E(2+) and β2 trends in Er, Yb, and Hf nuclei where the minima and maxima occur at neutron midshell, N = 104.

Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes

PubMed Central

Ai, Rizi; Hammaker, Deepa; Boyle, David L.; Morgan, Rachel; Walsh, Alice M.; Fan, Shicai; Firestein, Gary S.; Wang, Wei

2016-01-01

Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signalling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-sequencing. Double-evidenced genes that are both differentially methylated and expressed include multiple HOX genes. Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients. PMID:27282753

Electromyographic and Neuromuscular Force Patterns Associated with Unexpectedly Loaded Rapid Limb Movements.

ERIC Educational Resources Information Center

Richardson, Charles; Simmons, Roger W.

Bi-articular, unidirectional arm movements were studied to evaluate the electromyographic (EMG) and neuromuscular force patterns that occur when a limb is unexpectedly perturbed. A series of training trials were continued with a control load spring attached to the apparatus until a pre-specified criterion for learning was attained. The limb was…

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Specification Reformulation During Specification Validation

NASA Technical Reports Server (NTRS)

Benner, Kevin M.

1992-01-01

The goal of the ARIES Simulation Component (ASC) is to uncover behavioral errors by 'running' a specification at the earliest possible points during the specification development process. The problems to be overcome are the obvious ones the specification may be large, incomplete, underconstrained, and/or uncompilable. This paper describes how specification reformulation is used to mitigate these problems. ASC begins by decomposing validation into specific validation questions. Next, the specification is reformulated to abstract out all those features unrelated to the identified validation question thus creating a new specialized specification. ASC relies on a precise statement of the validation question and a careful application of transformations so as to preserve the essential specification semantics in the resulting specialized specification. This technique is a win if the resulting specialized specification is small enough so the user my easily handle any remaining obstacles to execution. This paper will: (1) describe what a validation question is; (2) outline analysis techniques for identifying what concepts are and are not relevant to a validation question; and (3) identify and apply transformations which remove these less relevant concepts while preserving those which are relevant.

Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape.

PubMed

Leitman, Ellen M; Thobakgale, Christina F; Adland, Emily; Ansari, M Azim; Raghwani, Jayna; Prendergast, Andrew J; Tudor-Williams, Gareth; Kiepiela, Photini; Hemelaar, Joris; Brener, Jacqui; Tsai, Ming-Han; Mori, Masahiko; Riddell, Lynn; Luzzi, Graz; Jooste, Pieter; Ndung'u, Thumbi; Walker, Bruce D; Pybus, Oliver G; Kellam, Paul; Naranbhai, Vivek; Matthews, Philippa C; Gall, Astrid; Goulder, Philip J R

2017-11-06

Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in "shock-and-kill" cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to "corner" the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection. © 2017 Leitman et al.

Sudden unexpected death from oligodendroglioma: a case report and review of the literature.

PubMed

Manousaki, Maria; Papadaki, Helen; Papavdi, Asteria; Kranioti, Elena F; Mylonakis, Panagiotis; Varakis, John; Michalodimitrakis, Manolis

2011-12-01

Sudden and unexpected deaths due to asymptomatic 5 primary brain tumors are extremely rare, with an incidence that ranges from 0.16 to 3.2%. Usually, such tumors are glioblastomas or, less commonly, astrocytomas. Asymptomatic oligodendrogliomas causing sudden death are hardly ever reported among medico-legal investigated cases.We report a rare case of sudden and unexpected death from a previously asymptomatic and undiagnosed, well-differentiated, grade II oligodendrogloioma (WHO classification). According to the autopsy and the microscopic findings brain edema as a result of obstruction of the cerebrospinal fluid flow due to hemorrhagic leakage of the oligodendroglioma is incriminated as the most probable physiopathological mechanism for the sudden death. Diagnosis is mainly based on the special microscopic features of the tumor cells (typical "fried-egg" appearance), interrupted by a dense network of branching capillaries. We discuss further the pathophysiological mechanisms of death and present a short review of literature.

A novel assay to identify the trafficking proteins that bind to specific vesicle populations

PubMed Central

Bentley, Marvin; Banker, Gary

2016-01-01

Here we describe a method capable of identifying interactions between candidate trafficking proteins and a defined vesicle population in intact cells. The assay involves the expression of an FKBP12-rapamycin–binding domain (FRB)–tagged candidate vesicle-binding protein that can be inducibly linked to an FKBP-tagged molecular motor. If the FRB-tagged candidate protein binds the labeled vesicles, then linking the FRB and FKBP domains recruits motors to the vesicles and causes a predictable, highly distinctive change in vesicle trafficking. We describe two versions of the assay: a general protocol for use in cells with a typical microtubule-organizing center and a specialized protocol designed to detect protein-vesicle interactions in cultured neurons. We have successfully used this assay to identify kinesins and Rabs that bind to a variety of different vesicle populations. In principle, this assay could be used to investigate interactions between any category of vesicle trafficking proteins and any vesicle population that can be specifically labeled. PMID:26621371

Beta Atomic Contacts: Identifying Critical Specific Contacts in Protein Binding Interfaces

PubMed Central

Liu, Qian; Kwoh, Chee Keong; Hoi, Steven C. H.

2013-01-01

Specific binding between proteins plays a crucial role in molecular functions and biological processes. Protein binding interfaces and their atomic contacts are typically defined by simple criteria, such as distance-based definitions that only use some threshold of spatial distance in previous studies. These definitions neglect the nearby atomic organization of contact atoms, and thus detect predominant contacts which are interrupted by other atoms. It is questionable whether such kinds of interrupted contacts are as important as other contacts in protein binding. To tackle this challenge, we propose a new definition called beta (β) atomic contacts. Our definition, founded on the β-skeletons in computational geometry, requires that there is no other atom in the contact spheres defined by two contact atoms; this sphere is similar to the van der Waals spheres of atoms. The statistical analysis on a large dataset shows that β contacts are only a small fraction of conventional distance-based contacts. To empirically quantify the importance of β contacts, we design βACV, an SVM classifier with β contacts as input, to classify homodimers from crystal packing. We found that our βACV is able to achieve the state-of-the-art classification performance superior to SVM classifiers with distance-based contacts as input. Our βACV also outperforms several existing methods when being evaluated on several datasets in previous works. The promising empirical performance suggests that β contacts can truly identify critical specific contacts in protein binding interfaces. β contacts thus provide a new model for more precise description of atomic organization in protein quaternary structures than distance-based contacts. PMID:23630569

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.

An analysis of possible mechanisms of unexpected death occurring in hydatid disease (echinococcosis).

PubMed

Byard, Roger W

2009-07-01

Most cases of hydatid disease in human populations are due to Echinococcus granulosus. The hydatid life cycle involves passage between definitive hosts such as dogs and intermediate hosts such as sheep. Humans become accidental intermediate hosts following ingestion of food or water contaminated with eggs or by contact with infected dogs. Although hydatid disease may remain asymptomatic, occasional cases of sudden and unexpected death present to autopsy. Causes of rapid clinical decline involve a wide range of mechanisms including anaphylaxis (with or without cyst rupture), cardiac outflow obstruction or conduction tract disturbance, pulmonary and cerebral embolism, pericarditis, cardiac tamponade, myocardial ischemia, pulmonary hypertension, peritonitis, hollow organ perforation, intracerebral mass effect, obstructive hydrocephalus, seizures, cerebral ischemia/infarction, and pregnancy complications. The autopsy assessment of cases therefore requires careful examination of all organ systems for characteristic cystic lesions, as multiorgan involvement is common, with integration of findings so that possible mechanisms of death can be determined. Measurement of serum tryptase and specific IgE levels should be undertaken for possible anaphylaxis.

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization in C. elegans.

PubMed

Wojtyniak, Martin; Brear, Andrea G; O'Halloran, Damien M; Sengupta, Piali

2013-10-01

Primary cilia are ubiquitous sensory organelles that concentrate transmembrane signaling proteins essential for sensing environmental cues. Mislocalization of crucial ciliary signaling proteins, such as the tetrameric cyclic nucleotide-gated (CNG) channels, can lead to cellular dysfunction and disease. Although several cis- and trans-acting factors required for ciliary protein trafficking and localization have been identified, whether these mechanisms act in a protein- and cell-specific manner is largely unknown. Here, we show that CNG channel subunits can be localized to discrete ciliary compartments in individual sensory neurons in C. elegans, suggesting that channel composition is heterogeneous across the cilium. We demonstrate that ciliary localization of CNG channel subunits is interdependent on different channel subunits in specific cells, and identify sequences required for efficient ciliary targeting and localization of the TAX-2 CNGB and TAX-4 CNGA subunits. Using a candidate gene approach, we show that Inversin, transition zone proteins, intraflagellar transport motors and a MYND-domain protein are required to traffic and/or localize CNG channel subunits in both a cell- and channel subunit-specific manner. We further find that TAX-2 and TAX-4 are relatively immobile in specific sensory cilia subcompartments, suggesting that these proteins undergo minimal turnover in these domains in mature cilia. Our results uncover unexpected diversity in the mechanisms that traffic and localize CNG channel subunits to cilia both within and across cell types, highlighting the essential contribution of this process to cellular functions.

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization in C. elegans

PubMed Central

Wojtyniak, Martin; Brear, Andrea G.; O'Halloran, Damien M.; Sengupta, Piali

2013-01-01

Summary Primary cilia are ubiquitous sensory organelles that concentrate transmembrane signaling proteins essential for sensing environmental cues. Mislocalization of crucial ciliary signaling proteins, such as the tetrameric cyclic nucleotide-gated (CNG) channels, can lead to cellular dysfunction and disease. Although several cis- and trans-acting factors required for ciliary protein trafficking and localization have been identified, whether these mechanisms act in a protein- and cell-specific manner is largely unknown. Here, we show that CNG channel subunits can be localized to discrete ciliary compartments in individual sensory neurons in C. elegans, suggesting that channel composition is heterogeneous across the cilium. We demonstrate that ciliary localization of CNG channel subunits is interdependent on different channel subunits in specific cells, and identify sequences required for efficient ciliary targeting and localization of the TAX-2 CNGB and TAX-4 CNGA subunits. Using a candidate gene approach, we show that Inversin, transition zone proteins, intraflagellar transport motors and a MYND-domain protein are required to traffic and/or localize CNG channel subunits in both a cell- and channel subunit-specific manner. We further find that TAX-2 and TAX-4 are relatively immobile in specific sensory cilia subcompartments, suggesting that these proteins undergo minimal turnover in these domains in mature cilia. Our results uncover unexpected diversity in the mechanisms that traffic and localize CNG channel subunits to cilia both within and across cell types, highlighting the essential contribution of this process to cellular functions. PMID:23886944

"Please Read Loose": Intimate Grammars and Unexpected Languages in Contemporary Navajo Literature

ERIC Educational Resources Information Center

Webster, Anthony K.

2011-01-01

This paper uses Philip Deloria's "Indians in Unexpected Places" as a lens by which to understand the expectations and reviews of Navajo author Blackhorse Mitchell's "Miracle Hill." Written in Navajo English, the book, from an introduction by T. D. Allen to a number of reviews of the book in the popular press, consistently misrecognized the…

Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

PubMed Central

van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W.J.H.; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; de Craen, Anton J.M.; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Adrienne Cupples, L.; Neerincx, Pieter B.T.; Elbers, Clara C.; Francesco Palamara, Pier; Pe'er, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F.J.; Stoneking, Mark; de Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; van den Berg, Leonard H.; Byelas, Heorhiy; den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Joeri van der Velde, K.; van Setten, Jessica; Kattenberg, Mathijs; van Schaik, Barbera D.C.; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric-Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D.; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; Jukema, J. Wouter; van der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke-Jan; Uitterlinden, Andre G.; Swertz, Morris A.; van Ommen, Gert-Jan B.; de Bakker, Paul I.W.; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; van Duijn, Cornelia M.

2015-01-01

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10−4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. PMID:25751400

Sudden unexpected death under acute influence of cannabis.

PubMed

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

2014-04-01

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

Novel and unexpected clearance mechanisms for cold platelets

PubMed Central

Rumjantseva, Viktoria; Hoffmeister, Karin M.

2015-01-01

Storage at room temperature is limited to 5 days because of the risk of bacterial growth and loss of platelet functionality. Platelet refrigeration remains impossible, because once chilled, platelets are rapidly removed from circulation. Chilling platelets (<4 h) clusters glycoprotein (GP) Ibα receptors, and β2 integrins on hepatic macrophages recognize clustered βGlcNAc residues leading to rapid clearance of acutely chilled platelets. Prolonged refrigeration increases the exposure of galactose residues such that, unexpectedly, hepatocytes remove platelets using their asialoglycoprotein receptors. Here we review current knowledge of the mechanisms of platelet removal, the existing knowledge of refrigerated platelet function, and methods to preserve platelet concentrates long-term for transfusion. PMID:19932055

LC-QTOF-MS identification of porcine-specific peptide in heat treated pork identifies candidate markers for meat species determination.

PubMed

Sarah, S A; Faradalila, W N; Salwani, M S; Amin, I; Karsani, S A; Sazili, A Q

2016-05-15

The purpose of this study was to identify porcine-specific peptide markers from thermally processed meat that could differentiate pork from beef, chevon and chicken meat. In the initial stage, markers from tryptic digested protein of chilled, boiled and autoclaved pork were identified using LC-QTOF-MS. An MRM method was then established for verification. A thorough investigation of LC-QTOF-MS data showed that only seven porcine-specific peptides were consistently detected. Among these peptides, two were derived from lactate dehydrogenase, one from creatine kinase, and four from serum albumin protein. However, MRM could only detect four peptides (EVTEFAK, LVVITAGAR, FVIER and TVLGNFAAFVQK) that were consistently present in pork samples. In conclusion, meat species determination through a tandem mass spectrometry platform shows high potential in providing scientifically valid and reliable results even at peptide level. Besides, the specificity and selectivity offered by the proteomics approach also provide a robust platform for Halal authentication. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Investigation to Validate the Grammar and Phonology Screening (GAPS) Test to Identify Children with Specific Language Impairment

PubMed Central

van der Lely, Heather K. J.; Payne, Elisabeth; McClelland, Alastair

2011-01-01

Background The extraordinarily high incidence of grammatical language impairments in developmental disorders suggests that this uniquely human cognitive function is “fragile”. Yet our understanding of the neurobiology of grammatical impairments is limited. Furthermore, there is no “gold-standard” to identify grammatical impairments and routine screening is not undertaken. An accurate screening test to identify grammatical abilities would serve the research, health and education communities, further our understanding of developmental disorders, and identify children who need remediation, many of whom are currently un-diagnosed. A potential realistic screening tool that could be widely administered is the Grammar and Phonology Screening (GAPS) test – a 10 minute test that can be administered by professionals and non-professionals alike. Here we provide a further step in evaluating the validity and accuracy (sensitivity and specificity) of the GAPS test in identifying children who have Specific Language Impairment (SLI). Methods and Findings We tested three groups of children; two groups aged 3;6–6:6, a typically developing (n = 30) group, and a group diagnosed with SLI: (n = 11) (Young (Y)-SLI), and a further group aged 6;9–8;11 with SLI (Older (O)-SLI) (n = 10) who were above the test age norms. We employed a battery of language assessments including the GAPS test to assess the children's language abilities. For Y-SLI children, analyses revealed a sensitivity and specificity at the 5th and 10th percentile of 1.00 and 0.98, respectively, and for O-SLI children at the 10th and 15th percentile .83 and .90, respectively. Conclusions The findings reveal that the GAPS is highly accurate in identifying impaired vs. non-impaired children up to 6;8 years, and has moderate-to-high accuracy up to 9 years. The results indicate that GAPS is a realistic tool for the early identification of grammatical abilities and impairment in young children. A larger

A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making.

PubMed

Jain, Roshan A; Wolman, Marc A; Marsden, Kurt C; Nelson, Jessica C; Shoenhard, Hannah; Echeverry, Fabio A; Szi, Christina; Bell, Hannah; Skinner, Julianne; Cobbs, Emilia N; Sawada, Keisuke; Zamora, Amy D; Pereda, Alberto E; Granato, Michael

2018-05-07

Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood. We demonstrate that CaSR promotes sensorimotor decision making acutely through Gα i/o and Gα q/11 signaling, modulated by clathrin-mediated endocytosis. Combined, our results identify the first set of genes critical for behavioral choice modulation in a vertebrate and reveal an unexpected critical role for CaSR in sensorimotor decision making. Copyright © 2018 Elsevier Ltd. All rights reserved.

Measuring the Electronic Properties of DNA-Specific Schottky Diodes Towards Detecting and Identifying Basidiomycetes DNA

PubMed Central

Periasamy, Vengadesh; Rizan, Nastaran; Al-Ta’ii, Hassan Maktuff Jaber; Tan, Yee Shin; Tajuddin, Hairul Annuar; Iwamoto, Mitsumasa

2016-01-01

The discovery of semiconducting behavior of deoxyribonucleic acid (DNA) has resulted in a large number of literatures in the study of DNA electronics. Sequence-specific electronic response provides a platform towards understanding charge transfer mechanism and therefore the electronic properties of DNA. It is possible to utilize these characteristic properties to identify/detect DNA. In this current work, we demonstrate a novel method of DNA-based identification of basidiomycetes using current-voltage (I-V) profiles obtained from DNA-specific Schottky barrier diodes. Electronic properties such as ideality factor, barrier height, shunt resistance, series resistance, turn-on voltage, knee-voltage, breakdown voltage and breakdown current were calculated and used to quantify the identification process as compared to morphological and molecular characterization techniques. The use of these techniques is necessary in order to study biodiversity, but sometimes it can be misleading and unreliable and is not sufficiently useful for the identification of fungi genera. Many of these methods have failed when it comes to identification of closely related species of certain genus like Pleurotus. Our electronics profiles, both in the negative and positive bias regions were however found to be highly characteristic according to the base-pair sequences. We believe that this simple, low-cost and practical method could be useful towards identifying and detecting DNA in biotechnology and pathology. PMID:27435636

Measuring the Electronic Properties of DNA-Specific Schottky Diodes Towards Detecting and Identifying Basidiomycetes DNA

NASA Astrophysics Data System (ADS)

Periasamy, Vengadesh; Rizan, Nastaran; Al-Ta'Ii, Hassan Maktuff Jaber; Tan, Yee Shin; Tajuddin, Hairul Annuar; Iwamoto, Mitsumasa

2016-07-01

The discovery of semiconducting behavior of deoxyribonucleic acid (DNA) has resulted in a large number of literatures in the study of DNA electronics. Sequence-specific electronic response provides a platform towards understanding charge transfer mechanism and therefore the electronic properties of DNA. It is possible to utilize these characteristic properties to identify/detect DNA. In this current work, we demonstrate a novel method of DNA-based identification of basidiomycetes using current-voltage (I-V) profiles obtained from DNA-specific Schottky barrier diodes. Electronic properties such as ideality factor, barrier height, shunt resistance, series resistance, turn-on voltage, knee-voltage, breakdown voltage and breakdown current were calculated and used to quantify the identification process as compared to morphological and molecular characterization techniques. The use of these techniques is necessary in order to study biodiversity, but sometimes it can be misleading and unreliable and is not sufficiently useful for the identification of fungi genera. Many of these methods have failed when it comes to identification of closely related species of certain genus like Pleurotus. Our electronics profiles, both in the negative and positive bias regions were however found to be highly characteristic according to the base-pair sequences. We believe that this simple, low-cost and practical method could be useful towards identifying and detecting DNA in biotechnology and pathology.

Crude oil as a microbial seed bank with unexpected functional potentials

PubMed Central

Cai, Man; Nie, Yong; Chi, Chang-Qiao; Tang, Yue-Qin; Li, Yan; Wang, Xing-Biao; Liu, Ze-Shen; Yang, Yunfeng; Zhou, Jizhong; Wu, Xiao-Lei

2015-01-01

It was widely believed that oil is a harsh habitat for microbes because of its high toxicity and hydrophobicity. However, accumulating evidence has revealed the presence of live microbes in crude oil. Therefore, it’s of value to conduct an in-depth investigation on microbial communities in crude oil. To this end, microorganisms in oil and water phases were collected from four oil-well production mixtures in Qinghai Oilfield, China, and analyzed for their taxonomic and functional compositions via pyrosequencing and GeoChip, respectively. Hierarchical clustering of 16S rRNA gene sequences and functional genes clearly separated crude oil and water phases, suggestive of distinct taxonomic and functional gene compositions between crude oil and water phases. Unexpectedly, Pseudomonas dominated oil phase where diverse functional gene groups were identified, which significantly differed from those in the corresponding water phases. Meanwhile, most functional genes were significantly more abundant in oil phase, which was consistent with their important roles in facilitating survival of their host organisms in crude oil. These findings provide strong evidence that crude oil could be a “seed bank” of functional microorganisms with rich functional potentials. This offers novel insights for industrial applications of microbial-enhanced oil recovery and bioremediation of petroleum-polluted environments. PMID:26525361

Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer.

PubMed

Rosenthal, Eben L; Moore, Lindsay S; Tipirneni, Kiranya; de Boer, Esther; Stevens, Todd M; Hartman, Yolanda E; Carroll, William R; Zinn, Kurt R; Warram, Jason M

2017-08-15

Purpose: Comprehensive cervical lymphadenectomy can be associated with significant morbidity and poor quality of life. This study evaluated the sensitivity and specificity of cetuximab-IRDye800CW to identify metastatic disease in patients with head and neck cancer. Experimental Design: Consenting patients scheduled for curative resection were enrolled in a clinical trial to evaluate the safety and specificity of cetuximab-IRDye800CW. Patients ( n = 12) received escalating doses of the study drug. Where indicated, cervical lymphadenectomy accompanied primary tumor resection, which occurred 3 to 7 days following intravenous infusion of cetuximab-IRDye800CW. All 471 dissected lymph nodes were imaged with a closed-field, near-infrared imaging device during gross processing of the fresh specimens. Intraoperative imaging of exposed neck levels was performed with an open-field fluorescence imaging device. Blinded assessments of the fluorescence data were compared to histopathology to calculate sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results: Of the 35 nodes diagnosed pathologically positive, 34 were correctly identified with fluorescence imaging, yielding a sensitivity of 97.2%. Of the 435 pathologically negative nodes, 401 were correctly assessed using fluorescence imaging, yielding a specificity of 92.7%. The NPV was determined to be 99.7%, and the PPV was 50.7%. When 37 fluorescently false-positive nodes were sectioned deeper (1 mm) into their respective blocks, metastatic cancer was found in 8.1% of the recut nodal specimens, which altered staging in two of those cases. Conclusions: Fluorescence imaging of lymph nodes after systemic cetuximab-IRDye800CW administration demonstrated high sensitivity and was capable of identifying additional positive nodes on deep sectioning. Clin Cancer Res; 23(16); 4744-52. ©2017 AACR . ©2017 American Association for Cancer Research.

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.

Control of fast elbow movement: a study of electromyographic patterns during movements against unexpectedly decreased inertial load.

PubMed

Latash, M L

1994-01-01

Predictions of three models of single-joint motor control were compared with experimental observations of the changes in electromyographic (EMG) patterns during fast voluntary movements against an unexpectedly reduced inertial load. The subjects performed elbow flexions over 40 degrees "as fast as possible" in two series. During the first series, an approximately 40% decrease in inertia, simulated by a torque-motor, might occur unpredictably on half of the trials (unloaded trials). During the second series, all the trials were unloaded. The major findings are: (1) no differences in the antagonist burst latency in unexpectedly unloaded and unperturbed trials; (2) a decrease in the antagonist latency during expected unloadings; (3) a small, statistically non significant decrease in the first agonist burst EMG integral; and (4) a larger, statistically significant increase in the antagonist burst EMG integral in unexpectedly unloaded trials as compared to unperturbed trials. The data are in good correspondence with a version of the equilibrium-point hypothesis that assumes central programming of the beginning of the antagonist burst and incorporates the possibility of reflex-induced changes in EMG amplitudes.

Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology.

PubMed

Liu, Tao; Sims, David; Baum, Buzz

2009-01-01

In recent years RNAi screening has proven a powerful tool for dissecting gene functions in animal cells in culture. However, to date, most RNAi screens have been performed in a single cell line, and results then extrapolated across cell types and systems. Here, to dissect generic and cell type-specific mechanisms underlying cell morphology, we have performed identical kinome RNAi screens in six different Drosophila cell lines, derived from two distinct tissues of origin. This analysis identified a core set of kinases required for normal cell morphology in all lines tested, together with a number of kinases with cell type-specific functions. Most significantly, the screen identified a role for minibrain (mnb/DYRK1A), a kinase associated with Down's syndrome, in the regulation of actin-based protrusions in CNS-derived cell lines. This cell type-specific requirement was not due to the peculiarities in the morphology of CNS-derived cells and could not be attributed to differences in mnb expression. Instead, it likely reflects differences in gene expression that constitute the cell type-specific functional context in which mnb/DYRK1A acts. Using parallel RNAi screens and gene expression analyses across cell types we have identified generic and cell type-specific regulators of cell morphology, which include mnb/DYRK1A in the regulation of protrusion morphology in CNS-derived cell lines. This analysis reveals the importance of using different cell types to gain a thorough understanding of gene function across the genome and, in the case of kinases, the difficulties of using the differential gene expression to predict function.

TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.

PubMed

Xu, Yan; Chen, Yan; Li, Daliang; Liu, Qing; Xuan, Zhenyu; Li, Wen-Hong

2017-02-01

MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

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

Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection

PubMed Central

Choi, Young-Jun; Fuchs, Jeremy F.; Mayhew, George F.; Yu, Helen E.; Christensen, Bruce M.

2012-01-01

Hemocytes are integral components of mosquito immune mechanisms such as phagocytosis, melanization, and production of antimicrobial peptides. However, our understanding of hemocyte-specific molecular processes and their contribution to shaping the host immune response remains limited. To better understand the immunophysiological features distinctive of hemocytes, we conducted genome-wide analysis of hemocyte-enriched transcripts, and examined how tissue-enriched expression patterns change with the immune status of the host. Our microarray data indicate that the hemocyte-enriched trascriptome is dynamic and context-dependent. Analysis of transcripts enriched after bacterial challenge in circulating hemocytes with respect to carcass added a dimension to evaluating infection-responsive genes and immune-related gene families. We resolved patterns of transcriptional change unique to hemocytes from those that are likely shared by other immune responsive tissues, and identified clusters of genes preferentially induced in hemocytes, likely reflecting their involvement in cell type specific functions. In addition, the study revealed conserved hemocyte-enriched molecular repertoires which might be implicated in core hemocyte function by cross-species meta-analysis of microarray expression data from Anopheles gambiae and Drosophila melanogaster. PMID:22796331

Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development

PubMed Central

Kohn, Anat; Dong, Yufeng; Mirando, Anthony J.; Jesse, Alana M.; Honjo, Tasuku; Zuscik, Michael J.; O’Keefe, Regis J.; Hilton, Matthew J.

2012-01-01

The Notch signaling pathway has emerged as an important regulator of endochondral bone formation. Although recent studies have examined the role of Notch in mesenchymal and chondro-osteo progenitor cell populations, there has yet to be a true examination of Notch signaling specifically within developing and committed chondrocytes, or a determination of whether cartilage and bone formation are regulated via RBPjκ-dependent or -independent Notch signaling mechanisms. To develop a complete understanding of Notch signaling during cartilage and bone development we generated and compared general Notch gain-of-function (Rosa-NICDf/+), RBPjκ-deficient (Rbpjκf/f), and RBPjκ-deficient Notch gain-of-function (Rosa-NICDf/+;Rbpjκf/f) conditional mutant mice, where activation or deletion of floxed alleles were specifically targeted to mesenchymal progenitors (Prx1Cre) or committed chondrocytes (inducible Col2CreERT2). These data demonstrate, for the first time, that Notch regulation of chondrocyte maturation is solely mediated via the RBPjκ-dependent pathway, and that the perichodrium or osteogenic lineage probably influences chondrocyte terminal maturation and turnover of the cartilage matrix. Our study further identifies the cartilage-specific RBPjκ-independent pathway as crucial for the proper regulation of chondrocyte proliferation, survival and columnar chondrocyte organization. Unexpectedly, the RBPjκ-independent Notch pathway was also identified as an important long-range cell non-autonomous regulator of perichondral bone formation and an important cartilage-derived signal required for coordinating chondrocyte and osteoblast differentiation during endochondral bone development. Finally, cartilage-specific RBPjκ-independent Notch signaling likely regulates Ihh responsiveness during cartilage and bone development. PMID:22354840

Unexpected matching insensitivity in DTL of GTA accelerator

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

Yuan, V.W.; Gilpatrick, J.D.; Johnson, K.F.

1995-05-01

The Intertank Matching Section (IMS) of the Ground Test Accelerator (GTA) contains four variable-field quadrupoles (VFQs) and is designed to match beam exiting the Radio-Frequency Quadrupole to the first tank of the Drift-tube LINAC (DTL-1). By varying the VFQ field strengths to create a range of beam mismatches at the entrance to DTL-1, one can test the sensitivity of the DTL-1 output beam to variations in the DTL-1 input beam. Experimental studies made during commissioning of the GTA indicate an unexpected result: the beam exiting DTL-1 shows little variation for a range of mismatches produced at the entrance. Results ofmore » the experiment and simulation studies are presented.« less

Specification of Drosophila Corpora Cardiaca Neuroendocrine Cells from Mesoderm Is Regulated by Notch Signaling

PubMed Central

Park, Sangbin; Bustamante, Erika L.; Antonova, Julie; McLean, Graeme W.; Kim, Seung K.

2011-01-01

Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism. PMID:21901108

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.

Sparse Feature Selection Identifies H2A.Z as a Novel, Pattern-Specific Biomarker for Asymmetrically Self-Renewing Distributed Stem Cells

PubMed Central

Huh, Yang Hoon; Noh, Minsoo; Burden, Frank R.; Chen, Jennifer C.; Winkler, David A.; Sherley, James L.

2015-01-01

There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs) in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow). Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify DSC such useful and specific biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ. PMID:25636161

Willingness to revise own testimony: 3- and 4-year-olds' selective trust in unexpected testimony from accurate and inaccurate informants.

PubMed

Li, Xiaoqian; Yow, W Quin

2018-09-01

Prior work has shown that young children trust single accurate and inaccurate individuals to a similar extent in their endorsement of novel information. However, it remains unknown to what extent children trust a credible or noncredible individual when given information that is pitted against their own beliefs. The current study examined whether children, when given unexpected testimony that contradicted their initial beliefs but was not completely unbelievable, would selectively revise their beliefs depending on the informant's past history of accuracy. The participants (3- and 4-year-olds; N = 100) were familiarized with an informant who labeled a series of common objects either accurately or inaccurately. Following that, all children saw a picture of an ambiguous hybrid artifact that consisted of features of two typical common artifacts and were asked to identify the hybrid object with their own label. Subsequently, children watched the previously accurate or inaccurate informant give the same hybrid object a different but plausible label. Children expressed a greater tendency to override their initial judgments and endorse the unexpected testimony from a previously accurate informant than from someone who had consistently made naming errors. The findings provide novel understandings of the circumstances under which 3- and 4-year-old preschoolers may or may not rely on the informant's prior reliability in their selective learning. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-08-01

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

Sex-Specific Genetic Loci for Femoral Neck Bone Mass and Strength Identified in Inbred COP and DA Rats

PubMed Central

Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L; Carr, Lucinda G; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

Introduction Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans identified chromosomal regions linked to hip size and bone mass. Animal models, particularly the inbred rat, serve as complementary approaches for studying the genetic influence on hip fragility. The purpose of this study is to identify sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti (DA) rats. Materials and Methods A total of 828 (405 males and 423 females) F2 progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip), neck width, ultimate force, and energy to break. A whole genome screen was performed using 93 microsatellite markers with an average intermarker distance of 20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the COP × DA F2 data and compared with published Rat Genome Database (RGD) maps. These maps were used for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. Results Significant evidence of linkage (p < 0.01) for sex-independent QTLs were detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2) femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1% and 4%. Conclusions We detected evidence that sex-independent and sex-specific QTLs contribute to hip fragility in the inbred rat. Several QTLs regions identified in this study are homologous to human chromosomal regions previously linked to

Unexpected decline in tuberculosis cases coincident with economic recession -- United States, 2009

PubMed Central

2011-01-01

Background Since 1953, through the cooperation of state and local health departments, the U.S. Centers for Disease Control and Prevention (CDC) has collected information on incident cases of tuberculosis (TB) disease in the United States. In 2009, TB case rates declined -11.4%, compared to an average annual -3.8% decline since 2000. The unexpectedly large decline raised concerns that TB cases may have gone unreported. To address the unexpected decline, we examined trends from multiple sources on TB treatment initiation, medication sales, and laboratory and genotyping data on culture-positive TB. Methods We analyzed 142,174 incident TB cases reported to the U. S. National Tuberculosis Surveillance System (NTSS) during January 1, 2000-December 31, 2009; TB control program data from 59 public health reporting areas; self-reported data from 50 CDC-funded public health laboratories; monthly electronic prescription claims for new TB therapy prescriptions; and complete genotyping results available for NTSS cases. Accounting for prior trends using regression and time-series analyses, we calculated the deviation between observed and expected TB cases in 2009 according to patient and clinical characteristics, and assessed at what point in time the deviation occurred. Results The overall deviation in TB cases in 2009 was -7.9%, with -994 fewer cases reported than expected (P < .001). We ruled out evidence of surveillance underreporting since declines were seen in states that used new software for case reporting in 2009 as well as states that did not, and we found no cases unreported to CDC in our examination of over 5400 individual line-listed reports in 11 areas. TB cases decreased substantially among both foreign-born and U.S.-born persons. The unexpected decline began in late 2008 or early 2009, and may have begun to reverse in late 2009. The decline was greater in terms of case counts among foreign-born than U.S.-born persons; among the foreign-born, the declines were

Commentary: Unexpected Benefits that Challenge the Orthodoxy of DBS Outcomes.

PubMed

Ford, Paul

2016-10-01

The case of Ms. L. provides a wonderful opportunity to highlight the underlying value commitments that often deeply influence decisionmaking in medicine and more specifically in innovative neurosurgical procedures. In order to give a fair opinion on how Dr. Impf, as clinician and researcher, should act, a much richer and thicker understanding of the actual perspectives of the stakeholders would be necessary. Because this is not available, I highlight three important elements: the terms under which the deep brain stimulation (DBS) is implanted, the proper goals of a healthcare team, and the fallacy of a "natural" or immutable self. These elements are brought together in this case by a set of unexpected effects on the patient that were not intended and that are judged and categorized differently by various stakeholders within the case. In the end, I hope that there was full transparency and agreement about obligations, responsibilities, and outcomes prior to the implantation of the DBS between the physician and patient. Further, it is important to remember that just because a result is serendipitous does not mean that it should be discounted as a proper benefit. Finally, each person authors variations on their own self that are molded by environment and social networks. If Ms. L. continues to demonstrate an ability to author a desired self, the DBS is no more inappropriate a tool than many other artifacts that are used regularly by others to mold themselves.

Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants contributing to lipid levels and coronary artery disease

PubMed Central

Lu, Xiangfeng; Peloso, Gina M; Liu, Dajiang J.; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N.; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H.-H.; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B.; Adair, Linda S.; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; da Chen, Yii-Der I; Shu, XiaoOu; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K.; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars; Nielsen, Jonas Bille; Tse, Hung-fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y. Eugene; Zheng, Wei; Tai, E Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; Consortium, GLGC; Kathiresan, Sekar; Mohlke, Karen L.; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; Willer, Cristen J

2017-01-01

Most genome-wide association studies have been conducted in European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we examined protein-coding genetic variants in 47,532 East Asian individuals using an exome array. We identified 255 variants at 41 loci reaching chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After meta-analysis with > 300,000 European samples, we identified an additional 9 novel loci. The same 16 genes were identified by the protein-altering variants in both East Asians and Europeans, likely pointing to the functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population-specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci. PMID:29083407

Experimental muscle pain challenges the postural stability during quiet stance and unexpected posture perturbation.

PubMed

Hirata, Rogério Pessoto; Ervilha, Ulysses Fernandes; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

2011-08-01

Musculoskeletal pain impairs postural control and stability. Nine subjects stood as quietly as possible on a moveable force platform before, during, and after experimental pain in the right leg muscles. A moveable force platform was used to measure the center of pressure and provided unexpected perturbations. Lower limb muscle activity, joint angles, and foot pressure distributions were measured. Hypertonic saline was used to induce pain in the vastus lateralis, vastus medialis, or biceps femoris muscle of the right leg. Compared to baseline and control sessions, pain in the knee extensor muscles during quiet standing evoked: 1) larger sway area, greater medial-lateral center of pressure displacement and higher speed (P < .05); 2) increased sway displacement in the anterior-posterior direction (P < .05); and 3) increased electromyography (EMG) activity for left tibialis anterior and left erector spinae muscles (P < .05). Pain provoked longer time to return to an equilibrium posture after forward EMG activity for, and pain in vastus medialis muscle decreased the time for the maximum hip flexion during this perturbation (P < .05). These results show that muscle pain impairs postural stability during quiet standing and after unexpected perturbation, which suggest that people suffering from leg muscle pain are more vulnerable to falls. This article presents the acute responses to leg muscle pain on the postural control. This measure could potentially help clinicians who seek to assess how pain responses may contribute to patient's postural control and stability during quiet standing and after recovering from unexpected perturbations. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Attentional gain and processing capacity limits predict the propensity to neglect unexpected visual stimuli.

PubMed

Papera, Massimiliano; Richards, Anne

2016-05-01

Exogenous allocation of attentional resources allows the visual system to encode and maintain representations of stimuli in visual working memory (VWM). However, limits in the processing capacity to allocate resources can prevent unexpected visual stimuli from gaining access to VWM and thereby to consciousness. Using a novel approach to create unbiased stimuli of increasing saliency, we investigated visual processing during a visual search task in individuals who show a high or low propensity to neglect unexpected stimuli. When propensity to inattention is high, ERP recordings show a diminished amplification concomitantly with a decrease in theta band power during the N1 latency, followed by a poor target enhancement during the N2 latency. Furthermore, a later modulation in the P3 latency was also found in individuals showing propensity to visual neglect, suggesting that more effort is required for conscious maintenance of visual information in VWM. Effects during early stages of processing (N80 and P1) were also observed suggesting that sensitivity to contrasts and medium-to-high spatial frequencies may be modulated by low-level saliency (albeit no statistical group differences were found). In accordance with the Global Workplace Model, our data indicate that a lack of resources in low-level processors and visual attention may be responsible for the failure to "ignite" a state of high-level activity spread across several brain areas that is necessary for stimuli to access awareness. These findings may aid in the development of diagnostic tests and intervention to detect/reduce inattention propensity to visual neglect of unexpected stimuli. © 2016 Society for Psychophysiological Research.

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

System among the corticosteroids: specificity and molecular dynamics

PubMed Central

Brookes, Jennifer C.; Galigniana, Mario D.; Harker, Anthony H.; Stoneham, A. Marshall; Vinson, Gavin P.

2012-01-01

Understanding how structural features determine specific biological activities has often proved elusive. With over 161 000 steroid structures described, an algorithm able to predict activity from structural attributes would provide manifest benefits. Molecular simulations of a range of 35 corticosteroids show striking correlations between conformational mobility and biological specificity. Thus steroid ring A is important for glucocorticoid action, and is rigid in the most specific (and potent) examples, such as dexamethasone. By contrast, ring C conformation is important for the mineralocorticoids, and is rigid in aldosterone. Other steroids that are less specific, or have mixed functions, or none at all, are more flexible. One unexpected example is 11-deoxycorticosterone, which the methods predict (and our activity studies confirm) is not only a specific mineralocorticoid, but also has significant glucocorticoid activity. These methods may guide the design of new corticosteroid agonists and antagonists. They will also have application in other examples of ligand–receptor interactions. PMID:21613285

Substrate specificity of the ubiquitin and Ubl proteases

PubMed Central

Ronau, Judith A; Beckmann, John F; Hochstrasser, Mark

2016-01-01

Conjugation and deconjugation of ubiquitin and ubiquitin-like proteins (Ubls) to cellular proteins are highly regulated processes integral to cellular homeostasis. Most often, the C-termini of these small polypeptides are attached to lysine side chains of target proteins by an amide (isopeptide) linkage. Deubiquitinating enzymes (DUBs) and Ubl-specific proteases (ULPs) comprise a diverse group of proteases that recognize and remove ubiquitin and Ubls from their substrates. How DUBs and ULPs distinguish among different modifiers, or different polymeric forms of these modifiers, remains poorly understood. The specificity of ubiquitin/Ubl-deconjugating enzymes for particular substrates depends on multiple factors, ranging from the topography of specific substrate features, as in different polyubiquitin chain types, to structural elements unique to each enzyme. Here we summarize recent structural and biochemical studies that provide insights into mechanisms of substrate specificity among various DUBs and ULPs. We also discuss the unexpected specificities of non-eukaryotic proteases in these families. PMID:27012468

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

PubMed Central

2012-01-01

Background Since 2002, adults have been able to choose oral health care services in the public sector or in the private sector in Finland. Though various subsidies for care exist in both sectors, the Public Dental Service (PDS) is a cheaper option for the patient but, on the other hand, there are no waiting lists for private care. The aim of this study was to assess middle-aged adults' use of dental services, willingness to pay (WTP) and ability to pay (ATP) for unexpected, urgent dental treatment. Methods Postal questionnaires on use of dental services were sent to a random sample of 1500 47-59 year old adults living in three large municipalities in the Helsinki region. The initial response rate was 65.8%. Two hypothetical scenarios were presented: "What would be the highest price you would be prepared to pay to have a lost filling replaced immediately, or, at the latest, the day after losing the filling?" and " How much could you pay for unexpected dental expenses at two weeks notice, if you suddenly needed more comprehensive treatment?" Logistic regression analysis was used to analyse factors related to WTP and ATP. Results Most respondents (89.6%) had visited a dentist recently and a majority (76.1%) had used private services. For immediate replacement of a lost filling, almost all respondents (93.2%) were willing to pay the lower price charged in the PDS and 46.2% were willing to pay the private fee. High income and no subjective need for dental treatment were positively associated with the probability of paying a higher price. Most respondents (93.0%) were able to pay a low fee, EUR 50 and almost half (41.6%) at least EUR 300 for unexpected treatment at short notice. High income and male sex were associated with high ATP. Conclusion There was a strong and statistically significant relationship between income and WTP and ATP for urgent dental care, indicating that access to publicly provided services improved equity for persons with low income. PMID:22935077

Do you really represent my task? Sequential adaptation effects to unexpected events support referential coding for the joint Simon effect.

PubMed

Klempova, Bibiana; Liepelt, Roman

2016-07-01

Recent findings suggest that a Simon effect (SE) can be induced in Individual go/nogo tasks when responding next to an event-producing object salient enough to provide a reference for the spatial coding of one's own action. However, there is skepticism against referential coding for the joint Simon effect (JSE) by proponents of task co-representation. In the present study, we tested assumptions of task co-representation and referential coding by introducing unexpected double response events in a joint go/nogo and a joint independent go/nogo task. In Experiment 1b, we tested if task representations are functionally similar in joint and standard Simon tasks. In Experiment 2, we tested sequential updating of task co-representation after unexpected single response events in the joint independent go/nogo task. Results showed increased JSEs following unexpected events in the joint go/nogo and joint independent go/nogo task (Experiment 1a). While the former finding is in line with the assumptions made by both accounts (task co-representation and referential coding), the latter finding supports referential coding. In contrast to Experiment 1a, we found a decreased SE after unexpected events in the standard Simon task (Experiment 1b), providing evidence against the functional equivalence assumption between joint and two-choice Simon tasks of the task co-representation account. Finally, we found an increased JSE also following unexpected single response events (Experiment 2), ruling out that the findings of the joint independent go/nogo task in Experiment 1a were due to a re-conceptualization of the task situation. In conclusion, our findings support referential coding also for the joint Simon effect.

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.

Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

PubMed Central

Asher, Tedi E.; Wilson, Nancy A.; Nason, Martha C.; Brenchley, Jason M.; Metzler, Ian S.; Venturi, Vanessa; Gostick, Emma; Chattopadhyay, Pratip K.; Roederer, Mario; Davenport, Miles P.; Watkins, David I.; Douek, Daniel C.

2009-01-01

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection. PMID:19349463

[Investigation of the causes of infant sudden unexpected death in children younger than one year in Bariloche city and surrounding areas].

PubMed

Gil, Leonardo; Herbón, Fabiana; Little, Andrés; López, Mónica; Martínez, Lucía; Cancilliere, María del Carmen

2008-12-01

In the beginning of 2002 there were an unusually high number of sudden unexpected infant deaths. A prospective study was started to determine the cause of unexpected deaths in infants younger than 1 year. Investigate the possible causes of sudden and unexpected death in infants of Bariloche and surrounding areas, using a protocol created for that purpose. All infants under 1 year of age who died unexpectedly between May 2002 and April 2007 were studied. A complete physical examination, a thorough interrogation to the parents and an autopsy were performed. According to the findings a definitive diagnosis was made on each case. During the study period 10 infants younger than 1 year died. One case was excluded because the autopsy could not be done. The mean age was 74 days, 6 were males. All died while sleeping and no sign of disease were noticed in any case. In 6 cases, the autopsy findings explained the death. In the 3 others no cause for the death was found. The implementation of this protocol allowed to find out the cause of death in 6 cases, that could not have been achieved without the autopsy.

Sudden unexpected death in epilepsy (SUDEP): development of a safety checklist.

PubMed

Shankar, Rohit; Cox, David; Jalihal, Virupakshi; Brown, Scott; Hanna, Jane; McLean, Brendan

2013-12-01

The incidence of sudden death appears to be 20 times higher in patients with epilepsy compared with the general population. Epilepsy-related death, particularly sudden unexpected death in epilepsy (SUDEP), is still underestimated by healthcare professionals and this may reflect the mistaken belief that epilepsy is a benign condition. The risk of death associated with epilepsy appeared rarely to have been discussed with patients or their families. It appears the decision to discuss SUDEP and also to peg SUDEP risk is arbitrary and clinical. Unfortunately there is no structured evidenced mechanism at present to represent person centered risk of SUDEP and there is currently no easy manner or template to have this discussion with the family and the patient. We conducted a detailed literature review in Medline, Embase and Psychinfo databases to extract the common risk factors as evidenced from literature till date. Research into risk factors has identified a number of risk factors for SUDEP, some of which are potentially modifiable. Based on the literature review, we believe that the ascertained risk factors could be employed in clinical practice as a checklist to reduce an individual patient's risk of SUDEP. The SUDEP safety checklist may be of practical use in reducing risks in some individuals and is definitely of use in helping communication. An evidence based checklist identifying the major risk factors can help both clinicians and patients to focus on minimizing certain risk factors and promote safety by focusing on the modifiable factors and guide treatment. It can be a tool to open a person centered discussion with patients and to outline how individual behaviors could impact on risk. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

PGL germ granule assembly protein is a base-specific, single-stranded RNase

PubMed Central

Aoki, Scott T.; Kershner, Aaron M.; Bingman, Craig A.; Wickens, Marvin; Kimble, Judith

2016-01-01

Cellular RNA-protein (RNP) granules are ubiquitous and have fundamental roles in biology and RNA metabolism, but the molecular basis of their structure, assembly, and function is poorly understood. Using nematode “P-granules” as a paradigm, we focus on the PGL granule scaffold protein to gain molecular insights into RNP granule structure and assembly. We first identify a PGL dimerization domain (DD) and determine its crystal structure. PGL-1 DD has a novel 13 α-helix fold that creates a positively charged channel as a homodimer. We investigate its capacity to bind RNA and discover unexpectedly that PGL-1 DD is a guanosine-specific, single-stranded endonuclease. Discovery of the PGL homodimer, together with previous results, suggests a model in which the PGL DD dimer forms a fundamental building block for P-granule assembly. Discovery of the PGL RNase activity expands the role of RNP granule assembly proteins to include enzymatic activity in addition to their job as structural scaffolds. PMID:26787882

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

PubMed

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

2017-02-13

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

Single measure and gated screening approaches for identifying students at-risk for academic problems: Implications for sensitivity and specificity.

PubMed

Van Norman, Ethan R; Nelson, Peter M; Klingbeil, David A

2017-09-01

Educators need recommendations to improve screening practices without limiting students' instructional opportunities. Repurposing previous years' state test scores has shown promise in identifying at-risk students within multitiered systems of support. However, researchers have not directly compared the diagnostic accuracy of previous years' state test scores with data collected during fall screening periods to identify at-risk students. In addition, the benefit of using previous state test scores in conjunction with data from a separate measure to identify at-risk students has not been explored. The diagnostic accuracy of 3 types of screening approaches were tested to predict proficiency on end-of-year high-stakes assessments: state test data obtained during the previous year, data from a different measure administered in the fall, and both measures combined (i.e., a gated model). Extant reading and math data (N = 2,996) from 10 schools in the Midwest were analyzed. When used alone, both measures yielded similar sensitivity and specificity values. The gated model yielded superior specificity values compared with using either measure alone, at the expense of sensitivity. Implications, limitations, and ideas for future research are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses.

PubMed

Byrd-Leotis, Lauren; Liu, Renpeng; Bradley, Konrad C; Lasanajak, Yi; Cummings, Sandra F; Song, Xuezheng; Heimburg-Molinaro, Jamie; Galloway, Summer E; Culhane, Marie R; Smith, David F; Steinhauer, David A; Cummings, Richard D

2014-06-03

Influenza viruses bind to host cell surface glycans containing terminal sialic acids, but as studies on influenza binding become more sophisticated, it is becoming evident that although sialic acid may be necessary, it is not sufficient for productive binding. To better define endogenous glycans that serve as viral receptors, we have explored glycan recognition in the pig lung, because influenza is broadly disseminated in swine, and swine have been postulated as an intermediary host for the emergence of pandemic strains. For these studies, we used the technology of "shotgun glycomics" to identify natural receptor glycans. The total released N- and O-glycans from pig lung glycoproteins and glycolipid-derived glycans were fluorescently tagged and separated by multidimensional HPLC, and individual glycans were covalently printed to generate pig lung shotgun glycan microarrays. All viruses tested interacted with one or more sialylated N-glycans but not O-glycans or glycolipid-derived glycans, and each virus demonstrated novel and unexpected differences in endogenous N-glycan recognition. The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis.

Colitis cystica profunda of the rectum: An unexpected operative finding

PubMed Central

Ayantunde, Abraham A; Strauss, Claire; Sivakkolunthu, Malathi; Malhotra, Anu

2016-01-01

Colitis cystic profunda is a rare entity benign condition of the colon and rectum that can mimic suspicious polyps or malignancy. The commonest sites of affectation are the rectum and the sigmoid colon but it can be unusually widely distributed in the colon. The aetiology of this condition is not fully elucidated and confident diagnosis can only be made on histological features. We hereby describe a patient who presented with significant rectal symptoms and an unexpected finding of a submucosal mucous cyst mimicking a suspicious rectal polyp and highlighted its significance and the review of the literature. PMID:27458593

Colitis cystica profunda of the rectum: An unexpected operative finding.

PubMed

Ayantunde, Abraham A; Strauss, Claire; Sivakkolunthu, Malathi; Malhotra, Anu

2016-07-16

Colitis cystic profunda is a rare entity benign condition of the colon and rectum that can mimic suspicious polyps or malignancy. The commonest sites of affectation are the rectum and the sigmoid colon but it can be unusually widely distributed in the colon. The aetiology of this condition is not fully elucidated and confident diagnosis can only be made on histological features. We hereby describe a patient who presented with significant rectal symptoms and an unexpected finding of a submucosal mucous cyst mimicking a suspicious rectal polyp and highlighted its significance and the review of the literature.

Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

PubMed

Condie, Brian G; Urbanski, William M

2014-01-01

Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

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

Grandparentage assignments identify unexpected adfluvial life history tactic contributing offspring to a reintroduced population.

PubMed

Sard, Nicholas M; Jacobson, Dave P; Banks, Michael A

2016-10-01

Diversity in life history tactics contributes to the persistence of a population because it helps to protect against stochastic environments by varying individuals in space and time. However, some life history tactics may not be accounted for when assessing the demographic viability of a population. One important factor in demographic viability assessments is cohort replacement rate (CRR), which is defined as the number of future adults produced by an adult. We assessed if precocial resident males (identified 31 precocial resident males and 48 probable adfluvial Chinook salmon produced by anadromous mate pairs from 2007 to 2012. Previously published CRR estimates for the 2007 and 2008 reintroduced adults, based on only anadromous returning adult offspring, were 0.40 and 0.31, respectively. By incorporating adfluvial females, we found CRR estimates increased by 17% (CRR: 0.46) and 13% (CRR: 0.35) for the 2007 and 2008 cohorts, respectively.

Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors.

PubMed

Polimanti, Renato; Zhao, Hongyu; Farrer, Lindsay A; Kranzler, Henry R; Gelernter, Joel

2017-12-01

We previously mapped loci for the genome-wide association studies (GWAS) and genome-wide gene-by-alcohol dependence interaction (GW-GxAD) analyses of risky sexual behaviors (RSB). This study extends those findings by analyzing the ancestry- and sex-specific AD-stratified effects on RSB. We examined the concordance of findings for the AD-stratified GWAS and the GW-GxAD analysis of RSB, with concordance defined as genome-wide significance in one analysis and at least nominal significance in the second analysis. A total of 2,173 African-American (AA) and 1,751 European-American (EA) subjects were investigated. Information regarding RSB (lifetime experiences of unprotected sex and multiple sexual partners) and DSM-IV diagnosis of lifetime AD were derived from the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). In our ancestry- and sex-specific analyses, we identified four independent genome-wide significant (GWS) loci (p < 5*10 -8 ) and one suggestive locus (p < 6*10 -8 ). In men, we observed a GWS signal in FAM162A (rs2002594, p = 4.96*10 -8 ). In women, there was a suggestive locus in PLGRKT (rs3824435, p = 5.52*10 -8 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p = 1.25*10 -9 ). In AA men, we observed an intergenic GWS signal (rs12898370, p = 4.49*10 -8 ) near LINGO1. In EA men, there was a GWS signal in CCSER1 (rs62313897; p = 7.93*10 -10 ). The loci identified in this GWAS implicate molecular mechanisms related to psychiatric illness and personality features, suggesting that the interplay between AD and RSB is mediated by alleles associated with behavioral traits. © 2017 Wiley Periodicals, Inc.

Subclinical hyperthyroidism and sudden unexpected death in epilepsy.

PubMed

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

2010-04-01

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

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

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

Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease.

PubMed

Lu, Xiangfeng; Peloso, Gina M; Liu, Dajiang J; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-Man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H-H; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B; Adair, Linda S; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; Chen, Yii-Der Ida; Shu, Xiao-Ou; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars G; Nielsen, Jonas Bille; Tse, Hung-Fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y Eugene; Zheng, Wei; Tai, E Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; Kathiresan, Sekar; Mohlke, Karen L; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; Willer, Cristen J

2017-12-01

Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

Non-targeted analysis of unexpected food contaminants using LC-HRMS.

PubMed

Kunzelmann, Marco; Winter, Martin; Åberg, Magnus; Hellenäs, Karl-Erik; Rosén, Johan

2018-03-29

A non-target analysis method for unexpected contaminants in food is described. Many current methods referred to as "non-target" are capable of detecting hundreds or even thousands of contaminants. However, they will typically still miss all other possible contaminants. Instead, a metabolomics approach might be used to obtain "true non-target" analysis. In the present work, such a method was optimized for improved detection capability at low concentrations. The method was evaluated using 19 chemically diverse model compounds spiked into milk samples to mimic unknown contamination. Other milk samples were used as reference samples. All samples were analyzed with UHPLC-TOF-MS (ultra-high-performance liquid chromatography time-of-flight mass spectrometry), using reversed-phase chromatography and electrospray ionization in positive mode. Data evaluation was performed by the software TracMass 2. No target lists of specific compounds were used to search for the contaminants. Instead, the software was used to sort out all features only occurring in the spiked sample data, i.e., the workflow resembled a metabolomics approach. Procedures for chemical identification of peaks were outside the scope of the study. Method, study design, and settings in the software were optimized to minimize manual evaluation and faulty or irrelevant hits and to maximize hit rate of the spiked compounds. A practical detection limit was established at 25 μg/kg. At this concentration, most compounds (17 out of 19) were detected as intact precursor ions, as fragments or as adducts. Only 2 irrelevant hits, probably natural compounds, were obtained. Limitations and possible practical use of the approach are discussed.

Dark Adaptation at High Altitude: An Unexpected Pupillary Response to Chronic Hypoxia in Andean Highlanders.

PubMed

Healy, Katherine; Labrique, Alain B; Miranda, J Jaime; Gilman, Robert H; Danz, David; Davila-Roman, Victor G; Huicho, Luis; León-Velarde, Fabiola; Checkley, William

2016-09-01

Healy, Katherine, Alain B. Labrique, J. Jaime Miranda, Robert H. Gilman, David Danz, Victor G. Davila-Roman, Luis Huicho, Fabiola León-Velarde, and William Checkley. Dark adaptation at high altitude: an unexpected pupillary response to chronic hypoxia in Andean highlanders. High Alt Med Biol. 17:208-213, 2016.-Chronic mountain sickness is a maladaptive response to high altitude (>2500 m above sea level) and is characterized by excessive erythrocytosis and hypoxemia resulting from long-term hypobaric hypoxia. There is no known early predictor of chronic mountain sickness and the diagnosis is based on the presence of excessive erythrocytosis and clinical features. Impaired dark adaptation, or an inability to visually adjust from high- to low-light settings, occurs in response to mild hypoxia and may serve as an early predictor of hypoxemia and chronic mountain sickness. We aimed to evaluate the association between pupillary response assessed by dark adaptometry and daytime hypoxemia in resident Andean highlanders aged ≥35 years living in Puno, Peru. Oxyhemoglobin saturation (SpO 2 ) was recorded using a handheld pulse oximeter. Dark adaptation was quantitatively assessed as the magnitude of pupillary contraction to light stimuli of varying intensities (-2.9 to 0.1 log-cd/m 2 ) using a portable dark adaptometer. Individual- and stimulus-specific multilevel analyses were conducted using mixed-effect models to elicit the relationship between SpO 2 and pupillary responsiveness. Among 93 participants, mean age was 54.9 ± 11.0 years, 48% were male, 44% were night blind, and mean SpO 2 was 89.3% ± 3.4%. The magnitude of pupillary contraction was greater with lower SpO 2 (p < 0.01), and this dose relationship remained significant in multiple variable analyses (p = 0.047). Pupillary responsiveness to light stimuli under dark-adapted conditions was exaggerated with hypoxemia and may serve as an early predictor of chronic mountain sickness. This

Genome-wide Association Study Identifies African-Specific Susceptibility Loci in African Americans with Inflammatory Bowel Disease

PubMed Central

Brant, Steven R.; Okou, David T.; Simpson, Claire L.; Cutler, David J.; Haritunians, Talin; Bradfield, Jonathan P.; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W.; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J.; Klapproth, Jan-Micheal A.; Quiros, Antonio J.; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S.; Baldassano, Robert N.; Dudley-Brown, Sharon; Cross, Raymond K.; Dassopoulos, Themistocles; Denson, Lee A.; Dhere, Tanvi A.; Dryden, Gerald W.; Hanson, John S.; Hou, Jason K.; Hussain, Sunny Z.; Hyams, Jeffrey S.; Isaacs, Kim L.; Kader, Howard; Kappelman, Michael D.; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S.; Kuemmerle, John F.; Kwon, John H.; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E.; Newberry, Rodney D.; Osuntokun, Bankole O.; Patel, Ashish S.; Saeed, Shehzad A.; Targan, Stephan R.; Valentine, John F.; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Hakonarson, Hakon; Zwick, Michael E.; McGovern, Dermot P.B.; Kugathasan, Subra

2016-01-01

Background & Aims The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. Methods We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified [IBD-U]) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P<5.0×10−8 in meta-analysis with a nominal evidence (P<.05) in each scan were considered to have genome-wide significance. Results We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance associations for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P<1.6×10−6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B, PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. Conclusions We performed a genome-wide association study of African Americans with IBD and identified loci associated with CD and UC in only this population; we also replicated loci identified in European populations. The detection of variants associated with IBD risk in only

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

PubMed

Brant, Steven R; Okou, David T; Simpson, Claire L; Cutler, David J; Haritunians, Talin; Bradfield, Jonathan P; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J; Klapproth, Jan-Micheal A; Quiros, Antonio J; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S; Baldassano, Robert N; Dudley-Brown, Sharon; Cross, Raymond K; Dassopoulos, Themistocles; Denson, Lee A; Dhere, Tanvi A; Dryden, Gerald W; Hanson, John S; Hou, Jason K; Hussain, Sunny Z; Hyams, Jeffrey S; Isaacs, Kim L; Kader, Howard; Kappelman, Michael D; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S; Kuemmerle, John F; Kwon, John H; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E; Newberry, Rodney D; Osuntokun, Bankole O; Patel, Ashish S; Saeed, Shehzad A; Targan, Stephan R; Valentine, John F; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D; Duerr, Richard H; Silverberg, Mark S; Cho, Judy H; Hakonarson, Hakon; Zwick, Michael E; McGovern, Dermot P B; Kugathasan, Subra

2017-01-01

The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10 -8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10 -6 ): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the

Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.

PubMed

Chen, Xiaowei Sylvia; Reader, Rose H; Hoischen, Alexander; Veltman, Joris A; Simpson, Nuala H; Francks, Clyde; Newbury, Dianne F; Fisher, Simon E

2017-04-25

A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential "multiple-hit" cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation.

Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment

PubMed Central

Chen, Xiaowei Sylvia; Reader, Rose H.; Hoischen, Alexander; Veltman, Joris A.; Simpson, Nuala H.; Francks, Clyde; Newbury, Dianne F.; Fisher, Simon E.

2017-01-01

A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential “multiple-hit” cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation. PMID:28440294

Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs

PubMed Central

Below, Jennifer E.; Parra, Esteban J.; Gamazon, Eric R.; Torres, Jason; Krithika, S.; Candille, Sophie; Lu, Yingchang; Manichakul, Ani; Peralta-Romero, Jesus; Duan, Qing; Li, Yun; Morris, Andrew P.; Gottesman, Omri; Bottinger, Erwin; Wang, Xin-Qun; Taylor, Kent D.; Ida Chen, Y.-D.; Rotter, Jerome I.; Rich, Stephen S.; Loos, Ruth J. F.; Tang, Hua; Cox, Nancy J.; Cruz, Miguel; Hanis, Craig L.; Valladares-Salgado, Adan

2016-01-01

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci. PMID:26780889

Sudden unexpected nocturnal death in Chiari type 1 malformation and potential role of opioid analgesics

PubMed Central

Roohi, Fereydoon; Gropen, Toby; Kula, Roger W.

2014-01-01

Background: Chiari malformation type 1 (CM1) is a common congenital anomaly of the craniocervical junction. CM1 is reported to run a usually benign course and patients typically experience no symptoms or chronic, slowly progressive symptoms. However, recent reports indicate that a subset of patients with CM1 may present with acute deterioration and sudden unexpected death (SUD). We report a case of SUD during sleep in a young man with CM1, which we believe was related to the administration of common and therapeutic doses of narcotic analgesics for the management of pain. We will clarify the pathophysiology of acute deterioration and SUD in CM1 and the possibility that the adverse effects of opiate analgesics likely were the leading cause of death in our patient. Case Description: In this review, we present a 29-year-old male with worsening headache secondary to previously diagnosed CM1. The patient died suddenly and unexpectedly after administration of common and therapeutic doses of narcotic analgesics for the management of pain. Conclusion: The mechanism(s) of acute neurological deterioration and sudden death in patients with CM1 remains poorly understood. We believe the rapid fatal deterioration in our patient following administration of opioids suggests that this category of medication may cause sudden unexpected “neurogenic” cardiac death in CM1 patients by inducing sleep-related breathing difficulties and associated hypercapnia. Hypercapnia by further increasing intracranial pressure can result in a sudden pressure-induced decompensation of the cardiopulmonary control centers in the brain stem and cause instantaneous cardiorespiratory arrest. PMID:24778905

[Identifying the specific causes of kidney allograft loss: A population-based study].

PubMed

Lohéac, Charlotte; Aubert, Olivier; Loupy, Alexandre; Legendre, Christophe

2018-04-01

Results of kidney transplantation have been improving but long-term allograft survival remains disappointing. The objective of the present study was to identify the specific causes of renal allograft loss, to assess their incidence and long-term outcomes. A total of 4783 patients from four French centres, transplanted between January 2004 and January 2014 were prospectively included. A total of 9959 kidney biopsies (protocol and for cause) performed between January 2004 and March 2015 were included. Donor and recipient clinical and biological parameters as well as anti-HLA antibody directed against the donor were included. The main outcome was the long-term kidney allograft survival, including the study of the associated causes of graft loss, the delay of graft loss according to their causes and the determinants of graft loss. There were 732 graft losses during the follow-up period (median time: 4.51 years) with an identified cause in 95.08 %. Kidney allograft survival at 9 years post-transplant was 78 %. The causes of allograft loss were: antibody-mediated rejection (31.69 %), thrombosis (25.55 %), medical intercurrent disease (14.62 %), recurrence of primary renal disease (7.1 %), BK- or CMV-associated nephropathy (n=35, 4.78 %), T cell-mediated rejection (4.78 %), urological disease (2.46 %) and calcineurin inhibitor nephrotoxicity (1.09 %). The main causes of allograft loss were antibody-mediated rejection and thrombosis. These results encourage efforts to prevent and detect these complications earlier in order to improve allograft survival. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Gastric Cancer-Specific Protein Profile Identified Using Endoscopic Biopsy Samples via MALDI Mass Spectrometry

PubMed Central

Kim, Hark Kyun; Reyzer, Michelle L.; Choi, Il Ju; Kim, Chan Gyoo; Kim, Hee Sung; Oshima, Akira; Chertov, Oleg; Colantonio, Simona; Fisher, Robert J.; Allen, Jamie L.; Caprioli, Richard M.; Green, Jeffrey E.

2012-01-01

To date, proteomic analyses on gastrointestinal cancer tissue samples have been performed using surgical specimens only, which are obtained after a diagnosis is made. To determine if a proteomic signature obtained from endoscopic biopsy samples could be found to assist with diagnosis, frozen endoscopic biopsy samples collected from 63 gastric cancer patients and 43 healthy volunteers were analyzed using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. A statistical classification model was developed to distinguish tumor from normal tissues using half the samples and validated with the other half. A protein profile was discovered consisting of 73 signals that could classify 32 cancer and 22 normal samples in the validation set with high predictive values (positive and negative predictive values for cancer, 96.8% and 91.3%; sensitivity, 93.8%; specificity, 95.5%). Signals overexpressed in tumors were identified as α-defensin-1, α-defensin-2, calgranulin A, and calgranulin B. A protein profile was also found to distinguish pathologic stage Ia (pT1N0M0) samples (n = 10) from more advanced stage (Ib or higher) tumors (n = 48). Thus, protein profiles obtained from endoscopic biopsy samples may be useful in assisting with the diagnosis of gastric cancer and, possibly, in identifying early stage disease. PMID:20557134

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Identifying wide, cold planets within 8pc

NASA Astrophysics Data System (ADS)

Deacon, Niall; Kraus, Adam; Crossfield, Ian

2014-12-01

Direct imaging exoplanet studies have recently unveiled a previously-unexpected population of massive planets (up to 15 M_Jup) in wide orbits (>100AU). Although most of these discoveries have been around younger stars and have been of similar temperatures to field brown dwarfs, one object (WD 0806-661B), is the coldest planet known outside our solar system. We propose a survey of all stars and brown dwarfs within 8pc to identify massive planetary companions in the 150-1500AU separation range. We will 1) Measure the fraction of wide planetary mass companions to stars in the Solar neighbourhood. 2) Identify all planets within 8 parsecs with masses above 8 Jupiter masses in our chosen projected separation range with lower mass limits for closer and younger stars. 3) Identify approximately 8 planets, four of which will have temperatures below 300K making them ideal targets to study water clouds in cold atmospheres with both JWST and the next generation of ground-based extremely large telescopes. Our survey will be the most complete survey for wide planets to-date and will provide both a measurement of the wide planet population and a legacy of cold, well constrained targets for future observatories.

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

EPA Science Inventory

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

Systematic VCP-UBXD Adaptor Network Proteomics Identifies a Role for UBXN10 in Regulating Ciliogenesis

PubMed Central

Raman, Malavika; Sergeev, Mikhail; Garnaas, Maija; Lydeard, John R.; Huttlin, Edward L.; Goessling, Wolfram; Shah, Jagesh V.; Harper, J. Wade

2015-01-01

The AAA-ATPase VCP (also known as p97 or CDC48) uses ATP hydrolysis to “segregate” ubiquitinated proteins from their binding partners. VCP acts via UBX-domain containing adaptors that provide target specificity, but targets and functions of UBXD proteins remain poorly understood. Through systematic proteomic analysis of UBXD proteins in human cells, we reveal a network of over 195 interacting proteins, implicating VCP in diverse cellular pathways. We have explored one such complex between an unstudied adaptor UBXN10 and the intraflagellar transport B (IFT-B) complex, which regulates anterograde transport into cilia. UBXN10 localizes to cilia in a VCP-dependent manner and both VCP and UBXN10 are required for ciliogenesis. Pharmacological inhibition of VCP destabilized the IFT-B complex and increased trafficking rates. Depletion of UBXN10 in zebrafish embryos causes defects in left-right asymmetry, which depends on functional cilia. This study provides a resource for exploring the landscape of UBXD proteins in biology and identifies an unexpected requirement for VCP-UBXN10 in ciliogenesis. PMID:26389662

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

[Analysis of how elderly internet users react to unexpected situations].

PubMed

Haesner, Marten; Steinert, Anika; O'Sullivan, Julie Lorraine; Steinhagen-Thiessen, Elisabeth

2015-12-01

Although internet usage among older adults is steadily increasing, there is still a digital divide between generations. Younger internet users seem to be more open towards new media. Recent studies showed the negative influence of computer anxiety on internet usage. It is not known how older adults deal with computer and internet issues in their home environment and which problem-solving strategies they apply. The behavior of elderly people in unexpected situations when using an internet portal was analyzed to establish whether older users can solve the problems without assistance and what individual reactions (e.g. facial expressions and gesticulations) they show during the interaction. In a clinical trial with 50 older adults aged 60 years and older various typical problems which may occur while using web platforms were simulated and user behavior was analyzed using logging data, videography and with questionnaires to measure the subjective opinion of the study participants. The study participants had severe problems in solving the tasks on their own and many of them could not find a suitable solution at all. Overall, the videography data indicated an increased concentration of the participants during the whole session, which is in contrast to the low levels of perceived mental workload reported by the participants. Regarding task completion, no differences were found between seniors with and without cognitive impairment. The results showed the serious difficulties of older adults when dealing with unexpected events while using a web platform. For developers of internet platforms for inexperienced seniors, it seems to be crucial to incorporate a simple integration of all available features within the platform, without including features requiring high multi-tasking skills.

Unexpected findings of a female team in Xochimilco, Mexico.

PubMed

Martínez-Salgado, C

1999-01-01

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

Unexpected School Reform: Academisation of Primary Schools in England. CEP Discussion Paper No. 1455

ERIC Educational Resources Information Center

Eyles, Andrew; Machin, Stephen; McNally, Sandra

2016-01-01

The change of government in 2010 provoked a large structural change in the English education landscape. Unexpectedly, the new government offered primary schools the chance to have "the freedom and the power to take control of their own destiny", with better performing schools given a green light to convert to become an academy school on…

Sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students susceptible to psychosis.

PubMed

Ma, Wei-Fen; Wu, Po-Lun; Yang, Shu-Ju; Cheng, Kuang-Fu; Chiu, Hsien-Tsai; Lane, Hsien-Yuan

2010-12-01

Early interventions can improve treatment outcomes for individuals with major psychiatric disorders and with nonspecific symptoms but increasingly impaired cognitive perception, emotions, and behaviour. One way used to identify people susceptible to psychosis is through the schizotypal personality trait. Persons with schizotypal characteristics have been identified with the widely used Schizotypal Personality Questionnaire-Brief. However, no suitable instruments are available to screen individuals in the Taiwanese population for evidence of early psychotic symptoms. The purpose of this study was to test the sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students' susceptibility to psychosis. Two-stage, cross-sectional survey design. The self-administered scale was tested in a convenience sample of 618 undergraduate students at a medical university in Taiwan. Among these students, 54 completed the scale 2 weeks apart for test-retest reliability, and 80 were tested to identify their susceptibility to psychosis. In Stage I, participants with scores in the top 6.5% were classified as the high-score group (n=40). The control group (n=40) was randomly selected from the remaining participants with scores <15 and matched by gender. These 80 students were asked to participate in psychiatric interviews in Stage II. The instrument was tested for reliability using intraclass correlation coefficients and the Kuder-Richardson formula 20. The instrument was analysed for optimal sensitivity and specificity using odds-ratio analysis and receiver operating characteristic curves. The 22-item Chinese version of the Schizotypal Personality Questionnaire-Brief had a 2-week test-retest reliability of 0.82 and internal consistency of 0.76. The optimal cut-off score was 17, with odds ratios of 24.4 and an area under the receiver operating characteristic curves of 0.83. The instrument had a sensitivity of

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.

Encountering the Unexpected: Revelations of Trust, Vulnerability, and Embodied Ways of Knowing.

PubMed

Russell, Laura D

2018-05-31

Health communication scholars grapple with complex issues, many of which probe embodied sensibilities. This essay narrates a profound, unexpected moment that gives rise to notions of trust, vulnerability, and risks involved when conducting fieldwork. The author explains how embodied interactions bring forth latent constructs pertinent to health communication research, both for investigative practices and applied purposes. Furthermore, the author questions how symbolic acts demonstrated by research participants may illuminate powerful meanings yet simultaneously pose potential dangers for researchers.

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

ERIC Educational Resources Information Center

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

2014-01-01

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

Fluorescently labeled dengue viruses as probes to identify antigen-specific memory B cells by multiparametric flow cytometry.

PubMed

Woda, Marcia; Mathew, Anuja

2015-01-01

Low frequencies of memory B cells in the peripheral blood make it challenging to measure the functional and phenotypic characteristics of this antigen experienced subset of B cells without in vitro culture. To date, reagents are lacking to measure ex vivo frequencies of dengue virus (DENV)-specific memory B cells. We wanted to explore the possibility of using fluorescently labeled DENV as probes to detect antigen-specific memory B cells in the peripheral blood of DENV immune individuals. Alexa Fluor dye-labeled DENV yielded viable virus that could be stored at -80°C for long periods of time. Using a careful gating strategy and methods to decrease non-specific binding, we were able to identify a small frequency of B cells from dengue immune individuals that bound labeled DENV. Sorted DENV(+) B cells from immune, but not naïve donors secreted antibodies that bound DENV after in vitro stimulation. Overall, Alexa Fluor dye-labeled DENVs are useful reagents to enable the detection and characterization of memory B cells in DENV immune individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

Fluorescently labeled dengue viruses as probes to identify antigen-specific memory B cells by multiparametric flow cytometry

PubMed Central

Woda, Marcia; Mathew, Anuja

2015-01-01

Low frequencies of memory B cells in the peripheral blood make it challenging to measure the functional and phenotypic characteristics of this antigen experienced subset of B cells without in vitro culture. To date, reagents are lacking to measure ex vivo frequencies of dengue virus (DENV)-specific memory B cells. We wanted to explore the possibility of using fluorescently labeled DENV as probes to detect antigen-specific memory B cells in the peripheral blood of DENV immune individuals. Alexa Fluor dye-labeled DENV yielded viable virus that could be stored at −80°C for long periods of time. Using a careful gating strategy and methods to decrease non-specific binding, we were able to identify a small frequency of B cells from dengue immune individuals that bound labeled DENV. Sorted DENV+ B cells from immune, but not naïve donors secreted antibodies that bound intact virions after in vitro stimulation. Overall, Alexa Fluor dye labeled -DENV are useful reagents to enable the detection and characterization of memory B cells in DENV immune individuals. PMID:25497702

Specific PCR primers directed to identify cryI and cryIII genes within a Bacillus thuringiensis strain collection.

PubMed Central

Cerón, J; Ortíz, A; Quintero, R; Güereca, L; Bravo, A

1995-01-01

In this paper we describe a PCR strategy that can be used to rapidly identify Bacillus thuringiensis strains that harbor any of the known cryI or cryIII genes. Four general PCR primers which amplify DNA fragments from the known cryI or cryIII genes were selected from conserved regions. Once a strain was identified as an organism that contains a particular type of cry gene, it could be easily characterized by performing additional PCR with specific cryI and cryIII primers selected from variable regions. The method described in this paper can be used to identify the 10 different cryI genes and the five different cryIII genes. One feature of this screening method is that each cry gene is expected to produce a PCR product having a precise molecular weight. The genes which produce PCR products having different sizes probably represent strains that harbor a potentially novel cry gene. Finally, we present evidence that novel crystal genes can be identified by the method described in this paper. PMID:8526493

Genome-wide Association Study Identifies Peanut Allergy-Specific Loci and Evidence of Epigenetic Mediation in U.S. Children

PubMed Central

Hong, Xiumei; Hao, Ke; Ladd-Acosta, Christine; Hansen, Kasper D; Tsai, Hui-Ju; Liu, Xin; Xu, Xin; Thornton, Timothy A.; Caruso, Deanna; Keet, Corinne A; Sun, Yifei; Wang, Guoying; Luo, Wei; Kumar, Rajesh; Fuleihan, Ramsay; Singh, Anne Marie; Kim, Jennifer S; Story, Rachel E; Gupta, Ruchi S; Gao, Peisong; Chen, Zhu; Walker, Sheila O.; Bartell, Tami R; Beaty, Terri H; Fallin, M Daniele; Schleimer, Robert; Holt, Patrick G; Nadeau, Kari Christine; Wood, Robert A; Pongracic, Jacqueline A; Weeks, Daniel E; Wang, Xiaobin

2015-01-01

Food allergy (FA) affects 2–10% of U.S. children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk, and egg) in 2,759 U.S. participants (1,315 children; 1,444 parents) from the Chicago Food Allergy Study; and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (p=5.5×10−8) and rs9275596 (p=6.8×10−10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (p<5×10−8); and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region likely poses significant genetic risk for PA. PMID:25710614

ETIOLOGY, TRIGGERS AND NEUROCHEMICAL CIRCUITS ASSOCIATED WITH UNEXPECTED, EXPECTED, AND LABORATORY-INDUCED PANIC ATTACKS

PubMed Central

Johnson, Philip L.; Federici, Lauren M.; Shekhar, Anantha

2014-01-01

Panic disorder (PD) is a severe anxiety disorder that is characterized by recurrent panic attacks (PA), which can be unexpected (uPA, i.e., no clear identifiable trigger) or expected (ePA). Panic typically involves an abrupt feeling of catastrophic fear or distress accompanied by physiological symptoms such as palpitations, racing heart, thermal sensations, and sweating. Recurrent uPA and ePA can also lead to agoraphobia, where subjects with PD avoid situations that were associated with PA. Here we will review recent developments in our understanding of PD, which includes discussions on: symptoms and signs associated with uPA and ePAs; Diagnosis of PD and the new DSM-V; biological etiology such as heritability and gene x environment and gene x hormonal development interactions; comparisons between laboratory and naturally occurring uPAs and ePAs; neurochemical systems that are associated with clinical PAs (e.g. gene associations; targets for triggering or treating PAs), adaptive fear and panic response concepts in the context of new NIH RDoc approach; and finally strengths and weaknesses of translational animal models of adaptive and pathological panic states. PMID:25130976

Application of DNA markers to identify the individual-specific hosts of tsetse feeding on cattle.

PubMed

Torr, S J; Wilson, P J; Schofield, S; Mangwiro, T N; Akber, S; White, B N

2001-03-01

Primer sets for five different ungulate loci were used to obtain individual microsatellite DNA profiles for 29 Mashona cattle from a herd in Zimbabwe. There were 3-13 alleles for each locus and, using the entire suite of five loci, each animal within the herd, including closely related individuals, could be unequivocally distinguished. Wild-caught Glossina pallidipes Austen (Diptera: Glossinidae) were fed on specific cattle and the bloodmeal was profiled 0.5-72 h after feeding. The individual specific sources of the bloodmeals, including mixe meals produced by allowing tsetse to feed on two different cattle, were reliabl identified up to 24 h after feeding. The technique was used in field studies of hos selection by G. pallidipes and G. morsitans morsitans Westwood (Diptera Glossinidae) attracted to pairs of cattle. When the pair comprised an adult and a calf, 100% of meals were from the adult. For some pairs of adult cattle, tsetse were biased significantly towards feeding on one animal, whereas for other pairs there was no such bias. In general, feeding was greater on the animal known to have lower rate of host defensive behaviour. Results suggest that relatively slight differences in the inherent defensive behaviour of cattle produce large difference in host-specific feeding rates when the hosts are adjacent. For flies attracted to pair of cattle, < 2% contained blood from both hosts. The DNA profiling technique will be useful in studying the epidemiology of vector-borne diseases of livestock.

Identifying Specific Learning Disabilities: Legislation, Regulation, and Court Decisions

ERIC Educational Resources Information Center

Zumeta, Rebecca O.; Zirkel, Perry A.; Danielson, Louis

2014-01-01

Specific learning disability (SLD) identification and eligibility practices are evolving and sometimes contentious. This article describes the historical context and current status of the SLD definition, legislation, regulation, and case law related to the identification of students eligible for special education services. The first part traces…

Genetic Screening Identifies Cyanogenesis-Deficient Mutants of Lotus japonicus and Reveals Enzymatic Specificity in Hydroxynitrile Glucoside Metabolism[W][OA

PubMed Central

Takos, Adam; Lai, Daniela; Mikkelsen, Lisbeth; Abou Hachem, Maher; Shelton, Dale; Motawia, Mohammed Saddik; Olsen, Carl Erik; Wang, Trevor L.; Martin, Cathie; Rook, Fred

2010-01-01

Cyanogenesis, the release of hydrogen cyanide from damaged plant tissues, involves the enzymatic degradation of amino acid–derived cyanogenic glucosides (α-hydroxynitrile glucosides) by specific β-glucosidases. Release of cyanide functions as a defense mechanism against generalist herbivores. We developed a high-throughput screening method and used it to identify cyanogenesis deficient (cyd) mutants in the model legume Lotus japonicus. Mutants in both biosynthesis and catabolism of cyanogenic glucosides were isolated and classified following metabolic profiling of cyanogenic glucoside content. L. japonicus produces two cyanogenic glucosides: linamarin (derived from Val) and lotaustralin (derived from Ile). Their biosynthesis may involve the same set of enzymes for both amino acid precursors. However, in one class of mutants, accumulation of lotaustralin and linamarin was uncoupled. Catabolic mutants could be placed in two complementation groups, one of which, cyd2, encoded the β-glucosidase BGD2. Despite the identification of nine independent cyd2 alleles, no mutants involving the gene encoding a closely related β-glucosidase, BGD4, were identified. This indicated that BGD4 plays no role in cyanogenesis in L. japonicus in vivo. Biochemical analysis confirmed that BGD4 cannot hydrolyze linamarin or lotaustralin and in L. japonicus is specific for breakdown of related hydroxynitrile glucosides, such as rhodiocyanoside A. By contrast, BGD2 can hydrolyze both cyanogenic glucosides and rhodiocyanosides. Our genetic analysis demonstrated specificity in the catabolic pathways for hydroxynitrile glucosides and implied specificity in their biosynthetic pathways as well. In addition, it has provided important tools for elucidating and potentially modifying cyanogenesis pathways in plants. PMID:20453117

Identifying sex-specific risk factors for low bone mineral density in adolescent runners.

PubMed

Tenforde, Adam Sebastian; Fredericson, Michael; Sayres, Lauren Carter; Cutti, Phil; Sainani, Kristin Lynn

2015-06-01

Adolescent runners may be at risk for low bone mineral density (BMD) associated with sports participation. Few prior investigations have evaluated bone health in young runners, particularly males. To characterize sex-specific risk factors for low BMD in adolescent runners. Cross-sectional study; Level of evidence, 3. Training characteristics, fracture history, eating behaviors and attitudes, and menstrual history were measured using online questionnaires. A food frequency questionnaire was used to identify dietary patterns and measure calcium intake. Runners (female: n = 94, male: n = 42) completed dual-energy x-ray absorptiometry (DXA) to measure lumbar spine (LS) and total body less head (TBLH) BMD and body composition values, including android-to-gynoid (A:G) fat mass ratio. The BMD was standardized to Z-scores using age, sex, and race/ethnicity reference values. Questionnaire values were combined with DXA values to determine risk factors associated with differences in BMD Z-scores in LS and TBLH and low bone mass (defined as BMD Z-score ≤-1). In multivariable analyses, risk factors for lower LS BMD Z-scores in girls included lower A:G ratio, being shorter, and the combination of (interaction between) current menstrual irregularity and a history of fracture (all P < .01). Later age of menarche, lower A:G ratio, lower lean mass, and drinking less milk were associated with lower TBLH BMD Z-scores (P < .01). In boys, lower body mass index (BMI) Z-scores and the belief that being thinner improves performance were associated with lower LS and TBLH BMD Z-scores (all P < .05); lower A:G ratio was additionally associated with lower TBLH Z-scores (P < .01). Thirteen girls (14%) and 9 boys (21%) had low bone mass. Girls with a BMI ≤17.5 kg/m(2) or both menstrual irregularity and a history of fracture were significantly more likely to have low bone mass. Boys with a BMI ≤17.5 kg/m(2) and belief that thinness improves performance were significantly more likely to have

Omics of Brucella: Species-Specific sRNA-Mediated Gene Ontology Regulatory Networks Identified by Computational Biology.

PubMed

Vishnu, Udayakumar S; Sankarasubramanian, Jagadesan; Gunasekaran, Paramasamy; Sridhar, Jayavel; Rajendhran, Jeyaprakash

2016-06-01

Brucella is an intracellular bacterium that causes the zoonotic infectious disease, brucellosis. Brucella species are currently intensively studied with a view to developing novel global health diagnostics and therapeutics. In this context, small RNAs (sRNAs) are one of the emerging topical areas; they play significant roles in regulating gene expression and cellular processes in bacteria. In the present study, we forecast sRNAs in three Brucella species that infect humans, namely Brucella melitensis, Brucella abortus, and Brucella suis, using a computational biology analysis. We combined two bioinformatic algorithms, SIPHT and sRNAscanner. In B. melitensis 16M, 21 sRNA candidates were identified, of which 14 were novel. Similarly, 14 sRNAs were identified in B. abortus, of which four were novel. In B. suis, 16 sRNAs were identified, and five of them were novel. TargetRNA2 software predicted the putative target genes that could be regulated by the identified sRNAs. The identified mRNA targets are involved in carbohydrate, amino acid, lipid, nucleotide, and coenzyme metabolism and transport, energy production and conversion, replication, recombination, repair, and transcription. Additionally, the Gene Ontology (GO) network analysis revealed the species-specific, sRNA-based regulatory networks in B. melitensis, B. abortus, and B. suis. Taken together, although sRNAs are veritable modulators of gene expression in prokaryotes, there are few reports on the significance of sRNAs in Brucella. This report begins to address this literature gap by offering a series of initial observations based on computational biology to pave the way for future experimental analysis of sRNAs and their targets to explain the complex pathogenesis of Brucella.

Safe sleep practices in a New Zealand community and development of a Sudden Unexpected Death in Infancy (SUDI) risk assessment instrument.

PubMed

Galland, Barbara C; Gray, Andrew; Sayers, Rachel M; Heath, Anne-Louise M; Lawrence, Julie; Taylor, Rachael; Taylor, Barry J

2014-10-13

Interventions to prevent sudden unexpected death in infancy (SUDI) have generally been population wide interventions instituted after case-control studies identified specific childcare practices associated with sudden death. While successful overall, in New Zealand (NZ), the rates are still relatively high by international comparison. This study aims to describe childcare practices related to SUDI prevention messages in a New Zealand community, and to develop and explore the utility of a risk assessment instrument based on international guidelines and evidence. Prospective longitudinal study of 209 infants recruited antenatally. Participant characteristics and infant care data were collected by questionnaire at: baseline (third trimester), and monthly from infant age 3 weeks through 23 weeks. Published meta-analyses data were used to estimate individual risk ratios for 6 important SUDI risk factors which, when combined, yielded a "SUDI risk score". Most infants were at low risk for SUDI with 72% at the lowest or slightly elevated risk (combined risk ratio ≤1.5). There was a high prevalence of the safe practices: supine sleeping (86-89% over 3-19 weeks), mother not smoking (90-92% over 3-19 weeks), and not bed sharing at a young age (87% at 3 weeks). Five independent predictors of a high SUDI risk score were: higher parity (P =0.028), younger age (P =0.030), not working or caring for other children antenatally (P =0.031), higher depression scores antenatally (P =0.036), and lower education (P =0.042). Groups within the community identified as priorities for education about safe sleep practices beyond standard care are mothers who are young, have high parity, low educational levels, and have symptoms of depression antenatally. These findings emphasize the importance of addressing maternal depression as a modifiable risk factor in pregnancy.

Explaining the unexpected success of the smoking ban in Italy: political strategy and transition to practice, 2000–2005.

PubMed

Mele, Valentina; Compagni, Amelia

2010-01-01

The approval (2003) and enforcement (2005) of a smoking ban in Italy have been viewed by many as an unexpectedly successful example of policy change. The present paper, by applying a processualist approach, concentrates on two policy cycles between 2000 and 2005. These had opposing outcomes: an incomplete decisional stage and an authoritative decision, enforced two years later. Through the analysis of the different phases of agenda setting, alternative specification and decision making, we have compared the quality of participation of policy entrepreneurs in the two cycles, their political strategies and, in these, the relevance of issue image. The case allows us to direct the attention of scholars and practitioners to an early phase of the policy implementation process – which we have named "transition to practice". This, managed with political strategy, might have strongly contributed to the final successful policy outcome.

Data sets for manuscript titled Unexpected benefits of reducing aerosol cooling effects

EPA Pesticide Factsheets

These data sets were created using extensive model simulation results from the WRF-CMAQ model, population distributions, and through the use of an health impact assessment model - see manuscript for details.This dataset is associated with the following publication:Xing, J., J. Wang, R. Mathur , J. Pleim , S. Wang, C. Hogrefe , C. Gan, D. Wong , and J. Hao. Unexpected Benefits of Reducing Aerosol Cooling Effects. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 50(14): 7527–7534, (2016).

Task-specific Aspects of Goal-directed Word Generation Identified via Simultaneous EEG-fMRI.

PubMed

Shapira-Lichter, Irit; Klovatch, Ilana; Nathan, Dana; Oren, Noga; Hendler, Talma

2016-09-01

Generating words according to a given rule relies on retrieval-related search and postretrieval control processes. Using fMRI, we recently characterized neural patterns of word generation in response to episodic, semantic, and phonemic cues by comparing free recall of wordlists, category fluency, and letter fluency [Shapira-Lichter, I., Oren, N., Jacob, Y., Gruberger, M., & Hendler, T. Portraying the unique contribution of the default mode network to internally driven mnemonic processes. Proceedings of the National Academy of Sciences, U.S.A., 110, 4950-4955, 2013]. Distinct selectivity for each condition was evident, representing discrete aspects of word generation-related memory retrieval. For example, the precuneus, implicated in processing spatiotemporal information, emerged as a key contributor to the episodic condition, which uniquely requires this information. Gamma band is known to play a central role in memory, and increased gamma power has been observed before word generation. Yet, gamma modulation in response to task demands has not been investigated. To capture the task-specific modulation of gamma power, we analyzed the EEG data recorded simultaneously with the aforementioned fMRI, focusing on the activity locked to and immediately preceding word articulation. Transient increases in gamma power were identified in a parietal electrode immediately before episodic and semantic word generation, however, within a different time frame relative to articulation. Gamma increases were followed by an alpha-theta decrease in the episodic condition, a gamma decrease in the semantic condition. This pattern indicates a task-specific modulation of the gamma signal corresponding to the specific demands of each word generation task. The gamma power and fMRI signal from the precuneus were correlated during the episodic condition, implying the existence of a common cognitive construct uniquely required for this task, possibly the reactivation or processing of

Subfamily-Specific Fluorescent Probes for Cysteine Proteases Display Dynamic Protease Activities during Seed Germination.

PubMed

Lu, Haibin; Chandrasekar, Balakumaran; Oeljeklaus, Julian; Misas-Villamil, Johana C; Wang, Zheming; Shindo, Takayuki; Bogyo, Matthew; Kaiser, Markus; van der Hoorn, Renier A L

2015-08-01

Cysteine proteases are an important class of enzymes implicated in both developmental and defense-related programmed cell death and other biological processes in plants. Because there are dozens of cysteine proteases that are posttranslationally regulated by processing, environmental conditions, and inhibitors, new methodologies are required to study these pivotal enzymes individually. Here, we introduce fluorescence activity-based probes that specifically target three distinct cysteine protease subfamilies: aleurain-like proteases, cathepsin B-like proteases, and vacuolar processing enzymes. We applied protease activity profiling with these new probes on Arabidopsis (Arabidopsis thaliana) protease knockout lines and agroinfiltrated leaves to identify the probe targets and on other plant species to demonstrate their broad applicability. These probes revealed that most commercially available protease inhibitors target unexpected proteases in plants. When applied on germinating seeds, these probes reveal dynamic activities of aleurain-like proteases, cathepsin B-like proteases, and vacuolar processing enzymes, coinciding with the remobilization of seed storage proteins. © 2015 American Society of Plant Biologists. All Rights Reserved.

Genome-wide histone state profiling of fibroblasts from the opossum, Monodelphis domestica, identifies the first marsupial-specific imprinted gene

PubMed Central

2014-01-01

Background Imprinted genes have been extensively documented in eutherian mammals and found to exhibit significant interspecific variation in the suites of genes that are imprinted and in their regulation between tissues and developmental stages. Much less is known about imprinted loci in metatherian (marsupial) mammals, wherein studies have been limited to a small number of genes previously known to be imprinted in eutherians. We describe the first ab initio search for imprinted marsupial genes, in fibroblasts from the opossum, Monodelphis domestica, based on a genome-wide ChIP-seq strategy to identify promoters that are simultaneously marked by mutually exclusive, transcriptionally opposing histone modifications. Results We identified a novel imprinted gene (Meis1) and two additional monoallelically expressed genes, one of which (Cstb) showed allele-specific, but non-imprinted expression. Imprinted vs. allele-specific expression could not be resolved for the third monoallelically expressed gene (Rpl17). Transcriptionally opposing histone modifications H3K4me3, H3K9Ac, and H3K9me3 were found at the promoters of all three genes, but differential DNA methylation was not detected at CpG islands at any of these promoters. Conclusions In generating the first genome-wide histone modification profiles for a marsupial, we identified the first gene that is imprinted in a marsupial but not in eutherian mammals. This outcome demonstrates the practicality of an ab initio discovery strategy and implicates histone modification, but not differential DNA methylation, as a conserved mechanism for marking imprinted genes in all therian mammals. Our findings suggest that marsupials use multiple epigenetic mechanisms for imprinting and support the concept that lineage-specific selective forces can produce sets of imprinted genes that differ between metatherian and eutherian lines. PMID:24484454

An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B.

PubMed

Winter, Georg E; Rix, Uwe; Lissat, Andrej; Stukalov, Alexey; Müllner, Markus K; Bennett, Keiryn L; Colinge, Jacques; Nijman, Sebastian M; Kubicek, Stefan; Kovar, Heinrich; Kontny, Udo; Superti-Furga, Giulio

2011-10-01

Ewing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option.

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 .

Identifying and tracing potential energy surfaces of electronic excitations with specific character via their transition origins: application to oxirane.

PubMed

Li, Jian-Hao; Zuehlsdorff, T J; Payne, M C; Hine, N D M

2015-05-14

We show that the transition origins of electronic excitations identified by quantified natural transition orbital (QNTO) analysis can be employed to connect potential energy surfaces (PESs) according to their character across a wide range of molecular geometries. This is achieved by locating the switching of transition origins of adiabatic potential surfaces as the geometry changes. The transition vectors for analysing transition origins are provided by linear response time-dependent density functional theory (TDDFT) calculations under the Tamm-Dancoff approximation. We study the photochemical CO ring opening of oxirane as an example and show that the results corroborate the traditional Gomer-Noyes mechanism derived experimentally. The knowledge of specific states for the reaction also agrees well with that given by previous theoretical work using TDDFT surface-hopping dynamics that was validated by high-quality quantum Monte Carlo calculations. We also show that QNTO can be useful for considerably larger and more complex systems: by projecting the excitations to those of a reference oxirane molecule, the approach is able to identify and analyse specific excitations of a trans-2,3-diphenyloxirane molecule.

Unexpected photoreactivation of Vibrio harveyi bacteria living in ionization environment

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

Alifano, P.; Tala, A.; Tredici, S. M.

2011-05-15

Bacteria undergoing environmental effects is extremely interesting for structural, mechanistic, and evolutionary implications. Luminescent bacteria that have evolved in a specific ambient have developed particular responses and their behavior can give us new suggestions on the task and production of luciferina proteins. To analyze the UV interaction under controlled laboratory conditions, we used photoluminescent bacterial strains belonging to a new species evolutionarily close to Vibrio harveyi sampled from a coastal cave with a high radon content that generates ionizing radiation. The survival of the bacterial strains was analyzed, in the light and in the dark, following a variety of genotoxicmore » treatments including UV radiation exposure. The strains were irradiated by a germicide lamp. The results demonstrated that most of the strains exhibited a low rate of survival after the UV exposure. After irradiation by visible light following the UV exposure, all strains showed a high capability of photoreactivation when grown. This capability was quite unexpected because these bacteria were sampled from a dark ambient without UV radiation. This leads us to hypothesize that the photoreactivation in these bacteria might have been evolved to repair DNA lesions also induced by different radiation sources other than UV (e.g., x-ray) and that the luminescent bacteria might use their own light emission to carry out the photoreactivation. The high capability of photoreactivation of these bacteria was also justified by the results of deconvolution. The deconvolution was applied to the emission spectra and it was able to show evidence of different light peaks. The presence of the visible peak could control the photolysis enzyme.« less

Unexpected persistence of extended-spectrum β-lactamase-producing Enterobacteriaceae in the faecal microbiota of hospitalised patients treated with imipenem.

PubMed

Grall, N; Lazarevic, V; Gaïa, N; Couffignal, C; Laouénan, C; Ilic-Habensus, E; Wieder, I; Plesiat, P; Angebault, C; Bougnoux, M E; Armand-Lefevre, L; Andremont, A; Duval, X; Schrenzel, J

2017-07-01

Imipenem is active against extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) but favours the intestinal emergence of resistance. The effects of imipenem on intestinal microbiota have been studied using culture-based techniques. In this study, the effects were investigated in patients using culture and metagenomic techniques. Seventeen hospitalised adults receiving imipenem were included in a multicentre study (NCT01703299, http://www.clinicaltrials.gov). Most patients had a history of antibiotic use and/or hospitalisation. Stools were collected before, during and after imipenem treatment. Bacterial and fungal colonisation was assessed by culture, and microbiota changes were assessed using metagenomics. Unexpectedly, high colonisation rates by imipenem-susceptible ESBL-E before treatment (70.6%) remained stable over time, suggesting that imipenem intestinal concentrations were very low. Carriage rates of carbapenem-resistant Gram-negative bacilli (0-25.0%) were also stable over time, whereas those of yeasts (64.7% before treatment) peaked at 76.5% during treatment and decreased thereafter. However, these trends were not statistically significant. Yeasts included highly diverse colonising Candida spp. Metagenomics showed no global effect of imipenem on the bacterial taxonomic profiles at the sequencing depth used but demonstrated specific changes in the microbiota not detected with culture, attributed to factors other than imipenem, including sampling site or treatment with other antibiotics. In conclusion, culture and metagenomics were highly complementary in characterising the faecal microbiota of patients. The changes observed during imipenem treatment were unexpectedly limited, possibly because the microbiota was already disturbed by previous antibiotic exposure or hospitalisation. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Identifying Specific Reading Disability Subtypes for Effective Educational Remediation

ERIC Educational Resources Information Center

Feifer, Steven G.; Nader, Rebecca Gerhardstein; Flanagan, Dawn P.; Fitzer, Kim R.; Hicks, Kelly

2014-01-01

The primary purpose of this study was to investigate the various neurocognitive processes concomitant to reading by attempting to identify various subtypes of reading disorders in a referred sample. Participants were 216 elementary school students in grades two through five who were given select subtests of the Woodcock Johnson-III Tests of…

Identifying Specific Combinations of Multimorbidity that Contribute to Health Care Resource Utilization: An Analytic Approach.

PubMed

Schiltz, Nicholas K; Warner, David F; Sun, Jiayang; Bakaki, Paul M; Dor, Avi; Given, Charles W; Stange, Kurt C; Koroukian, Siran M

2017-03-01

Multimorbidity affects the majority of elderly adults and is associated with higher health costs and utilization, but how specific patterns of morbidity influence resource use is less understood. The objective was to identify specific combinations of chronic conditions, functional limitations, and geriatric syndromes associated with direct medical costs and inpatient utilization. Retrospective cohort study using the Health and Retirement Study (2008-2010) linked to Medicare claims. Analysis used machine-learning techniques: classification and regression trees and random forest. A population-based sample of 5771 Medicare-enrolled adults aged 65 and older in the United States. Main covariates: self-reported chronic conditions (measured as none, mild, or severe), geriatric syndromes, and functional limitations. Secondary covariates: demographic, social, economic, behavioral, and health status measures. Medicare expenditures in the top quartile and inpatient utilization. Median annual expenditures were $4354, and 41% were hospitalized within 2 years. The tree model shows some notable combinations: 64% of those with self-rated poor health plus activities of daily living and instrumental activities of daily living disabilities had expenditures in the top quartile. Inpatient utilization was highest (70%) in those aged 77-83 with mild to severe heart disease plus mild to severe diabetes. Functional limitations were more important than many chronic diseases in explaining resource use. The multimorbid population is heterogeneous and there is considerable variation in how specific combinations of morbidity influence resource use. Modeling the conjoint effects of chronic conditions, functional limitations, and geriatric syndromes can advance understanding of groups at greatest risk and inform targeted tailored interventions aimed at cost containment.

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress.

PubMed

Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; DePietro, Thomas; Chamness, Marisa; Schneider, Elizabeth K; Keller, Samantha M; Lawless, Caroline

2018-04-02

Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Observational Progress in Identifying and Characterizing Tidal Disruption Flares

NASA Astrophysics Data System (ADS)

Cenko, S. Bradley

I present an overview of observational efforts across the electromagnetic spectrum to identify and study tidal disruption flares (TDFs), when a star wanders too close to a super-massive black hole and is torn apart by tidal forces. In particular I will focus on four unexpected surprises that challenge the most basic analytic picture of these events: 1) large inferred radii for the optical/UV-emitting material; 2) the ubiquity of outflows, detected at radio, X-ray, and UV wavelengths, ranging from speeds of 100 km/s to near the speed of light; 3) the peculiar atomic abundances observed in the UV and optical spectra of these objects; and, 4) the preference for these events to occur in post-starburst galaxies.

Valence-specific conflict moderation in the dorso-medial PFC and the caudate head in emotional speech.

PubMed

Kotz, Sonja A; Dengler, Reinhard; Wittfoth, Matthias

2015-02-01

Emotional speech comprises of complex multimodal verbal and non-verbal information that allows deducting others' emotional states or thoughts in social interactions. While the neural correlates of verbal and non-verbal aspects and their interaction in emotional speech have been identified, there is very little evidence on how we perceive and resolve incongruity in emotional speech, and whether such incongruity extends to current concepts of task-specific prediction errors as a consequence of unexpected action outcomes ('negative surprise'). Here, we explored this possibility while participants listened to congruent and incongruent angry, happy or neutral utterances and categorized the expressed emotions by their verbal (semantic) content. Results reveal valence-specific incongruity effects: negative verbal content expressed in a happy tone of voice increased activation in the dorso-medial prefrontal cortex (dmPFC) extending its role from conflict moderation to appraisal of valence-specific conflict in emotional speech. Conversely, the caudate head bilaterally responded selectively to positive verbal content expressed in an angry tone of voice broadening previous accounts of the caudate head in linguistic control to moderating valence-specific control in emotional speech. Together, these results suggest that control structures of the human brain (dmPFC and subcompartments of the basal ganglia) impact emotional speech differentially when conflict arises. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Two unexpected promiscuous activities of the iron-sulfur protein IspH in production of isoprene and isoamylene.

PubMed

Ge, Deyong; Xue, Yanfen; Ma, Yanhe

2016-05-11

Bacillus species, possessing the methylerythritol phosphate (MEP) pathway for the synthesis of isoprenoid feedstock, are the highest producers of isoprene among bacteria; however, the enzyme responsible for isoprene synthesis has not been identified. The iron-sulfur protein IspH is the final enzyme of the MEP pathway and catalyses the reductive dehydration of (E)-4-hydroxy-3-methyl-2-butenyl diphosphate (HMBPP) to form isopentenyl diphosphate and dimethylallyl diphosphate (DMAPP). In this study, we demonstrated two unexpected promiscuous activities of IspH from alkaliphilic Bacillus sp. N16-5, which can produce high levels of isoprene. Bacillus sp. N16-5 IspH could catalyse the formation of isoprene from HMBPP and the conversion of DMAPP into a mixture of 2-methyl-2-butene and 3-methyl-1-butene. Both reactions require an electron transfer system, such as that used for HMBPP dehydration. Isoprene and isoamylene synthesis in Bacillus sp. N16-5 was investigated and the reaction system was reconstituted in vitro, including IspH, ferredoxin and ferredoxin-NADP(+)-reductase proteins and NADPH. The roles of specific IspH protein residues were also investigated by site-directed mutagenesis experiments; two variants (H131N and E133Q) were found to have lost the HMBPP reductase activity but could still catalyse the formation of isoprene. Overexpression of IspH H131N in Bacillus sp. N16-5 resulted in a twofold enhancement of isoprene production, and the yield of isoprene from the strain expressing E133Q was increased 300% compared with the wild-type strain. IspH from Bacillus sp. N16-5 is a promiscuous enzyme that can catalyse formation of isoprene and isoamylene. This enzyme, especially the H131N and E133Q variants, could be used for the production of isoprene from HMBPP.

Descriptions of Adverse Drug Reactions Are Less Informative in Forums Than in the French Pharmacovigilance Database but Provide More Unexpected Reactions

PubMed Central

Karapetiantz, Pierre; Bellet, Florelle; Audeh, Bissan; Lardon, Jérémy; Leprovost, Damien; Aboukhamis, Rim; Morlane-Hondère, François; Grouin, Cyril; Burgun, Anita; Katsahian, Sandrine; Jaulent, Marie-Christine; Beyens, Marie-Noëlle; Lillo-Le Louët, Agnès; Bousquet, Cédric

2018-01-01

Background: Social media have drawn attention for their potential use in Pharmacovigilance. Recent work showed that it is possible to extract information concerning adverse drug reactions (ADRs) from posts in social media. The main objective of the Vigi4MED project was to evaluate the relevance and quality of the information shared by patients on web forums about drug safety and its potential utility for pharmacovigilance. Methods: After selecting websites of interest, we manually evaluated the relevance of the content of posts for pharmacovigilance related to six drugs (agomelatine, baclofen, duloxetine, exenatide, strontium ranelate, and tetrazepam). We compared forums to the French Pharmacovigilance Database (FPVD) to (1) evaluate whether they contained relevant information to characterize a pharmacovigilance case report (patient’s age and sex; treatment indication, dose and duration; time-to-onset (TTO) and outcome of the ADR, and drug dechallenge and rechallenge) and (2) perform impact analysis (nature, seriousness, unexpectedness, and outcome of the ADR). Results: The cases in the FPVD were significantly more informative than posts in forums for patient description (age, sex), treatment description (dose, duration, TTO), and outcome of the ADR, but the indication for the treatment was more often found in forums. Cases were more often serious in the FPVD than in forums (46% vs. 4%), but forums more often contained an unexpected ADR than the FPVD (24% vs. 17%). Moreover, 197 unexpected ADRs identified in forums were absent from the FPVD and the distribution of the MedDRA System Organ Classes (SOCs) was different between the two data sources. Discussion: This study is the first to evaluate if patients’ posts may qualify as potential and informative case reports that should be stored in a pharmacovigilance database in the same way as case reports submitted by health professionals. The posts were less informative (except for the indication) and focused on less

Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β

PubMed Central

Yim, Kendrick H.; Prince, Thomas L.; Qu, Shiwei; Bai, Fang; Jennings, Patricia A.; Onuchic, José N.; Theodorakis, Emmanuel A.; Neckers, Leonard

2016-01-01

Because of their importance in maintaining protein homeostasis, molecular chaperones, including heat-shock protein 90 (Hsp90), represent attractive drug targets. Although a number of Hsp90 inhibitors are in preclinical/clinical development, none strongly differentiate between constitutively expressed Hsp90β and stress-induced Hsp90α, the two cytosolic paralogs of this molecular chaperone. Thus, the importance of inhibiting one or the other paralog in different disease states remains unknown. We show that the natural product, gambogic acid (GBA), binds selectively to a site in the middle domain of Hsp90β, identifying GBA as an Hsp90β-specific Hsp90 inhibitor. Furthermore, using computational and medicinal chemistry, we identified a GBA analog, referred to as DAP-19, which binds potently and selectively to Hsp90β. Because of its unprecedented selectivity for Hsp90β among all Hsp90 paralogs, GBA thus provides a new chemical tool to study the unique biological role of this abundantly expressed molecular chaperone in health and disease. PMID:27466407

Unexpectedly high leprosy seroprevalence detected using a random surveillance strategy in midwestern Brazil: A comparison of ELISA and a rapid diagnostic test

PubMed Central

Bernardes Filho, Fred; de Abreu, Marilda M. M.; Botini, Patrícia; Duthie, Malcolm S.; Spencer, John S.; Soares, Rosa Castália F. R.

2017-01-01

Background Leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. We conducted a temporary campaign to detect previously unknown leprosy cases in midwestern Brazil and to compare the performance of different serological tests. Methods A mobile clinic was stationed at the main bus terminal in Brasília, Brazil. Volunteers were quizzed and given a clinical exam to allow categorization as either patients, known contacts of patients or non-contacts, and blood was collected to determine anti-PGL-I and anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New cases of leprosy and the impact of performing this broad random surveillance strategy were evaluated. Accuracy values and concordance between the test results were evaluated among all groups. Results Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were diagnosed with leprosy. Borderline forms were the most frequent presentation. Both tests presented higher positivity in those individuals with multibacillary disease. Serological tests demonstrated specificities arround 70% for anti-PGL-1 and anti-LID ELISA; and arround 40% for NDO-LID. Sensitivities ranged from 48 to 62%. A substantial agreement between NDO-LID and ELISA with concomitant positive results was found within leprosy patients (Kappa index = 0.79 CI95% 0.36–1.22). Conclusions The unexpectedly high leprosy prevalence in this population indicates ongoing community-based exposure to Mycobacterium leprae antigens and high rates of subclinical infection. All tests showed low specificity and sensitivity values and therefore cannot be considered for use as stand-alone diagnostics. Rather, considering their positivity among MB patients and non-patients, these tests can be considered effective tools for screening and identifying individuals at high risk who might benefit from regular monitoring. PMID:28231244

Unexpectedly high leprosy seroprevalence detected using a random surveillance strategy in midwestern Brazil: A comparison of ELISA and a rapid diagnostic test.

PubMed

Frade, Marco Andrey C; de Paula, Natália A; Gomes, Ciro M; Vernal, Sebastian; Bernardes Filho, Fred; Lugão, Helena B; de Abreu, Marilda M M; Botini, Patrícia; Duthie, Malcolm S; Spencer, John S; Soares, Rosa Castália F R; Foss, Norma T

2017-02-01

Leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. We conducted a temporary campaign to detect previously unknown leprosy cases in midwestern Brazil and to compare the performance of different serological tests. A mobile clinic was stationed at the main bus terminal in Brasília, Brazil. Volunteers were quizzed and given a clinical exam to allow categorization as either patients, known contacts of patients or non-contacts, and blood was collected to determine anti-PGL-I and anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New cases of leprosy and the impact of performing this broad random surveillance strategy were evaluated. Accuracy values and concordance between the test results were evaluated among all groups. Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were diagnosed with leprosy. Borderline forms were the most frequent presentation. Both tests presented higher positivity in those individuals with multibacillary disease. Serological tests demonstrated specificities arround 70% for anti-PGL-1 and anti-LID ELISA; and arround 40% for NDO-LID. Sensitivities ranged from 48 to 62%. A substantial agreement between NDO-LID and ELISA with concomitant positive results was found within leprosy patients (Kappa index = 0.79 CI95% 0.36-1.22). The unexpectedly high leprosy prevalence in this population indicates ongoing community-based exposure to Mycobacterium leprae antigens and high rates of subclinical infection. All tests showed low specificity and sensitivity values and therefore cannot be considered for use as stand-alone diagnostics. Rather, considering their positivity among MB patients and non-patients, these tests can be considered effective tools for screening and identifying individuals at high risk who might benefit from regular monitoring.

Unexpected and just missed: the separate influence of the appraisals of expectancy and proximity on negative emotions.

PubMed

Bossuyt, Evelien; Moors, Agnes; De Houwer, Jan

2014-04-01

Previous research has suggested that a goal-incongruent outcome leads to more intense negative emotions when it is unexpected and close to a goal-congruent outcome. Until now, however, no studies have disentangled the influence of the appraisals of expectancy and proximity on emotions. We experimentally manipulated each of these variables in 3 slot machine experiments and measured emotions via differences in motivation (i.e., the tendency to repair the goal incongruence) and feelings (i.e., disappointment, frustration, and anger). The experiments consisted of a series of trials that each started with the sequential presentation of 3 symbols. In case of a win trial, all symbols were equal (e.g., AAA) and the participant gained 10 cents; in case of a loss trial, one or more of the symbols differed and the participant gained 0 cents. Three different loss trials were compared: unexpected proximal ones (e.g., AAB), expected proximal ones (e.g., ABA), and expected distal ones (e.g., ABC). The tendency to repair was measured online via behavior as well as retrospectively via self-reports; feelings were measured retrospectively (Experiments 1 and 2) or online (Experiment 3). Unexpected losses seemed to increase the tendency to repair as well as feelings of disappointment (in all experiments) and feelings of frustration and anger (in Experiments 1 and 3). Proximal losses increased only the tendency to repair (in all experiments). This suggests that the appraisals of expectancy and proximity have a distinct influence on emotions.

Geriatric-specific triage criteria are more sensitive than standard adult criteria in identifying need for trauma center care in injured older adults.

PubMed

Ichwan, Brian; Darbha, Subrahmanyam; Shah, Manish N; Thompson, Laura; Evans, David C; Boulger, Creagh T; Caterino, Jeffrey M

2015-01-01

We evaluate the sensitivity of Ohio's 2009 emergency medical services (EMS) geriatric trauma triage criteria compared with the previous adult triage criteria in identifying need for trauma center care among older adults. We studied a retrospective cohort of injured patients aged 16 years or older in the 2006 to 2011 Ohio Trauma Registry. Patients aged 70 years or older were considered geriatric. We identified whether each patient met the geriatric and the adult triage criteria. The outcome measure was need for trauma center care, defined by surrogate markers: Injury Severity Score greater than 15, operating room in fewer than 48 hours, any ICU stay, and inhospital mortality. We calculated sensitivity and specificity of both triage criteria for both age groups. We included 101,577 patients; 33,379 (33%) were geriatric. Overall, 57% of patients met adult criteria and 68% met geriatric criteria. Using Injury Severity Score, for older adults geriatric criteria were more sensitive for need for trauma center care (93%; 95% confidence interval [CI] 92% to 93%) than adult criteria (61%; 95% CI 60% to 62%). Geriatric criteria decreased specificity in older adults from 61% (95% CI 61% to 62%) to 49% (95% CI 48% to 49%). Geriatric criteria in older adults (93% sensitivity, 49% specificity) performed similarly to the adult criteria in younger adults (sensitivity 87% and specificity 44%). Similar patterns were observed for other outcomes. Standard adult EMS triage guidelines provide poor sensitivity in older adults. Ohio's geriatric trauma triage guidelines significantly improve sensitivity in identifying Injury Severity Score and other surrogate markers of the need for trauma center care, with modest decreases in specificity for older adults. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

76 FR 53295 - Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-25

...-12 of August 8, 2011--Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa... Migration Needs Related to the Horn of Africa Memorandum for the Secretary of State By the authority vested...) of the Migration and Refugee Assistance Act of 1962 (the ``Act''), as amended, (22 U.S.C. 2601(c)(1...

Age-related changes in posture response under a continuous and unexpected perturbation.

PubMed

Tsai, Yi-Ching; Hsieh, Lin-Fen; Yang, Saiwei

2014-01-22

Aging is a critical factor to influence the functional performance during daily life. Without an appropriate posture control response when experiencing an unexpected external perturbation, fall may occur. A novel six-degree-of freedom platform with motion control protocol was designed to provide a real-life simulation of unexpected disturbance in order to discriminate the age-related changes of the balance control and the recovery ability. Twenty older adults and 20 healthy young adults participated in the study. The subjects stood barefoot on the novel movable platform, data of the center of mass (COM) excursion, joint rotation angle and electromyography (EMG) were recorded and compared. The results showed that the older adults had similar patterns of joint movement and COM excursion as the young adults during the balance reactive-recovery. However, larger proximal joint rotation in elderly group induced larger COM sway envelop and therefore loss of the compensatory strategy of posture recovery. The old adults also presented a lower muscle power. In order to keep an adequate joint stability preventing from falling, the EMG activity was increased, but the asymmetric pattern might be the key reason of unstable postural response. This novel design of moveable platform and test protocol comprised the computerized dynamic posturography (CDP) demonstrate its value to assess the possible sensory, motor, and central adaptive impairments to balance control and could be the training tool for posture inability person. © 2013 Elsevier Ltd. All rights reserved.

Unexpected optical limiting properties from MoS2 nanosheets modified by a semiconductive polymer.

PubMed

Zhao, Min; Chang, Meng-Jie; Wang, Qiang; Zhu, Zhen-Tong; Zhai, Xin-Ping; Zirak, Mohammad; Moshfegh, Alireza Z; Song, Ying-Lin; Zhang, Hao-Li

2015-08-07

Direct solvent exfoliation of bulk MoS2 with the assistance of poly(3-hexylthiophene) (P3HT) produces a novel two-dimensional organic/inorganic semiconductor hetero-junction. The obtained P3HT-MoS2 nanohybrid exhibits unexpected optical limiting properties in contrast to the saturated absorption behavior of both P3HT and MoS2, showing potential in future photoelectric applications.

Cobalt-catalyzed hydrogenation of esters to alcohols: unexpected reactivity trend indicates ester enolate intermediacy.

PubMed

Srimani, Dipankar; Mukherjee, Arup; Goldberg, Alexander F G; Leitus, Gregory; Diskin-Posner, Yael; Shimon, Linda J W; Ben David, Yehoshoa; Milstein, David

2015-10-12

The atom-efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious-metal-based catalysts, with few exceptions. Presented here is the first cobalt-catalyzed hydrogenation of esters to the corresponding alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables.

PubMed

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C; Downing, James R; Lamba, Jatinder

2009-08-15

In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org.

An unexpected disruption of the atmospheric quasi-biennial oscillation.

PubMed

Osprey, Scott M; Butchart, Neal; Knight, Jeff R; Scaife, Adam A; Hamilton, Kevin; Anstey, James A; Schenzinger, Verena; Zhang, Chunxi

2016-09-23

One of the most repeatable phenomena seen in the atmosphere, the quasi-biennial oscillation (QBO) between prevailing eastward and westward wind jets in the equatorial stratosphere (approximately 16 to 50 kilometers altitude), was unexpectedly disrupted in February 2016. An unprecedented westward jet formed within the eastward phase in the lower stratosphere and cannot be accounted for by the standard QBO paradigm based on vertical momentum transport. Instead, the primary cause was waves transporting momentum from the Northern Hemisphere. Seasonal forecasts did not predict the disruption, but analogous QBO disruptions are seen very occasionally in some climate simulations. A return to more typical QBO behavior within the next year is forecast, although the possibility of more frequent occurrences of similar disruptions is projected for a warming climate. Copyright © 2016, American Association for the Advancement of Science.

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

PubMed

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

2011-10-01

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

Specific Language Impairment, Nonverbal IQ, Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Cochlear Implants, Bilingualism, and Dialectal Variants: Defining the Boundaries, Clarifying Clinical Conditions, and Sorting Out Causes

PubMed Central

2016-01-01

Purpose The purpose of this research forum article is to provide an overview of a collection of invited articles on the topic “specific language impairment (SLI) in children with concomitant health conditions or nonmainstream language backgrounds.” Topics include SLI, attention-deficit/hyperactivity disorder, autism spectrum disorder, cochlear implants, bilingualism, and dialectal language learning contexts. Method The topic is timely due to current debates about the diagnosis of SLI. An overarching comparative conceptual framework is provided for comparisons of SLI with other clinical conditions. Comparisons of SLI in children with low-normal or normal nonverbal IQ illustrate the unexpected outcomes of 2 × 2 comparison designs. Results Comparative studies reveal unexpected relationships among speech, language, cognitive, and social dimensions of children's development as well as precise ways to identify children with SLI who are bilingual or dialect speakers. Conclusions The diagnosis of SLI is essential for elucidating possible causal pathways of language impairments, risks for language impairments, assessments for identification of language impairments, linguistic dimensions of language impairments, and long-term outcomes. Although children's language acquisition is robust under high levels of risk, unexplained individual variations in language acquisition lead to persistent language impairments. PMID:26502218

Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis.

PubMed

Raman, Malavika; Sergeev, Mikhail; Garnaas, Maija; Lydeard, John R; Huttlin, Edward L; Goessling, Wolfram; Shah, Jagesh V; Harper, J Wade

2015-10-01

The AAA-ATPase VCP (also known as p97 or CDC48) uses ATP hydrolysis to 'segregate' ubiquitylated proteins from their binding partners. VCP acts through UBX-domain-containing adaptors that provide target specificity, but the targets and functions of UBXD proteins remain poorly understood. Through systematic proteomic analysis of UBXD proteins in human cells, we reveal a network of over 195 interacting proteins, implicating VCP in diverse cellular pathways. We have explored one such complex between an unstudied adaptor UBXN10 and the intraflagellar transport B (IFT-B) complex, which regulates anterograde transport into cilia. UBXN10 localizes to cilia in a VCP-dependent manner and both VCP and UBXN10 are required for ciliogenesis. Pharmacological inhibition of VCP destabilized the IFT-B complex and increased trafficking rates. Depletion of UBXN10 in zebrafish embryos causes defects in left-right asymmetry, which depends on functional cilia. This study provides a resource for exploring the landscape of UBXD proteins in biology and identifies an unexpected requirement for VCP-UBXN10 in ciliogenesis.

Theoretical and Numerical Modeling of Transport of Land Use-Specific Fecal Source Identifiers

NASA Astrophysics Data System (ADS)

Bombardelli, F. A.; Sirikanchana, K. J.; Bae, S.; Wuertz, S.

2008-12-01

Microbial contamination in coastal and estuarine waters is of particular concern to public health officials. In this work, we advocate that well-formulated and developed mathematical and numerical transport models can be combined with modern molecular techniques in order to predict continuous concentrations of microbial indicators under diverse scenarios of interest, and that they can help in source identification of fecal pollution. As a proof of concept, we present initially the theory, numerical implementation and validation of one- and two-dimensional numerical models aimed at computing the distribution of fecal source identifiers in water bodies (based on Bacteroidales marker DNA sequences) coming from different land uses such as wildlife, livestock, humans, dogs or cats. These models have been developed to allow for source identification of fecal contamination in large bodies of water. We test the model predictions using diverse velocity fields and boundary conditions. Then, we present some preliminary results of an application of a three-dimensional water quality model to address the source of fecal contamination in the San Pablo Bay (SPB), United States, which constitutes an important sub-embayment of the San Francisco Bay. The transport equations for Bacteroidales include the processes of advection, diffusion, and decay of Bacteroidales. We discuss the validation of the developed models through comparisons of numerical results with field campaigns developed in the SPB. We determine the extent and importance of the contamination in the bay for two decay rates obtained from field observations, corresponding to total host-specific Bacteroidales DNA and host-specific viable Bacteroidales cells, respectively. Finally, we infer transport conditions in the SPB based on the numerical results, characterizing the fate of outflows coming from the Napa, Petaluma and Sonoma rivers.

From unwitnessed fatality to witnessed rescue: Nonpharmacologic interventions in sudden unexpected death in epilepsy.

PubMed

Rugg-Gunn, Fergus; Duncan, John; Hjalgrim, Helle; Seyal, Masud; Bateman, Lisa

2016-01-01

Sudden unexpected death in epilepsy (SUDEP) risk reduction remains a critical aim in epilepsy care. To date, only aggressive medical and surgical efforts to control seizures have been demonstrated to be of benefit. Incomplete understanding of SUDEP mechanisms limits the development of more specific interventions. Periictal cardiorespiratory dysfunction is implicated in SUDEP; postictal electroencephalography (EEG) suppression, coma, and immobility may also play a role. Nocturnal supervision is protective against SUDEP, presumably by permitting intervention in the case of a life-threatening event. Resuscitative efforts were implemented promptly in near-SUDEP cases but delayed in SUDEP deaths in the Mortality in Epilepsy Monitoring Unit Study (MORTEMUS) study. Nursing interventions--including repositioning, oral suctioning, and oxygen administration--reduce seizure duration, respiratory dysfunction, and EEG suppression in the epilepsy monitoring unit (EMU), but have not been studied in outpatients. Cardiac pacemakers or cardioverter-defibrillator devices may be of benefit in a few select individuals. A role for implantable neurostimulators has not yet been established. Seizure detection devices, including those that monitor generalized tonic-clonic seizure-associated movements or cardiorespiratory parameters, may provide a means to permit timely periictal intervention. However, these and other devices, such as antisuffocation pillows, have not been adequately investigated with respect to SUDEP prevention. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Specificity and Sensitivity of Claims-Based Algorithms for Identifying Members of Medicare+Choice Health Plans That Have Chronic Medical Conditions

PubMed Central

Rector, Thomas S; Wickstrom, Steven L; Shah, Mona; Thomas Greeenlee, N; Rheault, Paula; Rogowski, Jeannette; Freedman, Vicki; Adams, John; Escarce, José J

2004-01-01

Objective To examine the effects of varying diagnostic and pharmaceutical criteria on the performance of claims-based algorithms for identifying beneficiaries with hypertension, heart failure, chronic lung disease, arthritis, glaucoma, and diabetes. Study Setting Secondary 1999–2000 data from two Medicare+Choice health plans. Study Design Retrospective analysis of algorithm specificity and sensitivity. Data Collection Physician, facility, and pharmacy claims data were extracted from electronic records for a sample of 3,633 continuously enrolled beneficiaries who responded to an independent survey that included questions about chronic diseases. Principal Findings Compared to an algorithm that required a single medical claim in a one-year period that listed the diagnosis, either requiring that the diagnosis be listed on two separate claims or that the diagnosis to be listed on one claim for a face-to-face encounter with a health care provider significantly increased specificity for the conditions studied by 0.03 to 0.11. Specificity of algorithms was significantly improved by 0.03 to 0.17 when both a medical claim with a diagnosis and a pharmacy claim for a medication commonly used to treat the condition were required. Sensitivity improved significantly by 0.01 to 0.20 when the algorithm relied on a medical claim with a diagnosis or a pharmacy claim, and by 0.05 to 0.17 when two years rather than one year of claims data were analyzed. Algorithms that had specificity more than 0.95 were found for all six conditions. Sensitivity above 0.90 was not achieved all conditions. Conclusions Varying claims criteria improved the performance of case-finding algorithms for six chronic conditions. Highly specific, and sometimes sensitive, algorithms for identifying members of health plans with several chronic conditions can be developed using claims data. PMID:15533190

The genetics of alcoholism: identifying specific genes through family studies.

PubMed

Edenberg, Howard J; Foroud, Tatiana

2006-09-01

Alcoholism is a complex disorder with both genetic and environmental risk factors. Studies in humans have begun to elucidate the genetic underpinnings of the risk for alcoholism. Here we briefly review strategies for identifying individual genes in which variations affect the risk for alcoholism and related phenotypes, in the context of one large study that has successfully identified such genes. The Collaborative Study on the Genetics of Alcoholism (COGA) is a family-based study that has collected detailed phenotypic data on individuals in families with multiple alcoholic members. A genome-wide linkage approach led to the identification of chromosomal regions containing genes that influenced alcoholism risk and related phenotypes. Subsequently, single nucleotide polymorphisms (SNPs) were genotyped in positional candidate genes located within the linked chromosomal regions, and analyzed for association with these phenotypes. Using this sequential approach, COGA has detected association with GABRA2, CHRM2 and ADH4; these associations have all been replicated by other researchers. COGA has detected association to additional genes including GABRG3, TAS2R16, SNCA, OPRK1 and PDYN, results that are awaiting confirmation. These successes demonstrate that genes contributing to the risk for alcoholism can be reliably identified using human subjects.

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

Unexpected deaths in cardiology outpatients - what can we learn from case review?

PubMed

Kitz, Thomas Michael; Burnand, Nikki; Ortner, Astrid; Rudd, Ian G; Sampson, Rod; Rushworth, Gordon F; Leslie, Stephen James

2016-12-01

A proportion of cardiac patients managed at a cardiology outpatient clinic will die between clinic visits. This study aimed to identify the cause of death, to determine if case review occurred and if a formal review of such cases might be useful. Single-centre retrospective cohort study. A remote regional centre in the North of Scotland. All patients who had been removed from the cardiology outpatient clinic due to death in the community. Cause of death, comorbidities and treatments were collected from hospital records and the national register of deaths. Chi-squared test and Student's t -test were used with significance taken at the 5% level. Of 10,606 patients who attended the cardiology outpatient clinic, 75 (0.7%) patients died in the community. The majority (57.0%) died from a non-cardiac cause. Eleven patients (14.9%) died due to an unexpected cardiac death. A detailed case note review was undertaken. In only two (18.2%) cases was any note made as to the cause of death in the hospital records and in only one was there details of post mortem discussion between primary and secondary care. A small proportion of patients attending a cardiology outpatient clinic died in the community. Documentation of the death in the hospital notes was very poor and evidence of post mortem communication between primary and secondary care was absent in all but one case. Better documentation and communication between primary and secondary care would seem desirable.

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.

Preformed Frequencies of Cytomegalovirus (CMV)–Specific Memory T and B Cells Identify Protected CMV-Sensitized Individuals Among Seronegative Kidney Transplant Recipients

PubMed Central

Lúcia, Marc; Crespo, Elena; Melilli, Edoardo; Cruzado, Josep M.; Luque, Sergi; Llaudó, Inés; Niubó, Jordi; Torras, Joan; Fernandez, Núria; Grinyó, Josep M.; Bestard, Oriol

2014-01-01

Background. Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers. Methods. We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG–seronegative (sR−) and 86 CMV IgG–seropositive (sR+) patients. Clinical outcome was evaluated in both groups. Results. All sR+ patients showed a wide range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell frequencies were also clearly detected in 30% of sR− patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test. Conclusions. Assessment of CMV-specific memory T- and B-cell responses before kidney transplantation among sR− recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection. PMID:25048845

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

PubMed Central

Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

2017-01-01

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403

Recent Visual Experience Shapes Visual Processing in Rats through Stimulus-Specific Adaptation and Response Enhancement.

PubMed

Vinken, Kasper; Vogels, Rufin; Op de Beeck, Hans

2017-03-20

From an ecological point of view, it is generally suggested that the main goal of vision in rats and mice is navigation and (aerial) predator evasion [1-3]. The latter requires fast and accurate detection of a change in the visual environment. An outstanding question is whether there are mechanisms in the rodent visual system that would support and facilitate visual change detection. An experimental protocol frequently used to investigate change detection in humans is the oddball paradigm, in which a rare, unexpected stimulus is presented in a train of stimulus repetitions [4]. A popular "predictive coding" theory of cortical responses states that neural responses should decrease for expected sensory input and increase for unexpected input [5, 6]. Despite evidence for response suppression and enhancement in noninvasive scalp recordings in humans with this paradigm [7, 8], it has proven challenging to observe both phenomena in invasive action potential recordings in other animals [9-11]. During a visual oddball experiment, we recorded multi-unit spiking activity in rat primary visual cortex (V1) and latero-intermediate area (LI), which is a higher area of the rodent ventral visual stream. In rat V1, there was only evidence for response suppression related to stimulus-specific adaptation, and not for response enhancement. However, higher up in area LI, spiking activity showed clear surprise-based response enhancement in addition to stimulus-specific adaptation. These results show that neural responses along the rat ventral visual stream become increasingly sensitive to changes in the visual environment, suggesting a system specialized in the detection of unexpected events. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans

PubMed Central

Bentley, Amy R.; Chen, Guanjie; Shriner, Daniel; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Mullikin, James C.; Blakesley, Robert W.; Hansen, Nancy F.; Bouffard, Gerard G.; Cherukuri, Praveen F.; Maskeri, Baishali; Young, Alice C.; Adeyemo, Adebowale; Rotimi, Charles N.

2014-01-01

Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a “European” vs. “African” genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2–3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA. PMID:24603370

Initial Treatment for Nonsyndromic Early-Life Epilepsy: An Unexpected Consensus.

PubMed

Shellhaas, Renée A; Berg, Anne T; Grinspan, Zachary M; Wusthoff, Courtney J; Millichap, John J; Loddenkemper, Tobias; Coryell, Jason; Saneto, Russell P; Chu, Catherine J; Joshi, Sucheta M; Sullivan, Joseph E; Knupp, Kelly G; Kossoff, Eric H; Keator, Cynthia; Wirrell, Elaine C; Mytinger, John R; Valencia, Ignacio; Massey, Shavonne; Gaillard, William D

2017-10-01

There are no evidence-based guidelines on the preferred approach to treating early-life epilepsy. We examined initial therapy selection in a contemporary US cohort of children with newly diagnosed, nonsyndromic, early-life epilepsy (onset before age three years). Seventeen pediatric epilepsy centers participated in a prospective cohort study of children with newly diagnosed epilepsy with onset under 36 months of age. Details regarding demographics, seizure types, and initial medication selections were obtained from medical records. About half of the 495 enrolled children with new-onset, nonsyndromic epilepsy were less than 12 months old at the time of diagnosis (n = 263, 53%) and about half (n = 260, 52%) had epilepsy with focal features. Of 464 who were treated with monotherapy, 95% received one of five drugs: levetiracetam (n = 291, 63%), oxcarbazepine (n = 67, 14%), phenobarbital (n = 57, 12%), topiramate (n = 16, 3.4%), and zonisamide (n = 13, 2.8%). Phenobarbital was prescribed first for 50 of 163 (31%) infants less than six months old versus seven of 300 (2.3%) of children six months or older (P < 0.0001). Although the first treatment varied across study centers (P < 0.0001), levetiracetam was the most commonly prescribed medication regardless of epilepsy presentation (focal, generalized, mixed/uncertain). Between the first and second treatment choices, 367 (74%) of children received levetiracetam within the first year after diagnosis. Without any specific effort, the pediatric epilepsy community has developed an unexpectedly consistent approach to initial treatment selection for early-life epilepsy. This suggests that a standard practice is emerging and could be utilized as a widely acceptable basis of comparison in future drug studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

PubMed

Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

2013-04-01

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Comparing the effectiveness of using generic and specific search terms in electronic databases to identify health outcomes for a systematic review: a prospective comparative study of literature search methods

PubMed Central

MacLean, Alice; Sweeting, Helen; Hunt, Kate

2012-01-01

Objective To compare the effectiveness of systematic review literature searches that use either generic or specific terms for health outcomes. Design Prospective comparative study of two electronic literature search strategies. The ‘generic’ search included general terms for health such as ‘adolescent health’, ‘health status’, ‘morbidity’, etc. The ‘specific’ search focused on terms for a range of specific illnesses, such as ‘headache’, ‘epilepsy’, ‘diabetes mellitus’, etc. Data sources The authors searched Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Education Resources Information Center for studies published in English between 1992 and April 2010. Main outcome measures Number and proportion of studies included in the systematic review that were identified from each search. Results The two searches tended to identify different studies. Of 41 studies included in the final review, only three (7%) were identified by both search strategies, 21 (51%) were identified by the generic search only and 17 (41%) were identified by the specific search only. 5 of the 41 studies were also identified through manual searching methods. Studies identified by the two ELS differed in terms of reported health outcomes, while each ELS uniquely identified some of the review's higher quality studies. Conclusions Electronic literature searches (ELS) are a vital stage in conducting systematic reviews and therefore have an important role in attempts to inform and improve policy and practice with the best available evidence. While the use of both generic and specific health terms is conventional for many reviewers and information scientists, there are also reviews that rely solely on either generic or specific terms. Based on the findings, reliance on only the generic or specific approach could increase the risk of systematic reviews missing important evidence and, consequently, misinforming decision makers

Systematic screening of isogenic cancer cells identifies DUSP6 as context-specific synthetic lethal target in melanoma

PubMed Central

Wittig-Blaich, Stephanie; Wittig, Rainer; Schmidt, Steffen; Lyer, Stefan; Bewerunge-Hudler, Melanie; Gronert-Sum, Sabine; Strobel-Freidekind, Olga; Müller, Carolin; List, Markus; Jaskot, Aleksandra; Christiansen, Helle; Hafner, Mathias; Schadendorf, Dirk; Block, Ines; Mollenhauer, Jan

2017-01-01

Next-generation sequencing has dramatically increased genome-wide profiling options and conceptually initiates the possibility for personalized cancer therapy. State-of-the-art sequencing studies yield large candidate gene sets comprising dozens or hundreds of mutated genes. However, few technologies are available for the systematic downstream evaluation of these results to identify novel starting points of future cancer therapies. We improved and extended a site-specific recombination-based system for systematic analysis of the individual functions of a large number of candidate genes. This was facilitated by a novel system for the construction of isogenic constitutive and inducible gain- and loss-of-function cell lines. Additionally, we demonstrate the construction of isogenic cell lines with combinations of the traits for advanced functional in vitro analyses. In a proof-of-concept experiment, a library of 108 isogenic melanoma cell lines was constructed and 8 genes were identified that significantly reduced viability in a discovery screen and in an independent validation screen. Here, we demonstrate the broad applicability of this recombination-based method and we proved its potential to identify new drug targets via the identification of the tumor suppressor DUSP6 as potential synthetic lethal target in melanoma cell lines with BRAF V600E mutations and high DUSP6 expression. PMID:28423600

Whole genome co-expression analysis of soybean cytochrome P450 genes identifies nodulation-specific P450 monooxygenases

PubMed Central

2010-01-01

Background Cytochrome P450 monooxygenases (P450s) catalyze oxidation of various substrates using oxygen and NAD(P)H. Plant P450s are involved in the biosynthesis of primary and secondary metabolites performing diverse biological functions. The recent availability of the soybean genome sequence allows us to identify and analyze soybean putative P450s at a genome scale. Co-expression analysis using an available soybean microarray and Illumina sequencing data provides clues for functional annotation of these enzymes. This approach is based on the assumption that genes that have similar expression patterns across a set of conditions may have a functional relationship. Results We have identified a total number of 332 full-length P450 genes and 378 pseudogenes from the soybean genome. From the full-length sequences, 195 genes belong to A-type, which could be further divided into 20 families. The remaining 137 genes belong to non-A type P450s and are classified into 28 families. A total of 178 probe sets were found to correspond to P450 genes on the Affymetrix soybean array. Out of these probe sets, 108 represented single genes. Using the 28 publicly available microarray libraries that contain organ-specific information, some tissue-specific P450s were identified. Similarly, stress responsive soybean P450s were retrieved from 99 microarray soybean libraries. We also utilized Illumina transcriptome sequencing technology to analyze the expressions of all 332 soybean P450 genes. This dataset contains total RNAs isolated from nodules, roots, root tips, leaves, flowers, green pods, apical meristem, mock-inoculated and Bradyrhizobium japonicum-infected root hair cells. The tissue-specific expression patterns of these P450 genes were analyzed and the expression of a representative set of genes were confirmed by qRT-PCR. We performed the co-expression analysis on many of the 108 P450 genes on the Affymetrix arrays. First we confirmed that CYP93C5 (an isoflavone synthase gene) is

Unexpected stimulation of soil methane uptake as emergent property of agricultural soils following bio-based residue application.

PubMed

Ho, Adrian; Reim, Andreas; Kim, Sang Yoon; Meima-Franke, Marion; Termorshuizen, Aad; de Boer, Wietse; van der Putten, Wim H; Bodelier, Paul L E

2015-10-01

Intensification of agriculture to meet the global food, feed, and bioenergy demand entail increasing re-investment of carbon compounds (residues) into agro-systems to prevent decline of soil quality and fertility. However, agricultural intensification decreases soil methane uptake, reducing, and even causing the loss of the methane sink function. In contrast to wetland agricultural soils (rice paddies), the methanotrophic potential in well-aerated agricultural soils have received little attention, presumably due to the anticipated low or negligible methane uptake capacity in these soils. Consequently, a detailed study verifying or refuting this assumption is still lacking. Exemplifying a typical agricultural practice, we determined the impact of bio-based residue application on soil methane flux, and determined the methanotrophic potential, including a qualitative (diagnostic microarray) and quantitative (group-specific qPCR assays) analysis of the methanotrophic community after residue amendments over 2 months. Unexpectedly, after amendments with specific residues, we detected a significant transient stimulation of methane uptake confirmed by both the methane flux measurements and methane oxidation assay. This stimulation was apparently a result of induced cell-specific activity, rather than growth of the methanotroph population. Although transient, the heightened methane uptake offsets up to 16% of total gaseous CO2 emitted during the incubation. The methanotrophic community, predominantly comprised of Methylosinus may facilitate methane oxidation in the agricultural soils. While agricultural soils are generally regarded as a net methane source or a relatively weak methane sink, our results show that methane oxidation rate can be stimulated, leading to higher soil methane uptake. Hence, even if agriculture exerts an adverse impact on soil methane uptake, implementing carefully designed management strategies (e.g. repeated application of specific residues) may

Strain-specific priming of resistance in the red flour beetle, Tribolium castaneum

PubMed Central

Roth, Olivia; Sadd, Ben M; Schmid-Hempel, Paul; Kurtz, Joachim

2008-01-01

As invertebrates lack the molecular machinery employed by the vertebrate adaptive immune system, it was thought that they consequently lack the ability to produce lasting and specific immunity. However, in recent years, it has been demonstrated that the immune defence of invertebrates is by far more complicated and specific than previously envisioned. Lasting immunity following an initial exposure that proves protection on a secondary exposure has been shown in several species of invertebrates. This phenomenon has become known as immune priming. In the cases where it is explicitly tested, this priming can also be highly specific. In this study, we used survival assays to test for specific priming of resistance in the red flour beetle, Tribolium castaneum, using bacteria of different degrees of relatedness. Our results suggest an unexpected degree of specificity that even allows for differentiation between different strains of the same bacterium. However, our findings also demonstrate that specific priming of resistance in insects may not be ubiquitous across all bacteria. PMID:18796392

Cannibalistic-morph Tiger Salamanders in unexpected ecological contexts

USGS Publications Warehouse

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

2016-01-01

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

Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

PubMed

San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

2014-12-01

Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

Spontaneous abortion and unexpected death: a critical discussion of Marquis on abortion.

PubMed

Coleman, Mary Clayton

2013-02-01

In his classic paper, 'Why abortion is immoral', Don Marquis argues that what makes killing an adult seriously immoral is that it deprives the victim of the valuable future he/she would have otherwise had. Moreover, Marquis contends, because abortion deprives a fetus of the very same thing, aborting a fetus is just as seriously wrong as killing an adult. Marquis' argument has received a great deal of critical attention in the two decades since its publication. Nonetheless, there is a potential challenge to it that seems to have gone unnoticed. A significant percentage of fetuses are lost to spontaneous abortion. Once we bring this fact to our attention, it becomes less clear whether Marquis can use his account of the wrongness of killing to show that abortion is the moral equivalent of murder. In this paper, I explore the relevance of the rate of spontaneous abortion to Marquis' classic anti-abortion argument. I introduce a case I call Unexpected Death in which someone is about to commit murder, but, just as the would-be murderer is about to strike, his would-be victim dies unexpectedly. I then ask: what does Marquis' account of killing imply about the moral status of what the would-be murderer was about to do? I consider four responses Marquis could give to this question, and I examine what implications these responses have for Marquis' strategy of using his account of the wrongness of killing an adult to show that abortion is in the same moral category.

Comparison of various methods to determine bulk specific gravity of cores : an investigation of high values using AASHTO T275 - paraffin-coated method.

DOT National Transportation Integrated Search

2012-07-01

A report from a MoDOT asphalt paving project was that unexpected results were obtained when adhering to the standard for determination of bulk specific gravity of compacted asphalt mixture (Gmb) specimens, AASHTO T 166. The test method requires speci...

m6A-Driver: Identifying Context-Specific mRNA m6A Methylation-Driven Gene Interaction Networks

PubMed Central

Zhang, Song-Yao; Zhang, Shao-Wu; Liu, Lian; Huang, Yufei

2016-01-01

As the most prevalent mammalian mRNA epigenetic modification, N6-methyladenosine (m6A) has been shown to possess important post-transcriptional regulatory functions. However, the regulatory mechanisms and functional circuits of m6A are still largely elusive. To help unveil the regulatory circuitry mediated by mRNA m6A methylation, we develop here m6A-Driver, an algorithm for predicting m6A-driven genes and associated networks, whose functional interactions are likely to be actively modulated by m6A methylation under a specific condition. Specifically, m6A-Driver integrates the PPI network and the predicted differential m6A methylation sites from methylated RNA immunoprecipitation sequencing (MeRIP-Seq) data using a Random Walk with Restart (RWR) algorithm and then builds a consensus m6A-driven network of m6A-driven genes. To evaluate the performance, we applied m6A-Driver to build the context-specific m6A-driven networks for 4 known m6A (de)methylases, i.e., FTO, METTL3, METTL14 and WTAP. Our results suggest that m6A-Driver can robustly and efficiently identify m6A-driven genes that are functionally more enriched and associated with higher degree of differential expression than differential m6A methylated genes. Pathway analysis of the constructed context-specific m6A-driven gene networks further revealed the regulatory circuitry underlying the dynamic interplays between the methyltransferases and demethylase at the epitranscriptomic layer of gene regulation. PMID:28027310

Compounds with species and cell type specific toxicity identified in a 2000 compound drug screen of neural stem cells and rat mixed cortical neurons.

PubMed

Malik, Nasir; Efthymiou, Anastasia G; Mather, Karly; Chester, Nathaniel; Wang, Xiantao; Nath, Avindra; Rao, Mahendra S; Steiner, Joseph P

2014-12-01

Human primary neural tissue is a vital component for the quick and simple determination of chemical compound neurotoxicity in vitro. In particular, such tissue would be ideal for high-throughput screens that can be used to identify novel neurotoxic or neurotherapeutic compounds. We have previously established a high-throughput screening platform using human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) and neurons. In this study, we conducted a 2000 compound screen with human NSCs and rat cortical cells to identify compounds that are selectively toxic to each group. Approximately 100 of the tested compounds showed specific toxicity to human NSCs. A secondary screen of a small subset of compounds from the primary screen on human iPSCs, NSC-derived neurons, and fetal astrocytes validated the results from >80% of these compounds with some showing cell specific toxicity. Amongst those compounds were several cardiac glycosides, all of which were selectively toxic to the human cells. As the screen was able to reliably identify neurotoxicants, many with species and cell-type specificity, this study demonstrates the feasibility of this NSC-driven platform for higher-throughput neurotoxicity screens. Published by Elsevier B.V.

ERP correlates of unexpected word forms in a picture–word study of infants and adults

PubMed Central

Duta, M.D.; Styles, S.J.; Plunkett, K.

2012-01-01

We tested 14-month-olds and adults in an event-related potentials (ERPs) study in which pictures of familiar objects generated expectations about upcoming word forms. Expected word forms labelled the picture (word condition), while unexpected word forms mismatched by either a small deviation in word medial vowel height (mispronunciation condition) or a large deviation from the onset of the first speech segment (pseudoword condition). Both infants and adults showed sensitivity to both types of unexpected word form. Adults showed a chain of discrete effects: positivity over the N1 wave, negativity over the P2 wave (PMN effect) and negativity over the N2 wave (N400 effect). Infants showed a similar pattern, including a robust effect similar to the adult P2 effect. These observations were underpinned by a novel visualisation method which shows the dynamics of the ERP within bands of the scalp over time. The results demonstrate shared processing mechanisms across development, as even subtle deviations from expected word forms were indexed in both age groups by a reduction in the amplitude of characteristic waves in the early auditory evoked potential. PMID:22483072

Insect immunity shows specificity in protection upon secondary pathogen exposure.

PubMed

Sadd, Ben M; Schmid-Hempel, Paul

2006-06-20

Immunological memory in vertebrates, conferring lasting specific protection after an initial pathogen exposure, has implications for a broad spectrum of evolutionary, epidemiological, and medical phenomena . However, the existence of specificity in protection upon secondary pathogen exposure in invertebrates remains controversial . To separate this functional phenomenon from a particular mechanism, we refer to it as specific immune priming. We investigate the presence of specific immune priming in workers of the social insect Bombus terrestris. Using three bacterial pathogens, we test whether a prior homologous pathogen exposure gives a benefit in terms of long-term protection against a later challenge, over and above a heterologous combination. With a reciprocally designed initial and second-exposure protocol (i.e., all combinations of bacteria were tested), we demonstrate, even several weeks after the clearance of a first exposure, increased protection and narrow specificity upon secondary exposure. This demonstrates that the invertebrate immune system is functionally capable of unexpectedly specific and durable induced protection. Ultimately, despite general broad differences between vertebrates and invertebrates, the ability of both immune systems to show specificity in protection suggests that their immune defenses have found comparable solutions to similar selective pressures over evolutionary time.

Unexpected Hospitalisations at a 23-Hour Observation Unit in a Paediatric Emergency Department of Northern India

PubMed Central

Mahajan, Vidushi; Arora, Sumant; Kaur, Tarundeep; Gupta, Sorab; Guglani, Vishal

2013-01-01

Background: The 23-hour Observation Unit (OU) is a novel and an effective means for tackling overcrowding in busy Paediatric Emergency Departments (PED) worldwide. However, unexpected hospitalisations in the OU involve transfer of care and they reduce the efficiency of the OU. Hence, we aimed to study the presenting diagnoses which were responsible for the unexpected hospitalisations in a 23-hour OU. Methods and Design: A prospective cohort study Setting: The PED at a tertiary care teaching hospital. Duration: 15th Feb-15th March 2011. Protocol: Consecutive children were triaged at presentation to the PED, according to the WHO paediatric emergency triage algorithm. Those who were transferred to the 23-hour OU, were further followed up for duration of the stay, the hospital course, and the outcome (discharge/hospitalisation). Results: Three hundred (228 males, 72 females) consecutive children who attended the PED over one month were enrolled. All the children, at presentation, were triaged by the medical intern/s who was/were posted in the PED, and they were crosschecked by a PED consultant. A majority (55%, n=165) of the children were triaged as non-urgent, 32% (n=97) as priority and 13% (n=38) as emergent. Out of the 300 children, 173(58%) were transferred to the 23-hour OU. Of these, 16 (9.1%) required unexpected hospitalisations. The children who required hospitalisations had the following diagnoses: bronchiolitis (4), bronchopneumonia (4), seizure (2), viral hepatitis (2), high fever (1), bronchial asthma (1), severe anaemia (1), and urticaria (1). The mean duration of the stay in the OU was 19 hours for those who needed hospitalisation, as against 13 hours for those who were discharged from the OU. Conclusion: The children with respiratory complaints (bronchiolitis and bronchopneumonia) need frequent monitoring in the 23-hour OU, as they have high hospitalisation rates in the OU. PMID:23998079

Variola Virus-Specific Diagnostic Assays: Characterization, Sensitivity, and Specificity

PubMed Central

Kondas, Ashley V.; Olson, Victoria A.; Li, Yu; Abel, Jason; Laker, Miriam; Rose, Laura; Wilkins, Kimberly; Turner, Jonathan; Kline, Richard

2015-01-01

A public health response relies upon rapid and reliable confirmation of disease by diagnostic assays. Here, we detail the design and validation of two variola virus-specific real-time PCR assays, since previous assays cross-reacted with newly identified cowpox viruses. The assay specificity must continually be reassessed as other closely related viruses are identified. PMID:25673790

Driving performance changes of middle-aged experienced taxi drivers due to distraction tasks during unexpected situations.

PubMed

Kim, Hyung-Sik; Choi, Mi-Hyun; Choi, Jin-Seung; Kim, Hyun-Joo; Hong, Sang-Pyo; Jun, Jae-Hoon; Tack, Gye-Rae; Kim, Boseong; Min, Ung-Chan; Lim, Dae-Woon; Chung, Soon-Cheol

2013-10-01

This study investigated the effects of distraction taskssuch as sending a text message with a cellphone and searching navigation with car navigation system-on the driving performance of 29 highly experienced taxi drivers in their 50s. All participants were instructed to drive using a driving simulator for 2 min. while maintaining a constant distance from the vehicle in front and a constant speed. Participants drove without any distractions for the first minute. For an additional minute, they performed Driving Only or performed a task while driving (Driving + Sending Text Message or Driving + Searching Navigation). An unexpected situation, in which the participant had to stop abruptly due to a sudden stop of the preceding vehicle, occurred during this period. Driving performance during the unexpected situation was evaluated by car control variables, medial-lateral coefficient of variation and brake time, and by motion variables such as the jerk-cost function. Compared to Driving Only, jerk-cost function, medial-lateral coefficient of variation, and brake time increased during Driving + Sending Text Message or Driving + Searching Navigation.

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.

Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity

PubMed Central

Bosi, Emanuele; Monk, Jonathan M.; Aziz, Ramy K.; Fondi, Marco; Nizet, Victor; Palsson, Bernhard Ø.

2016-01-01

Staphylococcus aureus is a preeminent bacterial pathogen capable of colonizing diverse ecological niches within its human host. We describe here the pangenome of S. aureus based on analysis of genome sequences from 64 strains of S. aureus spanning a range of ecological niches, host types, and antibiotic resistance profiles. Based on this set, S. aureus is expected to have an open pangenome composed of 7,411 genes and a core genome composed of 1,441 genes. Metabolism was highly conserved in this core genome; however, differences were identified in amino acid and nucleotide biosynthesis pathways between the strains. Genome-scale models (GEMs) of metabolism were constructed for the 64 strains of S. aureus. These GEMs enabled a systems approach to characterizing the core metabolic and panmetabolic capabilities of the S. aureus species. All models were predicted to be auxotrophic for the vitamins niacin (vitamin B3) and thiamin (vitamin B1), whereas strain-specific auxotrophies were predicted for riboflavin (vitamin B2), guanosine, leucine, methionine, and cysteine, among others. GEMs were used to systematically analyze growth capabilities in more than 300 different growth-supporting environments. The results identified metabolic capabilities linked to pathogenic traits and virulence acquisitions. Such traits can be used to differentiate strains responsible for mild vs. severe infections and preference for hosts (e.g., animals vs. humans). Genome-scale analysis of multiple strains of a species can thus be used to identify metabolic determinants of virulence and increase our understanding of why certain strains of this deadly pathogen have spread rapidly throughout the world. PMID:27286824

Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

NASA Astrophysics Data System (ADS)

Gao, Rong; Cheng, Jianhua; Fan, Chunlei; Shi, Xiaofeng; Cao, Yuan; Sun, Bo; Ding, Huiguo; Hu, Chengjin; Dong, Fangting; Yan, Xianzhong

2015-12-01

Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography-time of flight-mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and β-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.

The French prospective multisite registry on sudden unexpected infant death (OMIN): rationale and study protocol

PubMed Central

Levieux, Karine; Patural, Hugues; Harrewijn, Inge; Briand Huchet, Elisabeth; de Visme, Sophie; Gallot, Géraldine; Chalumeau, Martin; Gras Le Guen, Christèle; Hanf, Matthieu; Garcia-Meric, Patricia

2018-01-01

Introduction Even after ‘back-to-sleep’ campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1 month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area. Methods and analysis This observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths. Ethics and dissemination The French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l’Informatique et des Libertés: number 915273) and by an independent ethics committee (Groupe Nantais

Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

PubMed Central

O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik

2015-01-01

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329

Managing unexpected events in the manufacturing of biologic medicines.

PubMed

Grampp, Gustavo; Ramanan, Sundar

2013-08-01

The manufacturing of biologic medicines (biologics) requires robust process and facility design, rigorous regulatory compliance, and a well-trained workforce. Because of the complex attributes of biologics and their sensitivity to production and handling conditions, manufacturing of these medicines also requires a high-reliability manufacturing organization. As required by regulators, such an organization must monitor the state-of-control for the manufacturing process. A high-reliability organization also invests in an experienced and fully engaged technical support staff and fosters a management culture that rewards in-depth analysis of unexpected results, robust risk assessments, and timely and effective implementation of mitigation measures. Such a combination of infrastructure, technology, human capital, management, and a science-based operations culture does not occur without a strong organizational and financial commitment. These attributes of a high-reliability biologics manufacturer are difficult to achieve and may be differentiating factors as the supply of biologics diversifies in future years.

The Unexpected Awakening of Chaitén Volcano, Chile

NASA Astrophysics Data System (ADS)

Carn, Simon A.; Pallister, John S.; Lara, Luis; Ewert, John W.; Watt, Sebastian; Prata, Alfred J.; Thomas, Ronald J.; Villarosa, Gustavo

2009-06-01

On 2 May 2008, a large eruption began unexpectedly at the inconspicuous Chaitén volcano in Chile's southern volcanic zone. Ash columns abruptly jetted from the volcano into the stratosphere, followed by lava dome effusion and continuous low-altitude ash plumes [Lara, 2009]. Apocalyptic photographs of eruption plumes suffused with lightning were circulated globally. Effects of the eruption were extensive. Floods and lahars inundated the town of Chaitén, and its 4625 residents were evacuated. Widespread ashfall and drifting ash clouds closed regional airports and cancelled hundreds of domestic flights in Argentina and Chile and numerous international flights [Guffanti et al., 2008]. Ash heavily affected the aquaculture industry in the nearby Gulf of Corcovado, curtailed ecotourism, and closed regional nature preserves. To better prepare for future eruptions, the Chilean government has boosted support for monitoring and hazard mitigation at Chaitén and at 42 other highly hazardous, active volcanoes in Chile.

The Unexpected Awakening of Chaitén Volcano, Chile

USGS Publications Warehouse

Carn, Simon A.; Zogorski, John S.; Lara, Luis; Ewert, John W.; Watt, Sebastian; Prata, Alfred J.; Thomas, Ronald J.; Villarosa, Gustavo

2009-01-01

On 2 May 2008, a large eruption began unexpectedly at the inconspicuous Chaitén volcano in Chile's southern volcanic zone. Ash columns abruptly jetted from the volcano into the stratosphere, followed by lava dome effusion and continuous low-altitude ash plumes [Lara, 2009]. Apocalyptic photographs of eruption plumes suffused with lightning were circulated globally. Effects of the eruption were extensive. Floods and lahars inundated the town of Chaitén, and its 4625 residents were evacuated. Widespread ashfall and drifting ash clouds closed regional airports and cancelled hundreds of domestic flights in Argentina and Chile and numerous international flights [Guffanti et al., 2008]. Ash heavily affected the aquaculture industry in the nearby Gulf of Corcovado, curtailed ecotourism, and closed regional nature preserves. To better prepare for future eruptions, the Chilean government has boosted support for monitoring and hazard mitigation at Chaitén and at 42 other highly hazardous, active volcanoes in Chile.

Specific Detection and Identification of American Mulberry-Infecting and Italian Olive-Associated Strains of Xylella fastidiosa by Polymerase Chain Reaction

PubMed Central

Guan, Wei; Shao, Jonathan; Elbeaino, Toufic; Davis, Robert E.; Zhao, Tingchang; Huang, Qi

2015-01-01

Xylella fastidiosa causes bacterial leaf scorch in many landscape trees including elm, oak, sycamore and mulberry, but methods for specific identification of a particular tree host species-limited strain or differentiation of tree-specific strains are lacking. It is also unknown whether a particular landscape tree-infecting X. fastidiosa strain is capable of infecting multiple landscape tree species in an urban environment. We developed two PCR primers specific for mulberry-infecting strains of X. fastidiosa based on the nucleotide sequence of a unique open reading frame identified only in mulberry-infecting strains among all the North and South American strains of X. fastidiosa sequenced to date. PCR using the primers allowed for detection and identification of mulberry-infecting X. fastidiosa strains in cultures and in samples collected from naturally infected mulberry trees. In addition, no mixed infections with or non-specific detections of the mulberry-infecting strains of X. fastidiosa were found in naturally X. fastidiosa-infected oak, elm and sycamore trees growing in the same region where naturally infected mulberry trees were grown. This genotype-specific PCR assay will be valuable for disease diagnosis, studies of strain-specific infections in insects and plant hosts, and management of diseases caused by X. fastidiosa. Unexpectedly but interestingly, the unique open reading frame conserved in the mulberry-infecting strains in the U. S. was also identified in the recently sequenced olive-associated strain CoDiRO isolated in Italy. When the primer set was tested against naturally infected olive plant samples collected in Italy, it allowed for detection of olive-associated strains of X. fastidiosa in Italy. This PCR assay, therefore, will also be useful for detection and identification of the Italian group of X. fastidiosa strains to aid understanding of the occurrence, evolution and biology of this new group of X. fastidiosa strains. PMID:26061051

Specific Detection and Identification of American Mulberry-Infecting and Italian Olive-Associated Strains of Xylella fastidiosa by Polymerase Chain Reaction.

PubMed

Guan, Wei; Shao, Jonathan; Elbeaino, Toufic; Davis, Robert E; Zhao, Tingchang; Huang, Qi

2015-01-01

Xylella fastidiosa causes bacterial leaf scorch in many landscape trees including elm, oak, sycamore and mulberry, but methods for specific identification of a particular tree host species-limited strain or differentiation of tree-specific strains are lacking. It is also unknown whether a particular landscape tree-infecting X. fastidiosa strain is capable of infecting multiple landscape tree species in an urban environment. We developed two PCR primers specific for mulberry-infecting strains of X. fastidiosa based on the nucleotide sequence of a unique open reading frame identified only in mulberry-infecting strains among all the North and South American strains of X. fastidiosa sequenced to date. PCR using the primers allowed for detection and identification of mulberry-infecting X. fastidiosa strains in cultures and in samples collected from naturally infected mulberry trees. In addition, no mixed infections with or non-specific detections of the mulberry-infecting strains of X. fastidiosa were found in naturally X. fastidiosa-infected oak, elm and sycamore trees growing in the same region where naturally infected mulberry trees were grown. This genotype-specific PCR assay will be valuable for disease diagnosis, studies of strain-specific infections in insects and plant hosts, and management of diseases caused by X. fastidiosa. Unexpectedly but interestingly, the unique open reading frame conserved in the mulberry-infecting strains in the U. S. was also identified in the recently sequenced olive-associated strain CoDiRO isolated in Italy. When the primer set was tested against naturally infected olive plant samples collected in Italy, it allowed for detection of olive-associated strains of X. fastidiosa in Italy. This PCR assay, therefore, will also be useful for detection and identification of the Italian group of X. fastidiosa strains to aid understanding of the occurrence, evolution and biology of this new group of X. fastidiosa strains.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables

PubMed Central

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R.; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C.; Downing, James R.; Lamba, Jatinder

2009-01-01

Motivation: In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Results: Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Availability: Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org. Contact: stanley.pounds@stjude.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19528086

Unexpected Stability of Bacteroidetes and Firmicutes Communities in Laboratory Biogas Reactors Fed with Different Defined Substrates

PubMed Central

Ratering, S.; Kramer, I.; Schmidt, M.; Zerr, W.; Schnell, S.

2012-01-01

In the present study, bacterial communities in 200-liter biogas reactors containing liquid manure consecutively fed with casein, starch, and cream were investigated over a period of up to 33 days. A 16S rRNA gene clone library identified Bacteroidetes and Firmicutes as the most abundant bacterial groups in the starting material, at 58.9% and 30.1% of sequences, respectively. The community development of both groups was monitored by real-time PCR and single-strand conformation polymorphism (SSCP) analysis. The Firmicutes and Bacteroidetes communities were unexpectedly stable and hardly influenced by batch-feeding events. The continuous feeding of starch led to community shifts that nevertheless contributed to a stable reactor performance. A longer starving period and a change in the pH value resulted in further community shifts within the Bacteroidetes but did not influence the Firmicutes. Predominant DNA bands from SSCP gels were cloned and sequenced. Sequences related to Peptococcaceae, Cytophagales, and Petrimonas sulfuriphila were found in all samples from all experiments. Real-time PCR demonstrated the abundance of members of the phylum Bacteroidetes and also reflected changes in gene copy numbers in conjunction with a changing pH value and acetate accumulation. PMID:22247168

Genome-wide association studies identify four ER negative–specific breast cancer risk loci

PubMed Central

Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

2013-01-01

Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

Falls-risk post-stroke: Examining contributions from paretic versus non paretic limbs to unexpected forward gait slips.

PubMed

Kajrolkar, Tejal; Bhatt, Tanvi

2016-09-06

Community-dwelling stroke survivors show a high incidence of falls with unexpected external perturbations during dynamic activities like walking. Previous evidence has demonstrated the importance of compensatory stepping to restore dynamic stability in response to perturbations in hemiparetic stroke survivors. However, these studies were limited to either stance perturbations or perturbation induced under the unaffected limb. This study aimed to compare the differences, if any, between the non-paretic and paretic sides in dynamic stability and protective stepping strategies when exposed to unexpected external perturbation during walking. Twenty hemiparetic subjects experienced an unexpected forward slip during walking on the laboratory walkway either on the paretic (n=10) or the nonparetic limb (n=10). Both groups demonstrated a backward loss of balance with a compensatory stepping response, with the nonparetic-side slip group resorting mainly to an aborted step response (60%) and the paretic-side slip group mainly exhibiting a recovery step response (90%). Although both groups showed an equal incidence of falls, the nonparetic-side slip group demonstrated a higher stability at recovery step touchdown, resulting from lower perturbation magnitudes (slip displacement and velocity) compared to the paretic-side slip group. The results indicate that the paretic side had difficulty initiating and executing a successful stepping response (nonparetic-side slip) and also in reactive limb control while in stance (paretic-side slip). Based on these results it is suggested that intervention strategies for fall-prevention in chronic stroke survivors should focus on paretic limb training for both reactive stepping and weight bearing for improving balance control for recovery from unpredictable perturbations during dynamic activities such as walking. Copyright © 2016. Published by Elsevier Ltd.

Unexpectedly High Levels of Cryptic Diversity Uncovered by a Complete DNA Barcoding of Reptiles of the Socotra Archipelago.

PubMed

Vasconcelos, Raquel; Montero-Mendieta, Santiago; Simó-Riudalbas, Marc; Sindaco, Roberto; Santos, Xavier; Fasola, Mauro; Llorente, Gustavo; Razzetti, Edoardo; Carranza, Salvador

2016-01-01

Few DNA barcoding studies of squamate reptiles have been conducted. Due to the significance of the Socotra Archipelago (a UNESCO Natural World Heritage site and a biodiversity hotspot) and the conservation interest of its reptile fauna (94% endemics), we performed the most comprehensive DNA barcoding study on an island group to date to test its applicability to specimen identification and species discovery. Reptiles constitute Socotra's most important vertebrate fauna, yet their taxonomy remains under-studied. We successfully DNA-barcoded 380 individuals of all 31 presently recognized species. The specimen identification success rate is moderate to high, and almost all species presented local barcoding gaps. The unexpected high levels of intra-specific variability found within some species suggest cryptic diversity. Species richness may be under-estimated by 13.8-54.4%. This has implications in the species' ranges and conservation status that should be considered for conservation planning. Other phylogenetic studies using mitochondrial and nuclear markers are congruent with our results. We conclude that, despite its reduced length (663 base pairs), cytochrome c oxidase 1, COI, is very useful for specimen identification and for detecting intra-specific diversity, and has a good phylogenetic signal. We recommend DNA barcoding to be applied to other biodiversity hotspots for quickly and cost-efficiently flagging species discovery, preferentially incorporated into an integrative taxonomic framework.

Unexpectedly High Levels of Cryptic Diversity Uncovered by a Complete DNA Barcoding of Reptiles of the Socotra Archipelago

PubMed Central

Simó-Riudalbas, Marc; Sindaco, Roberto; Santos, Xavier; Fasola, Mauro; Llorente, Gustavo; Razzetti, Edoardo; Carranza, Salvador

2016-01-01

Few DNA barcoding studies of squamate reptiles have been conducted. Due to the significance of the Socotra Archipelago (a UNESCO Natural World Heritage site and a biodiversity hotspot) and the conservation interest of its reptile fauna (94% endemics), we performed the most comprehensive DNA barcoding study on an island group to date to test its applicability to specimen identification and species discovery. Reptiles constitute Socotra’s most important vertebrate fauna, yet their taxonomy remains under-studied. We successfully DNA-barcoded 380 individuals of all 31 presently recognized species. The specimen identification success rate is moderate to high, and almost all species presented local barcoding gaps. The unexpected high levels of intra-specific variability found within some species suggest cryptic diversity. Species richness may be under-estimated by 13.8–54.4%. This has implications in the species’ ranges and conservation status that should be considered for conservation planning. Other phylogenetic studies using mitochondrial and nuclear markers are congruent with our results. We conclude that, despite its reduced length (663 base pairs), cytochrome c oxidase 1, COI, is very useful for specimen identification and for detecting intra-specific diversity, and has a good phylogenetic signal. We recommend DNA barcoding to be applied to other biodiversity hotspots for quickly and cost-efficiently flagging species discovery, preferentially incorporated into an integrative taxonomic framework. PMID:26930572

Curated collection of yeast transcription factor DNA binding specificity data reveals novel structural and gene regulatory insights

PubMed Central

2011-01-01

Background Transcription factors (TFs) play a central role in regulating gene expression by interacting with cis-regulatory DNA elements associated with their target genes. Recent surveys have examined the DNA binding specificities of most Saccharomyces cerevisiae TFs, but a comprehensive evaluation of their data has been lacking. Results We analyzed in vitro and in vivo TF-DNA binding data reported in previous large-scale studies to generate a comprehensive, curated resource of DNA binding specificity data for all characterized S. cerevisiae TFs. Our collection comprises DNA binding site motifs and comprehensive in vitro DNA binding specificity data for all possible 8-bp sequences. Investigation of the DNA binding specificities within the basic leucine zipper (bZIP) and VHT1 regulator (VHR) TF families revealed unexpected plasticity in TF-DNA recognition: intriguingly, the VHR TFs, newly characterized by protein binding microarrays in this study, recognize bZIP-like DNA motifs, while the bZIP TF Hac1 recognizes a motif highly similar to the canonical E-box motif of basic helix-loop-helix (bHLH) TFs. We identified several TFs with distinct primary and secondary motifs, which might be associated with different regulatory functions. Finally, integrated analysis of in vivo TF binding data with protein binding microarray data lends further support for indirect DNA binding in vivo by sequence-specific TFs. Conclusions The comprehensive data in this curated collection allow for more accurate analyses of regulatory TF-DNA interactions, in-depth structural studies of TF-DNA specificity determinants, and future experimental investigations of the TFs' predicted target genes and regulatory roles. PMID:22189060

Four unexpected lanthanide coordination polymers involving in situ reaction of solvent N, N-Dimethylformamide

NASA Astrophysics Data System (ADS)

Jin, Jun-Cheng; Tong, Wen-Quan; Fu, Ai-Yun; Xie, Cheng-Gen; Chang, Wen-Gui; Wu, Ju; Xu, Guang-Nian; Zhang, Ya-Nan; Li, Jun; Li, Yong; Yang, Peng-Qi

2015-05-01

Four unexpected 2D lanthanide coordination polymers have been synthesized through in situ reactions of DMF solvent under solvothermal conditions. The isostructural complexes 1-3 contain four types of 21 helical chains. While the Nd(III) ions are bridged through μ2-HIDC2- and oxalate to form a 2D sheet along the bc plane without helical character in 4. Therefore, complex 1 exhibits bright red solid-state phosphorescence upon exposure to UV radiation at room temperature.

Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer.

PubMed

Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

2016-07-04

The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns.

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

PubMed Central

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

2015-01-01

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

Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained

PubMed Central

Wu, Ying; Waite, Lindsay L.; Jackson, Anne U.; Sheu, Wayne H-H.; Buyske, Steven; Absher, Devin; Arnett, Donna K.; Boerwinkle, Eric; Bonnycastle, Lori L.; Carty, Cara L.; Cheng, Iona; Cochran, Barbara; Croteau-Chonka, Damien C.; Dumitrescu, Logan; Eaton, Charles B.; Franceschini, Nora; Guo, Xiuqing; Henderson, Brian E.; Hindorff, Lucia A.; Kim, Eric; Kinnunen, Leena; Komulainen, Pirjo; Lee, Wen-Jane; Le Marchand, Loic; Lin, Yi; Lindström, Jaana; Lingaas-Holmen, Oddgeir; Mitchell, Sabrina L.; Narisu, Narisu; Robinson, Jennifer G.; Schumacher, Fred; Stančáková, Alena; Sundvall, Jouko; Sung, Yun-Ju; Swift, Amy J.; Wang, Wen-Chang; Wilkens, Lynne; Wilsgaard, Tom; Young, Alicia M.; Adair, Linda S.; Ballantyne, Christie M.; Bůžková, Petra; Chakravarti, Aravinda; Collins, Francis S.; Duggan, David; Feranil, Alan B.; Ho, Low-Tone; Hung, Yi-Jen; Hunt, Steven C.; Hveem, Kristian; Juang, Jyh-Ming J.; Kesäniemi, Antero Y.; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lee, I-Te; Leppert, Mark F.; Matise, Tara C.; Moilanen, Leena; Njølstad, Inger; Peters, Ulrike; Quertermous, Thomas; Rauramaa, Rainer; Rotter, Jerome I.; Saramies, Jouko; Tuomilehto, Jaakko; Uusitupa, Matti; Wang, Tzung-Dau; Mohlke, Karen L.

2013-01-01

Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1×10−4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies. PMID:23555291

New Hepatitis B Virus of Cranes That Has an Unexpected Broad Host Range

PubMed Central

Prassolov, Alexej; Hohenberg, Heinz; Kalinina, Tatyana; Schneider, Carola; Cova, Lucyna; Krone, Oliver; Frölich, Kai; Will, Hans; Sirma, Hüseyin

2003-01-01

All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation. PMID:12525630

New hepatitis B virus of cranes that has an unexpected broad host range.

PubMed

Prassolov, Alexej; Hohenberg, Heinz; Kalinina, Tatyana; Schneider, Carola; Cova, Lucyna; Krone, Oliver; Frölich, Kai; Will, Hans; Sirma, Hüseyin

2003-02-01

All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation.

Caveolin1 Identifies a Specific Subpopulation of Cerebral Cortex Callosal Projection Neurons (CPN) Including Dual Projecting Cortical Callosal/Frontal Projection Neurons (CPN/FPN)

PubMed Central

2018-01-01

Abstract The neocortex is composed of many distinct subtypes of neurons that must form precise subtype-specific connections to enable the cortex to perform complex functions. Callosal projection neurons (CPN) are the broad population of commissural neurons that connect the cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes and connectivity is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We identify in mouse that the lipid-bound scaffolding domain protein Caveolin 1 (CAV1) is specifically expressed by a unique subpopulation of Layer V CPN that maintain dual ipsilateral frontal projections to premotor cortex. CAV1 is expressed by over 80% of these dual projecting callosal/frontal projection neurons (CPN/FPN), with expression peaking early postnatally as axonal and dendritic targets are being reached and refined. CAV1 is localized to the soma and dendrites of CPN/FPN, a unique population of neurons that shares information both between hemispheres and with premotor cortex, suggesting function during postmitotic development and refinement of these neurons, rather than in their specification. Consistent with this, we find that Cav1 function is not necessary for the early specification of CPN/FPN, or for projecting to their dual axonal targets. CPN subtype-specific expression of Cav1 identifies and characterizes a first molecular component that distinguishes this functionally unique projection neuron population, a population that expands in primates, and is prototypical of additional dual and higher-order projection neuron subtypes. PMID:29379878

Identifying the determinants of premature mortality in Russia: overcoming a methodological challenge.

PubMed

Tomkins, Susannah; Shkolnikov, Vladimir; Andreev, Evgueni; Kiryanov, Nikolay; Leon, David A; McKee, Martin; Saburova, Lyudmila

2007-11-28

It is thought that excessive alcohol consumption is related to the high mortality among working age men in Russia. Moreover it has been suggested that alcohol is a key proximate driver of the very sharp fluctuations in mortality seen in this group since the mid-1980s. Designing an individual-level study suitable to address the potential acute effects of alcohol consumption on mortality in Russia has posed a challenge to epidemiologists, especially because of the need to identify factors that could underlie the rapid changes up and down in mortality rates that have been such a distinctive feature of the Russian mortality crisis. In order to address this study question which focuses on exposures acting shortly before sudden death, a cohort would be unfeasibly large and would suffer from recruitment bias. Although the situation in Russia is unusual, with a very high death rate characterised by many sudden and apparently unexpected deaths in young men, the methodological problem is common to research on any cause of death where many deaths are sudden. We describe the development of an innovative approach that has overcome some of these challenges: a case-control study employing proxy informants and external data sources to collect information about proximate determinants of mortality. This offers a set of principles that can be adopted by epidemiologists studying sudden and unexpected deaths in other settings.

The Unexpected Effects of Inclusion on the Families of Students with Learning Disabilities: A Focus-Group Study

ERIC Educational Resources Information Center

Dyson, Lily L.

2007-01-01

This study investigated the unexpected effects of inclusion on the families of students with learning disabilities. A focus group interview was conducted with 13 parents who have children with learning disabilities. The children's ages ranged from 5 to 24 years. Findings are reported regarding participants' comments in response to two guiding…

Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

PubMed

Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher; Bagnall, Richard D; Sisodiya, Sanjay; Cooper, Paul N

2016-01-01

Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Classification System for the Sudden Unexpected Infant Death Case Registry and its Application

PubMed Central

Shapiro-Mendoza, Carrie K.; Camperlengo, Lena; Ludvigsen, Rebecca; Cottengim, Carri; Anderson, Robert N.; Andrew, Thomas; Covington, Theresa; Hauck, Fern R.; Kemp, James; MacDorman, Marian

2015-01-01

Sudden unexpected infant deaths (SUID) accounted for 1 in 3 postneonatal deaths in 2010. Sudden infant death syndrome and accidental sleep-related suffocation are among the most frequently reported types of SUID. The causes of these SUID usually are not obvious before a medico-legal investigation and may remain unexplained even after investigation. Lack of consistent investigation practices and an autopsy marker make it difficult to distinguish sudden infant death syndrome from other SUID. Standardized categories might assist in differentiating SUID subtypes and allow for more accurate monitoring of the magnitude of SUID, as well as an enhanced ability to characterize the highest risk groups. To capture information about the extent to which cases are thoroughly investigated and how factors like unsafe sleep may contribute to deaths, CDC created a multistate SUID Case Registry in 2009. As part of the registry, the Centers for Disease Control and Prevention developed a classification system that recognizes the uncertainty about how suffocation or asphyxiation may contribute to death and that accounts for unknown and incomplete information about the death scene and autopsy. This report describes the classification system, including its definitions and decision-making algorithm, and applies the system to 436 US SUID cases that occurred in 2011 and were reported to the registry. These categories, although not replacing official cause-of-death determinations, allow local and state programs to track SUID subtypes, creating a valuable tool to identify gaps in investigation and inform SUID reduction strategies. PMID:24913798

A method for identifying color vision deficiency malingering.

PubMed

Pouw, Andrew; Karanjia, Rustum; Sadun, Alfredo

2017-03-01

To propose a new test to identify color vision deficiency malingering. An online survey was distributed to 130 truly color vision deficient participants and 160 participants willing to simulate color vision deficiency. The survey contained three sets of six color-adjusted versions of the standard Ishihara color plates each, as well as one set of six control plates. The plates that best discriminated both participant groups were selected for a "balanced" test emphasizing both sensitivity and specificity. A "specific" test that prioritized high specificity was also created by selecting from these plates. Statistical measures of the test (sensitivity, specificity, and Youden index) were assessed at each possible cut-off threshold, and a receiver operating characteristic (ROC) function with its area under the curve (AUC) charted. The redshift plate set was identified as having the highest difference of means between groups (-58%, CI: -64 to -52%), as well as the widest gap between group modes. Statistical measures of the "balanced" test show an optimal cut-off of at least two incorrectly identified plates to suggest malingering (Youden index: 0.773, sensitivity: 83.3%, specificity: 94.0%, AUC of ROC 0.918). The "specific" test was able to identify color vision deficiency simulators with a specificity of 100% when using a cut-off of at least two incorrectly identified plates (Youden index 0.599, sensitivity 59.9%, specificity 100%, AUC of ROC 0.881). Our proposed test for identifying color vision deficiency malingering demonstrates a high degree of reliability with AUCs of 0.918 and 0.881 for the "balanced" and "specific" tests, respectively. A cut-off threshold of at least two missed plates on the "specific" test was able to identify color vision deficiency simulators with 100% specificity.

Variola virus-specific diagnostic assays: characterization, sensitivity, and specificity.

PubMed

Kondas, Ashley V; Olson, Victoria A; Li, Yu; Abel, Jason; Laker, Miriam; Rose, Laura; Wilkins, Kimberly; Turner, Jonathan; Kline, Richard; Damon, Inger K

2015-04-01

A public health response relies upon rapid and reliable confirmation of disease by diagnostic assays. Here, we detail the design and validation of two variola virus-specific real-time PCR assays, since previous assays cross-reacted with newly identified cowpox viruses. The assay specificity must continually be reassessed as other closely related viruses are identified. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Misbheaving Faults: The Expanding Role of Geodetic Imaging in Unraveling Unexpected Fault Slip Behavior

NASA Astrophysics Data System (ADS)

Barnhart, W. D.; Briggs, R.

2015-12-01

Geodetic imaging techniques enable researchers to "see" details of fault rupture that cannot be captured by complementary tools such as seismology and field studies, thus providing increasingly detailed information about surface strain, slip kinematics, and how an earthquake may be transcribed into the geological record. For example, the recent Haiti, Sierra El Mayor, and Nepal earthquakes illustrate the fundamental role of geodetic observations in recording blind ruptures where purely geological and seismological studies provided incomplete views of rupture kinematics. Traditional earthquake hazard analyses typically rely on sparse paleoseismic observations and incomplete mapping, simple assumptions of slip kinematics from Andersonian faulting, and earthquake analogs to characterize the probabilities of forthcoming ruptures and the severity of ground accelerations. Spatially dense geodetic observations in turn help to identify where these prevailing assumptions regarding fault behavior break down and highlight new and unexpected kinematic slip behavior. Here, we focus on three key contributions of space geodetic observations to the analysis of co-seismic deformation: identifying near-surface co-seismic slip where no easily recognized fault rupture exists; discerning non-Andersonian faulting styles; and quantifying distributed, off-fault deformation. The 2013 Balochistan strike slip earthquake in Pakistan illuminates how space geodesy precisely images non-Andersonian behavior and off-fault deformation. Through analysis of high-resolution optical imagery and DEMs, evidence emerges that a single fault map slip as both a strike slip and dip slip fault across multiple seismic cycles. These observations likewise enable us to quantify on-fault deformation, which account for ~72% of the displacements in this earthquake. Nonetheless, the spatial distribution of on- and off-fault deformation in this event is highly spatially variable- a complicating factor for comparisons

Unexpectedly high pressure for molecular dissociation in liquid hydrogen by electronic simulation.

PubMed

Mazzola, Guglielmo; Yunoki, Seiji; Sorella, Sandro

2014-03-19

The study of the high pressure phase diagram of hydrogen has continued with renewed effort for about one century as it remains a fundamental challenge for experimental and theoretical techniques. Here we employ an efficient molecular dynamics based on the quantum Monte Carlo method, which can describe accurately the electronic correlation and treat a large number of hydrogen atoms, allowing a realistic and reliable prediction of thermodynamic properties. We find that the molecular liquid phase is unexpectedly stable, and the transition towards a fully atomic liquid phase occurs at much higher pressure than previously believed. The old standing problem of low-temperature atomization is, therefore, still far from experimental reach.

Unexpectedly high mercury concentration in commercial fish feed

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

Choi, H.; Cech, J. Jr.

1995-12-31

Unexpectedly high mercury was found in a commercial fish pellet which has been widely used to feed fish in laboratory and fish farm settings. Researchers working with fish in mercury studies need to know that fish pellets contain mercury and consider the pellets, influence in their results. Mean mercury concentration in the commercial fish pellet was 47.4 ug/g (ranging from 35 to 56 ug Hg/g). Total mercury (T-Hg) in the blood of Sacramento blackfish (orthodon microlepidotus), fed the commercial feed for 8 months, was determined by inductively coupled plasma-mass spectrometry (ICP-MS). Mean blood T-Hg reached a steady state at 41more » ug Hg/L (ranging from 34 to 51 ug Hg/L) during 5 months of feeding after capture from Clear Lake in California. The accumulation of mercury in blood followed a monoexponential pattern, in accordance with a one-compartment model. There were great variations in mercury levels in blood between individual fishes. The mercury concentrations in the blood did not tend to increase with the growth of the fish. In summary, feed sources of mercury need to be considered in mercury exposure experiments.« less

Electrocardiographic features of sudden unexpected death in epilepsy.

PubMed

Chyou, Janice Y; Friedman, Daniel; Cerrone, Marina; Slater, William; Guo, Yu; Taupin, Daniel; O'Rourke, Sean; Priori, Silvia G; Devinsky, Orrin

2016-07-01

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. We hypothesized that electrocardiography (ECG) features may distinguish SUDEP cases from living subjects with epilepsy. Using a matched case-control design, we compared ECG studies of 12 consecutive cases of SUDEP over 10 years and 22 epilepsy controls matched for age, sex, epilepsy type (focal, generalized, or unknown/mixed type), concomitant antiepileptic, and psychotropic drug classes. Conduction intervals and prevalence of abnormal ventricular conduction diagnosis (QRS ≥110 msec), abnormal ventricular conduction pattern (QRS <110 msec, morphology of incomplete right or left bundle branch block or intraventricular conduction delay), early repolarization, and features of inherited cardiac channelopathies were assessed. Abnormal ventricular conduction diagnosis and pattern distinguished SUDEP cases from matched controls. Abnormal ventricular conduction diagnosis was present in two cases and no controls. Abnormal ventricular conduction pattern was more common in cases than controls (58% vs. 18%, p = 0.04). Early repolarization was similarly prevalent in cases and controls, but the overall prevalence exceeded that of published community-based cohorts. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Single-cell transcriptomes identify human islet cell signatures and reveal cell-type–specific expression changes in type 2 diabetes

PubMed Central

Bolisetty, Mohan; Kursawe, Romy; Sun, Lili; Sivakamasundari, V.; Kycia, Ina

2017-01-01

Blood glucose levels are tightly controlled by the coordinated action of at least four cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 (T2D) diabetes. Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet (dys)function, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single-cell transcriptomes for 638 cells from nondiabetic (ND) and T2D human islet samples. Analyses of ND single-cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single-cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell-type–specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis. PMID:27864352

Mapping the mouse Allelome reveals tissue-specific regulation of allelic expression

PubMed Central

Andergassen, Daniel; Dotter, Christoph P; Wenzel, Daniel; Sigl, Verena; Bammer, Philipp C; Muckenhuber, Markus; Mayer, Daniela; Kulinski, Tomasz M; Theussl, Hans-Christian; Penninger, Josef M; Bock, Christoph; Barlow, Denise P; Pauler, Florian M; Hudson, Quanah J

2017-01-01

To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta. DOI: http://dx.doi.org/10.7554/eLife.25125.001 PMID:28806168

Identifying Gender-Specific Developmental Trajectories of Nonviolent and Violent Delinquency from Adolescence to Young Adulthood

PubMed Central

Zheng, Yao; Cleveland, H. Harrington

2013-01-01

Most research examining gender differences in developmental trajectories of antisocial behavior does not consider subtypes of antisocial behavior and is difficult to generalize due to small nonrepresentative samples. The current study investigated gender difference in developmental trajectories from adolescence to young adulthood while addressing those limitations. Analyses were limited to respondents ages 15 and 16 in wave 1 (16–17 in wave 2, and 21–22 in wave 3) of the National Longitudinal Study of Adolescent Health (n = 6244, 49.5% males). Self-report nonviolent and violent delinquencies were simultaneously entered into latent class analysis. Four latent classes were identified: low, desister, decliner, and chronic (male-only). In addition to finding a male-specific chronic class, gender differences included differences in levels of nonviolent and violent delinquency between synonymous classes of males and females, and differences in prevalence of classes across genders. Neighborhood disadvantage and family support predicted trajectories. PMID:23375843

"Re"storying the Present by "Re"visiting the Past: Unexpected Moments of Discovery and Illumination through Museum Learning

ERIC Educational Resources Information Center

Kawalilak, Colleen; Groen, Janet

2016-01-01

Two adult educators, guided by autoethnography as methodology, share the restorying of their own lifelong learning narratives and unexpected insights gained from having experienced the powerful potential of museum learning and culture. Having previously regarded museum visits as an experience that primarily tapped the intellectual, cognitive…

Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.

PubMed

Tromp, Angelino T; Van Gent, Michiel; Abrial, Pauline; Martin, Amandine; Jansen, Joris P; De Haas, Carla J C; Van Kessel, Kok P M; Bardoel, Bart W; Kruse, Elisabeth; Bourdonnay, Emilie; Boettcher, Michael; McManus, Michael T; Day, Christopher J; Jennings, Michael P; Lina, Gérard; Vandenesch, François; Van Strijp, Jos A G; Jan Lebbink, Robert; Haas, Pieter-Jan A; Henry, Thomas; Spaan, András N

2018-05-07

The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1 KI ) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1 KI mice. Compared to humans, murine hC5aR1 KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1 KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.

Should I Stay or Should I Go? Attentional Disengagement from Visually Unique and Unexpected Items at Fixation

ERIC Educational Resources Information Center

Brockmole, James R.; Boot, Walter R.

2009-01-01

Distinctive aspects of a scene can capture attention even when they are irrelevant to one's goals. The authors address whether visually unique, unexpected, but task-irrelevant features also tend to hold attention. Observers searched through displays in which the color of each item was irrelevant. At the start of search, all objects changed color.…

Unexpected Early Triassic marine ecosystem and the rise of the Modern evolutionary fauna

PubMed Central

Brayard, Arnaud; Krumenacker, L. J.; Botting, Joseph P.; Jenks, James F.; Bylund, Kevin G.; Fara, Emmanuel; Vennin, Emmanuelle; Olivier, Nicolas; Goudemand, Nicolas; Saucède, Thomas; Charbonnier, Sylvain; Romano, Carlo; Doguzhaeva, Larisa; Thuy, Ben; Hautmann, Michael; Stephen, Daniel A.; Thomazo, Christophe; Escarguel, Gilles

2017-01-01

In the wake of the end-Permian mass extinction, the Early Triassic (~251.9 to 247 million years ago) is portrayed as an environmentally unstable interval characterized by several biotic crises and heavily depauperate marine benthic ecosystems. We describe a new fossil assemblage—the Paris Biota—from the earliest Spathian (middle Olenekian, ~250.6 million years ago) of the Bear Lake area, southeastern Idaho, USA. This highly diversified assemblage documents a remarkably complex marine ecosystem including at least seven phyla and 20 distinct metazoan orders, along with algae. Most unexpectedly, it combines early Paleozoic and middle Mesozoic taxa previously unknown from the Triassic strata, among which are primitive Cambrian-Ordovician leptomitid sponges (a 200–million year Lazarus taxon) and gladius-bearing coleoid cephalopods, a poorly documented group before the Jurassic (~50 million years after the Early Triassic). Additionally, the crinoid and ophiuroid specimens show derived anatomical characters that were thought to have evolved much later. Unlike previous works that suggested a sluggish postcrisis recovery and a low diversity for the Early Triassic benthic organisms, the unexpected composition of this exceptional assemblage points toward an early and rapid post-Permian diversification for these clades. Overall, it illustrates a phylogenetically diverse, functionally complex, and trophically multileveled marine ecosystem, from primary producers up to top predators and potential scavengers. Hence, the Paris Biota highlights the key evolutionary position of Early Triassic fossil ecosystems in the transition from the Paleozoic to the Modern marine evolutionary fauna at the dawn of the Mesozoic era. PMID:28246643

Unexpected Early Triassic marine ecosystem and the rise of the Modern evolutionary fauna.

PubMed

Brayard, Arnaud; Krumenacker, L J; Botting, Joseph P; Jenks, James F; Bylund, Kevin G; Fara, Emmanuel; Vennin, Emmanuelle; Olivier, Nicolas; Goudemand, Nicolas; Saucède, Thomas; Charbonnier, Sylvain; Romano, Carlo; Doguzhaeva, Larisa; Thuy, Ben; Hautmann, Michael; Stephen, Daniel A; Thomazo, Christophe; Escarguel, Gilles

2017-02-01

In the wake of the end-Permian mass extinction, the Early Triassic (~251.9 to 247 million years ago) is portrayed as an environmentally unstable interval characterized by several biotic crises and heavily depauperate marine benthic ecosystems. We describe a new fossil assemblage-the Paris Biota-from the earliest Spathian (middle Olenekian, ~250.6 million years ago) of the Bear Lake area, southeastern Idaho, USA. This highly diversified assemblage documents a remarkably complex marine ecosystem including at least seven phyla and 20 distinct metazoan orders, along with algae. Most unexpectedly, it combines early Paleozoic and middle Mesozoic taxa previously unknown from the Triassic strata, among which are primitive Cambrian-Ordovician leptomitid sponges (a 200-million year Lazarus taxon) and gladius-bearing coleoid cephalopods, a poorly documented group before the Jurassic (~50 million years after the Early Triassic). Additionally, the crinoid and ophiuroid specimens show derived anatomical characters that were thought to have evolved much later. Unlike previous works that suggested a sluggish postcrisis recovery and a low diversity for the Early Triassic benthic organisms, the unexpected composition of this exceptional assemblage points toward an early and rapid post-Permian diversification for these clades. Overall, it illustrates a phylogenetically diverse, functionally complex, and trophically multileveled marine ecosystem, from primary producers up to top predators and potential scavengers. Hence, the Paris Biota highlights the key evolutionary position of Early Triassic fossil ecosystems in the transition from the Paleozoic to the Modern marine evolutionary fauna at the dawn of the Mesozoic era.

Mapping the fine specificity of ABO monoclonal reagents with A and B type-specific function-spacer-lipid constructs in kodecytes and inkjet printed on paper.

PubMed

Barr, Katie; Korchagina, Elena; Ryzhov, Ivan; Bovin, Nicolai; Henry, Stephen

2014-10-01

Monoclonal (MoAb) reagents are routinely used and are usually very reliable for the serologic determination of ABO blood types. However, the fine specificity and cross-reactivity of these reagents are often unknown, particularly against synthetic antigens used in some diagnostic assays. If nonserologic assays or very sensitive techniques other than those specifically prescribed by the manufacturer are used, then there is a risk of incorrect interpretation of results. Forty-seven MoAbs and two polyclonal ABO reagents were tested against red blood cell (RBC) kodecytes prepared with A trisaccharide, A Type 1, A Type 2, A Type 3, A Type 4, B trisaccharide, B Type 1, B Type 2, acquired B trisaccharide, and Le(a) trisaccharide function-spacer-lipid (FSL) constructs. Natural RBCs were tested in parallel. In addition these FSL constructs were printed onto paper with a desktop inkjet printer and used in a novel immunoassay that identifies reactivity through the appearance of alphanumeric characters. Mapping of MoAbs with kodecytes and printed FSL constructs revealed a series of broad recognition patterns. All ABO MoAbs tested were reactive with the RBC dominant Type 2 ABO antigens. Unexpectedly some anti-A reagents were reactive against the B Type 1 antigen, while others were poorly reactive with trisaccharide antigens. All ABO MoAbs detect the RBC dominant Type 2 ABO antigens; however, some reagents may show minor reactivity with inappropriate blood group antigens, which needs to be considered when using these reagents in alternative or highly sensitive analytic systems. © 2014 AABB.

Analysis of SEER Adenosquamous Carcinoma Data to Identify Cause Specific Survival Predictors and Socioeconomic Disparities.

PubMed

Cheung, Rex

2016-01-01

This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) adenosquamous carcinoma data to identify predictive models and potential disparities in outcome. This study analyzed socio-economic, staging and treatment factors available in the SEER database for adenosquamous carcinoma. For the risk modeling, each factor was fitted by a generalized linear model to predict the cause specific survival. An area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A total of 20,712 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 54.2 (78.4) months. Some 2/3 of the patients were female. The mean (S.D.) age was 63 (13.8) years. SEER stage was the most predictive factor of outcome (ROC area of 0.71). 13.9% of the patients were un-staged and had risk of cause specific death of 61.3% that was higher than the 45.3% risk for the regional disease and lower than the 70.3% for metastatic disease. Sex, site, radiotherapy, and surgery had ROC areas of about 0.55-0.65. Rural residence and race contributed to socioeconomic disparity for treatment outcome. Radiotherapy was underused even with localized and regional stages when the intent was curative. This under use was most pronounced in older patients. Anatomic stage was predictive and useful in treatment selection. Under-staging may have contributed to poor outcome.

Distinct ontogenic and regional expressions of newly identified Cajal-Retzius cell-specific genes during neocorticogenesis.

PubMed

Yamazaki, Hiroshi; Sekiguchi, Mariko; Takamatsu, Masako; Tanabe, Yasuto; Nakanishi, Shigetada

2004-10-05

Cajal-Retzius (CR) cells are early-generated transient neurons and are important in the regulation of cortical neuronal migration and cortical laminar formation. Molecular entities characterizing the CR cell identity, however, remain largely elusive. We purified mouse cortical CR cells expressing GFP to homogeneity by fluorescence-activated cell sorting and examined a genome-wide expression profile of cortical CR cells at embryonic and postnatal periods. We identified 49 genes that exceeded hybridization signals by >10-fold in CR cells compared with non-CR cells at embryonic day 13.5, postnatal day 2, or both. Among these CR cell-specific genes, 25 genes, including the CR cell marker genes such as the reelin and calretinin genes, are selectively and highly expressed in both embryonic and postnatal CR cells. These genes, which encode generic properties of CR cell specificity, are eminently characterized as modulatory composites of voltage-dependent calcium channels and sets of functionally related cellular components involved in cell migration, adhesion, and neurite extension. Five genes are highly expressed in CR cells at the early embryonic period and are rapidly down-regulated thereafter. Furthermore, some of these genes have been shown to mark two distinctly different focal regions corresponding to the CR cell origins. At the late prenatal and postnatal periods, 19 genes are selectively up-regulated in CR cells. These genes include functional molecules implicated in synaptic transmission and modulation. CR cells thus strikingly change their cellular phenotypes during cortical development and play a pivotal role in both corticogenesis and cortical circuit maturation.

Cell Death Pathways in Mutant Rhodopsin Rat Models Identifies Genotype-Specific Targets Controlling Retinal Degeneration.

PubMed

Viringipurampeer, Ishaq A; Gregory-Evans, Cheryl Y; Metcalfe, Andrew L; Bashar, Emran; Moritz, Orson L; Gregory-Evans, Kevin

2018-06-18

Retinitis pigmentosa (RP) is a group of inherited neurological disorders characterized by rod photoreceptor cell death, followed by secondary cone cell death leading to progressive blindness. Currently, there are no viable treatment options for RP. Due to incomplete knowledge of the molecular signaling pathways associated with RP pathogenesis, designing therapeutic strategies remains a challenge. In particular, preventing secondary cone photoreceptor cell loss is a key goal in designing potential therapies. In this study, we identified the main drivers of rod cell death and secondary cone loss in the transgenic S334ter rhodopsin rat model, tested the efficacy of specific cell death inhibitors on retinal function, and compared the effect of combining drugs to target multiple pathways in the S334ter and P23H rhodopsin rat models. The primary driver of early rod cell death in the S334ter model was a caspase-dependent process, whereas cone cell death occurred though RIP3-dependent necroptosis. In comparison, rod cell death in the P23H model was via necroptotic signaling, whereas cone cell loss occurred through inflammasome activation. Combination therapy of four drugs worked better than the individual drugs in the P23H model but not in the S334ter model. These differences imply that treatment modalities need to be tailored for each genotype. Taken together, our data demonstrate that rationally designed genotype-specific drug combinations will be an important requisite to effectively target primary rod cell loss and more importantly secondary cone survival.

Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue.

PubMed

Fritsch, Michael K; Bridge, Julia A; Schuster, Amy E; Perlman, Elizabeth J; Argani, Pedram

2003-01-01

Pediatric small round cell tumors still pose tremendous diagnostic problems. In difficult cases, the ability to detect tumor-specific gene fusion transcripts for several of these neoplasms, including Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumor (DSRCT) using reverse transcriptase-polymerase chain reaction (RT-PCR), can be extremely helpful. Few studies to date, however, have systematically examined several different tumor types for the presence of multiple different fusion transcripts in order to determine the specificity and sensitivity of the RT-PCR method, and no study has addressed this issue for formalin-fixed material. The objectives of this study were to address the specificity, sensitivity, and practicality of such an assay applied strictly to formalin-fixed tissue blocks. Our results demonstrate that, for these tumors, the overall sensitivity for detecting each fusion transcript is similar to that reported in the literature for RT-PCR on fresh or formalin-fixed tissues. The specificity of the assay is very high, being essentially 100% for each primer pair when interpreting the results from visual inspection of agarose gels. However, when these same agarose gels were examined using Southern blotting, a small number of tumors also yielded reproducibly detectable weak signals for unexpected fusion products, in addition to a strong signal for the expected fusion product. Fluorescence in situ hybridization (FISH) studies in one such case indicated that a rearrangement that would account for the unexpected fusion was not present, while another case was equivocal. The overall specificity for each primer pair used in this assay ranged from 94 to 100%. Therefore, RT-PCR using formalin-fixed paraffin-embedded tissue sections can be used to detect chimeric transcripts as a reliable, highly sensitive, and highly specific diagnostic assay. However, we

Unexpected pulmonary hypertensive crisis after surgery for ocular malignant melanoma.

PubMed

Sato, Kaori; Saji, Tsutomu; Kaneko, Taku; Takahashi, Kei; Sugi, Kaoru

2014-11-24

To report a case of unexpected pulmonary hypertensive crisis caused by endothelin release from melanoma cells after surgery for choroidal melanoma. A 56-year-old man suddenly developed dyspnea after resection of choroidal melanoma. Worsening hypoxia required intensive treatment, including percutaneous cardiopulmonary support, after which a series of tests were immediately performed. The tentative diagnosis was idiopathic pulmonary arterial hypertension. Previous studies noted a significant association between melanoma and endothelin (ET)-1. We hypothesized that a substantial amount of ET-1 had been released from malignant melanoma cells during resection, thus triggering the pulmonary hypertensive crisis in our patient. The patient fully recovered after intensive treatment and administration of the endothelin receptor antagonist bosentan. The success of bosentan treatment, along with the extremely high level of ET-1 on pathologic analysis, confirmed our hypothesis regarding the increase in plasma ET-1 level. Copyright © 2014 Elsevier Inc. All rights reserved.

Identifying N6-methyladenosine sites using multi-interval nucleotide pair position specificity and support vector machine

NASA Astrophysics Data System (ADS)

Xing, Pengwei; Su, Ran; Guo, Fei; Wei, Leyi

2017-04-01

N6-methyladenosine (m6A) refers to methylation of the adenosine nucleotide acid at the nitrogen-6 position. It plays an important role in a series of biological processes, such as splicing events, mRNA exporting, nascent mRNA synthesis, nuclear translocation and translation process. Numerous experiments have been done to successfully characterize m6A sites within sequences since high-resolution mapping of m6A sites was established. However, as the explosive growth of genomic sequences, using experimental methods to identify m6A sites are time-consuming and expensive. Thus, it is highly desirable to develop fast and accurate computational identification methods. In this study, we propose a sequence-based predictor called RAM-NPPS for identifying m6A sites within RNA sequences, in which we present a novel feature representation algorithm based on multi-interval nucleotide pair position specificity, and use support vector machine classifier to construct the prediction model. Comparison results show that our proposed method outperforms the state-of-the-art predictors on three benchmark datasets across the three species, indicating the effectiveness and robustness of our method. Moreover, an online webserver implementing the proposed predictor has been established at http://server.malab.cn/RAM-NPPS/. It is anticipated to be a useful prediction tool to assist biologists to reveal the mechanisms of m6A site functions.

Identifying Country-Specific Cultures of Physics Education: A differential item functioning approach

NASA Astrophysics Data System (ADS)

Mesic, Vanes

2012-11-01

In international large-scale assessments of educational outcomes, student achievement is often represented by unidimensional constructs. This approach allows for drawing general conclusions about country rankings with respect to the given achievement measure, but it typically does not provide specific diagnostic information which is necessary for systematic comparisons and improvements of educational systems. Useful information could be obtained by exploring the differences in national profiles of student achievement between low-achieving and high-achieving countries. In this study, we aimed to identify the relative weaknesses and strengths of eighth graders' physics achievement in Bosnia and Herzegovina in comparison to the achievement of their peers from Slovenia. For this purpose, we ran a secondary analysis of Trends in International Mathematics and Science Study (TIMSS) 2007 data. The student sample consisted of 4,220 students from Bosnia and Herzegovina and 4,043 students from Slovenia. After analysing the cognitive demands of TIMSS 2007 physics items, the correspondent differential item functioning (DIF)/differential group functioning contrasts were estimated. Approximately 40% of items exhibited large DIF contrasts, indicating significant differences between cultures of physics education in Bosnia and Herzegovina and Slovenia. The relative strength of students from Bosnia and Herzegovina showed to be mainly associated with the topic area 'Electricity and magnetism'. Classes of items which required the knowledge of experimental method, counterintuitive thinking, proportional reasoning and/or the use of complex knowledge structures proved to be differentially easier for students from Slovenia. In the light of the presented results, the common practice of ranking countries with respect to universally established cognitive categories seems to be potentially misleading.

[Unexpected outings of Alzheimer patients living in retirement homes: Therapeutic perspectives].

PubMed

Brossard, F; Caron, R

2016-10-01

Various behavior disorders can occur during Alzheimer's disease, in particular unexpected outings. This article aims at understanding the diverse mechanisms present during a "runaway" episode, which can manifest in an acute way. The authors bring to light through clinical examples what is at work from a psychological perspective in order to create new accompaniment methods. First, the authors reviewed the literature on runaway episodes in order to point out necessary themes for reflection. Then, from a Freudian theoretical model, they brought to light four fundamental mechanisms: hallucinations, false recognition, non-recognition, and recognition. These are mainly, although not exhaustively, understood from perceptions, memory-traces, indications of quality, and memories. This theory was questioned by means of presented clinical cases. Various post-Freudian models allowed the authors to emphasize the pathological experience in the role of perceptions and the functions, which come into play in the psychic economy. By going back and forth between theory and clinical cases, the authors underline the importance of perception in the phenomenon of unexpected outings. Finally, the Lacanian psychoanalytical theories provide a framework to question clinical cases but also provide answers to the criticisms found in the diverse reserved models. Through this study the authors hypothesize that the runaway episodes are not senseless but result from the interaction between the effects of the brain damage and the anxiety, which they arouse in the subjectivity of the person suffering from Alzheimer's. Leaning on false-recognitions, hallucinations, and non-recognitions such as were described in "Project for a scientific psychology", the authors put forward the hypothesis that these mechanisms express themselves in an imaginary relation, as in psychosis. The question of whether the runaway episodes of Alzheimer's sufferers can be classified as psychotic breakouts with a loss of touch

A rapid method to identify Salmonella enterica serovar Gallinarum biovar Pullorum using a specific target gene ipaJ.

PubMed

Xu, Lijuan; Liu, Zijian; Li, Yang; Yin, Chao; Hu, Yachen; Xie, Xiaolei; Li, Qiuchun; Jiao, Xinan

2018-06-01

Salmonella enterica serovar Gallinarum biovar Pullorum (S. Pullorum) is the pathogen of pullorum disease, which leads to severe economic losses in many developing countries. Traditional methods to identify S. enterica have relied on biochemical reactions and serotyping, which are time-consuming with accurate identification if properly carried out. In this study, we developed a rapid polymerase chain reaction (PCR) method targeting the specific gene ipaJ to detect S. Pullorum. Among the 650 S. Pullorum strains isolated from 1962 to 2016 all over China, 644 strains were identified to harbour ipaJ gene in the plasmid pSPI12, accounting for a detection rate of 99.08%. Six strains were ipaJ negative because pSPI12 was not found in these strains according to whole genome sequencing results. There was no cross-reaction with other Salmonella serotypes, including Salmonella enterica serovar Gallinarum biovar Gallinarum (S. Gallinarum), which show a close genetic relationship with S. Pullorum. This shows that the PCR method could distinguish S. Gallinarum from S. Pullorum in one-step PCR without complicated biochemical identification. The limit of detection of this PCR method was as low as 90 fg/μl or 10 2 CFU, which shows a high sensitivity. Moreover, this method was applied to identify Salmonella isolated from the chicken farm and the results were consistent with what we obtained from biochemical reactions and serotyping. Together, all the results demonstrated that this one-step PCR method is simple and feasible to efficiently identify S. Pullorum.

Genetic investigation of sudden unexpected death in epilepsy cohort by panel target resequencing.

PubMed

Coll, Monica; Allegue, Catarina; Partemi, Sara; Mates, Jesus; Del Olmo, Bernat; Campuzano, Oscar; Pascali, Vincenzo; Iglesias, Anna; Striano, Pasquale; Oliva, Antonio; Brugada, Ramon

2016-03-01

Sudden unexpected death in epilepsy (SUDEP) is defined as the abrupt, no traumatic, witnessed or unwitnessed death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus (seizure duration ≥ 30 min or seizures without recovery), and in which postmortem examination does not reveal a cause of death. Although the physiopathological mechanisms that underlie SUDEP remain to be clarified, the genetic background has been described to play a role in this disorder. Pathogenic variants in genes associated with epilepsy and encoding cardiac ion channels could explain the SUDEP phenotype. To test this we use the next-generation sequencing technology to sequence a cohort of SUDEP cases and its translation into clinical and forensic fields. A panel target resequencing was used to study 14 SUDEP cases from both postmortem (2 cases) and from living patients (12 cases). Genes already associated with SUDEP and also candidate genes had been investigated. Overall, 24 rare genetic variants were identified in 13 SUDEP cases. Four cases showed rare variants with complete segregation in the SCN1A, FBN1, HCN1, SCN4A, and EFHC1 genes, and one case with a rare variant in KCNQ1 gene showed incomplete pattern of inheritance. In four cases, rare variants were detected in CACNA1A, SCN11A and SCN10A, and KCNQ1 genes, but familial segregation was not possible due to lack of DNA from relatives. Finally, in the four remaining cases, the rare variants did not segregate in the family. This study confirms the link between epilepsy, sudden death, and cardiac disease. In addition, we identified new potential candidate genes for SUDEP: FBN1, HCN1, SCN4A, EFHC1, CACNA1A, SCN11A, and SCN10A. Further confirmation in larger cohorts will be necessary especially if genetic screening for SUDEP is applied to forensic and clinical medicine. Nevertheless, this study supports the emerging concept of a genetically

Identifying Decadal to Multi-decadal Variability in the Pacific by Empirical Mode Decomposition

NASA Astrophysics Data System (ADS)

Sommers, L. A.; Hamlington, B.; Cheon, S. H.

2016-12-01

Large scale climate variability in the Pacific Ocean like that associated with ENSO and the Pacific Decadal Oscillation (PDO) has been shown to have a significant impact on climate and sea level across a range of timescales. The changes related to these climate signals have worldwide impacts on fisheries, weather, and precipitation patterns among others. Understanding these inter-annual to multi-decadal oscillations is imperative to longer term climate forecasts and understanding how climate will behave, and its effect on changes in sea level. With a 110-year reconstruction of sea level, we examine decadal to multi-decadal variability seen in the sea level fluctuations in the Pacific Ocean. Using empirical mode decomposition (EMD), we break down regional sea level into a series of intrinsic mode functions (IMFs) and attempt attribution of these IMFs to specific climate modes of variability. In particular, and not unexpectedly, we identify IMFs associated with the PDO, finding correlations between the PDO Index and IMFs in the Pacific Ocean upwards of 0.6-0.8 over the 110-year reconstructed record. Perhaps more significantly, we also find evidence of a longer multi-decadal signal ( 50-60 years) in the higher order IMFs. This lower frequency variability has been suggested in previous literature as influencing GMSL, but here we find a regional pattern associated with this multi-decadal signal. By identifying and separating these periodic climate signals, we can gain a better understanding of how the sea level variability associated with these modes can impact sea level on short timescales and serve to exacerbate the effects of long-term sea level change.

Malaria's contribution to World War One - the unexpected adversary.

PubMed

Brabin, Bernard J

2014-12-16

Malaria in the First World War was an unexpected adversary. In 1914, the scientific community had access to new knowledge on transmission of malaria parasites and their control, but the military were unprepared, and underestimated the nature, magnitude and dispersion of this enemy. In summarizing available information for allied and axis military forces, this review contextualizes the challenge posed by malaria, because although data exist across historical, medical and military documents, descriptions are fragmented, often addressing context specific issues. Military malaria surveillance statistics have, therefore, been summarized for all theatres of the War, where available. These indicated that at least 1.5 million solders were infected, with case fatality ranging from 0.2 -5.0%. As more countries became engaged in the War, the problem grew in size, leading to major epidemics in Macedonia, Palestine, Mesopotamia and Italy. Trans-continental passages of parasites and human reservoirs of infection created ideal circumstances for parasite evolution. Details of these epidemics are reviewed, including major epidemics in England and Italy, which developed following home troop evacuations, and disruption of malaria control activities in Italy. Elsewhere, in sub-Saharan Africa many casualties resulted from high malaria exposure combined with minimal control efforts for soldiers considered semi-immune. Prevention activities eventually started but were initially poorly organized and dependent on local enthusiasm and initiative. Nets had to be designed for field use and were fundamental for personal protection. Multiple prevention approaches adopted in different settings and their relative utility are described. Clinical treatment primarily depended on quinine, although efficacy was poor as relapsing Plasmodium vivax and recrudescent Plasmodium falciparum infections were not distinguished and managed appropriately. Reasons for this are discussed and the clinical trial data

Language and music: differential hemispheric dominance in detecting unexpected errors in the lyrics and melody of memorized songs.

PubMed

Yasui, Takuya; Kaga, Kimitaka; Sakai, Kuniyoshi L

2009-02-01

Using magnetoencephalography (MEG), we report here the hemispheric dominance of the auditory cortex that is selectively modulated by unexpected errors in the lyrics and melody of songs (lyrics and melody deviants), thereby elucidating under which conditions the lateralization of auditory processing changes. In experiment 1 using familiar songs, we found that the dipole strength of responses to the lyrics deviants was left-dominant at 140 ms (M140), whereas that of responses to the melody deviants was right-dominant at 130 ms (M130). In experiment 2 using familiar songs with a constant syllable or pitch, the dipole strength of frequency mismatch negativity elicited by oddballs was left-dominant. There were significant main effects of experiment (1 and 2) for the peak latencies and for the coordinates of the dipoles, indicating that the M140 and M130 were not the frequency mismatch negativity. In experiment 3 using newly memorized songs, the right-dominant M130 was observed only when the presented note was unexpected one, independent of perceiving unnatural pitch transitions (i.e., perceptual saliency) and of selective attention to the melody of songs. The consistent right-dominance of the M130 between experiments 1 and 3 suggests that the M130 in experiment 1 is due to unexpected notes deviating from well-memorized songs. On the other hand, the left-dominant M140 was elicited by lyrics deviants, suggesting the influence of top-down linguistic information and the memory of the familiar songs. We thus conclude that the left- lateralized M140 and right-lateralized M130 reflect the expectation based on top-down information of language and music, respectively.

Unexpectedly high mercury level in pelleted commercial fish feed

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

Choi, M.H.; Cech, J.J. Jr.

1998-10-01

An unexpectedly high mercury (Hg) level was found in a pelleted commercial fish feed used to feed fish in laboratory and fish farm settings. Mean total Hg (T-Hg) concentration in the commercial fish pellets was 66 ppb. Mean total selenium (T-Se) concentration in the pellets was 1,120 ppb (ranging from 790 to 1,360 ppb). Total Hg and Se in the whole blood of Sacramento blackfish and in the fish feed were determined by inductively coupled plasma-mass spectrometry (ICP-MS). During a 10-week sampling period T-Hg in blood fluctuated between 35 and 56 ppb. A highly significant, positive correlation was found betweenmore » T-Hg in the fish blood and in the fish feed through the sampling period. On the other hand, no correlation was found between T-Se in the fish feed and T-Hg or T-Se blood level. Researchers working with fish in Hg studies need to know that fish pellets may contain Hg and to consider the influence of these pellets in their results.« less

Unexpectedly large charge radii of neutron-rich calcium isotopes

DOE PAGES

Garcia Ruiz, R. F.; Bissell, M. L.; Blaum, K.; ...

2016-02-08

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

Treatments for the prevention of Sudden Unexpected Death in Epilepsy (SUDEP).

PubMed

Maguire, Melissa J; Jackson, Cerian F; Marson, Anthony G; Nolan, Sarah J

2016-07-19

Sudden Unexpected Death in Epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic or non-drowning death of people with epilepsy, with or without evidence of a seizure, excluding documented status epilepticus and in whom postmortem examination does not reveal a structural or toxicological cause for death. SUDEP has a reported incidence of 1 to 2 per 1000 patient years and represents the most common epilepsy-related cause of death. The presence and frequency of generalised tonic-clonic seizures (GTCS), male sex, early age of seizure onset, duration of epilepsy, and polytherapy are all predictors of risk of SUDEP. The exact pathophysiology of SUDEP is currently unknown, although GTCS-induced cardiac, respiratory, and brainstem dysfunction appears likely. Appropriately chosen antiepileptic drug treatment can render around 70% of patients free of all seizures. However, around one-third will remain drug refractory despite polytherapy. Continuing seizures place patients at risk of SUDEP, depression, and reduced quality of life. Preventative strategies for SUDEP include reducing the occurrence of GTCS by timely referral for presurgical evaluation in people with lesional epilepsy and advice on lifestyle measures; detecting cardiorespiratory distress through clinical observation and seizure, respiratory, and heart rate monitoring devices; preventing airway obstruction through nocturnal supervision and safety pillows; reducing central hypoventilation through physical stimulation and enhancing serotonergic mechanisms of respiratory regulation using selective serotonin reuptake inhibitors (SSRIs); reducing adenosine and endogenous opioid-induced brain and brainstem depression. To assess the effectiveness of interventions in preventing SUDEP in people with epilepsy by synthesising evidence from randomised controlled trials of interventions and cohort and case-control non-randomised studies. We searched the following databases: Cochrane

An extended data mining method for identifying differentially expressed assay-specific signatures in functional genomic studies.

PubMed

Rollins, Derrick K; Teh, Ailing

2010-12-17

Microarray data sets provide relative expression levels for thousands of genes for a small number, in comparison, of different experimental conditions called assays. Data mining techniques are used to extract specific information of genes as they relate to the assays. The multivariate statistical technique of principal component analysis (PCA) has proven useful in providing effective data mining methods. This article extends the PCA approach of Rollins et al. to the development of ranking genes of microarray data sets that express most differently between two biologically different grouping of assays. This method is evaluated on real and simulated data and compared to a current approach on the basis of false discovery rate (FDR) and statistical power (SP) which is the ability to correctly identify important genes. This work developed and evaluated two new test statistics based on PCA and compared them to a popular method that is not PCA based. Both test statistics were found to be effective as evaluated in three case studies: (i) exposing E. coli cells to two different ethanol levels; (ii) application of myostatin to two groups of mice; and (iii) a simulated data study derived from the properties of (ii). The proposed method (PM) effectively identified critical genes in these studies based on comparison with the current method (CM). The simulation study supports higher identification accuracy for PM over CM for both proposed test statistics when the gene variance is constant and for one of the test statistics when the gene variance is non-constant. PM compares quite favorably to CM in terms of lower FDR and much higher SP. Thus, PM can be quite effective in producing accurate signatures from large microarray data sets for differential expression between assays groups identified in a preliminary step of the PCA procedure and is, therefore, recommended for use in these applications.

Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

PubMed

Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

2017-07-01

Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p < 5×10 -8 ) from the NHGRI-EBI Catalog across seven disease/trait categories: cancer, cardiovascular disease, diabetes, autoimmune disease, psychiatric disease, neurological disease, and anthropometric traits. SNPs were annotated using HaploReg for the eight functional elements across any tissue: DNase sites, expression quantitative trait loci (eQTL), sequence conservation, enhancers, promoters, missense variants, sequence motifs, and protein binding sites. In addition, tissue-specific annotations were considered for brain vs. blood. Disease/trait SNPs were compared to a control set of 4809 SNPs matched to the GWAS SNPs (N = 1639) on allele frequency, gene density, distance to nearest gene, and linkage disequilibrium at ~3:1 ratio. Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

Strategies for identifying new prions in yeast

PubMed Central

MacLea, Kyle S

2011-01-01

The unexpected discovery of two prions, [URE3] and [PSI+], in Saccharomyces cerevisiae led to questions about how many other proteins could undergo similar prion-based structural conversions. However, [URE3] and [PSI+] were discovered by serendipity in genetic screens. Cataloging the full range of prions in yeast or in other organisms will therefore require more systematic search methods. Taking advantage of some of the unique features of prions, various researchers have developed bioinformatic and experimental methods for identifying novel prion proteins. These methods have generated long lists of prion candidates. The systematic testing of some of these prion candidates has led to notable successes; however, even in yeast, where rapid growth rate and ease of genetic manipulation aid in testing for prion activity, such candidate testing is laborious. Development of better methods to winnow the field of prion candidates will greatly aid in the discovery of new prions, both in yeast and in other organisms, and help us to better understand the role of prions in biology. PMID:22052351

Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity in the first sarin gas terrorism.

PubMed

Okudera, H; Morita, H; Iwashita, T; Shibata, T; Otagiri, T; Kobayashi, S; Yanagisawa, N

1997-09-01

This report describes the rescue activities and the exposure of rescue and hospital personnel from the first unexpected nerve gas terrorist attack using sarin (isopropyl methylphophonofluoridate) in the city of Matsumoto at midnight on June 27, 1994. The details of the emergency activities in the disaster were studied based on the records from emergency departments of the affiliated hospitals and records from the firehouse. About 600 people, including residents and rescue staff, were exposed to sarin gas. Fifty-eight residents were admitted to hospitals, and 7 died. Among 95 rescuers and the duty doctor from the doctor car, 8 had mild symptoms of poisoning. All the rescue activity took place without gas masks or decontamination procedures. In this case of unexpected mass exposure to sarin gas, the emergency rescue system for a large disaster in Matsumoto city, which had been established for a conflagration or a local earthquake, was effective.

A screen for kinase inhibitors identifies antimicrobial imidazopyridine aminofurazans as specific inhibitors of the Listeria monocytogenes PASTA kinase PrkA

PubMed Central

Schaenzer, Adam J.; Wlodarchak, Nathan; Drewry, David H.; Zuercher, William J.; Rose, Warren E.; Striker, Rob; Sauer, John-Demian

2017-01-01

Bacterial signaling systems such as protein kinases and quorum sensing have become increasingly attractive targets for the development of novel antimicrobial agents in a time of rising antibiotic resistance. The family of bacterial Penicillin-binding-protein And Serine/Threonine kinase-Associated (PASTA) kinases is of particular interest due to the role of these kinases in regulating resistance to β-lactam antibiotics. As such, small-molecule kinase inhibitors that target PASTA kinases may prove beneficial as treatments adjunctive to β-lactam therapy. Despite this interest, only limited progress has been made in identifying functional inhibitors of the PASTA kinases that have both activity against the intact microbe and high kinase specificity. Here, we report the results of a small-molecule screen that identified GSK690693, an imidazopyridine aminofurazan-type kinase inhibitor that increases the sensitivity of the intracellular pathogen Listeria monocytogenes to various β-lactams by inhibiting the PASTA kinase PrkA. GSK690693 potently inhibited PrkA kinase activity biochemically and exhibited significant selectivity for PrkA relative to the Staphylococcus aureus PASTA kinase Stk1. Furthermore, other imidazopyridine aminofurazans could effectively inhibit PrkA and potentiate β-lactam antibiotic activity to varying degrees. The presence of the 2-methyl-3-butyn-2-ol (alkynol) moiety was important for both biochemical and antimicrobial activity. Finally, mutagenesis studies demonstrated residues in the back pocket of the active site are important for GSK690693 selectivity. These data suggest that targeted screens can successfully identify PASTA kinase inhibitors with both biochemical and antimicrobial specificity. Moreover, the imidazopyridine aminofurazans represent a family of PASTA kinase inhibitors that have the potential to be optimized for selective PASTA kinase inhibition. PMID:28821610

A screen for kinase inhibitors identifies antimicrobial imidazopyridine aminofurazans as specific inhibitors of the Listeria monocytogenes PASTA kinase PrkA.

PubMed

Schaenzer, Adam J; Wlodarchak, Nathan; Drewry, David H; Zuercher, William J; Rose, Warren E; Striker, Rob; Sauer, John-Demian

2017-10-13

Bacterial signaling systems such as protein kinases and quorum sensing have become increasingly attractive targets for the development of novel antimicrobial agents in a time of rising antibiotic resistance. The family of bacterial P enicillin-binding-protein A nd S erine/ T hreonine kinase- A ssociated (PASTA) kinases is of particular interest due to the role of these kinases in regulating resistance to β-lactam antibiotics. As such, small-molecule kinase inhibitors that target PASTA kinases may prove beneficial as treatments adjunctive to β-lactam therapy. Despite this interest, only limited progress has been made in identifying functional inhibitors of the PASTA kinases that have both activity against the intact microbe and high kinase specificity. Here, we report the results of a small-molecule screen that identified GSK690693, an imidazopyridine aminofurazan-type kinase inhibitor that increases the sensitivity of the intracellular pathogen Listeria monocytogenes to various β-lactams by inhibiting the PASTA kinase PrkA. GSK690693 potently inhibited PrkA kinase activity biochemically and exhibited significant selectivity for PrkA relative to the Staphylococcus aureus PASTA kinase Stk1. Furthermore, other imidazopyridine aminofurazans could effectively inhibit PrkA and potentiate β-lactam antibiotic activity to varying degrees. The presence of the 2-methyl-3-butyn-2-ol (alkynol) moiety was important for both biochemical and antimicrobial activity. Finally, mutagenesis studies demonstrated residues in the back pocket of the active site are important for GSK690693 selectivity. These data suggest that targeted screens can successfully identify PASTA kinase inhibitors with both biochemical and antimicrobial specificity. Moreover, the imidazopyridine aminofurazans represent a family of PASTA kinase inhibitors that have the potential to be optimized for selective PASTA kinase inhibition.

Unexpected Solubility Enhancement of Drug Bases in the Presence of a Dimethylaminoethyl Methacrylate Copolymer.

PubMed

Saal, Wiebke; Ross, Alfred; Wyttenbach, Nicole; Alsenz, Jochem; Kuentz, Martin

2018-01-02

The methacrylate copolymer Eudragit EPO (EPO) has previously shown to greatly enhance solubilization of acidic drugs via ionic interactions and by multiple hydrophobic contacts with polymeric side chains. The latter type of interaction could also play a role for solubilization of other compounds than acids. The aim of this study was therefore to investigate the solubility of six poorly soluble bases in presence and absence of EPO by quantitative ultrapressure liquid chromatography with concomitant X-ray powder diffraction analysis of the solid state. For a better mechanistic understanding, spectra and diffusion data were obtained by 1 H nuclear magnetic resonance (NMR) spectroscopy. Unexpected high solubility enhancement (up to 360-fold) was evidenced in the presence of EPO despite the fact that bases and polymer were both carrying positive charges. This exceptional and unexpected solubilization was not due to a change in the crystalline solid state. NMR spectra and measured diffusion coefficients indicated both strong drug-polymer interactions in the bulk solution, and diffusion data suggested conformational changes of the polymer in solution. Such conformational changes may have increased the accessibility and extent of hydrophobic contacts thereby leading to increased overall molecular interactions. These initially surprising solubilization results demonstrate that excipient selection should not be based solely on simple considerations of, for example, opposite charges of drug and excipient, but it requires a more refined molecular view. Different solution NMR techniques are especially promising tools to gain such mechanistic insights.

Infrasound radiated by the Gerdec and Chelopechene explosions: propagation along unexpected paths

NASA Astrophysics Data System (ADS)

Green, David N.; Vergoz, Julien; Gibson, Robert; Le Pichon, Alexis; Ceranna, Lars

2011-05-01

Infrasound propagation paths through the atmosphere are controlled by the temporally and spatially varying sound speed and wind speed amplitudes. Because of the complexity of atmospheric acoustic propagation it is often difficult to reconcile observed infrasonic arrivals with the sound speed profiles predicted by meteorological specifications. This paper provides analyses of unexpected arrivals recorded in Europe and north Africa from two series of accidental munitions dump explosions, recorded at ranges greater than 1000 km: two explosions at Gerdec, Albania, on 2008 March 15 and four explosions at Chelopechene, Bulgaria, on 2008 July 3. The recorded signal characteristics include multiple pulsed arrivals, celerities between 0.24 and 0.34 km s-1 and some signal frequency content above 1 Hz. Often such characteristics are associated with waves that have propagated within a ground-to-stratosphere waveguide, although the observed celerities extend both above and below the conventional range for stratospheric arrivals. However, state-of-the-art meteorological specifications indicate that either weak, or no, ground-to-stratosphere waveguides are present along the source-to-receiver paths. By incorporating realistic gravity-wave induced horizontal velocity fluctuations into time-domain Parabolic Equation models the pulsed nature of the signals is simulated, and arrival times are predicted to within 30 s of the observed values (<1 per cent of the source-to-receiver transit time). Modelling amplitudes is highly dependent upon estimates of the unknown acoustic source strength (or equivalent chemical explosive yield). Current empirical explosive yield relationships, derived from infrasonic amplitude measurements from point-source chemical explosions, suggest that the equivalent chemical yield of the largest Gerdec explosion was of the order of 1 kt and the largest Chelopechene explosion was of the order of 100 t. When incorporating these assumed yields, the Parabolic

Embedded Prompting May Function as Embedded Punishment: Detection of Unexpected Behavioral Processes within a Typical Preschool Teaching Strategy

ERIC Educational Resources Information Center

Heal, Nicole A.; Hanley, Gregory P.

2011-01-01

This study describes an unexpected behavioral process that influenced behavior during the teaching of concepts to a 4-year-old girl. The efficacy of and preference for three strategies that varied in teacher directedness were assessed in a multielement design and concurrent-chains arrangement, respectively. The strategy that involved the most…

The unexpected detection of varicella-zoster virus in genital specimens using the Lyra™ Direct HSV 1+2/VZV Assay.

PubMed

Granato, Paul A; DeGilio, Marcia A; Wilson, Elsie M

2016-11-01

The Lyra™ Direct HSV 1+2/VZV Assay is a moderately complex, multiplex PCR assay that qualitatively detects the presence of HSV 1, HSV 2, and VZV DNA in cutaneous and mucocutaneous specimens with a time-to-result of less than 60min. To report a one-year laboratory experience using Lyra assay for testing cutaneous and mucocutaneous specimens for HSV and VZV that resulted in the unexpected detection of VZV in 14 male and female genital specimens. Over a one-year period, 2113 cutaneous and mucocutaneous specimens from male and female patients were submitted for testing using the Lyra assay. An unexpected 14 genital specimens were positive for the presence VZV DNA. Eleven of the 14 specimens were available for confirmatory testing using two alternative molecular methods and Sanger sequencing. Fourteen male and female genital specimens were positive for the presence of VZV DNA. All of the 11 specimens (9 female and 2 male) that were available for confirmatory testing by the alternative molecular method and Sanger sequencing were confirmed as containing VZV DNA. Using of the Lyra assay over a one-year time period, VZV DNA was detected in 126 specimens of which 14 (11.1%) were from male and female genital sites. This rare and unexpected finding suggests that the appearance of zoster lesions in the genital area may not be as uncommon as previously thought and that this finding would have considerable impact on patient counseling and public health considerations. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Global Sensitivity Analysis of OnGuard Models Identifies Key Hubs for Transport Interaction in Stomatal Dynamics1[CC-BY

PubMed Central

Vialet-Chabrand, Silvere; Griffiths, Howard

2017-01-01

The physical requirement for charge to balance across biological membranes means that the transmembrane transport of each ionic species is interrelated, and manipulating solute flux through any one transporter will affect other transporters at the same membrane, often with unforeseen consequences. The OnGuard systems modeling platform has helped to resolve the mechanics of stomatal movements, uncovering previously unexpected behaviors of stomata. To date, however, the manual approach to exploring model parameter space has captured little formal information about the emergent connections between parameters that define the most interesting properties of the system as a whole. Here, we introduce global sensitivity analysis to identify interacting parameters affecting a number of outputs commonly accessed in experiments in Arabidopsis (Arabidopsis thaliana). The analysis highlights synergies between transporters affecting the balance between Ca2+ sequestration and Ca2+ release pathways, notably those associated with internal Ca2+ stores and their turnover. Other, unexpected synergies appear, including with the plasma membrane anion channels and H+-ATPase and with the tonoplast TPK K+ channel. These emergent synergies, and the core hubs of interaction that they define, identify subsets of transporters associated with free cytosolic Ca2+ concentration that represent key targets to enhance plant performance in the future. They also highlight the importance of interactions between the voltage regulation of the plasma membrane and tonoplast in coordinating transport between the different cellular compartments. PMID:28432256

Unexpected Far-Ultraviolet Photometric Characteristics On Mimas

NASA Astrophysics Data System (ADS)

Royer, E. M.; Hendrix, A. R.

2013-12-01

While infrared and visible are the most common wavelength domains used to investigate planetary surfaces, ultraviolet (UV) data are significant and useful. Here, we present the first far-UV phase curves of Mimas, thus displaying another piece of the Saturnian System puzzle. Our preliminary results shows that, one more time, Mimas surface properties are far from what we was expected. Namely, we observe a leading hemisphere brighter than the trailing hemisphere at some far-UV wavelengths. We used the far-UV channel of the Cassini/UVIS instrument, ranging from 118 to 190 nm. Disk-integrated phase curves for the leading hemisphere and the trailing hemisphere, at 180nm, have been produced. Data points span from 0.5 to 163.5 degrees in phase angle. Mimas displays a leading hemisphere brighter than its trailing hemisphere, when theory and previous Voyager observations at longer wavelengths attest of a brighter trailing hemisphere due to the impact of the E-ring grains on this face of the satellite. Surprisingly, UVIS data show a very bright opposition effect on Mimas leading hemisphere, greater than what is observed on Tethys or Dione leading hemisphere at the same wavelength of 180 nm. Preliminary results of photometric properties modeling seem to indicate an important contribution of the coherent-backscattering process in the opposition surge. Exogenic processes such as bombardment by energetic electrons and/or E-ring grains are discussed to explain this unexpected surface property of Mimas.

CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

PubMed

Taghizadeh, Rouzbeh; Noh, Minsoo; Huh, Yang Hoon; Ciusani, Emilio; Sigalotti, Luca; Maio, Michele; Arosio, Beatrice; Nicotra, Maria R; Natali, PierGiorgio; Sherley, James L; La Porta, Caterina A M

2010-12-22

A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone. The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

The draft genomes of soft–shell turtle and green sea turtle yield insights into the development and evolution of the turtle–specific body plan

PubMed Central

Niimura, Yoshihito; Huang, Zhiyong; Li, Chunyi; White, Simon; Xiong, Zhiqiang; Fang, Dongming; Wang, Bo; Ming, Yao; Chen, Yan; Zheng, Yuan; Kuraku, Shigehiro; Pignatelli, Miguel; Herrero, Javier; Beal, Kathryn; Nozawa, Masafumi; Li, Qiye; Wang, Juan; Zhang, Hongyan; Yu, Lili; Shigenobu, Shuji; Wang, Junyi; Liu, Jiannan; Flicek, Paul; Searle, Steve; Wang, Jun; Kuratani, Shigeru; Yin, Ye; Aken, Bronwen; Zhang, Guojie; Irie, Naoki

2014-01-01

The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ~267.9–248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell. PMID:23624526

The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan.

PubMed

Wang, Zhuo; Pascual-Anaya, Juan; Zadissa, Amonida; Li, Wenqi; Niimura, Yoshihito; Huang, Zhiyong; Li, Chunyi; White, Simon; Xiong, Zhiqiang; Fang, Dongming; Wang, Bo; Ming, Yao; Chen, Yan; Zheng, Yuan; Kuraku, Shigehiro; Pignatelli, Miguel; Herrero, Javier; Beal, Kathryn; Nozawa, Masafumi; Li, Qiye; Wang, Juan; Zhang, Hongyan; Yu, Lili; Shigenobu, Shuji; Wang, Junyi; Liu, Jiannan; Flicek, Paul; Searle, Steve; Wang, Jun; Kuratani, Shigeru; Yin, Ye; Aken, Bronwen; Zhang, Guojie; Irie, Naoki

2013-06-01

The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ∼267.9-248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell.

Identifying the determinants of premature mortality in Russia: overcoming a methodological challenge

PubMed Central

Tomkins, Susannah; Shkolnikov, Vladimir; Andreev, Evgueni; Kiryanov, Nikolay; Leon, David A; McKee, Martin; Saburova, Lyudmila

2007-01-01

Background It is thought that excessive alcohol consumption is related to the high mortality among working age men in Russia. Moreover it has been suggested that alcohol is a key proximate driver of the very sharp fluctuations in mortality seen in this group since the mid-1980s. Designing an individual-level study suitable to address the potential acute effects of alcohol consumption on mortality in Russia has posed a challenge to epidemiologists, especially because of the need to identify factors that could underlie the rapid changes up and down in mortality rates that have been such a distinctive feature of the Russian mortality crisis. In order to address this study question which focuses on exposures acting shortly before sudden death, a cohort would be unfeasibly large and would suffer from recruitment bias. Methods Although the situation in Russia is unusual, with a very high death rate characterised by many sudden and apparently unexpected deaths in young men, the methodological problem is common to research on any cause of death where many deaths are sudden. Results We describe the development of an innovative approach that has overcome some of these challenges: a case-control study employing proxy informants and external data sources to collect information about proximate determinants of mortality. Conclusion This offers a set of principles that can be adopted by epidemiologists studying sudden and unexpected deaths in other settings. PMID:18045487

A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation

PubMed Central

Viader, Andreu; Ogasawara, Daisuke; Joslyn, Christopher M; Sanchez-Alavez, Manuel; Mori, Simone; Nguyen, William; Conti, Bruno; Cravatt, Benjamin F

2016-01-01

Metabolic specialization among major brain cell types is central to nervous system function and determined in large part by the cellular distribution of enzymes. Serine hydrolases are a diverse enzyme class that plays fundamental roles in CNS metabolism and signaling. Here, we perform an activity-based proteomic analysis of primary mouse neurons, astrocytes, and microglia to furnish a global portrait of the cellular anatomy of serine hydrolases in the brain. We uncover compelling evidence for the cellular compartmentalization of key chemical transmission pathways, including the functional segregation of endocannabinoid (eCB) biosynthetic enzymes diacylglycerol lipase-alpha (DAGLα) and –beta (DAGLβ) to neurons and microglia, respectively. Disruption of DAGLβ perturbed eCB-eicosanoid crosstalk specifically in microglia and suppressed neuroinflammatory events in vivo independently of broader effects on eCB content. Mapping the cellular distribution of metabolic enzymes thus identifies pathways for regulating specialized inflammatory responses in the brain while avoiding global alterations in CNS function. DOI: http://dx.doi.org/10.7554/eLife.12345.001 PMID:26779719

Broadening the cofactor specificity of a thermostable alcohol dehydrogenase using rational protein design introduces novel kinetic transient behavior.

PubMed

Campbell, Elliot; Wheeldon, Ian R; Banta, Scott

2010-12-01

Cofactor specificity in the aldo-keto reductase (AKR) superfamily has been well studied, and several groups have reported the rational alteration of cofactor specificity in these enzymes. Although most efforts have focused on mesostable AKRs, several putative AKRs have recently been identified from hyperthermophiles. The few that have been characterized exhibit a strong preference for NAD(H) as a cofactor, in contrast to the NADP(H) preference of the mesophilic AKRs. Using the design rules elucidated from mesostable AKRs, we introduced two site-directed mutations in the cofactor binding pocket to investigate cofactor specificity in a thermostable AKR, AdhD, which is an alcohol dehydrogenase from Pyrococcus furiosus. The resulting double mutant exhibited significantly improved activity and broadened cofactor specificity as compared to the wild-type. Results of previous pre-steady-state kinetic experiments suggest that the high affinity of the mesostable AKRs for NADP(H) stems from a conformational change upon cofactor binding which is mediated by interactions between a canonical arginine and the 2'-phosphate of the cofactor. Pre-steady-state kinetics with AdhD and the new mutants show a rich conformational behavior that is independent of the canonical arginine or the 2'-phosphate. Additionally, experiments with the highly active double mutant using NADPH as a cofactor demonstrate an unprecedented transient behavior where the binding mechanism appears to be dependent on cofactor concentration. These results suggest that the structural features involved in cofactor specificity in the AKRs are conserved within the superfamily, but the dynamic interactions of the enzyme with cofactors are unexpectedly complex. © 2010 Wiley Periodicals, Inc.

Evidence against barium in the mushroom Trogia venenata as a cause of sudden unexpected deaths in Yunnan, China.

PubMed

Zhang, Ying; Li, Yanchun; Wu, Gang; Feng, Bang; Yoell, Shanze; Yu, Zefen; Zhang, Keqin; Xu, Jianping

2012-12-01

This study examined barium concentrations in the mushroom Trogia venenata, the leading culprit for sudden unexpected deaths in Yunnan, southwest China. We found that barium concentrations in T. venenata from Yunnan were low and comparable to other foods, inconsistent with barium concentrations in this mushroom as a significant contributor to these deaths.

76 FR 35719 - Unexpected Urgent Refugee and Migration Needs Related to Libya and C[ocirc]te d'Ivoire

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... June 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya and C[ocirc]te d'Ivoire... laws of the United States, including section 2(c)(1) of the Migration and Refugee Assistance Act of... amount not to exceed $15 million from the United States Emergency Refugee and Migration Assistance Fund...

Specific surface area of a crushed welded tuff before and after aqueous dissolution

USGS Publications Warehouse

Reddy, M.M.; Claassen, H.C.

1994-01-01

Specific surface areas were measured for several reference minerals (anorthoclase, labradorite and augite), welded tuff and stream sediments from Snowshoe Mountain, near Creede, Colorado. Crushed and sieved tuff had an unexpectedly small variation in specific surface area over a range of size fractions. Replicate surface area measurements of the largest and smallest tuff particle size fractions examined (1-0.3 mm and <0.212 mm) were 2.3 ?? 0.2 m2/g for each size fraction. Reference minerals prepared in the same way as the tuff had smaller specific surface areas than that of the tuff of the same size fraction. Higher than expected tuff specific surface areas appear to be due to porous matrix. Tuff, reacted in solutions with pH values from 2 to 6, had little change in specific surface area in comparison with unreacted tuff. Tuff, reacted with solutions having high acid concentrations (0.1 M hydrochloric acid or sulfuric-hydrofluoric acid), exhibited a marked increase in specific surface area compared to unreacted tuff. ?? 1994.

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.

Unexpected fold in the circumsporozoite protein target of malaria vaccines

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

Doud, Michael B.; Koksal, Adem C.; Mi, Li-Zhi

Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an '{alpha}TSR' domain. The {alpha}TSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but {alpha}TSR does not. Interestingly, polymorphic T-cell epitopes map to specialized {alpha}TSR regions.more » The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket.« less

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

PubMed Central

Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

2015-01-01

Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children.

PubMed

Gonzalez Ballesteros, Luisa F; Ma, Nina S; Gordon, Rebecca J; Ward, Leanne; Backeljauw, Philippe; Wasserman, Halley; Weber, David R; DiMeglio, Linda A; Gagne, Julie; Stein, Robert; Cody, Declan; Simmons, Kimber; Zimakas, Paul; Topor, Lisa Swartz; Agrawal, Sungeeta; Calabria, Andrew; Tebben, Peter; Faircloth, Ruth; Imel, Erik A; Casey, Linda; Carpenter, Thomas O

2017-04-01

Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us

Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni

PubMed Central

Lockyer, Anne E; Spinks, Jenny; Kane, Richard A; Hoffmann, Karl F; Fitzpatrick, Jennifer M; Rollinson, David; Noble, Leslie R; Jones, Catherine S

2008-01-01

Background Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. Results We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1

Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni.

PubMed

Lockyer, Anne E; Spinks, Jenny; Kane, Richard A; Hoffmann, Karl F; Fitzpatrick, Jennifer M; Rollinson, David; Noble, Leslie R; Jones, Catherine S

2008-12-29

Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1, cytoplasmic intermediate

Alternative Effector-Function Profiling Identifies Broad HIV-Specific T-Cell Responses in Highly HIV-Exposed Individuals Who Remain Uninfected

PubMed Central

Ruiz-Riol, Marta; Llano, Anuska; Ibarrondo, Javier; Zamarreño, Jennifer; Yusim, Karina; Bach, Vanessa; Mothe, Beatriz; Perez-Alvarez, Susana; Fernandez, Marco A.; Requena, Gerard; Meulbroek, Michael; Pujol, Ferran; Leon, Agathe; Cobarsi, Patricia; Korber, Bette T.; Clotet, Bonaventura; Ganoza, Carmela; Sanchez, Jorge; Coll, Josep; Brander, Christian

2015-01-01

The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine–like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders. PMID:25249264

Iridium double perovskite Sr2YIrO6 : A combined structural and specific heat study

NASA Astrophysics Data System (ADS)

Corredor, L. T.; Aslan-Cansever, G.; Sturza, M.; Manna, Kaustuv; Maljuk, A.; Gass, S.; Dey, T.; Wolter, A. U. B.; Kataeva, Olga; Zimmermann, A.; Geyer, M.; Blum, C. G. F.; Wurmehl, S.; Büchner, B.

2017-02-01

Recently, the iridate double perovskite Sr2YIrO6 has attracted considerable attention due to the report of unexpected magnetism in this Ir5 + (5 d4 ) material, in which according to the Jeff model, a nonmagnetic ground state is expected. However, in recent works on polycrystalline samples of the series Ba2 -xSrxYIrO6 no indication of magnetic transitions have been found. We present a structural, magnetic, and thermodynamic characterization of Sr2YIrO6 single crystals, with emphasis on the temperature and magnetic field dependence of the specific heat. As determined by x-ray diffraction, the Sr2YIrO6 single crystals have a cubic structure, with space group F m 3 ¯m . In agreement with the expected nonmagnetic ground state of Ir5 + (5d 4 ) in Sr2YIrO6 , no magnetic transition is observed down to 430 mK. Moreover, our results suggest that the low-temperature anomaly observed in the specific heat is not related to the onset of long-range magnetic order. Instead, it is identified as a Schottky anomaly caused by paramagnetic impurities present in the sample, of the order of n ˜0.5 (2 )% . These impurities lead to non-negligible spin correlations, which nonetheless, are not associated with long-range magnetic ordering.