DOE Office of Scientific and Technical Information (OSTI.GOV)
Peter Daum
2008-10-06
Brookhaven researcher Peter Daum discusses an international field experiment designed to make observations of critical components of the climate system of the southeastern Pacific. Because elements of this system are poorly understood and poorly represent
Peter Daum
2017-12-09
Brookhaven researcher Peter Daum discusses an international field experiment designed to make observations of critical components of the climate system of the southeastern Pacific. Because elements of this system are poorly understood and poorly represent
Auditory Processing Disorders: Acquisition and Treatment
ERIC Educational Resources Information Center
Moore, David R.
2007-01-01
Auditory processing disorder (APD) describes a mixed and poorly understood listening problem characterised by poor speech perception, especially in challenging environments. APD may include an inherited component, and this may be major, but studies reviewed here of children with long-term otitis media with effusion (OME) provide strong evidence…
The water balance components of undisturbed tropical woodlands in the Brazilian cerrado
USDA-ARS?s Scientific Manuscript database
Deforestation of the Brazilian cerrado region has caused major changes in hydrological processes. These changes in water balance components are still poorly understood but are important for making land management decisions in this region. To better understand pre-deforestation conditions, we determi...
K.A. Magrini; R.J. Evans; C.M. Hoover; C.C. Elam; M.F. Davis
2002-01-01
The components of soil organic matter (SOM) and their degradation dynamics in forest soils are difficult to study and thus poorly understood,due to time-consuming sample collection, preparation, and difficulty of analyzing and identifying major components. As a result, changes in soil organic matter chemical composition as a function of age, forest type, or disturbance...
Genotype-specific responses of apple roots to pathogenic infection by Pythium ultimum
USDA-ARS?s Scientific Manuscript database
Resistance mechanisms employed to defend against soilborne necrotrophic pathogens are poorly understood, particularly with respect to perennial tree fruit crops such as apple. Pythium ultimum is a component of the pathogen complex that incites apple replant disease (ARD). Different levels of tolera...
Sugary beverage intake and preclinical Alzheimer's disease in the community
USDA-ARS?s Scientific Manuscript database
IMPORTANCE: Sugary beverages are a key component of the Western diet, yet the long-term effects of these beverages on the brain are poorly understood. OBJECTIVE: To determine whether habitual sugary beverage consumption is associated with markers of preclinical Alzheimers disease (AD) and/or vascu...
Drought and leaf herbivory influence floral volatiles and pollinator attraction
Laura A. Burkle; Justin B. Runyon
2016-01-01
The effects of climate change on species interactions are poorly understood. Investigating the mechanisms by which species interactions may shift under altered environmental conditions will help form a more predictive understanding of such shifts. In particular, components of climate change have the potential to strongly influence floral volatile organic...
Understanding Authority in Classrooms: A Review of Theory, Ideology, and Research
ERIC Educational Resources Information Center
Pace, Judith L.; Hemmings, Annette
2007-01-01
Authority is a fundamental, problematic, and poorly understood component of classroom life. A better understanding of classroom authority can be achieved by reviewing writings on social theory, educational ideology, and qualitative research in schools. Social theories provide important analytical tools for examining the constitutive elements of…
Secondary organic aerosols (SOA), known to form in the atmosphere from oxidation of volatile organic compounds (VOCs) emitted by anthropogenic and biogenic sources, are a poorly understood but substantial component of atmospheric particles. In this study, we examined the chemic...
Statistical Word Learning in Children with Autism Spectrum Disorder and Specific Language Impairment
ERIC Educational Resources Information Center
Haebig, Eileen; Saffran, Jenny R.; Ellis Weismer, Susan
2017-01-01
Background: Word learning is an important component of language development that influences child outcomes across multiple domains. Despite the importance of word knowledge, word-learning mechanisms are poorly understood in children with specific language impairment (SLI) and children with autism spectrum disorder (ASD). This study examined…
Mosquito host choices on livestock amplifiers of Rift Valley fever virus in Kenya
USDA-ARS?s Scientific Manuscript database
Animal hosts may vary in their attraction and acceptability as components of the host location process for assessing biting rates of vectors and risk of exposure to pathogens. However, these parameters remain poorly understood for mosquito vectors of the Rift Valley fever (RVF), an arboviral disease...
How Do Teachers View Their Own Pedagogical Authority?
ERIC Educational Resources Information Center
Harjunen, Elina
2009-01-01
Authority, a fundamental part of the teaching-studying-learning process, is a problematic and poorly understood component of classroom life. It can be said, in practical terms, that pedagogical authority is constructed in classrooms, in teacher-student interaction and in the spirit of their physical presence, confidence, appreciation,…
Academic Performance of Transfer Versus "Native" Students in Natural Resources & Sciences
ERIC Educational Resources Information Center
Johnson, Matthew D.
2005-01-01
Transfer students comprise a substantial component of the student body in many 4-year academic colleges, but the factors affecting students' success once they have transferred are poorly understood. Using data from standard university records, academic performance was examined for 2,467 students enrolled in natural resource majors at a mid-sized…
Principles of Cancer Screening.
Pinsky, Paul F
2015-10-01
Cancer screening has long been an important component of the struggle to reduce the burden of morbidity and mortality from cancer. Notwithstanding this history, many aspects of cancer screening remain poorly understood. This article presents a summary of basic principles of cancer screening that are relevant for researchers, clinicians, and public health officials alike. Published by Elsevier Inc.
Genetic Influences on Mechanically-Assessed Activity Level in Children
ERIC Educational Resources Information Center
Wood, Alexis C.; Saudino, Kimberly J.; Rogers, Hannah; Asherson, Philip; Kuntsi, Jonna
2007-01-01
Background: Activity level is an important component of children's temperament, as well as being part of the core symptom domain of hyperactivity-impulsivity within attention deficit hyperactivity disorder (ADHD). Yet it is poorly understood, due partly to limitations on parent and teacher ratings, which are typically used as measurements of these…
USDA-ARS?s Scientific Manuscript database
Hemicelluloses are major components of plant biomass, but their fermentation in the rumens of cattle and other ruminants is poorly understood. We compared four species of the ruminally dominant genus Prevotella and the well-known hemicellulose utilizer, Butyrivibrio fibrisolvens, with respect to deg...
Migration is one of the most poorly understood components of a bird’s life cycle. For that reason, migratory stopover habitats are often not part of conservation planning and may be overlooked when planning new development projects. This project highlights and addresses an overl...
The PH gene determines fruit acidity and contributes to the evolution of sweet melons
USDA-ARS?s Scientific Manuscript database
Acids are one of the three major components of fleshy fruit taste, together with sugars and volatile flavor compounds. However, the molecular-genetic control of acid accumulation in fruit is poorly understood and, to date, no genes responsible for acid accumulation in fleshy fruit have been function...
USDA-ARS?s Scientific Manuscript database
The effects of acute stressor exposure on proximal (growth hormone; GH) and distal (insulin-like growth factor-I; IGF-I and IGF-binding proteins) components of the somatotropic axis are poorly understood in finfish. We exposed rainbow trout (Oncorhynchus mykiss) to a 5-minute handling disturbance to...
Downed Wood in micronesian mangrove Forests
James A. Allen; Katherine C. Ewel; Bobby D. Keeland; Tara Tara; Thomas J. Smith
2000-01-01
Dead, downed wood is an important component of upland forest and aquatic ecosystems, but its role in wetland ecosystems, including mangroves, is poorly understood. We measured downed wood in ten sites on the western Pacific islands of Kosrae, Pohnpei, and Yap, all located within the Federated States of Micronesia. Our goals were to examine patterns of variability in...
USDA-ARS?s Scientific Manuscript database
Aim: The microbial ecology of feedlot Escherichia coli is poorly understood. It is a minority component of feces and must interact with many other bacteria. Use of wet distiller’s grains with solubles (WDGS) in cattle feed creates a gastrointestinal environment where some bacterial species are enri...
ERIC Educational Resources Information Center
Feldman, Ruth; Gordon, Ilanit; Zagoory-Sharon, Orna
2011-01-01
Studies in mammals have implicated the neuropeptide oxytocin (OT) in processes of bond formation and stress modulation, yet the involvement of OT in human bonding throughout life remains poorly understood. We assessed OT in the plasma, saliva, and urine of 112 mothers and fathers interacting with their 4-6-month-old infants. Parent-infant…
ERIC Educational Resources Information Center
Kaufmann, Liane; Nuerk, Hans-Christoph
2008-01-01
ADHD (attention-deficit hyperactivity disorder) and academic difficulties are frequently associated, but to date this link is poorly understood. In order to explore which components of number processing and calculation skills may be disturbed in children with ADHD we presented a series of respective tasks to 9- to 12-year-old children with…
John E. Lundquist; Jose F. Negron
2000-01-01
Disturbances are natural and essential components of healthy ecosystems, but their ecological roles in the maintenance of endemic conditions for an area (that is, long-established levels of activity that are of low magnitude and relatively static intensity and cause unnoticed or relatively low amounts of tree killing, defoliation, or deformation) are poorly understood...
Dara, Lily; Hewett, Jennifer; Lim, Joseph Kartaik
2008-01-01
Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxicity, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the setting of Hydroxycut exposure and describe possible mechanisms of liver injury. We also comprehensively review and summarize the existing literature on commonly used weight loss supplements, and their individual components which have demonstrated potential for liver toxicity. An increased effort to screen for and educate patients and physicians about supplement-associated hepatotoxicity is warranted. PMID:19058338
Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala
Murray, Elisabeth A.; Wise, Steven P.; Drevets, Wayne C.
2010-01-01
Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of ‘self’ underlies the core disorder in MDD; the medial frontal cortex represents ‘self’; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD. PMID:21111403
Polyelectrolyte Structure and Interactions in Model Cystic Fibrosis Sputum
NASA Astrophysics Data System (ADS)
Slimmer, Scott; Angelini, Thomas; Liang, Hongjun; Butler, John; Wong, Gerard C. L.
2002-03-01
Cystic fibrosis sputum is a complex fluid consisting of a number of components, including mucin (a glycoprotein), lysozyme (a cationic polypeptide), water, salt, as well as a high concentration of a number of anionic biological polyelectrolytes such as DNA and F-actin. The interactions governing these components are poorly understood, but may have important clinical consequences. For example, the formation of these biological polyelectrolytes into ordered gel phases may contribute significantly to the observed high viscosity of CF sputum. In this work, a number of model systems were created to simulate CF sputum in vitro, in order to elucidate the contributions of the different components. Preliminary results will be presented. This work was supported by NSF DMR-0071761, DOE DEFG02-91ER45439, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.
Vital effects in coral skeletal composition display strict three-dimensional control
Meibom, A.; Yurimoto, H.; Cuif, J.-P.; Domart-Coulon, I.; Houlbreque, F.; Constantz, B.; Dauphin, Y.; Tambutte, E.; Tambutte, S.; Allemand, D.; Wooden, J.; Dunbar, R.
2006-01-01
Biological control over coral skeletal composition is poorly understood but critically important to paleoenvironmental reconstructions. We present microanalytical measurements of trace-element abundances as well as oxygen and carbon isotopic compositions of individual skeletal components in the zooxanthellate coral Colpophyllia sp. Our data show that centers of calcification (COC) have higher trace element concentrations and distinctly lighter isotopic compositions than the fibrous components of the skeleton. These observations necessitate that COC and the fibrous skeleton are precipitated by different mechanisms, which are controlled by specialized domains of the calicoblastic cell-layer. Biological processes control the composition of the skeleton even at the ultra-structure level. Copyright 2006 by the American Geophysical Union.
He, Haijin; Gonzalez, Marlyn; Zhang, Fan; Li, Fei
2014-06-01
Genetic information stored in DNA is accurately copied and transferred to subsequent generations through DNA replication. This process is accomplished through the concerted actions of highly conserved DNA replication components. Epigenetic information stored in the form of histone modifications and DNA methylation, constitutes a second layer of regulatory information important for many cellular processes, such as gene expression regulation, chromatin organization, and genome stability. During DNA replication, epigenetic information must also be faithfully transmitted to subsequent generations. How this monumental task is achieved remains poorly understood. In this review, we will discuss recent advances on the role of DNA replication components in the inheritance of epigenetic marks, with a particular focus on epigenetic regulation in fission yeast. Based on these findings, we propose that specific DNA replication components function as key regulators in the replication of epigenetic information across the genome.
The Hygroscopicity Parameter of Marine Organics in Sea Spray Aerosols
NASA Astrophysics Data System (ADS)
Boyer, M.; Chang, R. Y. W.
2015-12-01
The effects of aerosols on climate are poorly understood, specifically with respect to their influence on cloud properties. Since oceans cover >70% of Earth's surface, sea spray aerosols (SSA), which act efficiently as cloud condensation nuclei (CCN), may have important implications on Earth's radiation budget. Surface active organic species readily accumulate in the sea surface microlayer (SML), located at the ocean-atmosphere interface, and transfer onto nascent SSA. While it is understood that SSA are commonly enriched with organics, the resulting effect of the organic content on CCN activation remains unresolved. The hygroscopicity parameter, kappa (k), allows for the cloud nucleating properties of individual components to be predicted in particles of mixed composition; however, most studies typically infer k from ambient measurements without assessing the contribution of the individual components to the overall k. In this study, a method for quantifying the cloud nucleating properties of the organic species in surface seawater using k-Kohler theory is proposed. Ambient SML and bulk water samples will be collected and atomized to generate particles such that the overall k can be inferred from CCN measurements. The inorganic and organic components will be quantified, and the organic component will be separated so that the hygroscopicity of only the organic constituents can be determined. By comparing the inferred k values for the samples before and after removal of the inorganic component, the hygroscopicity of the organic constituents alone can be calculated, providing insight on the effect of organic species on CCN activation in SSA.
Observations On Some Upper Amazonian Wetlands of Southeastern Peru
NASA Astrophysics Data System (ADS)
Householder, J. E.; Muttiah, R.; Khanal, S.
2007-05-01
Upper Amazonian wetlands represent little studied, poorly understood, and grossly under protected systems. Scientific investigation of Amazonian wetlands is in its infancy; nor is there much known about their ecological services. Regionally, wetlands form a ubiquitous and significant component of floodplain habitat fed by perennial springs as well as overland runoff. Locally, wetland vegetation forms bewilderingly complex vegetation mosaics that seem to be governed by local topography and hydrology. Drawing upon intensive field campaigns and remotely sensed imagery, we summarize the results and experiences gathered in wetlands of southeastern Peru.
Cannon, Daniel T; White, Ailish C; Andriano, Melina F; Kolkhorst, Fred W; Rossiter, Harry B
2011-02-01
The mechanisms determining exercise intolerance are poorly understood. A reduction in work efficiency in the form of an additional energy cost and oxygen requirement occurs during high-intensity exercise and contributes to exercise limitation. Muscle fatigue and subsequent recruitment of poorly efficient muscle fibres has been proposed to mediate this decline. These data demonstrate in humans, that muscle fatigue, generated in the initial minutes of exercise, is correlated with the increasing energy demands of high-intensity exercise. Surprisingly, however, while muscle fatigue reached a plateau, oxygen uptake continued to increase throughout 8 min of exercise. This suggests that additional recruitment of inefficient muscle fibres may not be the sole mechanism contributing to the decline in work efficiency during high-intensity exercise.
Air pollution: mechanisms of neuroinflammation and CNS disease.
Block, Michelle L; Calderón-Garcidueñas, Lilian
2009-09-01
Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components. Here we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease.
Yavuz, Sevil; Warren, Graham
2017-01-01
A single Golgi stack is duplicated and partitioned into two daughter cells during the cell cycle of the protozoan parasite Trypanosoma brucei. The source of components required to generate the new Golgi and the mechanism by which it forms are poorly understood. Using photoactivatable GFP, we show that the existing Golgi supplies components directly to the newly forming Golgi in both intact and semipermeabilized cells. The movement of a putative glycosyltransferase, GntB, requires the Sar1 and ARF1 GTPases in intact cells. In addition, we show that transfer of GntB from the existing Golgi to the new Golgi can be recapitulated in semipermeabilized cells and is sensitive to the GTP analogue GTPγS. We suggest that the existing Golgi is a key source of components required to form the new Golgi and that this process is regulated by small GTPases. PMID:28495798
NASA Astrophysics Data System (ADS)
Liu, Yang; Cao, Sheng-Le
2017-06-01
It was known that hydrological regime was the main influencing factor of river ecosystem, but the regime of different flow rates of urban rivers was poorly understood. We collected daily inflows at the Huangtai station of the Xiaoqing River from 1960 to 2014 and divided the data into three periods. Then we calculated hydrological parameters by the method of EFCs (Environmental Flow Components) and analyzed the tendency and change rates of each component respectively in the three periods. Combined with the ecological significance of environmental flow components, we identified the small and medium flood had the greatest impact on the river regime and ecosystem. And then we used the hydraulic parameters in the good ecosystem period as control conditions, to calculate the ecological threshold of the flow component under the current situation. This study could provide technical support for restoring and improving hydrological regime and ecological environment of the Xiaoqing River in Jinan city.
Knuckles, Philip; Lence, Tina; Haussmann, Irmgard U.; Jacob, Dominik; Kreim, Nastasja; Carl, Sarah H.; Masiello, Irene; Hares, Tina; Villaseñor, Rodrigo; Hess, Daniel; Andrade-Navarro, Miguel A.; Biggiogera, Marco; Helm, Mark; Soller, Matthias; Bühler, Marc; Roignant, Jean-Yves
2018-01-01
N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m6A is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of m6A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m6A levels and is involved in sex determination in Drosophila. We demonstrate that Flacc promotes m6A deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the m6A machinery. PMID:29535189
Deconstructing and Reconstructing Cognitive Performance in Sleep Deprivation
Jackson, Melinda L.; Gunzelmann, Glenn; Whitney, Paul; Hinson, John M.; Belenky, Gregory; Rabat, Arnaud; Van Dongen, Hans P. A.
2012-01-01
Summary Mitigation of cognitive impairment due to sleep deprivation in operational settings is critical for safety and productivity. Achievements in this area are hampered by limited knowledge about the effects of sleep loss on actual job tasks. Sleep deprivation has different effects on different cognitive performance tasks, but the mechanisms behind this task-specificity are poorly understood. In this context it is important to recognize that cognitive performance is not a unitary process, but involves a number of component processes. There is emerging evidence that these component processes are differentially affected by sleep loss. Experiments have been conducted to decompose sleep-deprived performance into underlying cognitive processes using cognitive-behavioral, neuroimaging and cognitive modeling techniques. Furthermore, computational modeling in cognitive architectures has been employed to simulate sleep-deprived cognitive performance on the basis of the constituent cognitive processes. These efforts are beginning to enable quantitative prediction of the effects of sleep deprivation across different task contexts. This paper reviews a rapidly evolving area of research, and outlines a theoretical framework in which the effects of sleep loss on cognition may be understood from the deficits in the underlying neurobiology to the applied consequences in real-world job tasks. PMID:22884948
Deconstructing and reconstructing cognitive performance in sleep deprivation.
Jackson, Melinda L; Gunzelmann, Glenn; Whitney, Paul; Hinson, John M; Belenky, Gregory; Rabat, Arnaud; Van Dongen, Hans P A
2013-06-01
Mitigation of cognitive impairment due to sleep deprivation in operational settings is critical for safety and productivity. Achievements in this area are hampered by limited knowledge about the effects of sleep loss on actual job tasks. Sleep deprivation has different effects on different cognitive performance tasks, but the mechanisms behind this task-specificity are poorly understood. In this context it is important to recognize that cognitive performance is not a unitary process, but involves a number of component processes. There is emerging evidence that these component processes are differentially affected by sleep loss. Experiments have been conducted to decompose sleep-deprived performance into underlying cognitive processes using cognitive-behavioral, neuroimaging and cognitive modeling techniques. Furthermore, computational modeling in cognitive architectures has been employed to simulate sleep-deprived cognitive performance on the basis of the constituent cognitive processes. These efforts are beginning to enable quantitative prediction of the effects of sleep deprivation across different task contexts. This paper reviews a rapidly evolving area of research, and outlines a theoretical framework in which the effects of sleep loss on cognition may be understood from the deficits in the underlying neurobiology to the applied consequences in real-world job tasks. Copyright © 2012 Elsevier Ltd. All rights reserved.
Formation of Silicate Grains in Circumstellar Environments: Experiment, Theory and Observations
NASA Technical Reports Server (NTRS)
Castleman, A., Jr.; Reber, A.; Clayborne, P.; Reveles, J.; Khanna, S.; Ali, A.
2006-01-01
Amongst chemical reactions (1) in the molecular universe (2), condensation reaction is probably the most poorly understood. The condensation of a solid from its components in the gas phase occurs in many parts of our galaxy such as stellar mass outflows, the terrestrial region of protoplanetary disks and in primordial solar nebula (3). But how does the transition occur from molecules to intermediate clusters to macroscopic grains? The major focus of the present work is the identification of chemical condensation reaction pathways that lead to the formation of stoichiometry, composition and crystallinity of cosmic silicates from vapor phase species.
Similar and contrasting dimensions of social cognition in schizophrenia and healthy subjects.
Mehta, Urvakhsh Meherwan; Thirthalli, Jagadisha; Bhagyavathi, H D; Keshav Kumar, J; Subbakrishna, D K; Gangadhar, Bangalore N; Eack, Shaun M; Keshavan, Matcheri S
2014-08-01
Schizophrenia patients experience substantial impairments in social cognition (SC) and these deficits are associated with their poor functional outcome. Though SC is consistently shown to emerge as a cognitive dimension distinct from neurocognition, the dimensionality of SC is poorly understood. Moreover, comparing the components of SC between schizophrenia patients and healthy comparison subjects would provide specific insights on the construct validity of SC. We conducted principal component analyses of eight SC test scores (representing four domains of SC, namely, theory of mind, emotion processing, social perception and attributional bias) independently in 170 remitted schizophrenia patients and 111 matched healthy comparison subjects. We also conducted regression analyses to evaluate the relative contribution of individual SC components to other symptom dimensions, which are important clinical determinants of functional outcome (i.e., neurocognition, negative symptoms, motivational deficits and insight) in schizophrenia. A three-factor solution representing socio-emotional processing, social-inferential ability and external attribution components emerged in the patient group that accounted for 64.43% of the variance. In contrast, a two-factor solution representing socio-emotional processing and social-inferential ability was derived in the healthy comparison group that explained 56.5% of the variance. In the patient group, the social-inferential component predicted negative symptoms and motivational deficits. Our results suggest the presence of a multidimensional SC construct. The dimensionality of SC observed across the two groups, though not identical, displayed important parallels. Individual components also demonstrated distinct patterns of association with other symptom dimensions, thus supporting their external validity. Copyright © 2014 Elsevier B.V. All rights reserved.
Laboratory tests for mumps vaccines.
Minor, P D
1997-03-01
The action of live attenuated vaccines against mumps is poorly understood although their clinical efficacy is beyond doubt. The attenuated character of the vaccine is assured by consistency of production related to clinical trials, and limited studies of vaccine seeds in primates. Potency is assessed by infectivity in vitro and is subject to poorly understood sources of variation. Molecular biological studies are at an early stage.
NASA Astrophysics Data System (ADS)
Mukherji, Debashish; Marques, Carlos M.; Kremer, Kurt
2018-01-01
In this work we discuss two mirror but distinct phenomena of polymer paradoxical properties in mixed solvents: co-non-solvency and co-solvency. When a polymer collapses in a mixture of two miscible good solvents the phenomenon is known as co-non-solvency, while co-solvency is a phenomenon that is associated with the swelling of a polymer in poor solvent mixtures. A typical example of co-non-solvency is provided by poly(N-isopropylacrylamide) in aqueous alcohol, while poly(methyl methacrylate) in aqueous alcohol shows co-solvency. We discuss these two phenomena to compare their microscopic origins and show that both can be understood within generic universal concepts. A broad range of polymers is therefore expected to exhibit these phenomena where specific chemical details play a lesser role than the appropriate combination of interactions between the trio of molecular components.
NASA Technical Reports Server (NTRS)
Hale, Leslie C.
1994-01-01
In an attempt to explain numerous atmospheric electrical phenomena, the elements of the global electrical circuit are reexamined. In addition to being a 'quasi-static 'DC' generator' and source of radiated energy at VLF and higher, the thunderstorm is found to be a pulse generator, with most of the external energy contained in ELF and ULF pulse currents to the ionosphere (and Earth). The pulse energy is found to deposit largely in the middle atmosphere above the thunderstorm. The VLF and above components are well understood, as are the ULF components due to the conductivity gradient. However, a previously poorly understood ELF component on the millsecond timescale, or 'slow tail,' contains a large fraction of the electrical energy. This component couples strongly to the ionosphere and also launches a unipolar transverse electromagnetic (TEM) wavelet in the radial Earth-ionosphere transmission line. The increase in charge with distance associated with such wavelets, and their ensemble sum at a point, may explain some large mesospheric 'DC' fields but there are still difficulties explaining other than rare occurrences, except for antipodal reconvergence. These millisecond duration unipolar wavelets also coupled to the ionosphere and may trigger other lightning at a distance. A schema is elucidated by which the charge of MeV particles deposited in the middle atmosphere persists for much longer than the local relaxation time. This also gives rise to unipolar waves of global extent which may explain lower-latitude field perturbations associated with solar/geomagnetic events.
Morris, Aaron H.; Chang, Julie; Kyriakides, Themis R.
2016-01-01
Abstract Decellularized tissue scaffolds are commonly used in the clinic because they can be used as substitutes for more traditional biomaterials, while imparting additional physiological effects. Nevertheless, reports of complications associated with their use are widespread and poorly understood. This study probes possible causes of these complications by examining cell viability and apoptosis in response to eluents from decellularized dermis. Using multiple sources of decellularized dermis, this study shows that typical decellularized scaffolds (prepared with commonly used laboratory techniques, as well as purchased from commercial sources) contain soluble components that are cytotoxic and that these components can be removed by extensive washes in cell culture media. In addition, this study demonstrates that these observed in vitro phenotypes correlate with increased apoptosis and acute inflammation when implanted subcutaneously in mice. PMID:27500014
The properties and causes of rippling in quasi-perpendicular collisionless shock fronts
NASA Astrophysics Data System (ADS)
Lowe, R. E.; Burgess, D.
2003-03-01
The overall structure of quasi-perpendicular, high Mach number collisionless shocks is controlled to a large extent by ion reflection at the shock ramp. Departure from a strictly one-dimensional structure is indicated by simulation results showing that the surface of such shocks is rippled, with variations in the density and all field components. We present a detailed analysis of these shock ripples, using results from a two-dimensional hybrid (particle ions, electron fluid) simulation. The process that generates the ripples is poorly understood, because the large gradients at the shock ramp make it difficult to identify instabilities. Our analysis reveals new features of the shock ripples, which suggest the presence of a surface wave mode dominating the shock normal magnetic field component of the ripples, as well as whistler waves excited by reflected ions.
Implementation strategies: recommendations for specifying and reporting
2013-01-01
Implementation strategies have unparalleled importance in implementation science, as they constitute the ‘how to’ component of changing healthcare practice. Yet, implementation researchers and other stakeholders are not able to fully utilize the findings of studies focusing on implementation strategies because they are often inconsistently labelled and poorly described, are rarely justified theoretically, lack operational definitions or manuals to guide their use, and are part of ‘packaged’ approaches whose specific elements are poorly understood. We address the challenges of specifying and reporting implementation strategies encountered by researchers who design, conduct, and report research on implementation strategies. Specifically, we propose guidelines for naming, defining, and operationalizing implementation strategies in terms of seven dimensions: actor, the action, action targets, temporality, dose, implementation outcomes addressed, and theoretical justification. Ultimately, implementation strategies cannot be used in practice or tested in research without a full description of their components and how they should be used. As with all intervention research, their descriptions must be precise enough to enable measurement and ‘reproducibility.’ We propose these recommendations to improve the reporting of implementation strategies in research studies and to stimulate further identification of elements pertinent to implementation strategies that should be included in reporting guidelines for implementation strategies. PMID:24289295
Implementation strategies: recommendations for specifying and reporting.
Proctor, Enola K; Powell, Byron J; McMillen, J Curtis
2013-12-01
Implementation strategies have unparalleled importance in implementation science, as they constitute the 'how to' component of changing healthcare practice. Yet, implementation researchers and other stakeholders are not able to fully utilize the findings of studies focusing on implementation strategies because they are often inconsistently labelled and poorly described, are rarely justified theoretically, lack operational definitions or manuals to guide their use, and are part of 'packaged' approaches whose specific elements are poorly understood. We address the challenges of specifying and reporting implementation strategies encountered by researchers who design, conduct, and report research on implementation strategies. Specifically, we propose guidelines for naming, defining, and operationalizing implementation strategies in terms of seven dimensions: actor, the action, action targets, temporality, dose, implementation outcomes addressed, and theoretical justification. Ultimately, implementation strategies cannot be used in practice or tested in research without a full description of their components and how they should be used. As with all intervention research, their descriptions must be precise enough to enable measurement and 'reproducibility.' We propose these recommendations to improve the reporting of implementation strategies in research studies and to stimulate further identification of elements pertinent to implementation strategies that should be included in reporting guidelines for implementation strategies.
Freeman, Scott A; Moon, Summer D; Spencer, James M
2012-12-01
Rosacea is a common, chronic, and poorly understood dermatological condition characterized by an inflammatory component composed of papules and pustules and a vascular component composed of flushing and erythema. Current treatment options include topical, systemic, and light-based methods, each of which focuses on either the inflammatory or the vascular component. Retinoids are not routinely indicated as treatment because of the common conception that they would be too inflammatory for the sensitive rosacea patient. However, photodamage may play a role in rosacea and tretinoin is well-known to repair photodamage. Thirty rosacea subjects were enrolled to assess their response to the use of clindamycin phosphate 1.2% and tretinoin 0.025% gel (ZIANA; Medicis Pharmaceutical Corporation, Scottsdale, AZ) for a period of 12 weeks. The results showed a dramatic decrease in pustules and papules without any significant inflammation or overall intolerance. No improvement in facial redness was achieved. Based on our results, more investigation of topical retinoids for rosacea treatment is prudent.
Behar, Marcelo; Dohlman, Henrik G.; Elston, Timothy C.
2007-01-01
Intracellular signaling pathways that share common components often elicit distinct physiological responses. In most cases, the biochemical mechanisms responsible for this signal specificity remain poorly understood. Protein scaffolds and cross-inhibition have been proposed as strategies to prevent unwanted cross-talk. Here, we report a mechanism for signal specificity termed “kinetic insulation.” In this approach signals are selectively transmitted through the appropriate pathway based on their temporal profile. In particular, we demonstrate how pathway architectures downstream of a common component can be designed to efficiently separate transient signals from signals that increase slowly over time. Furthermore, we demonstrate that upstream signaling proteins can generate the appropriate input to the common pathway component regardless of the temporal profile of the external stimulus. Our results suggest that multilevel signaling cascades may have evolved to modulate the temporal profile of pathway activity so that stimulus information can be efficiently encoded and transmitted while ensuring signal specificity. PMID:17913886
Analysis of Free Modeling Predictions by RBO Aleph in CASP11
Mabrouk, Mahmoud; Werner, Tim; Schneider, Michael; Putz, Ines; Brock, Oliver
2015-01-01
The CASP experiment is a biannual benchmark for assessing protein structure prediction methods. In CASP11, RBO Aleph ranked as one of the top-performing automated servers in the free modeling category. This category consists of targets for which structural templates are not easily retrievable. We analyze the performance of RBO Aleph and show that its success in CASP was a result of its ab initio structure prediction protocol. A detailed analysis of this protocol demonstrates that two components unique to our method greatly contributed to prediction quality: residue–residue contact prediction by EPC-map and contact–guided conformational space search by model-based search (MBS). Interestingly, our analysis also points to a possible fundamental problem in evaluating the performance of protein structure prediction methods: Improvements in components of the method do not necessarily lead to improvements of the entire method. This points to the fact that these components interact in ways that are poorly understood. This problem, if indeed true, represents a significant obstacle to community-wide progress. PMID:26492194
The Nature and Origin of Aromatic Organic Matter in the Tagish Lake Meteorite
NASA Technical Reports Server (NTRS)
Clemett, S. J.; Keller, L. P.; Nakamura, K.; McKay, D. S.
2004-01-01
The Tagish Lake meteorite is an unusual carbonaceous chondrite that does not fit well within existing chondrite taxonomy. Bulk analyses suggest approx. 5 wt.% C of which approx. 1 wt.% is in the form of organic matter and the remainder is present as inorganic carbonate. The exact nature and form of this organic component is, as is the case with the other ordinary and carbonaceous chondrites, still poorly understood. Yet its significance has far reaching implications, from contributing to the abiotic evolution of the early Earth and Mars, to providing geothermal constraints in the evolution of the Solar nebula.
The role of skeletal muscle in the pathophysiology and management of knee osteoarthritis.
Krishnasamy, Priathashini; Hall, Michelle; Robbins, Sarah R
2018-05-01
The role of skeletal muscle in the pathophysiology of knee OA is poorly understood. To date, the majority of literature has focused on the association of muscle strength with OA symptoms, disease onset and progression. However, deficits or improvements in skeletal muscle strength do not fully explain the mechanisms behind outcome measures in knee OA, such as pain, function and structural disease. This review aims to summarize components of skeletal muscle, providing a holistic view of skeletal muscle mechanisms that includes muscle function, quality and composition and their interactions. Similarly, the role of skeletal muscle in the management of knee OA will be discussed.
Gridley, T; Silva, M F P; Wilkinson, C; Seakamela, S M; Elwen, S H
2018-04-01
Humpback whales (Megaptera novaeangliae) are well known for their complex song which is culturally transmitted and produced by males. However, the function of singing behavior remains poorly understood. Song was observed from 57 min of acoustic recording in the presence of feeding humpback whales aggregated in the near-shore waters on the west coast of South Africa. The structural organization of the song components, lack of overlap between song units, and consistency in relative received level suggest the song was produced by one "singer." The unusual timing and location of song production adds further evidence of plasticity in song production.
Brain evolution and development: adaptation, allometry and constraint
Barton, Robert A.
2016-01-01
Phenotypic traits are products of two processes: evolution and development. But how do these processes combine to produce integrated phenotypes? Comparative studies identify consistent patterns of covariation, or allometries, between brain and body size, and between brain components, indicating the presence of significant constraints limiting independent evolution of separate parts. These constraints are poorly understood, but in principle could be either developmental or functional. The developmental constraints hypothesis suggests that individual components (brain and body size, or individual brain components) tend to evolve together because natural selection operates on relatively simple developmental mechanisms that affect the growth of all parts in a concerted manner. The functional constraints hypothesis suggests that correlated change reflects the action of selection on distributed functional systems connecting the different sub-components, predicting more complex patterns of mosaic change at the level of the functional systems and more complex genetic and developmental mechanisms. These hypotheses are not mutually exclusive but make different predictions. We review recent genetic and neurodevelopmental evidence, concluding that functional rather than developmental constraints are the main cause of the observed patterns. PMID:27629025
Activation of Corticostriatal Circuitry Relieves Chronic Neuropathic Pain
Lee, Michelle; Manders, Toby R.; Eberle, Sarah E.; Su, Chen; D'amour, James; Yang, Runtao; Lin, Hau Yueh; Deisseroth, Karl; Froemke, Robert C.
2015-01-01
Neural circuits that determine the perception and modulation of pain remain poorly understood. The prefrontal cortex (PFC) provides top-down control of sensory and affective processes. While animal and human imaging studies have shown that the PFC is involved in pain regulation, its exact role in pain states remains incompletely understood. A key output target for the PFC is the nucleus accumbens (NAc), an important component of the reward circuitry. Interestingly, recent human imaging studies suggest that the projection from the PFC to the NAc is altered in chronic pain. The function of this corticostriatal projection in pain states, however, is not known. Here we show that optogenetic activation of the PFC produces strong antinociceptive effects in a rat model (spared nerve injury model) of persistent neuropathic pain. PFC activation also reduces the affective symptoms of pain. Furthermore, we show that this pain-relieving function of the PFC is likely mediated by projections to the NAc. Thus, our results support a novel role for corticostriatal circuitry in pain regulation. PMID:25834050
The Role of Microbial Iron Reduction in the Formation of Proterozoic Molar Tooth Structures
NASA Astrophysics Data System (ADS)
Hodgskiss, M. S. W.; Kunzmann, M.; Halverson, G. P.; Poirier, A.
2016-12-01
Molar tooth structures are poorly understood early diagenetic, microspar-filled voids in clay-rich carbonate sediments. They are a common structure in sedimentary successions dating from 2600-720 Ma, but do not occur in rocks older or younger. Despite being volumetrically significant in carbonate rocks of this age, their formation and disappearance are poorly understood. Here, we present iron isotope data, supported by carbon and oxygen isotopes, major and minor element concentrations, and total organic carbon and pyrite contents for samples from ten regions spanning 1870-635 Ma. The iron isotopic composition of molar tooth structures is almost always lighter (modal depletion of 2‰) than the carbonate or siliciclastic components in the host sediment, whereas carbon isotopes are indistinguishable. We interpret the isotopically light iron in molar tooth structures to have been produced by microbial iron reduction utilising Fe-oxyhydroxides and smectites. The microbial conversion of smectite to illite results in a volume reduction of clay minerals ( 30%), while locally increasing pore water alkalinity. Therefore, this biogeochemical process is a viable mechanism to produce voids and subsequently precipitate carbonate minerals. The disappearance of molar tooth structures is likely linked to a combination of a decrease in smectite abundance, a decline in the marine DIC reservoir, and increase in the concentration of O2 in shallow seawater in the mid-Neoproterozoic.
Learning a Foreign Language: A New Path to Enhancement of Cognitive Functions.
Shoghi Javan, Sara; Ghonsooly, Behzad
2018-02-01
The complicated cognitive processes involved in natural (primary) bilingualism lead to significant cognitive development. Executive functions as a fundamental component of human cognition are deemed to be affected by language learning. To date, a large number of studies have investigated how natural (primary) bilingualism influences executive functions; however, the way acquired (secondary) bilingualism manipulates executive functions is poorly understood. To fill this gap, controlling for age, gender, IQ, and socio-economic status, the researchers compared 60 advanced learners of English as a foreign language (EFL) to 60 beginners on measures of executive functions involving Stroop, Wisconsin Card Sorting Task (WCST) and Wechsler's digit span tasks. The results suggested that mastering English as a foreign language causes considerable enhancement in two components of executive functions, namely cognitive flexibility and working memory. However, no significant difference was observed in inhibitory control between the advanced EFL learners and beginners.
Pedophilic brain potential responses to adult erotic stimuli.
Knott, Verner; Impey, Danielle; Fisher, Derek; Delpero, Emily; Fedoroff, Paul
2016-02-01
Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults. Copyright © 2016. Published by Elsevier B.V.
POSH regulates Hippo signaling through ubiquitin-mediated expanded degradation.
Ma, Xianjue; Guo, Xiaowei; Richardson, Helena E; Xu, Tian; Xue, Lei
2018-02-27
The Hippo signaling pathway is a master regulator of organ growth, tissue homeostasis, and tumorigenesis. The activity of the Hippo pathway is controlled by various upstream components, including Expanded (Ex), but the precise molecular mechanism of how Ex is regulated remains poorly understood. Here we identify Plenty of SH3s (POSH), an E3 ubiquitin ligase, as a key component of Hippo signaling in Drosophila POSH overexpression synergizes with loss of Kibra to induce overgrowth and up-regulation of Hippo pathway target genes. Furthermore, knockdown of POSH impedes dextran sulfate sodium-induced Yorkie-dependent intestinal stem cell renewal, suggesting a physiological role of POSH in modulating Hippo signaling. Mechanistically, POSH binds to the C-terminal of Ex and is essential for the Crumbs-induced ubiquitination and degradation of Ex. Our findings establish POSH as a crucial regulator that integrates the signal from the cell surface to negatively regulate Ex-mediated Hippo activation in Drosophila .
Kanev, Ivan; Mei, Wai-Ning; Mizuno, Akira; DeHaai, Kristi; Sanmann, Jennifer; Hess, Michelle; Starr, Lois; Grove, Jennifer; Dave, Bhavana; Sanger, Warren
2013-01-01
Our studies reveal previously unidentified electrical properties of chromosomes: (1) chromosomes are amazingly similar in construction and function to electrical transformers; (2) chromosomes possess in their construction and function, components similar to those of electric generators, conductors, condensers, switches, and other components of electrical circuits; (3) chromosomes demonstrate in nano-scale level electromagnetic interactions, resonance, fusion and other phenomena similar to those described by equations in classical physics. These electrical properties and phenomena provide a possible explanation for unclear and poorly understood mechanisms in clinical genetics including: (a) electrically based mechanisms responsible for breaks, translocations, fusions, and other chromosomal abnormalities associated with cancer, intellectual disability, infertility, pregnancy loss, Down syndrome, and other genetic disorders; (b) electrically based mechanisms involved in crossing over, non-disjunction and other events during meiosis and mitosis; (c) mechanisms demonstrating heterochromatin to be electrically active and genetically important. PMID:24688715
Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP.
Perederina, Anna; Khanova, Elena; Quan, Chao; Berezin, Igor; Esakova, Olga; Krasilnikov, Andrey S
2011-10-01
Ribonuclease (RNase) MRP is a multicomponent ribonucleoprotein complex closely related to RNase P. RNase MRP and eukaryotic RNase P share most of their protein components, as well as multiple features of their catalytic RNA moieties, but have distinct substrate specificities. While RNase P is practically universally found in all three domains of life, RNase MRP is essential in eukaryotes. The structural organizations of eukaryotic RNase P and RNase MRP are poorly understood. Here, we show that Pop5 and Rpp1, protein components found in both RNase P and RNase MRP, form a heterodimer that binds directly to the conserved area of the putative catalytic domain of RNase MRP RNA. The Pop5/Rpp1 binding site corresponds to the protein binding site in bacterial RNase P RNA. Structural and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are discussed.
Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP
Perederina, Anna; Khanova, Elena; Quan, Chao; Berezin, Igor; Esakova, Olga; Krasilnikov, Andrey S.
2011-01-01
Ribonuclease (RNase) MRP is a multicomponent ribonucleoprotein complex closely related to RNase P. RNase MRP and eukaryotic RNase P share most of their protein components, as well as multiple features of their catalytic RNA moieties, but have distinct substrate specificities. While RNase P is practically universally found in all three domains of life, RNase MRP is essential in eukaryotes. The structural organizations of eukaryotic RNase P and RNase MRP are poorly understood. Here, we show that Pop5 and Rpp1, protein components found in both RNase P and RNase MRP, form a heterodimer that binds directly to the conserved area of the putative catalytic domain of RNase MRP RNA. The Pop5/Rpp1 binding site corresponds to the protein binding site in bacterial RNase P RNA. Structural and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are discussed. PMID:21878546
Users matter : multi-agent systems model of high performance computing cluster users.
DOE Office of Scientific and Technical Information (OSTI.GOV)
North, M. J.; Hood, C. S.; Decision and Information Sciences
2005-01-01
High performance computing clusters have been a critical resource for computational science for over a decade and have more recently become integral to large-scale industrial analysis. Despite their well-specified components, the aggregate behavior of clusters is poorly understood. The difficulties arise from complicated interactions between cluster components during operation. These interactions have been studied by many researchers, some of whom have identified the need for holistic multi-scale modeling that simultaneously includes network level, operating system level, process level, and user level behaviors. Each of these levels presents its own modeling challenges, but the user level is the most complex duemore » to the adaptability of human beings. In this vein, there are several major user modeling goals, namely descriptive modeling, predictive modeling and automated weakness discovery. This study shows how multi-agent techniques were used to simulate a large-scale computing cluster at each of these levels.« less
Lee, Ji-Young; Acosta, Eliana G.; Stoeck, Ina Karen; Long, Gang; Hiet, Marie-Sophie; Mueller, Birthe; Fackler, Oliver T.; Kallis, Stephanie
2014-01-01
ABSTRACT The assembly of infectious hepatitis C virus (HCV) particles is tightly linked to components of the very-low-density lipoprotein (VLDL) pathway. We and others have shown that apolipoprotein E (ApoE) plays a major role in production of infectious HCV particles. However, the mechanism by which ApoE contributes to virion assembly/release and how it gets associated with the HCV particle is poorly understood. We found that knockdown of ApoE reduces titers of infectious intra- and extracellular HCV but not of the related dengue virus. ApoE depletion also reduced amounts of extracellular HCV core protein without affecting intracellular core amounts. Moreover, we found that ApoE depletion affected neither formation of nucleocapsids nor their envelopment, suggesting that ApoE acts at a late step of assembly, such as particle maturation and infectivity. Importantly, we demonstrate that ApoE interacts with the HCV envelope glycoproteins, most notably E2. This interaction did not require any other viral proteins and depended on the transmembrane domain of E2 that also was required for recruitment of HCV envelope glycoproteins to detergent-resistant membrane fractions. These results suggest that ApoE plays an important role in HCV particle maturation, presumably by direct interaction with viral envelope glycoproteins. IMPORTANCE The HCV replication cycle is tightly linked to host cell lipid pathways and components. This is best illustrated by the dependency of HCV assembly on lipid droplets and the VLDL component ApoE. Although the role of ApoE for production of infectious HCV particles is well established, it is still poorly understood how ApoE contributes to virion formation and how it gets associated with HCV particles. Here, we provide experimental evidence that ApoE likely is required for an intracellular maturation step of HCV particles. Moreover, we demonstrate that ApoE associates with the viral envelope glycoproteins. This interaction appears to be dispensable for envelopment of virus particles but likely contributes to the quality control of secreted infectious virions. These results shed new light on the exploitation of host cell lipid pathways by HCV and the link of viral particle assembly to the VLDL component ApoE. PMID:25122793
Winners and losers in the competition for space in tropical forest canopies.
Kellner, James R; Asner, Gregory P
2014-05-01
Trees compete for space in the canopy, but where and how individuals or their component parts win or lose is poorly understood. We developed a stochastic model of three-dimensional dynamics in canopies using a hierarchical Bayesian framework, and analysed 267,533 positive height changes from 1.25 m pixels using data from airborne LiDAR within 43 ha on the windward flank of Mauna Kea. Model selection indicates a strong resident's advantage, with 97.9% of positions in the canopy retained by their occupants over 2 years. The remaining 2.1% were lost to a neighbouring contender. Absolute height was a poor predictor of success, but short stature greatly raised the risk of being overtopped. Growth in the canopy was exponentially distributed with a scaling parameter of 0.518. These findings show how size and spatial proximity influence the outcome of competition for space, and provide a general framework for the analysis of canopy dynamics. © 2014 John Wiley & Sons Ltd/CNRS.
Why Do Lithium-Oxygen Batteries Fail: Parasitic Chemical Reactions and Their Synergistic Effect.
Yao, Xiahui; Dong, Qi; Cheng, Qingmei; Wang, Dunwei
2016-09-12
As an electrochemical energy-storage technology with the highest theoretical capacity, lithium-oxygen batteries face critical challenges in terms of poor stabilities and low charge/discharge round-trip efficiencies. It is generally recognized that these issues are connected to the parasitic chemical reactions at the anode, electrolyte, and cathode. While the detailed mechanisms of these reactions have been studied separately, the possible synergistic effects between these reactions remain poorly understood. To fill in the knowledge gap, this Minireview examines literature reports on the parasitic chemical reactions and finds the reactive oxygen species a key chemical mediator that participates in or facilitates nearly all parasitic chemical reactions. Given the ubiquitous presence of oxygen in all test cells, this finding is important. It offers new insights into how to stabilize various components of lithium-oxygen batteries for high-performance operations and how to eventually materialize the full potentials of this promising technology. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Etiological Distinction of Working Memory Components in Relation to Mathematics
Lukowski, Sarah L.; Soden, Brooke; Hart, Sara A.; Thompson, Lee A.; Kovas, Yulia; Petrill, Stephen A.
2014-01-01
Working memory has been consistently associated with mathematics achievement, although the etiology of these relations remains poorly understood. The present study examined the genetic and environmental underpinnings of math story problem solving, timed calculation, and untimed calculation alongside working memory components in 12-year-old monozygotic (n = 105) and same-sex dizygotic (n = 143) twin pairs. Results indicated significant phenotypic correlation between each working memory component and all mathematics outcomes (r = 0.18 – 0.33). Additive genetic influences shared between the visuo-spatial sketchpad and mathematics achievement was significant, accounting for roughly 89% of the observed correlation. In addition, genetic covariance was found between the phonological loop and math story problem solving. In contrast, despite there being a significant observed relationship between phonological loop and timed and untimed calculation, there was no significant genetic or environmental covariance between the phonological loop and timed or untimed calculation skills. Further analyses indicated that genetic overlap between the visuo-spatial sketchpad and math story problem solving and math fluency was distinct from general genetic factors, whereas g, phonological loop, and mathematics shared generalist genes. Thus, although each working memory component was related to mathematics, the etiology of their relationships may be distinct. PMID:25477699
Chemical Weathering on a Cold and Wet Ancient Mars: New Insights from a Glacial Mars Analog Site
NASA Astrophysics Data System (ADS)
Scudder, N.; Horgan, B. H. N.; Rutledge, A. M.; Rampe, E. B.
2016-12-01
If cold climates prevailed on ancient Mars, we should expect to see corroborating mineralogical evidence preserved in the geologic record. However, the extent to which the diverse alteration mineralogy observed on Mars can be explained by cold climate weathering is currently unknown, as the alteration phases that result from weathering by snow and ice are poorly understood. If cold climate weathering produces distinct alteration signatures, they may be a useful climate indicator on Mars. On Earth, poorly crystalline or short order silicates, such as allophane, tend to dominate in alpine and arctic soils where weathering mainly occurs through rapid seasonal melting of ice and snow. This mineralogy is distinct from the crystalline phyllosilicates that are common in more temperate climates. Thus, we hypothesize that high abundances of poorly crystalline material could indicate cold climate weathering. Here we report new results from a field campaign at the mafic and glaciated Three Sisters volcanic complex in Oregon, USA, to determine the mineralogy and chemistry of cold climate weathering in a Mars analog environment. We find that high abundances of poorly crystalline phases are generated in this environment and that these phases may be detectable using orbital spectroscopy. Ongoing chemical and mineralogical analyses of glacial till and sediments from glacier-fed lakes and streams will allow us to determine the specific distribution and composition of mineral phases in Mars-relevant glacial environments. Poorly crystalline phases have been detected on Mars: modeling of TES data suggests a regionally distributed allophane component, while MER and MSL results indicate up to 40-50% amorphous components in rocks and sediments at Gusev and Gale Craters. We hypothesize that these could be the result of weathering by ice and snow. However, it is not clear that more crystalline alteration phases observed elsewhere on Mars could be formed under a globally cold climate.
Jaillon, Sébastien; Moalli, Federica; Ragnarsdottir, Bryndis; Bonavita, Eduardo; Puthia, Manoj; Riva, Federica; Barbati, Elisa; Nebuloni, Manuela; Cvetko Krajinovic, Lidija; Markotic, Alemka; Valentino, Sonia; Doni, Andrea; Tartari, Silvia; Graziani, Giorgio; Montanelli, Alessandro; Delneste, Yves; Svanborg, Catharina; Garlanda, Cecilia; Mantovani, Alberto
2014-04-17
Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs. Copyright © 2014 Elsevier Inc. All rights reserved.
Aram, Lior; Braun, Tslil; Braverman, Carmel; Kaplan, Yosef; Ravid, Liat; Levin-Zaidman, Smadar; Arama, Eli
2016-04-04
How cells avoid excessive caspase activity and unwanted cell death during apoptotic caspase-mediated removal of large cellular structures is poorly understood. We investigate caspase-mediated extrusion of spermatid cytoplasmic contents in Drosophila during spermatid individualization. We show that a Krebs cycle component, the ATP-specific form of the succinyl-CoA synthetase β subunit (A-Sβ), binds to and activates the Cullin-3-based ubiquitin ligase (CRL3) complex required for caspase activation in spermatids. In vitro and in vivo evidence suggests that this interaction occurs on the mitochondrial surface, thereby limiting the source of CRL3 complex activation to the vicinity of this organelle and reducing the potential rate of caspase activation by at least 60%. Domain swapping between A-Sβ and the GTP-specific SCSβ (G-Sβ), which functions redundantly in the Krebs cycle, show that the metabolic and structural roles of A-Sβ in spermatids can be uncoupled, highlighting a moonlighting function of this Krebs cycle component in CRL activation. Copyright © 2016 Elsevier Inc. All rights reserved.
Morrow, E H; Leijon, A; Meerupati, A
2008-11-01
Spermatozoa are the most diverse of all animal cells. Variation in size alone is enormous and yet there are still no clear evolutionary explanations that can account for such diversity. The basic genetics of sperm form is also poorly understood, although sperm size is known to have a strong genetic component. Here, using hemiclonal analysis of Drosophila melanogaster, we demonstrate that there is not only a significant additive genetic component contributing to phenotypic variation in sperm length but also a significant environmental effect. Furthermore, the plasticity of sperm size has a significant genetic component to it (a genotype x environment interaction). A genotype x environment interaction could contribute to the maintenance of the substantial genetic variation in this trait and thereby explain the persistent inter-male differences in sperm size seen in numerous taxa. We suggest that the low conditional dependence and high heritability but low evolvability (the coefficient of additive genetic variation) of sperm length is more consistent with a history of stabilizing selection rather than either sexual selection or strong directional selection.
Analysis of free modeling predictions by RBO aleph in CASP11.
Mabrouk, Mahmoud; Werner, Tim; Schneider, Michael; Putz, Ines; Brock, Oliver
2016-09-01
The CASP experiment is a biannual benchmark for assessing protein structure prediction methods. In CASP11, RBO Aleph ranked as one of the top-performing automated servers in the free modeling category. This category consists of targets for which structural templates are not easily retrievable. We analyze the performance of RBO Aleph and show that its success in CASP was a result of its ab initio structure prediction protocol. A detailed analysis of this protocol demonstrates that two components unique to our method greatly contributed to prediction quality: residue-residue contact prediction by EPC-map and contact-guided conformational space search by model-based search (MBS). Interestingly, our analysis also points to a possible fundamental problem in evaluating the performance of protein structure prediction methods: Improvements in components of the method do not necessarily lead to improvements of the entire method. This points to the fact that these components interact in ways that are poorly understood. This problem, if indeed true, represents a significant obstacle to community-wide progress. Proteins 2016; 84(Suppl 1):87-104. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
The Arabidopsis EIN2 restricts organ growth by retarding cell expansion
Feng, Guanping; Liu, Gang; Xiao, Jianhua
2015-01-01
The growth of plant organ to its characteristic size is a fundamental developmental process, but the mechanism is still poorly understood. Plant hormones play a great role in organ size control by modulating cell division and/or cell expansion. ETHYLENE INSENSITVE 2 (EIN2) was first identified by a genetic screen for ethylene insensitivity and is regarded as a central component of ethylene signaling, but its role in cell growth has not been reported. Here we demonstrate that changed expression of EIN2 led to abnormity of cell expansion by morphological and cytological analyses of EIN2 loss-of-function mutants and the overexpressing transgenic plant. Our findings suggest that EIN2 controls final organ size by restricting cell expansion. PMID:26039475
EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.
Dong, Yixin; Isono, Kyo-Ichi; Ohbo, Kazuyuki; Endo, Takaho A; Ohara, Osamu; Maekawa, Mamiko; Toyama, Yoshiro; Ito, Chizuru; Toshimori, Kiyotaka; Helin, Kristian; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Yamagata, Kazutsune; Kitabayashi, Issay; Koseki, Haruhiko
2017-10-01
Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome. Copyright © 2017 American Society for Microbiology.
Wu, Ling; Velander, Paul; Liu, Dongmin; Xu, Bin
2017-09-26
Oleuropein, a natural product derived from olive leaves, has reported anti-diabetic functions. However, detailed molecular mechanisms for how it affects β-cell functions remain poorly understood. Here, we present evidence that oleuropein promotes glucose-stimulated insulin secretion (GSIS) in β-cells. The effect is dose-dependent and stimulates the ERK/MAPK signaling pathway. We further demonstrated that oleuropein inhibits the cytotoxicity induced by amylin amyloids, a hallmark feature of type 2 diabetes. We demonstrated that these dual functions are structure-specific: we identified the 3-hydroxytyrosol moiety of oleuropein as the main functional entity responsible for amyloid inhibition, but the novel GSIS function requires the entire structure scaffold of the molecule.
Reinders, Yvonne; Felthaus, Oliver; Brockhoff, Gero; Pohl, Fabian; Prantl, Lukas; Haubner, Frank
2017-01-01
Platelet-rich plasma is a current subject of studies on chronic wound healing therapy due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of platelet-rich plasma on irradiated cells of the cutaneous wound healing process are poorly understood so far. In this study, the interaction of endothelial cells and adipose-derived stem cells in conjunction with treatment with platelet-rich plasma is investigated in the context of radiation effects. Therefore, the expression of surface-marker CD90 and CD31 was determined. Moreover, cell proliferation and viability after external radiation was analyzed with and without treatment by platelet-rich plasma. PMID:28829358
Cocoa Bioactive Compounds: Significance and Potential for the Maintenance of Skin Health
Scapagnini, Giovanni; Davinelli, Sergio; Di Renzo, Laura; De Lorenzo, Antonino; Olarte, Hector Hugo; Micali, Giuseppe; Cicero, Arrigo F.; Gonzalez, Salvador
2014-01-01
Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health. PMID:25116848
Friction coefficient dependence on electrostatic tribocharging
Burgo, Thiago A. L.; Silva, Cristiane A.; Balestrin, Lia B. S.; Galembeck, Fernando
2013-01-01
Friction between dielectric surfaces produces patterns of fixed, stable electric charges that in turn contribute electrostatic components to surface interactions between the contacting solids. The literature presents a wealth of information on the electronic contributions to friction in metals and semiconductors but the effect of triboelectricity on friction coefficients of dielectrics is as yet poorly defined and understood. In this work, friction coefficients were measured on tribocharged polytetrafluoroethylene (PTFE), using three different techniques. As a result, friction coefficients at the macro- and nanoscales increase many-fold when PTFE surfaces are tribocharged, but this effect is eliminated by silanization of glass spheres rolling on PTFE. In conclusion, tribocharging may supersede all other contributions to macro- and nanoscale friction coefficients in PTFE and probably in other insulating polymers. PMID:23934227
Spitzer Observations of the X-ray Sources of NGC 4485/90
NASA Astrophysics Data System (ADS)
Vazquez, Gerardo A.; Colbert, E.; Hornschemeier, A.; Malhotra, S.; Roberts, T.; Ward, M.
2006-06-01
The mechanism for forming (or igniting) so-called Ultra-Luminous X- ray sources (ULXs) is very poorly understood. In order to investigate the stellar and gaseous environment of ULXs, we have observed the nearby starburst galaxy system NGC 4485/90 with Spitzer's IRAC and IRS instruments. High-quality mid-infrared images and spectra are used to characterize the stellar history of stars near the ULXs, and the ionization state of the surrounding gas. NGC 4485/90 fortuitively hosts six ULXs, and we have analyzed IRAC images and IRS spectra of all six regions. We also observed two "comparison" regions with no X-ray sources. Here we present our preliminary findings on the similarities and differences between the stellar and gaseous components near the ULXs.
Mechano-adaptation of the stem cell nucleus.
Heo, Su-Jin; Cosgrove, Brian D; Dai, Eric N; Mauck, Robert L
2018-01-01
Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this "mechano-adaptation" are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation.
Mechano-adaptation of the stem cell nucleus
Heo, Su-Jin; Cosgrove, Brian D.; Dai, Eric N.; Mauck, Robert L.
2018-01-01
ABSTRACT Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this “mechano-adaptation” are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation. PMID:29099288
Global Analysis Reveals the Complexity of the Human Glomerular Extracellular Matrix
Byron, Adam; Humphries, Jonathan D.; Randles, Michael J.; Carisey, Alex; Murphy, Stephanie; Knight, David; Brenchley, Paul E.; Zent, Roy; Humphries, Martin J.
2014-01-01
The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the cellular components have helped to build understanding of glomerular disease; however, the full composition and regulation of glomerular ECM remains poorly understood. We used mass spectrometry-based proteomics of enriched ECM extracts for a global analysis of human glomerular ECM in vivo and identified a tissue-specific proteome of 144 structural and regulatory ECM proteins. This catalog includes all previously identified glomerular components plus many new and abundant components. Relative protein quantification showed a dominance of collagen IV, collagen I, and laminin isoforms in the glomerular ECM together with abundant collagen VI and TINAGL1. Protein network analysis enabled the creation of a glomerular ECM interactome, which revealed a core of highly connected structural components. More than one half of the glomerular ECM proteome was validated using colocalization studies and data from the Human Protein Atlas. This study yields the greatest number of ECM proteins relative to previous investigations of whole glomerular extracts, highlighting the importance of sample enrichment. It also shows that the composition of glomerular ECM is far more complex than previously appreciated and suggests that many more ECM components may contribute to glomerular development and disease processes. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000456. PMID:24436468
Garg, Mayur; Burrell, Louise M; Velkoska, Elena; Griggs, Karen; Angus, Peter W; Gibson, Peter R; Lubel, John S
2015-09-01
The relationship between intestinal inflammation and circulating components of the renin-angiotensin system (RAS) is poorly understood. Demographic and clinical data were obtained from healthy controls and patients with inflammatory bowel disease (IBD). Plasma concentrations of the classical RAS components (angiotensin-converting enzyme (ACE) and angiotensin II (Ang II)) and alternative RAS components (ACE2 and angiotensin (1-7) (Ang (1-7))) were analysed by radioimmuno- and enzymatic assays. Systemic inflammation was assessed using serum C-reactive protein (CRP), white cell count, platelet count and albumin, and intestinal inflammation by faecal calprotectin. Nineteen healthy controls (11 female; mean age 38 years, range 23-68), 19 patients with Crohn's disease (11 female; aged 45 years, range 23-76) and 15 patients with ulcerative colitis (6 female; aged 42 years, 26-64) were studied. Circulating classical RAS component levels were similar across the three groups, whereas ACE2 activity and Ang (1-7) concentrations were higher in patients with IBD compared to controls (ACE2: 21.5 vs 13.3 pmol/ml/min, p<0.05; Ang (1-7): 22.8 vs 14.1 pg/ml, p<0.001). Ang (1-7) correlated weakly with platelet and white cell counts, but not calprotectin or CRP, in patients with IBD. Circulating components of the alternative RAS are increased in patients with IBD. © The Author(s) 2014.
Aravind, L.; Burroughs, A. Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M.
2014-01-01
Epigenetic information, which plays a major role in eukaryotic biology, is transmitted by covalent modifications of nuclear proteins (e.g., histones) and DNA, along with poorly understood processes involving cytoplasmic/secreted proteins and RNAs. The origin of eukaryotes was accompanied by emergence of a highly developed biochemical apparatus for encoding, resetting, and reading covalent epigenetic marks in proteins such as histones and tubulins. The provenance of this apparatus remained unclear until recently. Developments in comparative genomics show that key components of eukaryotic epigenetics emerged as part of the extensive biochemical innovation of secondary metabolism and intergenomic/interorganismal conflict systems in prokaryotes, particularly bacteria. These supplied not only enzymatic components for encoding and removing epigenetic modifications, but also readers of some of these marks. Diversification of these prokaryotic systems and subsequently eukaryotic epigenetics appear to have been considerably influenced by the great oxygenation event in the Earth’s history. PMID:24984775
Aravind, L; Burroughs, A Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M
2014-07-01
Epigenetic information, which plays a major role in eukaryotic biology, is transmitted by covalent modifications of nuclear proteins (e.g., histones) and DNA, along with poorly understood processes involving cytoplasmic/secreted proteins and RNAs. The origin of eukaryotes was accompanied by emergence of a highly developed biochemical apparatus for encoding, resetting, and reading covalent epigenetic marks in proteins such as histones and tubulins. The provenance of this apparatus remained unclear until recently. Developments in comparative genomics show that key components of eukaryotic epigenetics emerged as part of the extensive biochemical innovation of secondary metabolism and intergenomic/interorganismal conflict systems in prokaryotes, particularly bacteria. These supplied not only enzymatic components for encoding and removing epigenetic modifications, but also readers of some of these marks. Diversification of these prokaryotic systems and subsequently eukaryotic epigenetics appear to have been considerably influenced by the great oxygenation event in the Earth's history. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.
Murakami, Masayoshi; Shteingart, Hanan; Loewenstein, Yonatan; Mainen, Zachary F
2017-05-17
The selection and timing of actions are subject to determinate influences such as sensory cues and internal state as well as to effectively stochastic variability. Although stochastic choice mechanisms are assumed by many theoretical models, their origin and mechanisms remain poorly understood. Here we investigated this issue by studying how neural circuits in the frontal cortex determine action timing in rats performing a waiting task. Electrophysiological recordings from two regions necessary for this behavior, medial prefrontal cortex (mPFC) and secondary motor cortex (M2), revealed an unexpected functional dissociation. Both areas encoded deterministic biases in action timing, but only M2 neurons reflected stochastic trial-by-trial fluctuations. This differential coding was reflected in distinct timescales of neural dynamics in the two frontal cortical areas. These results suggest a two-stage model in which stochastic components of action timing decisions are injected by circuits downstream of those carrying deterministic bias signals. Copyright © 2017 Elsevier Inc. All rights reserved.
Immobile myosin-II plays a scaffolding role during cytokinesis in budding yeast
Wloka, Carsten; Vallen, Elizabeth A.; Thé, Lydia; Fang, Xiaodong; Oh, Younghoon
2013-01-01
Core components of cytokinesis are conserved from yeast to human, but how these components are assembled into a robust machine that drives cytokinesis remains poorly understood. In this paper, we show by fluorescence recovery after photobleaching analysis that Myo1, the sole myosin-II in budding yeast, was mobile at the division site before anaphase and became immobilized shortly before cytokinesis. This immobility was independent of actin filaments or the motor domain of Myo1 but required a small region in the Myo1 tail that is thought to be involved in higher-order assembly. As expected, proteins involved in actin ring assembly (tropomyosin and formin) and membrane trafficking (myosin-V and exocyst) were dynamic during cytokinesis. Strikingly, proteins involved in septum formation (the chitin synthase Chs2) and/or its coordination with the actomyosin ring (essential light chain, IQGAP, F-BAR, etc.) displayed Myo1-dependent immobility during cytokinesis, suggesting that Myo1 plays a scaffolding role in the assembly of a cytokinesis machine. PMID:23358243
The bioactive acidic serine- and aspartate-rich motif peptide.
Minamizaki, Tomoko; Yoshiko, Yuji
2015-01-01
The organic component of the bone matrix comprises 40% dry weight of bone. The organic component is mostly composed of type I collagen and small amounts of non-collagenous proteins (NCPs) (10-15% of the total bone protein content). The small integrin-binding ligand N-linked glycoprotein (SIBLING) family, a NCP, is considered to play a key role in bone mineralization. SIBLING family of proteins share common structural features and includes the arginine-glycine-aspartic acid (RGD) motif and acidic serine- and aspartic acid-rich motif (ASARM). Clinical manifestations of gene mutations and/or genetically modified mice indicate that SIBLINGs play diverse roles in bone and extraskeletal tissues. ASARM peptides might not be primary responsible for the functional diversity of SIBLINGs, but this motif is suggested to be a key domain of SIBLINGs. However, the exact function of ASARM peptides is poorly understood. In this article, we discuss the considerable progress made in understanding the role of ASARM as a bioactive peptide.
Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing
2016-11-15
Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.
F-box-like domain in the polerovirus protein P0 is required for silencing suppressor function
Pazhouhandeh, Maghsoud; Dieterle, Monika; Marrocco, Katia; Lechner, Esther; Berry, Bassam; Brault, Véronique; Hemmer, Odile; Kretsch, Thomas; Richards, Kenneth E.; Genschik, Pascal; Ziegler-Graff, Véronique
2006-01-01
Plants employ small RNA-mediated posttranscriptional gene silencing as a virus defense mechanism. In response, plant viruses encode proteins that can suppress RNA silencing, but the mode of action of most such proteins is poorly understood. Here, we show that the silencing suppressor protein P0 of two Arabidopsis-infecting poleroviruses interacts by means of a conserved minimal F-box motif with Arabidopsis thaliana orthologs of S-phase kinase-related protein 1 (SKP1), a component of the SCF family of ubiquitin E3 ligases. Point mutations in the F-box-like motif abolished the P0–SKP1 ortholog interaction, diminished virus pathogenicity, and inhibited the silencing suppressor activity of P0. Knockdown of expression of a SKP1 ortholog in Nicotiana benthamiana rendered the plants resistant to polerovirus infection. Together, the results support a model in which P0 acts as an F-box protein that targets an essential component of the host posttranscriptional gene silencing machinery. PMID:16446454
GINS complex protein Sld5 recruits SIK1 to activate MCM helicase during DNA replication.
Joshi, Kiranmai; Shah, Varun Jayeshkumar; Maddika, Subbareddy
2016-12-01
In eukaryotes, proper loading and activation of MCM helicase at chromosomal origins plays a central role in DNA replication. Activation of MCM helicase requires its association with CDC45-GINS complex, but the mechanism of how this complex activates MCM helicase is poorly understood. Here we identified SIK1 (salt-inducible kinase 1), an AMPK related protein kinase, as a molecular link that connects GINS complex with MCM helicase activity. We demonstrated that Sld5 a component of GINS complex interacts with SIK1 and recruits it to the sites of DNA replication at the onset of S phase. Depletion of SIK1 leads to defective DNA replication. Further, we showed that SIK1 phosphorylates MCM2 at five conserved residues at its N-terminus, which is essential for the activation of MCM helicase. Collectively, our results suggest SIK1 as a novel integral component of CMG replicative helicase during eukaryotic DNA replication. Copyright © 2016 Elsevier Inc. All rights reserved.
A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling.
Bai, Zhiyong; Grant, Barth D
2015-03-24
Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1-positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42-associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling.
A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling
Bai, Zhiyong; Grant, Barth D.
2015-01-01
Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1–positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42–associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling. PMID:25775511
Forest biomass, productivity and carbon cycling along a rainfall gradient in West Africa.
Moore, Sam; Adu-Bredu, Stephen; Duah-Gyamfi, Akwasi; Addo-Danso, Shalom D; Ibrahim, Forzia; Mbou, Armel T; de Grandcourt, Agnès; Valentini, Riccardo; Nicolini, Giacomo; Djagbletey, Gloria; Owusu-Afriyie, Kennedy; Gvozdevaite, Agne; Oliveras, Imma; Ruiz-Jaen, Maria C; Malhi, Yadvinder
2018-02-01
Net Primary Productivity (NPP) is one of the most important parameters in describing the functioning of any ecosystem and yet it arguably remains a poorly quantified and understood component of carbon cycling in tropical forests, especially outside of the Americas. We provide the first comprehensive analysis of NPP and its carbon allocation to woody, canopy and root growth components at contrasting lowland West African forests spanning a rainfall gradient. Using a standardized methodology to study evergreen (EF), semi-deciduous (SDF), dry forests (DF) and woody savanna (WS), we find that (i) climate is more closely related with above and belowground C stocks than with NPP (ii) total NPP is highest in the SDF site, then the EF followed by the DF and WS and that (iii) different forest types have distinct carbon allocation patterns whereby SDF allocate in excess of 50% to canopy production and the DF and WS sites allocate 40%-50% to woody production. Furthermore, we find that (iv) compared with canopy and root growth rates the woody growth rate of these forests is a poor proxy for their overall productivity and that (v) residence time is the primary driver in the productivity-allocation-turnover chain for the observed spatial differences in woody, leaf and root biomass across the rainfall gradient. Through a systematic assessment of forest productivity we demonstrate the importance of directly measuring the main components of above and belowground NPP and encourage the establishment of more permanent carbon intensive monitoring plots across the tropics. © 2017 John Wiley & Sons Ltd.
NASA Astrophysics Data System (ADS)
Buchner, Johannes; Bauer, Franz E.
2017-03-01
The 'torus' obscurer of active galactic nuclei (AGN) is poorly understood in terms of its density, sub-structure and physical mechanisms. Large X-ray surveys provide model boundary constraints, for both Compton-thin and Compton-thick levels of obscuration, as obscured fractions are mean covering factors fcov. However, a major remaining uncertainty is host-galaxy obscuration. In Paper I, we discovered a relation of {NH} ∝ M_{star }^{1/3} for the obscuration of galaxy-scale gas. Here, we apply this observational relation to the AGN population, and find that galaxy-scale gas is responsible for a luminosity-independent fraction of Compton-thin AGN, but does not produce Compton-thick columns. With the host-galaxy obscuration understood, we present a model of the remaining nuclear obscurer, which is consistent with a range of observations. Our radiation-lifted torus model consists of a Compton-thick component (fcov ∼ 35 per cent) and a Compton-thin component (fcov ∼ 40 per cent), which depends on both black hole mass and luminosity. This provides a useful summary of observational constraints for torus modellers who attempt to reproduce this behaviour. It can also be employed as a sub-grid recipe in cosmological simulations that do not resolve the torus. We also investigate host-galaxy X-ray obscuration inside cosmological, hydrodynamic simulations (Evolution and Assembly of Galaxies and their Environment; Illustris). The obscuration from ray-traced galaxy gas can agree with observations, but is highly sensitive to the chosen feedback assumptions.
NASA Astrophysics Data System (ADS)
Wonaschuetz, Anna
Atmospheric aerosols are a highly relevant component of the climate system affecting atmospheric radiative transfer and the hydrological cycle. As opposed to other key atmospheric constituents with climatic relevance, atmospheric aerosol particles are highly heterogeneous in time and space with respect to their size, concentration, chemical composition and physical properties. Many aspects of their life cycle are not understood, making them difficult to represent in climate models and hard to control as a pollutant. Aerosol-cloud interactions in particular are infamous as a major source of uncertainty in future climate predictions. Field measurements are an important source of information for the modeling community and can lead to a better understanding of chemical and microphysical processes. In this study, field data from urban, marine, and arid settings are analyzed and the impact of meteorological conditions on the evolution of aerosol particles while in the atmosphere is investigated. Particular attention is given to organic aerosols, which are a poorly understood component of atmospheric aerosols. Local wind characteristics, solar radiation, relative humidity and the presence or absence of clouds and fog are found to be crucial factors in the transport and chemical evolution of aerosol particles. Organic aerosols in particular are found to be heavily impacted by processes in the liquid phase (cloud droplets and aerosol water). The reported measurements serve to improve the process-level understanding of aerosol evolution in different environments and to inform the modeling community by providing realistic values for input parameters and validation of model calculations.
Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kim, Jihye; Kang, Jaewoo; Tan, Aik Choon
2018-04-04
Traditional Chinese Medicine (TCM) has been practiced over thousands of years in China and other Asian countries for treating various symptoms and diseases. However, the underlying molecular mechanisms of TCM are poorly understood, partly due to the "multi-component, multi-target" nature of TCM. To uncover the molecular mechanisms of TCM, we perform comprehensive gene expression analysis using connectivity map. We interrogated gene expression signatures obtained 102 TCM components using the next generation Connectivity Map (CMap) resource. We performed systematic data mining and analysis on the mechanism of action (MoA) of these TCM components based on the CMap results. We clustered the 102 TCM components into four groups based on their MoAs using next generation CMap resource. We performed gene set enrichment analysis on these components to provide additional supports for explaining these molecular mechanisms. We also provided literature evidence to validate the MoAs identified through this bioinformatics analysis. Finally, we developed the Traditional Chinese Medicine Drug Repurposing Hub (TCM Hub) - a connectivity map resource to facilitate the elucidation of TCM MoA for drug repurposing research. TCMHub is freely available in http://tanlab.ucdenver.edu/TCMHub. Molecular mechanisms of TCM could be uncovered by using gene expression signatures and connectivity map. Through this analysis, we identified many of the TCM components possess diverse MoAs, this may explain the applications of TCM in treating various symptoms and diseases. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Beaussart, Audrey; Herman, Philippe; El-Kirat-Chatel, Sofiane; Lipke, Peter N.; Kucharíková, Soňa; van Dijck, Patrick; Dufrêne, Yves F.
2013-10-01
Despite the clinical importance of bacterial-fungal interactions, their molecular details are poorly understood. A hallmark of such medically important interspecies associations is the interaction between the two nosocomial pathogens Staphylococcus aureus and Candida albicans, which can lead to mixed biofilm-associated infections with enhanced antibiotic resistance. Here, we use single-cell force spectroscopy (SCFS) to quantify the forces engaged in bacterial-fungal co-adhesion, focusing on the poorly investigated S. epidermidis-C. albicans interaction. Force curves recorded between single bacterial and fungal germ tubes showed large adhesion forces (~5 nN) with extended rupture lengths (up to 500 nm). By contrast, bacteria poorly adhered to yeast cells, emphasizing the important role of the yeast-to-hyphae transition in mediating adhesion to bacterial cells. Analysis of mutant strains altered in cell wall composition allowed us to distinguish the main fungal components involved in adhesion, i.e. Als proteins and O-mannosylations. We suggest that the measured co-adhesion forces are involved in the formation of mixed biofilms, thus possibly as well in promoting polymicrobial infections. In the future, we anticipate that this SCFS platform will be used in nanomedicine to decipher the molecular mechanisms of a wide variety of pathogen-pathogen interactions and may help in designing novel anti-adhesion agents.
Designing the ideal habitat for entomopathogen use in nursery production.
Nielsen, Anne L; Lewis, Edwin E
2012-07-01
Greenhouse and nursery producers use entomopathogens (nematodes and fungi) to control soil pests. Although it is known that the physical and chemical properties of mineral soil significantly impact upon soil pathogens, the influence of soilless media used for plant production on entomopathogen performance is poorly understood. Survival and foraging distance were differently affected by sand:peat, bark and sawdust media for entomopathogenic nematodes, but not for the immobile fungus Metarhizium anisopliae. Redwood sawdust medium consistently had a negative impact upon entomopathogenic nematodes. Dividing media into individual components supported the hypothesis that redwood sawdust reduced foraging and infection abilities of S. riobrave and H. bacteriophora. Physically altering the components by adding sand significantly improved foraging and infection success for S. riobrave in media not optimum for foraging. This study is the first to highlight the importance of selecting the appropriate soilless media and pathogen species combinations to increase efficacy of biological control. H. bacteriophora was able to find hosts in a wider diversity of medium components than S. riobrave, although both nematode species performed well in peat moss and recycled plant material. These results suggest that peat moss, recycled plant material and hardwood bark are components amenable to EPN biological control programs. Copyright © 2012 Society of Chemical Industry.
Epidemiology, biology and treatment of sarcomatoid RCC: current state of the art.
Lebacle, Cedric; Pooli, Aydin; Bessede, Thomas; Irani, Jacques; Pantuck, Allan J; Drakaki, Alexandra
2018-06-01
Long recognized to confer an extremely poor prognosis, sarcomatoid dedifferentiation of renal cell carcinoma (sRCC) is a tumor phenotype that is finally beginning to be better understood on the molecular and genetic levels. With an overall incidence that ranges from 1 to 32% depending on associated RCC subtype, the survival of sarcomatoid RCC patients rarely exceeds 2 years. The main reasons for its poor outcome include its aggressive biology, its tendency to present at an advanced or metastatic stage at the time of diagnosis, its high rate of tumor recurrence after nephrectomy, and its limited response to systemic therapies. Molecular pathology studies suggest that sarcomatoid dedifferentiation originates from a focal epithelial-mesenchymal transition (EMT) arising in the carcinomatous component of the tumor. It is hoped that the growing understanding of the molecular biology of sRCC will soon make it possible to adapt treatments based on the identification of actionable tumor alterations. The deliberate inclusion of these patients in the multicenter clinical trials of immune, targeted and combination therapies is a necessary next step in pioneering future treatment strategies.
Research Review: The Neurobiology and Genetics of Maltreatment and Adversity
ERIC Educational Resources Information Center
McCrory, Eamon; De Brito, Stephane A.; Viding, Essi
2010-01-01
The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual's genetic make-up influence neurobiological development across infancy and childhood, which in…
Ghorai, Suman; Wang, Bingbing; Tivanski, Alexei; Laskin, Alexander
2014-02-18
Atmospheric aging of naturally emitted marine aerosol often leads to formation of internally mixed particles composed of sea salts and water-soluble organic compounds of anthropogenic origin. Mixing of sea salt and organic components has profound effects on the evolving chemical composition and hygroscopic properties of the resulted particles, which are poorly understood. Here, we have studied chemical composition and hygroscopic properties of laboratory generated NaCl particles mixed with malonic acid (MA) and glutaric acid (GA) at different molar ratios using micro-FTIR spectroscopy, atomic force microscopy, and X-ray elemental microanalysis. Hygroscopic properties of internally mixed NaCl and organic acid particles were distinctly different from pure components and varied significantly with the type and amount of organic compound present. Experimental results were in a good agreement with the AIM modeling calculations of gas/liquid/solid partitioning in studied systems. X-ray elemental microanalysis of particles showed that Cl/Na ratio decreased with increasing organic acid component in the particles with MA yielding lower ratios relative to GA. We attribute the depletion of chloride to the formation of sodium malonate and sodium glutarate salts resulted by HCl evaporation from dehydrating particles.
Tripartite ATP-independent periplasmic (TRAP) transporters in bacteria and archaea.
Mulligan, Christopher; Fischer, Marcus; Thomas, Gavin H
2011-01-01
The tripartite ATP-independent periplasmic (TRAP) transporters are the best-studied family of substrate-binding protein (SBP)-dependent secondary transporters and are ubiquitous in prokaryotes, but absent from eukaryotes. They are comprised of an SBP of the DctP or TAXI families and two integral membrane proteins of unequal sizes that form the DctQ and DctM protein families, respectively. The SBP component has a structure comprised of two domains connected by a hinge that closes upon substrate binding. In DctP-TRAP transporters, substrate binding is mediated through a conserved and specific arginine/carboxylate interaction in the SBP. While the SBP component has now been relatively well characterized, the membrane components of TRAP transporters are still poorly understood both in terms of their structure and function. We review the expanding repertoire of substrates and physiological roles for experimentally characterized TRAP transporters in bacteria and discuss mechanistic aspects of these transporters using data primarily from the sialic acid-specific TRAP transporter SiaPQM from Haemophilus influenzae, which suggest that TRAP transporters are high-affinity, Na(+)-dependent unidirectional secondary transporters. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ghorai, Suman; Wang, Bingbing; Tivanski, Alexei V.
Atmospheric aging of naturally emitted marine aerosol often leads to formation of internally mixed particles composed of sea salts and water soluble organic compounds of anthropogenic origin. Mixing of sea salt and organic components has profound effects on the evolving chemical composition and hygroscopic properties of the resulted particles, which are poorly understood. Here, we have studied chemical composition and hygroscopic properties of laboratory generated NaCl particles mixed with malonic acid (MA) and glutaric acid (GA) at different molar ratios using micro-FTIR spectroscopy and X-ray elemental microanalysis.Hygroscopic properties of inte rnally mixed NaCl and organic acid particles were distinctly differentmore » from pure components and varied significantly with the type and amount of organic compound present. Experimental results were in a good agreement with the AIM modeling calculations of gas/liquid/solid partitioning in studied systems. X-ray elemental microanalysis of particles showed that Cl/Na ratio decreased with increasing organic acid component in the particles with MA yielding lower ratios relative to GA. We attribute the depletion of chloride to the formation of Na-malonate and Na-glutarate salts resulted by HCl evaporation from dehydrating particles.« less
The alterations in the extracellular matrix composition guide the repair of damaged liver tissue
Klaas, Mariliis; Kangur, Triin; Viil, Janeli; Mäemets-Allas, Kristina; Minajeva, Ave; Vadi, Krista; Antsov, Mikk; Lapidus, Natalia; Järvekülg, Martin; Jaks, Viljar
2016-01-01
While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is still poorly understood. We utilized a proteomics-based approach to identify the shifts in ECM composition after CCl4 or DDC treatment and studied their effect on the proliferation of liver cells by combining biophysical and cell culture methods. We identified notable alterations in the ECM structural components (eg collagens I, IV, V, fibronectin, elastin) as well as in non-structural proteins (eg olfactomedin-4, thrombospondin-4, armadillo repeat-containing x-linked protein 2 (Armcx2)). Comparable alterations in ECM composition were seen in damaged human livers. The increase in collagen content and decrease in elastic fibers resulted in rearrangement and increased stiffness of damaged liver ECM. Interestingly, the alterations in ECM components were nonhomogenous and differed between periportal and pericentral areas and thus our experiments demonstrated the differential ability of selected ECM components to regulate the proliferation of hepatocytes and biliary cells. We define for the first time the alterations in the ECM composition of livers recovering from damage and present functional evidence for a coordinated ECM remodelling that ensures an efficient restoration of liver tissue. PMID:27264108
Auditory Resting-State Network Connectivity in Tinnitus: A Functional MRI Study
Maudoux, Audrey; Lefebvre, Philippe; Cabay, Jean-Evrard; Demertzi, Athena; Vanhaudenhuyse, Audrey; Laureys, Steven; Soddu, Andrea
2012-01-01
The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI “resting-state” connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress leading to disabling chronic tinnitus. PMID:22574141
Linardon, Jake; Phillipou, Andrea; Newton, Richard; Fuller-Tyszkiewicz, Matthew; Jenkins, Zoe; Cistullo, Leonardo L; Castle, David
2018-05-25
Although empirical evidence identifies dietary restraint as a transdiagnostic eating disorder maintaining mechanism, the distinctiveness and significance of the different behavioural and cognitive components of dietary restraint are poorly understood. The present study examined the relative associations of the purportedly distinct dietary restraint components (intention to restrict, delayed eating, food avoidance, and diet rules) with measures of psychological distress (depression, anxiety, and stress), disability, and core eating disorder symptoms (overvaluation and binge eating) in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Data were analysed from a treatment-seeking sample of individuals with AN (n = 124) and BN (n = 54). Intention to restrict, food avoidance, and diet rules were strongly related to each other (all r's > 0.78), but only weakly-moderately related to delayed eating behaviours (all r's < 0.47). In subsequent moderated ridge regression analyses, delayed eating was the only restraint component to independently predict variance in measures of psychological distress. Patient diagnosis did not moderate these associations. Overall, findings indicate that delayed eating behaviours may be a distinct component from other indices of dietary restraint (e.g., intention to restrict, food avoidance, diet rules). This study highlights the potential importance of ensuring that delayed eating behaviours are screened, assessed, and targeted early in treatment for patients with AN and BN. Copyright © 2018 Elsevier Ltd. All rights reserved.
NASA Aims to Create First-Ever Space-Based Sodium Lidar to Study Poorly Understood Mesosphere
2017-12-08
Caption: Mike Krainak (left) and Diego Janches recently won NASA follow-on funding to advance a spaceborne sodium lidar needed to probe Earth’s poorly understood mesosphere. Credits: NASA/W. Hrybyk More: A team of NASA scientists and engineers now believes it can leverage recent advances in a greenhouse-detecting instrument to build the world’s first space-based sodium lidar to study Earth’s poorly understood mesosphere. Scientist Diego Janches and laser experts Mike Krainak and Tony Yu, all of whom work at NASA’s Goddard Space Flight Center in Greenbelt, Maryland, are leading a research-and-development effort to further advance the sodium lidar, which the group plans to deploy on the International Space Station if it succeeds in proving its flightworthiness. Read more: go.nasa.gov/2rcGpSM NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram
Optical metabolic imaging for monitoring tracheal health
NASA Astrophysics Data System (ADS)
Sharick, Joe T.; Gil, Daniel A.; Choma, Michael A.; Skala, Melissa C.
2016-04-01
The health of the tracheal mucosa and submucosa is a vital yet poorly understood component of critical care medicine, and a minimally-invasive method is needed to monitor tracheal health in patients. Of particular interest are the ciliated cells of the tracheal epithelium that move mucus away from the lungs and prevent respiratory infection. Optical metabolic imaging (OMI) allows cellular-level measurement of metabolism, and is a compelling method for assessing tracheal health because ciliary motor proteins require ATP to function. In this pilot study, we apply multiphoton imaging of the fluorescence intensities and lifetimes of metabolic co-enzymes NAD(P)H and FAD to the mucosa and submucosa of ex vivo mouse trachea. We demonstrate the feasibility and potential diagnostic utility of these measurements for assessing tracheal health and pathophysiology at the single-cell level.
NASA Technical Reports Server (NTRS)
Winslow, J. W.; Silveira, C. de
1993-01-01
It has long been known that solder joints under mechanical stress are subject to failure. In early electronic systems, such failures were avoided primarily by avoiding the use of solder as a mechanical structural component. The rule was first to make sound wire connections that did not depend mechanically on solder, and only then to solder them. Careful design and miniaturization in modern electronic systems limits the mechanical stresses exerted on solder joints to values less than their yield points, and these joints have become integral parts of the mechanical structures. Unfortunately, while these joints are strong enough when new, they have proven vulnerable to fatigue failures as they age. Details of the fatigue process are poorly understood, making predictions of expected lifetimes difficult.
Actin - Lysozyme Interactions in Model Cystic Fibrosis Sputum
NASA Astrophysics Data System (ADS)
Sanders, Lori; Slimmer, Scott; Angelini, Thomas; Wong, Gerard C. L.
2003-03-01
Cystic fibrosis sputum is a complex fluid consisting of mucin (a glycoprotein), lysozyme (a cationic polypeptide), water, salt, as well as a high concentration of a number of anionic biological polyelectrolytes such as DNA and F-actin. The interactions governing these components are poorly understood, but may have important clinical consequences. For example, the formation of these biological polyelectrolytes into ordered gel phases may contribute significantly to the observed high viscosity of CF sputum. In this work, a number of model systems containing actin, lysozyme, and KCl were created to simulate CF sputum in vitro. These model systems were studied using small angle x-ray scattering and confocal fluorescence microscopy. Preliminary results will be presented. This work was supported by NSF DMR-0071761, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.
Physicochemical basis for water-actuated movement and stress generation in nonliving plant tissues.
Bertinetti, L; Fischer, F D; Fratzl, P
2013-12-06
Generating stresses and strains through water uptake from atmospheric humidity is a common process in nature, e.g., in seed dispersal. Actuation depends on a balance between chemical interactions and the elastic energy required to accomplish the volume change. In order to study the poorly understood chemical interactions, we combine mechanosorption experiments with theoretical calculations of the swelling behavior to estimate the mechanical energy and extract the contribution of the chemical energy per absorbed water molecule. The latter is highest in the completely dry state and stays almost constant at about 1.2 kT for higher hydrations. This suggests that water bound to the macromolecular components of the wood tissues acquires one additional hydrogen bond per eight water molecules, thus providing energy for actuation.
The choreography of neuroinflammation in Huntington’s disease
Crotti, Andrea; Glass, Christopher K.
2016-01-01
Currently, the concept of ‘neuroinflammation’ includes inflammation associated with neurodegenerative diseases, in which there is little or no infiltration of blood-derived immune cells into the brain. The roles of brain-resident and peripheral immune cells in these inflammatory settings are poorly understood, and it is unclear whether neuroinflammation results from immune reaction to neuronal dysfunction/degeneration, and/or represents cell-autonomous phenotypes of dysfunctional immune cells. Here, we review recent studies examining these questions in the context of Huntington’s disease (HD), where mutant Huntingtin (HTT) is expressed in both neurons and glia. Insights into the cellular and molecular mechanisms underlying neuroinflammation in HD may provide a better understanding of inflammation in more complex neurodegenerative disorders, and of the contribution of the neuroinflammatory component to neurodegenerative disease pathogenesis. PMID:26001312
Roberts, Richard D; Schulze, Ralf; O'Brien, Kristin; MacCann, Carolyn; Reid, John; Maul, Andy
2006-11-01
Emotions measures represent an important means of obtaining construct validity evidence for emotional intelligence (EI) tests because they have the same theoretical underpinnings. Additionally, the extent to which both emotions and EI measures relate to intelligence is poorly understood. The current study was designed to address these issues. Participants (N = 138) completed the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), two emotions measures, as well as four intelligence tests. Results provide mixed support for the model hypothesized to underlie the MSCEIT, with emotions research and EI measures failing to load on the same factor. The emotions measures loaded on the same factor as intelligence measures. The validity of certain EI components (in particular, Emotion Perception), as currently assessed, appears equivocal. Copyright 2006 APA, all rights reserved.
Introduced Species, Disease Ecology, and Biodiversity-Disease Relationships.
Young, Hillary S; Parker, Ingrid M; Gilbert, Gregory S; Sofia Guerra, Ana; Nunn, Charles L
2017-01-01
Species introductions are a dominant component of biodiversity change but are not explicitly included in most discussions of biodiversity-disease relationships. This is a major oversight given the multitude of effects that introduced species have on both parasitism and native hosts. Drawing on both animal and plant systems, we review the competing mechanistic pathways by which biological introductions influence parasite diversity and prevalence. While some mechanisms - such as local changes in phylogenetic composition and global homogenization - have strong explanatory potential, the net effects of introduced species, especially at local scales, remain poorly understood. Integrative, community-scale studies that explicitly incorporate introduced species are needed to make effective predictions about the effects of realistic biodiversity change and conservation action on disease. Copyright © 2016 Elsevier Ltd. All rights reserved.
Heterosis, the catapult effect and establishment success of a colonizing bird
Drake, John M
2006-01-01
The genetic basis of population colonization is poorly understood, particularly in animals. Here, I introduce the idea of a ‘catapult effect’ to explain how the effects of transient increases in fitness can be retained in population demography diminishing the chance of extinction. I tested this idea using information on historical introductions of hybrid and non-hybrid pheasants in the United States. I found that hybrid pheasants were 2.2 times more likely to establish than non-hybrid strains. Analysis of fitness components failed to support the alternative that the increased odds of establishment resulted from increased genetic variation conferring permanent fitness benefits through directional selection or by purging deleterious alleles. These results show that even ephemeral increases in fitness can affect the persistence of small populations. PMID:17148389
Computational design and multiscale modeling of a nanoactuator using DNA actuation.
Hamdi, Mustapha
2009-12-02
Developments in the field of nanobiodevices coupling nanostructures and biological components are of great interest in medical nanorobotics. As the fundamentals of bio/non-bio interaction processes are still poorly understood in the design of these devices, design tools and multiscale dynamics modeling approaches are necessary at the fabrication pre-project stage. This paper proposes a new concept of optimized carbon nanotube based servomotor design for drug delivery and biomolecular transport applications. The design of an encapsulated DNA-multi-walled carbon nanotube actuator is prototyped using multiscale modeling. The system is parametrized by using a quantum level approach and characterized by using a molecular dynamics simulation. Based on the analysis of the simulation results, a servo nanoactuator using ionic current feedback is simulated and analyzed for application as a drug delivery carrier.
Air Pollution: Mechanisms of Neuroinflammation & CNS Disease
Block, Michelle L.; Calderón-Garcidueñas, Lilian
2009-01-01
Emerging evidence implicates air pollution as a chronic source of neuroinflammation, reactive oxygen species (ROS), and neuropathology instigating central nervous system (CNS) disease. Stroke incidence, and Alzheimer’s and Parkinson’s disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain. Further, systemic effects known to impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that activation of microglia and changes in the blood brain barrier may be key to this process. Here, we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS culpable in CNS disease. PMID:19716187
Feltes, Bruno César; de Faria Poloni, Joice; Notari, Daniel Luis; Bonatto, Diego
2013-01-01
The physiological and molecular effects of tobacco smoke in adult humans and the development of cancer have been well described. In contrast, how tobacco smoke affects embryonic development remains poorly understood. Morphological studies of the fetuses of smoking pregnant women have shown various physical deformities induced by constant fetal exposure to tobacco components, especially nicotine. In addition, nicotine exposure decreases fetal body weight and bone/cartilage growth in addition to decreasing cranial diameter and tibia length. Unfortunately, the molecular pathways leading to these morphological anomalies are not completely understood. In this study, we applied interactome data mining tools and small compound interaction networks to elucidate possible molecular pathways associated with the effects of tobacco smoke components during embryonic development in pregnant female smokers. Our analysis showed a relationship between nicotine and 50 additional harmful substances involved in a variety of biological process that can cause abnormal proliferation, impaired cell differentiation, and increased oxidative stress. We also describe how nicotine can negatively affect retinoic acid signaling and cell differentiation through inhibition of retinoic acid receptors. In addition, nicotine causes a stress reaction and/or a pro-inflammatory response that inhibits the agonistic action of retinoic acid. Moreover, we show that the effect of cigarette smoke on the developing fetus could represent systemic and aggressive impacts in the short term, causing malformations during certain stages of development. Our work provides the first approach describing how different tobacco constituents affect a broad range of biological process in human embryonic development.
Feltes, Bruno César; Poloni, Joice de Faria; Notari, Daniel Luis; Bonatto, Diego
2013-01-01
The physiological and molecular effects of tobacco smoke in adult humans and the development of cancer have been well described. In contrast, how tobacco smoke affects embryonic development remains poorly understood. Morphological studies of the fetuses of smoking pregnant women have shown various physical deformities induced by constant fetal exposure to tobacco components, especially nicotine. In addition, nicotine exposure decreases fetal body weight and bone/cartilage growth in addition to decreasing cranial diameter and tibia length. Unfortunately, the molecular pathways leading to these morphological anomalies are not completely understood. In this study, we applied interactome data mining tools and small compound interaction networks to elucidate possible molecular pathways associated with the effects of tobacco smoke components during embryonic development in pregnant female smokers. Our analysis showed a relationship between nicotine and 50 additional harmful substances involved in a variety of biological process that can cause abnormal proliferation, impaired cell differentiation, and increased oxidative stress. We also describe how nicotine can negatively affect retinoic acid signaling and cell differentiation through inhibition of retinoic acid receptors. In addition, nicotine causes a stress reaction and/or a pro-inflammatory response that inhibits the agonistic action of retinoic acid. Moreover, we show that the effect of cigarette smoke on the developing fetus could represent systemic and aggressive impacts in the short term, causing malformations during certain stages of development. Our work provides the first approach describing how different tobacco constituents affect a broad range of biological process in human embryonic development. PMID:23637898
Isotopic signals of summer denitrification in a northern hardwood forested catchment
Sarah K. Wexler; Christine L. Goodale; Kevin J. McGuire; Scott W. Bailey; Peter M. Groffman
2014-01-01
Despite decades of measurements, the nitrogen balance of temperate forest catchments remains poorly understood. Atmospheric nitrogen deposition often greatly exceeds streamwater nitrogen losses; the fate of the remaining nitrogen is highly uncertain. Gaseous losses of nitrogen to denitrification are especially poorly documented and are often ignored. Here, we provide...
Punishment and Welfare: Paternal Incarceration and Families' Receipt of Public Assistance
ERIC Educational Resources Information Center
Sugie, Naomi F.
2012-01-01
The United States criminal justice and welfare systems are two important government institutions in the lives of the poor. Despite many theoretical discussions about their relationship, their operation at the level of offenders and families remains poorly understood. This paper utilizes Fragile Families and Child Wellbeing data to examine how…
Respiratory-deficient mutants of the unicellular green alga Chlamydomonas: a review.
Salinas, Thalia; Larosa, Véronique; Cardol, Pierre; Maréchal-Drouard, Laurence; Remacle, Claire
2014-05-01
Genetic manipulation of the unicellular green alga Chlamydomonas reinhardtii is straightforward. Nuclear genes can be interrupted by insertional mutagenesis or targeted by RNA interference whereas random or site-directed mutagenesis allows the introduction of mutations in the mitochondrial genome. This, combined with a screen that easily allows discriminating respiratory-deficient mutants, makes Chlamydomonas a model system of choice to study mitochondria biology in photosynthetic organisms. Since the first description of Chlamydomonas respiratory-deficient mutants in 1977 by random mutagenesis, many other mutants affected in mitochondrial components have been characterized. These respiratory-deficient mutants increased our knowledge on function and assembly of the respiratory enzyme complexes. More recently some of these mutants allowed the study of mitochondrial gene expression processes poorly understood in Chlamydomonas. In this review, we update the data concerning the respiratory components with a special focus on the assembly factors identified on other organisms. In addition, we make an inventory of different mitochondrial respiratory mutants that are inactivated either on mitochondrial or nuclear genes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Bruns, Merissa M; Kakarla, Prathusha; Floyd, Jared T; Mukherjee, Mun Mun; Ponce, Robert C; Garcia, John A; Ranaweera, Indrika; Sanford, Leslie M; Hernandez, Alberto J; Willmon, T Mark; Tolson, Grace L; Varela, Manuel F
2017-10-01
The causative agent of cholera, Vibrio cholerae, is a public health concern. Multidrug-resistant V. cholerae variants may reduce chemotherapeutic efficacies of severe cholera. We previously reported that the multidrug efflux pump EmrD-3 from V. cholerae confers resistance to multiple structurally distinct antimicrobials. Medicinal plant compounds are potential candidates for EmrD-3 efflux pump modulation. The antibacterial activities of garlic Allium sativum, although poorly understood, predicts that a main bioactive component, allyl sulfide, modulates EmrD-3 efflux. Thus, we tested whether A. sativum extract acts in synergy with antimicrobials and that a main bioactive component allyl sulfide inhibits EmrD-3 efflux. We found that A. sativum extract and allyl sulfide inhibited ethidium bromide efflux in cells harboring EmrD-3 and that A. sativum lowered the MICs of multiple antibacterials. We conclude that A. sativum and allyl sulfide inhibit EmrD-3 and that A. sativum extract synergistically enhances antibacterial agents.
Savary, Serge; Delbac, Lionel; Rochas, Amélie; Taisant, Guillaume; Willocquet, Laetitia
2009-08-01
Dual epidemics are defined as epidemics developing on two or several plant organs in the course of a cropping season. Agricultural pathosystems where such epidemics develop are often very important, because the harvestable part is one of the organs affected. These epidemics also are often difficult to manage, because the linkage between epidemiological components occurring on different organs is poorly understood, and because prediction of the risk toward the harvestable organs is difficult. In the case of downy mildew (DM) and powdery mildew (PM) of grapevine, nonlinear modeling and logistic regression indicated nonlinearity in the foliage-cluster relationships. Nonlinear modeling enabled the parameterization of a transmission coefficient that numerically links the two components, leaves and clusters, in DM and PM epidemics. Logistic regression analysis yielded a series of probabilistic models that enabled predicting preset levels of cluster infection risks based on DM and PM severities on the foliage at successive crop stages. The usefulness of this framework for tactical decision-making for disease control is discussed.
The cuticle modulates ultraviolet reflectance of avian eggshells
Fecheyr-Lippens, Daphne C.; Igic, Branislav; D'Alba, Liliana; Hanley, Daniel; Verdes, Aida; Holford, Mande; Waterhouse, Geoffrey I. N.; Grim, Tomas; Hauber, Mark E.; Shawkey, Matthew D.
2015-01-01
ABSTRACT Avian eggshells are variedly coloured, yet only two pigments, biliverdin and protoporphyrin IX, are known to contribute to the dramatic diversity of their colours. By contrast, the contributions of structural or other chemical components of the eggshell are poorly understood. For example, unpigmented eggshells, which appear white to the human eye, vary in their ultraviolet (UV) reflectance, which may be detectable by birds. We investigated the proximate mechanisms for the variation in UV-reflectance of unpigmented bird eggshells using spectrophotometry, electron microscopy, chemical analyses, and experimental manipulations. We specifically tested how UV-reflectance is affected by the eggshell cuticle, the outermost layer of most avian eggshells. The chemical dissolution of the outer eggshell layers, including the cuticle, increased UV-reflectance for only eggshells that contained a cuticle. Our findings demonstrate that the outer eggshell layers, including the cuticle, absorb UV-light, probably because they contain higher levels of organic components and other chemicals, such as calcium phosphates, compared to the predominantly calcite-based eggshell matrix. These data highlight the need to examine factors other than the known pigments in studies of avian eggshell colour. PMID:25964661
Irion, Uwe; Frohnhöfer, Hans Georg; Krauss, Jana; Çolak Champollion, Tuǧba; Maischein, Hans-Martin; Geiger-Rudolph, Silke; Weiler, Christian; Nüsslein-Volhard, Christiane
2014-01-01
Interactions between all three pigment cell types are required to form the stripe pattern of adult zebrafish (Danio rerio), but their molecular nature is poorly understood. Mutations in leopard (leo), encoding Connexin 41.8 (Cx41.8), a gap junction subunit, cause a phenotypic series of spotted patterns. A new dominant allele, leotK3, leads to a complete loss of the pattern, suggesting a dominant negative impact on another component of gap junctions. In a genetic screen, we identified this component as Cx39.4 (luchs). Loss-of-function alleles demonstrate that luchs is required for stripe formation in zebrafish; however, the fins are almost not affected. Double mutants and chimeras, which show that leo and luchs are only required in xanthophores and melanophores, but not in iridophores, suggest that both connexins form heteromeric gap junctions. The phenotypes indicate that these promote homotypic interactions between melanophores and xanthophores, respectively, and those cells instruct the patterning of the iridophores. DOI: http://dx.doi.org/10.7554/eLife.05125.001 PMID:25535837
Prasad, B Ram; Senapati, Sanjib
2009-04-09
Flue gas is greatly responsible for acid rain formation and global warming. New generation ionic liquids (ILs) have potential in controlling the flue gas emissions, as they acquire high absorptivity for the component gases SO(2), CO(2), etc. The association of the IL-gas interactions to the absorptivity of gas molecules in ILs is, however, poorly understood. In this paper, we present a molecular level description of the interactions of ILs with SO(2), CO(2), and N(2) and show its implications to the differential gas solubility. Our results indicate that the IL anion-gas interactions play a key role in deciding the gas solubility in ILs, particularly for polar gases such as SO(2). On the other hand, regular solution assumption applies to N(2) solubility. In accordance with the previous theoretical and experimental findings, our results also imply that the IL anions dominate the interactions with gas molecules while the cations play a secondary role and the underlying fluid structures of the ILs remain unperturbed by the addition of gas molecules.
NASA Astrophysics Data System (ADS)
Wáng, Yì Xiáng J.; Idée, Jean-Marc; Corot, Claire
2015-10-01
Designing of theranostics and dual or multi-modality contrast agents are currently two of the hottest topics in biotechnology and biomaterials science. However, for single entity theranostics, a right ratio of their diagnostic component and their therapeutic component may not always be realized in a composite suitable for clinical application. For dual/multiple modality molecular imaging agents, after in vivo administration, there is an optimal time window for imaging, when an agent is imaged by one modality, the pharmacokinetics of this agent may not allow imaging by another modality. Due to reticuloendothelial system clearance, efficient in vivo delivery of nanoparticles to the lesion site is sometimes difficult. The toxicity of these entities also remains poorly understood. While the medical need of theranostics is admitted, the business model remains to be established. There is an urgent need for a global and internationally harmonized re-evaluation of the approval and marketing processes of theranostics. However, a reasonable expectation exists that, in the near future, the current obstacles will be removed, thus allowing the wide use of these very promising agents.
δ 13C of free and macromolecular aromatic structures in the murchison meteorite
NASA Astrophysics Data System (ADS)
Sephton, M. A.; Pillinger, C. T.; Gilmour, I.
1998-05-01
Analyses of the organic compounds in the Murchison meteorite have led to a greater understanding of the nature of extraterrestrial organic materials. However, the relationship between low and high molecular weight material remains poorly understood. To investigate this relationship, untreated Murchison was subjected to supercritical fluid extraction (SFE) to obtain the free organic components in the meteorite. Toluene and other volatile aromatic hydrocarbons dominated the extract, and the carbon isotopic composition of these molecules was determined by gas chromatography-isotope ratio-mass spectrometry (GCIRMS). δ 13C values of the aromatic hydrocarbons ranged from -28.8 to -5.8‰. These compounds displayed a 13C-enrichment with increasing carbon number suggesting an origin by cracking. The high molecular weight organic material in the meteorite was isolated and subjected to hydrous pyrolysis. This procedure produced a number of aromatic products, the majority of which were volatile aromatic hydrocarbons, particularly toluene. SFE was used to extract and successfully retain them. This enabled the first carbon isotopic analysis of this poorly understood material to be performed at the molecular level by GCIRMS. δ 13C values for aromatic pyrolysis products occupied a range from -24.6 to -5.6‰. The trend of 13C-enrichment with increasing carbon number, observed in the free compounds, was also evident in the macromolecular fragments. Furthermore, the organic fragments of the macromolecular material were consistently 13C-enriched when compared to structurally identical free molecules. This suggested that the free aromatic hydrocarbons in Murchison were produced by the preterrestrial degradation of the organic macromolecular material. This natural degradation event was extended by the hydrous pyrolysis experiment.
Crawford, LaTasha K; Rahman, Shumaia F; Beck, Sheryl G
2013-01-16
Anxiety disorders are among the most prevalent psychiatric disorders, yet much is unknown about the underlying mechanisms. The dorsal raphe (DR) is at the crux of the anxiety-inducing effects of uncontrollable stress, a key component of models of anxiety. Though DR serotonin (5-HT) neurons play a prominent role, anxiety-associated changes in the physiology of 5-HT neurons remain poorly understood. A 5-day social defeat model of anxiety produced a multifaceted, anxious phenotype in intruder mice that included increased avoidance behavior in the open field test, increased stress-evoked grooming, and increased bladder and heart weights when compared to control mice. Intruders were further compared to controls using electrophysiology recordings conducted in midbrain slices wherein recordings targeted 5-HT neurons of the ventromedial (vmDR) and lateral wing (lwDR) subfields of the DR. Though defining membrane characteristics of 5-HT neurons were unchanged, γ-aminobutyric-acid-mediated (GABAergic) synaptic regulation of 5-HT neurons was altered in a topographically specific way. In the vmDR of intruders, there was a decrease in the frequency and amplitude of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs). However, in the lwDR, there was an increase in the strength of inhibitory signals due to slower sIPSC kinetics. Synaptic changes were selective for GABAergic input, as glutamatergic synaptic input was unchanged in intruders. The distinct inhibitory regulation of DR subfields provides a mechanism for increased 5-HT output in vmDR target regions and decreased 5-HT output in lwDR target regions, divergent responses to uncontrollable stress that have been reported in the literature but were previously poorly understood.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Syed, Aleem
Systematic spatial and temporal fluctuations are a fundamental part of any biological process. For example, lateral diffusion of membrane proteins is one of the key mechanisms in their cellular function. Lateral diffusion governs how membrane proteins interact with intracellular, transmembrane, and extracellular components to achieve their function. Herein, fluorescence-based techniques are used to elucidate the dynamics of receptor for advanced glycation end-products (RAGE) and integrin membrane proteins. RAGE is a transmembrane protein that is being used as a biomarker for various diseases. RAGE dependent signaling in numerous pathological conditions is well studied. However, RAGE lateral diffusion in the cell membranemore » is poorly understood. For this purpose, effect of cholesterol, cytoskeleton dynamics, and presence of ligand on RAGE lateral diffusion is investigated.« less
Breakdown of an ant-plant mutualism follows the loss of large herbivores from an African savanna.
Palmer, Todd M; Stanton, Maureen L; Young, Truman P; Goheen, Jacob R; Pringle, Robert M; Karban, Richard
2008-01-11
Mutualisms are key components of biodiversity and ecosystem function, yet the forces maintaining them are poorly understood. We investigated the effects of removing large mammals on an ant-Acacia mutualism in an African savanna. Ten years of large-herbivore exclusion reduced the nectar and housing provided by plants to ants, increasing antagonistic behavior by a mutualistic ant associate and shifting competitive dominance within the plant-ant community from this nectar-dependent mutualist to an antagonistic species that does not depend on plant rewards. Trees occupied by this antagonist suffered increased attack by stem-boring beetles, grew more slowly, and experienced doubled mortality relative to trees occupied by the mutualistic ant. These results show that large mammals maintain cooperation within a widespread symbiosis and suggest complex cascading effects of megafaunal extinction.
Stimulation of IKK-gamma oligomerization by the human T-cell leukemia virus oncoprotein Tax.
Huang, Guo Jin; Zhang, Zhi Qing; Jin, Dong Yan
2002-11-20
Human T-cell leukemia virus type 1 oncoprotein Tax activates NF-kappaB through direct binding to IKK-gamma, the regulatory component of the IkappaB kinase complex. Mechanisms by which IKK-gamma adapts the Tax signal to the IkappaB kinase are poorly understood. Here we demonstrate that IKK-gamma forms homodimer and homotrimer both in vitro and in yeast or mammalian cells through a C-terminal domain comprising amino acids 251-419. In contrast, Tax protein targets a central region of IKK-gamma, which consists of amino acids 201-250. Interestingly, Tax stimulates the oligomerization of IKK-gamma, likely through direct binding. Taken together, our findings suggest a new model of Tax activation of NF-kappaB, in which Tax interacts with IKK-gamma to stimulate its oligomerization.
Dias, Sheila; D'Amico, Angela; Cretney, Erika; Liao, Yang; Tellier, Julie; Bruggeman, Christine; Almeida, Francisca F; Leahy, Jamie; Belz, Gabrielle T; Smyth, Gordon K; Shi, Wei; Nutt, Stephen L
2017-01-17
FoxP3-expressing regulatory T (Treg) cells are essential for maintaining immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly expresses genes critical for Treg cell function, although how this process is coordinated on a transcriptional level is poorly understood. Here, we demonstrate that mice lacking the transcription factor Myb in Treg cells succumbed to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells. The combination of transcriptome and genomic footprint analyses revealed that Myb directly regulated a large proportion of the gene expression specific to effector Treg cells, identifying Myb as a critical component of the gene regulatory network controlling effector Treg cell differentiation and function. Copyright © 2017 Elsevier Inc. All rights reserved.
FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth
Slebe, Felipe; Rojo, Federico; Vinaixa, Maria; García-Rocha, Mar; Testoni, Giorgia; Guiu, Marc; Planet, Evarist; Samino, Sara; Arenas, Enrique J.; Beltran, Antoni; Rovira, Ana; Lluch, Ana; Salvatella, Xavier; Yanes, Oscar; Albanell, Joan; Guinovart, Joan J.; Gomis, Roger R.
2016-01-01
The mechanisms that allow breast cancer (BCa) cells to metabolically sustain rapid growth are poorly understood. Here we report that BCa cells are dependent on a mechanism to supply precursors for intracellular lipid production derived from extracellular sources and that the endothelial lipase (LIPG) fulfils this function. LIPG expression allows the import of lipid precursors, thereby contributing to BCa proliferation. LIPG stands out as an essential component of the lipid metabolic adaptations that BCa cells, and not normal tissue, must undergo to support high proliferation rates. LIPG is ubiquitously and highly expressed under the control of FoxA1 or FoxA2 in all BCa subtypes. The downregulation of either LIPG or FoxA in transformed cells results in decreased proliferation and impaired synthesis of intracellular lipids. PMID:27045898
NASA Technical Reports Server (NTRS)
Cao, T.; Nakamura-Messenger, K.; Berger, E. L.; Burton, A. S.; Messenger, S.; Clemett, S. J.
2016-01-01
Primitive carbonaceous chondrites contain a wide variety of organic material, ranging from soluble discrete molecules to insoluble unstructured kerogen-like component as well as structured nano-globules of macromolecular carbon. The relationship between the soluble organic molecules, macromolecular organic material, and host minerals are poorly understood. Due to the differences in extractability of soluble and insoluble organic materials, the analysis methods for each differ and are often performed independently. The combination of soluble and insoluble analyses, when performed concurrently, can provide a wider understanding on spatial distribution, and elemental, structural and isotopic composition of organic material in primitive meteorites. Furthermore, they can provide broader perspective on how extraterrestrial organic ma-terials potentially contributed to the synthesis of life's essential compounds such as amino acids, sugar acids, activated phosphates and nucleobases.
Proton electrochemical gradient: Driving and regulating neurotransmitter uptake.
Farsi, Zohreh; Jahn, Reinhard; Woehler, Andrew
2017-05-01
Accumulation of neurotransmitters in the lumen of synaptic vesicles (SVs) relies on the activity of the vacuolar-type H + -ATPase. This pump drives protons into the lumen, generating a proton electrochemical gradient (Δμ H+ ) across the membrane. Recent work has demonstrated that the balance between the chemical (ΔpH) and electrical (ΔΨ) components of Δμ H+ is regulated differently by some distinct vesicle types. As different neurotransmitter transporters use ΔpH and ΔΨ with different relative efficiencies, regulation of this gradient balance has the potential to influence neurotransmitter uptake. Nevertheless, the underlying mechanisms responsible for this regulation remain poorly understood. In this review, we provide an overview of current neurotransmitter uptake models, with a particular emphasis on the distinct roles of the electrical and chemical gradients and current hypotheses for regulatory mechanisms. © 2017 WILEY Periodicals, Inc.
Felemban, Majed; Dorgau, Birthe; Hunt, Nicola Claire; Hallam, Dean; Zerti, Darin; Bauer, Roman; Ding, Yuchun; Collin, Joseph; Steel, David; Krasnogor, Natalio; Al-Aama, Jumana; Lindsay, Susan; Mellough, Carla; Lako, Majlinda
2018-05-17
The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied. Our data indicate that basement membrane ECMs (Fibronectin and Collagen IV) were expressed in Bruch's membrane and the inner limiting membrane of the developing human retina, whilst the hyalectins (Versican and Brevican), cluster of differentiation 44 (CD44), photoreceptor-specific ECMs Interphotoreceptor Matrix Proteoglycan 1 (IMPG1) and Interphotoreceptor Matrix Proteoglycan 2 (IMPG2) were detected in the developing interphotoreceptor matrix (IPM). The expression of IMPG1, Versican and Brevican in the developing IPM was conserved between human developing retina and human pluripotent stem cell-derived retinal organoids. Blocking the action of CD44 and IMPG1 in pluripotent stem cell derived retinal organoids affected the development of photoreceptors, their inner/outer segments and connecting cilia and disrupted IPM formation, with IMPG1 having an earlier and more significant impact. Together, our data suggest an important role for IMPG1 and CD44 in the development of photoreceptors and IPM formation during human retinogenesis. The expression and the role of many extracellular matrix (ECM) components during human retinal development is not fully understood. In this study, expression of key ECM components (Collagen IV, Fibronectin, Brevican, Versican, IMPG1 and IMPG2) was investigated during human retinal ontogenesis. Collagen IV and Fibronectin were expressed in Bruch's membrane; whereas Brevican, Versican, IMPG1 & IMPG2 in the developing interphotoreceptor matrix (IPM). Retinal organoids were successfully generated from pluripotent stem cells. The expression of ECM components was examined in the retinal organoids and found to recapitulate human retinal development in vivo. Using functional blocking experiments, we were able to highlight an important role for IMPG1 and CD44 in the development of photoreceptors and IPM formation. Copyright © 2018 Acta Materialia Inc. All rights reserved.
Chen, Jianming; Rood, Julian I; McClane, Bruce A
2011-01-01
Clostridium perfringens type B and D strains cause enterotoxemias and enteritis in livestock after proliferating in the intestines and producing epsilon-toxin (ETX), alpha-toxin (CPA), and, usually, perfringolysin O (PFO). Although ETX is one of the most potent bacterial toxins, the regulation of ETX production by type B or D strains remains poorly understood. The present work determined that the type D strain CN3718 upregulates production of ETX upon close contact with enterocyte-like Caco-2 cells. This host cell-induced upregulation of ETX expression was mediated at the transcriptional level. Using an isogenic agrB null mutant and complemented strain, the agr operon was shown to be required when CN3718 produces ETX in broth culture or, via a secreted signal consistent with a quorum-sensing (QS) effect, upregulates ETX production upon contact with host cells. These findings provide the first insights into the regulation of ETX production, as well as additional evidence that the Agr-like QS system functions as a global regulator of C. perfringens toxin production. Since it was proposed previously that the Agr-like QS system regulates C. perfringens gene expression via the VirS/VirR two-component regulatory system, an isogenic virR null mutant of CN3718 was constructed to evaluate the importance of VirS/VirR for CN3718 toxin production. This mutation affected production of CPA and PFO, but not ETX, by CN3718. These results provide the first indication that C. perfringens toxin expression regulation by the Agr-like quorum-sensing system may not always act via the VirS/VirR two-component system. IMPORTANCE Mechanisms by which Clostridium perfringens type B and D strains regulate production of epsilon-toxin (ETX), a CDC class B select toxin, are poorly understood. Production of several other toxins expressed by C. perfringens is wholly or partially regulated by both the Agr-like quorum-sensing (QS) system and the VirS/VirR two-component regulatory system, so the present study tested whether ETX expression by type D strain CN3718 also requires these regulatory systems. The agr operon was shown to be essential for signaling CN3718 to produce ETX in broth culture or to upregulate ETX production upon close contact with enterocyte-like Caco-2 cells, which may have pathogenic relevance since ETX is produced intestinally. However, ETX production remained at wild-type levels after inactivation of the VirS/VirR system in CN3718. These findings provide the first information regarding regulation of ETX production and suggest Agr-like QS toxin production regulation in C. perfringens does not always require the VirS/VirR system.
Evolution of a sediment wave in an experimental channel
Thomas E. Lisle; James E. Pizzuto; Hiroshi Ikeda; Fujiko Iseya; Yoshinori Kodama
1997-01-01
Abstract - The routing of bed material through channels is poorly understood. We approach the problem by observing and modeling the fate of a low-amplitude sediment wave of poorly sorted sand that we introduced into an experimental channel transporting sediment identical to that of the introduced wave. The wave essentially dispersed upstream and downstream without...
Independent Learning--What We Do When You're Not There
ERIC Educational Resources Information Center
Hockings, Christine; Thomas, Liz; Ottaway, Jim; Jones, Rob
2018-01-01
Independent learning is one of the cornerstones of UK higher education yet it is poorly understood by students and is seen by politicians as a poor substitute for face to face teaching. This paper explores students' understandings, approaches and experiences of independent learning and how they may become more effective independent learners. This…
The role of bedrock groundwater in rainfall-runoff response at hillslope and catchment scales
C. Gabrielli; J.J. McDonnell; W.T. Jarvis
2012-01-01
Bedrock groundwater dynamics in headwater catchments are poorly understood and poorly characterized. Direct hydrometric measurements have been limited due to the logistical challenges associated with drilling through hard rock in steep, remote and often roadless terrain. We used a new portable bedrock drilling system to explore bedrock groundwater dynamics aimed at...
Asian and Pacific Islander American Poverty: The Working Poor and the Jobless Poor.
ERIC Educational Resources Information Center
Toji, Dean S.; Johnson, James H.
1992-01-01
Assesses the incidence of Asian-American and Pacific Islander-American poverty, and offers a theoretical explanation for its existence. It is argued that poverty of Americans of Asian and Pacific Island descent is best understood in the context of the linkage of labor migration and U.S. labor market segmentation. (SLD)
Determinants to trigger memory reconsolidation: The role of retrieval and updating information.
Rodriguez-Ortiz, Carlos J; Bermúdez-Rattoni, Federico
2017-07-01
Long-term memories can undergo destabilization/restabilization processes, collectively called reconsolidation. However, the parameters that trigger memory reconsolidation are poorly understood and are a matter of intense investigation. Particularly, memory retrieval is widely held as requisite to initiate reconsolidation. This assumption makes sense since only relevant cues will induce reconsolidation of a specific memory. However, recent studies show that pharmacological inhibition of retrieval does not avoid memory from undergoing reconsolidation, indicating that memory reconsolidation occurs through a process that can be dissociated from retrieval. We propose that retrieval is not a unitary process but has two dissociable components; one leading to the expression of memory and the other to reconsolidation, referred herein as executer and integrator respectively. The executer would lead to the behavioral expression of the memory. This component would be the one disrupted on the studies that show reconsolidation independence from retrieval. The integrator would deal with reconsolidation. This component of retrieval would lead to long-term memory destabilization when specific conditions are met. We think that an important number of reports are consistent with the hypothesis that reconsolidation is only initiated when updating information is acquired. We suggest that the integrator would initiate reconsolidation to integrate updating information into long-term memory. Copyright © 2016 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Spence, Adrian; Kelleher, Brian P.
2016-03-01
As a primary decomposition process in terrestrial biosystems, biodegradation has been extensively studied with regard to its impact on soil organic matter transformation. However, the biotransformation of soil microbial biomass (a primary source of soil organic carbon) remains poorly understood, and even less is known about the fate of microbial-derived carbon under photodegradation. Here, we combine infrared and diffusion editing NMR spectroscopies to provide molecular-level information on the photodegradation of major biochemical components in soil microbial biomass and leachates over time. Results indicate a considerable enrichment in aliphatic components, presumably polymethylenic-C [(C-H2)n] and the simultaneous loss of carbohydrate and protein structures in the biomass. An immediate conclusion is that photodegradation increased the conversion of macromolecular carbohydrates and proteins to smaller components. However, further analysis reveals that macromolecular carbohydrates and proteins may be more resistant to photodegradation than initially thought and are found in the leachates. Although attenuated, there is also evidence to suggest that some aliphatic structures persist in the leachates. Overall, the photodegradation pathway reported here is remarkably similar to that of biodegradation, suggesting that under rapidly expanding anthropogenic land disturbances, photodegradation could be an important driver of the transformation of microbial-derived organic matter in terrestrial biosystems.
NASA Astrophysics Data System (ADS)
Schneider, A.; Mittlefehldt, D.
2006-10-01
The Mars Exploration Rover Opportunity discovered hematite-rich spherules (``blueberries'') believed to be diagenetic concretions formed in the bedrock in stagnant or slow-moving groundwater. These spherules likely precipitated from solution, but their origins are poorly understood. Three formation mechanisms are possible: inclusive, replacive and displacive. The first would result in a distinct spherule composition compared to the other two. We propose that chemical clues may help to constrain the nature of blueberry formation. We used Alpha Particle X-ray Spectrometer data for undisturbed soils that were blueberry-free and with visible blueberries at the surface in Microscopic Imager images. We made plots of the elements versus iron for the spherule-rich soils and compared them to a mixing line representative of a pure hematite end member spherule (called ``the zero model''). This modeled the replacive formation mechanism, in which pure hematite would replace all of the original material. If the spherules grew inclusively, chemical data should reflect a compositional component of the rock grains included during formation. Four models were developed to test for possible compositions of a rock component. These models could not easily explain the APXS data and thus demonstrate that the most plausible rock compositions are not components of blueberries.
UAP56 is a conserved crucial component of a divergent mRNA export pathway in Toxoplasma gondii.
Serpeloni, Mariana; Jiménez-Ruiz, Elena; Vidal, Newton Medeiros; Kroeber, Constanze; Andenmatten, Nicole; Lemgruber, Leandro; Mörking, Patricia; Pall, Gurman S; Meissner, Markus; Ávila, Andréa R
2016-11-01
Nucleo-cytoplasmic RNA export is an essential post-transcriptional step to control gene expression in eukaryotic cells and is poorly understood in apicomplexan parasites. With the exception of UAP56, a component of TREX (Transcription Export) complex, other components of mRNA export machinery are not well conserved in divergent supergroups. Here, we use Toxoplasma gondii as a model system to functionally characterize TgUAP56 and its potential interaction factors. We demonstrate that TgUAP56 is crucial for mRNA export and that functional interference leads to significant accumulation of mRNA in the nucleus. It was necessary to employ bioinformatics and phylogenetic analysis to identify orthologs related to mRNA export, which show a remarkable low level of conservation in T. gondii. We adapted a conditional Cas9/CRISPR system to carry out a genetic screen to verify if these factors were involved in mRNA export in T. gondii. Only the disruption of TgRRM_1330 caused accumulation of mRNA in the nucleus as found with TgUAP56. This protein is potentially a divergent partner of TgUAP56, and provides insight into a divergent mRNA export pathway in apicomplexans. © 2016 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.
UAP56 is a conserved crucial component of a divergent mRNA export pathway in Toxoplasma gondii
Serpeloni, Mariana; Jiménez‐Ruiz, Elena; Vidal, Newton Medeiros; Kroeber, Constanze; Andenmatten, Nicole; Lemgruber, Leandro; Mörking, Patricia; Pall, Gurman S.
2016-01-01
Summary Nucleo‐cytoplasmic RNA export is an essential post‐transcriptional step to control gene expression in eukaryotic cells and is poorly understood in apicomplexan parasites. With the exception of UAP56, a component of TREX (Transcription Export) complex, other components of mRNA export machinery are not well conserved in divergent supergroups. Here, we use Toxoplasma gondii as a model system to functionally characterize TgUAP56 and its potential interaction factors. We demonstrate that TgUAP56 is crucial for mRNA export and that functional interference leads to significant accumulation of mRNA in the nucleus. It was necessary to employ bioinformatics and phylogenetic analysis to identify orthologs related to mRNA export, which show a remarkable low level of conservation in T. gondii. We adapted a conditional Cas9/CRISPR system to carry out a genetic screen to verify if these factors were involved in mRNA export in T. gondii. Only the disruption of TgRRM_1330 caused accumulation of mRNA in the nucleus as found with TgUAP56. This protein is potentially a divergent partner of TgUAP56, and provides insight into a divergent mRNA export pathway in apicomplexans. PMID:27542978
Omori, Yoshihiro; Kubo, Shun; Kon, Tetsuo; Furuhashi, Mayu; Narita, Hirotaka; Kominami, Taro; Ueno, Akiko; Tsutsumi, Ryotaro; Chaya, Taro; Yamamoto, Haruka; Suetake, Isao; Ueno, Shinji; Koseki, Haruhiko; Furukawa, Takahisa
2017-01-01
Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7-null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7-deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity. PMID:28900001
Omori, Yoshihiro; Kubo, Shun; Kon, Tetsuo; Furuhashi, Mayu; Narita, Hirotaka; Kominami, Taro; Ueno, Akiko; Tsutsumi, Ryotaro; Chaya, Taro; Yamamoto, Haruka; Suetake, Isao; Ueno, Shinji; Koseki, Haruhiko; Nakagawa, Atsushi; Furukawa, Takahisa
2017-09-26
Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7- null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7 -deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity.
The potential of critical social theory as an educational framework for people with epilepsy.
Bennett, Louise; Bergin, Michael; Wells, John S G
2016-01-01
Effective education can support people with epilepsy to develop the attributes and skills required to function as equal partners with clinical service providers, make informed decisions, and competently self-manage their healthcare. However, despite knowledge deficits, unmet information needs, and a poor sense of empowerment, the study of education for people with epilepsy is often neglected and is a poorly understood component of holistic practice within epilepsy healthcare. Historically, the only debate with regard to education and people with epilepsy has been guided either within a positivist or within a constructivist philosophy. We argue that new pedagogies are warranted, recognizing the views of people with epilepsy regarding their illness. Therefore, this paper explores the potential of an educational framework for people with epilepsy based upon critical social theory (CST). By utilizing a CST approach for education, people with epilepsy are engaged with as active 'participants'. This is a key difference that distinguishes CST from other metatheoretical frameworks. It has the potential to support people with epilepsy to acquire the skills and confidence to manage the biopsychosocial challenges associated with their condition. Copyright © 2015 Elsevier Inc. All rights reserved.
Achieving Operability via the Mission System Paradigm
NASA Technical Reports Server (NTRS)
Hammer, Fred J.; Kahr, Joseph R.
2006-01-01
In the past, flight and ground systems have been developed largely-independently, with the flight system taking the lead, and dominating the development process. Operability issues have been addressed poorly in planning, requirements, design, I&T, and system-contracting activities. In many cases, as documented in lessons-learned, this has resulted in significant avoidable increases in cost and risk. With complex missions and systems, operability is being recognized as an important end-to-end design issue. Never-the-less, lessons-learned and operability concepts remain, in many cases, poorly understood and sporadically applied. A key to effective application of operability concepts is adopting a 'mission system' paradigm. In this paradigm, flight and ground systems are treated, from an engineering and management perspective, as inter-related elements of a larger mission system. The mission system consists of flight hardware, flight software, telecom services, ground data system, testbeds, flight teams, science teams, flight operations processes, procedures, and facilities. The system is designed in functional layers, which span flight and ground. It is designed in response to project-level requirements, mission design and an operations concept, and is developed incrementally, with early and frequent integration of flight and ground components.
Effects of forest fire on soil nutrients in Turkish pine (Pinus brutia, Ten) ecosystems.
Yildiz, Oktay; Esen, Derya; Sarginci, Murat; Toprak, Bulent
2010-01-01
Fire is a long-standing and poorly understood component of the Mediterranean forestlands in Turkey. Fire can alter plant composition, destroy biomass, alter soil physical and chemical properties and reduce soil nutrient pools. However fire can also promote productivity of certain ecosystems by mineralizing soil nutrients and promoting fast growing nitrogen fixing plant species. Fire effects on soils and ecosystems in Turkey and Mediterranean regions are not well understood. This study uses a retrospective space-for-time substitution to study soil macro-nutrient changes on sites which were burned at different times during the last 8 years. The study sites are in the Fethiye Forest Management Directorate in the western Mediterranean Sea region of Turkey. Our samples show 40% less Soil C, and cation exchange capacity (CEC) at 0-20 cm soil depth two weeks after the fire. Soil C and CEC appear to recover to pre-fire level in one year. Concentrations of Mg were significantly lower on new-burn sites, but returned to pre-fire levels in one year. Total soil N concentrations one and two years after fire were 90% higher than other sites, and total P was 9 times higher on new-burn site than averages from other sites. Some implications of these results for forest managers are discussed.
The neural bases of feeling understood and not understood
Torre, Jared B.; Eisenberger, Naomi I.
2014-01-01
Past research suggests that feeling understood enhances both personal and social well-being. However, little research has examined the neurobiological bases of feeling understood and not understood. We addressed these gaps by experimentally inducing felt understanding and not understanding as participants underwent functional magnetic resonance imaging. The results demonstrated that feeling understood activated neural regions previously associated with reward and social connection (i.e. ventral striatum and middle insula), while not feeling understood activated neural regions previously associated with negative affect (i.e. anterior insula). Both feeling understood and not feeling understood activated different components of the mentalizing system (feeling understood: precuneus and temporoparietal junction; not feeling understood: dorsomedial prefrontal cortex). Neural responses were associated with subsequent feelings of social connection and disconnection and were modulated by individual differences in rejection sensitivity. Thus, this study provides insight into the psychological processes underlying feeling understood (or not) and may suggest new avenues for targeted interventions that amplify the benefits of feeling understood or buffer individuals from the harmful consequences of not feeling understood. PMID:24396002
Liangjun Hu; Qinfeng Guo
2013-01-01
How species diversity relates to productivity remains a major debate. To date, however, the underlying mechanisms that regulate the ecological processes involved are still poorly understood. Three major issues persist in early efforts at resolution. First, in the context that productivity drives species diversity, how the pathways operate is poorly-explained. Second,...
USDA-ARS?s Scientific Manuscript database
Stunting affects ~25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood. The purpose of this study was to identify altered metabolic pathways associated with child stunting...
Añez, Germán; Heisey, Daniel A. R.; Chancey, Caren; Fares, Rafaelle C. G.; Espina, Luz M.; Souza, Kátia P. R.; Teixeira-Carvalho, Andréa; Krysztof, David E.; Foster, Gregory A.; Stramer, Susan L.; Rios, Maria
2016-01-01
Background Dengue is a mosquito-borne viral disease caused by the four dengue viruses (DENV-1 to 4) that can also be transmitted by blood transfusion and organ transplantation. The distribution of DENV in the components of blood from infected donors is poorly understood. Methods We used an in-house TaqMan qRT-PCR assay to test residual samples of plasma, cellular components of whole blood (CCWB), serum and clot specimens from the same collection from blood donors who were DENV-RNA-reactive in a parallel blood safety study. To assess whether DENV RNA detected by TaqMan was associated with infectious virus, DENV infectivity in available samples was determined by culture in mosquito cells. Results DENV RNA was detected by TaqMan in all tested blood components, albeit more consistently in the cellular components; 78.8% of CCWB, 73.3% of clots, 86.7% of sera and 41.8% of plasma samples. DENV-1 was detected in 48 plasma and 97 CCWB samples while DENV-4 was detected in 21 plasma and 31 CCWB samples. In mosquito cell cultures, 29/111 (26.1%) plasma and 32/97 (32.7%) CCWB samples were infectious. A subset of samples from 29 donors was separately analyzed to compare DENV viral loads in the available blood components. DENV viral loads did not differ significantly between components and ranged from 3–8 log10 PCR-detectable units/ml. Conclusions DENV was present in all tested components from most donors, and viral RNA was not preferentially distributed in any of the tested components. Infectious DENV was also present in similar proportions in cultured plasma, clot and CCWB samples, indicating that these components may serve as a resource when sample sizes are limited. However, these results suggest that the sensitivity of the nucleic acid tests (NAT) for these viruses would not be improved by testing whole blood or components other than plasma. PMID:26871560
Anez, German; Heisey, Daniel A. R.; Chancey, Caren; ...
2016-02-12
Dengue is a mosquito-borne viral disease caused by the four dengue viruses (DENV-1 to 4) that can also be transmitted by blood transfusion and organ transplantation. The distribution of DENV in the components of blood from infected donors is poorly understood. Here, we used an in-house TaqMan qRT-PCR assay to test residual samples of plasma, cellular components of whole blood (CCWB), serum and clot specimens from the same collection from blood donors who were DENV-RNA-reactive in a parallel blood safety study. To assess whether DENV RNA detected by TaqMan was associated with infectious virus, DENV infectivity in available samples wasmore » determined by culture in mosquito cells. As a result, DENV RNA was detected by TaqMan in all tested blood components, albeit more consistently in the cellular components; 78.8% of CCWB, 73.3% of clots, 86.7% of sera and 41.8% of plasma samples. DENV-1 was detected in 48 plasma and 97 CCWB samples while DENV-4 was detected in 21 plasma and 31 CCWB samples. In mosquito cell cultures, 29/111 (26.1%) plasma and 32/97 (32.7%) CCWB samples were infectious. A subset of samples from 29 donors was separately analyzed to compare DENV viral loads in the available blood components. DENV viral loads did not differ significantly between components and ranged from 3–8 log 10 PCR-detectable units/ml. In conclusion, DENV was present in all tested components from most donors, and viral RNA was not preferentially distributed in any of the tested components. Infectious DENV was also present in similar proportions in cultured plasma, clot and CCWB samples, indicating that these components may serve as a resource when sample sizes are limited. However, these results suggest that the sensitivity of the nucleic acid tests (NAT) for these viruses would not be improved by testing whole blood or components other than plasma.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Anez, German; Heisey, Daniel A. R.; Chancey, Caren
Dengue is a mosquito-borne viral disease caused by the four dengue viruses (DENV-1 to 4) that can also be transmitted by blood transfusion and organ transplantation. The distribution of DENV in the components of blood from infected donors is poorly understood. Here, we used an in-house TaqMan qRT-PCR assay to test residual samples of plasma, cellular components of whole blood (CCWB), serum and clot specimens from the same collection from blood donors who were DENV-RNA-reactive in a parallel blood safety study. To assess whether DENV RNA detected by TaqMan was associated with infectious virus, DENV infectivity in available samples wasmore » determined by culture in mosquito cells. As a result, DENV RNA was detected by TaqMan in all tested blood components, albeit more consistently in the cellular components; 78.8% of CCWB, 73.3% of clots, 86.7% of sera and 41.8% of plasma samples. DENV-1 was detected in 48 plasma and 97 CCWB samples while DENV-4 was detected in 21 plasma and 31 CCWB samples. In mosquito cell cultures, 29/111 (26.1%) plasma and 32/97 (32.7%) CCWB samples were infectious. A subset of samples from 29 donors was separately analyzed to compare DENV viral loads in the available blood components. DENV viral loads did not differ significantly between components and ranged from 3–8 log 10 PCR-detectable units/ml. In conclusion, DENV was present in all tested components from most donors, and viral RNA was not preferentially distributed in any of the tested components. Infectious DENV was also present in similar proportions in cultured plasma, clot and CCWB samples, indicating that these components may serve as a resource when sample sizes are limited. However, these results suggest that the sensitivity of the nucleic acid tests (NAT) for these viruses would not be improved by testing whole blood or components other than plasma.« less
Watt, Michelle; Silk, Wendy K; Passioura, John B
2006-05-01
Roots growing in soil encounter physical, chemical and biological environments that influence their rhizospheres and affect plant growth. Exudates from roots can stimulate or inhibit soil organisms that may release nutrients, infect the root, or modify plant growth via signals. These rhizosphere processes are poorly understood in field conditions. We characterize roots and their rhizospheres and rates of growth in units of distance and time so that interactions with soil organisms can be better understood in field conditions. We review: (1) distances between components of the soil, including dead roots remnant from previous plants, and the distances between new roots, their rhizospheres and soil components; (2) characteristic times (distance(2)/diffusivity) for solutes to travel distances between roots and responsive soil organisms; (3) rates of movement and growth of soil organisms; (4) rates of extension of roots, and how these relate to the rates of anatomical and biochemical ageing of root tissues and the development of the rhizosphere within the soil profile; and (5) numbers of micro-organisms in the rhizosphere and the dependence on the site of attachment to the growing tip. We consider temporal and spatial variation within the rhizosphere to understand the distribution of bacteria and fungi on roots in hard, unploughed soil, and the activities of organisms in the overlapping rhizospheres of living and dead roots clustered in gaps in most field soils. Rhizosphere distances, characteristic times for solute diffusion, and rates of root and organism growth must be considered to understand rhizosphere development. Many values used in our analysis were estimates. The paucity of reliable data underlines the rudimentary state of our knowledge of root-organism interactions in the field.
Population Pulsation Resonances of Excitons in Monolayer MoSe 2 with Sub-1 μeV Linewidths
Schaibley, John R.; Karin, Todd; Yu, Hongyi; ...
2015-04-01
Monolayer transition metal dichalcogenides, a new class of atomically thin semiconductors, possess optically coupled 2D valley excitons. The nature of exciton relaxation in these systems is currently poorly understood. In this paper, we investigate exciton relaxation in monolayer MoSe 2 using polarization-resolved coherent nonlinear optical spectroscopy with high spectral resolution. We report strikingly narrow population pulsation resonances with two different characteristic linewidths of 1 and <0.2 μeV at low temperature. These linewidths are more than 3 orders of magnitude narrower than the photoluminescence and absorption linewidth, and indicate that a component of the exciton relaxation dynamics occurs on time scalesmore » longer than 1 ns. Finally, the ultranarrow resonance (<0.2 μeV) emerges with increasing excitation intensity, and implies the existence of a long-lived state whose lifetime exceeds 6 ns.« less
TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.
Cebola, Inês; Rodríguez-Seguí, Santiago A; Cho, Candy H-H; Bessa, José; Rovira, Meritxell; Luengo, Mario; Chhatriwala, Mariya; Berry, Andrew; Ponsa-Cobas, Joan; Maestro, Miguel Angel; Jennings, Rachel E; Pasquali, Lorenzo; Morán, Ignasi; Castro, Natalia; Hanley, Neil A; Gomez-Skarmeta, Jose Luis; Vallier, Ludovic; Ferrer, Jorge
2015-05-01
The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas.
Effect of Grain Refining on Defect Formation in DC Cast Al-Zn-Mg-Cu Alloy Billet
NASA Astrophysics Data System (ADS)
Nadella, Ravi; Eskin, Dmitry; Katgerman, Laurens
In direct chill (DC) casting, the effect of grain refining on the prominent defects such as hot cracking and macrosegregation remains poorly understood, especially for multi-component commercial aluminum alloys. In this work, DC casting experiments were conducted on a 7075 alloy with and without grain refining at two casting speeds. The grain refiner was introduced either in the launder or in the furnace. The concentration profiles of Zn, Cu and Mg, measured along the billet diameter, showed that the increasing casting speed raises the segregation levels but grain refining does not seem to have a noticeable effect. However, hot cracking tendency is significantly reduced with grain refining and it is observed that crack is terminated with the introduction of grain refiner at a lower casting speed. These experimental results are correlated with microstructural observations such as grain size and morphology, and the occurrence of floating grains.
Oberding, Lisa; Gieg, Lisa M
2016-01-05
Hydrocarbon compounds can be biodegraded by anaerobic microorganisms to form methane through an energetically interdependent metabolic process known as syntrophy. The microorganisms that perform this process as well as the energy transfer mechanisms involved are difficult to study and thus are still poorly understood, especially on an environmental scale. Here, metagenomic data was analyzed for specific clusters of orthologous groups (COGs) related to key energy transfer genes thus far identified in syntrophic bacteria, and principal component analysis was used in order to determine whether potentially syntrophic environments could be distinguished using these syntroph related COGs as opposed to universally present COGs. We found that COGs related to hydrogenase and formate dehydrogenase genes were able to distinguish known syntrophic consortia and environments with the potential for syntrophy from non-syntrophic environments, indicating that these COGs could be used as a tool to identify syntrophic hydrocarbon biodegrading environments using metagenomic data.
Thiol reductive stress induces cellulose-anchored biofilm formation in Mycobacterium tuberculosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Trivedi, Abhishek; Mavi, Parminder Singh; Bhatt, Deepak
Mycobacterium tuberculosis (Mtb) forms biofilms harbouring antibiotic-tolerant bacilli in vitro, but the factors that induce biofilm formation and the nature of the extracellular material that holds the cells together are poorly understood. Here we show that intracellular thiol reductive stress (TRS) induces formation of Mtb biofilms in vitro, which harbour drug-tolerant but metabolically active bacteria with unchanged levels of ATP/ADP, NAD +/NADH and NADP +/NADPH. The development of these biofilms requires DNA, RNA and protein synthesis. Transcriptional analysis suggests that Mtb modulates only similar to 7% of its genes for survival in biofilms. In addition to proteins, lipids and DNA,more » the extracellular material in these biofilms is primarily composed of polysaccharides, with cellulose being a key component. Lastly, our results contribute to a better understanding of the mechanisms underlying Mtb biofilm formation, although the clinical relevance of Mtb biofilms in human tuberculosis remains unclear.« less
The role of water content in triboelectric charging of wind-blown sand.
Gu, Zhaolin; Wei, Wei; Su, Junwei; Yu, Chuck Wah
2013-01-01
Triboelectric charging is common in desert sandstorms and dust devils on Earth; however, it remains poorly understood. Here we show a charging mechanism of sands with the adsorbed water on micro-porous surface in wind-blown sand based on the fact that water content is universal but usually a minor component in most particle systems. The triboelectric charging could be resulted due to the different mobility of H(+)/OH(-) between the contacting sands with a temperature difference. Computational fluid dynamics (CFD) and discrete element method (DEM) were used to demonstrate the dynamics of the sand charging. The numerically simulated charge-to-mass ratios of sands and electric field strength established in wind tunnel agreed well with the experimental data. The charging mechanism could provide an explanation for the charging process of all identical granular systems with water content, including Martian dust devils, wind-blown snow, even powder electrification in industrial processes.
The neural correlates of reciprocity are sensitive to prior experience of reciprocity.
Cáceda, Ricardo; Prendes-Alvarez, Stefania; Hsu, Jung-Jiin; Tripathi, Shanti P; Kilts, Clint D; James, G Andrew
2017-08-14
Reciprocity is central to human relationships and is strongly influenced by multiple factors including the nature of social exchanges and their attendant emotional reactions. Despite recent advances in the field, the neural processes involved in this modulation of reciprocal behavior by ongoing social interaction are poorly understood. We hypothesized that activity within a discrete set of neural networks including a putative moral cognitive neural network is associated with reciprocity behavior. Nineteen healthy adults underwent functional magnetic resonance imaging scanning while playing the trustee role in the Trust Game. Personality traits and moral development were assessed. Independent component analysis was used to identify task-related functional brain networks and assess their relationship to behavior. The saliency network (insula and anterior cingulate) was positively correlated with reciprocity behavior. A consistent array of brain regions supports the engagement of emotional, self-referential and planning processes during social reciprocity behavior. Published by Elsevier B.V.
Memory retrieval and the parietal cortex: a review of evidence from a dual-process perspective.
Vilberg, Kaia L; Rugg, Michael D
2008-01-01
Although regions of the parietal cortex have been consistently implicated in episodic memory retrieval, the functional roles of these regions remain poorly understood. The present review presents a meta-analysis of findings from event-related fMRI studies reporting the loci of retrieval effects associated with familiarity- and recollection-related recognition judgments. The results of this analysis support previous suggestions that retrieval-related activity in lateral parietal cortex dissociates between superior regions, where activity likely reflects the task relevance of different classes of recognition test items, and more inferior regions where retrieval-related activity appears closely linked to successful recollection. It is proposed that inferior lateral parietal cortex forms part of a neural network supporting the 'episodic buffer' [Baddeley, A. D. (2000). The episodic buffer: A new component of working memory? Trends in Cognitive Sciences, 4, 417-423].
The Migraine-Ischemic Stroke Relation in Young Adults
Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro
2011-01-01
In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470
Linking acute kidney injury to chronic kidney disease: the missing links.
Kaballo, Mohammed A; Elsayed, Mohamed E; Stack, Austin G
2017-08-01
Acute kidney injury (AKI) is considered to be a major public health problem around the globe, and it is associated with major adverse clinical outcomes and significant health care costs. There is growing evidence suggesting that AKI is associated with the subsequent development of chronic kidney disease (CKD). While recovery of kidney function occurs in the majority of patients surviving an AKI episode, a large number of patients do not recover completely. Similarly, CKD is a well-known risk factor for the development of AKI. Recent studies suggest that both AKI and CKD are not separate disease entities but are in fact components of a far more closely interconnected disease continuum. However, the true nature of this relationship is complex and poorly understood. This review explores potential relationships between AKI and CKD, and seeks to uncover a number of "missing links" in this tentative emerging relationship.
Cascade of neural processing orchestrates cognitive control in human frontal cortex
Tang, Hanlin; Yu, Hsiang-Yu; Chou, Chien-Chen; Crone, Nathan E; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel
2016-01-01
Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex. DOI: http://dx.doi.org/10.7554/eLife.12352.001 PMID:26888070
Discovery of a proteinaceous cellular receptor for a norovirus
Orchard, Robert C.; Wilen, Craig B.; Doench, John G.; Baldridge, Megan T.; McCune, Broc T.; Lee, Ying-Chiang J.; Lee, Sanghyun; Pruett-Miller, Shondra M.; Nelson, Christopher A.; Fremont, Daved H.; Virgin, Herbert W.
2017-01-01
Human noroviruses (NoV) are a leading cause of gastroenteritis globally, yet host factors required for NoV infection are poorly understood. We identified host molecules essential for murine NoV (MNoV) induced cell death including CD300lf as a proteinaceous receptor. CD300lf is essential for MNoV binding and replication in cell lines and primary cells. Additionally, Cd300lf−/− mice are resistant to MNoV infection. Expression of CD300lf in human cells breaks the species barrier restricting MNoV replication. The crystal structure of the CD300lf ectodomain revealed a potential ligand binding cleft composed of residues critical for MNoV infection. Therefore, the presence of a proteinaceous receptor is the primary determinant of MNoV species tropism while other components of cellular machinery required for NoV replication are conserved between humans and mice. PMID:27540007
GroEL stimulates protein folding through forced unfolding
Lin, Zong; Madan, Damian; Rye, Hays S
2013-01-01
Many proteins cannot fold without the assistance of chaperonin machines like GroEL and GroES. The nature of this assistance, however, remains poorly understood. Here we demonstrate that unfolding of a substrate protein by GroEL enhances protein folding. We first show that capture of a protein on the open ring of a GroEL–ADP–GroES complex, GroEL’s physiological acceptor state for non-native proteins in vivo, leaves the substrate protein in an unexpectedly compact state. Subsequent binding of ATP to the same GroEL ring causes rapid, forced unfolding of the substrate protein. Notably, the fraction of the substrate protein that commits to the native state following GroES binding and protein release into the GroEL–GroES cavity is proportional to the extent of substrate-protein unfolding. Forced protein unfolding is thus a central component of the multilayered stimulatory mechanism used by GroEL to drive protein folding. PMID:18311152
Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling.
Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K; Marmer, Barry; Goldberg, Gregory I; Neuman, Keir C
2016-07-26
Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal-strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments.
From Embryonic Development to Human Diseases: The Functional Role of Caveolae/Caveolin
Sohn, Jihee; Brick, Rachel M.; Tuan, Rocky S.
2017-01-01
Caveolae, an almost ubiquitous, structural component of the plasma membrane, play a critical role in many functions essential for proper cell function, including membrane trafficking, signal transduction, extracellular matrix remodeling, and tissue regeneration. Three main types of caveolin proteins have been identified from caveolae since the discovery of caveolin-1 in the early 1990s. All three (Cav-1, Cav-2, and Cav-3) play crucial roles in mammalian physiology, and can effect pathogenesis in a wide range of human diseases. While many biological activities of caveolins have been uncovered since its discovery, their role and regulation in embryonic develop remain largely poorly understood, although there is increasing evidence that caveolins may be linked to lung and brain birth defects. Further investigations are clearly needed to decipher how caveolae/caveolins mediate cellular functions and activities of normal embryogenesis and how their perturbations contribute to developmental disorders. PMID:26991990
The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis
Zhang, Weiwei; Ran, Qian; Xiang, Yang; Zhong, Jiang F.; Li, Shengwen Calvin
2018-01-01
Bone marrow mesenchymal stem cells (BMSCs), the important component and regulator of bone marrow microenvironment, give rise to hematopoietic-supporting stromal cells and form hematopoietic niches for hematopoietic stem cells (HSCs). However, how BMSC differentiation affects hematopoiesis is poorly understood. In this review, we focus on the role of BMSC differentiation in hematopoiesis. We discussed the role of BMSCs and their progeny in hematopoiesis. We also examine the mechanisms that cause differentiation bias of BMSCs in stress conditions including aging, irradiation, and chemotherapy. Moreover, the differentiation balance of BMSCs is crucial to hematopoiesis. We highlight the negative effects of differentiation bias of BMSCs on hematopoietic recovery after bone marrow transplantation. Keeping the differentiation balance of BMSCs is critical for hematopoietic recovery. This review summarises current understanding about how BMSC differentiation affects hematopoiesis and its potential application in improving hematopoietic recovery after bone marrow transplantation. PMID:29765406
Introduction and historical perspective.
Gunning, Peter
2008-01-01
Tropomyosin is a coiled coil dimer which forms a polymer along the major groove of the majority of actin filaments. It is therefore one of the two primary components of the actin filament. Our understanding of the biological function of tropomyosin has been driven almost entirely by its role in striated muscle. This reflects both its original discovery as part of the thin filament in skeletal muscle and its pivotal role in regulating muscle contraction. In contrast, its role in the function of the cytoskeleton of all cells has been poorly understood due, at least in part, to the technical challenge of deciphering the function of a large number of isoforms. This book has brought together many of the leading researchers who have defined the function of tropomyosin in both normal and pathological conditions. Each author brings their own perspective in a series of stand alone reviews of the areas of tropomyosin research they have played a major role in defining.
Local time dependence of turbulent magnetic fields in Saturn's magnetodisc
NASA Astrophysics Data System (ADS)
Kaminker, V.; Delamere, P. A.; Ng, C. S.; Dennis, T.; Otto, A.; Ma, X.
2017-04-01
Net plasma transport in magnetodiscs around giant planets is outward. Observations of plasma temperature have shown that the expanding plasma is heating nonadiabatically during this process. Turbulence has been suggested as a source of heating. However, the mechanism and distribution of magnetic fluctuations in giant magnetospheres are poorly understood. In this study we attempt to quantify the radial and local time dependence of fluctuating magnetic field signatures that are suggestive of turbulence, quantifying the fluctuations in terms of a plasma heating rate density. In addition, the inferred heating rate density is correlated with magnetic field configurations that include azimuthal bend forward/back and magnitude of the equatorial normal component of magnetic field relative to the dipole. We find a significant local time dependence in magnetic fluctuations that is consistent with flux transport triggered in the subsolar and dusk sectors due to magnetodisc reconnection.
Thiol reductive stress induces cellulose-anchored biofilm formation in Mycobacterium tuberculosis
Trivedi, Abhishek; Mavi, Parminder Singh; Bhatt, Deepak; ...
2016-04-25
Mycobacterium tuberculosis (Mtb) forms biofilms harbouring antibiotic-tolerant bacilli in vitro, but the factors that induce biofilm formation and the nature of the extracellular material that holds the cells together are poorly understood. Here we show that intracellular thiol reductive stress (TRS) induces formation of Mtb biofilms in vitro, which harbour drug-tolerant but metabolically active bacteria with unchanged levels of ATP/ADP, NAD +/NADH and NADP +/NADPH. The development of these biofilms requires DNA, RNA and protein synthesis. Transcriptional analysis suggests that Mtb modulates only similar to 7% of its genes for survival in biofilms. In addition to proteins, lipids and DNA,more » the extracellular material in these biofilms is primarily composed of polysaccharides, with cellulose being a key component. Lastly, our results contribute to a better understanding of the mechanisms underlying Mtb biofilm formation, although the clinical relevance of Mtb biofilms in human tuberculosis remains unclear.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wood, Graham
2008-01-15
The evaluation and communication of the significance of environmental effects remains a critical yet poorly understood component of EIA theory and practice. Following a conceptual overview of the generic dimensions of impact significance in EIA, this paper reports upon the findings of an empirical study of recent environmental impact statements that considers the treatment of significance for impacts concerning landscape ('see no evil') and noise ('hear no evil'), focussing specifically upon the evaluation and communication of impact significance ('speak no evil') in UK practice. Particular attention is given to the use of significance criteria and thresholds, including the development ofmore » a typology of approaches applied within the context of noise and landscape/visual impacts. Following a broader discussion of issues surrounding the formulation, application and interpretation of significance criteria, conclusions and recommendations relevant to wider EIA practice are suggested.« less
Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair.
Lu, Wei-Ting; Hawley, Ben R; Skalka, George L; Baldock, Robert A; Smith, Ewan M; Bader, Aldo S; Malewicz, Michal; Watts, Felicity Z; Wilczynska, Ania; Bushell, Martin
2018-02-07
The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells.
Predictive codes of familiarity and context during the perceptual learning of facial identities
NASA Astrophysics Data System (ADS)
Apps, Matthew A. J.; Tsakiris, Manos
2013-11-01
Face recognition is a key component of successful social behaviour. However, the computational processes that underpin perceptual learning and recognition as faces transition from unfamiliar to familiar are poorly understood. In predictive coding, learning occurs through prediction errors that update stimulus familiarity, but recognition is a function of both stimulus and contextual familiarity. Here we show that behavioural responses on a two-option face recognition task can be predicted by the level of contextual and facial familiarity in a computational model derived from predictive-coding principles. Using fMRI, we show that activity in the superior temporal sulcus varies with the contextual familiarity in the model, whereas activity in the fusiform face area covaries with the prediction error parameter that updated facial familiarity. Our results characterize the key computations underpinning the perceptual learning of faces, highlighting that the functional properties of face-processing areas conform to the principles of predictive coding.
The Effects of Performance Fatigability on Postural Control and Rehabilitation in the Older Patient
Hassan, Mahdi; Bugnariu, Nicoleta
2016-01-01
Fatigue is common in older adults and has a significant effect on quality of life. Despite the high prevalence of fatigue in older individuals, several aspects are poorly understood. It is important to differentiate subjective fatigue complaints from fatigability of motor performance because the two are independent constructs with potentially distinct consequences on mobility. Performance fatigability is the magnitude of change in a performance criterion over a given time of task performance. Performance fatigability is a compulsory element of any strength training program, yet strength training is an important component of rehabilitation programs for older adults. The consequences of fatigability for older adults suggest that acute exercise of various types may result in acute impairments in postural control. The effects of performance fatigability on postural control in older adults are evaluated here to aid the rehabilitation clinician in making recommendations for evaluation of fall risks and exercise prescription. PMID:28154794
The Effects of Performance Fatigability on Postural Control and Rehabilitation in the Older Patient.
Papa, Evan V; Hassan, Mahdi; Bugnariu, Nicoleta
2016-09-01
Fatigue is common in older adults and has a significant effect on quality of life. Despite the high prevalence of fatigue in older individuals, several aspects are poorly understood. It is important to differentiate subjective fatigue complaints from fatigability of motor performance because the two are independent constructs with potentially distinct consequences on mobility. Performance fatigability is the magnitude of change in a performance criterion over a given time of task performance. Performance fatigability is a compulsory element of any strength training program, yet strength training is an important component of rehabilitation programs for older adults. The consequences of fatigability for older adults suggest that acute exercise of various types may result in acute impairments in postural control. The effects of performance fatigability on postural control in older adults are evaluated here to aid the rehabilitation clinician in making recommendations for evaluation of fall risks and exercise prescription.
Drought sensitivity of the Amazon rainforest.
Phillips, Oliver L; Aragão, Luiz E O C; Lewis, Simon L; Fisher, Joshua B; Lloyd, Jon; López-González, Gabriela; Malhi, Yadvinder; Monteagudo, Abel; Peacock, Julie; Quesada, Carlos A; van der Heijden, Geertje; Almeida, Samuel; Amaral, Iêda; Arroyo, Luzmila; Aymard, Gerardo; Baker, Tim R; Bánki, Olaf; Blanc, Lilian; Bonal, Damien; Brando, Paulo; Chave, Jerome; de Oliveira, Atila Cristina Alves; Cardozo, Nallaret Dávila; Czimczik, Claudia I; Feldpausch, Ted R; Freitas, Maria Aparecida; Gloor, Emanuel; Higuchi, Niro; Jiménez, Eliana; Lloyd, Gareth; Meir, Patrick; Mendoza, Casimiro; Morel, Alexandra; Neill, David A; Nepstad, Daniel; Patiño, Sandra; Peñuela, Maria Cristina; Prieto, Adriana; Ramírez, Fredy; Schwarz, Michael; Silva, Javier; Silveira, Marcos; Thomas, Anne Sota; Steege, Hans Ter; Stropp, Juliana; Vásquez, Rodolfo; Zelazowski, Przemyslaw; Alvarez Dávila, Esteban; Andelman, Sandy; Andrade, Ana; Chao, Kuo-Jung; Erwin, Terry; Di Fiore, Anthony; Honorio C, Eurídice; Keeling, Helen; Killeen, Tim J; Laurance, William F; Peña Cruz, Antonio; Pitman, Nigel C A; Núñez Vargas, Percy; Ramírez-Angulo, Hirma; Rudas, Agustín; Salamão, Rafael; Silva, Natalino; Terborgh, John; Torres-Lezama, Armando
2009-03-06
Amazon forests are a key but poorly understood component of the global carbon cycle. If, as anticipated, they dry this century, they might accelerate climate change through carbon losses and changed surface energy balances. We used records from multiple long-term monitoring plots across Amazonia to assess forest responses to the intense 2005 drought, a possible analog of future events. Affected forest lost biomass, reversing a large long-term carbon sink, with the greatest impacts observed where the dry season was unusually intense. Relative to pre-2005 conditions, forest subjected to a 100-millimeter increase in water deficit lost 5.3 megagrams of aboveground biomass of carbon per hectare. The drought had a total biomass carbon impact of 1.2 to 1.6 petagrams (1.2 x 10(15) to 1.6 x 10(15) grams). Amazon forests therefore appear vulnerable to increasing moisture stress, with the potential for large carbon losses to exert feedback on climate change.
Meta-Analysis of the Core Aroma Components of Grape and Wine Aroma
Ilc, Tina; Werck-Reichhart, Danièle; Navrot, Nicolas
2016-01-01
Wine aroma strongly influences wine quality, yet its composition and its evolution during the winemaking process are poorly understood. Volatile compounds that constitute wine aroma are traditionally divided into three classes according to their origin: grape, fermentation, and maturation aroma. We challenge this view with meta-analysis and review of grape and wine volatiles and their precursors from 82 profiling experiments. We compiled a list of 141 common grape and wine volatiles and quantitatively compared 43 of them. Our work offers insight into complex relationships between biosynthesis of aroma in grapes and the changes during the winemaking process. Monoterpenes are one of the largest and most researched wine aroma compounds. We show that their diversity in wines is mainly due to the oxidative metabolism of linalool in grapes. Furthermore, we demonstrate that most of the linalool produced in grapes is converted to these oxidized derivatives. PMID:27746799
Thiol reductive stress induces cellulose-anchored biofilm formation in Mycobacterium tuberculosis
Trivedi, Abhishek; Mavi, Parminder Singh; Bhatt, Deepak; Kumar, Ashwani
2016-01-01
Mycobacterium tuberculosis (Mtb) forms biofilms harbouring antibiotic-tolerant bacilli in vitro, but the factors that induce biofilm formation and the nature of the extracellular material that holds the cells together are poorly understood. Here we show that intracellular thiol reductive stress (TRS) induces formation of Mtb biofilms in vitro, which harbour drug-tolerant but metabolically active bacteria with unchanged levels of ATP/ADP, NAD+/NADH and NADP+/NADPH. The development of these biofilms requires DNA, RNA and protein synthesis. Transcriptional analysis suggests that Mtb modulates only ∼7% of its genes for survival in biofilms. In addition to proteins, lipids and DNA, the extracellular material in these biofilms is primarily composed of polysaccharides, with cellulose being a key component. Our results contribute to a better understanding of the mechanisms underlying Mtb biofilm formation, although the clinical relevance of Mtb biofilms in human tuberculosis remains unclear. PMID:27109928
Thiol reductive stress induces cellulose-anchored biofilm formation in Mycobacterium tuberculosis.
Trivedi, Abhishek; Mavi, Parminder Singh; Bhatt, Deepak; Kumar, Ashwani
2016-04-25
Mycobacterium tuberculosis (Mtb) forms biofilms harbouring antibiotic-tolerant bacilli in vitro, but the factors that induce biofilm formation and the nature of the extracellular material that holds the cells together are poorly understood. Here we show that intracellular thiol reductive stress (TRS) induces formation of Mtb biofilms in vitro, which harbour drug-tolerant but metabolically active bacteria with unchanged levels of ATP/ADP, NAD(+)/NADH and NADP(+)/NADPH. The development of these biofilms requires DNA, RNA and protein synthesis. Transcriptional analysis suggests that Mtb modulates only ∼7% of its genes for survival in biofilms. In addition to proteins, lipids and DNA, the extracellular material in these biofilms is primarily composed of polysaccharides, with cellulose being a key component. Our results contribute to a better understanding of the mechanisms underlying Mtb biofilm formation, although the clinical relevance of Mtb biofilms in human tuberculosis remains unclear.
Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1.
Ruthenborg, Robin J; Ban, Jae-Jun; Wazir, Anum; Takeda, Norihiko; Kim, Jung-Whan
2014-09-01
Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.
PINK1 deficiency enhances autophagy and mitophagy induction.
Gómez-Sánchez, Rubén; Yakhine-Diop, Sokhna M S; Bravo-San Pedro, José M; Pizarro-Estrella, Elisa; Rodríguez-Arribas, Mario; Climent, Vicente; Martin-Cano, Francisco E; González-Soltero, María E; Tandon, Anurag; Fuentes, José M; González-Polo, Rosa A
2016-03-01
Parkinson's disease (PD) is a neurodegenerative disorder with poorly understood etiology. Increasing evidence suggests that age-dependent compromise of the maintenance of mitochondrial function is a key risk factor. Several proteins encoded by PD-related genes are associated with mitochondria including PTEN-induced putative kinase 1 (PINK1), which was first identified as a gene that is upregulated by PTEN. Loss-of-function PINK1 mutations induce mitochondrial dysfunction and, ultimately, neuronal cell death. To mitigate the negative effects of altered cellular functions cells possess a degradation mechanism called autophagy for recycling damaged components; selective elimination of dysfunctional mitochondria by autophagy is termed mitophagy. Our study indicates that autophagy and mitophagy are upregulated in PINK1-deficient cells, and is the first report to demonstrate efficient fluxes by one-step analysis. We propose that autophagy is induced to maintain cellular homeostasis under conditions of non-regulated mitochondrial quality control.
PINK1 deficiency enhances autophagy and mitophagy induction
Gómez-Sánchez, Rubén; Yakhine-Diop, Sokhna M S; Bravo-San Pedro, José M; Pizarro-Estrella, Elisa; Rodríguez-Arribas, Mario; Climent, Vicente; Martin-Cano, Francisco E; González-Soltero, María E; Tandon, Anurag; Fuentes, José M; González-Polo, Rosa A
2016-01-01
Parkinson's disease (PD) is a neurodegenerative disorder with poorly understood etiology. Increasing evidence suggests that age-dependent compromise of the maintenance of mitochondrial function is a key risk factor. Several proteins encoded by PD-related genes are associated with mitochondria including PTEN-induced putative kinase 1 (PINK1), which was first identified as a gene that is upregulated by PTEN. Loss-of-function PINK1 mutations induce mitochondrial dysfunction and, ultimately, neuronal cell death. To mitigate the negative effects of altered cellular functions cells possess a degradation mechanism called autophagy for recycling damaged components; selective elimination of dysfunctional mitochondria by autophagy is termed mitophagy. Our study indicates that autophagy and mitophagy are upregulated in PINK1-deficient cells, and is the first report to demonstrate efficient fluxes by one-step analysis. We propose that autophagy is induced to maintain cellular homeostasis under conditions of non-regulated mitochondrial quality control. PMID:27308585
Outdoor Ambient Air Pollution and Neurodegenerative Diseases: the Neuroinflammation Hypothesis.
Jayaraj, Richard L; Rodriguez, Eric A; Wang, Yi; Block, Michelle L
2017-06-01
Accumulating research indicates that ambient outdoor air pollution impacts the brain and may affect neurodegenerative diseases, yet the potential underlying mechanisms are poorly understood. The neuroinflammation hypothesis holds that elevation of cytokines and reactive oxygen species in the brain mediates the deleterious effects of urban air pollution on the central nervous system (CNS). Studies in human and animal research document that neuroinflammation occurs in response to several inhaled pollutants. Microglia are a prominent source of cytokines and reactive oxygen species in the brain, implicated in the progressive neuron damage in diverse neurodegenerative diseases, and activated by inhaled components of urban air pollution through both direct and indirect pathways. The MAC1-NOX2 pathway has been identified as a mechanism through which microglia respond to different forms of air pollution, suggesting a potential common deleterious pathway. Multiple direct and indirect pathways in response to air pollution exposure likely interact in concert to exert CNS effects.
Chen, Wei-Shen; Antic, Dragana; Matis, Maja; Logan, Catriona Y.; Povelones, Michael; Anderson, Graham; Nusse, Roel; Axelrod, Jeffrey D.
2008-01-01
Acquisition of planar cell polarity (PCP) in epithelia involves intercellular communication, during which cells align their polarity with that of their neighbors. The transmembrane proteins Frizzled (Fz) and Van Gogh (Vang) are essential components of the intercellular communication mechanism, as loss of either strongly perturbs the polarity of neighboring cells. How Fz and Vang communicate polarity information between neighboring cells is poorly understood. The atypical cadherin, Flamingo (Fmi), is implicated in this process, yet whether Fmi acts permissively as a scaffold, or instructively as a signal is unclear. Here, we provide evidence that Fmi functions instructively to mediate Fz-Vang intercellular signal relay, recruiting Fz and Vang to opposite sides of cell boundaries. We propose that two functional forms of Fmi, one of which is induced by and physically interacts with Fz, form cadherin homodimers that signal bidirectionally and asymmetrically, instructing unequal responses in adjacent cell membranes to establish molecular asymmetry. PMID:18555784
Osmotic pressure induced tensile forces in tendon collagen
NASA Astrophysics Data System (ADS)
Masic, Admir; Bertinetti, Luca; Schuetz, Roman; Chang, Shu-Wei; Metzger, Till Hartmut; Buehler, Markus J.; Fratzl, Peter
2015-01-01
Water is an important component of collagen in tendons, but its role for the function of this load-carrying protein structure is poorly understood. Here we use a combination of multi-scale experimentation and computation to show that water is an integral part of the collagen molecule, which changes conformation upon water removal. The consequence is a shortening of the molecule that translates into tensile stresses in the range of several to almost 100 MPa, largely surpassing those of about 0.3 MPa generated by contractile muscles. Although a complete drying of collagen would be relevant for technical applications, such as the fabrication of leather or parchment, stresses comparable to muscle contraction already occur at small osmotic pressures common in biological environments. We suggest, therefore, that water-generated tensile stresses may play a role in living collagen-based materials such as tendon or bone.
Intravenous human immunoglobulin for treatment of folliculitis decalvans.
Ismail, Nuriah; Ralph, Nicola; Murphy, Gillian
2015-10-01
We report a case of folliculitis decalvans (FD) successfully treated with intravenous human immunoglobulin (HIG). Many conventional treatments with topical agents and oral antibiotics had failed to achieve disease remission, treatment with HIG at a dose of 2 g/kg for the first month, reduced to 1 g/kg for second to fourth months was therefore started, which resulted in rapid improvement and ultimately complete resolution of FD. Clinical improvement was noted after the first infusion of HIG and remission of inflammation was achieved after the fourth infusion. Disease remission was sustained for six months following the last HIG infusion. The exact mechanism of action of HIG is poorly understood. However, it is thought to act as an immunomodulatory agent by altering different components of immune functions. To our knowledge, this is the first case reported in the literature of FD successfully treated with intravenous HIG.
The role of water content in triboelectric charging of wind-blown sand
Gu, Zhaolin; Wei, Wei; Su, Junwei; Yu, Chuck Wah
2013-01-01
Triboelectric charging is common in desert sandstorms and dust devils on Earth; however, it remains poorly understood. Here we show a charging mechanism of sands with the adsorbed water on micro-porous surface in wind-blown sand based on the fact that water content is universal but usually a minor component in most particle systems. The triboelectric charging could be resulted due to the different mobility of H+/OH− between the contacting sands with a temperature difference. Computational fluid dynamics (CFD) and discrete element method (DEM) were used to demonstrate the dynamics of the sand charging. The numerically simulated charge-to-mass ratios of sands and electric field strength established in wind tunnel agreed well with the experimental data. The charging mechanism could provide an explanation for the charging process of all identical granular systems with water content, including Martian dust devils, wind-blown snow, even powder electrification in industrial processes. PMID:23434920
Review of progress in magnetic particle inspection
NASA Astrophysics Data System (ADS)
Eisenmann, David J.; Enyart, Darrel; Lo, Chester; Brasche, Lisa
2014-02-01
Magnetic particle inspection (MPI) has been widely utilized for decades, and sees considerable use in the aerospace industry with a majority of the steel parts being inspected with MPI at some point in the lifecycle. Typical aircraft locations inspected are landing gear, engine components, attachment hardware, and doors. In spite of its numerous applications the method remains poorly understood, and there are many aspects of that method which would benefit from in-depth study. This shortcoming is due to the fact that MPI combines the complicated nature of electromagnetics, metallurgical material effects, fluid-particle motion dynamics, and physiological human factors into a single inspection. To promote understanding of the intricate method issues that affect sensitivity, or to assist with the revision of industry specifications and standards, research studies will be prioritized through the guidance of a panel of industry experts, using an approach which has worked successfully in the past to guide fluorescent penetrant inspection (FPI) research efforts.
Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation
Annambhotla, Suman; Bourgeois, Sebastian; Wang, Xinwen; Lin, Peter H.; Yao, Qizhi; Chen, Changyi
2010-01-01
Abdominal Aortic Aneurysm (AAA) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of AAA formation remains poorly understood. Currently, the treatment for AAA remains primarily surgical with the lone innovation of endovascular therapy. With advance in the human genome, understanding precisely which molecules and genes mediate AAA development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of AAA formation including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA. PMID:18259804
Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling
Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K.; Marmer, Barry; Goldberg, Gregory I.; Neuman, Keir C.
2016-01-01
Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal–strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments. PMID:27402741
Attention Enhances Synaptic Efficacy and Signal-to-Noise in Neural Circuits
Briggs, Farran; Mangun, George R.; Usrey, W. Martin
2013-01-01
Summary Attention is a critical component of perception. However, the mechanisms by which attention modulates neuronal communication to guide behavior are poorly understood. To elucidate the synaptic mechanisms of attention, we developed a sensitive assay of attentional modulation of neuronal communication. In alert monkeys performing a visual spatial attention task, we probed thalamocortical communication by electrically stimulating neurons in the lateral geniculate nucleus of the thalamus while simultaneously recording shock-evoked responses from monosynaptically connected neurons in primary visual cortex. We found that attention enhances neuronal communication by (1) increasing the efficacy of presynaptic input in driving postsynaptic responses, (2) increasing synchronous responses among ensembles of postsynaptic neurons receiving independent input, and (3) decreasing redundant signals between postsynaptic neurons receiving common input. These results demonstrate that attention finely tunes neuronal communication at the synaptic level by selectively altering synaptic weights, enabling enhanced detection of salient events in the noisy sensory milieu. PMID:23803766
DOE Office of Scientific and Technical Information (OSTI.GOV)
McLachlan, M.S.
The digestive tract absorption of environmental contaminants is an important but poorly understood parameter in contaminant is an important but poorly understood parameter in contaminant risk assessments. The net absorption of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in a nursing infant was measured under natural conditions over 12 days. The levels of the substances in the mother's milk were typical for Germany. It was found that for almost all congeners over 90% of the ingested compound was absorbed. This indicates that the common assumption of 100% absorption in nursing infants is reasonable. No firm conclusions could be drawn regarding the absorptionmore » of Cl7- and Cl8DD/F due to high blank levels in the cotton diapers used.« less
Poorly Understood Aspects of Striated Muscle Contraction
Månsson, Alf
2015-01-01
Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs. PMID:25961006
Poorly understood aspects of striated muscle contraction.
Månsson, Alf; Rassier, Dilson; Tsiavaliaris, Georgios
2015-01-01
Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs.
Linking Early Environmental Exposures to Adult Diseases
... diseases. Given that many disorders arise during fetal development from disruptions in the dynamic but still poorly understood interplay of genes, environment and nutrition, prevention may have to occur decades ...
An inexpensive and portable drill rig for bedrock groundwater studies in headwater catchments
C. Gabrielli; J.J. McDonnell
2011-01-01
Bedrock groundwater dynamics in headwater catchments are poorly understood and poorly characterized. Here, we present an inexpensive and portable bedrock drilling system designed for use in remote locations. Our system is capable of drilling bedrock wells up to 11 m deep and 38 mm in diameter in a wide range of bedrock types. The drill consists of a lawn mower engine...
Bado, Patricia; Engel, Annerose; de Oliveira-Souza, Ricardo; Bramati, Ivanei E; Paiva, Fernando F; Basilio, Rodrigo; Sato, João R; Tovar-Moll, Fernanda; Moll, Jorge
2014-01-01
Humans spend a substantial share of their lives mind-wandering. This spontaneous thinking activity usually comprises autobiographical recall, emotional, and self-referential components. While neuroimaging studies have demonstrated that a specific brain “default mode network” (DMN) is consistently engaged by the “resting state” of the mind, the relative contribution of key cognitive components to DMN activity is still poorly understood. Here we used fMRI to investigate whether activity in neural components of the DMN can be differentially explained by active recall of relevant emotional autobiographical memories as compared with the resting state. Our study design combined emotional autobiographical memory, neutral memory and resting state conditions, separated by a serial subtraction control task. Shared patterns of activation in the DMN were observed in both emotional autobiographical and resting conditions, when compared with serial subtraction. Directly contrasting autobiographical and resting conditions demonstrated a striking dissociation within the DMN in that emotional autobiographical retrieval led to stronger activation of the dorsomedial core regions (medial prefrontal cortex, posterior cingulate cortex), whereas the resting state condition engaged a ventral frontal network (ventral striatum, subgenual and ventral anterior cingulate cortices) in addition to the IPL. Our results reveal an as yet unreported dissociation within the DMN. Whereas the dorsomedial component can be explained by emotional autobiographical memory, the ventral frontal one is predominantly associated with the resting state proper, possibly underlying fundamental motivational mechanisms engaged during spontaneous unconstrained ideation. Hum Brain Mapp 35:3302–3313, 2014. © 2013 Wiley Periodicals, Inc. PMID:25050426
Campos-Sánchez, Antonio; López-Núñez, Juan Antonio; Carriel, Víctor; Martín-Piedra, Miguel-Ángel; Sola, Tomás; Alaminos, Miguel
2014-03-10
The students' motivation to learn basic sciences in health science curricula is poorly understood. The purpose of this study was to investigate the influence of different components of motivation (intrinsic motivation, self-determination, self-efficacy and extrinsic -career and grade- motivation) on learning human histology in health science curricula and their relationship with the final performance of the students in histology. Glynn Science Motivation Questionnaire II was used to compare students' motivation components to learn histology in 367 first-year male and female undergraduate students enrolled in medical, dentistry and pharmacy degree programs. For intrinsic motivation, career motivation and self-efficacy, the highest values corresponded to medical students, whereas dentistry students showed the highest values for self-determination and grade motivation. Genders differences were found for career motivation in medicine, self-efficacy in dentistry, and intrinsic motivation, self-determination and grade motivation in pharmacy. Career motivation and self-efficacy components correlated with final performance in histology of the students corresponding to the three curricula. Our results show that the overall motivational profile for learning histology differs among medical, dentistry and pharmacy students. This finding is potentially useful to foster their learning process, because if they are metacognitively aware of their motivation they will be better equipped to self-regulate their science-learning behavior in histology. This information could be useful for instructors and education policy makers to enhance curricula not only on the cognitive component of learning but also to integrate students' levels and types of motivation into the processes of planning, delivery and evaluation of medical education.
Source processes of industrially-induced earthquakes at the Geysers geothermal area, California
Ross, A.; Foulger, G.R.; Julian, B.R.
1999-01-01
Microearthquake activity at The Geysers geothermal area, California, mirrors the steam production rate, suggesting that the earthquakes are industrially induced. A 15-station network of digital, three-component seismic stations was operated for one month in 1991, and 3,900 earthquakes were recorded. Highly-accurate moment tensors were derived for 30 of the best recorded earthquakes by tracing rays through tomographically derived 3-D VP and VP / VS structures, and inverting P-and S-wave polarities and amplitude ratios. The orientations of the P-and T-axes are very scattered, suggesting that there is no strong, systematic deviatoric stress field in the reservoir, which could explain why the earthquakes are not large. Most of the events had significant non-double-couple (non-DC) components in their source mechanisms with volumetric components up to ???30% of the total moment. Explosive and implosive sources were observed in approximately equal numbers, and must be caused by cavity creation (or expansion) and collapse. It is likely that there is a causal relationship between these processes and fluid reinjection and steam withdrawal. Compensated linear vector dipole (CLVD) components were up to 100% of the deviatoric component. Combinations of opening cracks and shear faults cannot explain all the observations, and rapid fluid flow may also be involved. The pattern of non-DC failure at The Geysers contrasts with that of the Hengill-Grensdalur area in Iceland, a largely unexploited water-dominated field in an extensional stress regime. These differences are poorly understood but may be linked to the contrasting regional stress regimes and the industrial exploitation at The Geysers.
The neural bases of feeling understood and not understood.
Morelli, Sylvia A; Torre, Jared B; Eisenberger, Naomi I
2014-12-01
Past research suggests that feeling understood enhances both personal and social well-being. However, little research has examined the neurobiological bases of feeling understood and not understood. We addressed these gaps by experimentally inducing felt understanding and not understanding as participants underwent functional magnetic resonance imaging. The results demonstrated that feeling understood activated neural regions previously associated with reward and social connection (i.e. ventral striatum and middle insula), while not feeling understood activated neural regions previously associated with negative affect (i.e. anterior insula). Both feeling understood and not feeling understood activated different components of the mentalizing system (feeling understood: precuneus and temporoparietal junction; not feeling understood: dorsomedial prefrontal cortex). Neural responses were associated with subsequent feelings of social connection and disconnection and were modulated by individual differences in rejection sensitivity. Thus, this study provides insight into the psychological processes underlying feeling understood (or not) and may suggest new avenues for targeted interventions that amplify the benefits of feeling understood or buffer individuals from the harmful consequences of not feeling understood. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
Intergalactic stellar populations in intermediate redshift clusters
NASA Astrophysics Data System (ADS)
Melnick, J.; Giraud, E.; Toledo, I.; Selman, F.; Quintana, H.
2012-11-01
A substantial fraction of the total stellar mass in rich clusters of galaxies resides in a diffuse intergalactic component usually referred to as the intracluster light (ICL). Theoretical models indicate that these intergalactic stars originate mostly from the tidal interaction of the cluster galaxies during the assembly history of the cluster, and that a significant fraction of these stars could have formed in situ from the late infall of cold metal-poor gas clouds on to the cluster. However, these models also overpredict the fraction of stellar mass in the ICL by a substantial margin, something that is still not well understood. The models also make predictions about the age distribution of the ICL stars, which may provide additional observational constraints. Here we present population synthesis models for the ICL of an intermediate redshift (z = 0.29) X-ray cluster that we have extensively studied in previous papers. The advantage of observing intermediate redshift clusters rather than nearby ones is that the former fit the field of view of multi-object spectrographs in 8-m telescopes and therefore permit us to encompass most of the ICL with only a few well-placed slits. In this paper we show that by stacking spectra at different locations within the ICL it is possible to reach sufficiently high signal-to-noise ratios to fit population synthesis models and derive meaningful results. The models provide ages and metallicities for the dominant populations at several different locations within the ICL and the brightest cluster galaxies (BCG) halo, as well as measures of the kinematics of the stars as a function of distance from the BCG. We thus find that the ICL in our cluster is dominated by old metal-rich stars, at odds with what has been found in nearby clusters where the stars that dominate the ICL are old and metal poor. While we see weak evidence of a young, metal-poor component, if real, these young stars would amount to less than 1 per cent of the total ICL mass, much less than the up to 30 per cent predicted by the models. We propose that the very metal-rich (i.e. 2.5× solar) stars in the ICL of our cluster, which comprise ˜40 per cent of the total mass, originate mostly from the central dumb-bell galaxy, while the remaining solar and metal-poor stars come from spiral, post-starburst (E+A) and metal-poor dwarf galaxies. About 16 per cent of the ICL stars are old and metal poor.
Researchers Realize Major Breakthrough in Understanding Endometriosis
... a rarely studied and poorly understood disease that affects many, many women.” Health Terms: Women's Health RELATED LINKS RSS LISTSERV YOUTUBE FACEBOOK TWITTER GOOGLE+ NIH...T URNING D ISCOVERY I ...
Sparks, Jackson T; Bohbot, Jonathan D; Ristic, Mihailo; Mišic, Danijela; Skoric, Marijana; Mattoo, Autar; Dickens, Joseph C
2017-07-01
Nepeta essential oil (Neo; catnip) and its major component, nepetalactone, have long been known to repel insects including mosquitoes. However, the neural mechanisms through which these repellents are detected by mosquitoes, including the yellow fever mosquito Aedes aegypti (L.), an important vector of Zika virus, were poorly understood. Here we show that Neo volatiles activate olfactory receptor neurons within the basiconic sensilla on the maxillary palps of female Ae. aegypti. A gustatory receptor neuron sensitive to the feeding deterrent quinine and housed within sensilla on the labella of females was activated by both Neo and nepetalactone. Activity of a second gustatory receptor neuron sensitive to the feeding stimulant sucrose was suppressed by both repellents. Our results provide neural pathways for the reported spatial repellency and feeding deterrence of these repellents. A better understanding of the neural input through which female mosquitoes make decisions to feed will facilitate design of new repellents and management strategies involving their use. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.
Suzuki, Tatsuo; Zhang, Jingping; Miyazawa, Shoko; Liu, Qian; Farzan, Michael R.; Yao, Wei-Dong
2011-01-01
Postsynaptic membrane rafts are believed to play important roles in synaptic signaling, plasticity, and maintenance. However, their molecular identities remain elusive. Further, how they interact with the well-established signaling specialization, the postsynaptic density (PSD), is poorly understood. We previously detected a number of conventional PSD proteins in detergent-resistant membranes (DRMs). Here, we have performed LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) analyses on postsynaptic membrane rafts and PSDs. Our comparative analysis identified an extensive overlap of protein components in the two structures. This overlapping could be explained, at least partly, by a physical association of the two structures. Meanwhile, a significant number of proteins displayed biased distributions to either rafts or PSDs, suggesting distinct roles for the two postsynaptic specializations. Using biochemical and electron microscopic methods, we directly detected membrane raft-PSD complexes. In vitro reconstitution experiments indicated that the formation of raft-PSD complexes was not due to the artificial reconstruction of once-solubilized membrane components and PSD structures, supporting that these complexes occurred in vivo. Taking together, our results provide evidence that postsynaptic membrane rafts and PSDs may be physically associated. Such association could be important in postsynaptic signal integration, synaptic function, and maintenance. PMID:21797867
Wolkow, Pawel P; Kosiniak-Kamysz, Wladyslaw; Osmenda, Grzegorz; Wilk, Grzegorz; Bujak-Gizycka, Beata; Ignacak, Adam; Kanitkar, Mihir; Walus-Miarka, Malgorzata; Harrison, David G; Korbut, Ryszard; Malecki, Maciej T; Guzik, Tomasz J
2014-01-01
The genetic background of atherosclerosis in type 2 diabetes mellitus (T2DM) is complex and poorly understood. Studying genetic components of intermediate phenotypes, such as endothelial dysfunction and oxidative stress, may aid in identifying novel genetic components for atherosclerosis in diabetic patients. Five polymorphisms forming two haplotype blocks within the GTP cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin synthesis, were studied in the context of flow and nitroglycerin mediated dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations of von Willebrand factor (vWF) and malondialdehyde (MDA). Rs841 was associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641 (which form a single haplotype) were associated with both MDA (p = 0.012, p = 0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03 and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also associated with MDA (p = 0.006). Haplotype analysis confirmed the association of both haplotypes with studied variables. Genetic variation of the GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM patients.
Ashnest, Joanne R; Huynh, Dung L; Dragwidge, Jonathan M; Ford, Brett A; Gendall, Anthony R
2015-11-01
The Arabidopsis intracellular sodium-proton exchanger (NHX) proteins AtNHX5 and AtNHX6 have a well-documented role in plant development, and have been used to improve salt tolerance in a variety of species. Despite evidence that intracellular NHX proteins are important in vacuolar trafficking, the mechanism of this role is poorly understood. Here we show that NHX5 and NHX6 are necessary for processing of the predominant seed storage proteins, and also influence the processing and activity of a vacuolar processing enzyme. Furthermore, we show by yeast two-hybrid and bimolecular fluorescence complementation (BiFC) technology that the C-terminal tail of NHX6 interacts with a component of Retromer, another component of the cell sorting machinery, and that this tail is critical for NHX6 activity. These findings demonstrate that NHX5 and NHX6 are important in processing and activity of vacuolar cargo, and suggest a mechanism by which NHX intracellular (IC)-II antiporters may be involved in subcellular trafficking. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
VanBlargan, Laura A.
2016-01-01
SUMMARY The antibody response plays a key role in protection against viral infections. While antiviral antibodies may reduce the viral burden via several mechanisms, the ability to directly inhibit (neutralize) infection of cells has been extensively studied. Eliciting a neutralizing-antibody response is a goal of many vaccine development programs and commonly correlates with protection from disease. Considerable insights into the mechanisms of neutralization have been gained from studies of monoclonal antibodies, yet the individual contributions and dynamics of the repertoire of circulating antibody specificities elicited by infection and vaccination are poorly understood on the functional and molecular levels. Neutralizing antibodies with the most protective functionalities may be a rare component of a polyclonal, pathogen-specific antibody response, further complicating efforts to identify the elements of a protective immune response. This review discusses advances in deconstructing polyclonal antibody responses to flavivirus infection or vaccination. Our discussions draw comparisons to HIV-1, a virus with a distinct structure and replication cycle for which the antibody response has been extensively investigated. Progress toward deconstructing and understanding the components of polyclonal antibody responses identifies new targets and challenges for vaccination strategies. PMID:27784796
Hur, Junho K.; Luo, Yicheng; Moon, Sungjin; Ninova, Maria; Marinov, Georgi K.; Chung, Yun D.; Aravin, Alexei A.
2016-01-01
The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA transcribed by RNA polymerase II in a splicing-dependent fashion; however, how TREX functions is poorly understood. Here we show that Thoc5 and other TREX components are essential for the biogenesis of piRNA, a distinct class of small noncoding RNAs that control expression of transposable elements (TEs) in the Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis, resulting in derepression of multiple TE families, gametogenesis defects, and sterility. TREX components are enriched on piRNA precursors transcribed from dual-strand piRNA clusters and colocalize in distinct nuclear foci that overlap with sites of piRNA transcription. The localization of TREX in nuclear foci and its loading on piRNA precursor transcripts depend on Cutoff, a protein associated with chromatin of piRNA clusters. Finally, we show that TREX is required for accumulation of nascent piRNA precursors. Our study reveals a novel splicing-independent mechanism for TREX loading on nascent RNA and its importance in piRNA biogenesis. PMID:27036967
Incubation period and immune function: A comparative field study among coexisting birds
Palacios, M.G.; Martin, T.E.
2006-01-01
Developmental periods are integral components of life history strategies that can have important fitness consequences and vary enormously among organisms. However, the selection pressures and mechanisms causing variation in length of developmental periods are poorly understood. Particularly puzzling are prolonged developmental periods, because their selective advantage is unclear. Here we tested the hypotheses that immune function is stronger in species that are attacked at a higher rate by parasites and that prolonged embryonic development allows the development of this stronger immune system. Through a comparative field study among 12 coexisting passerine bird species, we show that species with higher blood parasite prevalence mounted stronger cellular immune responses than species with lower prevalence. These results provide support for the hypothesis that species facing greater selection pressure from parasites invest more in immune function. However, species with longer incubation periods mounted weaker cellular immune responses than species with shorter periods. Therefore, cellular immune responses do not support the hypothesis that longer development time enhances immunocompentence. Future studies should assess other components of the immune system and test alternative causes of variation in incubation periods among bird species. ?? Springer-Verlag 2005.
Autophagy Driven by a Master Regulator of Hematopoiesis
Kang, Yoon-A; Sanalkumar, Rajendran; O'Geen, Henriette; Linnemann, Amelia K.; Chang, Chan-Jung; Bouhassira, Eric E.; Farnham, Peggy J.; Keles, Sunduz
2012-01-01
Developmental and homeostatic remodeling of cellular organelles is mediated by a complex process termed autophagy. The cohort of proteins that constitute the autophagy machinery functions in a multistep biochemical pathway. Though components of the autophagy machinery are broadly expressed, autophagy can occur in specialized cellular contexts, and mechanisms underlying cell-type-specific autophagy are poorly understood. We demonstrate that the master regulator of hematopoiesis, GATA-1, directly activates transcription of genes encoding the essential autophagy component microtubule-associated protein 1 light chain 3B (LC3B) and its homologs (MAP1LC3A, GABARAP, GABARAPL1, and GATE-16). In addition, GATA-1 directly activates genes involved in the biogenesis/function of lysosomes, which mediate autophagic protein turnover. We demonstrate that GATA-1 utilizes the forkhead protein FoxO3 to activate select autophagy genes. GATA-1-dependent LC3B induction is tightly coupled to accumulation of the active form of LC3B and autophagosomes, which mediate mitochondrial clearance as a critical step in erythropoiesis. These results illustrate a novel mechanism by which a master regulator of development establishes a genetic network to instigate cell-type-specific autophagy. PMID:22025678
Beauclercq, Stéphane; Nadal-Desbarats, Lydie; Hennequet-Antier, Christelle; Gabriel, Irène; Tesseraud, Sophie; Calenge, Fanny; Le Bihan-Duval, Elisabeth; Mignon-Grasteau, Sandrine
2018-04-27
The increasing cost of conventional feedstuffs has bolstered interest in genetic selection for digestive efficiency (DE), a component of feed efficiency, assessed by apparent metabolisable energy corrected to zero nitrogen retention (AMEn). However, its measurement is time-consuming and constraining, and its relationship with metabolic efficiency poorly understood. To simplify selection for this trait, we searched for indirect metabolic biomarkers through an analysis of the serum metabolome using nuclear magnetic resonance ( 1 H NMR). A partial least squares (PLS) model including six amino acids and two derivatives from butyrate predicted 59% of AMEn variability. Moreover, to increase our knowledge of the molecular mechanisms controlling DE, we investigated 1 H NMR metabolomes of ileal, caecal, and serum contents by fitting canonical sparse PLS. This analysis revealed strong associations between metabolites and DE. Models based on the ileal, caecal, and serum metabolome respectively explained 77%, 78%, and 74% of the variability of AMEn and its constitutive components (utilisation of starch, lipids, and nitrogen). In our conditions, the metabolites presenting the strongest associations with AMEn were proline in the serum, fumarate in the ileum and glucose in caeca. This study shows that serum metabolomics offers new opportunities to predict chicken DE.
Sensory adaptation for timing perception.
Roseboom, Warrick; Linares, Daniel; Nishida, Shin'ya
2015-04-22
Recent sensory experience modifies subjective timing perception. For example, when visual events repeatedly lead auditory events, such as when the sound and video tracks of a movie are out of sync, subsequent vision-leads-audio presentations are reported as more simultaneous. This phenomenon could provide insights into the fundamental problem of how timing is represented in the brain, but the underlying mechanisms are poorly understood. Here, we show that the effect of recent experience on timing perception is not just subjective; recent sensory experience also modifies relative timing discrimination. This result indicates that recent sensory history alters the encoding of relative timing in sensory areas, excluding explanations of the subjective phenomenon based only on decision-level changes. The pattern of changes in timing discrimination suggests the existence of two sensory components, similar to those previously reported for visual spatial attributes: a lateral shift in the nonlinear transducer that maps relative timing into perceptual relative timing and an increase in transducer slope around the exposed timing. The existence of these components would suggest that previous explanations of how recent experience may change the sensory encoding of timing, such as changes in sensory latencies or simple implementations of neural population codes, cannot account for the effect of sensory adaptation on timing perception.
The elementome of calcium-based urinary stones and its role in urolithiasis
Ramaswamy, Krishna; Killilea, David W.; Kapahi, Pankaj; Kahn, Arnold J.; Chi, Thomas; Stoller, Marshall L.
2016-01-01
Urolithiasis affects around 10% of the US population with an increasing rate of prevalence, recurrence and penetrance. The causes for the formation of most urinary calculi remain poorly understood, but obtaining the chemical composition of these stones might help identify key aspects of this process and new targets for treatment. The majority of urinary stones are composed of calcium that is complexed in a crystalline matrix with organic and inorganic components. Surprisingly, mitigation of urolithiasis risk by altering calcium homeostasis has not been very effective. Thus, studies to identify other therapeutic stone-specific targets, using proteomics, metabolomics and microscopy techniques, have been conducted, revealing a high level of complexity. The data suggest that numerous metals other than calcium and many nonmetals are present within calculi at measurable levels and several have distinct distribution patterns. Manipulation of the levels of some of these elemental components of calcium-based stones has resulted in clinically beneficial changes in stone chemistry and rate of stone formation. The elementome—the full spectrum of elemental content—of calcium-based urinary calculi is emerging as a new concept in stone research that continues to provide important insights for improved understanding and prevention of urinary stone disease. PMID:26334088
Zald, David H.; Woodward, Neil D.; Cowan, Ronald L.; Riccardi, Patrizia; Ansari, M. Sib; Baldwin, Ronald M.; Cowan, Ronald L.; Smith, Clarence E.; Hakyemez, Helene; Li, Rui; Kessler, Robert M.
2010-01-01
Individual differences in dopamine D2-like receptor availability arise across all brain regions expressing D2-like receptors. However, the inter-relationships in receptor availability across brain regions are poorly understood. To address this issue, we examined the relationship between D2-like binding potential (BPND) across striatal and extrastriatal regions in a sample of healthy participants. PET imaging was performed with the high affinity D2/D3 ligand [18F]fallypride in 45 participants. BPND images were submitted to voxel-wise principal components analysis to determine the pattern of associations across brain regions. Individual differences in D2-like BPND were explained by three distinguishable components. A single component explained almost all of the variance within the striatum, indicating that individual differences in receptor availability vary in a homogenous manner across the caudate, putamen, and ventral striatum. Cortical BPND was only modestly related to striatal BPND, and mostly loaded on a distinct component. After controlling for the general level of cortical D2-like BPND, an inverse relationship emerged between receptor availability in the striatum and the ventral temporal and ventromedial frontal cortices, suggesting possible cross-regulation of D2-like receptors in these regions. The analysis additionally revealed evidence of: 1) a distinct component involving the midbrain and limbic areas; 2) a dissociation between BPND in the medial and lateral temporal regions; and 3) a dissociation between BPND in the medial/midline and lateral thalamus. In summary, individual differences in D2-like receptor availability reflect several distinct patterns. This conclusion has significant implications for neuropsychiatric models that posit global or regionally specific relationships between dopaminergic tone and behavior. PMID:20149883
Putilov, Arcady A; Donskaya, Olga G
2016-01-01
Age-associated changes in different bandwidths of the human electroencephalographic (EEG) spectrum are well documented, but their functional significance is poorly understood. This spectrum seems to represent summation of simultaneous influences of several sleep-wake regulatory processes. Scoring of its orthogonal (uncorrelated) principal components can help in separation of the brain signatures of these processes. In particular, the opposite age-associated changes were documented for scores on the two largest (1st and 2nd) principal components of the sleep EEG spectrum. A decrease of the first score and an increase of the second score can reflect, respectively, the weakening of the sleep drive and disinhibition of the opposing wake drive with age. In order to support the suggestion of age-associated disinhibition of the wake drive from the antagonistic influence of the sleep drive, we analyzed principal component scores of the resting EEG spectra obtained in sleep deprivation experiments with 81 healthy young adults aged between 19 and 26 and 40 healthy older adults aged between 45 and 66 years. At the second day of the sleep deprivation experiments, frontal scores on the 1st principal component of the EEG spectrum demonstrated an age-associated reduction of response to eyes closed relaxation. Scores on the 2nd principal component were either initially increased during wakefulness or less responsive to such sleep-provoking conditions (frontal and occipital scores, respectively). These results are in line with the suggestion of disinhibition of the wake drive with age. They provide an explanation of why older adults are less vulnerable to sleep deprivation than young adults.
Antisomnogenic cytokines, quality of life, and chronic rhinosinusitis: a pilot study.
Alt, Jeremiah A; Sautter, Nathan B; Mace, Jess C; Detwiller, Kara Y; Smith, Timothy L
2014-04-01
Sleep disturbance, reduced quality of life (QOL), and other components of "sickness behavior" in patients with chronic rhinosinusitis (CRS) are poorly understood. These complex changes in central behavior are due to the effects of immune mediators acting in the brain. We hypothesized that immune mediators that have been associated with CRS are also associated with sickness behavior, somnifacient complaints, and CRS disease-specific QOL. Pilot study. Twenty patients with CRS were prospectively enrolled and completed the Pittsburgh Sleep Quality Index (PSQI), disease-specific QOL, and olfactory instruments. Ethmoid mucosa was obtained and reverse transcription-polymerase chain reaction was performed for the cytokines interleukin (IL)-4, -13, and transforming growth factor-β (TGF-β). Average change in crossover threshold was calculated, and differences in gene expression were correlated with sleep quality, CRS-specific QOL, and disease severity. Patients with CRS reported overall poor sleep quality and poor CRS-specific QOL with significant correlations between them. Increased expression of TGF-β (r = -0.443; P = .050) and IL-4 (r = -0.548; P = .012) correlated with sleep dysfunction, whereas IL-13 expression was linearly associated with worse sleep quality (PSQI scores r = -0.417; P = .075). IL-4 and TGF-β expression was not associated with CRS disease severity or QOL, whereas significantly higher levels of IL-13 expression correlated with worse CRS disease severity and QOL. Patients with CRS exhibited behavioral changes commonly referred to as sickness behavior, which include poor sleep quality and reduced QOL. The upregulation of IL-4 and TGF-β may contribute to inflammatory brain-mediated effects on sleep quality, whereas IL-13 may be a pleiotropic signaling molecule influencing sleep, QOL, and CRS disease severity. 2b. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.
76 FR 61379 - Final Recovery Plan, Bexar County Karst Invertebrates
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-04
... 200, Austin, TX (512-490-0057 ext. 223). FOR FURTHER INFORMATION CONTACT: Adam Zerrenner, at the above... poorly understood, recovery is also dependant on incorporating research findings into adaptive management...
Kierepka, E M; Latch, E K
2016-01-01
Landscape genetics is a powerful tool for conservation because it identifies landscape features that are important for maintaining genetic connectivity between populations within heterogeneous landscapes. However, using landscape genetics in poorly understood species presents a number of challenges, namely, limited life history information for the focal population and spatially biased sampling. Both obstacles can reduce power in statistics, particularly in individual-based studies. In this study, we genotyped 233 American badgers in Wisconsin at 12 microsatellite loci to identify alternative statistical approaches that can be applied to poorly understood species in an individual-based framework. Badgers are protected in Wisconsin owing to an overall lack in life history information, so our study utilized partial redundancy analysis (RDA) and spatially lagged regressions to quantify how three landscape factors (Wisconsin River, Ecoregions and land cover) impacted gene flow. We also performed simulations to quantify errors created by spatially biased sampling. Statistical analyses first found that geographic distance was an important influence on gene flow, mainly driven by fine-scale positive spatial autocorrelations. After controlling for geographic distance, both RDA and regressions found that Wisconsin River and Agriculture were correlated with genetic differentiation. However, only Agriculture had an acceptable type I error rate (3–5%) to be considered biologically relevant. Collectively, this study highlights the benefits of combining robust statistics and error assessment via simulations and provides a method for hypothesis testing in individual-based landscape genetics. PMID:26243136
Genome biogeography reveals the intraspecific spread of adaptive mutations for a complex trait.
Olofsson, Jill K; Bianconi, Matheus; Besnard, Guillaume; Dunning, Luke T; Lundgren, Marjorie R; Holota, Helene; Vorontsova, Maria S; Hidalgo, Oriane; Leitch, Ilia J; Nosil, Patrik; Osborne, Colin P; Christin, Pascal-Antoine
2016-12-01
Physiological novelties are often studied at macro-evolutionary scales such that their micro-evolutionary origins remain poorly understood. Here, we test the hypothesis that key components of a complex trait can evolve in isolation and later be combined by gene flow. We use C 4 photosynthesis as a study system, a derived physiology that increases plant productivity in warm, dry conditions. The grass Alloteropsis semialata includes C 4 and non-C 4 genotypes, with some populations using laterally acquired C 4 -adaptive loci, providing an outstanding system to track the spread of novel adaptive mutations. Using genome data from C 4 and non-C 4 A. semialata individuals spanning the species' range, we infer and date past migrations of different parts of the genome. Our results show that photosynthetic types initially diverged in isolated populations, where key C 4 components were acquired. However, rare but recurrent subsequent gene flow allowed the spread of adaptive loci across genetic pools. Indeed, laterally acquired genes for key C 4 functions were rapidly passed between populations with otherwise distinct genomic backgrounds. Thus, our intraspecific study of C 4 -related genomic variation indicates that components of adaptive traits can evolve separately and later be combined through secondary gene flow, leading to the assembly and optimization of evolutionary innovations. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.
Neuroanatomical basis of paroxysmal sympathetic hyperactivity: A diffusion tensor imaging analysis
Hinson, Holly E.; Puybasset, Louis; Weiss, Nicolas; Perlbarg, Vincent; Benali, Habib; Galanaud, Damien; Lasarev, Mike; Stevens, Robert D.
2015-01-01
Primary objective Paroxysmal sympathetic hyperactivity (PSH) is observed in a sub-set of patients with moderate-to-severe traumatic brain injury (TBI). The neuroanatomical basis of PSH is poorly understood. It is hypothesized that PSH is linked to changes in connectivity within the central autonomic network. Research design Retrospective analysis in a sub-set of patients from a multi-centre, prospective cohort study Methods and procedures Adult patients who were <3 weeks after severe TBI were enrolled and screened for PSH using a standard definition. Patients underwent multimodal MRI, which included quantitative diffusion tensor imaging. Main outcomes and results Principal component analysis (PCA) was used to resolve the set of tracts into components. Ability to predict PSH was evaluated via area under the receiver operating characteristic (AUROC) and tree-based classification analyses. Among 102 enrolled patients, 16 met criteria for PSH. The first principle component was significantly associated (p = 0.024, AUROC = 0.867) with PSH status even after controlling for age and admission GCS. In a classification tree analysis, age, GCS and decreased FA in the splenium of the corpus callosum and in the right posterior limb of the internal capsule discriminated PSH vs no PSH with an AUROC of 0.933. Conclusions Disconnection involving the posterior corpus callosum and of the posterior limb of the internal capsule may play a role in the pathogenesis or expression of PSH. PMID:25565392
Li, Wylie W Y; Lam, Wendy W T; Wong, Jennifer H F; Chiu, April; Chan, Miranda; Or, Amy; Kwong, Ava; Suen, Dacita; Chan, Sharon W W; Fielding, Richard
2012-12-01
Delayed consultation for potential cancer symptoms influences treatment outcomes and remains problematic. Delay components (Appraisal versus Utilization) and respective associations are poorly understood. Eligible participants were Cantonese-speaking Chinese women, ≥21 years old, with self-discovered breast symptoms, recruited in surgical clinics before their first consultation, and naïve to their diagnosis. Overall 425/433 (98%) women completed a questionnaire on psychosocial, demographic and medical factors, how and when women discovered their breast symptom(s), and their subsequent decision making; 135/425 women (32%) were later diagnosed with breast cancer. Twenty-two per cent of women delayed >3 months before consultation. Women with breast cancer (28%) more often had prolonged delay than women with benign disease (19%). Attributing symptom to a non-cancerous condition, low fear on symptom discovery, not disclosing symptoms to others, and no prior breast symptom history predicted prolonged (>60 days) Appraisal Delay. Low fear on symptom discovery, seldom thinking about the symptom, and consultation for other reasons predicted prolonged (>14 days) Utilization Delay. Factors predicting Appraisal and Utilization Delays differentiated cancer from non-cancer groups. Indecision over symptom meaning comprised the main component of Appraisal and Total Delay, suggesting that educational strategies targeting atypical symptoms should reduce avoidable delays following self-discovered breast symptoms. Copyright © 2011 John Wiley & Sons, Ltd.
NASA Astrophysics Data System (ADS)
Zhang, Xiaowen; Hutchings, Jack A.; Bianchi, Thomas S.; Liu, Yina; Arellano, Ana R.; Schuur, Edward A. G.
2017-04-01
Temperature rise in the Arctic is causing deepening of active layers and resulting in the mobilization of deep permafrost dissolved organic matter (DOM). However, the mechanisms of DOM mobilization from Arctic soils, especially upper soil horizons which are drained most frequently through a year, are poorly understood. Here we conducted a short-term leaching experiment on surface and deep organic active layer soils, from the Yukon River basin, to examine the effects of DOM transport on bulk and molecular characteristics. Our data showed a net release of DOM from surface soils equal to an average of 5% of soil carbon. Conversely, deep soils percolated with surface leachates retained up to 27% of bulk DOM while releasing fluorescent components (up to 107%), indicating selective release of aromatic components (e.g., lignin and tannin), while retaining nonchromophoric components, as supported by spectrofluorometric and ultrahigh-resolution mass spectroscopic techniques. Our findings highlight the importance of the lateral flux of DOM on ecosystem carbon balance as well as processing of DOM transport through organic active layer soils en route to rivers and streams. This work also suggests the potential role of leachate export as an important mechanism of C losses from Arctic soils, in comparison with the more traditional pathway from soil to atmosphere in a warming Arctic.
The circadian rhythm of core temperature: effects of physical activity and aging.
Weinert, Dietmar; Waterhouse, Jim
2007-02-28
The circadian rhythm of core temperature depends upon several interacting rhythms, of both endogenous and exogenous origin, but an understanding of the process requires these two components to be separated. Constant routines remove the exogenous (masking) component at source, but they are severely limited in their application. By contrast, several purification methods have successfully reduced the masking component of overt circadian rhythms measured in field circumstances. One important, but incidental, outcome from these methods is that they enable a quantitative estimate of masking effects to be obtained. It has been shown that these effects of activity upon the temperature rhythm show circadian rhythmicity, and more detailed investigations of this have aided our understanding of thermoregulation and the genesis of the circadian rhythm of core temperature itself. The observed circadian rhythm of body temperature varies with age; in comparison with adults, it is poorly developed in the neonate and deteriorates in the aged subject. Comparing masked and purified data enables the reasons for these differences--whether due to the body clock, the effector pathways or organs, or irregularities due to the individual's lifestyle--to begin to be understood. Such investigations stress the immaturity of the circadian rhythm in the human neonate and its deterioration in elderly compared with younger subjects, but they also indicate the robustness of the body clock itself into advanced age, at least in mice.
Yan, Ge; Kim, Guebuem
2017-10-17
Brown carbon (BrC) plays a significant role in the Earth's radiative balance, yet its sources and chemical composition remain poorly understood. In this work, we investigated BrC in the atmospheric environment of Seoul by characterizing dissolved organic matter in precipitation using excitation-emission matrix (EEM) fluorescence spectroscopy coupled with parallel factor analysis (PARAFAC). The two independent fluorescent components identified by PARAFAC were attributed to humic-like substance (HULIS) and biologically derived material based on their significant correlations with measured HULIS isolated using solid-phase extraction and total hydrolyzable tyrosine. The year-long observation shows that HULIS contributes to 66 ± 13% of total fluorescence intensity of our samples on average. By using dual carbon ( 13 C and 14 C) isotopic analysis conducted on isolated HULIS, the HULIS fraction of BrC was found to be primarily derived from biomass burning and emission of terrestrial biogenic gases and particles (>70%), with minor contributions from fossil-fuel combustion. The knowledge derived from this study could contribute to the establishment of a characterizing system of BrC components identified by EEM spectroscopy. Our work demonstrates that, EEM fluorescence spectroscopy is a powerful tool in BrC study, on the basis of its chromophore resolving power, allowing investigation into individual components of BrC by other organic matter characterization techniques.
Jonathan P. Benstead; James G. March; Catherine M. Pringle; Katherine C. Ewel; John W. Short
2009-01-01
Pacific island stream communities are species-poor because of the effects of extreme geographic isolation on colonization rates of taxa common to continental regions. The effects of such low species richness on stream ecosystem function are not well understood. Here, we provide data on community structure and leaf litter breakdown rate in a virtually pristine stream on...
Effects of primitive photosynthesis on Earth's early climate system
NASA Astrophysics Data System (ADS)
Ozaki, Kazumi; Tajika, Eiichi; Hong, Peng K.; Nakagawa, Yusuke; Reinhard, Christopher T.
2018-01-01
The evolution of different forms of photosynthetic life has profoundly altered the activity level of the biosphere, radically reshaping the composition of Earth's oceans and atmosphere over time. However, the mechanistic impacts of a primitive photosynthetic biosphere on Earth's early atmospheric chemistry and climate are poorly understood. Here, we use a global redox balance model to explore the biogeochemical and climatological effects of different forms of primitive photosynthesis. We find that a hybrid ecosystem of H2-based and Fe2+-based anoxygenic photoautotrophs—organisms that perform photosynthesis without producing oxygen—gives rise to a strong nonlinear amplification of Earth's methane (CH4) cycle, and would thus have represented a critical component of Earth's early climate system before the advent of oxygenic photosynthesis. Using a Monte Carlo approach, we find that a hybrid photosynthetic biosphere widens the range of geochemical conditions that allow for warm climate states well beyond either of these metabolic processes acting in isolation. Our results imply that the Earth's early climate was governed by a novel and poorly explored set of regulatory feedbacks linking the anoxic biosphere and the coupled H, C and Fe cycles. We suggest that similar processes should be considered when assessing the potential for sustained habitability on Earth-like planets with reducing atmospheres.
Septic shock: desperately seeking treatment.
Huet, Olivier; Chin-Dusting, Jaye P F
2014-01-01
Septic shock results from the dysregulation of the innate immune response following infection. Despite major advances in fundamental and clinical research, patients diagnosed with septic shock still have a poor prognostic outcome, with a mortality rate of up to 50%. Indeed, the reasons leading to septic shock are still poorly understood. First postulated 30 years ago, the general view of septic shock as an acute and overwhelming inflammatory response still prevails today. Recently, the fact that numerous clinical trials have failed to demonstrate any positive medical outcomes has caused us to question our fundamental understanding of this condition. New and sophisticated technologies now allow us to accurately profile the various stages and contributory components of the inflammatory response defining septic shock, and many studies now report a more complex inflammatory response, particularly during the early phase of sepsis. In addition, novel experimental approaches, using more clinically relevant animal models, to standardize and stratify research outcomes are now being argued for. In the present review, we discuss the most recent findings in relation to our understanding of the underlying mechanisms involved in septic shock, and highlight the attempts made to improve animal experimental models. We also review recent studies reporting promising results with two vastly different therapeutic approaches influencing the renin-angiotensin system and applying mesenchymal stem cells for clinical intervention.
NASA Technical Reports Server (NTRS)
Smith, R. J.; Horgan, B.; Rampe, E.; Dehouck, E.; Morris, R. V.
2017-01-01
X-ray diffraction (XRD) amorphous phases have been found as major components (approx.15-60 wt%) of all rock and soil samples measured by the CheMin XRD instrument in Gale Crater, Mars. The nature of these phases is not well understood and could be any combination of primary (e.g., glass) and secondary (e.g., allophane) phases. Amorphous phases form in abundance during surface weathering on Earth. Yet, these materials are poorly characterized, and it is not certain how properties like composition and structure change with formation environment. The presence of poorly crystalline phases can be inferred from XRD patterns by the appearance of a low angle rise (< or approx.10deg 2(theta)) or broad peaks in the background at low to moderate 2(theta) angles (amorphous humps). CheMin mineral abundances combined with bulk chemical composition measurements from the Alpha Particle X-ray Spectrometer (APXS) have been used to estimate the abundance and composition of the XRD amorphous materials in soil and rock samples on Mars. Here we apply a similar approach to a diverse suite of terrestrial samples - modern soils, glacial sediments, and paleosols - in order to determine how formation environment, climate, and diagenesis affect the abundance and composition of X-ray amorphous phases.
Of all foods bread is the most noble: Carl von Linné (Carl Linneaus) on bread1
Räsänen, Leena
2007-01-01
Carl von Linné was interested in dietetics, which in his time covered all aspects of a healthy life. As a utilitarian he understood the importance of private economy and paid attention to bread in many of his publications. Two texts, Ceres noverca arctoum and De pane diaetetico, were wholly devoted to bread and bread-making. Linné classified different types of bread, and described their nutritional value and health-related aspects, as well as milling, baking and storing, in detail. While discussing the food habits of social classes Linné accepted as a fact that the peasants and the poor should eat less tasty bread than the rich. The less palatable bread had, however, many nutritional and health advantages. Linné paid much attention to substitutes for grain to be used in times of famine, an important topic in eighteenth century Sweden. He regarded flour made of pine bark or water arum roots as excellent famine food, was enthusiastic about the new plant, maize, but considered potato only as a poor substitute for grain. Linné and his followers praised bread not only as the core component of diet, but also for its versatile role both in health and in disease.
The public's belief about biology.
Wolpert, L
2007-02-01
This short review is concerned with a topic that has been neglected and is still very poorly understood: what the general public think and believe about biology (including health and medicine, and bioethics), and, in particular, about biotechnology.
A Production Function Approach to Regional Environmental-Economic Assessments
Numerous difficulties await those creating regional-scale environmental assessments, from data having inconsistent spatial or temporal scales to poorly understood environmental processes and indicators. Including socioeconomic variables further complicates the situation. In place...
The evolution of transcriptional regulation in eukaryotes
NASA Technical Reports Server (NTRS)
Wray, Gregory A.; Hahn, Matthew W.; Abouheif, Ehab; Balhoff, James P.; Pizer, Margaret; Rockman, Matthew V.; Romano, Laura A.
2003-01-01
Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.
Horat, Sibylle K; Prévot, Anne; Richiardi, Jonas; Herrmann, François R; Favre, Grégoire; Merlo, Marco C G; Missonnier, Pascal
2017-01-01
The Ultimatum Game (UG) is a typical paradigm to investigate social decision-making. Although the behavior of humans in this task is already well established, the underlying brain processes remain poorly understood. Previous investigations using event-related potentials (ERPs) revealed three major components related to cognitive processes in participants engaged in the responder condition, the early ERP component P2, the feedback-related negativity (FRN) and a late positive wave (late positive component, LPC). However, the comparison of the ERP waveforms between the responder and proposer conditions has never been studied. Therefore, to investigate condition-related electrophysiological changes, we applied the UG paradigm and compared parameters of the P2, LPC and FRN components in twenty healthy participants. For the responder condition, we found a significantly decreased amplitude and delayed latency for the P2 component, whereas the mean amplitudes of the LPC and FRN increased compared to the proposer condition. Additionally, the proposer condition elicited an early component consisting of a negative deflection around 190 ms, in the upward slope of the P2, probably as a result of early conflict-related processing. Using independent component analysis (ICA), we extracted one functional component time-locked to this deflection, and with source reconstruction (LAURA) we found the anterior cingulate cortex (ACC) as one of the underlying sources. Overall, our findings indicate that intensity and time-course of neuronal systems engaged in the decision-making processes diverge between both UG conditions, suggesting differential cognitive processes. Understanding the electrophysiological bases of decision-making and social interactions in controls could be useful to further detect which steps are impaired in psychiatric patients in their ability to attribute mental states (such as beliefs, intents, or desires) to oneself and others. This ability is called mentalizing (also known as theory of mind).
Holzinger, Andreas; Karsten, Ulf
2013-01-01
Although most green algae typically occur in aquatic ecosystems, many species also live partly or permanently under aeroterrestrial conditions, where the cells are exposed to the atmosphere and hence regularly experience dehydration. The ability of algal cells to survive in an air-dried state is termed desiccation tolerance. The mechanisms involved in desiccation tolerance of green algae are still poorly understood, and hence the aim of this review is to summarize recent findings on the effects of desiccation and osmotic water loss. Starting from structural changes, physiological, and biochemical consequences of desiccation will be addressed in different green-algal lineages. The available data clearly indicate a range of strategies, which are rather different in streptophycean and non-streptophycean green algae. While members of the Trebouxiophyceae exhibit effective water loss-prevention mechanisms based on the biosynthesis and accumulation of particular organic osmolytes such as polyols, these compounds are so far not reported in representatives of the Streptophyta. In members of the Streptophyta such as Klebsormidium, the most striking observation is the appearance of cross-walls in desiccated samples, which are strongly undulating, suggesting a high degree of mechanical flexibility. This aids in maintaining structural integrity in the dried state and allows the cell to maintain turgor pressure for a prolonged period of time during the dehydration process. Physiological strategies in aeroterrestrial green algae generally include a rapid reduction of photosynthesis during desiccation, but also a rather quick recovery after rewetting, whereas aquatic species are sensitive to drying. The underlying mechanisms such as the affected molecular components of the photosynthetic machinery are poorly understood in green algae. Therefore, modern approaches based on transcriptomics, proteomics, and/or metabolomics are urgently needed to better understand the molecular mechanisms involved in desiccation-stress physiology of these organisms. The very limited existing information is described in the present review. PMID:23986769
Pelagic ecology of the South West Indian Ocean Ridge seamounts: Introduction and overview
NASA Astrophysics Data System (ADS)
Rogers, A. D.
2017-02-01
The Indian Ocean was described by Behrman (1981) as the "Forlorn Ocean", a region neglected by science up to the late-1950s. For example, the Challenger Expedition from 1872 to 1876 largely avoided the Indian Ocean, sailing from Cape Town into Antarctic waters sampling around the Prince Edward Islands, Kerguelen Island and Crozet Islands before heading to Melbourne. From 1876 to the 1950s there were expeditions on several vessels including the Valdivia, Gauss and Planet (Germany), the Snellius (Netherlands), Discovery II, MahaBiss (United Kingdom), Albatross (Sweden), Dana and Galathea (Denmark; Behrman, 1981). There was no coordination between these efforts and overall the Indian Ocean, especially the deep sea remained perhaps the most poorly explored of the world's oceans. This situation was largely behind the multilateral effort represented by the International Indian Ocean Expedition (IIEO), which was coordinated by the Scientific Committee for Ocean Research (SCOR), and which ran from 1959-1965. Work during this expedition focused on the Arabian Sea, the area to the northwest of Australia and the waters over the continental shelves and slopes of coastal states in the region. Subsequently several large-scale international oceanographic programmes have included significant components in the Indian Ocean, including the Joint Global Ocean Flux Study (JGOFS) and the World Ocean Circulation Experiment (WOCE). These studies were focused on physical oceanographic measurements and biogeochemistry and whilst the Indian Ocean is still less understood than other large oceans it is now integrated into the major ocean observation systems (Talley et al., 2011). This cannot be said for many aspects of the biology of the region, despite the fact that the Indian Ocean is one of the places where exploitation of marine living resources is still growing (FAO, 2016). The biology of the deep Indian Ocean outside of the Arabian Sea is particularly poorly understood given the presence of globally significant areas of seamounts, submarine plateaus, continental and island slopes.
Blaming the helpers: the marginalization of teachers and parents of the urban poor.
Farber, B A; Azar, S T
1999-10-01
The nature and origins of the current tendency toward disparaging parents and teachers of the urban poor are examined. It is suggested that the influence of parents and teachers must be understood in the context of multiple intervening variables. Several explanations are offered for the phenomenon of blame, including the fact that women constitute the great majority of teachers and are often the primary agents of parenting.
Neural activity tied to reading predicts individual differences in extended-text comprehension
Mossbridge, Julia A.; Grabowecky, Marcia; Paller, Ken A.; Suzuki, Satoru
2013-01-01
Reading comprehension depends on neural processes supporting the access, understanding, and storage of words over time. Examinations of the neural activity correlated with reading have contributed to our understanding of reading comprehension, especially for the comprehension of sentences and short passages. However, the neural activity associated with comprehending an extended text is not well-understood. Here we describe a current-source-density (CSD) index that predicts individual differences in the comprehension of an extended text. The index is the difference in CSD-transformed event-related potentials (ERPs) to a target word between two conditions: a comprehension condition with words from a story presented in their original order, and a scrambled condition with the same words presented in a randomized order. In both conditions participants responded to the target word, and in the comprehension condition they also tried to follow the story in preparation for a comprehension test. We reasoned that the spatiotemporal pattern of difference-CSDs would reflect comprehension-related processes beyond word-level processing. We used a pattern-classification method to identify the component of the difference-CSDs that accurately (88%) discriminated good from poor comprehenders. The critical CSD index was focused at a frontal-midline scalp site, occurred 400–500 ms after target-word onset, and was strongly correlated with comprehension performance. Behavioral data indicated that group differences in effort or motor preparation could not explain these results. Further, our CSD index appears to be distinct from the well-known P300 and N400 components, and CSD transformation seems to be crucial for distinguishing good from poor comprehenders using our experimental paradigm. Once our CSD index is fully characterized, this neural signature of individual differences in extended-text comprehension may aid the diagnosis and remediation of reading comprehension deficits. PMID:24223540
NASA Astrophysics Data System (ADS)
Ovreas, L.; Quince, C.; Sloan, W.; Lanzen, A.; Davenport, R.; Green, J.; Coulson, S.; Curtis, T.
2012-12-01
Arctic microbial soil communities are intrinsically interesting and poorly characterised. We have inferred the diversity and species abundance distribution of 6 Arctic soils: new and mature soil at the foot of a receding glacier, Arctic Semi Desert, the foot of bird cliffs and soil underlying Arctic Tundra Heath: all near Ny-Ålesund, Spitsbergen. Diversity, distribution and sample sizes were estimated using the rational method of Quince et al., (Isme Journal 2 2008:997-1006) to determine the most plausible underlying species abundance distribution. A log-normal species abundance curve was found to give a slightly better fit than an inverse Gaussian curve if, and only if, sequencing error was removed. The median estimates of diversity of operational taxonomic units (at the 3% level) were 3600-5600 (lognormal assumed) and 2825-4100 (inverse Gaussian assumed). The nature and origins of species abundance distributions are poorly understood but may yet be grasped by observing and analysing such distributions in the microbial world. The sample size required to observe the distribution (by sequencing 90% of the taxa) varied between ~ 106 and ~105 for the lognormal and inverse Gaussian respectively. We infer that between 5 and 50 GB of sequencing would be required to capture 90% or the metagenome. Though a principle components analysis clearly divided the sites into three groups there was a high (20-45%) degree of overlap in between locations irrespective of geographical proximity. Interestingly, the nearest relatives of the most abundant taxa at a number of most sites were of alpine or polar origin. Samples plotted on first two principal components together with arbitrary discriminatory OTUs
NASA Astrophysics Data System (ADS)
García Plaza, E.; Núñez López, P. J.
2018-01-01
The wavelet packet transform method decomposes a time signal into several independent time-frequency signals called packets. This enables the temporary location of transient events occurring during the monitoring of the cutting processes, which is advantageous in monitoring condition and fault diagnosis. This paper proposes the monitoring of surface roughness using a single low cost sensor that is easily implemented in numerical control machine tools in order to make on-line decisions on workpiece surface finish quality. Packet feature extraction in vibration signals was applied to correlate the sensor signals to measured surface roughness. For the successful application of the WPT method, mother wavelets, packet decomposition level, and appropriate packet selection methods should be considered, but are poorly understood aspects in the literature. In this novel contribution, forty mother wavelets, optimal decomposition level, and packet reduction methods were analysed, as well as identifying the effective frequency range providing the best packet feature extraction for monitoring surface finish. The results show that mother wavelet biorthogonal 4.4 in decomposition level L3 with the fusion of the orthogonal vibration components (ax + ay + az) were the best option in the vibration signal and surface roughness correlation. The best packets were found in the medium-high frequency DDA (6250-9375 Hz) and high frequency ADA (9375-12500 Hz) ranges, and the feed acceleration component ay was the primary source of information. The packet reduction methods forfeited packets with relevant features to the signal, leading to poor results for the prediction of surface roughness. WPT is a robust vibration signal processing method for the monitoring of surface roughness using a single sensor without other information sources, satisfactory results were obtained in comparison to other processing methods with a low computational cost.
PHYTOASSESSMENT OF ESTUARINE SEDIMENTS
Most sediment quality assessments and quality guidelines are based on the laboratory response of single animal species and benthic animal community composition. The role of plants in this hazard assessment process is poorly understood despite the fact that plant-dominated habitat...
FACTORS INFLUENCING LIGHT-INDUCED MORTALITY OF ENTEROCOCCI IN SEDIMENT SUSPENSIONS
Contamination of recreational waters by pathogenic microorganisms occurs through complex, poorly understood interactions involving variable microbial sources, hydrodynamic transport, arid microbial fate processes. Fecal indicator bacteria such as enterococci have been used to ass...
K. J. McFarlane; S. H. Schoenholtz; R. F. Powers
2009-01-01
Belowground C and N storage is important in maintaining forestproductivity and to CO2 sequestration. How these pools respondto management is poorly understood. We investigated effectsof repeated applications of complete fertilizer and competing...
Predictive Models of Liver Cancer
Predictive models of chemical-induced liver cancer face the challenge of bridging causative molecular mechanisms to adverse clinical outcomes. The latent sequence of intervening events from chemical insult to toxicity are poorly understood because they span multiple levels of bio...
What Can Plasticity Contribute to Insect Responses to Climate Change?
Sgrò, Carla M; Terblanche, John S; Hoffmann, Ary A
2016-01-01
Plastic responses figure prominently in discussions on insect adaptation to climate change. Here we review the different types of plastic responses and whether they contribute much to adaptation. Under climate change, plastic responses involving diapause are often critical for population persistence, but key diapause responses under dry and hot conditions remain poorly understood. Climate variability can impose large fitness costs on insects showing diapause and other life cycle responses, threatening population persistence. In response to stressful climatic conditions, insects also undergo ontogenetic changes including hardening and acclimation. Environmental conditions experienced across developmental stages or by prior generations can influence hardening and acclimation, although evidence for the latter remains weak. Costs and constraints influence patterns of plasticity across insect clades, but they are poorly understood within field contexts. Plastic responses and their evolution should be considered when predicting vulnerability to climate change-but meaningful empirical data lag behind theory.
Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing
Arenkiel, Benjamin R.; Hasegawa, Hiroshi; Yi, Jason J.; Larsen, Rylan S.; Wallace, Michael L.; Philpot, Benjamin D.; Wang, Fan; Ehlers, Michael D.
2011-01-01
The continued addition of new neurons to mature olfactory circuits represents a remarkable mode of cellular and structural brain plasticity. However, the anatomical configuration of newly established circuits, the types and numbers of neurons that form new synaptic connections, and the effect of sensory experience on synaptic connectivity in the olfactory bulb remain poorly understood. Using in vivo electroporation and monosynaptic tracing, we show that postnatal-born granule cells form synaptic connections with centrifugal inputs and mitral/tufted cells in the mouse olfactory bulb. In addition, newly born granule cells receive extensive input from local inhibitory short axon cells, a poorly understood cell population. The connectivity of short axon cells shows clustered organization, and their synaptic input onto newborn granule cells dramatically and selectively expands with odor stimulation. Our findings suggest that sensory experience promotes the synaptic integration of new neurons into cell type-specific olfactory circuits. PMID:22216277
The Multifactorial Epidemiology of Blackwater Fever.
Shanks, G Dennis
2017-12-01
Blackwater fever is a massive hemolytic event usually occurring in the context of repeated falciparum malaria infections and intermittent quinine use. Its etiology is poorly understood, and it is rarely seen today. Historical epidemiological observations from the 20th century demonstrated variable patterns in prisoners in Andaman Islands, refugees in Macedonia, canal workers in Panama, expatriates in Rhodesia, and Second World War soldiers. Rates of blackwater fever per 1,000 malaria cases varied over two orders of magnitude. Islands, such as the Andaman Islands and New Guinea, had lower blackwater fever rates than continental areas. During the Second World War, blackwater fever rates in British soldiers in West Africa and Australian soldiers in New Guinea differed by a factor of 40 despite similar treatment regimens and falciparum malaria transmission risks. Blackwater fever is a complex interaction between host erythrocyte, falciparum malaria, and antimalarial drugs which remains poorly understood.
Hou, Lifang; Zhang, Xiao; Zheng, Yinan; Wang, Sheng; Dou, Chang; Guo, Liqiong; Byun, Hyang-Min; Motta, Valeria; McCracken, John; Díaz, Anaité; Kang, Choong-Min; Koutrakis, Petros; Bertazzi, Pier Alberto; Li, Jingyun; Schwartz, Joel; Baccarelli, Andrea A.
2014-01-01
Exposure to particulate matter (PM) has been associated with lung cancer risk in epidemiology investigations. Elemental components of PM have been suggested to have critical roles in PM toxicity, but the molecular mechanisms underlying their association with cancer risks remain poorly understood. DNA methylation has emerged as a promising biomarker for environmental-related diseases, including lung cancer. In this study, we evaluated the effects of PM elemental components on methylation of three tandem repeats in a highly-exposed population in Beijing, China. The Beijing Truck Driver Air Pollution Study was conducted shortly before the 2008 Beijing Olympic Games (June 15-July 27, 2008) and included 60 truck drivers and 60 office workers. On two days separated by 1-2 weeks, we measured blood DNA methylation of SATα, NBL2, D4Z4, and personal exposure to eight elemental components in PM2.5, including aluminum (Al), silicon (Si), sulfur (S), potassium (K), calcium (Ca) titanium (Ti), iron (Fe), and zinc (Zn). We estimated the associations of individual elemental component with each tandem repeat methylation in generalized estimating equations (GEE) models adjusted for PM2.5 mass and other covariates. Out of the eight examined elements, NBL2 methylation was positively associated with concentrations of Si (0.121, 95%CI: 0.030; 0.212, FDR=0.047) and Ca (0.065, 95%CI: 0.014; 0.115, FDR=0.047) in truck drivers. In office workers, SATα methylation was positively associated with concentrations of S (0.115, 95%CI: 0.034; 0.196, FDR=0.042). PM-associated differences in blood tandem-repeat methylation may help detect biological effects of the exposure and identify individuals who may eventually experience higher lung cancer risk. PMID:24273195
Zhou, Wanli; Wang, Guohong; Wang, Chunmei; Ren, Fazheng; Hao, Yanling
2016-01-01
Upon exposure to exogenous pediocin-like bacteriocins, immunity proteins specifically bind to the target receptor of the mannose phosphotransferase system components (man-PTS IIC and IID), therefore preventing bacterial cell death. However, the specific recognition of immunity proteins and its associated target receptors remains poorly understood. In this study, we constructed hybrid receptors to identify the domains of IIC and/or IID recognized by the immunity protein PedB, which confers immunity to pediocin PA-1. Using Lactobacillus plantarum man-PTS EII mutant W903, the IICD components of four pediocin PA-1-sensitive strains (L. plantarum WQ0815, Leuconostoc mesenteroides 05-43, Lactobacillus salivarius REN and Lactobacillus acidophilus 05-172) were respectively co-expressed with the immunity protein PedB. Well-diffusions assays showed that only the complex formed by LpIICD from L. plantarum WQ0815 with pediocin PA-1 could be recognized by PedB. In addition, a two-step PCR approach was used to construct hybrid receptors by combining LpIIC or LpIID recognized by PedB with the other three heterologous IID or IIC compounds unrecognized by PedB, respectively. The results showed that all six hybrid receptors were recognized by pediocin PA-1. However, when IIC or IID of L. plantarum WQ0815 was replaced with any corresponding IIC or IID component from L. mesenteroides 05-43, L. salivarius REN and L. acidophilus 05-172, all the hybrid receptors could not be recognized by PedB. Taken altogether, we concluded that both IIC and IID components of the mannose phosphotransferase system play an important role in the specific recognition between the bacteriocin-receptor complex and the immunity protein PedB.
NASA Astrophysics Data System (ADS)
Gardner, Christopher B.; Litt, Guy F.; Lyons, W. Berry; Ogden, Fred L.
2017-10-01
In humid tropical watersheds, the hydrologic flow paths taken by rain event waters and how they interact with groundwater and soil matrix water to form streamflow are poorly understood. Preferential flow paths (PFPs) confound storm infiltration processes, especially in the humid tropics where PFPs are common. This work applies germanium (Ge) and silicon (Si) as natural flow path tracers in conjunction with water stable isotopes and electrical conductivity to examine the rapid delivery of shallow soil water, the activation of PFPs, and event water partitioning in an experimental catchment in central Panama. We employed a three-component mixing model for hydrograph separation using the following end-member waters: (i) base flow (high [Si], low [Ge], and low Ge/Si ratio), (ii) dilute canopy throughfall (low [Si] and low [Ge]), and (iii) shallow (<15 cm) soil matrix water (low [Si], high [Ge], and high Ge/Si ratio). These three end-members bounded all observed Ge/Si streamflow ratios. During small rain events (<˜24 mm), base flow and dilute canopy throughfall components dominated stormflow. During larger precipitation events (>˜35 mm), we detected the third shallow soil water component with an elevated [Ge] and Ge/Si ratio. This component reached its maximum during the hydrograph's receding limb coincident with the maximum event fraction, and increased proportionally to the total storm rainfall exceeding ˜35 mm. Only shallow (<15 cm) soil matrix water exhibited elevated Ge concentrations and high Ge/Si ratios. This third component represents rapidly delivered soil matrix water combined with shallow lateral PFP activation through which event waters interact with soil minerals.
2014-01-01
Background The students’ motivation to learn basic sciences in health science curricula is poorly understood. The purpose of this study was to investigate the influence of different components of motivation (intrinsic motivation, self-determination, self-efficacy and extrinsic -career and grade- motivation) on learning human histology in health science curricula and their relationship with the final performance of the students in histology. Methods Glynn Science Motivation Questionnaire II was used to compare students’ motivation components to learn histology in 367 first-year male and female undergraduate students enrolled in medical, dentistry and pharmacy degree programs. Results For intrinsic motivation, career motivation and self-efficacy, the highest values corresponded to medical students, whereas dentistry students showed the highest values for self-determination and grade motivation. Genders differences were found for career motivation in medicine, self-efficacy in dentistry, and intrinsic motivation, self-determination and grade motivation in pharmacy. Career motivation and self-efficacy components correlated with final performance in histology of the students corresponding to the three curricula. Conclusions Our results show that the overall motivational profile for learning histology differs among medical, dentistry and pharmacy students. This finding is potentially useful to foster their learning process, because if they are metacognitively aware of their motivation they will be better equipped to self-regulate their science-learning behavior in histology. This information could be useful for instructors and education policy makers to enhance curricula not only on the cognitive component of learning but also to integrate students’ levels and types of motivation into the processes of planning, delivery and evaluation of medical education. PMID:24612878
Hunt, Jennifer L
2006-01-01
Warthin tumors are controversial entities with a poorly understood etiology. Although some investigators have suggested a neoplastic origin, others have supported a developmental anomaly. A recent study described the absence of staining for hMLH1 and hMSH2 proteins in the epithelial component of Warthin tumors, suggesting that they arise secondary to defects in the DNA mismatch repair system. To determine if Warthin tumors exhibit evidence of DNA mismatch repair defects. Immunostains for hMLH1 and hMSH2 were performed using a standard approach. Microdissection of the epithelial component was followed by DNA extraction from the tissue fragments. Polymerase chain reaction and capillary electrophoresis analyses were performed for the following 5 National Cancer Institute-recommended microsatellites: D2s123, D5s346, D17s250, BAT25, and BAT26. Twelve patients with Warthin tumors were included. The immunostains for hMLH1 and hMSH2 showed preserved expression in the nuclei of the epithelial component of all Warthin tumors. No microsatellite instability was detected, and no loss of heterozygosity was seen. These results are not concordant with previously reported results showing loss of expression of the hMLH1 and hMSH2 DNA mismatch repair enzymes in the epithelial component of Warthin tumors. Furthermore, no microsatellite instability was detected in the 5 loci tested for each tumor in this series. These data demonstrate that Warthin tumors do not have evidence of DNA mismatch repair defects at the genomic or protein expression level.
Tracking contaminant flux from aquatic to terrestrial food webs
Aquatic insects provide a critical energy subsidy to riparian food webs, yet their role as vectors of contaminants to terrestrial ecosystems is poorly understood. We investigated aquatic resource utilization and contaminant exposure among riparian invertivores (spiders and herpt...
Asthma and Respiratory Allergic Disease
The pathogenesis of non-communicable diseases such as allergy is complex and poorly understood. The causes of chronic allergic diseases including asthma involve to a large extent, immunomodulation of the adaptive and particularly the innate immune systems and are markedly influen...
A Production Function Approach to Regional Environmental Economic Assessments
Regional-scale environmental assessments require integrating many available types of data having inconsistent spatial or temporal scales. Moreover, the relationships among the environmental variables in the assessment tend to be poorly understood, a situation made even more compl...
AtCHX13 is a plasma membrane K(+) transporter
USDA-ARS?s Scientific Manuscript database
Potassium (K+) homeostasis is essential for diverse cellular processes, although how various cation transporters collaborate to maintain a suitable K(+) required for growth and development is poorly understood. The Arabidopsis ("Arabidopsis thaliana") genome contains numerous cation:proton antiporte...
AtCHX13 is a plasma membrane K+ transporter
USDA-ARS?s Scientific Manuscript database
Potassium (K+) homeostasis is essential for diverse cellular processes, although how various cation transporters collaborate to maintain a suitable K+ required for growth and development is poorly understood. The Arabidopsis (Arabidopsis thaliana) genome contains numerous cation:proton antiporters (...
The 2011 National Wetland Condition Assessment
The ecological condition of wetland resources across the conterminous United States is poorly understood. To address this issue, the U.S. Environmental Protection Agency (USEPA), in collaboration with states, tribes, and other federal partners, is conducting the first-ever Natio...
Impacts of Human Activity on the Microbial Communities of Devon Island, Canadian High Arctic
NASA Astrophysics Data System (ADS)
Bywaters, K. B.; Burton, A. S.; Wallace, S. L.; Glass, B. J.
2016-09-01
The impacts of human activities on microbial communities in arctic environments are poorly understood. This project compares the distribution of microbes at the HMP Mars analog site prior to and after human settlement.
AN IMPROVED METHOD FOR DETECTING VIRUSES IN WATER
Enteroviruses are important etiological agents of waterborne disease and are responsible for outbreaks of gastroenteritis. However, the prevalence and occurrence of these pathogens in raw drinking water sources is poorly understood. This is primarily due to the limited methods ...
The mechanisms of intrarenal hemodynamic changes following acute arterial occlusion.
DOT National Transportation Integrated Search
1963-10-01
The hemodynamic response of the kidney to acute arterial occlusion is poorly understood. The purpose of the present study was to determine intrarenal hemodynamic changes in intact and isolated kidneys following arterial occlusion. : The relative role...
Prediction of Membership in Rehabilitation Counseling Professional Associations
ERIC Educational Resources Information Center
Phillips, Brian N.; Leahy, Michael J.
2012-01-01
Declining membership is a concerning yet poorly understood issue affecting professional associations across disciplines (Bauman, 2008). Rehabilitation counseling association membership is in decline even while number of certified rehabilitation counselors continues to increase (Leahy, 2009). Factors influencing rehabilitation counseling…
The prevalence and causes of autistic spectrum disorders.
Hainsworth, Terry
Autism and autistic spectrum disorders are still relatively poorly understood. This article outlines the results of new research into the prevalence of autism and into the causes of the condition and highlights implications for nurses from the findings.
Familiarity and Aptness in Metaphor Comprehension.
Damerall, Alison Whiteford; Kellogg, Ronald T
2016-01-01
The career of metaphor hypothesis suggests that novel metaphors are understood through a search for shared features between the topic and vehicle, but with repeated exposure, the figurative meaning is understood directly as a new category is established. The categorization hypothesis argues that instead good or apt metaphors are understood through a categorization process, whether or not they are familiar. Only poor metaphors ever invoke a literal comparison. In Experiment 1, with aptness equated, we found that high familiarity speeded comprehension time over low-familiarity metaphors. In Experiment 2a, providing a literal prime failed to facilitate interpretation of low-familiarity metaphors, contrary to the career of metaphor hypothesis. In Experiment 2b, with familiarity equated, high- and low-aptness metaphors did not differ, contrary to the categorization hypothesis.
Loneliness in psychosis: a systematic review.
Lim, Michelle H; Gleeson, John F M; Alvarez-Jimenez, Mario; Penn, David L
2018-03-01
The aim of the review is to understand the relationships between loneliness and related psychological and social factors in individuals with psychosis. Loneliness is poorly understood in people with psychosis. Given the myriad of social challenges facing individuals with psychosis, these findings can inform psychosocial interventions that specifically target loneliness in this vulnerable group. We adhered to the PRISMA guidelines and systematically reviewed empirical studies that measured loneliness either as a main outcome or as an associated variable in individuals with psychosis. A total of ten studies examining loneliness in people diagnosed with a psychotic disorder were examined. Heterogeneity in the assessment of loneliness was found, and there were contradictory findings on the relationship between loneliness and psychotic symptomatology. In individuals with psychosis, loneliness may be influenced by psychological and social factors such as increased depression, psychosis, and anxiety, poor social support, poor quality of life, more severe internalised stigma and perceived discrimination, and low self-esteem. The relationship between loneliness and psychosis remains poorly understood due to a lack of rigorous studies. Although having strong social relationships is crucial to facilitate recovery from serious mental illness, psychosocial interventions that specifically target loneliness in individuals with psychosis are lacking and sorely needed. Interventions targeting loneliness in those with psychosis will also need to account for additional barriers associated with psychosis (e.g., social skill deficits, impoverished social networks, and negative symptoms).
Mobility of pyroclastic density currents
NASA Astrophysics Data System (ADS)
Giordano, G.; Porreca, M.; Lesti, C.; Cas, R. A. F.
2012-04-01
Mobility of pyroclastic density currents is a hot topic largely still poorly understood. Here we review three case studies of low aspect ratio (10-4) ignimbrites that encompass the spectrum from small to large volume, from basic to felsic in composition and from hot magmatic to cold phreatomagmatic endmembers. The 0.87 km3, phreatomagmatic, K-foiditic, Peperino Albano ignimbrite (Colli Albani, Italy), was erupted from the Albano maar at < 23 ka. The ignimbrite displays both thick valley pond and veneer facies. The juvenile component is 30-40% of the total volume and is highly fragmented to ash, with only a very minor proportion of small, vesicular lapilli. The unit reaches 10 km from vent, where it is confined in major valleys. Emplacement temperatures retrieved from paleomagnetic data and field data are at 350°-100°C. The 69 km3, tephritic, Pozzolane Rosse ignimbrite was erupted from the caldera of Colli Albani at 460 ka. The succession starts with subplinian fallout of poorly vesicular scoria lapilli. The overlying ignimbrite cover more than 2000 km2 and relate to pyroclastic flows with significant mobility, able to surmount hills at more than 20 km from vent. The facies is almost ubiquitously massive and chaotic. Juvenile pyroclasts are made of variably porphyritic, poorly to moderately vesicular scoria and spatter lapilli, and coarse ash. The texture of juvenile clasts indicates that the presence of little fine ash is not due to elutriation but to weak fragmentation of poorly vesicular and poorly viscous magma. The > 500 km3, rhyodacitic Galan ignimbrite (Altiplano Puna, Argentina) was erupted at 2.1 Ma. There is no basal fallout deposit. The ignimbrite is lithic poor, very crystal rich, massive and chaotic throughout, emplaced above Curie temperature, and develops valley confined facies, but no veneer facies, from proximal to distal (> 80 km) locations. The three cases show that: - the mobility of pyroclastic flows does not necessarily relate to the conversion of potential energy into kinetic energy during the collapse of an initially buoyant column; - extreme fragmentation and entrapment of fine ash does not seem to be a pre-requisite for mobility; - temperature also seems not to be a pre-requisite.
Continuous-variable quantum key distribution protocols over noisy channels.
García-Patrón, Raúl; Cerf, Nicolas J
2009-04-03
A continuous-variable quantum key distribution protocol based on squeezed states and heterodyne detection is introduced and shown to attain higher secret key rates over a noisy line than any other one-way Gaussian protocol. This increased resistance to channel noise can be understood as resulting from purposely adding noise to the signal that is converted into the secret key. This notion of noise-enhanced tolerance to noise also provides a better physical insight into the poorly understood discrepancies between the previously defined families of Gaussian protocols.
Belief inhibition during thinking: not always winning but at least taking part.
De Neys, Wim; Franssens, Samuel
2009-10-01
Human thinking is often biased by intuitive beliefs. Inhibition of these tempting beliefs is considered a key component of human thinking, but the process is poorly understood. In the present study we clarify the nature of an inhibition failure and the resulting belief bias by probing the accessibility of cued beliefs after people reasoned. Results indicated that even the poorest reasoners showed an impaired memory access to words that were associated with cued beliefs after solving reasoning problems in which the beliefs conflicted with normative considerations (Experiment 1 and 2). The study further established that the impairment was only temporary in nature (Experiment 3) and did not occur when people were explicitly instructed to give mere intuitive judgments (Experiment 4). Findings present solid evidence for the postulation of an inhibition process and imply that belief bias does not result from a failure to recognize the need to inhibit inappropriate beliefs, but from a failure to complete the inhibition process. This indicates that people are far more logical than hitherto believed.
[Non-LTR retrotransposons: LINEs and SINEs in plant genome].
Cheng, Xu-Dong; Ling, Hong-Qing
2006-06-01
Retrotransposons are one of the drivers of genome evolution. They include LTR (long terminal repeat) retrotransposons, which widespread in Eukaryotagenomes, show structural similarity to retroviruses. Non-LTR retrotransposons were first discovered in animal genomes and then identified as ubiquitous components of nuclear genomes in many species across the plant kingdom. They constitute a large fraction of the repetitive DNA. Non-LTR retrotransposons are divided into LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements). Transposition of non-LTR retrotransposons is rarely observed in plants indicating that most of them are inactive and/or under regulation of the host genome. Transposition is poorly understood, but experimental evidence from other genetic systems shows that LINEs are able to transpose autonomously while non-autonomous SINEs depend on the reverse transcription machinery of other retrotransposons. Phylogenic analysis shows LINEs are probably the most ancient class of retrotransposons in plant genomes, while the origin of SINEs is unknown. This review sums up the above data and wants to show readers a clear picture of non-LTR retrotransposons.
Flexible attention deployment in threatening contexts: an instructed fear conditioning study.
Shechner, Tomer; Pelc, Tatiana; Pine, Daniel S; Fox, Nathan A; Bar-Haim, Yair
2012-10-01
Factors leading humans to shift attention away from danger cues remain poorly understood. Two laboratory experiments reported here show that context interacts with learning experiences to shape attention avoidance of mild danger cues. The first experiment exposed 18 participants to contextual threat of electric shock. Attention allocation to mild danger cues was then assessed with the dot-probe task. Results showed that contextual threat caused subjects to avert attention from danger cues. In the second experiment, 36 participants were conditioned to the same contextual threat used in Experiment 1. These subjects then were randomly assigned to either an experimental group, trained to shift attention toward danger cues, or a placebo group exposed to the same stimuli without the training component. As in Experiment 1, contextual threat again caused attention allocation away from danger in the control group. However, this did not occur in the experimental group. These experiments show that acute contextual threat and learning experiences interact to shape the deployment of attention away from danger cues.
Drosophila Neuropeptide F Signaling Independently Regulates Feeding and Sleep-Wake Behavior.
Chung, Brian Y; Ro, Jennifer; Hutter, Sabine A; Miller, Kylie M; Guduguntla, Lakshmi S; Kondo, Shu; Pletcher, Scott D
2017-06-20
Proper regulation of sleep-wake behavior and feeding is essential for organismal health and survival. While previous studies have isolated discrete neural loci and substrates important for either sleep or feeding, how the brain is organized to coordinate both processes with respect to one another remains poorly understood. Here, we provide evidence that the Drosophila Neuropeptide F (NPF) network forms a critical component of both adult sleep and feeding regulation. Activation of NPF signaling in the brain promotes wakefulness and adult feeding, likely through its cognate receptor NPFR. Flies carrying a loss-of-function NPF allele do not suppress sleep following prolonged starvation conditions, suggesting that NPF acts as a hunger signal to keep the animal awake. NPF-expressing cells, specifically those expressing the circadian photoreceptor cryptochrome, are largely responsible for changes to sleep behavior caused by NPF neuron activation, but not feeding, demonstrating that different NPF neurons separately drive wakefulness and hunger. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Hatahet, Feras; Blazyk, Jessica L; Martineau, Eugenie; Mandela, Eric; Zhao, Yongxin; Campbell, Robert E; Beckwith, Jonathan; Boyd, Dana
2015-12-08
Functional overexpression of polytopic membrane proteins, particularly when in a foreign host, is often a challenging task. Factors that negatively affect such processes are poorly understood. Using the mammalian membrane protein vitamin K epoxide reductase (VKORc1) as a reporter, we describe a genetic selection approach allowing the isolation of Escherichia coli mutants capable of functionally expressing this blood-coagulation enzyme. The isolated mutants map to components of membrane protein assembly and quality control proteins YidC and HslV. We show that changes in the VKORc1 sequence and in the YidC hydrophilic groove along with the inactivation of HslV promote VKORc1 activity and dramatically increase its expression level. We hypothesize that such changes correct for mismatches in the membrane topogenic signals between E. coli and eukaryotic cells guiding proper membrane integration. Furthermore, the obtained mutants allow the study of VKORc1 reaction mechanisms, inhibition by warfarin, and the high-throughput screening for potential anticoagulants.
Hatahet, Feras; Blazyk, Jessica L.; Martineau, Eugenie; Mandela, Eric; Zhao, Yongxin; Campbell, Robert E.; Beckwith, Jonathan; Boyd, Dana
2015-01-01
Functional overexpression of polytopic membrane proteins, particularly when in a foreign host, is often a challenging task. Factors that negatively affect such processes are poorly understood. Using the mammalian membrane protein vitamin K epoxide reductase (VKORc1) as a reporter, we describe a genetic selection approach allowing the isolation of Escherichia coli mutants capable of functionally expressing this blood-coagulation enzyme. The isolated mutants map to components of membrane protein assembly and quality control proteins YidC and HslV. We show that changes in the VKORc1 sequence and in the YidC hydrophilic groove along with the inactivation of HslV promote VKORc1 activity and dramatically increase its expression level. We hypothesize that such changes correct for mismatches in the membrane topogenic signals between E. coli and eukaryotic cells guiding proper membrane integration. Furthermore, the obtained mutants allow the study of VKORc1 reaction mechanisms, inhibition by warfarin, and the high-throughput screening for potential anticoagulants. PMID:26598701
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vijayakumar, M.; Nie, Zimin; Walter, Eric D.
Redox flow battery (RFB) is a promising candidate for energy storage component in designing resilient grid scale power supply due to the advantage of the separation of power and energy. However, poorly understood chemical and thermal stability issues of electrolytes currently limit the performance of RFB. Designing of high performance stable electrolytes requires comprehensive knowledge about the molecular level solvation structure and dynamics of their redox active species. The molecular level understanding of detrimental V2O5 precipitation process led to successful designing of mixed acid based electrolytes for vanadium redox flow batteries (VRFB). The higher stability of mixed acid based electrolytesmore » is attributed to the choice of hydrochloric acid as optimal co-solvent, which provides chloride anions for ligand exchange process in vanadium solvation structure. The role of chloride counter anion on solvation structure and dynamics of vanadium species were studied using combined magnetic resonance spectroscopy and DFT based theoretical methods. Finally, the solvation phenomenon of multiple vanadium species and their impact on VRFB electrolyte chemical stability were discussed.« less
Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix.
Kubow, Kristopher E; Vukmirovic, Radmila; Zhe, Lin; Klotzsch, Enrico; Smith, Michael L; Gourdon, Delphine; Luna, Sheila; Vogel, Viola
2015-08-14
Despite the crucial role of extracellular matrix (ECM) in directing cell fate in healthy and diseased tissues--particularly in development, wound healing, tissue regeneration and cancer--the mechanisms that direct the assembly and regulate hierarchical architectures of ECM are poorly understood. Collagen I matrix assembly in vivo requires active fibronectin (Fn) fibrillogenesis by cells. Here we exploit Fn-FRET probes as mechanical strain sensors and demonstrate that collagen I fibres preferentially co-localize with more-relaxed Fn fibrils in the ECM of fibroblasts in cell culture. Fibre stretch-assay studies reveal that collagen I's Fn-binding domain is responsible for the mechano-regulated interaction. Furthermore, we show that Fn-collagen interactions are reciprocal: relaxed Fn fibrils act as multivalent templates for collagen assembly, but once assembled, collagen fibres shield Fn fibres from being stretched by cellular traction forces. Thus, in addition to the well-recognized, force-regulated, cell-matrix interactions, forces also tune the interactions between different structural ECM components.
Oberding, Lisa; Gieg, Lisa M.
2016-01-01
Hydrocarbon compounds can be biodegraded by anaerobic microorganisms to form methane through an energetically interdependent metabolic process known as syntrophy. The microorganisms that perform this process as well as the energy transfer mechanisms involved are difficult to study and thus are still poorly understood, especially on an environmental scale. Here, metagenomic data was analyzed for specific clusters of orthologous groups (COGs) related to key energy transfer genes thus far identified in syntrophic bacteria, and principal component analysis was used in order to determine whether potentially syntrophic environments could be distinguished using these syntroph related COGs as opposed to universally present COGs. We found that COGs related to hydrogenase and formate dehydrogenase genes were able to distinguish known syntrophic consortia and environments with the potential for syntrophy from non-syntrophic environments, indicating that these COGs could be used as a tool to identify syntrophic hydrocarbon biodegrading environments using metagenomic data. PMID:27681901
NASA Technical Reports Server (NTRS)
Kring, David A.; Zurcher, Lukas; Horz, Freidrich; Mertzmann, Stanley A.
2004-01-01
Impact melts within complex impact craters are generally homogeneous, unless they differentiated, contain immiscible melt components, or were hydrothermally altered while cooling. The details of these processes, however, and their chemical consequences, are poorly understood. The best opportunity to unravel them may lie with the Chicxulub impact structure, because it is the world s most pristine (albeit buried) large impact crater. The Chicxulub Scientific Drilling Project recovered approx. 100 meters of impactites in a continuous core from the Yaxcopoil-1 (YAX-1) borehole. This dramatically increased the amount of melt available for analyses, which was previously limited to two small samples N17 and N19) recovered from the Yucatan-6 (Y-6) borehole and one sample (N10) recovered from the Chicxulub-1 (C-1) borehole. In this study, we describe the chemical compositions of six melt samples over an approx. 40 m section of the core and compare them to previous melt samples from the Y-6 and C-1 boreholes.
Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome
2013-01-01
Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis. PMID:24305068
Setting the pace of microswimmers: when increasing viscosity speeds up self-propulsion
NASA Astrophysics Data System (ADS)
Pande, Jayant; Merchant, Laura; Krüger, Timm; Harting, Jens; Smith, Ana-Sunčana
2017-05-01
It has long been known that some microswimmers seem to swim counter-intuitively faster when the viscosity of the surrounding fluid is increased, whereas others slow down. This conflicting dependence of the swimming velocity on the viscosity is poorly understood theoretically. Here we explain that any mechanical microswimmer with an elastic degree of freedom in a simple Newtonian fluid can exhibit both kinds of response to an increase in the fluid viscosity for different viscosity ranges, if the driving is weak. The velocity response is controlled by a single parameter Γ, the ratio of the relaxation time of the elastic component of the swimmer in the viscous fluid and the swimming stroke period. This defines two velocity-viscosity regimes, which we characterize using the bead-spring microswimmer model and analyzing the different forces acting on the parts of this swimmer. The analytical calculations are supported by lattice-Boltzmann simulations, which accurately reproduce the two velocity regimes for the predicted values of Γ.
Alderson-Day, Ben; McCarthy-Jones, Simon; Bedford, Sarah; Collins, Hannah; Dunne, Holly; Rooke, Chloe; Fernyhough, Charles
2014-01-01
Inner speech is a commonly experienced but poorly understood phenomenon. The Varieties of Inner Speech Questionnaire (VISQ; McCarthy-Jones & Fernyhough, 2011) assesses four characteristics of inner speech: dialogicality, evaluative/motivational content, condensation, and the presence of other people. Prior findings have linked anxiety and proneness to auditory hallucinations (AH) to these types of inner speech. This study extends that work by examining how inner speech relates to self-esteem and dissociation, and their combined impact upon AH-proneness. 156 students completed the VISQ and measures of self-esteem, dissociation and AH-proneness. Correlational analyses indicated that evaluative inner speech and other people in inner speech were associated with lower self-esteem and greater frequency of dissociative experiences. Dissociation and VISQ scores, but not self-esteem, predicted AH-proneness. Structural equation modelling supported a mediating role for dissociation between specific components of inner speech (evaluative and other people) and AH-proneness. Implications for the development of “hearing voices” are discussed. PMID:24980910
Abascal-Palacios, Guillermo; Schindler, Christina; Rojas, Adriana L; Bonifacino, Juan S.; Hierro, Aitor
2016-01-01
Summary The Golgi-Associated Retrograde Protein (GARP) is a tethering complex involved in the fusion of endosome-derived transport vesicles to the trans-Golgi network through interaction with components of the Syntaxin 6/Syntaxin 16/Vti1a/VAMP4 SNARE complex. The mechanisms by which GARP and other tethering factors engage the SNARE fusion machinery are poorly understood. Herein we report the structural basis for the interaction of the human Ang2 subunit of GARP with Syntaxin 6 and the closely related Syntaxin 10. The crystal structure of Syntaxin 6 Habc domain in complex with a peptide from the N terminus of Ang2 shows a novel binding mode in which a di-tyrosine motif of Ang2 interacts with a highly conserved groove in Syntaxin 6. Structure-based mutational analyses validate the crystal structure and support the phylogenetic conservation of this interaction. The same binding determinants are found in other tethering proteins and syntaxins, suggesting a general interaction mechanism. PMID:23932592
Exceptionally well-preserved Cretaceous microfossils reveal new biomineralization styles.
Wendler, Jens E; Bown, Paul
2013-01-01
Calcareous microplankton shells form the dominant components of ancient and modern pelagic sea-floor carbonates and are widely used in palaeoenvironmental reconstructions. The efficacy of these applications, however, is dependent upon minimal geochemical alteration during diagenesis, but these modifying processes are poorly understood. Here we report on new biomineralization architectures of previously unsuspected complexity in calcareous cell-wall coverings of extinct dinoflagellates (pithonellids) from a Tanzanian microfossil-lagerstätte. These Cretaceous 'calcispheres' have previously been considered biomineralogically unremarkable but our new observations show that the true nature of these tests has been masked by recrystallization. The pristine Tanzanian fossils are formed from fibre-like crystallites and show archeopyles and exquisitely constructed opercula, demonstrating the dinoflagellate affinity of pithonellids, which has long been uncertain. The interwoven fibre-like structures provide strength and flexibility enhancing the protective function of these tests. The low-density wall fabrics may represent specific adaptation for oceanic encystment life cycles, preventing the cells from rapid sinking.
Microplastic contamination of river beds significantly reduced by catchment-wide flooding
NASA Astrophysics Data System (ADS)
Hurley, Rachel; Woodward, Jamie; Rothwell, James J.
2018-04-01
Microplastic contamination of the oceans is one of the world's most pressing environmental concerns. The terrestrial component of the global microplastic budget is not well understood because sources, stores and fluxes are poorly quantified. We report catchment-wide patterns of microplastic contamination, classified by type, size and density, in channel bed sediments at 40 sites across urban, suburban and rural river catchments in northwest England. Microplastic contamination was pervasive on all river channel beds. We found multiple urban contamination hotspots with a maximum microplastic concentration of approximately 517,000 particles m-2. After a period of severe flooding in winter 2015/16, all sites were resampled. Microplastic concentrations had fallen at 28 sites and 18 saw a decrease of one order of magnitude. The flooding exported approximately 70% of the microplastic load stored on these river beds (equivalent to 0.85 ± 0.27 tonnes or 43 ± 14 billion particles) and eradicated microbead contamination at 7 sites. We conclude that microplastic contamination is efficiently flushed from river catchments during flooding.
Nanotubes mediate niche-stem cell signaling in the Drosophila testis
Inaba, Mayu; Buszczak, Michael; Yamashita, Yukiko M.
2015-01-01
Stem cell niches provide resident stem cells with signals that specify their identity. Niche signals act over a short-range such that only stem cells but not their differentiating progeny receive the self-renewing signals1. However, the cellular mechanisms that limit niche signaling to stem cells remain poorly understood. Here we show that the Drosophila male germline stem cells (GSCs) form previously unrecognized structures, microtubule-based (MT)-nanotubes, which extend into the hub, a major niche component. MT-nanotubes are observed specifically within GSC populations, and require IFT (intraflagellar transport) proteins for their formation. The BMP receptor Tkv localizes to MT-nanotubes. Perturbation of MT-nanotubes compromises activation of Dpp signaling within GSCs, leading to GSC loss. Moreover, Dpp ligand and Tkv receptor interaction is necessary and sufficient for MT-nanotube formation. We propose that MT-nanotubes provide a novel mechanism for selective receptor-ligand interaction, contributing to the short-range nature of niche-stem cell signaling. PMID:26131929
A long-term epigenetic memory switch controls bacterial virulence bimodality
Ronin, Irine; Katsowich, Naama; Rosenshine, Ilan; Balaban, Nathalie Q
2017-01-01
When pathogens enter the host, sensing of environmental cues activates the expression of virulence genes. Opposite transition of pathogens from activating to non-activating conditions is poorly understood. Interestingly, variability in the expression of virulence genes upon infection enhances colonization. In order to systematically detect the role of phenotypic variability in enteropathogenic E. coli (EPEC), an important human pathogen, both in virulence activating and non-activating conditions, we employed the ScanLag methodology. The analysis revealed a bimodal growth rate. Mathematical modeling combined with experimental analysis showed that this bimodality is mediated by a hysteretic memory-switch that results in the stable co-existence of non-virulent and hyper-virulent subpopulations, even after many generations of growth in non-activating conditions. We identified the per operon as the key component of the hysteretic switch. This unique hysteretic memory switch may result in persistent infection and enhanced host-to-host spreading. DOI: http://dx.doi.org/10.7554/eLife.19599.001 PMID:28178445
Inaba, Mayu; Venkei, Zsolt G; Yamashita, Yukiko M
2015-03-20
Many stem cells divide asymmetrically in order to balance self-renewal with differentiation. The essence of asymmetric cell division (ACD) is the polarization of cells and subsequent division, leading to unequal compartmentalization of cellular/extracellular components that confer distinct cell fates to daughter cells. Because precocious cell division before establishing cell polarity would lead to failure in ACD, these two processes must be tightly coupled; however, the underlying mechanism is poorly understood. In Drosophila male germline stem cells, ACD is prepared by stereotypical centrosome positioning. The centrosome orientation checkpoint (COC) further serves to ensure ACD by preventing mitosis upon centrosome misorientation. In this study, we show that Bazooka (Baz) provides a platform for the correct centrosome orientation and that Baz-centrosome association is the key event that is monitored by the COC. Our work provides a foundation for understanding how the correct cell polarity may be recognized by the cell to ensure productive ACD.
Evaluation of the membrane lipid selectivity of the pea defensin Psd1.
Gonçalves, Sónia; Teixeira, Alexandre; Abade, João; de Medeiros, Luciano Neves; Kurtenbach, Eleonora; Santos, Nuno C
2012-05-01
Psd1, a 46 amino acid residues defensin isolated from the pea Pisum sativum seeds, exhibits anti-fungal activity by a poorly understood mechanism of action. In this work, the interaction of Psd1 with biomembrane model systems of different lipid compositions was assessed by fluorescence spectroscopy. Partition studies showed a marked lipid selectivity of this antimicrobial peptide (AMP) toward lipid membranes containing ergosterol (the main sterol in fungal membranes) or specific glycosphingolipid components, with partition coefficients (K(p)) reaching uncommonly high values of 10(6). By the opposite, Psd1 does not partition to cholesterol-enriched lipid bilayers, such as mammalian cell membranes. The Psd1 mutants His36Lys and Gly12Glu present a membrane affinity loss relative to the wild type. Fluorescence quenching data obtained using acrylamide and membrane probes further clarify the mechanism of action of this peptide at the molecular level, pointing out the potential therapeutic use of Psd1 as a natural antimycotic agent. Copyright © 2012 Elsevier B.V. All rights reserved.
Su, Cai Xia; Chen, Jie; Shi, Fu Ming; Guo, Ming Shen; Chang, Yan Lin
2017-07-01
The acrosome complex plays an indispensable role in the normal function of mature spermatozoa. However, the dynamic process of acrosome complex formation in insect remains poorly understood. Gampsocleis gratiosa Brunner von Wattenwyl possesses the typical characteristic of insect sperms, which is tractable in terms of size, and therefore was selected for the acrosome formation study in this report. The results show that acrosome formation can be divided into six phases: round, rotating, rhombic, cylindrical, transforming and mature phase, based on the morphological dynamics of acrosome complex and nucleus. In addition, the cytoskeleton plays a critical role in the process of acrosome formation. The results from this study indicate that: (1) glycoprotein is the major component of the acrosome proper; (2) the microfilament is one element of the acrosome complex, and may mediate the morphologic change of the acrosome complex; (3) the microtubules might also shape the nucleus and acrosome complex during the acrosome formation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Commensal bacteria produce GPCR ligands that mimic human signaling molecules
Cohen, Louis J.; Esterhazy, Daria; Kim, Seong-Hwan; Lemetre, Christophe; Aguilar, Rhiannon R.; Gordon, Emma A.; Pickard, Amanda J.; Cross, Justin R.; Emiliano, Ana B.; Han, Sun M.; Chu, John; Vila-Farres, Xavier; Kaplitt, Jeremy; Rogoz, Aneta; Calle, Paula Y.; Hunter, Craig; Bitok, J. Kipchirchir; Brady, Sean F.
2017-01-01
Summary Statement Commensal bacteria are believed to play important roles in human health. The mechanisms by which they affect mammalian physiology are poorly understood; however, bacterial metabolites are likely to be key components of host interactions. Here, we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands although future studies are needed to define their potential physiologic role in humans. This work suggests that chemical mimicry of eukaryotic signaling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a new small molecule therapeutic modality (microbiome-biosynthetic-gene-therapy). PMID:28854168
Break-induced telomere synthesis underlies alternative telomere maintenance
Dilley, Robert L.; Verma, Priyanka; Cho, Nam Woo; Winters, Harrison D.; Wondisford, Anne R.; Greenberg, Roger A.
2017-01-01
Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10–15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (break-induced replisome) at telomeres or elsewhere in the mammalian genome is poorly understood. Here we define break-induced telomere synthesis and demonstrate that it utilizes a specialized replisome, which underlies ALT telomere maintenance. DNA double-strand breaks enact nascent telomere synthesis by long-tract unidirectional replication. Proliferating cell nuclear antigen (PCNA) loading by replication factor C (RFC) acts as the initial sensor of telomere damage to establish predominance of DNA polymerase δ (Pol δ) through its POLD3 subunit. Break-induced telomere synthesis requires the RFC–PCNA–Pol δ axis, but is independent of other canonical replisome components, ATM and ATR, or the homologous recombination protein Rad51. Thus, the inception of telomere damage recognition by the break-induced replisome orchestrates homology-directed telomere maintenance. PMID:27760120
Identification of a Druggable Pathway Controlling Glioblastoma Invasiveness.
Pencheva, Nora; de Gooijer, Mark C; Vis, Daniel J; Wessels, Lodewyk F A; Würdinger, Tom; van Tellingen, Olaf; Bernards, René
2017-07-05
Diffuse and uncontrollable brain invasion is a hallmark of glioblastoma (GBM), but its mechanism is understood poorly. We developed a 3D ex vivo organotypic model to study GBM invasion. We demonstrate that invading GBM cells upregulate a network of extracellular matrix (ECM) components, including multiple collagens, whose expression correlates strongly with grade and clinical outcome. We identify interferon regulatory factor 3 (IRF3) as a transcriptional repressor of ECM factors and show that IRF3 acts as a suppressor of GBM invasion. Therapeutic activation of IRF3 by inhibiting casein kinase 2 (CK2)-a negative regulator of IRF3-downregulated the expression of ECM factors and suppressed GBM invasion in ex vivo and in vivo models across a panel of patient-derived GBM cell lines representative of the main molecular GBM subtypes. Our data provide mechanistic insight into the invasive capacity of GBM tumors and identify a potential therapy to inhibit GBM invasion. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts.
Cellot, Giada; Cilia, Emanuele; Cipollone, Sara; Rancic, Vladimir; Sucapane, Antonella; Giordani, Silvia; Gambazzi, Luca; Markram, Henry; Grandolfo, Micaela; Scaini, Denis; Gelain, Fabrizio; Casalis, Loredana; Prato, Maurizio; Giugliano, Michele; Ballerini, Laura
2009-02-01
Carbon nanotubes have been applied in several areas of nerve tissue engineering to probe and augment cell behaviour, to label and track subcellular components, and to study the growth and organization of neural networks. Recent reports show that nanotubes can sustain and promote neuronal electrical activity in networks of cultured cells, but the ways in which they affect cellular function are still poorly understood. Here, we show, using single-cell electrophysiology techniques, electron microscopy analysis and theoretical modelling, that nanotubes improve the responsiveness of neurons by forming tight contacts with the cell membranes that might favour electrical shortcuts between the proximal and distal compartments of the neuron. We propose the 'electrotonic hypothesis' to explain the physical interactions between the cell and nanotube, and the mechanisms of how carbon nanotubes might affect the collective electrical activity of cultured neuronal networks. These considerations offer a perspective that would allow us to predict or engineer interactions between neurons and carbon nanotubes.
Contextual control of skin immunity and inflammation by Corynebacterium.
Ridaura, Vanessa K; Bouladoux, Nicolas; Claesen, Jan; Chen, Y Erin; Byrd, Allyson L; Constantinides, Michael G; Merrill, Eric D; Tamoutounour, Samira; Fischbach, Michael A; Belkaid, Yasmine
2018-03-05
How defined microbes influence the skin immune system remains poorly understood. Here we demonstrate that Corynebacteria , dominant members of the skin microbiota, promote a dramatic increase in the number and activation of a defined subset of γδ T cells. This effect is long-lasting, occurs independently of other microbes, and is, in part, mediated by interleukin (IL)-23. Under steady-state conditions, the impact of Corynebacterium is discrete and noninflammatory. However, when applied to the skin of a host fed a high-fat diet, Corynebacterium accolens alone promotes inflammation in an IL-23-dependent manner. Such effect is highly conserved among species of Corynebacterium and dependent on the expression of a dominant component of the cell envelope, mycolic acid. Our data uncover a mode of communication between the immune system and a dominant genus of the skin microbiota and reveal that the functional impact of canonical skin microbial determinants is contextually controlled by the inflammatory and metabolic state of the host. © 2018 Ridaura et al.
Hepp, Christof; Maier, Berenike
2017-10-01
Secretion systems enable bacteria to import and secrete large macromolecules including DNA and proteins. While most components of these systems have been identified, the molecular mechanisms of macromolecular transport remain poorly understood. Recent findings suggest that various bacterial secretion systems make use of the translocation ratchet mechanism for transporting polymers across the cell envelope. Translocation ratchets are powered by chemical potential differences generated by concentration gradients of ions or molecules that are specific to the respective secretion systems. Bacteria employ these potential differences for biasing Brownian motion of the macromolecules within the conduits of the secretion systems. Candidates for this mechanism include DNA import by the type II secretion/type IV pilus system, DNA export by the type IV secretion system, and protein export by the type I secretion system. Here, we propose that these three secretion systems employ different molecular implementations of the translocation ratchet mechanism. © 2017 The Authors. BioEssays Published by WILEY Periodicals, Inc.
Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin.
Erdogan, Begum; Ao, Mingfang; White, Lauren M; Means, Anna L; Brewer, Bryson M; Yang, Lijie; Washington, M Kay; Shi, Chanjuan; Franco, Omar E; Weaver, Alissa M; Hayward, Simon W; Li, Deyu; Webb, Donna J
2017-11-06
Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally. CAFs align the Fn matrix by increasing nonmuscle myosin II- and platelet-derived growth factor receptor α-mediated contractility and traction forces, which are transduced to Fn through α5β1 integrin. We further show that prostate cancer cells use αv integrin to migrate efficiently and directionally on CAF-derived matrices. We demonstrate that aligned Fn is a prominent feature of invasion sites in human prostatic and pancreatic carcinoma samples. Collectively, we present a new mechanism by which CAFs organize the Fn matrix and promote directional cancer cell migration. © 2017 Erdogan et al.
Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin
Ao, Mingfang; White, Lauren M.; Means, Anna L.; Yang, Lijie; Washington, M. Kay; Franco, Omar E.; Li, Deyu; Webb, Donna J.
2017-01-01
Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF–cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally. CAFs align the Fn matrix by increasing nonmuscle myosin II- and platelet-derived growth factor receptor α–mediated contractility and traction forces, which are transduced to Fn through α5β1 integrin. We further show that prostate cancer cells use αv integrin to migrate efficiently and directionally on CAF-derived matrices. We demonstrate that aligned Fn is a prominent feature of invasion sites in human prostatic and pancreatic carcinoma samples. Collectively, we present a new mechanism by which CAFs organize the Fn matrix and promote directional cancer cell migration. PMID:29021221
Arenavirus Budding: A Common Pathway with Mechanistic Differences
Wolff, Svenja; Ebihara, Hideki; Groseth, Allison
2013-01-01
The Arenaviridae is a diverse and growing family of viruses that includes several agents responsible for important human diseases. Despite the importance of this family for public health, particularly in Africa and South America, much of its biology remains poorly understood. However, in recent years significant progress has been made in this regard, particularly relating to the formation and release of new enveloped virions, which is an essential step in the viral lifecycle. While this process is mediated chiefly by the viral matrix protein Z, recent evidence suggests that for some viruses the nucleoprotein (NP) is also required to enhance the budding process. Here we highlight and compare the distinct budding mechanisms of different arenaviruses, concentrating on the role of the matrix protein Z, its known late domain sequences, and the involvement of cellular endosomal sorting complex required for transport (ESCRT) pathway components. Finally we address the recently described roles for the nucleoprotein NP in budding and ribonucleoprotein complex (RNP) incorporation, as well as discussing possible mechanisms related to its involvement. PMID:23435234
Identification of hair shaft progenitors that create a niche for hair pigmentation
Liao, Chung-Ping; Booker, Reid C.; Morrison, Sean J.; Le, Lu Q.
2017-01-01
Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20+ cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes. PMID:28465357
Identification of hair shaft progenitors that create a niche for hair pigmentation.
Liao, Chung-Ping; Booker, Reid C; Morrison, Sean J; Le, Lu Q
2017-04-15
Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20 + cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes. © 2017 Liao et al.; Published by Cold Spring Harbor Laboratory Press.
Prieur, Jacques; Barbu, Stéphanie; Blois-Heulin, Catherine; Pika, Simone
2017-12-01
Relationships between humans' manual laterality in non-communicative and communicative functions are still poorly understood. Recently, studies showed that chimpanzees' manual laterality is influenced by functional, interactional and individual factors and their mutual intertwinement. However, what about manual laterality in species living in stable social groups? We tackled this question by studying three groups of captive gorillas (N=35) and analysed their most frequent manual signals: three manipulators and 16 gesture types. Our multifactorial investigation showed that conspecific-directed gestures were overall more right-lateralized than conspecific-directed manipulators. Furthermore, it revealed a difference between conspecific- and human-directed gestural laterality for signallers living in one of the study groups. Our results support the hypothesis that gestural laterality is a relevant marker of language left-brain specialisation. We suggest that components of communication and of manipulation (not only of an object but also of a conspecific) do not share the same lateralised cerebral system in some primate species. Copyright © 2017 Elsevier Inc. All rights reserved.
A platform for high-throughput bioenergy production phenotype characterization in single cells
Kelbauskas, Laimonas; Glenn, Honor; Anderson, Clifford; Messner, Jacob; Lee, Kristen B.; Song, Ganquan; Houkal, Jeff; Su, Fengyu; Zhang, Liqiang; Tian, Yanqing; Wang, Hong; Bussey, Kimberly; Johnson, Roger H.; Meldrum, Deirdre R.
2017-01-01
Driven by an increasing number of studies demonstrating its relevance to a broad variety of disease states, the bioenergy production phenotype has been widely characterized at the bulk sample level. Its cell-to-cell variability, a key player associated with cancer cell survival and recurrence, however, remains poorly understood due to ensemble averaging of the current approaches. We present a technology platform for performing oxygen consumption and extracellular acidification measurements of several hundreds to 1,000 individual cells per assay, while offering simultaneous analysis of cellular communication effects on the energy production phenotype. The platform comprises two major components: a tandem optical sensor for combined oxygen and pH detection, and a microwell device for isolation and analysis of single and few cells in hermetically sealed sub-nanoliter chambers. Our approach revealed subpopulations of cells with aberrant energy production profiles and enables determination of cellular response variability to electron transfer chain inhibitors and ion uncouplers. PMID:28349963
Investigation of Prussian Blue Analogs by XMCD at the K-edge of transition metals
NASA Astrophysics Data System (ADS)
Bordage, A.; Nataf, L.; Baudelet, F.; Bleuzen, A.
2016-05-01
Despite transition metal (TM) K-edge x-ray magnetic circular dichroism (XMCD) seems an interesting tool to get magnetic and structural information at the atomic scale, the effects originating this signal are still poorly understood. We thus initiated a deep investigation of the TM K-edge XMCD using Prussian Blue analogs (PBA) as model-compounds. In a recent study of the NiFe PBA family, we demonstrated that the XMCD signals at the TM K-edges strongly vary with external (mechanical) or internal (chemical) pressure and so that they are highly sensitive to small structural distortions. Following these first results, we extended this approach to the MnFe and CoFe families to evaluate the effect of electronic parameters (number of unpaired electrons of the M II TM) on the XMCD signal. All the results set milestones in the disentanglement of the components originating the XMCD signals at the K-edge of TM and will eventually help in a better understanding of the photomagnetic properties of PBAs.
Light-induced spiral mass transport in azo-polymer films under vortex-beam illumination
Ambrosio, Antonio; Marrucci, Lorenzo; Borbone, Fabio; Roviello, Antonio; Maddalena, Pasqualino
2012-01-01
When an azobenzene-containing polymer film is exposed to non-uniform illumination, a light-induced mass migration process may be induced, leading to the formation of relief patterns on the polymer-free surface. Despite many years of research effort, several aspects of this phenomenon remain poorly understood. Here we report the appearance of spiral-shaped relief patterns on the polymer film under the illumination of focused Laguerre–Gauss beams with helical wavefronts and an optical vortex at their axis. The induced spiral reliefs are sensitive to the vortex topological charge and to the wavefront handedness. These findings are unexpected because the doughnut-shaped intensity profile of Laguerre–Gauss beams contains no information about the wavefront handedness. We propose a model that explains the main features of this phenomenon through the surface-mediated interference of the longitudinal and transverse components of the optical field. These results may find applications in optical nanolithography and optical-field nanoimaging. PMID:22871808
The microprotein Minion controls cell fusion and muscle formation
Zhang, Qiao; Vashisht, Ajay A.; O'Rourke, Jason; Corbel, Stéphane Y; Moran, Rita; Romero, Angelica; Miraglia, Loren; Zhang, Jia; Durrant, Eric; Schmedt, Christian; Sampath, Srinath C.; Sampath, Srihari C.
2017-01-01
Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, their function remains to be determined. Skeletal muscle development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process. Here we report the identification of Minion (microprotein inducer of fusion), a smORF encoding an essential skeletal muscle specific microprotein. Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally and demonstrate a marked reduction in fused muscle fibres. The fusogenic activity of Minion is conserved in the human orthologue, and co-expression of Minion and the transmembrane protein Myomaker is sufficient to induce cellular fusion accompanied by rapid cytoskeletal rearrangement, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component programme for the induction of mammalian cell fusion. Moreover, these data also significantly expand the known functions of smORF-encoded microproteins. PMID:28569745
Infrared emission spectra of candidate interstellar aromatic molecules
NASA Technical Reports Server (NTRS)
Schlemmer, S.; Balucani, N.; Wagner, D. R.; Steiner, B.; Saykally, R. J.
1996-01-01
Interstellar dust is responsible, through surface reactions, for the creation of molecular hydrogen, the main component of the interstellar clouds in which new stars form. Intermediate between small, gas-phase molecules and dust are the polycyclic aromatic hydrocarbons (PAHs). Such molecules could account for 2-30% of the carbon in the Galaxy, and may provide nucleation sites for the formation of carbonaceous dust. Although PAHs have been proposed as the sources of the unidentified infrared emission bands that are observed in the spectra of a variety of interstellar sources, the emission characteristics of such molecules are still poorly understood. Here we report laboratory emission spectra of several representative PAHs, obtained in conditions approximating those of the interstellar medium, and measured over the entire spectral region spanned by the unidentified infrared bands. We find that neutral PAHs of small and moderate size can at best make only a minor contribution to these emission bands. Cations of these molecules, as well as much larger PAHs and their cations, remain viable candidates for the sources of these bands.
Variability of broad and blueshifted component of [OIII]λ5007 in I ZWI
NASA Astrophysics Data System (ADS)
Wang, J.; Wei, J. Y.; He, X. T.
2005-04-01
Although the existence of asymmetrical profile of [OIII]λ5007 has been discovered for ages, its filiation and physics are poorly understood. Two new spectra of I ZWI taken on November 16, 2001 and on December 3, 2002 were compared with the spectra taken by BG92. Following results are obtained. (1) The certain variations of broad [OIII] during about 10 years separating the observations are identified. The inferred length scale of broad [OIII] emitting region ranges from 0.3 to 3 pc. By assuming a Keplerian motion in line emitting region, the material emitting broad [OIII] is likely to be located at the transient emission line region, between BLR and NLR. (2) We find a positive relation between the FeII emission and flux of Hβ (or continuum). On the other hand, the parameter RFe decreases with ionizing continuum marginally. (3) We detect a low ionized NLR in I ZWI, because of the low flux ratios [OIII]n/Hβn (∼1.7).
Lobanova, Anastasia; She, Robert; Pieraut, Simon; Clapp, Charlie; Maximov, Anton; Denchi, Eros Lazzerini
2017-04-01
Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans. © 2017 Lobanova et al.; Published by Cold Spring Harbor Laboratory Press.
Energetic costs of calcification under ocean acidification
NASA Astrophysics Data System (ADS)
Spalding, Christopher; Finnegan, Seth; Fischer, Woodward W.
2017-05-01
Anthropogenic ocean acidification threatens to negatively impact marine organisms that precipitate calcium carbonate skeletons. Past geological events, such as the Permian-Triassic Mass Extinction, together with modern experiments generally support these concerns. However, the physiological costs of producing a calcium carbonate skeleton under different acidification scenarios remain poorly understood. Here we present an idealized mathematical model to quantify whole-skeleton costs, concluding that they rise only modestly (up to ˜10%) under acidification expected for 2100. The modest magnitude of this effect reflects in part the low energetic cost of inorganic, calcium carbonate relative to the proteinaceous organic matrix component of skeletons. Our analysis does, however, point to an important kinetic constraint that depends on seawater carbonate chemistry, and we hypothesize that the impact of acidification is more likely to cause extinctions within groups where the timescale of larval development is tightly constrained. The cheapness of carbonate skeletons compared to organic materials also helps explain the widespread evolutionary convergence upon calcification within the metazoa.
A unique H2A histone variant occupies the transcriptional start site of active genes.
Soboleva, Tatiana A; Nekrasov, Maxim; Pahwa, Anuj; Williams, Rohan; Huttley, Gavin A; Tremethick, David J
2011-12-04
Transcriptional activation is controlled by chromatin, which needs to be unfolded and remodeled to ensure access to the transcription start site (TSS). However, the mechanisms that yield such an 'open' chromatin structure, and how these processes are coordinately regulated during differentiation, are poorly understood. We identify the mouse (Mus musculus) H2A histone variant H2A.Lap1 as a previously undescribed component of the TSS of active genes expressed during specific stages of spermatogenesis. This unique chromatin landscape also includes a second histone variant, H2A.Z. In the later stages of round spermatid development, H2A.Lap1 dynamically loads onto the inactive X chromosome, enabling the transcriptional activation of previously repressed genes. Mechanistically, we show that H2A.Lap1 imparts unique unfolding properties to chromatin. We therefore propose that H2A.Lap1 coordinately regulates gene expression by directly opening the chromatin structure of the TSS at genes regulated during spermatogenesis.
Unveiling the mystery of mitochondrial DNA replication in yeasts.
Chen, Xin Jie; Clark-Walker, George Desmond
2018-01-01
Conventional DNA replication is initiated from specific origins and requires the synthesis of RNA primers for both the leading and lagging strands. In contrast, the replication of yeast mitochondrial DNA is origin-independent. The replication of the leading strand is likely primed by recombinational structures and proceeded by a rolling circle mechanism. The coexistent linear and circular DNA conformers facilitate the recombination-based initiation. The replication of the lagging strand is poorly understood. Re-evaluation of published data suggests that the rolling circle may also provide structures for the synthesis of the lagging-strand by mechanisms such as template switching. Thus, the coupling of recombination with rolling circle replication and possibly, template switching, may have been selected as an economic replication mode to accommodate the reductive evolution of mitochondria. Such a replication mode spares the need for conventional replicative components, including those required for origin recognition/remodelling, RNA primer synthesis and lagging-strand processing. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
Yu, Shuying; Chen, Xuhui; Yuan, Zuoqing; Zhou, Luming; Pang, Qiuxiang; Mao, Bingyu; Zhao, Bosheng
2015-08-01
The myosin essential light chain (ELC) is a structure component of the actomyosin cross-bridge, however, the functions in the central nervous system (CNS) development and regeneration remain poorly understood. Planarian Dugesia japonica has revealed fundamental mechanisms and unique aspects of neuroscience and neuroregeneration. In this study, the cDNA DjElc, encoding a planarian essential light chain of myosin, was identified from the planarian Dugesia japonica cDNA library. It encodes a deduced protein with highly conserved functionally domains EF-Hand and Ca(2+) binding sites that shares significant similarity with other members of ELC. Whole mount in situ hybridization studies show that DjElc expressed in CNS during embryonic development and regeneration of adult planarians. Loss of function of DjElc by RNA interference during planarian regeneration inhibits brain lateral branches regeneration completely. In conclusion, these results demonstrated that DjElc is required for maintenance of neurons and neurite outgrowth, particularly for involving the brain later branch regeneration.
Two FGFRL-Wnt circuits organize the planarian anteroposterior axis.
Scimone, M Lucila; Cote, Lauren E; Rogers, Travis; Reddien, Peter W
2016-04-11
How positional information instructs adult tissue maintenance is poorly understood. Planarians undergo whole-body regeneration and tissue turnover, providing a model for adult positional information studies. Genes encoding secreted and transmembrane components of multiple developmental pathways are predominantly expressed in planarian muscle cells. Several of these genes regulate regional identity, consistent with muscle harboring positional information. Here, single-cell RNA-sequencing of 115 muscle cells from distinct anterior-posterior regions identified 44 regionally expressed genes, including multiple Wnt and ndk/FGF receptor-like (ndl/FGFRL) genes. Two distinct FGFRL-Wnt circuits, involving juxtaposed anterior FGFRL and posterior Wnt expression domains, controlled planarian head and trunk patterning. ndl-3 and wntP-2 inhibition expanded the trunk, forming ectopic mouths and secondary pharynges, which independently extended and ingested food. fz5/8-4 inhibition, like that of ndk and wntA, caused posterior brain expansion and ectopic eye formation. Our results suggest that FGFRL-Wnt circuits operate within a body-wide coordinate system to control adult axial positioning.
NASA Astrophysics Data System (ADS)
Norris, Zach; Mawson, Cara; Johnson, Kyron; Kessler, Sarah; Rebecca, Anne; Wolf, Nathan; Lim, Michael; Nucci, Nathaniel
Reverse micelles are molecular complexes that encapsulate a nanoscale pool of water in a surfactant shell dissolved in non-polar solvent. These complexes have a wide range of applications, and in all cases, the degree to which reverse micelles (RM) exchange their contents is relevant for their use. Despite its importance, this aspect of RM behavior is poorly understood. Photolithography is employed here to create micro and nano scale fluidic systems in which mixing rates can be precisely measured using fluorescence correlation spectroscopy (FCS). Micro-channel patterns are etched using reactive ion etching process into a layer of silicon dioxide on crystalline silicon substrates. Solutions containing mixtures of reverse micelles, proteins, and fluorophores are placed into reservoirs in the patterns, while diffusion and exchange between RMs is monitored using a FCS system built from a modified confocal Raman spectrometer. Using this approach, the diffusion and exchange rates for RM systems are measured as a function of the components of the RM mixture. Funding provided by Rowan University.
Stochastic Community Assembly: Does It Matter in Microbial Ecology?
Zhou, Jizhong; Ning, Daliang
2017-12-01
Understanding the mechanisms controlling community diversity, functions, succession, and biogeography is a central, but poorly understood, topic in ecology, particularly in microbial ecology. Although stochastic processes are believed to play nonnegligible roles in shaping community structure, their importance relative to deterministic processes is hotly debated. The importance of ecological stochasticity in shaping microbial community structure is far less appreciated. Some of the main reasons for such heavy debates are the difficulty in defining stochasticity and the diverse methods used for delineating stochasticity. Here, we provide a critical review and synthesis of data from the most recent studies on stochastic community assembly in microbial ecology. We then describe both stochastic and deterministic components embedded in various ecological processes, including selection, dispersal, diversification, and drift. We also describe different approaches for inferring stochasticity from observational diversity patterns and highlight experimental approaches for delineating ecological stochasticity in microbial communities. In addition, we highlight research challenges, gaps, and future directions for microbial community assembly research. Copyright © 2017 American Society for Microbiology.
Multiscale understanding of tricalcium silicate hydration reactions.
Cuesta, Ana; Zea-Garcia, Jesus D; Londono-Zuluaga, Diana; De la Torre, Angeles G; Santacruz, Isabel; Vallcorba, Oriol; Dapiaggi, Monica; Sanfélix, Susana G; Aranda, Miguel A G
2018-06-04
Tricalcium silicate, the main constituent of Portland cement, hydrates to produce crystalline calcium hydroxide and calcium-silicate-hydrates (C-S-H) nanocrystalline gel. This hydration reaction is poorly understood at the nanoscale. The understanding of atomic arrangement in nanocrystalline phases is intrinsically complicated and this challenge is exacerbated by the presence of additional crystalline phase(s). Here, we use calorimetry and synchrotron X-ray powder diffraction to quantitatively follow tricalcium silicate hydration process: i) its dissolution, ii) portlandite crystallization and iii) C-S-H gel precipitation. Chiefly, synchrotron pair distribution function (PDF) allows to identify a defective clinotobermorite, Ca 11 Si 9 O 28 (OH) 2 . 8.5H 2 O, as the nanocrystalline component of C-S-H. Furthermore, PDF analysis also indicates that C-S-H gel contains monolayer calcium hydroxide which is stretched as recently predicted by first principles calculations. These outcomes, plus additional laboratory characterization, yielded a multiscale picture for C-S-H nanocomposite gel which explains the observed densities and Ca/Si atomic ratios at the nano- and meso- scales.
Centromeres and kinetochores of Brassicaceae.
Lermontova, Inna; Sandmann, Michael; Demidov, Dmitri
2014-06-01
The centromere-the primary constriction of monocentric chromosomes-is essential for correct segregation of chromosomes during mitosis and meiosis. Centromeric DNA varies between different organisms in sequence composition and extension. The main components of centromeric and pericentromeric DNA of Brassicaceae species are centromeric satellite repeats. Centromeric DNA initiates assembly of the kinetochore, the large protein complex where the spindle fibers attach during nuclear division to pull sister chromatids apart. Kinetochore assembly is initiated by incorporation of the centromeric histone H3 cenH3 into centromeric nucleosomes. The spindle assembly checkpoint acts during mitosis and meiosis at centromeres and maintains genome stability by preventing chromosome segregation before all kinetochores are correctly attached to microtubules. The function of the spindle assembly checkpoint in plants is still poorly understood. Here, we review recent advances of studies on structure and functional importance of centromeric DNA of Brassicaceae, assembly and function of cenH3 in Arabidopsis thaliana and characterization of core SAC proteins of A. thaliana in comparison with non-plant homologues.
Hippo signaling regulates Microprocessor and links cell density-dependent miRNA biogenesis to cancer
Mori, Masaki; Triboulet, Robinson; Mohseni, Morvarid; Schlegelmilch, Karin; Shrestha, Kriti; Camargo, Fernando D.; Gregory, Richard I.
2014-01-01
SUMMARY Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. PMID:24581491
BLOC-1 is required for selective membrane protein trafficking from endosomes to primary cilia
2017-01-01
Primary cilia perceive the extracellular environment through receptors localized in the ciliary membrane, but mechanisms directing specific proteins to this domain are poorly understood. To address this question, we knocked down proteins potentially important for ciliary membrane targeting and determined how this affects the ciliary trafficking of fibrocystin, polycystin-2, and smoothened. Our analysis showed that fibrocystin and polycystin-2 are dependent on IFT20, GMAP210, and the exocyst complex, while smoothened delivery is largely independent of these components. In addition, we found that polycystin-2, but not smoothened or fibrocystin, requires the biogenesis of lysosome-related organelles complex-1 (BLOC-1) for ciliary delivery. Consistent with the role of BLOC-1 in sorting from the endosome, we find that disrupting the recycling endosome reduces ciliary polycystin-2 and causes its accumulation in the recycling endosome. This is the first demonstration of a role for BLOC-1 in ciliary assembly and highlights the complexity of pathways taken to the cilium. PMID:28576874
Helicobacter pylori shows asymmetric and polar cell divisome assembly associated with DNA replisome.
Kamran, Mohammad; Dubey, Priyanka; Verma, Vijay; Dasgupta, Santanu; Dhar, Suman K
2018-05-09
DNA replication and cell division are two fundamental processes in the life cycle of a cell. The majority of prokaryotic cells undergo division by means of binary fission in coordination with replication of the genome. Both processes, but especially their coordination, are poorly understood in Helicobacter pylori. Here, we studied the cell divisome assembly and the subsequent processes of membrane and peptidoglycan synthesis in the bacterium. To our surprise, we found the cell divisome assembly to be polar, which was well-corroborated by the asymmetric membrane and peptidoglycan synthesis at the poles. The divisome components showed its assembly to be synchronous with that of the replisome and the two remained associated throughout the cell cycle, demonstrating a tight coordination among chromosome replication, segregation and cell division in H. pylori. To our knowledge, this is the first report where both DNA replication and cell division along with their possible association have been demonstrated for this pathogenic bacterium. © 2018 Federation of European Biochemical Societies.
Yu, Shan; Su, Tiantian; Wu, Huijun; Liu, Shiheng; Wang, Di; Zhao, Tianhu; Jin, Zengjun; Du, Wenbin; Zhu, Mei-Jun; Chua, Song Lin; Yang, Liang; Zhu, Deyu; Gu, Lichuan; Ma, Luyan Z
2015-12-01
Biofilms are surface-associated communities of microorganism embedded in extracellular matrix. Exopolysaccharide is a critical component in the extracellular matrix that maintains biofilm architecture and protects resident biofilm bacteria from antimicrobials and host immune attack. However, self-produced factors that target the matrix exopolysaccharides, are still poorly understood. Here, we show that PslG, a protein involved in the synthesis of a key biofilm matrix exopolysaccharide Psl in Pseudomonas aeruginosa, prevents biofilm formation and disassembles existing biofilms within minutes at nanomolar concentrations when supplied exogenously. The crystal structure of PslG indicates the typical features of an endoglycosidase. PslG mainly disrupts the Psl matrix to disperse bacteria from biofilms. PslG treatment markedly enhances biofilm sensitivity to antibiotics and macrophage cells, resulting in improved biofilm clearance in a mouse implant infection model. Furthermore, PslG shows biofilm inhibition and disassembly activity against a wide range of Pseudomonas species, indicating its great potential in combating biofilm-related complications.
Hoogenraad, Casper C.; Popa, Ioana; Futai, Kensuke; Sanchez-Martinez, Emma; Wulf, Phebe S.; van Vlijmen, Thijs; Dortland, Bjorn R.; Oorschot, Viola; Govers, Roland; Monti, Maria; Heck, Albert J. R.; Sheng, Morgan; Klumperman, Judith; Rehmann, Holger; Jaarsma, Dick; Kapitein, Lukas C.; van der Sluijs, Peter
2010-01-01
The endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function and plasticity. However, the molecular mechanisms that organize specific endocytic trafficking routes are poorly understood. Here, we identify GRIP-associated protein-1 (GRASP-1) as a neuron-specific effector of Rab4 and key component of the molecular machinery that coordinates recycling endosome maturation in dendrites. We show that GRASP-1 is necessary for AMPA receptor recycling, maintenance of spine morphology, and synaptic plasticity. At the molecular level, GRASP-1 segregates Rab4 from EEA1/Neep21/Rab5-positive early endosomal membranes and coordinates the coupling to Rab11-labelled recycling endosomes by interacting with the endosomal SNARE syntaxin 13. We propose that GRASP-1 connects early and late recycling endosomal compartments by forming a molecular bridge between Rab-specific membrane domains and the endosomal SNARE machinery. The data uncover a new mechanism to achieve specificity and directionality in neuronal membrane receptor trafficking. PMID:20098723
Zhao, Yanmei; Sun, Wei; Zhang, Pan; Chi, Hao; Zhang, Mei-Jun; Song, Chun-Qing; Ma, Xuan; Shang, Yunlong; Wang, Bin; Hu, Youqiao; Hao, Zhiqi; Hühmer, Andreas F.; Meng, Fanxia; L'Hernault, Steven W.; He, Si-Min; Dong, Meng-Qiu; Miao, Long
2012-01-01
Spermiogenesis is a series of poorly understood morphological, physiological and biochemical processes that occur during the transition of immotile spermatids into motile, fertilization-competent spermatozoa. Here, we identified a Serpin (serine protease inhibitor) family protein (As_SRP-1) that is secreted from spermatids during nematode Ascaris suum spermiogenesis (also called sperm activation) and we showed that As_SRP-1 has two major functions. First, As_SRP-1 functions in cis to support major sperm protein (MSP)-based cytoskeletal assembly in the spermatid that releases it, thereby facilitating sperm motility acquisition. Second, As_SRP-1 released from an activated sperm inhibits, in trans, the activation of surrounding spermatids by inhibiting vas deferens-derived As_TRY-5, a trypsin-like serine protease necessary for sperm activation. Because vesicular exocytosis is necessary to create fertilization-competent sperm in many animal species, components released during this process might be more important modulators of the physiology and behavior of surrounding sperm than was previously appreciated. PMID:22307610
Waqa, Gade; Mavoa, Helen
2006-09-01
Few studies have addressed Sociocultural factors underlying healthy lifestyles. The Sociocultural component of the Obesity Prevention in Communities (OPIC) project explores social and cultural factors that may promote or protect against obesity via adolescents' values, attitudes, beliefs and explanations for their patterns of eating and physical activity, as well as preferred body size. This paper reports on semi-structured interviews conducted with a sub-sample of indigenous Fijian females in terms of their descriptions of and explanations for their at-school eating patterns. While participants understood which foods and drinks were healthy, many skipped breakfast, and ate junk at recess and after school. The main reasons for these unhealthy eating patterns were poor time management in the mornings, and access to discretionary spending money for junk food. Participants cited family members and friends as key influences on their eating patterns. Findings were used to develop intervention strategies to encourage the regular consumption of healthy food at home and at school.
Drosophila Perlecan Regulates Intestinal Stem Cell Activity via Cell-Matrix Attachment
You, Jia; Zhang, Yan; Li, Zhouhua; Lou, Zhefeng; Jin, Longjin; Lin, Xinhua
2014-01-01
Summary Stem cells require specialized local microenvironments, termed niches, for normal retention, proliferation, and multipotency. Niches are composed of cells together with their associated extracellular matrix (ECM). Currently, the roles of ECM in regulating niche functions are poorly understood. Here, we demonstrate that Perlecan (Pcan), a highly conserved ECM component, controls intestinal stem cell (ISC) activities and ISC-ECM attachment in Drosophila adult posterior midgut. Loss of Pcan from ISCs, but not other surrounding cells, causes ISCs to detach from underlying ECM, lose their identity, and fail to proliferate. These defects are not a result of a loss of epidermal growth factor receptor (EGFR) or Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling activity but partially depend on integrin signaling activity. We propose that Pcan secreted by ISCs confers niche properties to the adjacent ECM that is required for ISC maintenance of stem cell identity, activity, and anchorage to the niche. PMID:24936464
ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2
Jain, Devanshi; Puno, M Rhyan; Meydan, Cem; Lailler, Nathalie; Mason, Christopher E; Lima, Christopher D; Anderson, Kathryn V
2018-01-01
Mechanisms regulating mammalian meiotic progression are poorly understood. Here we identify mouse YTHDC2 as a critical component. A screen yielded a sterile mutant, ‘ketu’, caused by a Ythdc2 missense mutation. Mutant germ cells enter meiosis but proceed prematurely to aberrant metaphase and apoptosis, and display defects in transitioning from spermatogonial to meiotic gene expression programs. ketu phenocopies mutants lacking MEIOC, a YTHDC2 partner. Consistent with roles in post-transcriptional regulation, YTHDC2 is cytoplasmic, has 3′→5′ RNA helicase activity in vitro, and has similarity within its YTH domain to an N6-methyladenosine recognition pocket. Orthologs are present throughout metazoans, but are diverged in nematodes and, more dramatically, Drosophilidae, where Bgcn is descended from a Ythdc2 gene duplication. We also uncover similarity between MEIOC and Bam, a Bgcn partner unique to schizophoran flies. We propose that regulation of gene expression by YTHDC2-MEIOC is an evolutionarily ancient strategy for controlling the germline transition into meiosis. PMID:29360036
MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome
Siew, Wei-Hong; Tan, Kai-Leng; Babaei, Maryam Abbaspour; Cheah, Pike-See; Ling, King-Hwa
2013-01-01
Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395
Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases
Bencherif, Merouane; Lippiello, Patrick M.; Lucas, Rudolf; Marrero, Mario B.
2013-01-01
In recent years the etiopathology of a number of debilitating diseases such as type 2 diabetes, arthritis, atherosclerosis, psoriasis, asthma, cystic fibrosis, sepsis, and ulcerative colitis has increasingly been linked to runaway cytokine-mediated inflammation. Cytokine-based therapeutic agents play a major role in the treatment of these diseases. However, the temporospatial changes in various cytokines are still poorly understood and attempts to date have focused on the inhibition of specific cytokines such as TNF-α. As an alternative approach, a number of preclinical studies have confirmed the therapeutic potential of targeting alpha7 nicotinic acetylcholine receptor-mediated anti-inflammatory effects through modulation of proinflammatory cytokines. This “cholinergic anti-inflammatory pathway” modulates the immune system through cholinergic mechanisms that act on alpha7 receptors expressed on macrophages and immune cells. If the preclinical findings translate into human efficacy this approach could potentially provide new therapies for treating a broad array of intractable diseases and conditions with inflammatory components. PMID:20953658
Ávila, Andréa Rodrigues; Cabezas-Cruz, Alexjandro; Gissot, Mathieu
2018-01-25
Control of gene expression is crucial for parasite survival and is the result of a series of processes that are regulated to permit fine-tuning of gene expression in response to biological changes during the life-cycle of apicomplexan parasites. Control of mRNA nuclear export is a key process in eukaryotic cells but is poorly understood in apicomplexan parasites. Here, we review recent knowledge regarding this process with an emphasis on T. gondii. We describe the presence of divergent orthologs and discuss structural and functional differences in export factors between apicomplexans and other eukaryotic lineages. Undoubtedly, the use of the CRISPR/Cas9 system in high throughput screenings associated with the discovery of mRNA nuclear export complexes by proteomic analysis will contribute to identify these divergent factors. Ligand-based or structure-based strategies may be applied to investigate the potential use of these proteins as targets for new antiprotozoal agents.
Kasamatsu, Shinya; Hachiya, Akira; Fujimura, Tsutomu; Sriwiriyanont, Penkanok; Haketa, Keiichi; Visscher, Marty O.; Kitzmiller, William J.; Bello, Alexander; Kitahara, Takashi; Kobinger, Gary P.; Takema, Yoshinori
2011-01-01
UVB-induced cutaneous photodamage/photoaging is characterized by qualitative and quantitative deterioration in dermal extracellular matrix (ECM) components such as collagen and elastic fibers. Disappearance of microfibrillar-associated protein 4 (MFAP-4), a possible limiting factor for cutaneous elasticity, was documented in photoaged dermis, but its function is poorly understood. To characterize its possible contribution to photoprotection, MFAP-4 expression was either augmented or inhibited in a human skin xenograft photodamage murine model and human fibroblasts. Xenografted skin with enhanced MFAP-4 expression was protected from UVB-induced photodamage/photoaging accompanied by the prevention of ECM degradation and aggravated elasticity. Additionally, remarkably increased or decreased fibrillin-1-based microfibril development was observed when fibroblasts were treated with recombinant MFAP-4 or with MFAP-4-specific siRNA, respectively. Immunoprecipitation analysis confirmed direct interaction between MFAP-4 and fibrillin-1. Taken together, our findings reveal the essential role of MFAP-4 in photoprotection and offer new therapeutic opportunities to prevent skin-associated pathologies. PMID:22355679
Yue, Siyao; Ren, Hong; Fan, Songyun; Sun, Yele; Wang, Zifa; Fu, Pingqing
2016-07-29
Bioaerosols and humic-like substances (HULIS) are important components of atmospheric aerosols, which can affect regional climate by acting as cloud condensation nuclei and some of which can damage human health. Up to date, release of bioaerosols and HULIS initiated by precipitation is still poorly understood. Here we present different release processes for bioaerosols, non-bioaerosols and HULIS during a precipitation event in Beijing, China. Large fungal-spore-like aerosols were emitted at the onset and later weak stage of precipitation, the number concentration of which increased by more than two folds, while the number concentration of bacteria-like particles doubled when the precipitation strengthened. Besides, a good correlation between protein-like substances that were measured simultaneously by on-line and off-line fluorescence techniques consolidated their applications to measure bioaerosols. Furthermore, our EEM results suggest that the relative contribution of water-soluble HULIS to microbial materials was enhanced gradually by the rain event.
Yue, Siyao; Ren, Hong; Fan, Songyun; Sun, Yele; Wang, Zifa; Fu, Pingqing
2016-01-01
Bioaerosols and humic-like substances (HULIS) are important components of atmospheric aerosols, which can affect regional climate by acting as cloud condensation nuclei and some of which can damage human health. Up to date, release of bioaerosols and HULIS initiated by precipitation is still poorly understood. Here we present different release processes for bioaerosols, non-bioaerosols and HULIS during a precipitation event in Beijing, China. Large fungal-spore-like aerosols were emitted at the onset and later weak stage of precipitation, the number concentration of which increased by more than two folds, while the number concentration of bacteria-like particles doubled when the precipitation strengthened. Besides, a good correlation between protein-like substances that were measured simultaneously by on-line and off-line fluorescence techniques consolidated their applications to measure bioaerosols. Furthermore, our EEM results suggest that the relative contribution of water-soluble HULIS to microbial materials was enhanced gradually by the rain event. PMID:27470588
NASA Astrophysics Data System (ADS)
Yue, Siyao; Ren, Hong; Fan, Songyun; Sun, Yele; Wang, Zifa; Fu, Pingqing
2016-07-01
Bioaerosols and humic-like substances (HULIS) are important components of atmospheric aerosols, which can affect regional climate by acting as cloud condensation nuclei and some of which can damage human health. Up to date, release of bioaerosols and HULIS initiated by precipitation is still poorly understood. Here we present different release processes for bioaerosols, non-bioaerosols and HULIS during a precipitation event in Beijing, China. Large fungal-spore-like aerosols were emitted at the onset and later weak stage of precipitation, the number concentration of which increased by more than two folds, while the number concentration of bacteria-like particles doubled when the precipitation strengthened. Besides, a good correlation between protein-like substances that were measured simultaneously by on-line and off-line fluorescence techniques consolidated their applications to measure bioaerosols. Furthermore, our EEM results suggest that the relative contribution of water-soluble HULIS to microbial materials was enhanced gradually by the rain event.
Allen, Victoria W; Shirasu-Hiza, Mimi
2018-01-01
Despite being pervasive, the control of programmed grooming is poorly understood. We addressed this gap by developing a high-throughput platform that allows long-term detection of grooming in Drosophila melanogaster. In our method, a k-nearest neighbors algorithm automatically classifies fly behavior and finds grooming events with over 90% accuracy in diverse genotypes. Our data show that flies spend ~13% of their waking time grooming, driven largely by two major internal programs. One of these programs regulates the timing of grooming and involves the core circadian clock components cycle, clock, and period. The second program regulates the duration of grooming and, while dependent on cycle and clock, appears to be independent of period. This emerging dual control model in which one program controls timing and another controls duration, resembles the two-process regulatory model of sleep. Together, our quantitative approach presents the opportunity for further dissection of mechanisms controlling long-term grooming in Drosophila. PMID:29485401
Cardiac Cachexia: Perspectives for Prevention and Treatment.
Okoshi, Marina Politi; Capalbo, Rafael Verardino; Romeiro, Fernando G; Okoshi, Katashi
2017-01-01
Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment.
RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs.
McClintock, Mark A; Dix, Carly I; Johnson, Christopher M; McLaughlin, Stephen H; Maizels, Rory J; Hoang, Ha Thi; Bullock, Simon L
2018-06-26
Polarised mRNA transport is a prevalent mechanism for spatial control of protein synthesis. However, the composition of transported ribonucleoprotein particles (RNPs) and the regulation of their movement are poorly understood. We have reconstituted microtubule minus end-directed transport of mRNAs using purified components. A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin, thus defining a minimal transport-competent RNP. Unexpectedly, the RNA is required for robust activation of dynein motility. We show that a cis -acting RNA localisation signal promotes the interaction of Egl with BicD, which licenses the latter protein to recruit dynein and dynactin. Our data support a model for BicD activation based on RNA-induced occupancy of two Egl-binding sites on the BicD dimer. Scaffolding of adaptor protein assemblies by cargoes is an attractive mechanism for regulating intracellular transport. © 2018, McClintock et al.
Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex.
Lee, Kwangkook; Zhong, Xiaofen; Gu, Shenyan; Kruel, Anna Magdalena; Dorner, Martin B; Perry, Kay; Rummel, Andreas; Dong, Min; Jin, Rongsheng
2014-06-20
How botulinum neurotoxins (BoNTs) cross the host intestinal epithelial barrier in foodborne botulism is poorly understood. Here, we present the crystal structure of a clostridial hemagglutinin (HA) complex of serotype BoNT/A bound to the cell adhesion protein E-cadherin at 2.4 angstroms. The HA complex recognizes E-cadherin with high specificity involving extensive intermolecular interactions and also binds to carbohydrates on the cell surface. Binding of the HA complex sequesters E-cadherin in the monomeric state, compromising the E-cadherin-mediated intercellular barrier and facilitating paracellular absorption of BoNT/A. We reconstituted the complete 14-subunit BoNT/A complex using recombinantly produced components and demonstrated that abolishing either E-cadherin- or carbohydrate-binding of the HA complex drastically reduces oral toxicity of BoNT/A complex in vivo. Together, these studies establish the molecular mechanism of how HAs contribute to the oral toxicity of BoNT/A. Copyright © 2014, American Association for the Advancement of Science.
Interlocked feedforward loops control cell-type-specific Rhodopsin expression in the Drosophila eye.
Johnston, Robert J; Otake, Yoshiaki; Sood, Pranidhi; Vogt, Nina; Behnia, Rudy; Vasiliauskas, Daniel; McDonald, Elizabeth; Xie, Baotong; Koenig, Sebastian; Wolf, Reinhard; Cook, Tiffany; Gebelein, Brian; Kussell, Edo; Nakagoshi, Hideki; Desplan, Claude
2011-06-10
How complex networks of activators and repressors lead to exquisitely specific cell-type determination during development is poorly understood. In the Drosophila eye, expression patterns of Rhodopsins define at least eight functionally distinct though related subtypes of photoreceptors. Here, we describe a role for the transcription factor gene defective proventriculus (dve) as a critical node in the network regulating Rhodopsin expression. dve is a shared component of two opposing, interlocked feedforward loops (FFLs). Orthodenticle and Dve interact in an incoherent FFL to repress Rhodopsin expression throughout the eye. In R7 and R8 photoreceptors, a coherent FFL relieves repression by Dve while activating Rhodopsin expression. Therefore, this network uses repression to restrict and combinatorial activation to induce cell-type-specific expression. Furthermore, Dve levels are finely tuned to yield cell-type- and region-specific repression or activation outcomes. This interlocked FFL motif may be a general mechanism to control terminal cell-fate specification. Copyright © 2011 Elsevier Inc. All rights reserved.
Diversity of sharp-wave-ripple LFP signatures reveals differentiated brain-wide dynamical events.
Ramirez-Villegas, Juan F; Logothetis, Nikos K; Besserve, Michel
2015-11-17
Sharp-wave-ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R-triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions.
Diversity of sharp-wave–ripple LFP signatures reveals differentiated brain-wide dynamical events
Ramirez-Villegas, Juan F.; Logothetis, Nikos K.; Besserve, Michel
2015-01-01
Sharp-wave–ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R–triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions. PMID:26540729
Bieling, Peter; Li, Tai-De; Weichsel, Julian; McGorty, Ryan; Jreij, Pamela; Huang, Bo; Fletcher, Daniel A.; Mullins, R. Dyche
2016-01-01
Branched actin networks–created by the Arp2/3 complex, capping protein, and a nucleation promoting factor– generate and transmit forces required for many cellular processes, but their response to force is poorly understood. To address this, we assembled branched actin networks in vitro from purified components and used simultaneous fluorescence and atomic force microscopy to quantify their molecular composition and material properties under various forces. Remarkably, mechanical loading of these self-assembling materials increases their density, power, and efficiency. Microscopically, increased density reflects increased filament number and altered geometry, but no change in average length. Macroscopically, increased density enhances network stiffness and resistance to mechanical failure beyond those of isotropic actin networks. These effects endow branched actin networks with memory of their mechanical history that shapes their material properties and motor activity. This work reveals intrinsic force feedback mechanisms by which mechanical resistance makes self-assembling actin networks stiffer, stronger, and more powerful. PMID:26771487
Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling
Durak, Omer; Gao, Fan; Kaeser-Woo, Yea Jin; Rueda, Richard; Martorell, Anthony J.; Nott, Alexi; Liu, Carol Y.; Watson, L. Ashley; Tsai, Li-Huei
2016-01-01
De novo mutations in CHD8 are strongly associated with autism spectrum disorder (ASD), however the basic biology of CHD8 remains poor understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that while Chd8 stimulates the transcription of cell cycle genes, it also precludes the induction of neural specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of Chd8 expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the neurodevelopmental role of Chd8. PMID:27694995
Dobson, Philip F; Rocha, Mariana C; Grady, John P; Chrysostomou, Alexia; Hipps, Daniel; Watson, Sharon; Greaves, Laura C; Deehan, David J; Turnbull, Doug M
2016-08-24
Fragility fractures caused by osteoporosis affect millions of people worldwide every year with significant levels of associated morbidity, mortality and costs to the healthcare economy. The pathogenesis of declining bone mineral density is poorly understood but it is inherently related to increasing age. Growing evidence in recent years, especially that provided by mouse models, suggest that accumulating somatic mitochondrial DNA mutations may cause the phenotypic changes associated with the ageing process including osteoporosis. Methods to study mitochondrial abnormalities in individual osteoblasts, osteoclasts and osteocytes are limited and impair our ability to assess the changes seen with age and in animal models of ageing. To enable the assessment of mitochondrial protein levels, we have developed a quadruple immunofluorescence method to accurately quantify the presence of mitochondrial respiratory chain components within individual bone cells. We have applied this technique to a well-established mouse model of ageing and osteoporosis and show respiratory chain deficiency.
Inflammation and wound healing: The role of the macrophage
Koh, Timothy J.; DiPietro, Luisa Ann
2013-01-01
The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have been described to have many functions in wounds, including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound, and that the influence of these cells on each stage of repair varies with the specific phenotypes. While the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation and/or fibrosis in certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing and poorly healing wounds. Due to advances in the understanding of this multi-functional cell, the macrophage continues to be an attractive therapeutic target both to reduce fibrosis and scarring, and to improve healing of chronic wounds. PMID:21740602
Yu, Qian; Xiong, Youhua; Gao, Hang; Liu, Jianliang; Chen, Zhiqiang; Wang, Qin; Wen, Dongling
2015-08-04
Increasing evidence sugggest that in addition of balculovirus controling insect host, host cells also responds to balculovirus infection. However, compared to existing knowledge on virus gene, host cell responses are relatively poorly understood. In this study, Spodoptera frugiperda (Sf9) cells were infected with Autographa californica multiple nucleopolyhedrovirus (AcMNPV). The protein composition and protein changes of Spodoptera frugiperda (Sf9) cells of different infection stages were analysed by isobaric tag for relative and absolute quantification (iTRAQ) techniques. A total of 4004 Sf9 proteins were identified by iTRAQ and 413 proteins were found as more than 1.5-fold changes in abundance. The 413 proteins were categorised according to GO classification for insects and were categorised into: biological process, molecular function and cellular component. The determination of the protein changes in infected Sf9 cells would help to better understanding of host cell responses and facilitate better design of this virus-host cell interaction in pest insect control and other related fields.
A method for multiprotein assembly in cells reveals independent action of kinesins in complex
Norris, Stephen R.; Soppina, Virupakshi; Dizaji, Aslan S.; Schimert, Kristin I.; Sept, David; Cai, Dawen; Sivaramakrishnan, Sivaraj
2014-01-01
Teams of processive molecular motors are critical for intracellular transport and organization, yet coordination between motors remains poorly understood. Here, we develop a system using protein components to generate assemblies of defined spacing and composition inside cells. This system is applicable to studying macromolecular complexes in the context of cell signaling, motility, and intracellular trafficking. We use the system to study the emergent behavior of kinesin motors in teams. We find that two kinesin motors in complex act independently (do not help or hinder each other) and can alternate their activities. For complexes containing a slow kinesin-1 and fast kinesin-3 motor, the slow motor dominates motility in vitro but the fast motor can dominate on certain subpopulations of microtubules in cells. Both motors showed dynamic interactions with the complex, suggesting that motor–cargo linkages are sensitive to forces applied by the motors. We conclude that kinesin motors in complex act independently in a manner regulated by the microtubule track. PMID:25365993
Grahl, Nora; Dinamarco, Taisa Magnani; Willger, Sven D; Goldman, Gustavo H; Cramer, Robert A
2012-04-01
We previously observed that hypoxia is an important component of host microenvironments during pulmonary fungal infections. However, mechanisms of fungal growth in these in vivo hypoxic conditions are poorly understood. Here, we report that mitochondrial respiration is active in hypoxia (1% oxygen) and critical for fungal pathogenesis. We generated Aspergillus fumigatus alternative oxidase (aoxA) and cytochrome C (cycA) null mutants and assessed their ability to tolerate hypoxia, macrophage killing and virulence. In contrast to ΔaoxA, ΔcycA was found to be significantly impaired in conidia germination, growth in normoxia and hypoxia, and displayed attenuated virulence. Intriguingly, loss of cycA results in increased levels of AoxA activity, which results in increased resistance to oxidative stress, macrophage killing and long-term persistence in murine lungs. Thus, our results demonstrate a previously unidentified role for fungal mitochondrial respiration in the pathogenesis of aspergillosis, and lay the foundation for future research into its role in hypoxia signalling and adaptation. © 2012 Blackwell Publishing Ltd.
Extraordinary phylogenetic diversity and metabolic versatility in aquifer sediment
Castelle, Cindy J.; Hug, Laura A.; Wrighton, Kelly C.; ...
2013-08-27
Microorganisms in the subsurface represent a substantial but poorly understood component of the Earth’s biosphere. Subsurface environments are complex and difficult to characterize; thus, their microbiota have remained as a ‘dark matter’ of the carbon and other biogeochemical cycles. Here we deeply sequence two sediment-hosted microbial communities from an aquifer adjacent to the Colorado River, CO, USA. No single organism represents more than ~1% of either community. Remarkably, many bacteria and archaea in these communities are novel at the phylum level or belong to phyla lacking a sequenced representative. The dominant organism in deeper sediment, RBG-1, is a member ofmore » a new phylum. On the basis of its reconstructed complete genome, RBG-1 is metabolically versatile. Its wide respiration-based repertoire may enable it to respond to the fluctuating redox environment close to the water table. We document extraordinary microbial novelty and the importance of previously unknown lineages in sediment biogeochemical transformations.« less
Häcker, Georg
2017-11-04
Apoptosis is one of the principal responses that human cells have at their disposal when faced with changes in their environment. Microbial infection is a massive challenge to a cell, and it is unsurprising that the apoptosis apparatus has been implicated in numerous infections. However, looking at the available data, the impression is one of bewildering complexity. Microbial proteins and other molecules that are often poorly understood interact, with uncertain specificity, with host cell components of varying function, triggering signalling pathways that are ambiguously linked to the apoptotic machinery. Accordingly, many pathogens have been found in different studies both to induce and to inhibit apoptosis. I will here try to present some of the principles of apoptosis and of infection, and to provide a viewpoint on the question how the two are linked. I will further give the reasons for my personal opinion that apoptosis-induction is in most infections beneficial to the host. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Microbial Ecology in Vineyards
USDA-ARS?s Scientific Manuscript database
Soil health affects grapevine health, which, in turn, affects fruit quality. Soil health has chemical, physical, and biological components. The chemical components are the best understood, and there are relatively convenient methods to both evaluate and amend chemical soil fertility. The physical...
In situ observation of stishovite formation in shock-compressed fused silica
NASA Astrophysics Data System (ADS)
Tracy, Sally June; Turneaure, Stefan; Duffy, Thomas
2017-06-01
Silica, SiO2, has widespread applications ranging from optical components to refractory materials and is of geological importance as one of the major oxide components of the Earth's crust and mantle. The response of silica phases to dynamic loading has long been of interest for understanding the structural evolution of this fundamental oxide. Under shock compression both crystalline quartz and fused silica are characterized by the occurrence of a broad `mixed-phase region' (15-40 GPa) and a dense, high-pressure phase with much lower compressibility. Despite decades of study, the nature of this transformation and the identity of the high-pressure phase(s) remain poorly understood. In situ x-ray diffraction experiments on shock-compressed fused silica were conducted at the Dynamic Compression Sector of the Advanced Photon Source. The lattice-level structure was investigated through time-resolved x-ray diffraction measurements on samples reaching peak stress ranging from 12 to 47 GPa. Our results demonstrate that SiO2 adopts a dense amorphous structure in the `mixed-phase region' and abruptly transforms to stishovite above 34 GPa. These results provide clear evidence that high-pressure crystalline silicate phases can form from amorphous starting materials on the time-scale of laboratory shock experiments.
Verly, Marjolein; Verhoeven, Judith; Zink, Inge; Mantini, Dante; Peeters, Ronald; Deprez, Sabine; Emsell, Louise; Boets, Bart; Noens, Ilse; Steyaert, Jean; Lagae, Lieven; De Cock, Paul; Rommel, Nathalie; Sunaert, Stefan
2014-01-01
The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI. PMID:24567909
NASA Technical Reports Server (NTRS)
Schredder, J. M.; Fujita, T.
1984-01-01
The use of reversible chemical reactions for energy transport and storage for parabolic dish networks is considered. Performance and cost characteristics are estimated for systems using three reactions (sulfur-trioxide decomposition, steam reforming of methane, and carbon-dioxide reforming of methane). Systems are considered with and without storage, and in several energy-delivery configurations that give different profiles of energy delivered versus temperature. Cost estimates are derived assuming the use of metal components and of advanced ceramics. (The latter reduces the costs by three- to five-fold). The process that led to the selection of the three reactions is described, and the effects of varying temperatures, pressures, and heat exchanger sizes are addressed. A state-of-the-art survey was performed as part of this study. As a result of this survey, it appears that formidable technical risks exist for any attempt to implement the systems analyzed in this study, especially in the area of reactor design and performance. The behavior of all components and complete systems under thermal energy transients is very poorly understood. This study indicates that thermochemical storage systems that store reactants as liquids have efficiencies below 60%, which is in agreement with the findings of earlier investigators.
Wang, Jun-Jian; Guo, Ying-Ying; Guo, Da-Li; Yin, Sen-Lu; Kong, De-Liang; Liu, Yang-Sheng; Zeng, Hui
2012-01-17
Fine roots are critical components for plant mercury (Hg) uptake and removal, but the patterns of Hg distribution and turnover within the heterogeneous fine root components and their potential limiting factors are poorly understood. Based on root branching structure, we studied the total Hg (THg) and its cellular partitioning in fine roots in 6 Chinese subtropical trees species and the impacts of root morphological and stoichiometric traits on Hg partitioning. The THg concentration generally decreased with increasing root order, and was higher in cortex than in stele. This concentration significantly correlated with root length, diameter, specific root length, specific root area, and nitrogen concentration, whereas its cytosolic fraction (accounting for <10% of THg) correlated with root carbon and sulfur concentrations. The estimated Hg return flux from dead fine roots outweighed that from leaf litter, and ephemeral first-order roots that constituted 7.2-22.3% of total fine root biomass may have contributed most to this flux (39-71%, depending on tree species and environmental substrate). Our results highlight the high capacity of Hg stabilization and Hg return by lower-order roots and demonstrate that turnover of lower-order roots may be an effective strategy of detoxification in perennial tree species.
Hartwright, Charlotte E; Apperly, Ian A; Hansen, Peter C
2012-07-16
Belief-desire reasoning is a core component of 'Theory of Mind' (ToM), which can be used to explain and predict the behaviour of agents. Neuroimaging studies reliably identify a network of brain regions comprising a 'standard' network for ToM, including temporoparietal junction and medial prefrontal cortex. Whilst considerable experimental evidence suggests that executive control (EC) may support a functioning ToM, co-ordination of neural systems for ToM and EC is poorly understood. We report here use of a novel task in which psychologically relevant ToM parameters (true versus false belief; approach versus avoidance desire) were manipulated orthogonally. The valence of these parameters not only modulated brain activity in the 'standard' ToM network but also in EC regions. Varying the valence of both beliefs and desires recruits anterior cingulate cortex, suggesting a shared inhibitory component associated with negatively valenced mental state concepts. Varying the valence of beliefs additionally draws on ventrolateral prefrontal cortex, reflecting the need to inhibit self perspective. These data provide the first evidence that separate functional and neural systems for EC may be recruited in the service of different aspects of ToM. Copyright © 2012 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Wenyao; Li, Xuezhong; Xu, Tong
Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferationmore » and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.« less
Age- and cohort-related variance of type-A behavior over 24 years: the Young Finns Study.
Hintsa, Taina; Jokela, Markus; Pulkki-Råback, Laura; Keltikangas-Järvinen, Liisa
2014-12-01
Over the recent decades, the incidence of cardiovascular and heart diseases has decreased while levels of type-A behavior, i.e., a potential risk factor, appear to have increased. However, the long-term developmental patterns of type-A behavior is poorly understood. Both age- and cohort-related changes may be involved in these developments. The purpose of this study was to examine an age- and cohort-related changes of Hunter-Wolf type-A behavior from adolescence to adulthood. Type-A behavior and its components (aggressiveness, leadership, hard driving, and eagerness energy) were assessed using the Hunter-Wolf A-B rating scale at five time points (1983, 1986, 1989, 2001, and 2007) in a population-based sample consisting of six birth cohorts born between 1962 and 1977 (n = 3,341, a total of 10,506 person observations). Development of type-A behavior and its components was examined with cohort-sequential multilevel modeling. Aggressiveness decreased with age, eagerness energy, hard driving, and global type-A behavior increased, and leadership exhibited no mean level changes. Younger cohorts had higher aggressiveness, lower hard driving, and global type-A behavior. The findings suggest that in order to understand the health consequences of type-A behavior, both life span and societal changes should be considered.
Qian, Zhengyue; Huang, Cheng; Shen, Chenlin; Meng, Xiaoming; Chen, Zhaolin; Hu, Tingting; Li, Yangyang; Li, Jun
2016-08-01
1. Although emerging evidence indicates the therapeutic effects of Zhizi Bopi Decoction, the extent to which essential ingredients are absorbed and the possible synergistic actions are poorly understood. 2. In this study, MDCK cell model was used to determine the bi-directional permeability and interaction between the main components (geniposide, berberine and glycyrrhizic acid) of Zhizi Bopi Decoction. 3. The transport of the active ingredients was concentration-dependent in both directions. Moreover, the Papp (AP-BL) values of berberine and glycyrrhizic acid were significantly reduced when co-incubation with an ATP inhibitor. Additionally, uptake of berberine, glycyrrhizic acid were clearly inhibited by the inhibitors of P-glycoprotein and MRP2, indicating that P-gp and MRP2 may be involved in the transport of berberine and glycyrrhizic acid, respectively. However, it was found that geniposide may be purely passive diffusion. Furthermore, the combined incubation of geniposide with berberine and glycyrrhizic acid had a powerful sorbefacient effect than use of a single drug alone which may be regulated by tight junctions. 4. In summary, our study provides useful information for pharmacological applications of Zhizi Bopi Decoction and offers new insights into this ancient decoction for further researches, especially in drug synergism.
Trust and doubt, an examination of children's decision to believe what they are told about food
Nguyen, Simone P.; Gordon, Cameron L.; Chevalier, Tess; Girgis, Helena
2016-01-01
The domain of food is one that is highly relevant and vital to the everyday lives of children. However, children's reasoning about this domain is poorly understood within the field of developmental psychology. Because children's learning about food, including its evaluative components (e.g., health, taste) is so heavily dependent upon information conveyed by other people, a major developmental challenge that children face is determining who to distrust regarding food. In three studies, this investigation examined how 3- to 4-year-olds and adults (N = 312) use different cues to determine when to ignore informant information (i.e., distrust what an informant tells them by choosing an alternative) in food- and nonfood-specific scenarios. The results of Study 1 indicated that by age 4, children are less trusting of inaccurate sources of information compared with sources that have not demonstrated previous inaccuracy. Study 2 revealed that these results are applicable across the domain of objects. The results of Study 3 indicated that by age 4, children trust benevolent sources more often than malevolent ones. Thus, when reasoning about the evaluative components of food, by age 4, children appraise other people's untrustworthiness by paying attention to their inaccuracy and malevolence. PMID:26704303
A Method to Test the Effect of Environmental Cues on Mating Behavior in Drosophila melanogaster.
Gorter, Jenke A; Billeter, Jean-Christophe
2017-07-17
An individual's sexual drive is influenced by genotype, experience and environmental conditions. How these factors interact to modulate sexual behaviors remains poorly understood. In Drosophila melanogaster, environmental cues, such as food availability, affect mating activity offering a tractable system to investigate the mechanisms modulating sexual behavior. In D. melanogaster, environmental cues are often sensed via the chemosensory gustatory and olfactory systems. Here, we present a method to test the effect of environmental chemical cues on mating behavior. The assay consists of a small mating arena containing food medium and a mating couple. The mating frequency for each couple is continuously monitored for 24 h. Here we present the applicability of this assay to test environmental compounds from an external source through a pressurized air system as well as manipulation of the environmental components directly in the mating arena. The use of a pressurized air system is especially useful to test the effect of very volatile compounds, while manipulating components directly in the mating arena can be of value to ascertain a compound's presence. This assay can be adapted to answer questions about the influence of genetic and environmental cues on mating behavior and fecundity as well as other male and female reproductive behaviors.
Interaction of miltefosine with the lipid and protein components of the erythrocyte membrane.
Moreira, Rodrigo Alves; Mendanha, Sebastião Antonio; Hansen, Daiane; Alonso, Antonio
2013-05-01
Miltefosine (MT) is an alkylphospholipid that has been approved for the treatment of breast cancer metastasis and visceral leishmaniasis, although its mechanism of action remains poorly understood. Electron paramagnetic resonance spectroscopy of a spin-labeled lipid and a thiol-specific spin label showed that MT causes an increase in the molecular dynamics of erythrocyte ghost membranes and detergent-resistant membranes (DRMs) prepared from erythrocyte ghosts. In the vesicles of lipid raft constituents, it was shown that 20 mol % sphingomyelin could be replaced by 20 mol % MT with no change in the molecular dynamics. The effect of MT in DRMs was more pronounced than in erythrocyte ghosts, supporting the hypothesis that MT is a lipid raft modulator. At the reported MT-plasma concentrations found during the treatment of leishmaniasis (31-90 µg/mL), our measurements in the blood plasma indicated a hemolytic level of 2%-5%. The experiments indicated that MT acts predominantly on the protein component of the membrane. MT aggregates may wrap around the hydrophobic polypeptide chains, forming micelle-like structures that stabilize protein conformations more exposed to the solvent. Proteins with higher hydrophobicity may induce the penetration of the hydrophilic groups of MT into the membrane and cause it to rupture. Copyright © 2013 Wiley Periodicals, Inc.
Impacts of air pollution exposure on the allergenic properties of Arizona cypress pollens
NASA Astrophysics Data System (ADS)
Shahali, Y.; Pourpak, Z.; Moin, M.; Zare, A.; Majd, A.
2009-02-01
Epidemiological studies have demonstrated that urbanization and high levels of vehicle emissions correlated with the increasing trend of pollen-induced respiratory allergies. Numerous works have investigated the role of pollutants in the pathogenesis of respiratory diseases but impacts of anthropogenic pollution on pollen allergenic properties are still poorly understood. The objective of this survey was to evaluate impacts of the traffic-related pollution on the structure and allergenic protein content of Arizona cypress (Cupressus arizonica, CA) pollens, recognized as a rising cause of seasonal allergy in various regions worldwide. According to our results, traffic-related air pollution by its direct effects on the elemental composition of pollens considerably increased the fragility of the pollen exine, causing numerous cracks in its surface and facilitating pollen content liberation. Pollen grains were also covered by numerous submicronic orbicules which may act as effective vectors for pollen-released components into the lower regions of respiratory organs. On the other hand, this study provides us reliable explications about the low efficiency of standard commercial allergens in the diagnosis of the Arizona cypress pollen allergy in Tehran. Although traffic related pollution affects the allergenic components of CA pollens, the repercussions on the respiratory health of urban populations have yet to be clarified and need further investigations.
Li, Yue; Liu, Yinghui; Wu, Shanmei; Niu, Lei; Tian, Yuqiang
2015-01-01
The role of soil microbial variables in shaping the temporal variability of soil respiration has been well acknowledged but is poorly understood, particularly under elevated nitrogen (N) deposition conditions. We measured soil respiration along with soil microbial properties during the early, middle, and late growing seasons in temperate grassland plots that had been treated with N additions of 0, 2, 4, 8, 16, or 32 g N m−2 yr−1 for 10 years. Representing the averages over three observation periods, total (Rs) and heterotrophic (Rh) respiration were highest with 4 g N m−2 yr−1, but autotrophic respiration (Ra) was highest with 8 to 16 g N m−2 yr−1. Also, the responses of Rh and Ra were unsynchronized considering the periods separately. N addition had no significant impact on the temperature sensitivity (Q10) for Rs but inhibited the Q10 for Rh. Significant interactions between observation period and N level occurred in soil respiration components, and the temporal variations in soil respiration components were mostly associated with changes in microbial biomass carbon (MBC) and phospholipid fatty acids (PLFAs). Further observation on soil organic carbon and root biomass is needed to reveal the long-term effect of N deposition on soil C sequestration. PMID:26678303
Anomalous yield reduction in direct-drive deuterium/tritium implosions due to 3He addition
NASA Astrophysics Data System (ADS)
Herrmann, H. W.; Langenbrunner, J. R.; Mack, J. M.; Cooley, J. H.; Wilson, D. C.; Evans, S. C.; Sedillo, T. J.; Kyrala, G. A.; Caldwell, S. E.; Young, C. S.; Nobile, A.; Wermer, J.; Paglieri, S.; McEvoy, A. M.; Kim, Y.; Batha, S. H.; Horsfield, C. J.; Drew, D.; Garbett, W.; Rubery, M.; Glebov, V. Yu.; Roberts, S.; Frenje, J. A.
2009-05-01
Glass capsules were imploded in direct drive on the OMEGA laser [Boehly et al., Opt. Commun. 133, 495 (1997)] to look for anomalous degradation in deuterium/tritium (DT) yield and changes in reaction history with H3e addition. Such anomalies have previously been reported for D/H3e plasmas but had not yet been investigated for DT/H3e. Anomalies such as these provide fertile ground for furthering our physics understanding of inertial confinement fusion implosions and capsule performance. Anomalous degradation in the compression component of yield was observed, consistent with the "factor of 2" degradation previously reported by Massachusetts Institute of Technology (MIT) at a 50% H3e atom fraction in D2 using plastic capsules [Rygg, Phys. Plasmas 13, 052702 (2006)]. However, clean calculations (i.e., no fuel-shell mixing) predict the shock component of yield quite well, contrary to the result reported by MIT but consistent with Los Alamos National Laboratory results in D2/H3e [Wilson et al., J. Phys.: Conf. Ser. 112, 022015 (2008)]. X-ray imaging suggests less-than-predicted compression of capsules containing H3e. Leading candidate explanations are poorly understood equation of state for gas mixtures and unanticipated particle pressure variation with increasing H3e addition.
The Pharmacological Basis of Cannabis Therapy for Epilepsy.
Reddy, Doodipala Samba; Golub, Victoria M
2016-04-01
Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
Trust and doubt: An examination of children's decision to believe what they are told about food.
Nguyen, Simone P; Gordon, Cameron L; Chevalier, Tess; Girgis, Helana
2016-04-01
The domain of food is one that is highly relevant and vital to the everyday lives of children. However, children's reasoning about this domain is poorly understood within the field of developmental psychology. Because children's learning about food, including its evaluative components (e.g., health, taste) is so heavily dependent on information conveyed by other people, a major developmental challenge that children face is determining who to distrust regarding food. In three studies, this investigation examined how 3- and 4-year-olds and adults (N=312) use different cues to determine when to ignore informant information (i.e., distrust what an informant tells them by choosing an alternative) in food- and non-food-specific scenarios. The results of Study 1 indicated that by age 4 years, children are less trusting of inaccurate sources of information compared with sources that have not demonstrated previous inaccuracy. Study 2 revealed that these results are applicable across the domain of objects. The results of Study 3 indicated that by age 4, children trust benevolent sources more often than malevolent ones. Thus, when reasoning about the evaluative components of food, by age 4, children appraise other people's untrustworthiness by paying attention to their inaccuracy and malevolence. Copyright © 2015 Elsevier Inc. All rights reserved.
Simon, Matthew J; Murchison, Charles; Iliff, Jeffrey J
2018-02-01
Astrocytes play a critical role in regulating the interface between the cerebral vasculature and the central nervous system. Contributing to this is the astrocytic endfoot domain, a specialized structure that ensheathes the entirety of the vasculature and mediates signaling between endothelial cells, pericytes, and neurons. The astrocytic endfoot has been implicated as a critical element of the glymphatic pathway, and changes in protein expression profiles in this cellular domain are linked to Alzheimer's disease pathology. Despite this, basic physiological properties of this structure remain poorly understood including the developmental timing of its formation, and the protein components that localize there to mediate its functions. Here we use human transcriptome data from male and female subjects across several developmental stages and brain regions to characterize the gene expression profile of the dystrophin-associated complex (DAC), a known structural component of the astrocytic endfoot that supports perivascular localization of the astroglial water channel aquaporin-4. Transcriptomic profiling is also used to define genes exhibiting parallel expression profiles to DAC elements, generating a pool of candidate genes that encode gene products that may contribute to the physiological function of the perivascular astrocytic endfoot domain. We found that several genes encoding transporter proteins are transcriptionally associated with DAC genes. © 2017 Wiley Periodicals, Inc.
Wu, Delin; Jiang, Linqing; Wu, Hongjin; Wang, Shengqi; Zheng, Sidao; Yang, Jiyuan; Liu, Yuna; Ren, Jianxun; Chen, Xianbing
2013-01-01
Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited I K (I Kr, I Ks) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K+ channel. PMID:24069049
Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium
Lawrenson, Kate; Pakzamir, Elham; Liu, Biao; Lee, Janet M.; Delgado, Melissa K.; Duncan, Kara; Gayther, Simon A.; Liu, Song; Roman, Lynda; Mhawech-Fauceglia, Paulette
2015-01-01
Background The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses. Methodology/Principal Findings We studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035). Conclusion Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future. PMID:26132201
Climate variability and marine ecosystem impacts: a North Atlantic perspective
NASA Astrophysics Data System (ADS)
Parsons, L. S.; Lear, W. H.
In recent decades it has been recognized that in the North Atlantic climatic variability has been largely driven by atmospheric forcing related to the North Atlantic Oscillation (NAO). The NAO index began a pronounced decline around 1950 to a low in the 1960s. From 1970 onward the NAO index increased to its most extreme and persistent positive phase during the late 1980s and early 1990s. Changes in the pattern of the NAO have differential impacts on the opposite sides of the North Atlantic and differential impacts in the north and south. The changes in climate resulting from changes in the NAO appear to have had substantial impacts on marine ecosystems, in particular, on fish productivity, with the effects varying from region to region. An examination of several species and stocks, e.g. gadoids, herring and plankton in the Northeast Atlantic and cod and shellfish in the Northwest Atlantic, indicates that there is a link between long-term trends in the NAO and the productivity of various components of the marine ecosystem. While broad trends are evident, the mechanisms are poorly understood. Further research is needed to improve our understanding of how this climate variability affects the productivity of various components of the North Atlantic marine ecosystem.
Understanding the linkage between the physicochemical (PC) properties of nanoparticles (NP) and their activation of biological systems is poorly understood, yet fundamental to predicting nanotoxicity, idenitifying mode of actions and developing appropriate and effective regul...
Physiological benefits of nectar-feeding by a predatory beetle
USDA-ARS?s Scientific Manuscript database
Extrafloral nectar is an important food source for many animals, including predatory lady beetles (Coleoptera: Coccinellidae), although the physiological benefits of nectar consumption are poorly understood for most consumers. Under laboratory conditions, we confined new females of Coleomegilla macu...
Fructose, high fructose corn syrup, sucrose, and non-alcoholic liver disease
USDA-ARS?s Scientific Manuscript database
Nonalcoholic fatty liver disease (NAFLD), formerly called nonalcoholic steatohepatitis, is characterized by hepatic steatosis and abnormal triglyceride accumulation in liver cells. Its etiology, pathophysiology, and pathogenesis are still poorly understood. Some have suggested that the increased in...
Salary, Performance, and Superintendent Turnover
ERIC Educational Resources Information Center
Grissom, Jason A.; Mitani, Hajime
2016-01-01
Purpose: Superintendent retention is an important goal for many school districts, yet the factors contributing to superintendent turnover are poorly understood. Most prior quantitative studies of superintendent turnover have relied on small, cross-sectional samples, limiting the evidence base. Utilizing longitudinal administrative records from…
New perspectives on microbial community distortion after whole-genome amplification
Whole-genome amplification (WGA) has become an important tool to explore the genomic information of microorganisms in an environmental sample with limited biomass, however potential selective biases during the amplification processes are poorly understood. Here, we describe the e...
Abbassian, Ali; Thomas, Rhidian
2008-06-01
Ankle ligament injuries in the presence or in the absence of fractures are common. They often present a diagnostic challenge, and their management is poorly understood and subject to debate. This article reviews and discusses the current literature on the management and diagnosis of these injuries.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Xiaowen; Hutchings, Jack A.; Bianchi, Thomas S.
Temperature rise in the Arctic is causing deepening of active layers and resulting in the mobilization of deep permafrost dissolved organic matter (DOM). However, the mechanisms of DOM mobilization from Arctic soils, especially upper soil horizons which are drained most frequently through a year, are poorly understood. Here, we conducted a short-term leaching experiment on surface and deep organic active layer soils, from the Yukon River basin, to examine the effects of DOM transport on bulk and molecular characteristics. Our data showed a net release of DOM from surface soils equal to an average of 5% of soil carbon. Conversely,more » deep soils percolated with surface leachates retained up to 27% of bulk DOM-while releasing fluorescent components (up to 107%), indicating selective release of aromatic components (e.g. lignin, tannin), while retaining non-chromophoric components, as supported by spectrofluorometric and ultra high resolution mass spectroscopic techniques. Our findings highlight the importance of the lateral flux of DOM on ecosystem carbon balance as well as processing of DOM transport through organic active layer soils en route to rivers and streams. This work also suggests the potential role of leachate export as an important mechanism of C losses from Arctic soils, in comparison with the more traditional pathway from soil to atmosphere in a warming Arctic.« less
Anomalous yield reduction in direct-drive DT implosions due to 3He addition
DOE Office of Scientific and Technical Information (OSTI.GOV)
Herrmann, Hans W; Langenbrunner, James R; Mack, Joseph M
2008-01-01
Glass capsules were imploded in direct drive on the OMEGA laser [T. R. Boehly et aI., Opt. Commun. 133, 495, 1997] to look for anomalous degradation in deuterium/tritium (DT) yield (i.e., beyond what is predicted) and changes in reaction history with {sup 3}He addition. Such anomalies have previously been reported for D/{sup 3}He plasmas, but had not yet been investigated for DT/{sup 3}He. Anomalies such as these provide fertile ground for furthering our physics understanding of ICF implosions and capsule performance. A relatively short laser pulse (600 ps) was used to provide some degree of temporal separation between shock andmore » compression yield components for analysis. Anomalous degradation in the compression component of yield was observed, consistent with the 'factor of two' degradation previously reported by MIT at a 50% {sup 3}He atom fraction in D{sub 2} using plastic capsules [Rygg et aI., Phys. Plasmas 13, 052702 (2006)]. However, clean calculations (i.e., no fuel-shell mixing) predict the shock component of yield quite well, contrary to the result reported by MIT, but consistent with LANL results in D{sub 2}/{sup 3}He [Wilson, et aI., lml Phys: Conf Series 112, 022015 (2008)]. X-ray imaging suggests less-than-predicted compression ofcapsules containing {sup 3}He. Leading candidate explanations are poorly understood Equation-of-State (EOS) for gas mixtures, and unanticipated particle pressure variation with increasing {sup 3}He addition.« less
Farrell, Kristen B.; Grossman, Caitlin; Di Pietro, Santiago M.
2015-01-01
Despite the importance of clathrin-mediated endocytosis (CME) for cell biology, it is unclear if all components of the machinery have been discovered and many regulatory aspects remain poorly understood. Here, using Saccharomyces cerevisiae and a fluorescence microscopy screening approach we identify previously unknown regulatory factors of the endocytic machinery. We further studied the top scoring protein identified in the screen, Ubx3, a member of the conserved ubiquitin regulatory X (UBX) protein family. In vivo and in vitro approaches demonstrate that Ubx3 is a new coat component. Ubx3-GFP has typical endocytic coat protein dynamics with a patch lifetime of 45 ± 3 sec. Ubx3 contains a W-box that mediates physical interaction with clathrin and Ubx3-GFP patch lifetime depends on clathrin. Deletion of the UBX3 gene caused defects in the uptake of Lucifer Yellow and the methionine transporter Mup1 demonstrating that Ubx3 is needed for efficient endocytosis. Further, the UBX domain is required both for localization and function of Ubx3 at endocytic sites. Mechanistically, Ubx3 regulates dynamics and patch lifetime of the early arriving protein Ede1 but not later arriving coat proteins or actin assembly. Conversely, Ede1 regulates the patch lifetime of Ubx3. Ubx3 likely regulates CME via the AAA-ATPase Cdc48, a ubiquitin-editing complex. Our results uncovered new components of the CME machinery that regulate this fundamental process. PMID:26362318
Brand, Philipp; Lin, Wei; Johnson, Brian R.
2018-01-01
Plant cell wall components are the most abundant macromolecules on Earth. The study of the breakdown of these molecules is thus a central question in biology. Surprisingly, plant cell wall breakdown by herbivores is relatively poorly understood, as nearly all early work focused on the mechanisms used by symbiotic microbes to breakdown plant cell walls in insects such as termites. Recently, however, it has been shown that many organisms make endogenous cellulases. Insects, and other arthropods, in particular have been shown to express a variety of plant cell wall degrading enzymes in many gene families with the ability to break down all the major components of the plant cell wall. Here we report the genome of a walking stick, Medauroidea extradentata, an obligate herbivore that makes uses of endogenously produced plant cell wall degrading enzymes. We present a draft of the 3.3Gbp genome along with an official gene set that contains a diversity of plant cell wall degrading enzymes. We show that at least one of the major families of plant cell wall degrading enzymes, the pectinases, have undergone a striking lineage-specific gene family expansion in the Phasmatodea. This genome will be a useful resource for comparative evolutionary studies with herbivores in many other clades and will help elucidate the mechanisms by which metazoans breakdown plant cell wall components. PMID:29588379
SNMP is a signaling component required for pheromone sensitivity in Drosophila.
Jin, Xin; Ha, Tal Soo; Smith, Dean P
2008-08-05
The only known volatile pheromone in Drosophila, 11-cis-vaccenyl acetate (cVA), mediates a variety of behaviors including aggregation, mate recognition, and sexual behavior. cVA is detected by a small set of olfactory neurons located in T1 trichoid sensilla on the antennae of males and females. Two components known to be required for cVA reception are the odorant receptor Or67d and the extracellular pheromone-binding protein LUSH. Using a genetic screen for cVA-insensitive mutants, we have identified a third component required for cVA reception: sensory neuron membrane protein (SNMP). SNMP is a homolog of CD36, a scavenger receptor important for lipoprotein binding and uptake of cholesterol and lipids in vertebrates. In humans, loss of CD36 is linked to a wide range of disorders including insulin resistance, dyslipidemia, and atherosclerosis, but how CD36 functions in lipid transport and signal transduction is poorly understood. We show that SNMP is required in pheromone-sensitive neurons for cVA sensitivity but is not required for sensitivity to general odorants. Using antiserum to SNMP infused directly into the sensillum lymph, we show that SNMP function is required on the dendrites of cVA-sensitive neurons; this finding is consistent with a direct role in cVA signal transduction. Therefore, pheromone perception in Drosophila should serve as an excellent model to elucidate the role of CD36 members in transmembrane signaling.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Davis, Jonathan H.; Fairbairn, Malcolm, E-mail: jonathan.davis@kcl.ac.uk, E-mail: malcolm.fairbairn@kcl.ac.uk
We make projections for measuring the black hole birth rate from the diffuse supernova neutrino background (DSNB) by future neutrino experiments, and constrain the black hole merger fraction ε, when combined with information on the black hole merger rate from gravitational wave experiments such as LIGO. The DSNB originates from neutrinos emitted by all the supernovae in the Universe, and is expected to be made up of two components: neutrinos from neutron-star-forming supernovae, and a sub-dominant component at higher energies from black-hole-forming 'unnovae'. We perform a Markov Chain Monte Carlo analysis of simulated data of the DSNB in an experimentmore » similar to Hyper-Kamiokande, focusing on this second component. Since all knowledge of the neutrino emission from unnovae comes from simulations of collapsing stars, we choose two sets of priors: one where the unnovae are well-understood and one where their neutrino emission is poorly known. By combining the black hole birth rate from the DSNB with projected measurements of the black hole merger rate from LIGO, we show that the fraction of black holes which lead to binary mergers observed today ε could be constrained to be within the range 2 ⋅ 10{sup −4} ≤ ε ≤ 3 ⋅ 10{sup −2} at 3 σ confidence, after ten years of running an experiment like Hyper-Kamiokande.« less
Transverse kink oscillations in the presence of twist
NASA Astrophysics Data System (ADS)
Terradas, J.; Goossens, M.
2012-12-01
Context. Magnetic twist is thought to play an important role in coronal loops. The effects of magnetic twist on stable magnetohydrodynamic (MHD) waves is poorly understood because they are seldom studied for relevant cases. Aims: The goal of this work is to study the fingerprints of magnetic twist on stable transverse kink oscillations. Methods: We numerically calculated the eigenmodes of propagating and standing MHD waves for a model of a loop with magnetic twist. The azimuthal component of the magnetic field was assumed to be small in comparison to the longitudinal component. We did not consider resonantly damped modes or kink instabilities in our analysis. Results: For a nonconstant twist the frequencies of the MHD wave modes are split, which has important consequences for standing waves. This is different from the degenerated situation for equilibrium models with constant twist, which are characterised by an azimuthal component of the magnetic field that linearly increases with the radial coordinate. Conclusions: In the presence of twist standing kink solutions are characterised by a change in polarisation of the transverse displacement along the tube. For weak twist, and in the thin tube approximation, the frequency of standing modes is unaltered and the tube oscillates at the kink speed of the corresponding straight tube. The change in polarisation is linearly proportional to the degree of twist. This has implications with regard to observations of kink modes, since the detection of this variation in polarisation can be used as an indirect method to estimate the twist in oscillating loops.
NASA Technical Reports Server (NTRS)
Murphy, Kyle R.; Mann, Ian R.; Rae, I. Jonathan; Sibeck, David G.; Watt, Clare E. J.
2016-01-01
Wave-particle interactions play a crucial role in energetic particle dynamics in the Earths radiation belts. However, the relative importance of different wave modes in these dynamics is poorly understood. Typically, this is assessed during geomagnetic storms using statistically averaged empirical wave models as a function of geomagnetic activity in advanced radiation belt simulations. However, statistical averages poorly characterize extreme events such as geomagnetic storms in that storm-time ultralow frequency wave power is typically larger than that derived over a solar cycle and Kp is a poor proxy for storm-time wave power.
Brand, Serge; Kirov, Roumen; Kalak, Nadeem; Gerber, Markus; Pühse, Uwe; Lemola, Sakari; Correll, Christoph U; Cortese, Samuele; Meyer, Till; Holsboer-Trachsler, Edith
2015-01-01
Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation of poor sleep. Though perfectionism traits seem associated with poor sleep, the direct role of such traits seemed small, when mediating factors such as stress perception and emotion regulation were taken into account.
Brand, Serge; Kirov, Roumen; Kalak, Nadeem; Gerber, Markus; Pühse, Uwe; Lemola, Sakari; Correll, Christoph U; Cortese, Samuele; Meyer, Till; Holsboer-Trachsler, Edith
2015-01-01
Background Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Methods Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. Results Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation of poor sleep. Conclusion Though perfectionism traits seem associated with poor sleep, the direct role of such traits seemed small, when mediating factors such as stress perception and emotion regulation were taken into account. PMID:25678791
Taylor, Cliff D.; Giles, Stuart A.
2015-01-01
USGS review of PRISM-I data suggests that there is abundant documentation of the Bou Naga alkaline complex and to a lesser degree, the Guelb er Richat carbonatite complex, but that all other occurrences of U, Th, REE, and associated elements are poorly described, and poorly understood (Taylor, 2007)
Atherosclerosis associated with pericardial effusion in a central bearded dragon (Pogona vitticeps).
Schilliger, Lionel; Lemberger, Karin; Chai, Norin; Bourgeois, Aude; Charpentier, Maud
2010-09-01
Atherosclerosis is a common disease in pet birds, particularly in psittacines, and is frequently found when performing postmortem examinations on adult and old dogs, in which it is mainly associated with endocrine diseases, such as hypothyroidism and diabetes mellitus. However, atherosclerosis is poorly documented in reptiles and consequently poorly understood. In the current case report, atherosclerosis and pericardial effusion were diagnosed in a 2-year-old male central bearded dragon (Pogona vitticeps) based on ultrasound visualization, necropsy, and histologic examination.
USING MOLECULAR PROBES TO STUDY INTERFACIAL REDOX REACTION AT FE-BEARING SMECTITES
The interfacial electron transfer of clay-water systems has a wide range of significance in geochemical and biogeochernical environments. However the mechanism of interfacial electron transport is poorly understood. The electron transfer mechanism at the solid-water interfaces of...
Larval fish distribution in the St. Louis River estuary
Our objective was to determine what study design, environmental, and habitat variables contribute to the distribution and abundance of larval fish in the St. Louis River estuary. Larval fish habitat associations are poorly understood in Great Lakes coastal wetlands, yet critical ...
Post-traumatic unilateral plantar hyperhidrosis.
Eren, Y; Yavasoglu, N G; Comoglu, S S
2016-02-01
Localized unilateral hyperhidrosis is rare and poorly understood, sometimes stemming from trauma. Feet, quite vulnerable to trauma are affected by disease-mediated plantar hyperhidrosis, usually bilaterally. This report describes partial hyperhidrosis developing post-traumatically on the left plantar region of a 52-year-old male.
Predator-prey interaction reveals local effects of high-altitude insect migration
USDA-ARS?s Scientific Manuscript database
High-altitude nocturnal insect migrations represent significant pulses of resources, yet are difficult to study and poorly understood. Predator-prey interactions, specifically migratory moth consumption by high-flying bats, potentially reveal flows of migratory insects across a landscape. In North...
Assessing Effects of Pesticides on the Bee Immune System
Populations of some managed and wild pollinators are in decline as a result of multiple interacting factors including parasites, disease, poor nutrition and pesticides. The role that diminished immunity plays in these declines is not understood. The U.S. Environmental Protection ...
USDA-ARS?s Scientific Manuscript database
Colony development, which includes hyphal extension, branching, anastomosis and asexual sporulation are fundamental aspects of the lifecycle of filamentous fungi; genetic mechanisms underlying these phenomena are poorly understood. We conducted transcriptional profiling during colony development of...
USEPA RESEARCH ON FISH - HABITAT RELATIONSHIPS IN GREAT LAKES COASTAL MARSHES
Despite numerous studies documenting fish use of particular habitat elements, the role of habitat mosaics in supporting wetland fishes is poorly understood. USEPA's Mid-Continent Ecology Division has initiated research to identify relationships of fish and habitat in coastal mars...
A Cellular Game of Telephone: Trans Tissue Reprogramming of Responses to Toxic Stimuli
Exposure to air pollution is a leading cause of cardiopulmonary morbidity and mortality; however, while these effects outside the lung have been associated with aberrant oxidative stress and inflammation, the underlying molecular mechanisms are poorly understood. We hypothesized ...
Cellular Plasticity in the Diabetic Myocardium
2017-09-01
demonstrated that obese diabetic db/db mice in a C57Bl6J background exhibit cardiac remodeling, associated with modest ventricular dilation...HFpEF, the cellular basis for fibrotic remodeling of the ventricle is poorly understood. Metabolic diseases (such as obesity and diabetes) are
Reduce Confusion about Diffusion.
ERIC Educational Resources Information Center
Hebrank, Mary R.
1997-01-01
Presents activities that allow students to explore the fundamental but poorly understood concept of diffusion by appealing to their kinesthetic senses first, then challenging their analytical skills as they try to deduce the mathematical principle involved. Presents a computer simulation of diffusion and discusses diffusion's limitations and…
INTERNATIONAL CHILDHOOD CANCER COHORT CONSORTIUM (Journal Article)
Childhood cancers are rare conditions whose etiology is poorly understood. There is evidence that for some, the causal pathway may commence in utero or during peri-conception. One traditional epidemiologic approach to the study of rare diseases is the use of a retrospective cas...
A Multilevel Investigation of Neighborhood Effects on Parental Warmth
ERIC Educational Resources Information Center
Tendulkar, Shalini A.; Buka, Stephen; Dunn, Erin C.; Subramanian, S. V.; Koenen, Karestan C.
2010-01-01
Although researchers recognize that social contexts shape parenting behaviors, the relationship between neighborhood environment and parenting remains poorly understood. To address this gap, we investigated the associations between compositional and contextual (structural, social, and safety) characteristics of neighborhoods and parental warmth.…
Origins of Brain Tumor Macrophages.
De Palma, Michele
2016-12-12
The ontogeny of brain-tumor-associated macrophages is poorly understood. New findings indicate that both resident microglia and blood-derived monocytes generate the pool of macrophages that infiltrate brain tumors of either primary or metastatic origin. Copyright © 2016 Elsevier Inc. All rights reserved.
Pollinator guilds respond differently to urban habitat fragmentation in a oak-savannah ecosystem
USDA-ARS?s Scientific Manuscript database
Habitat fragmentation is widely thought to threaten biodiversity. However, response of pollinators to habitat fragmentation is still poorly understood, as pollinator communities are notoriously spatially variable. We investigated pollinator community structure in a highly fragmented oak-savannah ec...
Wetland creation, enhancement, and restoration activities are commonly implemented to compensate for wetland loss or degradation. However, functional equivalence in restored and created wetland habitats is often poorly understood. In estuarine habitats, changes in habitat qualit...
Ozone-Induced Metabolic Impairment is Attenuated in Adrenalectomized Wistar Kyoto Rats
Rationale: Air pollutants have been linked to increased incidence of metabolic syndrome however the mechanisms are poorly understood. We have recently shown that ozone exposure induces significant hyperglycemia together with elevated serum leptin and epinephrine in the Wistar Ky...
THE INTERACTION OF VAPOUR PHASE ORGANIC COMPOUNDS WITH INDOOR SINKS
The interaction of indoor air pollutants with interior surfaces (i.e., sinks) is a well known, but poorly understood, phenomenon. Studies have shown that re-emissions of adsorbed organic vapours can contribute to elevated concentrations of organics in indoor environments. Researc...
Preschool Executive Functioning Abilities Predict Early Mathematics Achievement
ERIC Educational Resources Information Center
Clark, Caron A. C.; Pritchard, Verena E.; Woodward, Lianne J.
2010-01-01
Impairments in executive function have been documented in school-age children with mathematical learning difficulties. However, the utility and specificity of preschool executive function abilities in predicting later mathematical achievement are poorly understood. This study examined linkages between children's developing executive function…
HYDRAULIC REDISTRIBUTION IN THE PACIFIC NORTHWEST: TWEAKING THE SYSTEM
Hydraulic redistribution (HR) has recently been documented in Pacific Northwest forests, but the controls governing this process and its importance to shallow-rooted species are poorly understood. Our objective in this study was to manipulate the soil-root system to tease apart ...
REVIEW OF QUANTITATIVE STANDARDS AND GUIDELINES FOR FUNGI IN INDOOR AIR
Exposure to fungal aerosols clearly causes human disease. However, methods for assessing exposure remain poorly understood, and guidelines for interpreting data are often contradictory. The purposes of this paper are to review and compare existing guidelines for indoor airborne...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stevenson, Simon; Ohme, Frank; Fairhurst, Stephen, E-mail: simon.stevenson@ligo.org
2015-09-01
The coalescence of compact binaries containing neutron stars or black holes is one of the most promising signals for advanced ground-based laser interferometer gravitational-wave (GW) detectors, with the first direct detections expected over the next few years. The rate of binary coalescences and the distribution of component masses is highly uncertain, and population synthesis models predict a wide range of plausible values. Poorly constrained parameters in population synthesis models correspond to poorly understood astrophysics at various stages in the evolution of massive binary stars, the progenitors of binary neutron star and binary black hole systems. These include effects such asmore » supernova kick velocities, parameters governing the energetics of common envelope evolution and the strength of stellar winds. Observing multiple binary black hole systems through GWs will allow us to infer details of the astrophysical mechanisms that lead to their formation. Here we simulate GW observations from a series of population synthesis models including the effects of known selection biases, measurement errors and cosmology. We compare the predictions arising from different models and show that we will be able to distinguish between them with observations (or the lack of them) from the early runs of the advanced LIGO and Virgo detectors. This will allow us to narrow down the large parameter space for binary evolution models.« less
Bockoven, Alison A.; Wilder, Shawn M.; Eubanks, Micky D.
2015-01-01
Individuals vary within a species in many ecologically important ways, but the causes and consequences of such variation are often poorly understood. Foraging behavior is among the most profitable and risky activities in which organisms engage and is expected to be under strong selection. Among social insects there is evidence that within-colony variation in traits such as foraging behavior can increase colony fitness, but variation between colonies and the potential consequences of such variation are poorly documented. In this study, we tested natural populations of the red imported fire ant, Solenopsis invicta, for the existence of colony and regional variation in foraging behavior and tested the persistence of this variation over time and across foraging habitats. We also reared single-lineage colonies in standardized environments to explore the contribution of colony lineage. Fire ants from natural populations exhibited significant and persistent colony and regional-level variation in foraging behaviors such as extra-nest activity, exploration, and discovery of and recruitment to resources. Moreover, colony-level variation in extra-nest activity was significantly correlated with colony growth, suggesting that this variation has fitness consequences. Lineage of the colony had a significant effect on extra-nest activity and exploratory activity and explained approximately half of the variation observed in foraging behaviors, suggesting a heritable component to colony-level variation in behavior. PMID:26197456
Hannigan, Geoffrey D; Meisel, Jacquelyn S; Tyldsley, Amanda S; Zheng, Qi; Hodkinson, Brendan P; SanMiguel, Adam J; Minot, Samuel; Bushman, Frederic D; Grice, Elizabeth A
2015-10-20
Viruses make up a major component of the human microbiota but are poorly understood in the skin, our primary barrier to the external environment. Viral communities have the potential to modulate states of cutaneous health and disease. Bacteriophages are known to influence the structure and function of microbial communities through predation and genetic exchange. Human viruses are associated with skin cancers and a multitude of cutaneous manifestations. Despite these important roles, little is known regarding the human skin virome and its interactions with the host microbiome. Here we evaluated the human cutaneous double-stranded DNA virome by metagenomic sequencing of DNA from purified virus-like particles (VLPs). In parallel, we employed metagenomic sequencing of the total skin microbiome to assess covariation and infer interactions with the virome. Samples were collected from 16 subjects at eight body sites over 1 month. In addition to the microenviroment, which is known to partition the bacterial and fungal microbiota, natural skin occlusion was strongly associated with skin virome community composition. Viral contigs were enriched for genes indicative of a temperate phage replication style and also maintained genes encoding potential antibiotic resistance and virulence factors. CRISPR spacers identified in the bacterial DNA sequences provided a record of phage predation and suggest a mechanism to explain spatial partitioning of skin phage communities. Finally, we modeled the structure of bacterial and phage communities together to reveal a complex microbial environment with a Corynebacterium hub. These results reveal the previously underappreciated diversity, encoded functions, and viral-microbial dynamic unique to the human skin virome. To date, most cutaneous microbiome studies have focused on bacterial and fungal communities. Skin viral communities and their relationships with their hosts remain poorly understood despite their potential to modulate states of cutaneous health and disease. Previous studies employing whole-metagenome sequencing without purification for virus-like particles (VLPs) have provided some insight into the viral component of the skin microbiome but have not completely characterized these communities or analyzed interactions with the host microbiome. Here we present an optimized virus purification technique and corresponding analysis tools for gaining novel insights into the skin virome, including viral "dark matter," and its potential interactions with the host microbiome. The work presented here establishes a baseline of the healthy human skin virome and is a necessary foundation for future studies examining viral perturbations in skin health and disease. Copyright © 2015 Hannigan et al.
Immunological network signatures of cancer progression and survival
2011-01-01
Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding of immune involvement in complex biological networks. The application of this approach to tumor immunity represents an automated systems strategy that quantifies the immunological component in complex disease. In so doing, it stratifies patients according to their immune profiles, which may lead to effective computational prognostic and clinical guides. PMID:21453479
Model development to study strategies of younger and older adults getting up from the floor.
Schwickert, L; Oberle, C; Becker, C; Lindemann, U; Klenk, J; Schwenk, M; Bourke, A; Zijlstra, W
2016-04-01
Long lies after a fall remain a public health challenge. Many successful fall prevention programmes have been developed but only few of them include recovery strategies after a fall. Once better understood, such movement strategies could be implemented into training interventions. A model of motion sequences describing successful movement strategies for rising from the floor in different age groups was developed. Possible risk factors for poor rising performance such as flexibility and muscle power were evaluated. Fourteen younger subjects between 20 and 50 years of age and 10 healthy older subjects (60+ years) were included. Movement strategies and key components of different rising sequences were determined from video analyses. The temporal parameters of transfers and number of components within the motion sequences were calculated. Possible explanatory variables for differences in rising performance were assessed (leg extension power, flexibility of the knee- and hip joints). Seven different components were identified for the lie-to-stand-walk transfer, labelled as lying, initiation, positioning, supporting, elevation, or stabilisation component followed by standing and/or walking. Median time to rise was significantly longer in older subjects (older 5.7s vs. younger 3.7s; p < 0.001), and leg extension power (left p = 0.002, right p = 0.013) and knee flexibility (left p = 0.019, right p = 0.025) were significantly lower. The number of components for rising was correlated with hip flexibility (r = 0.514) and maximal power (r = 0.582). The time to rise was correlated with minimal goniometric knee angle of the less flexible leg (r = 0.527) and maximal leg extension power (r = 0.725). A motion sequence model containing seven different components identified by individual key-frames could be established. Age-related differences in rising strategies and performance were identified.
The influence of spatial processes on population dynamics within river-stream networks is poorly understood. Utilizing spatially explicit analyses of temporal genetic variance, we examined whether persistence of Central Stonerollers (Campostoma anomalum) reflects differences in h...
Worldwide patterns of ancestry, divergence, and admixture in domesticated cattle
USDA-ARS?s Scientific Manuscript database
The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 anima...
ERIC Educational Resources Information Center
Blystone, Robert V.; Blodgett, Kevin
2006-01-01
The scientific method is the principal methodology by which biological knowledge is gained and disseminated. As fundamental as the scientific method may be, its historical development is poorly understood, its definition is variable, and its deployment is uneven. Scientific progress may occur without the strictures imposed by the formal…
From Movements to Actions: Two Mechanisms for Learning Action Sequences
ERIC Educational Resources Information Center
Endress, Ansgar D.; Wood, Justin N.
2011-01-01
When other individuals move, we interpret their movements as discrete, hierarchically-organized, goal-directed actions. However, the mechanisms that integrate visible movement features into actions are poorly understood. Here, we consider two sequence learning mechanisms--transitional probability-based (TP) and position-based encoding…
Accumulation of the Antibiotic Phenazine-1-Carboxylic Acid in the Rhizosphere of Dryland Cereals
USDA-ARS?s Scientific Manuscript database
Natural antibiotics are thought to function in the defense, fitness, competitiveness, biocontrol activity, communication and gene regulation of microorganisms. However, the scale and quantitative aspects of antibiotic production in natural settings are poorly understood. We addressed these fundament...
Background/Questions/Methods Large-bodied invertebrates (bivalves, polychaetes, burrowing shrimps) are common to infaunal communities of NE Pacific estuaries, but their contribution to estuarine community structure, function and ecosystem services is poorly understood because ...
Olfactory disruption: towards controlling important insect vectors of disease
USDA-ARS?s Scientific Manuscript database
Chemical repellents are used to decrease contacts between insect disease vectors and their hosts, thus reducing the probability of disease transmission. The molecular mechanisms by which repellents have their effects are poorly understood and remain a controversial topic. Here we present recent re...
USDA-ARS?s Scientific Manuscript database
Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. We measured serum metabolite...
LOCAL VS. REGIONAL EFFECTS ON FISH DIVERSITY AS MEDIATED BY STREAMFLOW DISTURBANCE REGIME
abstract
The interplay of local and regional processes on fish diversity is poorly understood, especially related to patterns of streamflow disturbance regime. Articulation of the relationship between flow disturbance patterns and river fishes across local to regional scal...
USDA-ARS?s Scientific Manuscript database
Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variatio...
The role of methionine metabolism in inflammatory bowel disease
USDA-ARS?s Scientific Manuscript database
Methionine (Met) cycle activity is critical for normal cell functions. Met metabolites S-adenosylmethionine (SAM) and methylthioadenosine (MTA) are anti-inflammatory, yet their role in inflammatory bowel disease (IBD) is poorly understood. We hypothesize that active IBD leads to changes in Met metab...
Molecular basis for the thermostability of Newcastle disease virus
USDA-ARS?s Scientific Manuscript database
Thermostable Newcastle disease virus (NDV) vaccines have been used widely to protect village chickens against Newcastle disease, due to their decreased dependence on cold chain for transport and storage. However, the genetic basis underlying the NDV thermostability is poorly understood. In this stud...
Development and preliminary validation of the Parenting around SNAcking Questionnaire (P-SNAQ)
USDA-ARS?s Scientific Manuscript database
Snacking makes significant contributions to children's dietary intake but is poorly understood from a parenting perspective. This research was designed to develop and evaluate the psychometrics of a theoretically grounded, empirically-informed measure of snack parenting. The Parenting around SNAckin...
Do boll weevils really diapause?
USDA-ARS?s Scientific Manuscript database
Boll weevil, Anthonomus grandis grandis Boheman, diapause has been poorly understood since the term was first used 50 yrs ago to describe the pest’s winter dormancy in temperate regions. This literature-based study found that low temperature and changes in photoperiod are the boll weevil diapause-i...
Effects of exurban development on trophic interactions in a desert landscape
USDA-ARS?s Scientific Manuscript database
Context Mechanisms of ecosystem change in urbanizing landscapes are poorly understood, especially in exurban areas featuring residential or commercial development set in a matrix of modified and natural vegetation. We asked how development altered trophic interactions and ecosystem processes in the ...
Secondary organic aerosol (SOA) might affect the atmospheric radiation balance through absorbing light at shorter visible and UV wavelengths. However, the composition and optical properties of light-absorbing SOA is poorly understood. In this work, SOA filter samples were collect...
Reproductive responses of northern goshawks to variable prey populations
Susan R. Salafsky; Richard T. Reynolds; Barry R. Noon; John A. Wiens
2007-01-01
Developing comprehensive conservation strategies requires knowledge of factors influencing population growth and persistence. Although variable prey resources are often associated with fluctuations in raptor demographic parameters, the mechanisms of food limitation are poorly understood, especially for a generalist predator like the northern goshawk (Accipiter...
Aquatic insects provide a critical nutrient subsidy to riparian food webs, yet their role as vectors of contaminants to terrestrial ecosystems is poorly understood. We investigated relationships between aquatic (resource utilization) and contaminant exposure for a riparian invert...
The geography of spatial synchrony
Jonathan A. Walter; Lawrence W. Sheppard; Thomas L. Anderson; Jude H. Kastens; Ottar N. Bjørnstad; Andrew M. Liebhold; Daniel C. Reuman; Bernd Blasius
2017-01-01
Spatial synchrony, defined as correlated temporal fluctuations among populations, is a fundamental feature of population dynamics, but many aspects of synchrony remain poorly understood. Few studies have examined detailed geographical patterns of synchrony; instead most focus on how synchrony declines with increasing linear distance between locations, making the...
Relations between Alcohol, Violence and Victimization in Adolescence
ERIC Educational Resources Information Center
Shepherd, J. P.; Sutherland, I.; Newcombe, R. G.
2006-01-01
Background: Compared to links between alcohol and aggression, links between alcohol and vulnerability are poorly understood. Objectives: To determine whether there is a significant relationship between vulnerability to physical violence and alcohol consumption in adolescence independent of a relationship between alcohol consumption and violent…
Heredity Factors in Spatial Visualization.
ERIC Educational Resources Information Center
Vandenberg, S. G.
Spatial visualization is not yet clearly understood. Some researchers have concluded that two factors or abilities are involved, spatial orientation and spatial visualization. Different definitions and different tests have been proposed for these two abilities. Several studies indicate that women generally perform more poorly on spatial tests than…
Mangrove wetland restoration and creation efforts are increasingly proposed as mechanisms to compensate for mangrove wetland loss. However, ecosystem development and functional equivalence in restored and created mangrove wetlands is poorly understood. We compared a 20-yr chrono...
ERIC Educational Resources Information Center
Brock, David
2009-01-01
Despite student interest, the heart is often a poorly understood topic in biology. To help students understand this vital organ's physiology, the author created this investigation activity involving the mammalian heart and its role in the circulatory system. Students design, build, and demonstrate working artificial "hearts" to exhibit what they…
ERIC Educational Resources Information Center
Harrow, Chris; Chin, Lillian
2014-01-01
Exploration, innovation, proof: For students, teachers, and others who are curious, keeping an open mind and being ready to investigate unusual or unexpected properties will always lead to learning something new. Technology can further this process, allowing various behaviors to be analyzed that were previously memorized or poorly understood. This…
Multi-scale assessment of human-induced changes to Amazonian instream habitats
Context: Land use change and forest degradation have myriad effects on tropical ecosystems. Yet their consequences for low-order streams remain very poorly understood, including in the world´s largest freshwater basin, the Amazon.Objectives: Determine the degree to which ph...
Child stunting is associated with low circulating essential amino acids
USDA-ARS?s Scientific Manuscript database
Stunting affects about one-quarter of children under five worldwide. The pathogenesis of stunting is poorly understood. Nutritional interventions have had only modest effects in reducing stunting. We hypothesized that insufficiency in essential amino acids may be limiting the linear growth of childr...
Introduction to the Thematic Minireview Series: Brain glycogen metabolism.
Carlson, Gerald M; Dienel, Gerald A; Colbran, Roger J
2018-05-11
The synthesis of glycogen allows for efficient intracellular storage of glucose molecules in a soluble form that can be rapidly released to enter glycolysis in response to energy demand. Intensive studies of glucose and glycogen metabolism, predominantly in skeletal muscle and liver, have produced innumerable insights into the mechanisms of hormone action, resulting in the award of several Nobel Prizes over the last one hundred years. Glycogen is actually present in all cells and tissues, albeit at much lower levels than found in muscle or liver. However, metabolic and physiological roles of glycogen in other tissues are poorly understood. This series of Minireviews summarizes what is known about the enzymes involved in brain glycogen metabolism and studies that have linked glycogen metabolism to multiple brain functions involving metabolic communication between astrocytes and neurons. Recent studies unexpectedly linking some forms of epilepsy to mutations in two poorly understood proteins involved in glycogen metabolism are also reviewed. © 2018 Carlson et al.
Immigrant dairy workers' perceptions of health and safety on the farm in America's Heartland.
Liebman, Amy King; Juarez-Carrillo, Patricia Margarita; Reyes, Iris Anne Cruz; Keifer, Matthew Charles
2016-03-01
Dairy farming is dangerous. Yearly, farms grow fewer and larger by employing immigrant workers, who have limited industrial agriculture experience and safety and health training. We examined results of five focus groups with 37 Hispanic, immigrant dairy workers. Analysis followed a grounded theory approach and employed ATLAS.ti. Reported injury experience affirmed the hazardous nature of dairy. Some workers received appropriate worker compensation benefits, whereas others were instructed to deny work-relatedness. Some employers covered medical injury costs out-of-pocket, whereas others did not. Cows were a major injury source. Pressure to work and weather were noted as injury risk factors. Worker compensation was poorly understood, and immigration status and fear of deportation influenced injury and hazard reporting. Injury management practices range from benevolent to threatening. Workers compensation is poorly understood and undocumented status is an occupational hazard. We underscore the need for further research and immigration policy change. © 2015 Wiley Periodicals, Inc.
Direct observation of closed magnetic flux trapped in the high-latitude magnetosphere.
Fear, R C; Milan, S E; Maggiolo, R; Fazakerley, A N; Dandouras, I; Mende, S B
2014-12-19
The structure of Earth's magnetosphere is poorly understood when the interplanetary magnetic field is northward. Under this condition, uncharacteristically energetic plasma is observed in the magnetotail lobes, which is not expected in the textbook model of the magnetosphere. Using satellite observations, we show that these lobe plasma signatures occur on high-latitude magnetic field lines that have been closed by the fundamental plasma process of magnetic reconnection. Previously, it has been suggested that closed flux can become trapped in the lobe and that this plasma-trapping process could explain another poorly understood phenomenon: the presence of auroras at extremely high latitudes, called transpolar arcs. Observations of the aurora at the same time as the lobe plasma signatures reveal the presence of a transpolar arc. The excellent correspondence between the transpolar arc and the trapped closed flux at high altitudes provides very strong evidence of the trapping mechanism as the cause of transpolar arcs. Copyright © 2014, American Association for the Advancement of Science.
Sea-level-induced seismicity and submarine landslide occurrence
Brothers, Daniel S.; Luttrell, Karen M.; Chaytor, Jason D.
2013-01-01
The temporal coincidence between rapid late Pleistocene sea-level rise and large-scale slope failures is widely documented. Nevertheless, the physical mechanisms that link these phenomena are poorly understood, particularly along nonglaciated margins. Here we investigate the causal relationships between rapid sea-level rise, flexural stress loading, and increased seismicity rates along passive margins. We find that Coulomb failure stress across fault systems of passive continental margins may have increased more than 1 MPa during rapid late Pleistocene–early Holocene sea-level rise, an amount sufficient to trigger fault reactivation and rupture. These results suggest that sea-level–modulated seismicity may have contributed to a number of poorly understood but widely observed phenomena, including (1) increased frequency of large-scale submarine landslides during rapid, late Pleistocene sea-level rise; (2) emplacement of coarse-grained mass transport deposits on deep-sea fans during the early stages of marine transgression; and (3) the unroofing and release of methane gas sequestered in continental slope sediments.
Wang, Yong Xin; Mandal, Deendayal; Wang, Suizhau; Hughes, Dennis; Pollock, Raphael E; Lev, Dina; Kleinerman, Eugenie; Hayes-Jordan, Andrea
2009-01-01
Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES. Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.
Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents.
Seibt, Julie; Richard, Clément J; Sigl-Glöckner, Johanna; Takahashi, Naoya; Kaplan, David I; Doron, Guy; de Limoges, Denis; Bocklisch, Christina; Larkum, Matthew E
2017-09-25
How sleep influences brain plasticity is not known. In particular, why certain electroencephalographic (EEG) rhythms are linked to memory consolidation is poorly understood. Calcium activity in dendrites is known to be necessary for structural plasticity changes, but this has never been carefully examined during sleep. Here, we report that calcium activity in populations of neocortical dendrites is increased and synchronised during oscillations in the spindle range in naturally sleeping rodents. Remarkably, the same relationship is not found in cell bodies of the same neurons and throughout the cortical column. Spindles during sleep have been suggested to be important for brain development and plasticity. Our results provide evidence for a physiological link of spindles in the cortex specific to dendrites, the main site of synaptic plasticity.Different stages of sleep, marked by particular electroencephalographic (EEG) signatures, have been linked to memory consolidation, but underlying mechanisms are poorly understood. Here, the authors show that dendritic calcium synchronisation correlates with spindle-rich sleep phases.
Wahlstrom-Helgren, Sarah
2016-01-01
Feed-forward inhibitory (FFI) circuits are important for many information-processing functions. FFI circuit operations critically depend on the balance and timing between the excitatory and inhibitory components, which undergo rapid dynamic changes during neural activity due to short-term plasticity (STP) of both components. How dynamic changes in excitation/inhibition (E/I) balance during spike trains influence FFI circuit operations remains poorly understood. In the current study we examined the role of STP in the FFI circuit functions in the mouse hippocampus. Using a coincidence detection paradigm with simultaneous activation of two Schaffer collateral inputs, we found that the spiking probability in the target CA1 neuron was increased while spike precision concomitantly decreased during high-frequency bursts compared with a single spike. Blocking inhibitory synaptic transmission revealed that dynamics of inhibition predominately modulates the spike precision but not the changes in spiking probability, whereas the latter is modulated by the dynamics of excitation. Further analyses combining whole cell recordings and simulations of the FFI circuit suggested that dynamics of the inhibitory circuit component may influence spiking behavior during bursts by broadening the width of excitatory postsynaptic responses and that the strength of this modulation depends on the basal E/I ratio. We verified these predictions using a mouse model of fragile X syndrome, which has an elevated E/I ratio, and found a strongly reduced modulation of postsynaptic response width during bursts. Our results suggest that changes in the dynamics of excitatory and inhibitory circuit components due to STP play important yet distinct roles in modulating the properties of FFI circuits. PMID:27605532
Cyril, Sheila; Smith, Ben J.; Possamai-Inesedy, Alphia; Renzaho, Andre M. N.
2015-01-01
Background Although community engagement (CE) is widely used in health promotion, components of CE models associated with improved health are poorly understood. This study aimed to examine the magnitude of the impact of CE on health and health inequalities among disadvantaged populations, which methodological approaches maximise the effectiveness of CE, and components of CE that are acceptable, feasible, and effective when used among disadvantaged populations. Design The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We carried out methodological assessments of the included studies using rating scales. The analysis focussed on model synthesis to identify the key CE components linked to positive study outcomes and comparative analysis between positive study outcomes, processes, and quality indicators of CE. Results Out of 24 studies that met our inclusion criteria, 21 (87.5%) had positively impacted health behaviours, public health planning, health service access, health literacy, and a range of health outcomes. More than half of the studies (58%) were of good quality, whereas 71% and 42% of studies showed good community involvement in research and achieved high levels of CE, respectively. Key CE components that affected health outcomes included real power-sharing, collaborative partnerships, bidirectional learning, incorporating the voice and agency of beneficiary communities in research protocol, and using bicultural health workers for intervention delivery. Conclusions The findings suggest that CE models can lead to improved health and health behaviours among disadvantaged populations if designed properly and implemented through effective community consultation and participation. We also found several gaps in the current measurement of CE in health intervention studies, which suggests the importance of developing innovative approaches to measure CE impact on health outcomes in a more rigorous way. PMID:26689460
Albalat, Ricard; Brunet, Frédéric; Laudet, Vincent; Schubert, Michael
2011-01-01
Although the physiological relevance of retinoids and steroids in vertebrates is very well established, the origin and evolution of the genetic machineries implicated in their metabolic pathways is still very poorly understood. We investigated the evolution of these genetic networks by conducting an exhaustive survey of components of the retinoid and steroid pathways in the genome of the invertebrate chordate amphioxus (Branchiostoma floridae). Due to its phylogenetic position at the base of chordates, amphioxus is a very useful model to identify and study chordate versus vertebrate innovations, both on a morphological and a genomic level. We have characterized more than 220 amphioxus genes evolutionarily related to vertebrate components of the retinoid and steroid pathways and found that, globally, amphioxus has orthologs of most of the vertebrate components of these two pathways, with some very important exceptions. For example, we failed to identify a vertebrate-like machinery for retinoid storage, transport, and delivery in amphioxus and were also unable to characterize components of the adrenal steroid pathway in this invertebrate chordate. The absence of these genes from the amphioxus genome suggests that both an elaboration and a refinement of the retinoid and steroid pathways took place at the base of the vertebrate lineage. In stark contrast, we also identified massive amplifications in some amphioxus gene families, most extensively in the short-chain dehydrogenase/reductase superfamily, which, based on phylogenetic and genomic linkage analyses, were likely the result of duplications specific to the amphioxus lineage. In sum, this detailed characterization of genes implicated in retinoid and steroid signaling in amphioxus allows us not only to reconstruct an outline of these pathways in the ancestral chordate but also to discuss functional innovations in retinoid homeostasis and steroid-dependent regulation in both cephalochordate and vertebrate evolution. PMID:21856648
Characterization of identification errors and uses in localization of poor modal correlation
NASA Astrophysics Data System (ADS)
Martin, Guillaume; Balmes, Etienne; Chancelier, Thierry
2017-05-01
While modal identification is a mature subject, very few studies address the characterization of errors associated with components of a mode shape. This is particularly important in test/analysis correlation procedures, where the Modal Assurance Criterion is used to pair modes and to localize at which sensors discrepancies occur. Poor correlation is usually attributed to modeling errors, but clearly identification errors also occur. In particular with 3D Scanning Laser Doppler Vibrometer measurement, many transfer functions are measured. As a result individual validation of each measurement cannot be performed manually in a reasonable time frame and a notable fraction of measurements is expected to be fairly noisy leading to poor identification of the associated mode shape components. The paper first addresses measurements and introduces multiple criteria. The error measures the difference between test and synthesized transfer functions around each resonance and can be used to localize poorly identified modal components. For intermediate error values, diagnostic of the origin of the error is needed. The level evaluates the transfer function amplitude in the vicinity of a given mode and can be used to eliminate sensors with low responses. A Noise Over Signal indicator, product of error and level, is then shown to be relevant to detect poorly excited modes and errors due to modal property shifts between test batches. Finally, a contribution is introduced to evaluate the visibility of a mode in each transfer. Using tests on a drum brake component, these indicators are shown to provide relevant insight into the quality of measurements. In a second part, test/analysis correlation is addressed with a focus on the localization of sources of poor mode shape correlation. The MACCo algorithm, which sorts sensors by the impact of their removal on a MAC computation, is shown to be particularly relevant. Combined with the error it avoids keeping erroneous modal components. Applied after removal of poor modal components, it provides spatial maps of poor correlation, which help localizing mode shape correlation errors and thus prepare the selection of model changes in updating procedures.
Uncertainty in Reference and Information Service
ERIC Educational Resources Information Center
VanScoy, Amy
2015-01-01
Introduction: Uncertainty is understood as an important component of the information seeking process, but it has not been explored as a component of reference and information service. Method: Interpretative phenomenological analysis was used to examine the practitioner perspective of reference and information service for eight academic research…
A missed Fe-S cluster handoff causes a metabolic shakeup.
Berteau, Olivier
2018-05-25
The general framework of pathways by which iron-sulfur (Fe-S) clusters are assembled in cells is well-known, but the cellular consequences of disruptions to that framework are not fully understood. Crooks et al. report a novel cellular system that creates an acute Fe-S cluster deficiency, using mutants of ISCU, the main scaffold protein for Fe-S cluster assembly. Surprisingly, the resultant metabolic reprogramming leads to the accumulation of lipid droplets, a situation encountered in many poorly understood pathological conditions, highlighting unanticipated links between Fe-S assembly machinery and human disease. © 2018 Berteau.
The mystery of a supposed massive star exploding in a brightest cluster galaxy
NASA Astrophysics Data System (ADS)
Hosseinzadeh, Griffin
2017-08-01
Most of the diversity of core-collapse supernovae results from late-stage mass loss by their progenitor stars. Supernovae that interact with circumstellar material (CSM) are a particularly good probe of these last stages of stellar evolution. Type Ibn supernovae are a rare and poorly understood class of hydrogen-poor explosions that show signs of interaction with helium-rich CSM. The leading hypothesis is that they are explosions of very massive Wolf-Rayet stars in which the supernova ejecta excites material previously lost by stellar winds. These massive stars have very short lifetimes, and therefore should only found in actively star-forming galaxies. However, PS1-12sk is a Type Ibn supernova found on the outskirts of a giant elliptical galaxy. As this is extraordinary unlikely, we propose to obtain deep UV images of the host environment of PS1-12sk in order to map nearby star formation and/or find a potential unseen star-forming host. If star formation is detected, its amount and location will provide deep insights into the progenitor picture for the poorly-understood Type Ibn class. If star formation is still not detected, these observations would challenge the well-accepted hypothesis that these are core-collapse supernovae at all.
Exposure to mixtures is frequent, but biologic pathways such as metabolic inhibition, are poorly understood. CHCl3 and TCE are model volatiles frequently co-occurring; combined exposure results in less than additive hepatotoxicity. Here, we explore the underlying metabolic inte...
DOT National Transportation Integrated Search
1998-03-01
The contribution of a cement-stabilized base course to the strength of the rigid pavement structure is poorly understood. The objective of this research was to obtain data on the response of the rigid pavement slab-joint-foundation system by conducti...
Childhood asthma is a multifactorial disease with a disturbingly high incidence in urbanized areas. The pathogenesis of asthma is poorly understood due to the complex relationship between genetic susceptibility and modulating environmental factors. The Mechanistic Indicators of C...
NITROGEN OUTPUTS FROM FECAL AND URINE DEPOSITION OF SMALL MAMMALS: IMPLICATIONS FOR NITROGEN CYCLING
The contribution of small mammals to nitrogen cycling is poorly understood, but it could have reverberations back to the producer community by maintaining or perhaps magnifying nitrogen availability. Our objective was to model nitrogen outputs (deposition of feces and urine) of ...
Accumulation of the antibiotic phenazine-1-carboxylic acid in the rhizosphere of dryland cereals
USDA-ARS?s Scientific Manuscript database
Natural antibiotics are thought to function in microbial defense, fitness, competitiveness, biocontrol, communication and gene regulation. However, the frequency and amount of antibiotics produced in nature are poorly understood. In this study, we assessed the geographic distribution of indigenous p...
Genomic medicine and ethnic differences in cardiovascular disease risk
USDA-ARS?s Scientific Manuscript database
The origins of health disparities are a poorly understood public health problem. The effects of culture, environmental hazards, and social marginalization differ between ethnicities and have strong effects on health differences. The role of the genome in health is well established and we present a s...
BACKGROUND: Influenza peaks during the wintertime in temperate regions and during the annual rainy season in tropical regions – however reasons for the observed differences in disease ecology are poorly understood. We hypothesize that episodes of extreme precipitation also result...
USDA-ARS?s Scientific Manuscript database
During polarized growth of pollen tubes, endomembrane trafficking and actin polymerization are two critical processes that establish membrane/wall homeostasis and maintain growth polarity. Fine-tuned interactions between these two processes are therefore necessary but poorly understood. To better un...
DOT National Transportation Integrated Search
2016-02-01
Rural intersections account for 30% of crashes in rural areas and 6% of all fatal crashes, representing a significant but poorly : understood safety problem. Transportation agencies have traditionally implemented countermeasures to address rural inte...
Flavonoids, alkali earth and rare earth elements affect germination of pecan pollen
USDA-ARS?s Scientific Manuscript database
The factors regulating pecan [Carya illinoinensis (Wangenh.) K. Koch] pollen grain germination on receptive stigmatic flower surfaces in vivo or in vitro in pollen viability assays are poorly understood. While there are many potential regulating factors, there is evidence for involvement of flavonol...
Neural Correlates of Socioeconomic Status in the Developing Human Brain
ERIC Educational Resources Information Center
Noble, Kimberly G.; Houston, Suzanne M.; Kan, Eric; Sowell, Elizabeth R.
2012-01-01
Socioeconomic disparities in childhood are associated with remarkable differences in cognitive and socio-emotional development during a time when dramatic changes are occurring in the brain. Yet, the neurobiological pathways through which socioeconomic status (SES) shapes development remain poorly understood. Behavioral evidence suggests that…
USDA-ARS?s Scientific Manuscript database
Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-r...
NITROGEN OUTPUTS OF SMALL MAMMALS FROM FECAL AND URINE DEPOSITION: IMPLICATIONS FOR NITROGEN CYCLING
The contribution of small mammals in nitrogen cycling is poorly understood and could have reverberations back to the producer community by maintaining or even magnifying increased nitrogen availability. Our objective was to model nitrogen outputs (deposition of feces and urine) ...
Feeding behavior and injury caused by Lygus hesperus
USDA-ARS?s Scientific Manuscript database
Despite the importance of Lygus hesperus as a crop pest in the western United States, key aspects of its feeding behavior and consequent injury to cotton are poorly understood. Previous studies of Lygus stage-dependent injury to cotton produced conflicting results. We sought to clarify these relat...
Structural Equations and Causal Explanations: Some Challenges for Causal SEM
ERIC Educational Resources Information Center
Markus, Keith A.
2010-01-01
One common application of structural equation modeling (SEM) involves expressing and empirically investigating causal explanations. Nonetheless, several aspects of causal explanation that have an impact on behavioral science methodology remain poorly understood. It remains unclear whether applications of SEM should attempt to provide complete…
USDA-ARS?s Scientific Manuscript database
Contamination of aquatic habitats with anthropogenic nutrients has been associated with an increase in mosquito larval populations but the underlying mechanisms remain poorly understood. We examined the individual and combined effects of two synthetic fertilizers (ammonium sulfate and potassium chlo...
Verbal Understanding and Pavlovian Processes
ERIC Educational Resources Information Center
Tonneau, François
2004-01-01
The behavioral processes through which people react appropriately to verbal descriptions remain poorly understood. I argue here that these processes are Pavlovian. Common objections to a Pavlovian account of symbolic behavior evidence a lack of familiarity with the relevant data or misunderstandings of operant theory. Although much remains to be…
Redefining the Longitude/Latitude Experience with a Scaffolded Geocache
ERIC Educational Resources Information Center
Hammond, Thomas; Bozdin, Alec M.; Stanlick, Sarah E.
2014-01-01
Latitude and longitude are foundational concepts for geography education, yet they are typically poorly understood by students and receive indifferent attention from instructors and publishers' materials. Social studies teachers can take advantage of increasingly ubiquitous geolocating devices such as Global Positions Systems (GPS) to provide…
Wheat streak mosaic virus coat protein is a host-specific long-distance transport determinant in oat
USDA-ARS?s Scientific Manuscript database
Viral determinants involved in systemic infection of hosts by monocot-infecting plant viruses are poorly understood. Wheat streak mosaic virus (WSMV, genus Tritimovirus, family Potyviridae) exclusively infects monocotyledonous crops such as wheat, oat, barley, maize, triticale, and rye. Previously, ...
The Structure of Integral Dimensions: Contrasting Topological and Cartesian Representations
ERIC Educational Resources Information Center
Jones, Matt; Goldstone, Robert L.
2013-01-01
Diverse evidence shows that perceptually integral dimensions, such as those composing color, are represented holistically. However, the nature of these holistic representations is poorly understood. Extant theories, such as those founded on multidimensional scaling or general recognition theory, model integral stimulus spaces using a Cartesian…
Speleothems as Examples of Chemical Equilibrium Processes.
ERIC Educational Resources Information Center
Wilson, James R.
1984-01-01
The chemical formation of speleothems such as stalactites and stalagmites is poorly understood by introductory geology instructors and misrepresented in most textbooks. Although evaporation may be a controlling factor in some caves, it is necessary to consider chemical precipitation as more important in controlling the diagenesis of calcium…
Aboveground and belowground net primary production
Hal O. Liechty; Mark H. Eisenbies
2000-01-01
The relationship among net primary productivity (NPP), hydroperiod, and fertility in forested wetlands is poorly understood (Burke and others 1999), particularly with respect to belowground NPP (Megonigal and others 1997). Although some researchers have studied aboveground and belowground primary production in depressional, forested wetland systems, e.g., Day and...
Remote Sensing and Underwater Glider Observations of a Springtime Plume in Western Lake Superior
Plumes are commonly observed in satellite imagery of western Lake Superior following storm events, and represent a significant cross-shelf pathway for sediment and other constituents. However, their subsurface extent is poorly understood. This study reports results from plume ob...
Effects of Rhododendron maximum L. on Acer rubrum L. Seedling Establishment
Barton D. Clinton; James M. Vose
1996-01-01
Rhododendron maximum L. restricts regeneration of overstory species; however, the mechanisms are poorly understood. Three treatments were used to examine the effects of R. maximum germination success and survival of Acer rubrum L. under a closed overstory canopy: (1) R. maximum understory, (2)...
The effects of anthropogenic contaminants on Gulf of Mexico plant communities are poorly understood despite the threatened condition of a number of seagrass communities and wetland habitats. In this study, we focused particular attention on the concern that elevated nutrient
l...
The Psychophysiological Mechanisms of Alexithymia in Autism Spectrum Disorder
ERIC Educational Resources Information Center
Gaigg, Sebastian B.; Cornell, Anna S. F.; Bird, Geoffrey
2018-01-01
Accumulating evidence indicates that co-occurring alexithymia underlies several facets of the social-emotional difficulties common in individuals with autism spectrum disorder. The mechanisms involved, however, remain poorly understood because measuring alexithymia relies heavily on self-report. To address this issue, carefully matched groups of…
Spread and development of Phytophthora ramorum in a California christmas tree farm
Gary A. Chastagner; Kathy Riley; Norm Dart
2008-01-01
The risk of conifers being infected by Phytophthora ramorum under natural conditions is poorly understood. In California, infected conifers commonly occur as understory plants beneath or adjacent to heavily infected plants like California bay laurel (Umbellularia californica). During wet periods, P. ramorum is...
Satellite observation of particulate organic carbon dynamics on the Louisiana continental shelf
Particulate organic carbon (POC) plays an important role in coastal carbon cycling and the formation of hypoxia. Yet, coastal POC dynamics are often poorly understood due to a lack of long-term POC observations and the complexity of coastal hydrodynamic and biogeochemical process...
HYDRAULIC REDISTRIBUTION IN A DOUGLAS-FIR FOREST: LESSONS FROM SYSTEM MANIPULATIONS
Hydraulic redistribution (HR) has been shown to slow drying of surface soils during drought in Pacific Northwest forests, but the controls governing this process and its importance to shallow-rooted species are poorly understood. Our objective in this study was to manipulate the...
Perfluoro compounds are ubiquitous contaminants in human blood. The pathways which result in near universal exposure to humans in modern societies are not clearly understood. Sources to environmental compartments and transport between compartments are only poorly studies, and thi...
Glucose supplementation has minimal effects on blood neutrophil functionand gene expression in vitro
USDA-ARS?s Scientific Manuscript database
During early lactation, glucose availability is low and the effect of glucose supply on bovine polymorphonuclear leukocyte (PMNL) function is poorly understood. The objective of this study was to determine the effect of glucose supplementation on the function and transcriptomic inflammatory respons...
Soil type and species diversity influence selection on physiology in Panicum virgatum
USDA-ARS?s Scientific Manuscript database
Species diversity influences the productivity and stability of plant communities, but its effect on the evolution of species within those communities is poorly understood. In this study, we tested whether species diversity and soil type influence selection on physiology in switchgrass (Panicum virga...
Mechanisms of increased lifespan in hypoxia in the alfalfa leafcutting bee, Megachile rotundata
USDA-ARS?s Scientific Manuscript database
Genetic variation accounts for a small amount of variation in lifespan, while environmental stressors are strong predictors. Hypoxia is an environmental stress that increases longevity in some contexts, but the mechanisms remain poorly understood. In the bee Megachile rotundata, lifespan doubles upo...
EFFECTS OF DIESEL PARTICLE FREE RADICALS AND ORGANICS ON CYTOTOXICITY AND CELL SIGNALING
Diesel exhaust particles (DEPs) have been reported to induce inflammatory lung diseases, although the major contributing components in DEPs and the mechanisms remain to be understood. Organic components of DEPs are suspected to be responsible for the observed toxic effects, in a...
Can Earth Sciences Help Alleviate Global Poverty?
NASA Astrophysics Data System (ADS)
Mutter, J. C.
2004-12-01
Poverty is not properly described solely in terms of economics. Certainly the billion people living on less than a dollar a day are the extreme poor and the two billion people who are living today on two dollars a day or less are poor also. One third of all humans live in poverty today. But poverty concerns deprivation - of good health, adequate nutrition, adequate education, properly paid employment, clean water, adequate housing and good sanitation. It is a fundamental denial of opportunity and a violation of basic human rights. Despite its prevalence and persistence of poverty and the attention given it by many scholars, the causes of poverty are not well understood and hence interventions to bring poor societies out of their condition often fail. One commonly missed component in the search for solutions to poverty is the fundamental co-dependence between the state of the Earth and the state of human well-being. These relationships, are compelling but often indirect and non-linear and sometimes deeply nuanced. They are also largely empirical in nature, lacking theory or models that describe the nature of the relationships. So while it is quite apparent that the poorest people are much more vulnerable than the rich to the Earths excesses and even to relatively small natural variations in places where the base conditions are poor, we do not presently know whether the recognized vulnerability is both an outcome of poverty and a contributing cause. Are societies poor, or held from development out of poverty because of their particular relationship to Earth's natural systems? Does how we live depend on where we live? Providing answers to these questions is one of the most fundamental research challenges of our time. That research lies in a domain squarely at the boundary between the natural and social sciences and cannot be answered by studies in either domain alone. What is clear even now, is that an understanding of the Earth gained from the natural sciences is essential and could hold the key to making gains toward alleviating the burden of global poverty.
Evidence synthesis and its role in evidence-based health care.
Pearson, Alan
2014-12-01
The central role of evidence synthesis (or the systematic review of evidence) in evidence-based health care is often poorly understood. There are numerous examples in the literature of poorly conceived and/or executed systematic reviews and of a lack of awareness of the international standards developed by the international leaders in systematic reviews. The Cochrane Collaboration has played a critical global role in developing and refining systematic review methods in relation to evidence of effects and of diagnostic accuracy. Copyright © 2014 Elsevier Inc. All rights reserved.
USDA-ARS?s Scientific Manuscript database
In lower vertebrates, the contribution of the spleen to anti-bacterial immunity is poorly understood. Researchers have previously reported a phenotypic and genetic correlation between resistance to Flavobacterium psychrophilum, the causative agent of bacterial cold water disease (BCWD) and spleen so...
A sprinkling experiment to quantify celerity-velocity differences at the hillslope scale
The difference between celerity and velocity of hillslope water flow is poorly understood. We assessed these differences by combining a 24-day hillslope sprinkling experiment with a spatially explicit hydrologic model analysis. We focused our work at Watershed 10 at the H.J. And...
Impaired Associative Taste Learning and Abnormal Brain Activation in Kinase-Defective eEF2K Mice
ERIC Educational Resources Information Center
Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W.; Proud, Chris G.; Rosenblum, Kobi
2012-01-01
Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular…