Behavioral Assessment of Feeding Problems of Individuals with Severe Disabilities.

ERIC Educational Resources Information Center

Munk, Dennis D.; Repp, Alan C.

1994-01-01

A behavioral assessment procedure was evaluated with five children with severe/profound mental retardation who exhibited feeding problems of limited intake. Subjects were fed various types of foods. Results indicated each subject fit into one of four categories: (1) total food refusal, (2) food type selectivity, (3) food texture selectivity, or…

Oral Language Comprehension Using Hearing Aids and Tactile Aids: Three Case Studies.

ERIC Educational Resources Information Center

Proctor, Adele

1990-01-01

Three prelinguistic, profoundly deaf children (aged three to four) used a wearable, single channel, vibrotactile communication aid in conjunction with hearing aids during individual speech and language therapy at school. Subjects exhibited a faster than average rate of learning to understand spoken language after the onset of vibrotactile…

Profound Bilateral Sensorineural Hearing Loss in Nigerian Children: Any Shift in Etiology?

ERIC Educational Resources Information Center

Dunmade, A. D.; Segun-Busari, S.; Olajide, T. G.; Ologe, F. E.

2007-01-01

Deafness, profound hearing loss, is a global problem. However, the causes of, attitudes toward, and management options for deafness differ considerably from region to region. This study seeks to identify the present causes of profound sensorineural hearing loss in Nigeria, which in our environment is almost synonymous to a life sentence of silence…

Real space flight travel is associated with ultrastructural changes, cytoskeletal disruption and premature senescence of HUVEC.

PubMed

Kapitonova, M Y; Muid, S; Froemming, G R A; Yusoff, W N W; Othman, S; Ali, A M; Nawawi, H M

2012-12-01

Microgravity, hypergravity, vibration, ionizing radiation and temperature fluctuations are major factors of outer space flight affecting human organs and tissues. There are several reports on the effect of space flight on different human cell types of mesenchymal origin while information regarding changes to vascular endothelial cells is scarce. Ultrastructural and cytophysiological features of macrovascular endothelial cells in outer space flight and their persistence during subsequent culturing were demonstrated in the present investigation. At the end of the space flight, endothelial cells displayed profound changes indicating cytoskeletal lesions and increased cell membrane permeability. Readapted cells of subsequent passages exhibited persisting cytoskeletal changes, decreased metabolism and cell growth indicating cellular senescence.

The educational settings of profoundly deaf children with cochlear implants compared with age-matched peers with hearing aids: implications for management.

PubMed

Archbold, Sue M; Nikolopoulos, Thomas P; Lutman, Mark E; O'Donoghue, Gerard M

2002-04-01

The educational settings of 42 implanted profoundly deaf children 3 years after implantation were compared with the respective settings of 635 age-matched severely deaf and 511 profoundly deaf children with hearing aids. All implanted children received their implants before beginning school. The results revealed that 3 years after implantation. 38% (16 children) of the implanted profoundly deaf children attended mainstream schools, whereas 57% (24 children) were in a unit, or special class, in a mainstream school, and 5% (two children) were in schools for the deaf. With regard to the age-matched profoundly deaf children with hearing aids, 12% (63 children) attended mainstream schools, whereas 55% (281 children) were in a unit of a mainstream school, and 33% (167 children) were in schools for the deaf. In the group of age-matched severely deaf children, 38% (239 children) attended mainstream schools, whereas 51% (326 children) were in a unit of a mainstream school, and 11% (70 children) were in schools for the deaf. Statistical analysis revealed a highly significant difference between the educational placement of implanted children and hearing-aided profoundly deaf children (p<0.00001), whereas there was no statistically significant difference between implanted children and hearing-aided severely deaf children. In conclusion, implanted profoundly deaf children who have received their implants before beginning school have the same profile of educational placement as aided severely deaf children rather than aided profoundly deaf children of the same age in the UK. This is likely to have significant implications for the future management of profoundly deaf children and to influence future planning of educational support services.

Severe to profound hearing impairment: quality of life, psychosocial consequences and audiological rehabilitation.

PubMed

Carlsson, Per-Inge; Hjaldahl, Jennie; Magnuson, Anders; Ternevall, Elisabeth; Edén, Margareta; Skagerstrand, Åsa; Jönsson, Radi

2015-01-01

To study the quality of life (QoL) and psychosocial consequences in terms of sick leave and audiological rehabilitation given to patients with severe to profound hearing impairment. A retrospective study of data on 2319 patients with severe to profound hearing impairment in The Swedish Quality Register of Otorhinolaryngology, followed by a posted questionnaire including The Hospital Anxiety and Depression Scale (HADS). The results indicate greater levels of anxiety and depression among patients with severe or profound hearing impairment than in the general population, and annoying tinnitus and vertigo had strong negative effects on QoL. The proportion of sick leave differed between the studied dimensions in the study. The proportion of patients who received extended audiological rehabilitation was 38% in the present study. Treatment focused on anxiety, depression, tinnitus and vertigo must be given early in the rehabilitation process in patients with severe or profound hearing impairment. Because sick leave differs greatly within this group of patients, collaboration with the regional Social Insurance Agency is crucial part of the rehabilitation. The study also shows that presently, only a small proportion of patients in Sweden with severe to profound hearing impairment receive extended audiological rehabilitation. Implications for Rehabilitation Greater levels of anxiety and depression have been found among patients with severe or profound hearing impairment than in the general population, and annoying tinnitus and vertigo have strong negative effects on QoL in this group of patients. Only a small proportion of patients with severe to profound hearing impairment receive extended audiological rehabilitation today, including medical, technical and psychosocial efforts. Extended audiological rehabilitation focused on anxiety, depression, tinnitus and vertigo must be given, together with technical rehabilitation, early in the rehabilitation process in patients with severe or profound hearing impairment.

Decreasing Self-Stimulating Behaviors with the Profoundly Mentally Retarded, While Acknowledging Obstacles and Frustrations.

ERIC Educational Resources Information Center

Smith, Susan J.; Solimani, Genevieve

Two studies examined different treatment procedures to suppress self-stimulating behaviors with the profoundly mentally retarded. In experiment 1, a fine mist of cold water from a spray bottle was applied to the neck of a teenaged student in a class for the profoundly retarded. The intervention was very successful in reducing inappropriate humming…

High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD)

USDA-ARS?s Scientific Manuscript database

Patients with advanced CKD exhibit profound changes in the composition and function of the gut microbiome. This is, in part, mediated by: I- heavy influx of urea in the intestinal tract leading to the dominance of urease-possessing bacteria and II- dietary restriction of potassium-rich fruits and ve...

Faculty Scholarship Has a Profound Positive Association with Student Evaluations of Teaching--Except When It Doesn't

ERIC Educational Resources Information Center

Carter, Robert E.

2016-01-01

Conventional wisdom holds that research-productive faculty are also the finest instructors. But, is this commonly held belief correct? In the current study, the notion that faculty scholarship exhibits a positive association with teaching evaluations is investigated. Reflecting the data structure of faculty nested within university, the current…

Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

PubMed

Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

2016-06-01

Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P < 0.05) than controls and exhibited hypoxemia and hypoglycemia, which contributed to 6.9-fold greater (P < 0.05) plasma norepinephrine and ∼53% lower (P < 0.05) plasma insulin concentrations. IUGR semitendinosus muscles contained less (P < 0.05) myosin heavy chain-I protein (MyHC-I) and proportionally fewer (P < 0.05) Type I and Type I/IIa fibers than controls, but MyHC-II protein concentrations, Type II fibers, and Type IIx fibers were not different. IUGR biceps femoris muscles exhibited similar albeit less dramatic differences in fiber type proportions. Type I and IIa fibers are more responsive to adrenergic and insulin regulation than Type IIx and may be more profoundly impaired by the high catecholamines and low insulin in our IUGR fetuses, leading to their proportional reduction. In both muscles, fibers of each type were uniformly smaller (P < 0.05) in IUGR fetuses than controls, which indicates that fiber hypertrophy is not dependent on type but rather on other factors such as myoblast differentiation or protein synthesis. Together, our findings show that IUGR fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

Ferroelectric order in liquid crystal phases of polar disk-shaped ellipsoids

NASA Astrophysics Data System (ADS)

Bose, Tushar Kanti; Saha, Jayashree

2014-05-01

The demonstration of a spontaneous macroscopic ferroelectric order in liquid phases in the absence of any long range positional order is considered an outstanding problem of both fundamental and technological interest. Recently, we reported that a system of polar achiral disklike ellipsoids can spontaneously exhibit a long searched ferroelectric nematic phase and a ferroelectric columnar phase with strong axial polarization. The major role is played by the dipolar interactions. The model system of interest consists of attractive-repulsive Gay-Berne oblate ellipsoids embedded with two parallel point dipoles positioned symmetrically on the equatorial plane of the ellipsoids. In the present work, we investigate in detail the profound effects of changing the separation between the two symmetrically placed dipoles and the strength of the dipoles upon the existence of different ferroelectric discotic liquid crystal phases via extensive off-lattice N-P-T Monte Carlo simulations. Ferroelectric biaxial phases are exhibited in addition to the uniaxial ferroelectric fluids where the phase biaxiality results from the dipolar interactions. The structures of all the ferroelectric configurations of interest are presented in detail. Simple phase diagrams are determined which include different polar and apolar discotic fluids generated by the system.

Unraveling the Complex Relationship Triad between Lipids, Obesity, and Inflammation

PubMed Central

Khan, Shahida A.; Khan, Sarah A.; Zahran, Solafa A.; Damanhouri, Ghazi

2014-01-01

Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs) and G protein coupled receptors (GPCRs). In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators. PMID:25258478

The Reconstruction of Greyfriars Kirkyard’s Sacred Space: From the Franciscan Order’s “Divinity Heaven Garden” into the Protestant’s “the Sacred Cemetery”

NASA Astrophysics Data System (ADS)

Li, Xin; Cao, Lei; Ma, Yifeng

2017-08-01

The Scottish Reformation in the sixteenth century had a profound influence on the layout and function of Greyfriars Kirkyard. Since the Reformation it has been used in various ways such as a public cemetery, a weapon exhibition and military exercises site, and as the Covenanters prison. By exhaustively perusing historical documents, comparing different layouts in Edinburgh antique maps, and analyzing the epitaphs and engraved monuments within the cemetery, I have concluded the reconstructive principles of the sacred space represent three major shifts. The space has moved from sacred to secular from a single faith to multiple denominational and from an oppressive environment to a supportive one.

Potential roles for transposable elements in creating imprinted expression.

PubMed

Anderson, Sarah N; Springer, Nathan M

2018-04-01

Changes in gene expression can have profound effects on phenotype. Nature has provided many complex patterns of gene regulation such as imprinting. Imprinted genes exhibit differences in the expression of the maternal and paternal alleles, even though they reside in the same nucleus with access to the same trans-acting factors. Significant attention has been focused on the potential reasons that imprinted expression could be beneficial and stabilized by selection. However, less attention has focused on understanding how imprinted expression might arise or decay. We discuss the evidence for frequent turnover of imprinted expression based on evolutionary analyses in plants and the potential role for transposable elements (TEs) in creating imprinted expression patterns. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mathematics and complex systems.

PubMed

Foote, Richard

2007-10-19

Contemporary researchers strive to understand complex physical phenomena that involve many constituents, may be influenced by numerous forces, and may exhibit unexpected or emergent behavior. Often such "complex systems" are macroscopic manifestations of other systems that exhibit their own complex behavior and obey more elemental laws. This article proposes that areas of mathematics, even ones based on simple axiomatic foundations, have discernible layers, entirely unexpected "macroscopic" outcomes, and both mathematical and physical ramifications profoundly beyond their historical beginnings. In a larger sense, the study of mathematics itself, which is increasingly surpassing the capacity of researchers to verify "by hand," may be the ultimate complex system.

The Yersiniabactin-Associated ATP Binding Cassette Proteins YbtP and YbtQ Enhance Escherichia coli Fitness during High-Titer Cystitis

PubMed Central

Koh, Eun-Ik; Hung, Chia S.

2016-01-01

The Yersinia high-pathogenicity island (HPI) is common to multiple virulence strategies used by Escherichia coli strains associated with urinary tract infection (UTI). Among the genes in this island are ybtP and ybtQ, encoding distinctive ATP binding cassette (ABC) proteins associated with iron(III)-yersiniabactin import in Yersinia pestis. In this study, we compared the impact of ybtPQ on a model E. coli cystitis strain during in vitro culture and experimental murine infections. A ybtPQ-null mutant exhibited no growth defect under standard culture conditions, consistent with nonessentiality in this background. A growth defect phenotype was observed and genetically complemented in vitro during iron(III)-yersiniabactin-dependent growth. Following inoculation into the bladders of C3H/HEN and C3H/HeOuJ mice, this strain exhibited a profound, 106-fold competitive infection defect in the subgroup of mice that progressed to high-titer bladder infections. These results identify a virulence role for YbtPQ in the highly inflammatory microenvironment characteristic of high-titer cystitis. The profound competitive defect may relate to the apparent selection of Yersinia HPI-positive E. coli in uncomplicated clinical UTIs. PMID:26883590

Executive Function Variation in Children with Conduct Problems: Influences of Coexisting Reading Difficulties

ERIC Educational Resources Information Center

Kallitsoglou, Angeliki

2018-01-01

It is unknown whether children with conduct problems (CP) and poor reading (PR) skills exhibit more profound executive function impairments than children with CP only and whether such impairments are explained by coexisting PR. Executive functions were compared in four groups of 7- to 8-year-old children: 26 CP only, 35 PR only, 27 CP-PR, and 31…

A Coordination Chemistry Approach to Fine-Tune the Physicochemical Parameters of Lanthanide Complexes Relevant to Medical Applications.

PubMed

Le Fur, Mariane; Molnár, Enikő; Beyler, Maryline; Kálmán, Ferenc K; Fougère, Olivier; Esteban-Gómez, David; Rousseaux, Olivier; Tripier, Raphaël; Tircsó, Gyula; Platas-Iglesias, Carlos

2018-03-02

The geometric features of two pyclen-based ligands possessing identical donor atoms but different site organization have a profound impact in their complexation properties toward lanthanide ions. The ligand containing two acetate groups and a picolinate arm arranged in a symmetrical fashion (L1) forms a Gd 3+ complex being two orders of magnitude less stable than its dissymmetric analogue GdL2. Besides, GdL1 experiences a much faster dissociation following the acid-catalyzed mechanism than GdL2. On the contrary, GdL1 exhibits a lower exchange rate of the coordinated water molecule compared to GdL2. These very different properties are related to different strengths of the Gd-ligand bonds associated to steric effects, which hinder the coordination of a water molecule in GdL2 and the binding of acetate groups in GdL1. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro production of azadirachtin from cell suspension cultures of Azadirachta indica.

PubMed

Sujanya, S; Devi, B Poornasri; Sai, Isha

2008-03-01

The present study aimed to elucidate the effect of nutritional alteration on biomass content and azadirachtin production in cell suspensions of the elite neem variety crida-8. Variations in total nitrogen availability in the medium in terms of different ratios of nitrate: ammonium showed that the ratio 4:1 revealed a profound effect, leading to a 1.5-fold increase in the total extracellular azadirachtin production (5.59 mg/l) over the standard MS medium. Reduction in sucrose (15 mg/l) in the medium exhibited a reduction in biomass and absence of azadirachtin, whereas total phosphate reduction raised intracellular azadirachtin production (6.98 mg/l). An altered medium with a nitrate: ammonium ratio of 4:1 coupled with complete elimination of phosphate enhanced biomass by 36% (59.36 g/l).

Analysis of Historic Copper Patinas. Influence of Inclusions on Patina Uniformity

PubMed Central

Chang, Tingru; Odnevall Wallinder, Inger; de la Fuente, Daniel; Chico, Belen; Morcillo, Manuel; Welter, Jean-Marie; Leygraf, Christofer

2017-01-01

The morphology and elemental composition of cross sections of eight historic copper materials have been explored. The materials were taken from copper roofs installed in different middle and northern European environments from the 16th to the 19th century. All copper substrates contain inclusions of varying size, number and composition, reflecting different copper ores and production methods. The largest inclusions have a size of up to 40 μm, with most inclusions in the size ranging between 2 and 10 μm. The most common element in the inclusions is O, followed by Pb, Sb and As. Minor elements include Ni, Sn and Fe. All historic patinas exhibit quite fragmentized bilayer structures, with a thin inner layer of cuprite (Cu2O) and a thicker outer one consisting mainly of brochantite (Cu4SO4(OH)6). The extent of patina fragmentation seems to depend on the size of the inclusions, rather than on their number and elemental composition. The larger inclusions are electrochemically nobler than the surrounding copper matrix. This creates micro-galvanic effects resulting both in a profound influence on the homogeneity and morphology of historic copper patinas and in a significantly increased ratio of the thicknesses of the brochantite and cuprite layers. The results suggest that copper patinas formed during different centuries exhibit variations in uniformity and corrosion protection ability. PMID:28772659

Capsicum and capsaicin--a review: case report of the use of hot peppers in child abuse.

PubMed

Tominack, R L; Spyker, D A

1987-01-01

Capsaicin, the active principle of hot peppers of the genus Capsicum, exhibits broad bioactivity. It targets neuronal structures which contain substance P, clinically seen as gastrointestinal and dermatologic irritation, bronchospasm and fibrinolysis. As a research tool, capsaicin profoundly alters neurologic anatomy and function. We review the toxicity of capsaicin and comment briefly on the use of hot peppers in child abuse.

Perceptions of variability in facial emotion influence beliefs about the stability of psychological characteristics.

PubMed

Weisbuch, Max; Grunberg, Rebecca L; Slepian, Michael L; Ambady, Nalini

2016-10-01

Beliefs about the malleability versus stability of traits (incremental vs. entity lay theories) have a profound impact on social cognition and self-regulation, shaping phenomena that range from the fundamental attribution error and group-based stereotyping to academic motivation and achievement. Less is known about the causes than the effects of these lay theories, and in the current work the authors examine the perception of facial emotion as a causal influence on lay theories. Specifically, they hypothesized that (a) within-person variability in facial emotion signals within-person variability in traits and (b) social environments replete with within-person variability in facial emotion encourage perceivers to endorse incremental lay theories. Consistent with Hypothesis 1, Study 1 participants were more likely to attribute dynamic (vs. stable) traits to a person who exhibited several different facial emotions than to a person who exhibited a single facial emotion across multiple images. Hypothesis 2 suggests that social environments support incremental lay theories to the extent that they include many people who exhibit within-person variability in facial emotion. Consistent with Hypothesis 2, participants in Studies 2-4 were more likely to endorse incremental theories of personality, intelligence, and morality after exposure to multiple individuals exhibiting within-person variability in facial emotion than after exposure to multiple individuals exhibiting a single emotion several times. Perceptions of within-person variability in facial emotion-rather than perceptions of simple diversity in facial emotion-were responsible for these effects. Discussion focuses on how social ecologies shape lay theories. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

KLF2 and KLF4 control endothelial identity and vascular integrity

PubMed Central

Sangwung, Panjamaporn; Zhou, Guangjin; Nayak, Lalitha; Chan, E. Ricky; Kang, Dong-Won; Zhang, Rongli; Lu, Yuan; Sugi, Keiki; Fujioka, Hisashi; Shi, Hong; Lapping, Stephanie D.; Ghosh, Chandra C.; Higgins, Sarah J.; Parikh, Samir M.; Jain, Mukesh K.

2017-01-01

Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome, thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal. PMID:28239661

Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms.

PubMed

Engler, Harald; Benson, Sven; Wegner, Alexander; Spreitzer, Ingo; Schedlowski, Manfred; Elsenbruch, Sigrid

2016-02-01

Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness response. Disturbance of these compensatory mechanisms by environmental factors such as stress may promote the development of affective disorders in women. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamics of GnRH Neuron Ionotropic GABA and Glutamate Synaptic Receptors Are Unchanged during Estrogen Positive and Negative Feedback in Female Mice.

PubMed

Liu, Xinhuai; Porteous, Robert; Herbison, Allan E

2017-01-01

Inputs from GABAergic and glutamatergic neurons are suspected to play an important role in regulating the activity of the gonadotropin-releasing hormone (GnRH) neurons. The GnRH neurons exhibit marked plasticity to control the ovarian cycle with circulating estradiol concentrations having profound "feedback" effects on their activity. This includes "negative feedback" responsible for suppressing GnRH neuron activity and "positive feedback" that occurs at mid-cycle to activate the GnRH neurons to generate the preovulatory luteinizing hormone surge. In the present study, we employed brain slice electrophysiology to question whether synaptic ionotropic GABA and glutamate receptor signaling at the GnRH neuron changed at times of negative and positive feedback. We used a well characterized estradiol (E)-treated ovariectomized (OVX) mouse model to replicate negative and positive feedback. Miniature and spontaneous postsynaptic currents (mPSCs and sPSCs) attributable to GABA A and glutamatergic receptor signaling were recorded from GnRH neurons obtained from intact diestrous, OVX, OVX + E (negative feedback), and OVX + E+E (positive feedback) female mice. Approximately 90% of GnRH neurons exhibited spontaneous GABA A -mPSCs in all groups but no significant differences in the frequency or kinetics of mPSCs were found at the times of negative or positive feedback. Approximately 50% of GnRH neurons exhibited spontaneous glutamate mPSCs but again no differences were detected. The same was true for spontaneous PSCs in all cases. These observations indicate that the kinetics of ionotropic GABA and glutamate receptor synaptic transmission to GnRH neurons remain stable across the different estrogen feedback states.

High transmittance hetero junctions based on n-ITO/p-CuO bilayer thin films

NASA Astrophysics Data System (ADS)

Jaya, T. P.; Pradyumnan, P. P.

2016-12-01

Oxide based bilayered n-ITO/p-CuO crystalline diodes were fabricated by plasma vapor deposition using radio frequency magnetron sputtering. The p-n hetero junction diodes were highly transparent in the visible region and exhibits rectifying I-V characteristics. The substrate temperature during fabrication of p-layer CuO was found to have a profound influence on I-V characteristics. The films deposited at substrate temperature of 150 °C and 230 °C exhibited diode ideality factors of (η value) 1.731 and 1.862 respectively. This high ideality factor, combined with an optical transparency of above 70% suggests the potential use of these bi-layers in optoelectronic applications.

Comparative Evaluation of the Auditory Responsiveness of Normal Infants and Profoundly Multihandicapped Children.

ERIC Educational Resources Information Center

Flexer, Carol; Gans, Donald P.

1985-01-01

Responses to sound were observed in two groups of children (one developmentally normal, the other older but profoundly multihandicapped). Results showed no significant differences between groups. In both groups, however, responsiveness was dependent on hearing level and bandwidth but not on meaningfulness. Results support the practice of…

A model for inferring transport rates from observed confinement times in field-reversed configurations

NASA Astrophysics Data System (ADS)

Steinhauer, Loren C.; Milroy, Richard D.; Slough, John T.

1985-03-01

A one-dimensional transport model is developed to simulate the confinement of plasma and magnetic flux in a field-reversed configuration. Given the resistivity, the confinement times can be calculated. Approximate expressions are found which yield the magnitude and gross profile of the resistivity if the confinement times are known. These results are applied to experimental data from experiments, primarily TRX-1, to uncover trends in the transport properties. Several important conclusions emerge. The transport depends profoundly, and inexplicably, on the plasma formation mode. The inferred transport differs in several ways from the predictions of local lower-hybrid-drift turbulence theory. Finally, the gross resistivity exhibits an unusual trend with xs (separatrix radius rs divided by the conducting wall radius rc ), and is peaked near the magnetic axis for certain predictable conditions.

Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer Therapeutics.

PubMed

Sarosiek, Kristopher A; Fraser, Cameron; Muthalagu, Nathiya; Bhola, Patrick D; Chang, Weiting; McBrayer, Samuel K; Cantlon, Adam; Fisch, Sudeshna; Golomb-Mello, Gail; Ryan, Jeremy A; Deng, Jing; Jian, Brian; Corbett, Chris; Goldenberg, Marti; Madsen, Joseph R; Liao, Ronglih; Walsh, Dominic; Sedivy, John; Murphy, Daniel J; Carrasco, Daniel Ruben; Robinson, Shenandoah; Moslehi, Javid; Letai, Anthony

2017-01-09

It is not understood why healthy tissues can exhibit varying levels of sensitivity to the same toxic stimuli. Using BH3 profiling, we find that mitochondria of many adult somatic tissues, including brain, heart, and kidneys, are profoundly refractory to pro-apoptotic signaling, leading to cellular resistance to cytotoxic chemotherapies and ionizing radiation. In contrast, mitochondria from these tissues in young mice and humans are primed for apoptosis, predisposing them to undergo cell death in response to genotoxic damage. While expression of the apoptotic protein machinery is nearly absent by adulthood, in young tissues its expression is driven by c-Myc, linking developmental growth to cell death. These differences may explain why pediatric cancer patients have a higher risk of developing treatment-associated toxicities. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

PubMed

Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

2015-08-01

In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical Applications of Hallucinogens: A Review

PubMed Central

Garcia-Romeu, Albert; Kersgaard, Brennan; Addy, Peter H.

2016-01-01

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. PMID:27454674

Toxic shock syndrome in two dogs.

PubMed

Slovak, Jennifer E; Parker, Valerie J; Deitz, Krysta L

2012-01-01

Two young, unrelated, spayed female Labrador retrievers were evaluated for severe, diffuse, generalized erythema and edema of the skin. Both dogs exhibited signs of disseminated intravascular coagulopathy and were euthanized. On postmortem examination, toxic shock syndrome (TSS) was diagnosed based on histopathology and supported by skin cultures. TSS is a rarely reported disease in veterinary medicine and can cause acute and profound clinical signs. Rapid recognition of this disease process and immediate treatment may improve the clinical outcome.

Development and characterization of a mouse with profound biotinidase deficiency: a biotin-responsive neurocutaneous disorder.

PubMed

Pindolia, Kirit; Jordan, Megan; Guo, Caiying; Matthews, Nell; Mock, Donald M; Strovel, Erin; Blitzer, Miriam; Wolf, Barry

2011-02-01

Biotinidase deficiency is the primary enzymatic defect in biotin-responsive, late-onset multiple carboxylase deficiency. Untreated children with profound biotinidase deficiency usually exhibit neurological symptoms including lethargy, hypotonia, seizures, developmental delay, sensorineural hearing loss and optic atrophy; and cutaneous symptoms including skin rash, conjunctivitis and alopecia. Although the clinical features of the disorder markedly improve or are prevented with biotin supplementation, some symptoms, once they occur, such as developmental delay, hearing loss and optic atrophy, are usually irreversible. To prevent development of symptoms, the disorder is screened for in the newborn period in essentially all states and in many countries. In order to better understand many aspects of the pathophysiology of the disorder, we have developed a transgenic biotinidase-deficient mouse. The mouse has a null mutation that results in no detectable serum biotinidase activity or cross-reacting material to antibody prepared against biotinidase. When fed a biotin-deficient diet these mice develop neurological and cutaneous symptoms, carboxylase deficiency, mild hyperammonemia, and exhibit increased urinary excretion of 3-hydroxyisovaleric acid and biotin and biotin metabolites. The clinical features are reversed with biotin supplementation. This biotinidase-deficient animal can be used to study systematically many aspects of the disorder and the role of biotinidase, biotin and biocytin in normal and in enzyme-deficient states. Copyright © 2010 Elsevier Inc. All rights reserved.

Nanocarbon Allotropes-Graphene and Nanocrystalline Diamond-Promote Cell Proliferation.

PubMed

Verdanova, Martina; Rezek, Bohuslav; Broz, Antonin; Ukraintsev, Egor; Babchenko, Oleg; Artemenko, Anna; Izak, Tibor; Kromka, Alexander; Kalbac, Martin; Hubalek Kalbacova, Marie

2016-05-01

Two profoundly different carbon allotropes - nanocrystalline diamond and graphene - are of considerable interest from the viewpoint of a wide range of biomedical applications including implant coating, drug and gene delivery, cancer therapy, and biosensing. Osteoblast adhesion and proliferation on nanocrystalline diamond and graphene are compared under various conditions such as differences in wettability, topography, and the presence or absence of protein interlayers between cells and the substrate. The materials are characterized in detail by means of scanning electron microscopy, atomic force microscopy, photoelectron spectroscopy, Raman spectroscopy, and contact angle measurements. In vitro experiments have revealed a significantly higher degree of cell proliferation on graphene than on nanocrystalline diamond and a tissue culture polystyrene control material. Proliferation is promoted, in particular, by hydrophobic graphene with a large number of nanoscale wrinkles independent of the presence of a protein interlayer, i.e., substrate fouling is not a problematic issue in this respect. Nanowrinkled hydrophobic graphene, thus, exhibits superior characteristics for those biomedical applications where high cell proliferation is required under differing conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Growth efficiency in transgenic tilapia (Oreochromis sp.) carrying a single copy of an homologous cDNA growth hormone.

PubMed

Martínez, R; Juncal, J; Zaldívar, C; Arenal, A; Guillén, I; Morera, V; Carrillo, O; Estrada, M; Morales, A; Estrada, M P

2000-01-07

Growth hormone (GH) has been shown to have a profound impact on fish physiology and metabolism. However, detailed studies in transgenic fish have not been conducted. We have characterized the food conversion efficiency, protein profile, and biochemical correlates of growth rate in transgenic tilapia expressing the tilapia GH cDNA under the control of human cytomegalovirus regulatory sequences. Transgenic tilapia exhibited about 3.6-fold less food consumption than nontransgenic controls (P < 0.001). The food conversion efficiency was significantly (P < 0.05) higher (290%) in transgenic tilapia (2.3 +/- 0.4) than in the control group (0.8 +/- 0.2). Efficiency of growth, synthesis retention, anabolic stimulation, and average protein synthesis were higher in transgenic than in nontransgenic tilapia. Distinctive metabolic differences were found in transgenic juvenile tilapia. We had found differences in hepatic glucose, and in agreement with previous results we observed differences in the level of enzymatic activities in target organs. We conclude that GH-transgenic juvenile tilapia show altered physiological and metabolic conditions and are biologically more efficient. Copyright 2000 Academic Press.

Trophic divergence despite morphological convergence in a continental radiation of snakes

PubMed Central

Grundler, Michael C.; Rabosky, Daniel L.

2014-01-01

Ecological and phenotypic convergence is a potential outcome of adaptive radiation in response to ecological opportunity. However, a number of factors may limit convergence during evolutionary radiations, including interregional differences in biogeographic history and clade-specific constraints on form and function. Here, we demonstrate that a single clade of terrestrial snakes from Australia—the oxyuranine elapids—exhibits widespread morphological convergence with a phylogenetically diverse and distantly related assemblage of snakes from North America. Australian elapids have evolved nearly the full spectrum of phenotypic modalities that occurs among North American snakes. Much of the convergence appears to involve the recurrent evolution of stereotyped morphologies associated with foraging mode, locomotion and habitat use. By contrast, analysis of snake diets indicates striking divergence in feeding ecology between these faunas, partially reflecting regional differences in ecological allometry between Australia and North America. Widespread phenotypic convergence with the North American snake fauna coupled with divergence in feeding ecology are clear examples of how independent continental radiations may converge along some ecological axes yet differ profoundly along others. PMID:24920479

Trophic divergence despite morphological convergence in a continental radiation of snakes.

PubMed

Grundler, Michael C; Rabosky, Daniel L

2014-07-22

Ecological and phenotypic convergence is a potential outcome of adaptive radiation in response to ecological opportunity. However, a number of factors may limit convergence during evolutionary radiations, including interregional differences in biogeographic history and clade-specific constraints on form and function. Here, we demonstrate that a single clade of terrestrial snakes from Australia--the oxyuranine elapids--exhibits widespread morphological convergence with a phylogenetically diverse and distantly related assemblage of snakes from North America. Australian elapids have evolved nearly the full spectrum of phenotypic modalities that occurs among North American snakes. Much of the convergence appears to involve the recurrent evolution of stereotyped morphologies associated with foraging mode, locomotion and habitat use. By contrast, analysis of snake diets indicates striking divergence in feeding ecology between these faunas, partially reflecting regional differences in ecological allometry between Australia and North America. Widespread phenotypic convergence with the North American snake fauna coupled with divergence in feeding ecology are clear examples of how independent continental radiations may converge along some ecological axes yet differ profoundly along others. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Sequence Determinants of Compaction in Intrinsically Disordered Proteins

PubMed Central

Marsh, Joseph A.; Forman-Kay, Julie D.

2010-01-01

Abstract Intrinsically disordered proteins (IDPs), which lack folded structure and are disordered under nondenaturing conditions, have been shown to perform important functions in a large number of cellular processes. These proteins have interesting structural properties that deviate from the random-coil-like behavior exhibited by chemically denatured proteins. In particular, IDPs are often observed to exhibit significant compaction. In this study, we have analyzed the hydrodynamic radii of a number of IDPs to investigate the sequence determinants of this compaction. Net charge and proline content are observed to be strongly correlated with increased hydrodynamic radii, suggesting that these are the dominant contributors to compaction. Hydrophobicity and secondary structure, on the other hand, appear to have negligible effects on compaction, which implies that the determinants of structure in folded and intrinsically disordered proteins are profoundly different. Finally, we observe that polyhistidine tags seem to increase IDP compaction, which suggests that these tags have significant perturbing effects and thus should be removed before any structural characterizations of IDPs. Using the relationships observed in this analysis, we have developed a sequence-based predictor of hydrodynamic radius for IDPs that shows substantial improvement over a simple model based upon chain length alone. PMID:20483348

Detoxification function of the Arabidopsis sulphotransferase AtSOT12 by sulphonation of xenobiotics.

PubMed

Chen, Jinhua; Gao, Liqiong; Baek, Dongwon; Liu, Chunlin; Ruan, Ying; Shi, Huazhong

2015-08-01

Cytosolic sulphotransferases have been implicated in inactivation of endogenous steroid hormones and detoxification of xenobiotics in human and animals. Yet, the function of plant sulphotransferases in xenobiotic sulphonation and detoxification has not been reported. In this study, we show that the Arabidopsis sulphotransferase AtSOT12 could sulphonate the bacterial-produced toxin cycloheximide. Loss-of-function mutant sot12 exhibited hypersensitive phenotype to cycloheximide, and expression of AtSOT12 protein in yeast cells conferred resistance to this toxic compound. AtSOT12 exhibited broad specificity and could sulphonate a variety of xenobiotics including phenolic and polycyclic compounds. Enzyme kinetics analysis indicated that AtSOT12 has different selectivity for simple phenolics with different side chains, and the position of the side chain in the simple phenolic compounds affects substrate binding affinity and catalytic efficiency. We proposed that the broad specificity and induced production of AtSOT12 may have rendered this enzyme to not only modify endogenous molecules such as salicylic acid as we previously reported, but also sulphonate pathogen-produced toxic small molecules to protect them from infection. Sulphonation of small molecules in plants may constitute a rapid way to inactivate or change the physiochemical properties of biologically active molecules that could have profound effects on plant growth, development and defence. © 2015 John Wiley & Sons Ltd.

The Documentation of Health Problems in Relation to Prescribed Medication in People with Profound Intellectual and Multiple Disabilities

ERIC Educational Resources Information Center

van der Heide, D. C.; van der Putten, A. A. J.; van den Berg, P. B.; Taxis, K.; Vlaskamp, C.

2009-01-01

Background: Persons with profound intellectual and multiple disabilities (PIMD) suffer from a wide range of health problems and use a wide range of different drugs. This study investigated for frequently used medication whether there was a health problem documented in the medical notes for the drug prescribed. Method: Persons with PIMD with an…

Trends and frontiers for the science and management of the oceans.

PubMed

Mumby, Peter J

2017-06-05

People have an enduring fascination with the biology of the oceans. When the BBC's 'Blue Planet' series first aired on British television almost a quarter of the nation tuned in. As the diversity of science in this special issue of Current Biology attests, the ocean presents a challenging environment for study while also exhibiting some of the most profound and disruptive symptoms of global change. Marine science has made major advances in the past few decades, which were primarily made possible through important technological innovations. This progress notwithstanding, there are persistent challenges in achieving an understanding of marine processes at appropriate scales and delivering meaningful insights to guide ocean policy and management. Naturally, the examples chosen below betray my ecological leanings, but I hope that many of the issues raised resonate with readers in many different disciplines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Developmental “Roots” in Mature Biological Knowledge

PubMed Central

Goldberg, Robert F.; Thompson-Schill, Sharon L.

2009-01-01

Young children tend to claim that moving artifacts and nonliving natural kinds are alive, but neglect to ascribe life to plants. This research tested whether adults exhibit similar confusions when verifying life status in a speeded classification task. Experiment 1 showed that undergraduates encounter greater difficulty (reduced accuracy and increased response times) in determining life status for plants, relative to animals, and for natural and moving nonliving things, relative to artifacts and non-moving things. Experiment 2 replicated these effects in university biology professors. The professors showed a significantly reduced effect size for living things, as compared with the students, but still showed greater difficulty for plants than animals, even as no differences from the students were apparent in their responses to nonliving things. These results suggest that mature biological knowledge relies on a developmental foundation that is not radically overwritten or erased with the profound conceptual changes that accompany mastery of the domain. PMID:19399979

Hacking the quantum revolution: 1925-1975

NASA Astrophysics Data System (ADS)

Schweber, Silvan S.

2015-01-01

I argue that the quantum revolution should be seen as an Ian Hacking type of scientific revolution: a profound, longue durée, multidisciplinary process of transforming our understanding of physical nature, with deep-rooted social components from the start. The "revolution" exhibits a characteristic style of reasoning - the hierarchization of physical nature - and developed and uses a specific language - quantum field theory (QFT). It is by virtue of that language that the quantum theory has achieved some of its deepest insights into the description of the dynamics of the physical world. However, the meaning of what a quantum field theory is and what it describes has deeply altered, and one now speaks of "effective" quantum field theories. Interpreting all present day quantum field theories as but "effective" field theories sheds additional light on Phillip Anderson's assertion that "More is different". This important element is addressed in the last part of the paper.

Developmental "roots" in mature biological knowledge.

PubMed

Goldberg, Robert F; Thompson-Schill, Sharon L

2009-04-01

Young children tend to claim that moving artifacts and nonliving natural kinds are alive, but neglect to ascribe life to plants. This research tested whether adults exhibit similar confusions when verifying life status in a speeded classification task. Experiment 1 showed that undergraduates encounter greater difficulty (reduced accuracy and increased response times) in determining life status for plants, relative to animals, and for natural and moving nonliving things, relative to artifacts and non-moving things. Experiment 2 replicated these effects in university biology professors. The professors showed a significantly reduced effect size for living things, as compared with the students, but still showed greater difficulty for plants than animals, even as no differences from the students were apparent in their responses to nonliving things. These results suggest that mature biological knowledge relies on a developmental foundation that is not radically overwritten or erased with the profound conceptual changes that accompany mastery of the domain.

Number of graphene layers exhibiting an influence on oxidation of DNA bases: analytical parameters.

PubMed

Goh, Madeline Shuhua; Pumera, Martin

2012-01-20

This article investigates the analytical performance of double-, few- and multi-layer graphene upon oxidation of adenine and guanine. We observed that the sensitivity of differential pulse voltammetric response of guanine and adenine is significantly higher at few-layer graphene surface than single-layer graphene. We use glassy carbon electrode as substrate coated with graphenes. Our findings shall have profound influence on construction of graphene based genosensors. Copyright © 2011 Elsevier B.V. All rights reserved.

Extreme Entropy-Enthalpy Compensation in a Drug Resistant Variant of HIV-1 Protease

PubMed Central

King, Nancy M.; Prabu-Jeyabalan, Moses; Bandaranayake, Rajintha M.; Nalam, Madhavi N. L.; Nalivaika, Ellen A.; Özen, Ayşegül; Haliloglu, Türkan; Yılmaz, Neşe Kurt; Schiffer, Celia A.

2012-01-01

The development of HIV-1 protease inhibitors has been the historic paradigm of rational structure-based drug design, where structural and thermodynamic analyses have assisted in the discovery of novel inhibitors. While the total enthalpy and entropy change upon binding determine the affinity, often the thermodynamics are considered in terms of inhibitor properties only. In the current study, profound changes are observed in the binding thermodynamics of a drug resistant variant compared to wild-type HIV-1 protease, irrespective of the inhibitor bound. This variant (Flap+) has a combination of flap and active site mutations and exhibits extremely large entropy-enthalpy compensation compared to wild-type protease, 5–15 kcal/mol, while losing only 1–3 kcal/mol in total binding free energy for any of six FDA approved inhibitors. Although entropy-enthalpy compensation has been previously observed for a variety of systems, never have changes of this magnitude been reported. The co-crystal structures of Flap+ protease with four of the inhibitors were determined and compared with complexes of both the wildtype protease and another drug resistant variant that does not exhibit this energetic compensation. Structural changes conserved across the Flap+ complexes, which are more pronounced for the flaps covering the active site, likely contribute to the thermodynamic compensation. The finding that drug resistant mutations can profoundly modulate the relative thermodynamic properties of a therapeutic target independent of the inhibitor presents a new challenge for rational drug design. PMID:22712830

[Inadequacy of the paradigms of special education to subjects with severe and profound grade intellectual disability - the need for pragmatic realism in psychiatry and special pedagogy].

PubMed

Sipowicz, Kasper; Żuraw, Hanna; Witusik, Andrzej; Mokros, Łukasz; Najbert, Edyta; Pietras, Tadeusz

2018-05-25

People with severe and profound grade disabilities are the subject of interest in psychiatry, clinical psychology and special pedagogy. Unfortunately, the paradigmatic approach to special education based on postmodern philosophy is in contrast to the biomedical approach that is based on the positivist and Cartesian models. The paper is an attempt to systematize the similarities and differences between the humanistic approach and the modern biomedical model, which, despite the apparent differences, do not differ so much from each other. Work with a person disabled intellectually in the severe or profound degree is governed by the principles of methodical realism, taking into account to an equal extent the principal deficits, the concomitant diseases, limitations and the social context. The deeper the impairment and disability is, the smaller is the role of the humanistic paradigm in work with the client in the medical management and educational process. Changing the paradigms of special pedagogy has drawn attention to the social context of disability, separating, however, special pedagogy from modern medicine and psychology, cognitive-oriented and psychometry-based. The postmodern paradigm has become an ideology, which makes it difficult to work with deeply disabled people. Only the multidirectional approach including a variety of paradigms makes it possible to provide integrational aid to people with severe and profound grade intellectual disabilities. Working with such a disabled person should take into account equally the biomedical and humanistic aspects. © 2018 MEDPRESS.

Foveal Processing Under Concurrent Peripheral Load in Profoundly Deaf Adults

PubMed Central

2016-01-01

Development of the visual system typically proceeds in concert with the development of audition. One result is that the visual system of profoundly deaf individuals differs from that of those with typical auditory systems. While past research has suggested deaf people have enhanced attention in the visual periphery, it is still unclear whether or not this enhancement entails deficits in central vision. Profoundly deaf and typically hearing adults were administered a variant of the useful field of view task that independently assessed performance on concurrent central and peripheral tasks. Identification of a foveated target was impaired by a concurrent selective peripheral attention task, more so in profoundly deaf adults than in the typically hearing. Previous findings of enhanced performance on the peripheral task were not replicated. These data are discussed in terms of flexible allocation of spatial attention targeted towards perceived task demands, and support a modified “division of labor” hypothesis whereby attentional resources co-opted to process peripheral space result in reduced resources in the central visual field. PMID:26657078

Clinical applications of hallucinogens: A review.

PubMed

Garcia-Romeu, Albert; Kersgaard, Brennan; Addy, Peter H

2016-08-01

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Deciphering landslide behavior using large-scale flume experiments

USGS Publications Warehouse

Reid, Mark E.; Iverson, Richard M.; Iverson, Neal R.; LaHusen, Richard G.; Brien, Dianne L.; Logan, Matthew

2008-01-01

Landslides can be triggered by a variety of hydrologic events and they can exhibit a wide range of movement dynamics. Effective prediction requires understanding these diverse behaviors. Precise evaluation in the field is difficult; as an alternative we performed a series of landslide initiation experiments in the large-scale, USGS debris-flow flume. We systematically investigated the effects of three different hydrologic triggering mechanisms, including groundwater exfiltration from bedrock, prolonged rainfall infiltration, and intense bursts of rain. We also examined the effects of initial soil porosity (loose or dense) relative to the soil’s critical-state porosity. Results show that all three hydrologic mechanisms can instigate landsliding, but water pathways, sensor response patterns, and times to failure differ. Initial soil porosity has a profound influence on landslide movement behavior. Experiments using loose soil show rapid soil contraction during failure, with elevated pore pressures liquefying the sediment and creating fast-moving debris flows. In contrast, dense soil dilated upon shearing, resulting in slow, gradual, and episodic motion. These results have fundamental implications for forecasting landslide behavior and developing effective warning systems.

Chronic Hypoxemia in Children With Congenital Heart Defect Impairs Airway Epithelial Sodium Transport.

PubMed

Kaskinen, Anu K; Helve, Otto; Andersson, Sture; Kirjavainen, Turkka; Martelius, Laura; Mattila, Ilkka P; Rautiainen, Paula; Pitkänen, Olli M

2016-01-01

Ambient hypoxia impairs the airway epithelial Na transport, which is crucial in lung edema reabsorption. Whether chronic systemic hypoxemia affects airway Na transport has remained largely unknown. We have therefore investigated whether chronic systemic hypoxemia in children with congenital heart defect affects airway epithelial Na transport, Na transporter-gene expression, and short-term lung edema accumulation. Prospective, observational study. Tertiary care medical center responsible for nationwide pediatric cardiac surgery. Ninety-nine children with congenital heart defect or acquired heart disease (age range, 6 d to 14.8 yr) were divided into three groups based on their level of preoperative systemic hypoxemia: 1) normoxemic patients (SpO2% ≥ 95%; n = 44), 2) patients with cyanotic congenital heart defect and moderate hypoxemia (SpO2 86-94%; n = 16), and 3) patients with cyanotic congenital heart defect and profound systemic hypoxemia (SpO2 ≤ 85%; n = 39). Nasal transepithelial potential difference served as a surrogate measure for epithelial Na transport of the respiratory tract. Profoundly hypoxemic patients had 29% lower basal nasal transepithelial potential difference (p = 0.02) and 55% lower amiloride-sensitive nasal transepithelial potential difference (p = 0.0003) than normoxemic patients. In profoundly hypoxemic patients, nasal epithelial messenger RNA expressions of two airway Na transporters (amiloride-sensitive epithelial Na channel and β1- Na-K-ATPase) were not attenuated, but instead α1-Na-K-ATPase messenger RNA levels were higher (p = 0.03) than in the normoxemic patients, indicating that posttranscriptional factors may impair airway Na transport. The chest radiograph lung edema score increased after congenital cardiac surgery in profoundly hypoxemic patients (p = 0.0004) but not in patients with normoxemia or moderate hypoxemia. The impaired airway epithelial amiloride-sensitive Na transport activity in profoundly hypoxemic children with cyanotic congenital heart defect may hinder defense against lung edema after cardiac surgery.

Profound seasonal shrinking and regrowth of the ossified braincase in phylogenetically distant mammals with similar life histories

PubMed Central

Dechmann, Dina K. N.; LaPoint, Scott; Dullin, Christian; Hertel, Moritz; Taylor, Jan R. E.; Zub, Karol; Wikelski, Martin

2017-01-01

Ontogenetic changes in skull shape and size are ubiquitous in altricial vertebrates, but typically unidirectional and minimal in full-grown animals. Red-toothed shrews exhibit a rare exception, where the shape, mass and size of the skull, brain, and several major organs, show significant bidirectional seasonal changes. We now show a similar but male-biased shrinking (16%) and regrowth (8%) in the standardized braincase depth of least weasels (Mustela nivalis). Juvenile weasels also exhibit a growth overshoot, followed by a shrinkage period lasting until the end of their first winter. Only male weasels then regrow during their second summer. High-resolution CT scans suggest areas of the skull are affected differently during shrinking and regrowth in both species. This suggests multiple evolutionary drivers: while the shrinking likely facilitates survival during seasonal low resource availability in these high-metabolic mammals with year-round activity, the regrowth may be most strongly influenced by high investment into reproduction and territories, which is male-biased in the weasels. Our data provide evidence for convergent evolution of skull and thus brain shrinkage and regrowth, with important implications for understanding adaptations to changing environments and for applied research on the correlated changes in bone structure, brain size and the many other affected organs. PMID:28211896

Attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy.

PubMed

Antonini, Tanya N; Ris, M Douglas; Grosshans, David R; Mahajan, Anita; Okcu, M Fatih; Chintagumpala, Murali; Paulino, Arnold; Child, Amanda E; Orobio, Jessica; Stancel, Heather H; Kahalley, Lisa S

2017-07-01

This study examines attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy (PBRT). We examined 39 survivors (age 6-19years) who were 3.61years post-PBRT on average. Craniospinal (CSI; n=21) and focal (n=18) subgroups were analyzed. Attention, processing speed, and executive functioning scores were compared to population norms, and clinical/demographic risk factors were examined. As a group, survivors treated with focal PBRT exhibited attention, processing speed, and executive functioning that did not differ from population norms (all p>0.05). Performance in the CSI group across attention scales was normative (all p>0.05), but areas of relative weakness were identified on one executive functioning subtest and several processing speed subtests (all p<0.01). Survivors treated with PBRT may exhibit relative resilience in cognitive domains traditionally associated with radiation late effects. Attention, processing speed, and executive functioning remained intact and within normal limits for survivors treated with focal PBRT. Among survivors treated with CSI, a score pattern emerged that was suggestive of difficulties in underlying component skills (i.e., processing speed) rather than true executive dysfunction. No evidence of profound cognitive impairment was found in either group. Copyright © 2017 Elsevier B.V. All rights reserved.

Social Cognition in Williams Syndrome: Face Tuning

PubMed Central

Pavlova, Marina A.; Heiz, Julie; Sokolov, Alexander N.; Barisnikov, Koviljka

2016-01-01

Many neurological, neurodevelopmental, neuropsychiatric, and psychosomatic disorders are characterized by impairments in visual social cognition, body language reading, and facial assessment of a social counterpart. Yet a wealth of research indicates that individuals with Williams syndrome exhibit remarkable concern for social stimuli and face fascination. Here individuals with Williams syndrome were presented with a set of Face-n-Food images composed of food ingredients and in different degree resembling a face (slightly bordering on the Giuseppe Arcimboldo style). The primary advantage of these images is that single components do not explicitly trigger face-specific processing, whereas in face images commonly used for investigating face perception (such as photographs or depictions), the mere occurrence of typical cues already implicates face presence. In a spontaneous recognition task, participants were shown a set of images in a predetermined order from the least to most resembling a face. Strikingly, individuals with Williams syndrome exhibited profound deficits in recognition of the Face-n-Food images as a face: they did not report seeing a face on the images, which typically developing controls effortlessly recognized as a face, and gave overall fewer face responses. This suggests atypical face tuning in Williams syndrome. The outcome is discussed in the light of a general pattern of social cognition in Williams syndrome and brain mechanisms underpinning face processing. PMID:27531986

Functional network centrality in obesity: A resting-state and task fMRI study.

PubMed

García-García, Isabel; Jurado, María Ángeles; Garolera, Maite; Marqués-Iturria, Idoia; Horstmann, Annette; Segura, Bàrbara; Pueyo, Roser; Sender-Palacios, María José; Vernet-Vernet, Maria; Villringer, Arno; Junqué, Carme; Margulies, Daniel S; Neumann, Jane

2015-09-30

Obesity is associated with structural and functional alterations in brain areas that are often functionally distinct and anatomically distant. This suggests that obesity is associated with differences in functional connectivity of regions distributed across the brain. However, studies addressing whole brain functional connectivity in obesity remain scarce. Here, we compared voxel-wise degree centrality and eigenvector centrality between participants with obesity (n=20) and normal-weight controls (n=21). We analyzed resting state and task-related fMRI data acquired from the same individuals. Relative to normal-weight controls, participants with obesity exhibited reduced degree centrality in the right middle frontal gyrus in the resting-state condition. During the task fMRI condition, obese participants exhibited less degree centrality in the left middle frontal gyrus and the lateral occipital cortex along with reduced eigenvector centrality in the lateral occipital cortex and occipital pole. Our results highlight the central role of the middle frontal gyrus in the pathophysiology of obesity, a structure involved in several brain circuits signaling attention, executive functions and motor functions. Additionally, our analysis suggests the existence of task-dependent reduced centrality in occipital areas; regions with a role in perceptual processes and that are profoundly modulated by attention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Endosymbiotic flexibility associates with environmental sensitivity in scleractinian corals.

PubMed

Putnam, Hollie M; Stat, Michael; Pochon, Xavier; Gates, Ruth D

2012-11-07

Flexibility in biological systems is seen as an important driver of macro-ecosystem function and stability. Spatially constrained endosymbiotic settings, however, are less studied, although environmental thresholds of symbiotic corals are linked to the function of their endosymbiotic dinoflagellate communities. Symbiotic flexibility is a hypothesized mechanism that corals may exploit to adapt to climate change. This study explores the flexibility of the coral-Symbiodinium symbiosis through quantification of Symbiodinium ITS2 sequence assemblages in a range of coral species and genera. Sequence assemblages are expressed as an index of flexibility incorporating phylogenetic divergence and relative abundance of Symbiodinium sequences recovered from the host. This comparative analysis reveals profound differences in the flexibility of corals for Symbiodinium, thereby classifying corals as generalists or specifists. Generalists such as Acropora and Pocillopora exhibit high intra- and inter-species flexibility in their Symbiodinium assemblages and are some of the most environmentally sensitive corals. Conversely, specifists such as massive Porites colonies exhibit low flexibility, harbour taxonomically narrow Symbiodinium assemblages, and are environmentally resistant corals. Collectively, these findings challenge the paradigm that symbiotic flexibility enhances holobiont resilience. This underscores the need for a deeper examination of the extent and duration of the functional benefits associated with endosymbiotic diversity and flexibility under environmental stress.

Profound seasonal shrinking and regrowth of the ossified braincase in phylogenetically distant mammals with similar life histories.

PubMed

Dechmann, Dina K N; LaPoint, Scott; Dullin, Christian; Hertel, Moritz; Taylor, Jan R E; Zub, Karol; Wikelski, Martin

2017-02-13

Ontogenetic changes in skull shape and size are ubiquitous in altricial vertebrates, but typically unidirectional and minimal in full-grown animals. Red-toothed shrews exhibit a rare exception, where the shape, mass and size of the skull, brain, and several major organs, show significant bidirectional seasonal changes. We now show a similar but male-biased shrinking (16%) and regrowth (8%) in the standardized braincase depth of least weasels (Mustela nivalis). Juvenile weasels also exhibit a growth overshoot, followed by a shrinkage period lasting until the end of their first winter. Only male weasels then regrow during their second summer. High-resolution CT scans suggest areas of the skull are affected differently during shrinking and regrowth in both species. This suggests multiple evolutionary drivers: while the shrinking likely facilitates survival during seasonal low resource availability in these high-metabolic mammals with year-round activity, the regrowth may be most strongly influenced by high investment into reproduction and territories, which is male-biased in the weasels. Our data provide evidence for convergent evolution of skull and thus brain shrinkage and regrowth, with important implications for understanding adaptations to changing environments and for applied research on the correlated changes in bone structure, brain size and the many other affected organs.

Social Cognition in Williams Syndrome: Face Tuning.

PubMed

Pavlova, Marina A; Heiz, Julie; Sokolov, Alexander N; Barisnikov, Koviljka

2016-01-01

Many neurological, neurodevelopmental, neuropsychiatric, and psychosomatic disorders are characterized by impairments in visual social cognition, body language reading, and facial assessment of a social counterpart. Yet a wealth of research indicates that individuals with Williams syndrome exhibit remarkable concern for social stimuli and face fascination. Here individuals with Williams syndrome were presented with a set of Face-n-Food images composed of food ingredients and in different degree resembling a face (slightly bordering on the Giuseppe Arcimboldo style). The primary advantage of these images is that single components do not explicitly trigger face-specific processing, whereas in face images commonly used for investigating face perception (such as photographs or depictions), the mere occurrence of typical cues already implicates face presence. In a spontaneous recognition task, participants were shown a set of images in a predetermined order from the least to most resembling a face. Strikingly, individuals with Williams syndrome exhibited profound deficits in recognition of the Face-n-Food images as a face: they did not report seeing a face on the images, which typically developing controls effortlessly recognized as a face, and gave overall fewer face responses. This suggests atypical face tuning in Williams syndrome. The outcome is discussed in the light of a general pattern of social cognition in Williams syndrome and brain mechanisms underpinning face processing.

Consanguinity Among Parents of Iranian Deaf Children.

PubMed

Ajallouyan, Mohammad; Radfar, Shokofeh; Nouhi, Sima; Tavallaie, Seid Abbas; Amirsalari, Susan; Yousefi, Jaleh; Hasanali Fard, Mahdieh

2016-11-01

It seems that there is a relationship between consanguinity and profound hearing loss but there is little data about the association of consanguinity and hearing loss in Iran. The aim of this study is to demonstrate the causes of profound bilateral sensorineural hearing loss among Iranian samples who are candidates for cochlear implantation. This study was retrospective, analytical, and designed to collect information about profound hearing impaired cases referred to the Baqiyatallah Cochlear implantation center using enumeration. A total of 310 children with profound hearing impairments participated in this study. They were aged from 6 months to 4 years old. The study was done between January 2007 and April 2009. Chi-square tests were used to show whether there was any statistical difference between the incidence of marital consanguinity of their parents and the normal population. Sixty-five percent of those 310 children had parents who had married with their relatives. Of the 203 (65%) parents that had consanguineous marriages, 132 were first cousins, which includes the children of two brothers (37 [11.8%] patrilateral parallel cousins), the children of two sisters (38 [12.2%] multi-lateral parallel cousins), or the children of a brother and a sister (57 [18.3%] cross cousins). Fifty-four (17.4%) of the parents were second cousins and 17 (5.2%) were beyond second cousins. Also, hearing loss etiology was obvious in 237 (76.3%) of the patients with profound hearing loss but was unknown in 73 (23.7%). Hereditary was identified as the most common cause in 33% of the cases. Our data demonstrated a 65% occurrence of consanguineous marriage among the parents of deaf children, which is statistically different from the percentage of consanguineous marriage among Iranian population (38%). This indicates an obvious relationship between severe hearing loss and consanguineous marriage.

Remodeling of brain lipidome in methamphetamine-sensitized mice.

PubMed

Jiang, Linhong; Gu, Hui; Lin, Yiyun; Xu, Wei; Zhu, Ruiming; Kong, Jueying; Luo, Li; Long, Hailei; Liu, Bing; Chen, Bo; Zhao, Yinglan; Cen, Xiaobo

2017-09-05

Lipids are predominant components of the brain and key regulators for neural structure and function. The effect of methamphetamine (METH) on behavior, cognition as well as memory has been intensively investigated; however, the impact of METH on brain lipid profiles is largely unknown. Here, we used a global lipidomic approach to investigate brain lipidome of METH-sensitized mice. We found that repeated METH significantly modified the lipidome in the hippocampus, prefrontal cortex (PFC) and striatum. Interestingly, nucleus accumbens showed no obvious alteration in lipidomic profiling. Phospholipid and sphingolipid metabolisms were profoundly modified in the hippocampus of METH-sensitized mice, exhibiting increased phosphatidic acid and ether phosphatidylcholine but decreased lysophosphatidylethanolamine, lactosylceramide and triglycerides. The fatty acyl length of phospholipids and diacylglycerol longer than 40 carbon were clearly decreased in the hippocampus, and that 36 carbon was decreased in the PFC. These results indicate METH can profoundly affect the metabolism of phospholipids, sphingolipids and glycerolipids in the brain. Our findings reveal a link between remodeled brain lipidome and neurobehavior induced by METH. Copyright © 2017 Elsevier B.V. All rights reserved.

Gender, culture, and mathematics performance

PubMed Central

Hyde, Janet S.; Mertz, Janet E.

2009-01-01

Using contemporary data from the U.S. and other nations, we address 3 questions: Do gender differences in mathematics performance exist in the general population? Do gender differences exist among the mathematically talented? Do females exist who possess profound mathematical talent? In regard to the first question, contemporary data indicate that girls in the U.S. have reached parity with boys in mathematics performance, a pattern that is found in some other nations as well. Focusing on the second question, studies find more males than females scoring above the 95th or 99th percentile, but this gender gap has significantly narrowed over time in the U.S. and is not found among some ethnic groups and in some nations. Furthermore, data from several studies indicate that greater male variability with respect to mathematics is not ubiquitous. Rather, its presence correlates with several measures of gender inequality. Thus, it is largely an artifact of changeable sociocultural factors, not immutable, innate biological differences between the sexes. Responding to the third question, we document the existence of females who possess profound mathematical talent. Finally, we review mounting evidence that both the magnitude of mean math gender differences and the frequency of identification of gifted and profoundly gifted females significantly correlate with sociocultural factors, including measures of gender equality across nations. PMID:19487665

Gender, culture, and mathematics performance.

PubMed

Hyde, Janet S; Mertz, Janet E

2009-06-02

Using contemporary data from the U.S. and other nations, we address 3 questions: Do gender differences in mathematics performance exist in the general population? Do gender differences exist among the mathematically talented? Do females exist who possess profound mathematical talent? In regard to the first question, contemporary data indicate that girls in the U.S. have reached parity with boys in mathematics performance, a pattern that is found in some other nations as well. Focusing on the second question, studies find more males than females scoring above the 95th or 99th percentile, but this gender gap has significantly narrowed over time in the U.S. and is not found among some ethnic groups and in some nations. Furthermore, data from several studies indicate that greater male variability with respect to mathematics is not ubiquitous. Rather, its presence correlates with several measures of gender inequality. Thus, it is largely an artifact of changeable sociocultural factors, not immutable, innate biological differences between the sexes. Responding to the third question, we document the existence of females who possess profound mathematical talent. Finally, we review mounting evidence that both the magnitude of mean math gender differences and the frequency of identification of gifted and profoundly gifted females significantly correlate with sociocultural factors, including measures of gender equality across nations.

Effects of ambient stimuli on measures of behavioral state and microswitch use in adults with profound multiple impairments.

PubMed

Murphy, Kathleen M; Saunders, Muriel D; Saunders, Richard R; Olswang, Lesley B

2004-01-01

The effects of different types and amounts of environmental stimuli (visual and auditory) on microswitch use and behavioral states of three individuals with profound multiple impairments were examined. The individual's switch use and behavioral states were measured under three setting conditions: natural stimuli (typical visual and auditory stimuli in a recreational situation), reduced visual stimuli, and reduced visual and auditory stimuli. Results demonstrated differential switch use in all participants with the varying environmental setting conditions. No consistent effects were observed in behavioral state related to environmental condition. Predominant behavioral state scores and switch use did not systematically covary with any participant. Results suggest the importance of considering environmental stimuli in relationship to switch use when working with individuals with profound multiple impairments.

Foveal Processing Under Concurrent Peripheral Load in Profoundly Deaf Adults.

PubMed

Dye, Matthew W G

2016-04-01

Development of the visual system typically proceeds in concert with the development of audition. One result is that the visual system of profoundly deaf individuals differs from that of those with typical auditory systems. While past research has suggested deaf people have enhanced attention in the visual periphery, it is still unclear whether or not this enhancement entails deficits in central vision. Profoundly deaf and typically hearing adults were administered a variant of the useful field of view task that independently assessed performance on concurrent central and peripheral tasks. Identification of a foveated target was impaired by a concurrent selective peripheral attention task, more so in profoundly deaf adults than in the typically hearing. Previous findings of enhanced performance on the peripheral task were not replicated. These data are discussed in terms of flexible allocation of spatial attention targeted towards perceived task demands, and support a modified "division of labor" hypothesis whereby attentional resources co-opted to process peripheral space result in reduced resources in the central visual field. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Phylogeny and size differentially influence dissolved Cd and Zn bioaccumulation parameters among closely related aquatic insects.

PubMed

Poteat, Monica D; Buchwalter, David B

2014-05-06

Evolutionarily distinct lineages can vary markedly in their accumulation of, and sensitivity to, contaminants. However, less is known about variability among closely related species. Here, we compared dissolved Cd and Zn bioaccumulation in 19 species spanning two species-rich aquatic insect families: Ephemerellidae (order Ephemeroptera (mayflies)), generalized to be metal sensitive, and Hydropsychidae (order Trichoptera (caddisflies)), generalized to be metal tolerant. Across all species, Zn and Cd uptake rate constants (k(u)s), efflux rate constants (k(e)s) and bioconcentration factors (BCFs) strongly covaried, suggesting that these metals share transport pathways in these distinct lineages. K(u)s and BCFs were substantially larger in Ephemerellidae than in Hydropsychidae, whereas k(e)s did not dramatically differ between the two families. Body size played an important role in driving ku differences among species, but had no influence on k(e)s. While familial differences in metal bioconcentration were striking, each family exhibited tremendous variability in all bioaccumulation parameters. At finer levels of taxonomic resolution (within families), phylogeny did not account for differences in metal bioaccumulation. These findings suggest that intrafamily variability can be profound and have important practical implications in that we need to better understand how well "surrogate species" represent their fellow congeners and family members.

Be different--the diversity of peroxisomes in the animal kingdom.

PubMed

Islinger, M; Cardoso, M J R; Schrader, M

2010-08-01

Peroxisomes represent so-called "multipurpose organelles" as they contribute to various anabolic as well as catabolic pathways. Thus, with respect to the physiological specialization of an individual organ or animal species, peroxisomes exhibit a functional diversity, which is documented by significant variations in their proteome. These differences are usually regarded as an adaptational response to the nutritional and environmental life conditions of a specific organism. Thus, human peroxisomes can be regarded as an in part physiologically unique organellar entity fulfilling metabolic functions that differ from our animal model systems. In line with this, a profound understanding on how peroxisomes acquired functional heterogeneity in terms of an evolutionary and mechanistic background is required. This review summarizes our current knowledge on the heterogeneity of peroxisomal physiology, providing insights into the genetic and cell biological mechanisms, which lead to the differential localization or expression of peroxisomal proteins and further gives an overview on peroxisomal biochemical pathways, which are specialized in different animal species and organs. Moreover, it addresses the impact of proteome studies on our understanding of differential peroxisome function describing the utility of mass spectrometry and computer-assisted algorithms to identify peroxisomal target sequences for the detection of new organ- or species-specific peroxisomal proteins. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Avalanches and diffusion in bubble rafts

NASA Astrophysics Data System (ADS)

Maloney, C. E.

2015-07-01

Energy dissipation distributions and particle displacement statistics are studied in the mean-field version of Durian's bubble model. A two-dimensional (2D) bi-disperse mixture is simulated at various strain rates, \\dotγ , and packing ratios, ϕ, above the rigidity onset at φ=φc . Well above φc , and at sufficiently low \\dotγ , the system responds in a highly bursty way, reminiscent of other dynamically critical systems with a power-law distribution of energy dissipation. As one increases \\dotγ at fixed ϕ or tunes φ→ φc at fixed \\dotγ , the bursty behavior vanishes. Displacement distributions are non-Fickian at short times but cross to a Fickian regime at a universal strain, Δγ* , independent of \\dotγ and ϕ. Despite the profound differences in short-time dynamics, at intermediate Δγ the systems exhibit qualitatively similar spatial patterns of deformation with lines of slip extending across large fractions of the simulation cell. These deformation patterns explain the observed diffusion constants and the universal crossover time to Fickian behavior.

The femur of Orrorin tugenensis exhibits morphometric affinities with both Miocene apes and later hominins.

PubMed

Almécija, Sergio; Tallman, Melissa; Alba, David M; Pina, Marta; Moyà-Solà, Salvador; Jungers, William L

2013-01-01

Orrorin tugenensis (Kenya, ca. 6 Ma) is one of the earliest putative hominins. Its proximal femur, BAR 1002'00, was originally described as being very human-like, although later multivariate analyses showed an australopith pattern. However, some of its traits (for example, laterally protruding greater trochanter, medially oriented lesser trochanter and presence of third trochanter) are also present in earlier Miocene apes. Here, we use geometric morphometrics to reassess the morphological affinities of BAR 1002'00 within a large sample of anthropoids (including fossil apes and hominins) and reconstruct hominoid proximal femur evolution using squared-change parsimony. Our results indicate that both hominin and modern great ape femora evolved in different directions from a primitive morphology represented by some fossil apes. Orrorin appears intermediate between Miocene apes and australopiths in shape space. This evidence is consistent with femoral shape similarities in extant great apes being derived and homoplastic and has profound implications for understanding the origins of human bipedalism.

Mutation Profile of the CDH23 Gene in 56 Probands with Usher Syndrome Type I

PubMed Central

Oshima, A.; Jaijo, T.; Aller, E.; Millan, J.M.; Carney, C.; Usami, S.; Moller, C.; Kimberling, W.J.

2008-01-01

Mutations in the human gene encoding cadherin 23 (CDH23) cause Usher syndrome type 1D (USH1D) and nonsyndromic hearing loss. Individuals with Usher syndrome type I have profound congenital deafness, vestibular areflexia and usually begin to exhibit signs of RP in early adolescence. In the present study, we carried out the mutation analysis in all 69 exons of the CDH23 gene in 56 Usher type 1 probands already screened for mutations in MYO7A. A total of 18 of 56 subjects (32.1%) were observed to have one or two CDH23 variants that are presumed to be pathologic. Twenty one different pathologic genome variants were observed of which 15 were novel. Out of a total of 112 alleles, 31 (27.7%) were considered pathologic. Based on our results it is estimated that about 20% of patients with Usher syndrome type I have CDH23 mutations. PMID:18429043

Temperature-Induced Large Broadening and Blue Shift in the Electronic Band Structure and Optical Absorption of Methylammonium Lead Iodide Perovskite.

PubMed

Yang, Jia-Yue; Hu, Ming

2017-08-17

The power conversion efficiency of hybrid halide perovskite solar cells is profoundly influenced by the operating temperature. Here we investigate the temperature influence on the electronic band structure and optical absorption of cubic CH 3 NH 3 PbI 3 from first-principles by accounting for both the electron-phonon interaction and thermal expansion. Within the framework of density functional perturbation theory, the electron-phonon coupling induces slightly enlarged band gap and strongly broadened electronic relaxation time as temperature increases. The large broadening effect is mainly due to the presence of cation organic atoms. Consequently, the temperature-dependent absorption peak exhibits blue-shift position, decreased amplitude, and broadened width. This work uncovers the atomistic origin of temperature influence on the optical absorption of cubic CH 3 NH 3 PbI 3 and can provide guidance to design high-performance hybrid halide perovskite solar cells at different operating temperatures.

Influence of Nano-HA Coated Bone Collagen to Acrylic (Polymethylmethacrylate) Bone Cement on Mechanical Properties and Bioactivity

PubMed Central

Li, Tao; Weng, Xisheng; Bian, Yanyan; Zhou, Lei; Cui, Fuzhai; Qiu, Zhiye

2015-01-01

Objective This research investigated the mechanical properties and bioactivity of polymethylmethacrylate (PMMA) bone cement after addition of the nano-hydroxyapatite(HA) coated bone collagen (mineralized collagen, MC). Materials & Methods The MC in different proportions were added to the PMMA bone cement to detect the compressive strength, compression modulus, coagulation properties and biosafety. The MC-PMMA was embedded into rabbits and co-cultured with MG 63 cells to exam bone tissue compatibility and gene expression of osteogenesis. Results 15.0%(wt) impregnated MC-PMMA significantly lowered compressive modulus while little affected compressive strength and solidification. MC-PMMA bone cement was biologically safe and indicated excellent bone tissue compatibility. The bone-cement interface crosslinking was significantly higher in MC-PMMA than control after 6 months implantation in the femur of rabbits. The genes of osteogenesis exhibited significantly higher expression level in MC-PMMA. Conclusions MC-PMMA presented perfect mechanical properties, good biosafety and excellent biocompatibility with bone tissues, which has profoundly clinical values. PMID:26039750

Influence of Nano-HA Coated Bone Collagen to Acrylic (Polymethylmethacrylate) Bone Cement on Mechanical Properties and Bioactivity.

PubMed

Li, Tao; Weng, Xisheng; Bian, Yanyan; Zhou, Lei; Cui, Fuzhai; Qiu, Zhiye

2015-01-01

This research investigated the mechanical properties and bioactivity of polymethylmethacrylate (PMMA) bone cement after addition of the nano-hydroxyapatite(HA) coated bone collagen (mineralized collagen, MC). The MC in different proportions were added to the PMMA bone cement to detect the compressive strength, compression modulus, coagulation properties and biosafety. The MC-PMMA was embedded into rabbits and co-cultured with MG 63 cells to exam bone tissue compatibility and gene expression of osteogenesis. 15.0%(wt) impregnated MC-PMMA significantly lowered compressive modulus while little affected compressive strength and solidification. MC-PMMA bone cement was biologically safe and indicated excellent bone tissue compatibility. The bone-cement interface crosslinking was significantly higher in MC-PMMA than control after 6 months implantation in the femur of rabbits. The genes of osteogenesis exhibited significantly higher expression level in MC-PMMA. MC-PMMA presented perfect mechanical properties, good biosafety and excellent biocompatibility with bone tissues, which has profoundly clinical values.

Long-distance communication by specialized cellular projections during pigment pattern development and evolution

PubMed Central

Eom, Dae Seok; Bain, Emily J; Patterson, Larissa B; Grout, Megan E; Parichy, David M

2015-01-01

Changes in gene activity are essential for evolutionary diversification. Yet, elucidating the cellular behaviors that underlie modifications to adult form remains a profound challenge. We use neural crest-derived adult pigmentation of zebrafish and pearl danio to uncover cellular bases for alternative pattern states. We show that stripes in zebrafish require a novel class of thin, fast cellular projection to promote Delta-Notch signaling over long distances from cells of the xanthophore lineage to melanophores. Projections depended on microfilaments and microtubules, exhibited meandering trajectories, and stabilized on target cells to which they delivered membraneous vesicles. By contrast, the uniformly patterned pearl danio lacked such projections, concomitant with Colony stimulating factor 1-dependent changes in xanthophore differentiation that likely curtail signaling available to melanophores. Our study reveals a novel mechanism of cellular communication, roles for differentiation state heterogeneity in pigment cell interactions, and an unanticipated morphogenetic behavior contributing to a striking difference in adult form. DOI: http://dx.doi.org/10.7554/eLife.12401.001 PMID:26701906

Dual targeting and retrograde translocation: regulators of plant nuclear gene expression can be sequestered by plastids.

PubMed

Krause, Kirsten; Oetke, Svenja; Krupinska, Karin

2012-01-01

Changes in the developmental or metabolic state of plastids can trigger profound changes in the transcript profiles of nuclear genes. Many nuclear transcription factors were shown to be controlled by signals generated in the organelles. In addition to the many different compounds for which an involvement in retrograde signaling is discussed, accumulating evidence suggests a role for proteins in plastid-to-nucleus communication. These proteins might be sequestered in the plastids before they act as transcriptional regulators in the nucleus. Indeed, several proteins exhibiting a dual localization in the plastids and the nucleus are promising candidates for such a direct signal transduction involving regulatory protein storage in the plastids. Among such proteins, the nuclear transcription factor WHIRLY1 stands out as being the only protein for which an export from plastids and translocation to the nucleus has been experimentally demonstrated. Other proteins, however, strongly support the notion that this pathway might be more common than currently believed.

Nanopore Confinement of C-O-H Fluids Relevant to Subsurface Energy Systems

NASA Astrophysics Data System (ADS)

Cole, D. R.

2016-12-01

Complex intermolecular interactions of C-O-H fluids (e.g., H2O, CO2, CH4) result in their unique thermophysical properties, including large deviations in the volumetric properties from ideality, vapor-liquid equilibria, and critical phenomena as these fluids encounter different pressure-temperature-pore network conditions in the crust. Development of a comprehensive understanding of the structures, dynamics, and reactivity at multiple length scales (molecular to macroscopic) over wide ranges of state conditions and composition is foundational to advances in quantifying geochemical processes involving mineral-fluid interfaces. The size, distribution and connectivity of these confined geometries dictate how fluids migrate into and through these micro- and nano-environments, wet and react with the solid. This presentation will provide an overview of the application of state-of-the-art experimental, analytical and computational tools to assess key features of the fluid-matrix interaction. The multidisciplinary approaches highlighted will include neutron scattering and NMR experiments, thermodynamic measurements and molecular-level simulations to quantitatively assess molecular properties of different mixtures of C-O-H fluids in nanpores. Key results include: (1) The addition of a second carbon-bearing phase or water has a profound effect on the competition for sorption sites, phase chemistry and the dynamical properties of all phases present in the pore. (2) Low solubility phases such as methane may exhibit profound increases in concentration in nanopores in the presence of water at elevated pressures and ambient temperature compared to bulk values. (3) Methane permeability through the hydrated pores is strongly dependent on the solid substrate and local properties of confined water, including its structure and, more importantly, evolution of solvation free energy and hydrogen bond structure. (4) Under certain conditions preferential adsorption of the fluids in the narrow pores can produce a shift in the equilibrium distribution of mixed volatiles present in adjoining fractures (aka the bulk portion of the system).

Does Aggressive Phototherapy Increase Mortality while Decreasing Profound Impairment among the Smallest and Sickest Newborns?

PubMed Central

Tyson, Jon E; Pedroza, Claudia; Langer, John; Green, Charles; Morris, Brenda; Stevenson, David; Van Meurs, Krisa P.; Oh, William; Phelps, Dale; O’Shea, Michael; McDavid, Georgia E.; Grisby, Cathy; Higgins, Rose

2013-01-01

Objective Aggressive phototherapy (AgPT) is widely used and assumed to be safe and effective for even the most immature infants. We assessed whether the benefits and hazards for the smallest and sickest infants differed from those for other extremely low birth weight (ELBW; (≤1000 g) infants in our Neonatal Research Network trial, the only large trial of AgPT. Study Design ELBW infants (n=1974) were randomized to AgPT or conservative phototherapy at age 12–36 hours. The effect of AgPT on outcomes (death; impairment; profound impairment; death or impairment [primary outcome], and death or profound impairment) at 18–22 months corrected age was related to BW stratum (501–750 g; 751–1000 g) and baseline severity of illness using multilevel regression equations. The probability of benefit and of harm was directly assessed with Bayesian analyses. Results Baseline illness severity was well characterized using mechanical ventilation and FiO2 at 24 hours age. Among mechanically ventilated infants ≤750 g BW (n =684), a reduction in impairment and in profound impairment was offset by higher mortality (p for interaction <0.05) with no significant effect on composite outcomes. Conservative Bayesian analyses of this subgroup identified a 99% (posterior) probability that AgPT increased mortality, a 97% probability that AgPT reduced impairment, and a 99% probability that AgPT reduced profound impairment. Conclusions Findings from the only large trial of AgPT suggest that AgPT may increase mortality while reducing impairment and profound impairment among the smallest and sickest infants. New approaches to reduce their serum bilirubin need development and rigorous testing. PMID:22652561

Differential high pressure survival in stationary-phase Escherichia coli MG1655

NASA Astrophysics Data System (ADS)

Griffin, Patrick L.; Kish, Adrienne; Steele, Andrew; Hemley, Russell J.

2011-06-01

Hydrostatic pressure exerts a profound influence on nearly all facets of cellular structure and function with exposures to sufficiently high pressure leading to microbial inactivation. We report the first observation of a persistent, pressure-resistant subpopulation within stationary-phase samples of Escherichia coli MG1655, a mesophilic bacterium adapted to surface pressure. This high pressure-resistant subpopulation exhibits pressure survival ranging from 0.6 to 2.0 orders of magnitude greater survival than high pressure treatments at pressures of 225-400 MPa. We also examine some aspects of pressure treatment protocol that may influence the measurements of high pressure survival.

Comparative study on the toxic effects of red tide flagellates Heterocapsa circularisquama and Chattonella marina on the short-necked clam (Ruditapes philippinarum).

PubMed

Kim, Daekyung; Choi, Kwang-Sik; Hong, Hyun-Ki; Jiang, Zedong; Zou, Yanan; Choi, Kyu-Sung; Yamasaki, Yasuhiro; Matsuyama, Yukihiko; Yamaguchi, Kenichi; Oda, Tatsuya

2011-01-01

Heterocapsa circularisquama showed much higher toxic effects on short-necked clams than Chattonella marina. Clams exposed to H. circularisquama exhibited morphological changes concomitant with an accumulation of mucus-like substances in the gills, a profound reduction in filtration activity, and lysosomal destabilization in hemocytes. Chattonella marina was less effective than H. circularisquama, and Heterocapsa triquetra was almost harmless in all these criteria. These results suggest that H. circularisquama exerted its lethal effect on short-necked clams through gill tissue damage and subsequent induction of physiological stress.

Theory of agent-based market models with controlled levels of greed and anxiety

NASA Astrophysics Data System (ADS)

Papadopoulos, P.; Coolen, A. C. C.

2010-01-01

We use generating functional analysis to study minority-game-type market models with generalized strategy valuation updates that control the psychology of agents' actions. The agents' choice between trend-following and contrarian trading, and their vigor in each, depends on the overall state of the market. Even in 'fake history' models, the theory now involves an effective overall bid process (coupled to the effective agent process) which can exhibit profound remanence effects and new phase transitions. For some models the bid process can be solved directly, others require Maxwell-construction-type approximations.

Immune Regulatory Activity of Vitamin D3 in Head and Neck Cancer

PubMed Central

Young, M. Rita I.; Day, Terry A.

2013-01-01

While vitamin D exhibits a multitude of cellular effects that can impact on cancer development and progression, this review focuses on its immune modulatory effects. These immune modulatory effects can be both direct and indirect. Compared to other cancer types, head and neck squamous cell carcinomas (HNSCC) have received less attention, but are a fascination immunologically because of the profound extent to which they inhibit immune defenses. This review describes the mechanisms of some of these immune inhibitory processes and how vitamin D can help overcome aspects of this immune suppression. PMID:24202334

Unusual two-dimensional behavior of iron-based superconductors with low anisotropy

NASA Astrophysics Data System (ADS)

Kalenyuk, A. A.; Pagliero, A.; Borodianskyi, E. A.; Aswartham, S.; Wurmehl, S.; Büchner, B.; Chareev, D. A.; Kordyuk, A. A.; Krasnov, V. M.

2017-10-01

We study angular-dependent magnetoresistance in iron-based superconductors Ba1 -xNaxFe2As2 and FeTe1 -xSex . Both superconductors have relatively small anisotropies γ ˜2 and exhibit a three-dimensional (3D) behavior at low temperatures. However, we observe that they start to exhibit a profound two-dimensional behavior at elevated temperatures and in applied magnetic field parallel to the surface. We conclude that the unexpected two-dimensional (2D) behavior of the studied low-anisotropic superconductors is not related to layeredness of the materials, but is caused by appearance of surface superconductivity when magnetic field exceeds the upper critical field Hc 2(T ) for destruction of bulk superconductivity. We argue that the corresponding 3D-2D bulk-to-surface dimensional transition can be used for accurate determination of the upper critical field.

Plasma vapor deposited n-indium tin oxide/p-copper indium oxide heterojunctions for optoelectronic device applications

NASA Astrophysics Data System (ADS)

Jaya, T. P.; Pradyumnan, P. P.

2017-12-01

Transparent crystalline n-indium tin oxide/p-copper indium oxide diode structures were fabricated on quartz substrates by plasma vapor deposition using radio frequency (RF) magnetron sputtering. The p-n heterojunction diodes were highly transparent in the visible region and exhibited rectifying current-voltage (I-V) characteristics with a good ideality factor. The sputter power during fabrication of the p-layer was found to have a profound effect on I-V characteristics, and the diode with the p-type layer deposited at a maximum power of 200 W exhibited the highest value of the diode ideality factor (η value) of 2.162, which suggests its potential use in optoelectronic applications. The ratio of forward current to reverse current exceeded 80 within the range of applied voltages of -1.5 to +1.5 V in all cases. The diode structure possessed an optical transmission of 60-70% in the visible region.

Towards clarifying what distinguishes cyanobacteria able to resurrect after desiccation from those that cannot: The photosynthetic aspect.

PubMed

Raanan, Hagai; Oren, Nadav; Treves, Haim; Keren, Nir; Ohad, Itzhak; Berkowicz, Simon M; Hagemann, Martin; Koch, Moriz; Shotland, Yoram; Kaplan, Aaron

2016-06-01

Organisms inhabiting biological soil crusts (BSCs) are able to cope with extreme environmental conditions including daily hydration/dehydration cycles, high irradiance and extreme temperatures. The photosynthetic machinery, potentially the main source of damaging reactive oxygen species during cessation of CO(2) fixation in desiccating cells, must be protected to avoid sustained photodamage. We compared certain photosynthetic parameters and the response to excess light of BCS-inhabiting, desiccation-tolerant cyanobacteria Leptolyngbya ohadii and Nostoc reinholdii with those observed in the "model" organisms Nostoc sp. PCC 7120, able to resurrect after mild desiccation, and Synechococcus elongatus PCC 7942 and Synechocystis sp. PCC 6803 that are unable to recover from dehydration. Desiccation-tolerant strains exhibited a transient decline in the photosynthetic rate at light intensities corresponding to the inflection point in the PI curve relating the O(2) evolution rate to light intensity. They also exhibited a faster and larger loss of variable fluorescence and profoundly faster Q(A)(-) re-oxidation rates after exposure to high illumination. Finally, a smaller difference was found in the temperature of maximal thermoluminescence signal in the absence or presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) than observed in "model" cyanobacteria. These parameters indicate specific functional differences of photosystem II (PSII) between desiccation tolerant and sensitive cyanobacteria. We propose that exposure to excess irradiation activates a non-radiative electron recombination route inside PSII that minimizes formation of damaging singlet oxygen in the desiccation-tolerant cyanobacteria and thereby reduces photodamage. Copyright © 2016 Elsevier B.V. All rights reserved.

Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs

PubMed Central

Jacques, Vincent; Czarnik, Anthony W.; Judge, Thomas M.; Van der Ploeg, Lex H. T.; DeWitt, Sheila H.

2015-01-01

Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using “deuterium-enabled chiral switching” (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (−)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics. PMID:25775521

Glutamatergic stimulation of the left dentate gyrus abolishes depressive-like behaviors in a rat learned helplessness paradigm.

PubMed

Seo, Jeho; Cho, Hojin; Kim, Gun Tae; Kim, Chul Hoon; Kim, Dong Goo

2017-10-01

Episodic experiences of stress have been identified as the leading cause of major depressive disorder (MDD). The occurrence of MDD is profoundly influenced by the individual's coping strategy, rather than the severity of the stress itself. Resting brain activity has been shown to alter in several mental disorders. However, the functional relationship between resting brain activity and coping strategies has not yet been studied. In the present study, we observed different patterns of resting brain activity in rats that had determined either positive (resilient to stress) or negative (vulnerable to stress) coping strategies, and examined whether modulation of the preset resting brain activity could influence the behavioral phenotype associated with negative coping strategy (i.e., depressive-like behaviors). We used a learned helplessness paradigm-a well-established model of MDD-to detect coping strategies. Differences in resting state brain activity between animals with positive and negative coping strategies were assessed using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glutamatergic stimulation was used to modulate resting brain activity. After exposure to repeated uncontrollable stress, seven of 23 rats exhibited positive coping strategies, while eight of 23 rats exhibited negative coping strategies. Increased resting brain activity was observed only in the left ventral dentate gyrus of the positive coping rats using FDG-PET. Furthermore, glutamatergic stimulation of the left dentate gyrus abolished depressive-like behaviors in rats with negative coping strategies. Increased resting brain activity in the left ventral dentate gyrus helps animals to select positive coping strategies in response to future stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Food availability at birth limited reproductive success in historical humans.

PubMed

Rickard, Ian J; Holopainen, Jari; Helama, Samuli; Helle, Samuli; Russell, Andrew F; Lummaa, Virpi

2010-12-01

Environmental conditions in early life can profoundly affect individual development and have consequences for reproductive success. Limited food availability may be one of the reasons for this, but direct evidence linking variation in early-life nutrition to reproductive performance in adulthood in natural populations is sparse. We combined historical agricultural data with detailed demographic church records to investigate the effect of food availability around the time of birth on the reproductive success of 927 men and women born in 18th-century Finland. Our study population exhibits natural mortality and fertility rates typical of many preindustrial societies, and individuals experienced differing access to resources due to social stratification. We found that among both men and women born into landless families (i.e., with low access to resources), marital prospects, probability of reproduction, and offspring viability were all positively related to local crop yield during the birth year. Such effects were generally absent among those born into landowning families. Among landless individuals born when yields of the two main crops, rye and barley, were both below median, only 50% of adult males and 55% of adult females gained any reproductive success in their lifetime, whereas 97% and 95% of those born when both yields were above the median did so. Our results suggest that maternal investment in offspring in prenatal or early postnatal life may have profound implications for the evolutionary fitness of human offspring, particularly among those for which resources are more limiting. Our study adds support to the idea that early nutrition can limit reproductive success in natural animal populations, and provides the most direct evidence to date that this process applies to humans.

Bridging Three Orders of Magnitude: Multiple Scattered Waves Sense Fractal Microscopic Structures via Dispersion

NASA Astrophysics Data System (ADS)

Lambert, Simon A.; Näsholm, Sven Peter; Nordsletten, David; Michler, Christian; Juge, Lauriane; Serfaty, Jean-Michel; Bilston, Lynne; Guzina, Bojan; Holm, Sverre; Sinkus, Ralph

2015-08-01

Wave scattering provides profound insight into the structure of matter. Typically, the ability to sense microstructure is determined by the ratio of scatterer size to probing wavelength. Here, we address the question of whether macroscopic waves can report back the presence and distribution of microscopic scatterers despite several orders of magnitude difference in scale between wavelength and scatterer size. In our analysis, monosized hard scatterers 5 μ m in radius are immersed in lossless gelatin phantoms to investigate the effect of multiple reflections on the propagation of shear waves with millimeter wavelength. Steady-state monochromatic waves are imaged in situ via magnetic resonance imaging, enabling quantification of the phase velocity at a voxel size big enough to contain thousands of individual scatterers, but small enough to resolve the wavelength. We show in theory, experiments, and simulations that the resulting coherent superposition of multiple reflections gives rise to power-law dispersion at the macroscopic scale if the scatterer distribution exhibits apparent fractality over an effective length scale that is comparable to the probing wavelength. Since apparent fractality is naturally present in any random medium, microstructure can thereby leave its fingerprint on the macroscopically quantifiable power-law exponent. Our results are generic to wave phenomena and carry great potential for sensing microstructure that exhibits intrinsic fractality, such as, for instance, vasculature.

Heat conduction in a chain of colliding particles with a stiff repulsive potential

NASA Astrophysics Data System (ADS)

Gendelman, Oleg V.; Savin, Alexander V.

2016-11-01

One-dimensional billiards, i.e., a chain of colliding particles with equal masses, is a well-known example of a completely integrable system. Billiards with different particle masses is generically not integrable, but it still exhibits divergence of a heat conduction coefficient (HCC) in the thermodynamic limit. Traditional billiards models imply instantaneous (zero-time) collisions between the particles. We relax this condition of instantaneous impact and consider heat transport in a chain of stiff colliding particles with the power-law potential of the nearest-neighbor interaction. The instantaneous collisions correspond to the limit of infinite power in the interaction potential; for finite powers, the interactions take nonzero time. This modification of the model leads to a profound physical consequence—the probability of multiple (in particular triple) -particle collisions becomes nonzero. Contrary to the integrable billiards of equal particles, the modified model exhibits saturation of the heat conduction coefficient for a large system size. Moreover, the identification of scattering events with triple-particle collisions leads to a simple definition of the characteristic mean free path and a kinetic description of heat transport. This approach allows us to predict both the temperature and density dependencies for the HCC limit values. The latter dependence is quite counterintuitive—the HCC is inversely proportional to the particle density in the chain. Both predictions are confirmed by direct numerical simulations.

Consanguinity Among Parents of Iranian Deaf Children

PubMed Central

Ajallouyan, Mohammad; Radfar, Shokofeh; Nouhi, Sima; Tavallaie, Seid Abbas; Amirsalari, Susan; Yousefi, Jaleh; Hasanali Fard, Mahdieh

2016-01-01

Background It seems that there is a relationship between consanguinity and profound hearing loss but there is little data about the association of consanguinity and hearing loss in Iran. Objectives The aim of this study is to demonstrate the causes of profound bilateral sensorineural hearing loss among Iranian samples who are candidates for cochlear implantation. Methods This study was retrospective, analytical, and designed to collect information about profound hearing impaired cases referred to the Baqiyatallah Cochlear implantation center using enumeration. A total of 310 children with profound hearing impairments participated in this study. They were aged from 6 months to 4 years old. The study was done between January 2007 and April 2009. Chi-square tests were used to show whether there was any statistical difference between the incidence of marital consanguinity of their parents and the normal population. Results Sixty-five percent of those 310 children had parents who had married with their relatives. Of the 203 (65%) parents that had consanguineous marriages, 132 were first cousins, which includes the children of two brothers (37 [11.8%] patrilateral parallel cousins), the children of two sisters (38 [12.2%] multi-lateral parallel cousins), or the children of a brother and a sister (57 [18.3%] cross cousins). Fifty-four (17.4%) of the parents were second cousins and 17 (5.2%) were beyond second cousins. Also, hearing loss etiology was obvious in 237 (76.3%) of the patients with profound hearing loss but was unknown in 73 (23.7%). Hereditary was identified as the most common cause in 33% of the cases. Conclusions Our data demonstrated a 65% occurrence of consanguineous marriage among the parents of deaf children, which is statistically different from the percentage of consanguineous marriage among Iranian population (38%). This indicates an obvious relationship between severe hearing loss and consanguineous marriage. PMID:28191326

Different populations of blacklegged tick nymphs exhibit differences in questing behavior that have implications for human lyme disease risk.

PubMed

Arsnoe, Isis M; Hickling, Graham J; Ginsberg, Howard S; McElreath, Richard; Tsao, Jean I

2015-01-01

Animal behavior can have profound effects on pathogen transmission and disease incidence. We studied the questing (= host-seeking) behavior of blacklegged tick (Ixodes scapularis) nymphs, which are the primary vectors of Lyme disease in the eastern United States. Lyme disease is common in northern but not in southern regions, and prior ecological studies have found that standard methods used to collect host-seeking nymphs in northern regions are unsuccessful in the south. This led us to hypothesize that there are behavior differences between northern and southern nymphs that alter how readily they are collected, and how likely they are to transmit the etiological agent of Lyme disease to humans. To examine this question, we compared the questing behavior of I. scapularis nymphs originating from one northern (Lyme disease endemic) and two southern (non-endemic) US regions at field sites in Wisconsin, Rhode Island, Tennessee, and Florida. Laboratory-raised uninfected nymphs were monitored in circular 0.2 m2 arenas containing wooden dowels (mimicking stems of understory vegetation) for 10 (2011) and 19 (2012) weeks. The probability of observing nymphs questing on these stems (2011), and on stems, on top of leaf litter, and on arena walls (2012) was much greater for northern than for southern origin ticks in both years and at all field sites (19.5 times greater in 2011; 3.6-11.6 times greater in 2012). Our findings suggest that southern origin I. scapularis nymphs rarely emerge from the leaf litter, and consequently are unlikely to contact passing humans. We propose that this difference in questing behavior accounts for observed geographic differences in the efficacy of the standard sampling techniques used to collect questing nymphs. These findings also support our hypothesis that very low Lyme disease incidence in southern states is, in part, a consequence of the type of host-seeking behavior exhibited by southern populations of the key Lyme disease vector.

Different populations of blacklegged tick nymphs exhibit differences in questing behavior that have implications for human lyme disease risk

USGS Publications Warehouse

Arsnoe, Isis M.; Hickling, Graham J.; Ginsberg, Howard S.; McElreath, Richard; Tsao, Jean I.

2015-01-01

Animal behavior can have profound effects on pathogen transmission and disease incidence. We studied the questing (= host-seeking) behavior of blacklegged tick (Ixodes scapularis) nymphs, which are the primary vectors of Lyme disease in the eastern United States. Lyme disease is common in northern but not in southern regions, and prior ecological studies have found that standard methods used to collect host-seeking nymphs in northern regions are unsuccessful in the south. This led us to hypothesize that there are behavior differences between northern and southern nymphs that alter how readily they are collected, and how likely they are to transmit the etiological agent of Lyme disease to humans. To examine this question, we compared the questing behavior of I. scapularis nymphs originating from one northern (Lyme disease endemic) and two southern (non-endemic) US regions at field sites in Wisconsin, Rhode Island, Tennessee, and Florida. Laboratory-raised uninfected nymphs were monitored in circular 0.2 m2 arenas containing wooden dowels (mimicking stems of understory vegetation) for 10 (2011) and 19 (2012) weeks. The probability of observing nymphs questing on these stems (2011), and on stems, on top of leaf litter, and on arena walls (2012) was much greater for northern than for southern origin ticks in both years and at all field sites (19.5 times greater in 2011; 3.6-11.6 times greater in 2012). Our findings suggest that southern origin I. scapularis nymphs rarely emerge from the leaf litter, and consequently are unlikely to contact passing humans. We propose that this difference in questing behavior accounts for observed geographic differences in the efficacy of the standard sampling techniques used to collect questing nymphs. These findings also support our hypothesis that very low Lyme disease incidence in southern states is, in part, a consequence of the type of host-seeking behavior exhibited by southern populations of the key Lyme disease vector.

Acidosis Differentially Modulates Inactivation in NaV1.2, NaV1.4, and NaV1.5 Channels

PubMed Central

Vilin, Yury Y.; Peters, Colin H.; Ruben, Peter C.

2012-01-01

NaV channels play a crucial role in neuronal and muscle excitability. Using whole-cell recordings we studied effects of low extracellular pH on the biophysical properties of NaV1.2, NaV1.4, and NaV1.5, expressed in cultured mammalian cells. Low pH produced different effects on different channel subtypes. Whereas NaV1.4 exhibited very low sensitivity to acidosis, primarily limited to partial block of macroscopic currents, the effects of low pH on gating in NaV1.2 and NaV1.5 were profound. In NaV1.2 low pH reduced apparent valence of steady-state fast inactivation, shifted the τ(V) to depolarizing potentials and decreased channels availability during onset to slow and use-dependent inactivation (UDI). In contrast, low pH delayed open-state inactivation in NaV1.5, right-shifted the voltage-dependence of window current, and increased channel availability during onset to slow and UDI. These results suggest that protons affect channel availability in an isoform-specific manner. A computer model incorporating these results demonstrates their effects on membrane excitability. PMID:22701426

Greenland ice sheet mass balance: a review.

PubMed

Khan, Shfaqat A; Aschwanden, Andy; Bjørk, Anders A; Wahr, John; Kjeldsen, Kristian K; Kjær, Kurt H

2015-04-01

Over the past quarter of a century the Arctic has warmed more than any other region on Earth, causing a profound impact on the Greenland ice sheet (GrIS) and its contribution to the rise in global sea level. The loss of ice can be partitioned into processes related to surface mass balance and to ice discharge, which are forced by internal or external (atmospheric/oceanic/basal) fluctuations. Regardless of the measurement method, observations over the last two decades show an increase in ice loss rate, associated with speeding up of glaciers and enhanced melting. However, both ice discharge and melt-induced mass losses exhibit rapid short-term fluctuations that, when extrapolated into the future, could yield erroneous long-term trends. In this paper we review the GrIS mass loss over more than a century by combining satellite altimetry, airborne altimetry, interferometry, aerial photographs and gravimetry data sets together with modelling studies. We revisit the mass loss of different sectors and show that they manifest quite different sensitivities to atmospheric and oceanic forcing. In addition, we discuss recent progress in constructing coupled ice-ocean-atmosphere models required to project realistic future sea-level changes.

Writing projects: lessening undergraduates' unique suicidal bereavement.

PubMed

Kovac, S H; Range, L M

2000-01-01

To assess if writing projects lessen undergraduates' grief following a loved one's suicide, 40 students whose loved one died by suicide in the past 2 years wrote on four occasions over 2 weeks about profound topics (e.g., events and emotions surrounding the death) or trivial topics (e.g., description of the previous meal). All participants completed pre- and posttest measures of grief and self-reported health visits, and 75% completed the same measures at 6-week mailed follow-up. As expected, individuals in the profound condition reported less grief associated with suicide at follow-up than those in the trivial condition. However, the trivial and profound groups were not significantly different in general grief or health visits. Writing about grief associated with the suicide of a loved one appeared to reduce suicidal grief associated with this event. However, this benefit did not extend to general grief or physical health.

Studying sea otter foraging ecology: A review of some methodological approaches

USGS Publications Warehouse

Tinker, M.T.; Estes, J.A.; Bodkin, James L.; Staedler, M.M.; Monson, Daniel H.; Maldini, Daniela; Calkins, Donald; Atkinson, Shannon; Meehan, Rosa

2004-01-01

The study of foraging ecology plays a central role in our understanding of animal populations and natural communities, and can also provide information necessary for the effective conservation of rare or endangered species. Sea otter researchers are interested in foraging ecology for many different reasons, but for heuristic purposes we identify three general types of research questions: (1) questions about the implications of foraging decisions to individual fitness, the evolutionary significance of feeding strategies, and the selective forces and constraints that shape an individual’s diet and feeding behavior; (2) questions about the population- level implications of foraging ecology; for example, how is the status of a population (with respect to carrying capacity) reflected by the foraging success or diet composition of individuals within the population (Fig. 1); and (3) questions about the community-level consequences of sea otter foraging. Sea otters provide an excellent study system for all three types of questions because they are a tractable species to study (generally feeding near shore and bringing all prey to the surface to consume), they exhibit a wide range of diets and foraging strategies in different habitats and at different population densities, they tend to have strong trophic interactions with their prey species, and their foraging behavior can have profound effects on community structure in the nearshore marine community.

Cytotoxicity of gold nanoparticles with different structures and surface-anchored chiral polymers.

PubMed

Deng, Jun; Yao, Mengyun; Gao, Changyou

2017-04-15

Nanoparticles (NPs) can have profound effects on cell biology. However, the potential adverse effects of gold nanoparticles (AuNPs) with different surface chirality and structures have not been elucidated. In this study, monolayers of poly(acryloyl-l(d)-valine (l(d)-PAV) chiral molecules were anchored on the surfaces of gold nanocubes (AuNCs) and nanooctahedras (AuNOs), respectively. The l-PAV-AuNCs and d-PAV-AuNCs, or the l-PAV-AuNOs and d-PAV-AuNOs, had identical physicochemical properties in terms of size, morphology and ligand density except of the reverse molecular chirality on the particle surfaces, respectively. The l-PAV capped AuNCs and AuNOs exhibited larger cytotoxicity to A549 cells than the D-PAV coated ones, and the PAV-AuNOs had larger cytotoxicity than PAV-AuNCs when being capped with the same type of enantiomers, respectively. The cytotoxicity was positively correlated with the cellular uptake amount, and thereby the production of intracellular reactive oxygen species (ROS). • Gold nanoparticles with different structure and surface chirality are fabricated. • The structure and surface chirality at the nanoscale can influence cytotoxicity and genotoxicity. • A new perspective on designing nanoparticles for drug delivery, bioimaging and diagnosis. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hypomorphic PCNA mutation underlies a human DNA repair disorder

PubMed Central

Baple, Emma L.; Chambers, Helen; Cross, Harold E.; Fawcett, Heather; Nakazawa, Yuka; Chioza, Barry A.; Harlalka, Gaurav V.; Mansour, Sahar; Sreekantan-Nair, Ajith; Patton, Michael A.; Muggenthaler, Martina; Rich, Phillip; Wagner, Karin; Coblentz, Roselyn; Stein, Constance K.; Last, James I.; Taylor, A. Malcolm R.; Jackson, Andrew P.; Ogi, Tomoo; Lehmann, Alan R.; Green, Catherine M.; Crosby, Andrew H.

2014-01-01

Numerous human disorders, including Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum, and trichothiodystrophy, result from the mutation of genes encoding molecules important for nucleotide excision repair. Here, we describe a syndrome in which the cardinal clinical features include short stature, hearing loss, premature aging, telangiectasia, neurodegeneration, and photosensitivity, resulting from a homozygous missense (p.Ser228Ile) sequence alteration of the proliferating cell nuclear antigen (PCNA). PCNA is a highly conserved sliding clamp protein essential for DNA replication and repair. Due to this fundamental role, mutations in PCNA that profoundly impair protein function would be incompatible with life. Interestingly, while the p.Ser228Ile alteration appeared to have no effect on protein levels or DNA replication, patient cells exhibited marked abnormalities in response to UV irradiation, displaying substantial reductions in both UV survival and RNA synthesis recovery. The p.Ser228Ile change also profoundly altered PCNA’s interaction with Flap endonuclease 1 and DNA Ligase 1, DNA metabolism enzymes. Together, our findings detail a mutation of PCNA in humans associated with a neurodegenerative phenotype, displaying clinical and molecular features common to other DNA repair disorders, which we showed to be attributable to a hypomorphic amino acid alteration. PMID:24911150

Profound loss of intestinal Tregs in acutely SIV-infected neonatal macaques.

PubMed

Wang, Xiaolei; Xu, Huanbin; Shen, Chanjuan; Alvarez, Xavier; Liu, David; Pahar, Bapi; Ratterree, Marion S; Doyle-Meyers, Lara A; Lackner, Andrew A; Veazey, Ronald S

2015-02-01

Impairment of the intestinal mucosal immune system is an early feature of HIV-infected children. Most infected children exhibit clinical gastrointestinal symptoms at some stage of infection, and persistent diarrhea is a marker for rapid disease progression. It is known that Tregs are especially important in mediating intestinal immune homeostasis and that loss of this subset may result in intestinal inflammation and associated clinical signs. Large numbers of FoxP3(+) T cells were found in all tissues in newborn macaques, which coexpressed high levels of CD25 and CD4, indicating that they were Tregs. Moreover, neonates had much greater percentages of Tregs in intestinal tissues compared with peripheral lymphoid tissues. After SIV infection, a significant loss of Tregs was detected in the intestine compared with age-matched normal infants. Finally, SIV-infected FoxP3(+) T cells were detected in tissues in neonates as early as 7 SIV dpi. These results demonstrate that Tregs constitute a significant fraction of CD4(+) T cells in neonatal intestinal tissues and that an early, profound loss of Tregs occurs in acute SIV infection, which may contribute to the intestinal disorders associated with neonatal HIV infection. © Society for Leukocyte Biology.

A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.

PubMed

Bitner-Glindzicz, M; Lindley, K J; Rutland, P; Blaydon, D; Smith, V V; Milla, P J; Hussain, K; Furth-Lavi, J; Cosgrove, K E; Shepherd, R M; Barnes, P D; O'Brien, R E; Farndon, P A; Sowden, J; Liu, X Z; Scanlan, M J; Malcolm, S; Dunne, M J; Aynsley-Green, A; Glaser, B

2000-09-01

Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa. It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E. Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K + (KATP) channels), which may be mutated in patients with hyperinsulinism. We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction. The molecular basis of the disorder is a homozygous 122-kb deletion of 11p14-15, which includes part of ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18. The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C. The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C.

Overexpression of suppressor of cytokine signaling 3 in the arcuate nucleus of juvenile Phodopus sungorus alters seasonal body weight changes.

PubMed

Ganjam, Goutham K; Benzler, Jonas; Pinkenburg, Olaf; Boucsein, Alisa; Stöhr, Sigrid; Steger, Juliane; Culmsee, Carsten; Barrett, Perry; Tups, Alexander

2013-12-01

The profound seasonal cycle in body weight exhibited by the Djungarian hamster (Phodopus sungorus) is associated with the development of hypothalamic leptin resistance during long day photoperiod (LD, 16:8 h light dark cycle), when body weight is elevated relative to short day photoperiod (SD, 8:16 h light dark cycle). We previously have shown that this seasonal change in physiology is associated with higher levels of mRNA for the potent inhibitor of leptin signaling, suppressor of cytokine signaling-3 (SOCS3), in the arcuate nucleus (ARC) of LD hamsters relative to hamsters in SD. The alteration in SOCS3 gene expression preceded the body weight change suggesting that SOCS3 might be the molecular switch of seasonal body weight changes. To functionally characterize the role of SOCS3 in seasonal body weight regulation, we injected SOCS3 expressing recombinant adeno-associated virus type-2 (rAAV2-SOCS3) constructs into the ARC of leptin sensitive SD hamsters immediately after weaning. Hamsters that received rAAV2 expressing enhanced green fluorescent protein (rAAV2-EGFP) served as controls. ARC-directed SOCS3 overexpression led to a significant increase in body weight over a period of 12 weeks without fully restoring the LD phenotype. This increase was partially due to elevated brown and white adipose tissue mass. Gene expression of pro-opiomelanocortin was increased while thyroid hormone converting enzyme DIO3 mRNA levels were reduced in SD hamsters with SOCS3 overexpression. In conclusion, our data suggest that ARC-directed SOCS3 overexpression partially overcomes the profound seasonal body weight cycle exhibited by the hamster which is associated with altered pro-opiomelanocortin and DIO3 gene expression.

Controlling the surface‐mediated release of DNA using ‘mixed multilayers’

PubMed Central

Appadoo, Visham; Carter, Matthew C. D.

2016-01-01

Abstract We report the design of erodible ‘mixed multilayer’ coatings fabricated using plasmid DNA and combinations of both hydrolytically degradable and charge‐shifting cationic polymer building blocks. Films fabricated layer‐by‐layer using combinations of a model poly(β‐amino ester) (polymer 1) and a model charge‐shifting polymer (polymer 2) exhibited DNA release profiles that were substantially different than those assembled using DNA and either polymer 1 or polymer 2 alone. In addition, the order in which layers of these two cationic polymers were deposited during assembly had a profound impact on DNA release profiles when these materials were incubated in physiological buffer. Mixed multilayers ∼225 nm thick fabricated by depositing layers of polymer 1/DNA onto films composed of polymer 2/DNA released DNA into solution over ∼60 days, with multi‐phase release profiles intermediate to and exhibiting some general features of polymer 1/DNA or polymer 2/DNA films (e.g., a period of rapid release, followed by a more extended phase). In sharp contrast, ‘inverted’ mixed multilayers fabricated by depositing layers of polymer 2/DNA onto films composed of polymer 1/DNA exhibited release profiles that were almost completely linear over ∼60‐80 days. These and other results are consistent with substantial interdiffusion and commingling (or mixing) among the individual components of these compound materials. Our results reveal this mixing to lead to new, unanticipated, and useful release profiles and provide guidance for the design of polymer‐based coatings for the local, surface‐mediated delivery of DNA from the surfaces of topologically complex interventional devices, such as intravascular stents, with predictable long‐term release profiles. PMID:27981243

Host species and developmental stage, but not host social structure, affects bacterial community structure in socially polymorphic bees.

PubMed

McFrederick, Quinn S; Wcislo, William T; Hout, Michael C; Mueller, Ulrich G

2014-05-01

Social transmission and host developmental stage are thought to profoundly affect the structure of bacterial communities associated with honey bees and bumble bees, but these ideas have not been explored in other bee species. The halictid bees Megalopta centralis and M. genalis exhibit intrapopulation social polymorphism, which we exploit to test whether bacterial communities differ by host social structure, developmental stage, or host species. We collected social and solitary Megalopta nests and sampled bees and nest contents from all stages of host development. To survey these bacterial communities, we used 16S rRNA gene 454 pyrosequencing. We found no effect of social structure, but found differences by host species and developmental stage. Wolbachia prevalence differed between the two host species. Bacterial communities associated with different developmental stages appeared to be driven by environmentally acquired bacteria. A Lactobacillus kunkeei clade bacterium that is consistently associated with other bee species was dominant in pollen provisions and larval samples, but less abundant in mature larvae and pupae. Foraging adults appeared to often reacquire L. kunkeei clade bacteria, likely while foraging at flowers. Environmental transmission appears to be more important than social transmission for Megalopta bees at the cusp between social and solitary behavior. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences.

PubMed

Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

2014-01-01

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug-fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug-fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid.

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences

PubMed Central

Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

2014-01-01

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug–fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug–fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid. PMID:25114504

The allelopathic effects of invasive plant Solidago canadensis on seed germination and growth of Lactuca sativa enhanced by different types of acid deposition.

PubMed

Wang, Congyan; Xiao, Hongguang; Zhao, Lulu; Liu, Jun; Wang, Lei; Zhang, Fei; Shi, Yanchun; Du, Daolin

2016-04-01

Invasive species can exhibit allelopathic effects on native species. Meanwhile, the types of acid deposition are gradually changing. Thus, the allelopathic effects of invasive species on seed germination and growth of native species may be altered or even enhanced under conditions with diversified acid deposition. This study aims to assess the allelopathic effects (using leaves extracts) of invasive plant Solidago canadensis on seed germination and growth of native species Lactuca sativa treated with five types of acid deposition with different SO4(2-) to NO3(-) ratios (1:0, sulfuric acid; 5:1, sulfuric-rich acid; 1:1, mixed acid; 1:5, nitric-rich acid; 0:1, nitric acid). Solidago canadensis leaf extracts exhibited significantly allelopathic effects on germination index, vigor index, and germination rate index of L. sativa. High concentration of S. canadensis leaf extracts also similarly exhibited significantly allelopathic effects on root length of L. sativa. This may be due to that S. canadensis could release allelochemicals and then trigger allelopathic effects on seed germination and growth of L. sativa. Acid deposition exhibited significantly negative effects on seedling biomass, root length, seedling height, germination index, vigor index, and germination rate index of L. sativa. This may be ascribed to the decreased soil pH values mediated by acid deposition which could produce toxic effects on seedling growth. Sulfuric acid deposition triggered more toxic effects on seedling biomass and vigor index of L. sativa than nitric acid deposition. This may be attributing to the difference in exchange capacity with hydroxyl groups (OH(-)) between SO4(2-) and NO3(-) as well as the fertilizing effects mediated by nitric deposition. All types of acid deposition significantly enhanced the allelopathic effects of S. canadensis on root length, germination index, vigor index, and germination rate index of L. sativa. This may be due to the negatively synergistic effects of acid deposition and S. canadensis on seed germination and growth of L. sativa. The ratio of SO4(2-) to NO3(-) in acid deposition was an important factor that profoundly affected the allelopathic effects of S. canadensis on the seed germination and growth of L. sativa possibly because the difference in exchange capacity with hydroxyl groups (OH(-)) between SO4(2-) and NO3(-) as well as the fertilizing effects triggered by nitric deposition. Thus, the allelopathic effects of invasive species on seed germination and growth of native plants might be enhanced under increased and diversified acid deposition.

Subjects harboring presenilin familial Alzheimer’s disease mutations exhibit diverse white matter biochemistry alterations

PubMed Central

Roher, Alex E; Maarouf, Chera L; Malek-Ahmadi, Michael; Wilson, Jeffrey; Kokjohn, Tyler A; Daugs, Ian D; Whiteside, Charisse M; Kalback, Walter M; Macias, MiMi P; Jacobson, Sandra A; Sabbagh, Marwan N; Ghetti, Bernardino; Beach, Thomas G

2013-01-01

Alzheimer’s disease (AD) dementia impacts all facets of higher order cognitive function and is characterized by the presence of distinctive pathological lesions in the gray matter (GM). The profound alterations in GM structure and function have fostered the view that AD impacts are primarily a consequence of GM damage. However, the white matter (WM) represents about 50% of the cerebrum and this area of the brain is substantially atrophied and profoundly abnormal in both sporadic AD (SAD) and familial AD (FAD). We examined the WM biochemistry by ELISA and Western blot analyses of key proteins in 10 FAD cases harboring mutations in the presenilin genes PSEN1 and PSEN2 as well as in 4 non-demented control (NDC) individuals and 4 subjects with SAD. The molecules examined were direct substrates of PSEN1 such as Notch-1 and amyloid precursor protein (APP). In addition, apolipoproteins, axonal transport molecules, cytoskeletal and structural proteins, neurotrophic factors and synaptic proteins were examined. PSEN-FAD subjects had, on average, higher amounts of WM amyloid-beta (Aβ) peptides compared to SAD, which may play a role in the devastating dysfunction of the brain. However, the PSEN-FAD mutations we examined did not produce uniform increases in the relative proportions of Aβ42 and exhibited substantial variability in total Aβ levels. These observations suggest that neurodegeneration and dementia do not depend solely on enhanced Aβ42 levels. Our data revealed additional complexities in PSEN-FAD individuals. Some direct substrates of γ-secretase, such as Notch, N-cadherin, Erb-B4 and APP, deviated substantially from the NDC group baseline for some, but not all, mutation types. Proteins that were not direct γ-secretase substrates, but play key structural and functional roles in the WM, likewise exhibited varied concentrations in the distinct PSEN mutation backgrounds. Detailing the diverse biochemical pathology spectrum of PSEN mutations may offer valuable insights into dementia progression and the design of effective therapeutic interventions for both SAD and FAD. PMID:24093083

Regenerating reptile retinas: a comparative approach to restoring retinal ganglion cell function.

PubMed

Williams, D L

2017-02-01

Transection or damage to the mammalian optic nerve generally results in loss of retinal ganglion cells by apoptosis. This cell death is seen less in fish or amphibians where retinal ganglion cell survival and axon regeneration leads to recovery of sight. Reptiles lie somewhere in the middle of this spectrum of nerve regeneration, and different species have been reported to have a significant variation in their retinal ganglion cell regenerative capacity. The ornate dragon lizard Ctenophoris ornatus exhibits a profound capacity for regeneration, whereas the Tenerife wall lizard Gallotia galloti has a more variable response to optic nerve damage. Some individuals regain visual activity such as the pupillomotor responses, whereas in others axons fail to regenerate sufficiently. Even in Ctenophoris, although the retinal ganglion cell axons regenerate adequately enough to synapse in the tectum, they do not make long-term topographic connections allowing recovery of complex visually motivated behaviour. The question then centres on where these intraspecies differences originate. Is it variation in the innate ability of retinal ganglion cells from different species to regenerate with functional validity? Or is it variances between different species in the substrate within which the nerves regenerate, the extracellular environment of the damaged nerve or the supporting cells surrounding the regenerating axons? Investigations of retinal ganglion cell regeneration between different species of lower vertebrates in vivo may shed light on these questions. Or perhaps more interesting are in vitro studies comparing axon regeneration of retinal ganglion cells from various species placed on differing substrates.

Ovarian cycling and reproductive state shape the vaginal microbiota in wild baboons.

PubMed

Miller, Elizabeth A; Livermore, Joshua A; Alberts, Susan C; Tung, Jenny; Archie, Elizabeth A

2017-01-19

The vaginal microbiome is an important site of bacterial-mammalian symbiosis. This symbiosis is currently best characterized for humans, where lactobacilli dominate the microbial community and may help defend women against infectious disease. However, lactobacilli do not dominate the vaginal microbiota of any other mammal studied to date, raising key questions about the forces that shape the vaginal microbiome in non-human mammals. We used Illumina sequencing of the bacterial 16S rRNA gene to investigate variation in the taxonomic composition of the vaginal microbiota in 48 baboons (Papio cynocephalus), members of a well-studied wild population in Kenya. Similar to prior studies, we found that the baboon vaginal microbiota was not dominated by lactobacilli. Despite this difference, and similar to humans, reproductive state was the dominant predictor of baboon vaginal microbiota, with pregnancy, postpartum amenorrhea, and ovarian cycling explaining 18% of the variance in community composition. Furthermore, among cycling females, a striking 39% of variance in community composition was explained by ovarian cycle phase, with an especially distinctive microbial community around ovulation. Periovulatory females exhibited the highest relative abundance of lactic acid-producing bacteria compared to any other phase, with a mean relative abundance of 44%. To a lesser extent, sexual behavior, especially a history of shared sexual partners, also predicted vaginal microbial similarity between baboons. Despite striking differences in their dominant microbes, both human and baboon vaginal microbiota exhibit profound changes in composition in response to reproductive state, ovarian cycle phase, and sexual behavior. We found major shifts in composition during ovulation, which may have implications for disease risk and conception success. These findings highlight the need for future studies to account for fine-scale differences in reproductive state, particularly differences between the various phases of the ovarian cycle. Overall, our work contributes to an emerging understanding of the forces that explain intra- and inter-individual variation in the mammalian vaginal microbiome, with particular emphasis on its role in host health and disease risk.

[Impacts of numerology on acupuncture].

PubMed

Chen, Min; Wu, Changqiu; Wu, Xueyi

2016-04-01

Numerology has a long history in China and has the profound impacts on every academic field in TCM, with acupuncture involved. In this paper, the impacts on acupuncture were discussed in different aspects such as the numbers of meridians, the length of meridian, the time taboo of acupuncture, acupuncture manipulation and time acupuncture. It was found that numerology had laid the critical impact on acupuncture and had the profound imprint nowadays. It is of great significance to study the numerology theory in its impacts on acupuncture, in the exploration on the theories behind acupuncture as well as the comprehensive understanding of acupuncture.

Effects of total body irradiation and cyclosporin a on the lethality of toxic shock syndrome toxin-1 in a rabbit model of toxic shock syndrome.

PubMed

Dinges, Martin M; Gregerson, Dale S; Tripp, Timothy J; McCormick, John K; Schlievert, Patrick M

2003-10-15

Toxic shock syndrome (TSS) may be mediated by superantigen-activated T cells, a theory we tested in rabbits, which are more susceptible to the lethal effects of superantigens, such as TSS toxin-1 (TSST-1), than are mice. Rabbits exposed to 10 cGy of total body irradiation exhibited T cell deficiency, with profound depletion of splenic lymphocytes and circulating CD4(+) lymphocytes, as well as an inability to manifest delayed-type hypersensitivity. Nevertheless, these rabbits remained completely susceptible to TSST-1, indicating that TSS can occur in the setting of marked immunosuppression.

Mechanisms and management of the heart in Myotonic Dystrophy

PubMed Central

McNally, Elizabeth M.; Sparano, Dina

2015-01-01

Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy and is caused by expansion of short nucleotide repeats that, in turn, produce toxic RNA aggregates within cells. DM is multisystemic, and the heart is primary site of pathology. DM patients exhibit cardiac conduction disorders including atrial fibrillation, atrio-ventricular heart block and ventricular arrhythmias. DM patients are also at risk for cardiomyopathy and congestive heart failure. Myotonic dystrophy is also characterized by myotonia, muscle weakness, and profound fatigue. The management of these symptoms requires input from the cardiologist and a team approach to minimize the debilitating aspects of the disorder and optimize cardiac function. PMID:21642660

Rheological properties of the product slurry of the Nitrate to Ammonia and Ceramic (NAC) process

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

Muguercia, I.; Yang, G.; Ebadian, M.A.

The Nitrate to Ammonia and Ceramic (NAC) process is an innovative technology for immobilizing the liquid from Low Level radioactive Waste (LLW). An experimental study was conducted to measure the rheological properties of the pipe flow of the NAC product slurry. Test results indicate that the NAC product slurry has a profound rheological behavior. At low solids concentration, the slurry exhibits a typical dilatant fluid (or shear thinning)fluid. The transition from dilatant fluid to pseudo-plastic fluid will occur at between 25% to 30% solids concentration in temperature ranges of 50--80{degree}C. Correlation equations are developed based on the test data.

Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation.

PubMed

Chambers, Anna R; Salazar, Juan J; Polley, Daniel B

2016-01-01

Neurons at higher stages of sensory processing can partially compensate for a sudden drop in peripheral input through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where >95% of afferent synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, auditory cortex (ACtx) processing and perception recover despite the absence of an auditory brainstem response (ABR) or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC), an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB) of awake mice. Sound driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory plasticity at the level of the auditory thalamus was less robust overall than previous observations in cortex or midbrain. Hierarchical differences in compensatory plasticity following sensorineural hearing loss may reflect differences in GABA circuit organization within the MGB, as compared to the ACtx or IC.

Specific needs of families of young adults with profound intellectual disability during and after transition to adulthood: What are we missing?

PubMed

Gauthier-Boudreault, Camille; Gallagher, Frances; Couture, Mélanie

2017-07-01

At the age of 21, the trajectory of services offered to youth with profound intellectual disability (ID) change significantly since access to specialised services is more limited. Despite the desire of parents to avoid any impact on their child, several factors can influence the course of this transition. However, there is little research on facilitators and obstacles to the transition to adulthood, and impacts on people with a profound ID. It is therefore difficult to provide solutions that meet their specific needs. The study aimed to document the needs of parents and young adults with profound ID during and after the transition to adulthood by exploring their transitioning experience and factors that influenced it. Using a descriptive qualitative design, two individual semi-structured interviews were conducted with fourteen (14) parents of young adults aged between 18 and 26 with a profound ID. At this point, many material, informative, cognitive and emotional needs of young adults and their parents are not met. Obstacles, mainly organisational, persist and result in a particularly difficult transition to adulthood experience. By knowing the specific needs of these families, it is possible to develop and implement solutions tailored to their reality. WHAT THE PAPERS ADDS?: The transition to adulthood is a critical period for families with young adults with an intellectual disability (ID), a reality observed internationally. Current literature on all levels of ID suggests some barriers to transition that lead to negative impacts on both parents and young adults with ID. However, presently, very little research exists on the reality of families of young adults with profound ID and factors influencing transition to adult life. Most of studies target people with mild to moderate ID. Considering the significant disabilities of people with profound ID, it is possible to imagine that their experience of transition will be even more difficult and they will present specific needs. The lack of understanding of these needs makes it difficult to introduce solutions tailored to their reality. The results of this current study suggest that many needs of young adults with profound ID and their parents are not met despite existent transition planning services. Transition to adulthood seems particularly difficult for these families who face many challenges. Parents in this study proposed different obstacles during transition to adulthood that could be improved for creation of future solutions adapted to their reality. Copyright © 2017. Published by Elsevier Ltd.

Steroid signaling system responds differently to temperature and hormone manipulation in the red-eared slider turtle (Trachemys scripta elegans), a reptile with temperature-dependent sex determination.

PubMed

Ramsey, M; Crews, D

2007-01-01

Many reptiles, including the red-eared slider turtle (Trachemys scripta elegans), exhibit temperature-dependent sex determination (TSD). Temperature determines gonadal sex during the middle of embryogenesis, or the temperature-sensitive period (TSP), when gonadal sex is labile to both temperature and hormones--particularly estrogen. The biological actions of steroid hormones are mediated by their receptors as defined here as the classic transcriptional regulation of target genes. To elucidate estrogen action during sex determination, we examined estrogen receptor alpha (Esr1, hereafter referred to as ERalpha), estrogen receptor beta (Esr2, hereafter referred to as ERbeta), and androgen receptor (Ar, hereafter referred to as AR) expression in slider turtle gonads before, during and after the TSP, as well as following sex reversal via temperature or steroid hormone manipulation. ERalpha and AR levels spike at the female-producing temperature while ovarian sex is determined, but none of the receptors exhibited sexually dimorphic localization within the gonad prior to morphological differentiation. All three receptors respond differentially to sex-reversing treatments. When shifted to female-producing temperatures, embryos maintain ERalpha and AR expression while ERbeta is reduced. When shifted to male-producing temperatures, medullary expression of all three receptors is reduced. Feminization via estradiol (E(2)) treatment at a male-producing temperature profoundly changed the expression patterns for all three receptors. ERalpha and ERbeta redirected to the cortex in E(2)-created ovaries, while AR medullary expression was transiently reduced. Although warmer incubation temperature and estrogen result in the same endpoint (ovarian development), our results indicate different steroid signaling patterns between temperature- and estrogen-induced feminization. 2007 S. Karger AG, Basel

Endocannabinoid signalling: has it got rhythm?

PubMed Central

Vaughn, Linda K; Denning, Gerene; Stuhr, Kara L; de Wit, Harriet; Hill, Matthew N; Hillard, Cecilia J

2010-01-01

Endogenous cannabinoid signalling is widespread throughout the body, and considerable evidence supports its modulatory role in many fundamental physiological processes. The daily and seasonal cycles of the relationship of the earth and sun profoundly affect the terrestrial environment. Terrestrial species have adapted to these cycles in many ways, most well studied are circadian rhythms and hibernation. The purpose of this review was to examine literature support for three hypotheses: (i) endocannabinoid signalling exhibits brain region-specific circadian rhythms; (ii) endocannabinoid signalling modulates the rhythm of circadian processes in mammals; and (iii) changes in endocannabinoid signalling contribute to the state of hibernation. The results of two novel studies are presented. First, we report the results of a study of healthy humans demonstrating that plasma concentrations of the endocannabinoid, N-arachidonylethanolamine (anandamide), exhibit a circadian rhythm. Concentrations of anandamide are threefold higher at wakening than immediately before sleep, a relationship that is dysregulated by sleep deprivation. Second, we investigated differences in endocannabinoids and congeners in plasma from Marmota monax obtained in the summer and during the torpor state of hibernation. We report that 2-arachidonoylglycerol is below detection in M. monax plasma and that concentrations of anandamide are not different. However, plasma concentrations of the anorexigenic lipid oleoylethanolamide were significantly lower in hibernation, while the concentrations of palmitoylethanolamide and 2-oleoylglycerol were significantly greater in hibernation. We conclude that available data support a bidirectional relationship between endocannabinoid signalling and circadian processes, and investigation of the contribution of endocannabinoid signalling to the dramatic physiological changes that occur during hibernation is warranted. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x PMID:20590563

Ganymede and Callisto: Beauty is only skin deep

NASA Technical Reports Server (NTRS)

Croft, S. K.

1985-01-01

Ganymede and Callisto, the two giant icy satellites of Jupiter, have very nearly the same size, composition, and location in the solar system, yet their surfaces are profoundly different. A new scenario of their geologic histories indicates that the differences may be only skin deep.

Tissue Extracellular Matrix Nanoparticle Presentation in Electrospun Nanofibers

PubMed Central

Gibson, Matt; Mao, Hai-Quan; Elisseeff, Jennifer

2014-01-01

Biomaterials derived from the decellularization of mature tissues retain biological and architectural features that profoundly influence cellular activity. However, the clinical utility of such materials remains limited as the shape and physical properties are difficult to control. In contrast, scaffolds based on synthetic polymers can be engineered to exhibit specific physical properties, yet often suffer from limited biological functionality. This study characterizes composite materials that present decellularized extracellular matrix (DECM) particles in combination with synthetic nanofibers and examines the ability of these materials to influence stem cell differentiation. Mechanical processing of decellularized tissues yielded particles with diameters ranging from 71 to 334 nm. Nanofiber scaffolds containing up to 10% DECM particles (wt/wt) derived from six different tissues were engineered and evaluated to confirm DECM particle incorporation and to measure bioactivity. Scaffolds containing bone, cartilage, and fat promoted osteogenesis at 1 and 3 weeks compared to controls. In contrast, spleen and lung DECM significantly reduced osteogenic outcomes compared to controls. These findings highlight the potential to incorporate appropriate source DECM nanoparticles within nanofiber composites to design a scaffold with bioactivity targeted to specific applications. PMID:24971329

Types A and B Niemann-Pick Disease.

PubMed

Schuchman, Edward H; Wasserstein, Melissa P

2016-06-01

Two distinct metabolic abnormalities are included under the eponym Niemann-Pick disease (NPD). The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM). Patients with ASM deficiency are classified as having types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit hepatosplenomegaly, frequent pulmonary infections, and profound central nervous system involvement in infancy. They rarely survive beyond two years of age. Type B patients also have hepatosplenomegaly and progressive alterations of their lungs, but there are usually no central nervous system signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Recently, patients with phenotypes intermediate between types A and B NPD also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the second category are designated as having type C NPD. Impaired intracellular trafficking of cholesterol causes type C NPD, and two distinct gene defects have been found. In this chapter only types A and B NPD will be discussed.

Structural power and the evolution of collective fairness in social networks.

PubMed

Santos, Fernando P; Pacheco, Jorge M; Paiva, Ana; Santos, Francisco C

2017-01-01

From work contracts and group buying platforms to political coalitions and international climate and economical summits, often individuals assemble in groups that must collectively reach decisions that may favor each part unequally. Here we quantify to which extent our network ties promote the evolution of collective fairness in group interactions, modeled by means of Multiplayer Ultimatum Games (MUG). We show that a single topological feature of social networks-which we call structural power-has a profound impact on the tendency of individuals to take decisions that favor each part equally. Increased fair outcomes are attained whenever structural power is high, such that the networks that tie individuals allow them to meet the same partners in different groups, thus providing the opportunity to strongly influence each other. On the other hand, the absence of such close peer-influence relationships dismisses any positive effect created by the network. Interestingly, we show that increasing the structural power of a network leads to the appearance of well-defined modules-as found in human social networks that often exhibit community structure-providing an interaction environment that maximizes collective fairness.

Evaluation of a noninvasive method for monitoring percutaneous absorption of lidocaine in vivo.

PubMed

Kushla, G P; Zatz, J L

1990-10-01

The pharmacodynamic measurement of in vivo skin penetration of lidocaine was explored with an instrument used in dentistry to determine tooth pulp vitality. The instrument delivers a low-current, pulsatile electrical waveform of increasing intensity with time. The readings, which are reproducible, are in arbitrary units on a scale of 0-80. Testing of naive sites showed variation as a function of location, even over relatively small distances. The response at a marked site over a 12-hr period generally was consistent in five subjects. Following intradermal administration of 1 or 2% lidocaine hydrochloride injection in one subject, the instrument reached its maximum value within 2 min. This was followed by a sustained plateau and then a gradual falloff of the effect. Topical formulations containing 5% lidocaine base and corresponding blank formulations were applied under occlusion within Hilltop chambers to intact skin on the forearms of human volunteers for 3 hr. While the response to a 40% propylene glycol formulation was not significantly different from the corresponding control, a cream exhibited slow development of profound anesthesia that lasted for several hours following chamber removal.

A comparison of latent class, K-means, and K-median methods for clustering dichotomous data.

PubMed

Brusco, Michael J; Shireman, Emilie; Steinley, Douglas

2017-09-01

The problem of partitioning a collection of objects based on their measurements on a set of dichotomous variables is a well-established problem in psychological research, with applications including clinical diagnosis, educational testing, cognitive categorization, and choice analysis. Latent class analysis and K-means clustering are popular methods for partitioning objects based on dichotomous measures in the psychological literature. The K-median clustering method has recently been touted as a potentially useful tool for psychological data and might be preferable to its close neighbor, K-means, when the variable measures are dichotomous. We conducted simulation-based comparisons of the latent class, K-means, and K-median approaches for partitioning dichotomous data. Although all 3 methods proved capable of recovering cluster structure, K-median clustering yielded the best average performance, followed closely by latent class analysis. We also report results for the 3 methods within the context of an application to transitive reasoning data, in which it was found that the 3 approaches can exhibit profound differences when applied to real data. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Spectroscopic Study of Local Interactions of Platinum in Small [CexOy]Ptx' - Clusters

NASA Astrophysics Data System (ADS)

Ray, Manisha; Kafader, Jared O.; Chick Jarrold, Caroline

2016-06-01

Cerium oxide is a good ionic conductor, and the conductivity can be enhanced with oxygen vacancies and doping. This conductivity may play an important role in the enhancement of noble or coinage metal toward the water-gas shift reaction when supported by cerium oxide. The ceria-supported platinum catalyst in particular has received much attention because of higher activity at lower temperatures (LT) compared to the most common commercial LT-WGS catalyst. We have used a combination of anion photoelectron spectroscopy and density functional theory calculations to study the interesting molecular and electronic structures and properties of cluster models of ceria-supported platinum. [CexOy]Ptx' - (x,x'=1,2 ; y≤2x') clusters exhibit evidence of ionic bonding possible because of the high electron affinity of Pt and the low ionization potential of cerium oxide clusters. In addition, Pt- is a common daughter ion resulting from photodissociation of [CexOy]Ptx' - clusters. Finally, several of the anion and neutral clusters have profoundly different structures. These features may play a role in the enhancement of catalytic activity toward the water-gas shift reaction.

Nanobiotechnology: synthetic biology meets materials science.

PubMed

Jewett, Michael C; Patolsky, Fernando

2013-08-01

Nanotechnology, the area of science focused on the control of matter in the nanometer scale, allows ground-breaking changes of the fundamental properties of matter that are often radically different compared to those exhibited by the bulk counterparts. In view of the fact that dimensionality plays a key role in determining the qualities of matter, the realization of the great potential of nanotechnology has opened the door to other disciplines such as life sciences and medicine, where the merging between them offers exciting new applications, along with basic science research. The application of nanotechnology in life sciences, nanobiotechnology, is now having a profound impact on biological circuit design, bioproduction systems, synthetic biology, medical diagnostics, disease therapy and drug delivery. This special issue is dedicated to the overview of how we are learning to control biopolymers and biological machines at the molecular- and nanoscale. In addition, it covers far-reaching progress in the design and synthesis of nanoscale materials, thus enabling the construction of integrated systems in which the component blocks are comparable in size to the chemical and biological entities under investigation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hsp70 and lipid peroxide levels following heat stress in Xeropicta derbentina (Krynicki 1836) (Gastropoda, Pulmonata) with regard to different colour morphs.

PubMed

Dieterich, A; Troschinski, S; Schwarz, S; Di Lellis, M A; Henneberg, A; Fischbach, U; Ludwig, M; Gärtner, U; Triebskorn, R; Köhler, H-R

2015-01-01

Terrestrial snails which live under dry and hot conditions need efficient mechanisms of adaptation to counteract the problems of desiccation and over-heating. A profoundly heat tolerant snail species is the Mediterranean Xeropicta derbentina, exhibiting different shell colour morphs ranging from pale white to darkly banded. Considering that dark-pigmented snails are believed to have a disadvantage due to faster heating, we investigated possible differences in the stress markers Hsp70 and lipid peroxideation between four pre-defined colour morphs which were exposed to different temperatures for eight hours. The highest Hsp70 levels were observed in response to 38-40 °C. Levels decreased when this temperature was exceeded. Snails of a pre-defined colour category 3 (with a large black band at the umbilicus side of the shell) showed the most prominent Hsp70 response. Lipid peroxideation levels also showed a maximum at 38 °C but displayed a second peak at rather high temperatures at which the Hsp70 level already had decreased (45-48 °C). Particularly pure white snails (category 1) and the most pigmented ones (category 4) were found to have different levels of lipid peroxidation at 38 °C and 45 °C compared to the other morphs. A hypothesis involving a combined two-phase defence mechanism, to which both, the Hsp70 protection system and the antioxidant defence system, may contribute, is discussed.

MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation.

PubMed

Makarewich, Catherine A; Baskin, Kedryn K; Munir, Amir Z; Bezprozvannaya, Svetlana; Sharma, Gaurav; Khemtong, Chalermchai; Shah, Akansha M; McAnally, John R; Malloy, Craig R; Szweda, Luke I; Bassel-Duby, Rhonda; Olson, Eric N

2018-06-26

Micropeptide regulator of β-oxidation (MOXI) is a conserved muscle-enriched protein encoded by an RNA transcript misannotated as non-coding. MOXI localizes to the inner mitochondrial membrane where it associates with the mitochondrial trifunctional protein, an enzyme complex that plays a critical role in fatty acid β-oxidation. Isolated heart and skeletal muscle mitochondria from MOXI knockout mice exhibit a diminished ability to metabolize fatty acids, while transgenic MOXI overexpression leads to enhanced β-oxidation. Additionally, hearts from MOXI knockout mice preferentially oxidize carbohydrates over fatty acids in an isolated perfused heart system compared to wild-type (WT) animals. MOXI knockout mice also exhibit a profound reduction in exercise capacity, highlighting the role of MOXI in metabolic control. The functional characterization of MOXI provides insight into the regulation of mitochondrial metabolism and energy homeostasis and underscores the regulatory potential of additional micropeptides that have yet to be identified. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Children's and adults' knowledge and models of reasoning about the ozone layer and its depletion

NASA Astrophysics Data System (ADS)

Leighton, Jacqueline P.; Bisanz, Gay L.

2003-01-01

As environmental concepts, the ozone layer and ozone hole are important to understand because they can profoundly influence our health. In this paper, we examined: (a) children's and adults' knowledge of the ozone layer and its depletion, and whether this knowledge increases with age' and (b) how the 'ozone layer' and 'ozone hole' might be structured as scientific concepts. We generated a standardized set of questions and used it to interview 24 kindergarten students, 48 Grade 3 students, 24 Grade 5 students, and 24 adults in university, in Canada. An analysis of participants' responses revealed that adults have more knowledge than children about the ozone layer and ozone hole, but both adults and children exhibit little knowledge about protecting themselves from the ozone hole. Moreover, only some participants exhibited 'mental models' in their conceptual understanding of the ozone layer and ozone hole. The implications of these results for health professionals, educators, and scientists are discussed.

Molecular Pathogenesis of Familial Wolff-Parkinson-White Syndrome.

PubMed

Licht, Miyamotoa

2018-01-01

Familial Wolff-Parkinson-White (WPW) syndrome is an autosomal dominant inherited disease and consists of a small percentage of WPW syndrome which exhibits ventricular pre-excitation by development of accessory atrioventricular pathway. A series of mutations in PRKAG2 gene encoding gamma2 subunit of 5'AMP-activated protein kinase (AMPK) has been identified as the cause of familial WPW syndrome. AMPK is one of the most important metabolic regulators of carbohydrates and lipids in many types of tissues including cardiac and skeletal muscles. Patients and animals with the mutation in PRKAG2 gene exhibit aberrant atrioventricular conduction associated with cardiac glycogen overload. Recent studies have revealed "novel" significance of canonical pathways leading to glycogen synthesis and provided us profound insights into molecular mechanism of the regulation of glycogen metabolism by AMPK. This review focuses on the molecular basis of the pathogenesis of cardiac abnormality due to PRKAG2 mutation and will provide current overviews of the mechanism of glycogen regulation by AMPK. J. Med. Invest. 65:1-8, February, 2018.

Larval gizzard shad characteristics in Lake Oahe, South Dakota: A species at the northern edge of its range

USGS Publications Warehouse

Fincel, Mark J.; Chipps, Steven R.; Graeb, Brian D. S.; Edwards, Kris R.

2013-01-01

Gizzard shad, Dorosoma cepedianum, have generally been restricted to the lower Missouri River impoundments in South Dakota. In recent years, gizzard shad numbers have increased in Lake Oahe, marking the northern-most natural population. These increases could potentially affect recreational fishes. Specifically, questions arise about larval gizzard shad growth dynamics and if age-0 gizzard shad in Lake Oahe will exhibit fast or slow growth, both of which can have profound effects on piscivore populations in this reservoir. In this study, we evaluated larval gizzard shad hatch timing, growth, and density in Lake Oahe. We collected larval gizzard shad from six sites from May to July 2008 and used sagittal otoliths to estimate the growth and back-calculate the hatch date. We found that larval gizzard shad hatched earlier in the upper part of the reservoir compared to the lower portion and that hatch date appeared to correspond to warming water temperatures. The peak larval gizzard shad density ranged from 0.6 to 33.6 (#/100 m3) and varied significantly among reservoir sites. Larval gizzard shad growth ranged from 0.24 to 0.57 (mm/d) and differed spatially within the reservoir. We found no relationship between the larval gizzard shad growth or density and small- or large-bodied zooplankton density (p > 0.05). As this population exhibits slow growth and low densities, gizzard shad should remain a suitable forage option for recreational fishes in Lake Oahe.

Morphometric analysis of Passiflora leaves: the relationship between landmarks of the vasculature and elliptical Fourier descriptors of the blade

PubMed Central

2017-01-01

Abstract Background: Leaf shape among Passiflora species is spectacularly diverse. Underlying this diversity in leaf shape are profound changes in the patterning of the primary vasculature and laminar outgrowth. Each of these aspects of leaf morphology—vasculature and blade—provides different insights into leaf patterning. Results: Here, we morphometrically analyze >3300 leaves from 40 different Passiflora species collected sequentially across the vine. Each leaf is measured in two different ways: using 1) 15 homologous Procrustes-adjusted landmarks of the vasculature, sinuses, and lobes; and 2) Elliptical Fourier Descriptors (EFDs), which quantify the outline of the leaf. The ability of landmarks, EFDs, and both datasets together are compared to determine their relative ability to predict species and node position within the vine. Pairwise correlation of x and y landmark coordinates and EFD harmonic coefficients reveals close associations between traits and insights into the relationship between vasculature and blade patterning. Conclusions: Landmarks, more reflective of the vasculature, and EFDs, more reflective of the blade contour, describe both similar and distinct features of leaf morphology. Landmarks and EFDs vary in ability to predict species identity and node position in the vine and exhibit a correlational structure (both within landmark or EFD traits and between the two data types) revealing constraints between vascular and blade patterning underlying natural variation in leaf morphology among Passiflora species. PMID:28369351

Viscoelasticity and structure of blood clots generated in-vitro by rheometry: A comparison between human, horse, rat, and camel.

PubMed

Dibiasi, Christoph; Plewka, Jacek; Ploszczanski, Leon; Glanz, Veronika; Lichtenegger, Helga; Windberger, Ursula

2018-04-14

Although the coagulation system is evolutionary well preserved, profound species differences exist in viscoelastic as well as in common laboratory tests of coagulation. Evaluating differences in clot formation and material characterisation of clots of four mammalian species on macro-, micro- and nanoscales by the means of rheometry, scanning electron microscopy (SEM) and small angle x-ray scattering (SAXS). Blood samples were collected from healthy human volunteers, laboratory rats (HL/LE inbred strain), warmblood horses and dromedary camels. Clot formation was observed by oscillating shear rheometry until plateau formation of the shear storage modulus G', at which point selected clots were prepared for scanning electron microscopy. SEM images were analysed for fibre diameter and fractal dimension. Additionally, scattering profiles for plasma and whole blood samples were obtained with SAXS. Viscoelasticity of clots showed great interspecies variation: clots of rats and horses exhibited shorter clotting times and higher G' plateau values, when compared to human clots. Camel clots showed unique clotting characteristics with no G' plateau formation in the timeframe observed. Less differentiating features were found with SEM and SAXS, although the rat fibre network appears to be more convoluted and dense, which resulted in a higher fractal dimension. Clotting kinetic differs between the species, which is not only of clinical interest, but could also be an important finding for animal models of blood coagulation.

Erratum to: Morphometric analysis of Passiflora leaves: the relationship between landmarks of the vasculature and elliptical Fourier descriptors of the blade.

PubMed

Chitwood, Daniel H; Otoni, Wagner C

2017-10-01

Leaf shape among Passiflora species is spectacularly diverse. Underlying this diversity in leaf shape are profound changes in the patterning of the primary vasculature and laminar outgrowth. Each of these aspects of leaf morphology-vasculature and blade-provides different insights into leaf patterning. Here, we morphometrically analyze >3300 leaves from 40 different Passiflora species collected sequentially across the vine. Each leaf is measured in two different ways: using 1) 15 homologous Procrustes-adjusted landmarks of the vasculature, sinuses, and lobes; and 2) Elliptical Fourier Descriptors (EFDs), which quantify the outline of the leaf. The ability of landmarks, EFDs, and both datasets together are compared to determine their relative ability to predict species and node position within the vine. Pairwise correlation of x and y landmark coordinates and EFD harmonic coefficients reveals close associations between traits and insights into the relationship between vasculature and blade patterning. Landmarks, more reflective of the vasculature, and EFDs, more reflective of the blade contour, describe both similar and distinct features of leaf morphology. Landmarks and EFDs vary in ability to predict species identity and node position in the vine and exhibit a correlational structure (both within landmark or EFD traits and between the two data types) revealing constraints between vascular and blade patterning underlying natural variation in leaf morphology among Passiflora species. © The Authors 2017. Published by Oxford University Press.

Morphometric analysis of Passiflora leaves: the relationship between landmarks of the vasculature and elliptical Fourier descriptors of the blade.

PubMed

Chitwood, Daniel H; Otoni, Wagner C

2017-01-01

Leaf shape among Passiflora species is spectacularly diverse. Underlying this diversity in leaf shape are profound changes in the patterning of the primary vasculature and laminar outgrowth. Each of these aspects of leaf morphology-vasculature and blade-provides different insights into leaf patterning. Here, we morphometrically analyze >3300 leaves from 40 different Passiflora species collected sequentially across the vine. Each leaf is measured in two different ways: using 1) 15 homologous Procrustes-adjusted landmarks of the vasculature, sinuses, and lobes; and 2) Elliptical Fourier Descriptors (EFDs), which quantify the outline of the leaf. The ability of landmarks, EFDs, and both datasets together are compared to determine their relative ability to predict species and node position within the vine. Pairwise correlation of x and y landmark coordinates and EFD harmonic coefficients reveals close associations between traits and insights into the relationship between vasculature and blade patterning. Landmarks, more reflective of the vasculature, and EFDs, more reflective of the blade contour, describe both similar and distinct features of leaf morphology. Landmarks and EFDs vary in ability to predict species identity and node position in the vine and exhibit a correlational structure (both within landmark or EFD traits and between the two data types) revealing constraints between vascular and blade patterning underlying natural variation in leaf morphology among Passiflora species. © The Author 2017. Published by Oxford University Press.

Role of Earth's plasmasphere in coupling of upper atmosphere

NASA Astrophysics Data System (ADS)

Singh, A. K.; Mishra, Sandhya; Dohare, S. K.

2010-02-01

The near-Earth space environment is a complex, ever changing system of magnetized plasmas whose behaviour has a profound impact upon our technology dependent society. The exploration of the cold, relatively dense, inner region of upper atmosphere (the plasmasphere) and its unexpectedly sharp outer boundary (the plasma pause) has proceeded through a combination of in-situ observations and ground based whistler observations. Studies have shown that plasmasphere is highly variable both spatially and temporally responding to changes in geomagnetic indices, ring current, penetration and shielding electric fields and subauroral electric fields. Consequently the plasmasphere exhibits erosion, emptying and refilling during active times. Infact, it is the electric field that plays one of the most important roles in coupling of upper atmosphere. The atmospheric dynamo is the main generator of the large-scale electric field in the upper atmosphere. It arises because of a special situation which electrons and ions move with different velocities across the magnetic field because of different collisions between electrons and neutral particles and ions with neutral particles. This process leads to charge separation and consequently to an electric field. In the present paper, storm/ quiet period VLF whistler data recorded at lower latitudes/mid latitudes are analyzed and attempt has been made to look at plasmasphere response on coupling of ionosphere and magnetosphere.

Impact of ethnicity on cardiac adaptation to exercise.

PubMed

Sheikh, Nabeel; Sharma, Sanjay

2014-04-01

The increasing globalization of sport has resulted in athletes from a wide range of ethnicities emerging onto the world stage. Fuelled by the untimely death of a number of young professional athletes, data generated from the parallel increase in preparticipation cardiovascular evaluation has indicated that ethnicity has a substantial influence on cardiac adaptation to exercise. From this perspective, the group most intensively studied comprises athletes of African or Afro-Caribbean ethnicity (black athletes), an ever-increasing number of whom are competing at the highest levels of sport and who often exhibit profound electrical and structural cardiac changes in response to exercise. Data on other ethnic cohorts are emerging, but remain incomplete. This Review describes our current knowledge on the impact of ethnicity on cardiac adaptation to exercise, starting with white athletes in whom the physiological electrical and structural changes--collectively termed the 'athlete's heart'--were first described. Discussion of the differences in the cardiac changes between ethnicities, with a focus on black athletes, and of the challenges that these variations can produce for the evaluating physician is also provided. The impact of ethnically mediated changes on preparticipation cardiovascular evaluation is highlighted, particularly with respect to false positive results, and potential genetic mechanisms underlying racial differences in cardiac adaptation to exercise are described.

Comparative histology of the adult electric organ among four species of the genus Campylomormyrus (Teleostei: Mormyridae).

PubMed

Paul, Christiane; Mamonekene, Victor; Vater, Marianne; Feulner, Philine G D; Engelmann, Jacob; Tiedemann, Ralph; Kirschbaum, Frank

2015-04-01

The electric organ (EO) of weakly electric mormyrids consists of flat, disk-shaped electrocytes with distinct anterior and posterior faces. There are multiple species-characteristic patterns in the geometry of the electrocytes and their innervation. To further correlate electric organ discharge (EOD) with EO anatomy, we examined four species of the mormyrid genus Campylomormyrus possessing clearly distinct EODs. In C. compressirostris, C. numenius, and C. tshokwe, all of which display biphasic EODs, the posterior face of the electrocytes forms evaginations merging to a stalk system receiving the innervation. In C. tamandua that emits a triphasic EOD, the small stalks of the electrocyte penetrate the electrocyte anteriorly before merging on the anterior side to receive the innervation. Additional differences in electrocyte anatomy among the former three species with the same EO geometry could be associated with further characteristics of their EODs. Furthermore, in C. numenius, ontogenetic changes in EO anatomy correlate with profound changes in the EOD. In the juvenile the anterior face of the electrocyte is smooth, whereas in the adult it exhibits pronounced surface foldings. This anatomical difference, together with disparities in the degree of stalk furcation, probably contributes to the about 12 times longer EOD in the adult.

The influence of fire on the assemblage structure of foraging birds in grasslands of the Serra da Canastra National Park, Brazil.

PubMed

Reis, Matheus G; Fieker, Carolline Z; Dias, Manoel M

2016-05-13

Grasslands are the most threatened physiognomies of the Cerrado biome (Brazilian savanna), a biodiversity hotspot with conservation as a priority. The Serra da Canastra National Park protects the most important remnants of the Cerrado's southern grasslands, which are under strong anthropogenic pressure. The present study describes the structure of bird assemblages that directly use food resources in burned areas, comparing areas affected by natural fire to the areas where controlled fires were set (a management strategy to combat arson). The tested null hypothesis was that different bird assemblages are structured in a similar manner, regardless of the post-fire period or assessed area. Between December/2012 and January/2015, 92 species were recorded foraging in the study areas. The results indicate that both types of burnings triggered profound and immediate changes in bird assemblages, increasing the number of species and individuals. Natural fires exhibited a more significant influence on the structure (diversity and dominance) than prescribed burnings. Nevertheless, all the differences were no longer noticeable after a relatively short time interval of 2-3 months after prescribed burnings and 3-4 after natural fires. The findings may help the understanding of prescribed burnings as a management strategy for bird conservation in grasslands.

Nuances in diet quality and quantity influence phenotypic dimorphism during honey bee (Apis mellifera) caste determination

USDA-ARS?s Scientific Manuscript database

Nutrition intake during the larval stage of holometabolous insect’s influences and fuels growth throughout metamorphosis. In social insects, differences in larval nutrition can regulate a profound reproductive division of labor. Provisioning by nurse bees differs between worker-destined and queen-de...

With Boys and Girls in Mind

ERIC Educational Resources Information Center

Gurian, Michael; Stevens, Kathy

2004-01-01

New positron emission tomography (PET) and MRI technologies, which allow looking inside the brains, show that the brains of boys and girls differ both structurally and functionally that profoundly affect the human learning. These gender differences in the brain are corroborated in males and females throughout the world and do not differ…

A Test of the Similar Sequence Hypothesis.

ERIC Educational Resources Information Center

Silverstein, A. B.; And Others

1982-01-01

Scales for object permanence and spatial relationships were administered to 98 severely and profoundly mentally retarded children (mean age 13 years) on three occasions, 6 months apart. Differences in the difficulty of the items were quite stable, but their order of difficulty differed appreciably from that for nonretarded infants. (Author/SB)

The Difference It Makes: A Resource Book on Gender for Educators.

ERIC Educational Resources Information Center

Chapman, Anne

The recent flood of new information on structuring human experience along gender lines and on the female component of human experience has profound implications for education. The new scholarship shows that much of what people once assumed to be innate gender difference is in fact produced by adults' different behavior toward boys and girls, of…

New cytotoxic natural products from the mangrove biome: covering the period 2007-2015.

PubMed

Pejin, Boris; Glumac, Miodrag

2018-01-15

Nowadays, the mangrove biome is considered to be a profound resource of natural products usually possessing cytotoxicity of a broader range. Covering the period 2007-2015, a total of 21 new naturally occurring compounds has stood out. For example, xylogranin B and swietephragmin C were found to exhibit very potent cytotoxic activity against the colon HCT-116 cells reaching IC 50 values of 0.05 and 0.06 μM, respectively. Bearing in mind the efficacy of the majority compounds in the preliminary in vitro screens, these studies should be expanded to both ex vivo and in vivo screens including the evaluation of the relevant toxicological profiles.

A holistic view of dietary carbohydrate utilization in lobster: digestion, postprandial nutrient flux, and metabolism.

PubMed

Rodríguez-Viera, Leandro; Perera, Erick; Casuso, Antonio; Perdomo-Morales, Rolando; Gutierrez, Odilia; Scull, Idania; Carrillo, Olimpia; Martos-Sitcha, Juan A; García-Galano, Tsai; Mancera, Juan Miguel

2014-01-01

Crustaceans exhibit a remarkable variation in their feeding habits and food type, but most knowledge on carbohydrate digestion and utilization in this group has come from research on few species. The aim of this study was to make an integrative analysis of dietary carbohydrate utilization in the spiny lobster Panulirus argus. We used complementary methodologies such as different assessments of digestibility, activity measurements of digestive and metabolic enzymes, and post-feeding flux of nutrients and metabolites. Several carbohydrates were well digested by the lobster, but maize starch was less digestible than all other starches studied, and its inclusion in diet affected protein digestibility. Most intense hydrolysis of carbohydrates in the gastric chamber of lobster occurred between 2-6 h after ingestion and afterwards free glucose increased in hemolymph. The inclusion of wheat in diet produced a slow clearance of glucose from the gastric fluid and a gradual increase in hemolymph glucose. More intense hydrolysis of protein in the gastric chamber occurred 6-12 h after ingestion and then amino acids tended to increase in hemolymph. Triglyceride concentration in hemolymph rose earlier in wheat-fed lobsters than in lobsters fed other carbohydrates, but it decreased the most 24 h later. Analyses of metabolite levels and activities of different metabolic enzymes revealed that intermolt lobsters had a low capacity to store and use glycogen, although it was slightly higher in wheat-fed lobsters. Lobsters fed maize and rice diets increased amino acid catabolism, while wheat-fed lobsters exhibited higher utilization of fatty acids. Multivariate analysis confirmed that the type of carbohydrate ingested had a profound effect on overall metabolism. Although we found no evidence of a protein-sparing effect of dietary carbohydrate, differences in the kinetics of their digestion and absorption impacted lobster metabolism determining the fate of other nutrients.

A Holistic View of Dietary Carbohydrate Utilization in Lobster: Digestion, Postprandial Nutrient Flux, and Metabolism

PubMed Central

Casuso, Antonio; Perdomo-Morales, Rolando; Gutierrez, Odilia; Scull, Idania; Carrillo, Olimpia; Martos-Sitcha, Juan A.; García-Galano, Tsai; Mancera, Juan Miguel

2014-01-01

Crustaceans exhibit a remarkable variation in their feeding habits and food type, but most knowledge on carbohydrate digestion and utilization in this group has come from research on few species. The aim of this study was to make an integrative analysis of dietary carbohydrate utilization in the spiny lobster Panulirus argus. We used complementary methodologies such as different assessments of digestibility, activity measurements of digestive and metabolic enzymes, and post-feeding flux of nutrients and metabolites. Several carbohydrates were well digested by the lobster, but maize starch was less digestible than all other starches studied, and its inclusion in diet affected protein digestibility. Most intense hydrolysis of carbohydrates in the gastric chamber of lobster occurred between 2–6 h after ingestion and afterwards free glucose increased in hemolymph. The inclusion of wheat in diet produced a slow clearance of glucose from the gastric fluid and a gradual increase in hemolymph glucose. More intense hydrolysis of protein in the gastric chamber occurred 6–12 h after ingestion and then amino acids tended to increase in hemolymph. Triglyceride concentration in hemolymph rose earlier in wheat-fed lobsters than in lobsters fed other carbohydrates, but it decreased the most 24 h later. Analyses of metabolite levels and activities of different metabolic enzymes revealed that intermolt lobsters had a low capacity to store and use glycogen, although it was slightly higher in wheat-fed lobsters. Lobsters fed maize and rice diets increased amino acid catabolism, while wheat-fed lobsters exhibited higher utilization of fatty acids. Multivariate analysis confirmed that the type of carbohydrate ingested had a profound effect on overall metabolism. Although we found no evidence of a protein-sparing effect of dietary carbohydrate, differences in the kinetics of their digestion and absorption impacted lobster metabolism determining the fate of other nutrients. PMID:25268641

Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development.

PubMed

Rossel, M; Capecchi, M R

1999-11-01

The analysis of mice mutant for both Hoxa1 and Hoxb1 suggests that these two genes function together to pattern the hindbrain. Separately, mutations in Hoxa1 and Hoxb1 have profoundly different effects on hindbrain development. Hoxa1 mutations disrupt the rhombomeric organization of the hindbrain, whereas Hoxb1 mutations do not alter the rhombomeric pattern, but instead influence the fate of cells originating in rhombomere 4. We suggest that these differences are not the consequences of different functional roles for these gene products, but rather reflect differences in the kinetics of Hoxa1 and Hoxb1 gene expression. In strong support of the idea that Hoxa1 and Hoxb1 have overlapping functions, Hoxa1/Hoxb1 double mutant homozygotes exhibit a plethora of defects either not seen, or seen only in a very mild form, in mice mutant for only Hoxa1 or Hoxb1. Examples include: the loss of both rhombomeres 4 and 5, the selective loss of the 2(nd) branchial arch, and the loss of most, but not all, 2(nd) branchial arch-derived tissues. We suggest that the early role for both of these genes in hindbrain development is specification of rhombomere identities and that the aberrant development of the hindbrain in Hoxa1/Hoxb1 double mutants proceeds through two phases, the misspecification of rhombomeres within the hindbrain, followed subsequently by size regulation of the misspecified hindbrain through induction of apoptosis.

Gradual emergence of spontaneous correlated brain activity during fading of general anesthesia in rats: Evidences from fMRI and local field potentials

PubMed Central

Bettinardi, Ruggero G.; Tort-Colet, Núria; Ruiz-Mejias, Marcel; Sanchez-Vives, Maria V.; Deco, Gustavo

2015-01-01

Intrinsic brain activity is characterized by the presence of highly structured networks of correlated fluctuations between different regions of the brain. Such networks encompass different functions, whose properties are known to be modulated by the ongoing global brain state and are altered in several neurobiological disorders. In the present study, we induced a deep state of anesthesia in rats by means of a ketamine/medetomidine peritoneal injection, and analyzed the time course of the correlation between the brain activity in different areas while anesthesia spontaneously decreased over time. We compared results separately obtained from fMRI and local field potentials (LFPs) under the same anesthesia protocol, finding that while most profound phases of anesthesia can be described by overall sparse connectivity, stereotypical activity and poor functional integration, during lighter states different frequency-specific functional networks emerge, endowing the gradual restoration of structured large-scale activity seen during rest. Noteworthy, our in vivo results show that those areas belonging to the same functional network (the default-mode) exhibited sustained correlated oscillations around 10 Hz throughout the protocol, suggesting the presence of a specific functional backbone that is preserved even during deeper phases of anesthesia. Finally, the overall pattern of results obtained from both imaging and in vivo-recordings suggests that the progressive emergence from deep anesthesia is reflected by a corresponding gradual increase of organized correlated oscillations across the cortex. PMID:25804643

The Formation of Chimeric Nanomorphologies, as a Reflection of Naturally Occurring Thermodynamic Processes

NASA Astrophysics Data System (ADS)

Naziris, N.; Demetzos, C.

2017-11-01

The self-assembly process of different in nature biomaterials leads to the morphogenesis of various nano-structures, where the individual molecule properties (e.g. hydrophilic-to-hydrophobic balance and elasticity), profoundly affect the intermediate surfaces’ interfacial thermodynamics. Herein, the mixing of a phospholipid and an amphiphilic block copolymer, through the thin-film hydration method, gave different morphologies, among which there were vesicles (i.e. liposomes and polymersomes), micelles and worm-like structures. The formation of such variety of structures is attributed to divergent entropic pathways, which are determined by a number of parameters, such as the lipid:polymer molar ratio and the polymer composition. The developed nanosystems are considered as chimeric/mixed, because of the two different in type biomaterials that compose them. The vesicles also exhibited membrane “irregularities”, which are connected with their biophysical behavior. Nature has “chosen” vesicular forms to be the thermodynamically stable “biological apartments”, in which life was enclosed and additionally, vesicles provided compartmentalized systems, where the intracellular environment was built. Phospholipid properties result in membranes/bilayers that harmonically assimilate other molecules, like proteins and retain their integrity and functionality, while gaining additional features. A cause that alters this relationship might induce changes in the membrane composition and morphology, with respect to lipid rafts/domains, what has been linked with the activation and development of certain human disorders/diseases. The self-assembly of two different biomaterials into various structures that present distinct membrane phenomena is believed to simulate these natural processes.

Effects of early auditory experience on the spoken language of deaf children at 3 years of age.

PubMed

Nicholas, Johanna Grant; Geers, Ann E

2006-06-01

By age 3, typically developing children have achieved extensive vocabulary and syntax skills that facilitate both cognitive and social development. Substantial delays in spoken language acquisition have been documented for children with severe to profound deafness, even those with auditory oral training and early hearing aid use. This study documents the spoken language skills achieved by orally educated 3-yr-olds whose profound hearing loss was identified and hearing aids fitted between 1 and 30 mo of age and who received a cochlear implant between 12 and 38 mo of age. The purpose of the analysis was to examine the effects of age, duration, and type of early auditory experience on spoken language competence at age 3.5 yr. The spoken language skills of 76 children who had used a cochlear implant for at least 7 mo were evaluated via standardized 30-minute language sample analysis, a parent-completed vocabulary checklist, and a teacher language-rating scale. The children were recruited from and enrolled in oral education programs or therapy practices across the United States. Inclusion criteria included presumed deaf since birth, English the primary language of the home, no other known conditions that interfere with speech/language development, enrolled in programs using oral education methods, and no known problems with the cochlear implant lasting more than 30 days. Strong correlations were obtained among all language measures. Therefore, principal components analysis was used to derive a single Language Factor score for each child. A number of possible predictors of language outcome were examined, including age at identification and intervention with a hearing aid, duration of use of a hearing aid, pre-implant pure-tone average (PTA) threshold with a hearing aid, PTA threshold with a cochlear implant, and duration of use of a cochlear implant/age at implantation (the last two variables were practically identical because all children were tested between 40 and 44 mo of age). Examination of the independent influence of these predictors through multiple regression analysis revealed that pre-implant-aided PTA threshold and duration of cochlear implant use (i.e., age at implant) accounted for 58% of the variance in Language Factor scores. A significant negative coefficient associated with pre-implant-aided threshold indicated that children with poorer hearing before implantation exhibited poorer language skills at age 3.5 yr. Likewise, a strong positive coefficient associated with duration of implant use indicated that children who had used their implant for a longer period of time (i.e., who were implanted at an earlier age) exhibited better language at age 3.5 yr. Age at identification and amplification was unrelated to language outcome, as was aided threshold with the cochlear implant. A significant quadratic trend in the relation between duration of implant use and language score revealed a steady increase in language skill (at age 3.5 yr) for each additional month of use of a cochlear implant after the first 12 mo of implant use. The advantage to language of longer implant use became more pronounced over time. Longer use of a cochlear implant in infancy and very early childhood dramatically affects the amount of spoken language exhibited by 3-yr-old, profoundly deaf children. In this sample, the amount of pre-implant intervention with a hearing aid was not related to language outcome at 3.5 yr of age. Rather, it was cochlear implantation at a younger age that served to promote spoken language competence. The previously identified language-facilitating factors of early identification of hearing impairment and early educational intervention may not be sufficient for optimizing spoken language of profoundly deaf children unless it leads to early cochlear implantation.

Ending the war between Sales & Marketing.

PubMed

Kotler, Philip; Rackham, Neil; Krishnaswamy, Suj

2006-01-01

Sales departments tend to believe that marketers are out of touch with what's really going on in the marketplace. Marketing people, in turn, believe the sales force is myopic--too focused on individual customer experiences, insufficiently aware of the larger market, and blind to the future. In short, each group undervalues the other's contributions. Both stumble (and organizational performance suffers) when they are out of sync. Yet few firms seem to make serious overtures toward analyzing and enhancing the relationship between these two critical functions. Curious about the misalignment between Sales and Marketing, the authors interviewed pairs of chief marketing officers and sales vice presidents to capture their perspectives. They looked in depth at the relationship between Sales and Marketing in a variety of companies in different industries. Their goal was to identify best practices that could enhance the joint performance and increase the contributions of these two functions. Among their findings: The marketing function takes different forms in different companies at different product life cycle stages. Marketing's increasing influence in each phase of an organization's growth profoundly affects its relationship with Sales. The strains between Sales and Marketing fall into two main categories: economic (a single budget is typically divided, between Sales and Marketing, and not always evenly) and cultural (the two functions attract very different types of people who achieve success by spending their time in very different ways). In this article, the authors describe the four types of relationships Sales and Marketing typically exhibit. They provide a diagnostic to help readers assess their companies' level of integration, and they offer recommendations for more closely aligning the two functions.

Encounters across Difference: The Digital Geographies of Inuit, The Arctic, and Environmental Management

ERIC Educational Resources Information Center

Young, Jason C.

2017-01-01

There is broad consensus amongst scholars across a wide range of disciplines that digital technologies are having profound effects on micro- and macropolitical processes across the world. However, research into digital geographies has not rigorously examined the role of the Internet in bridging epistemological difference. Rather, most of this…

Characterization of fecal concentrations in human and other animal sources by physical, culture-based, and quantitative real-time PCR methods

EPA Science Inventory

The characteristics of fecal sources, and the ways in which they are measured, can profoundly influence the interpretation of which sources are contaminating water. Although feces from various hosts are known to differ, it is not well understood how those differences compare acro...

Profound Effects of Population Density on Fitness-Related Traits in an Invasive Freshwater Snail

PubMed Central

Zachar, Nicholas; Neiman, Maurine

2013-01-01

Population density can profoundly influence fitness-related traits and population dynamics, and density dependence plays a key role in many prominent ecological and evolutionary hypotheses. Here, we evaluated how individual-level changes in population density affect growth rate and embryo production early in reproductive maturity in two different asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail that is an important model system for ecotoxicology and the evolution of sexual reproduction as well as a potentially destructive worldwide invader. We showed that population density had a major influence on individual growth rate and early-maturity embryo production, effects that were often apparent even when comparing treatments that differed in population density by only one individual. While individual growth rate generally decreased as population density increased, we detected a hump-shaped relationship between embryo production and density, with females from intermediate-density treatments producing the most embryos and females from low- and high-density treatments producing the fewest embryos. The two lineages responded similarly to the treatments, indicating that these effects of population density might apply more broadly across P. antipodarum. These results indicate that there are profound and complex relationships between population density, growth rate, and early-maturity embryo production in at least two lineages of this important model system, with potential implications for the study of invasive populations, research on the maintenance of sex, and approaches used in ecotoxicology. PMID:24278240

Profound effects of population density on fitness-related traits in an invasive freshwater snail.

PubMed

Zachar, Nicholas; Neiman, Maurine

2013-01-01

Population density can profoundly influence fitness-related traits and population dynamics, and density dependence plays a key role in many prominent ecological and evolutionary hypotheses. Here, we evaluated how individual-level changes in population density affect growth rate and embryo production early in reproductive maturity in two different asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail that is an important model system for ecotoxicology and the evolution of sexual reproduction as well as a potentially destructive worldwide invader. We showed that population density had a major influence on individual growth rate and early-maturity embryo production, effects that were often apparent even when comparing treatments that differed in population density by only one individual. While individual growth rate generally decreased as population density increased, we detected a hump-shaped relationship between embryo production and density, with females from intermediate-density treatments producing the most embryos and females from low- and high-density treatments producing the fewest embryos. The two lineages responded similarly to the treatments, indicating that these effects of population density might apply more broadly across P. antipodarum. These results indicate that there are profound and complex relationships between population density, growth rate, and early-maturity embryo production in at least two lineages of this important model system, with potential implications for the study of invasive populations, research on the maintenance of sex, and approaches used in ecotoxicology.

Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism

PubMed Central

Pfattheicher, Stefan; Schindler, Simon

2016-01-01

The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR) to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk) rated the profoundness of bullshit statements (using the BSR) and provided favorability ratings of three Democratic (Hillary Clinton, Martin O’Malley, and Bernie Sanders) and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump). Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O’Malley. Overall, small-to-medium sized correlations were found, indicating that far from all conservatives see profoundness in bullshit statements. PMID:27128318

Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism.

PubMed

Pfattheicher, Stefan; Schindler, Simon

2016-01-01

The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR) to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk) rated the profoundness of bullshit statements (using the BSR) and provided favorability ratings of three Democratic (Hillary Clinton, Martin O'Malley, and Bernie Sanders) and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump). Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O'Malley. Overall, small-to-medium sized correlations were found, indicating that far from all conservatives see profoundness in bullshit statements.

Antisense RNA Downregulation of Coenzyme A Transferase Combined with Alcohol-Aldehyde Dehydrogenase Overexpression Leads to Predominantly Alcohologenic Clostridium acetobutylicum Fermentations

PubMed Central

Tummala, Seshu B.; Junne, Stefan G.; Papoutsakis, Eleftherios T.

2003-01-01

Plasmid pAADB1 for the overexpression of the alcohol-aldehyde dehydrogenase (aad) gene and downregulation of the coenzyme A transferase (CoAT) using antisense RNA (asRNA) against ctfB (the second CoAT gene on the polycistronic aad-ctfA-ctfB message) was used in order to increase the butanol/acetone ratio of Clostridium acetobutylicum ATCC 824 fermentations. Acetone and butanol levels were drastically reduced in 824(pCTFB1AS) (expresses only an asRNA against ctfB) compared to 824(pSOS95del) (plasmid control). Compared to strain 824(pCTFB1AS), 824(pAADB1) fermentations exhibited two profound differences. First, butanol levels were ca. 2.8-fold higher in 824(pAADB1) and restored back to plasmid control levels, thus supporting the hypothesis that asRNA downregulation of ctfB leads to degradation of the whole aad-ctfA-ctfB transcript. Second, ethanol titers in 824(pAADB1) were ca. 23-fold higher and the highest (ca. 200 mM) ever reported in C. acetobutylicum. Western blot analysis confirmed that CoAT was downregulated in 824(pAADB1) at nearly the same levels as in strain 824(pCTFB1AS). Butyrate depletion in 824(pAADB1) fermentations suggested that butyryl-CoA was limiting butanol production in 824(pAADB1). This was confirmed by exogenously adding butyric acid to 824(pAADB1) fermentations to increase the butanol/ethanol ratio. DNA microarray analysis showed that aad overexpression profoundly affects the large-scale transcriptional program of the cells. Several classes of genes were differentially expressed [strain 824(pAADB1) versus strain 824(pCTFB1AS)], including genes of the stress response, sporulation, and chemotaxis. The expression patterns of the CoAT genes (ctfA and ctfB) and aad were consistent with the overexpression of aad and asRNA downregulation of ctfB. PMID:12775702

Antisense RNA downregulation of coenzyme A transferase combined with alcohol-aldehyde dehydrogenase overexpression leads to predominantly alcohologenic Clostridium acetobutylicum fermentations.

PubMed

Tummala, Seshu B; Junne, Stefan G; Papoutsakis, Eleftherios T

2003-06-01

Plasmid pAADB1 for the overexpression of the alcohol-aldehyde dehydrogenase (aad) gene and downregulation of the coenzyme A transferase (CoAT) using antisense RNA (asRNA) against ctfB (the second CoAT gene on the polycistronic aad-ctfA-ctfB message) was used in order to increase the butanol/acetone ratio of Clostridium acetobutylicum ATCC 824 fermentations. Acetone and butanol levels were drastically reduced in 824(pCTFB1AS) (expresses only an asRNA against ctfB) compared to 824(pSOS95del) (plasmid control). Compared to strain 824(pCTFB1AS), 824(pAADB1) fermentations exhibited two profound differences. First, butanol levels were ca. 2.8-fold higher in 824(pAADB1) and restored back to plasmid control levels, thus supporting the hypothesis that asRNA downregulation of ctfB leads to degradation of the whole aad-ctfA-ctfB transcript. Second, ethanol titers in 824(pAADB1) were ca. 23-fold higher and the highest (ca. 200 mM) ever reported in C. acetobutylicum. Western blot analysis confirmed that CoAT was downregulated in 824(pAADB1) at nearly the same levels as in strain 824(pCTFB1AS). Butyrate depletion in 824(pAADB1) fermentations suggested that butyryl-CoA was limiting butanol production in 824(pAADB1). This was confirmed by exogenously adding butyric acid to 824(pAADB1) fermentations to increase the butanol/ethanol ratio. DNA microarray analysis showed that aad overexpression profoundly affects the large-scale transcriptional program of the cells. Several classes of genes were differentially expressed [strain 824(pAADB1) versus strain 824(pCTFB1AS)], including genes of the stress response, sporulation, and chemotaxis. The expression patterns of the CoAT genes (ctfA and ctfB) and aad were consistent with the overexpression of aad and asRNA downregulation of ctfB.

IDENTIFICATION OF BACTERIA IN BLOOD CULTURES FROM CLINICALLY ILL CAPTIVE ANTILLEAN MANATEES (TRICHECHUS MANATUS MANATUS).

PubMed

Silva, Mariana C O; Attademo, Fernanda F L; Freire, Augusto C B; Sousa, Glaucia P; Luna, Fábia O; Lima, Débora C V; Mota, Rinaldo A; Mendes, Emiko S; Silva, Jean C R

2017-03-01

Between September 2001 and March 2013, 62 bacterial cultures (37 aerobic and 25 anaerobic) were performed on 37 blood samples from 23 Antillean manatees ( Trichechus manatus manatus) that were kept in captivity at the Brazilian National Center for Research and Conservation of Aquatic Mammals (CMA) in Pernambuco (CMA-PE) and Alagoas (CMA-AL), Brazil. All of the animals sampled exhibited clinical signs at the time of sampling including abscesses (n = 8), debilitation and anorexia (n = 22), and profound lethargy-moribundity (n = 7). The 4 animals with profound lethargy-moribundity died shortly after sampling of unknown causes. Bacteria were isolated from 15/37 (40.5%) and aerobic blood cultures from 13/23 animals (56.5%). None of the anaerobic cultures were positive. Aeromonas caviae , Aeromonas hydrophila , Aeromonas sp., Escherichia coli , Leclercia adecarboxylata , Pantoea agglomerans , Pseudomonas aeruginosa , Pseudomonas stutzeri , Pseudomonas sp., Sphingomonas paucimobilis , coagulase-negative Staphylococcus, and Staphylococcus epidermidis were each found in only one animal; Staphylococcus spp. was found in two; and Vibrio fluvialis in four. Thirteen samples had only one bacteria isolated, one sample had two bacteria, and one sample had three bacteria isolated. Regarding sex, age group, and origin among the manatees examined, 54.5% (6/11) of the females, 58.3% (7/12) of the males, 40% (2/5) of the calves, 66.7% (8/12) of the juveniles, 50% (3/6) of the adults, 55.5% (10/18) at CMA-PE, and 60% (3/5) at CMA-AL were found to be positive for bacterial growth during at least one sampling time. All Antillean manatees were clinically ill. Regarding clinical signs, bacteria were found in 50% (11/22) of blood samples of the animals showing debilitation and anorexia, 1 of 8 (12.5%) of blood samples of the animals showing abscesses, and 3 of 7 (42.9%) of blood samples of the animals showing profound lethargy-moribundity.

Somatic hypermutation and antigen-driven selection of B cells are altered in autoimmune diseases.

PubMed

Zuckerman, Neta S; Hazanov, Helena; Barak, Michal; Edelman, Hanna; Hess, Shira; Shcolnik, Hadas; Dunn-Walters, Deborah; Mehr, Ramit

2010-12-01

B cells have been found to play a critical role in the pathogenesis of several autoimmune (AI) diseases. A common feature amongst many AI diseases is the formation of ectopic germinal centers (GC) within the afflicted tissue or organ, in which activated B cells expand and undergo somatic hypermutation (SHM) and antigen-driven selection on their immunoglobulin variable region (IgV) genes. However, it is not yet clear whether these processes occurring in ectopic GCs are identical to those in normal GCs. The analysis of IgV mutations has aided in revealing many aspects concerning B cell expansion, mutation and selection in GC reactions. We have applied several mutation analysis methods, based on lineage tree construction, to a large set of data, containing IgV productive and non-productive heavy and light chain sequences from several different tissues, to examine three of the most profoundly studied AI diseases - Rheumatoid Arthritis (RA), Multiple Sclerosis (MS) and Sjögren's Syndrome (SS). We have found that RA and MS sequences exhibited normal mutation spectra and targeting motifs, but a stricter selection compared to normal controls, which was more apparent in RA. SS sequence analysis results deviated from normal controls in both mutation spectra and indications of selection, also showing differences between light and heavy chain IgV and between different tissues. The differences revealed between AI diseases and normal control mutation patterns may result from the different microenvironmental influences to which ectopic GCs are exposed, relative to those in normal secondary lymphoid tissues. Copyright © 2010 Elsevier Ltd. All rights reserved.

Individuals with Profound Disabilities: Instructional and Assistive Strategies. Third Edition.

ERIC Educational Resources Information Center

Sternberg, Les, Ed.

This collection of 14 essays focuses on the education of individuals with profound disabilities. The essays include: (1) "Individuals with Profound Disabilities: Definitions, Characteristics, and Conceptual Framework" (Les Sternberg); (2) "Creating Environments That Support and Enhance the Lives of All Individuals" (Lucille Zeph); (3) "Biomedical…

Phrenic nerve palsy associated with birth trauma--case reports and a literature review.

PubMed

Shiohama, Tadashi; Fujii, Katsunori; Hayashi, Masaharu; Hishiki, Tomoro; Suyama, Maiko; Mizuochi, Hiromi; Uchikawa, Hideki; Yoshida, Shigetoshi; Yoshida, Hideo; Kohno, Yoichi

2013-04-01

Phrenic nerve palsy is a peripheral nerve disorder caused by excessive cervical extension due to birth trauma or cardiac surgery. We describe two new patients with phrenic nerve palsy associated with birth trauma. Both patients exhibited profound dyspnea and general hypotonia immediately after birth. A chest roentgenogram and fluoroscopy revealed elevation of the diaphragm, leading to a diagnosis of phrenic nerve palsy associated with birth trauma. Since they had intermittently exhibited dyspnea and recurrent infection, we performed video-assisted thoracoscopic surgery (VATS) plication in both cases, at an early and a late stage, respectively. Both patients subsequently exhibited a dramatic improvement in dyspnea and recurrent respiratory infection. Interestingly, the late stage operated infant exhibited spontaneous recovery at 7 months with cessation of mechanical ventilation once. However, this recovery was transient and subsequently led to an increased ventilation volume demand, finally resulting in surgical treatment at 15 months. Histological examination of the diaphragm at this time showed grouped muscle atrophy caused by phrenic nerve degeneration. To our knowledge, this is the first pathologically proven report of grouped muscle atrophy of the diaphragm due to phrenic nerve degeneration, suggesting that partial impairment of phrenic nerves resulted in respiratory dysfunction with incomplete recovery. We conclude that recently developed VATS plication is a safe and effective treatment for infants with phrenic nerve palsy, and should be considered as a surgical treatment at an early period. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Perceptual analyses of spasmodic dysphonia before and after treatment.

PubMed

Cannito, Michael P; Woodson, Gayle E; Murry, Thomas; Bender, Brenda

2004-12-01

To evaluate expert listeners' perceptions of voice and fluency in persons with adductor spasmodic dysphonia (ADSD) before and after treatment with botulinum toxin type A (Botox), as a function of initial severity of the disorder (while controlling for patients' age at injection). Simple before-and-after trial with blinded randomized listener judgments. Ambulatory care clinic at a single medical center. Forty-two consecutive patients with ADSD who underwent examination, with a 3- to 6-week follow-up, after initial botulinum toxin type A injection. There were also 42 age- and sex-matched healthy control subjects. Injections of botulinum toxin type A into the thyroarytenoid muscle(s). Computer-implemented visual analog scaling judgments of voice quality and speech fluency made by expert listeners under psychoacoustically controlled conditions. Response to botulinum toxin type A varied markedly as a function of pretreatment severity of ADSD. More severe initial symptoms exhibited greater magnitudes of improvement. Patients with mild dysphonia did not exhibit pretreatment to posttreatment change. Following treatment, voice and fluency remained significantly (P<.05) poorer in ADSD than in healthy speakers. Older patients exhibited less improvement than younger patients when the effect of initial severity was statistically controlled. Voice quality and fluency improved for most patients following treatment, but older patients and those with milder dysphonia exhibited the least optimal responses to the procedure. Patients who were profoundly impaired demonstrated the greatest amount of improvement. Computer-implemented visual analog scaling provided a reliable clinical tool for determining treatment-related changes in those with ADSD.

Temporal and spatial profile of brain diffusion-weighted MRI after cardiac arrest

PubMed Central

Mlynash, M.; Campbell, D.M.; Leproust, E.M.; Fischbein, N.J.; Bammer, R.; Eyngorn, I.; Hsia, A.W.; Moseley, M.; Wijman, C.A.C.

2010-01-01

Background and Purpose Diffusion-weighted MRI (DWI) of the brain is a promising technique to help predict functional outcome in comatose survivors of cardiac arrest. We aimed to evaluate prospectively the temporal-spatial profile of brain apparent diffusion coefficient (ADC) changes in comatose survivors during the first 8 days after cardiac arrest. Methods ADC values were measured by two independent and blinded investigators in predefined brain regions in 18 good and 15 poor outcome patients with 38 brain MRIs, and compared with 14 normal controls. The same brain regions were also assessed qualitatively by two other independent and blinded investigators. Results In poor outcome patients, cortical structures, in particular the occipital and temporal lobes, and the putamen exhibited the most profound ADC reductions, which were noted as early as 1.5 days and reached nadir between 3 to 5 days after the arrest. Conversely, when compared to normal controls, good outcome patients exhibited increased diffusivity, in particular in the hippocampus, temporal and occipital lobes, and corona radiata. By the qualitative MRI readings, one or more cortical gray matter structures were read as moderately-to-severely abnormal in all poor outcome patients imaged beyond 54 hours after the arrest, but not in the three patients imaged earlier. Conclusions Brain DWI changes in comatose post-cardiac arrest survivors in the first week after the arrest are region- and time-dependent and differ between good and poor outcome patients. With the increasing use of MRI in this context, it is important to be aware of these relationships. PMID:20595666

Social Enrichment during Postnatal Development Induces Transgenerational Effects on Emotional and Reproductive Behavior in Mice

PubMed Central

Curley, James P.; Davidson, Stephanie; Bateson, Patrick; Champagne, Frances A.

2009-01-01

Across species there is evidence that the quality of the early social environment can have a profound impact on neurobiology and behavior. In the present study we explore the effect of communal rearing conditions (three dams with three litters per cage) during the postnatal period on offspring (F1) and grand-offspring (F2) anxiety-like and maternal behavior in Balb/c mice. Females rearing pups in communal nests exhibited increased levels of postpartum maternal care and communal rearing was found to abolish sex-differences in weaning weights. In adulthood, communally reared offspring were observed to display reduced anxiety-like behavior when placed in a novel environment. When rearing their own offspring under standard conditions, communally reared females demonstrated higher levels of motivation to retrieve pups, built higher quality nests, and exhibited higher levels of postpartum care compared to standard reared females. When exposed to an intruder male, communally reared females were more subordinate and less aggressive. F2 offspring of communally reared females were observed to engage in reduced anxiety-like behavior, have larger litter sizes and an increased frequency of nursing on PND 1. Analysis of neuropeptide receptor levels suggest that a communal rearing environment may exert sustained effects on behavior through modification of oxytocin and vasopressin (V1a) receptor densities. Though Balb-C mice are often considered “socially-incompetent” and high in anxiety-like behavior, our findings suggest that through enrichment of the postnatal environment, these behavioral and neuroendocrine deficits may be attenuated both within and across generations. PMID:19826497

Life Is Getting Better: Societal Evolution and Fit with Human Nature

ERIC Educational Resources Information Center

Veenhoven, Ruut

2010-01-01

Human society has changed much over the last centuries and this process of "modernization" has profoundly affected the lives of individuals; currently we live quite different lives from those forefathers lived only five generations ago. There is difference of opinion as to whether we live better now than before and consequently there is also…

Administration Modifications on the WISC-R Performance Scale with Different Categories of Deaf Children.

ERIC Educational Resources Information Center

Sullivan, Patricia M.

1982-01-01

Two studies investigated the effects of administration modifications on subtest scaled scores of the Wechsler-Intelligence Scale for Children-Revised (WISC-R). Performance scale rated different groups of 57 severely/profoundly hearing-impaired children. Total communication was found to result in higher scores on all subtests in the genetic and…

Epidemiology of fractures in people with severe and profound developmental disabilities

USGS Publications Warehouse

Glick, N.R.; Fischer, M.H.; Heisey, D.M.; Leverson, G.E.; Mann, D.C.

2005-01-01

Fractures are more prevalent among people with severe and profound developmental disabilities than in the general population. In order to characterize the tendency of these people to fracture, and to identify features that may guide the development of preventive strategies, we analyzed fracture epidemiology in people with severe and profound developmental disabilities who lived in a stable environment. Data from a 23-year longitudinal cohort registry of 1434 people with severe and profound developmental disabilities were analyzed to determine the effects of age, gender, mobility, bone fractured, month of fracture, and fracture history upon fracture rates. Eighty-five percent of all fractures involved the extremities. The overall fracture rate increased as mobility increased. In contrast, femoral shaft fracture risk was substantially higher in the least mobile [relative risk (RR), 10.36; 95% confidence interval (CI), 3.29-32.66] compared with the most mobile group. Although the overall fracture rate was not associated with age, the femoral shaft fractures decreased but hand/foot fractures increased with age. Overall fracture risk declined in August and September (RR, 0.70; 95% CI, 0.55-0.89), being especially prominent for tibial/fibular fractures (RR, 0.31; 95% CI, 0.13-0.70). Gender was not a factor in fracture risk. Two primary fracture mechanisms are apparent: one, largely associated with lack of weight-bearing in people with the least mobility, is exemplified by femoral fractures during non-traumatic events as simple as diapering or transfers; the other, probably due to movement- or fall-related trauma, is exemplified by hand/foot fractures in people who ambulate. The fracture experience of people with severe and profound developmental disabilities is unique and, because it differs qualitatively from postmenopausal osteoporosis, may require population-specific methods for assessing risk, for improving bone integrity, and for reduction of falls and accidents. ?? International Osteoporosis Foundation and National Osteoporosis Foundation 2004.

The Problem with Comparisons.

ERIC Educational Resources Information Center

Hurn, Christopher J.

1983-01-01

Contrasting American education with that of other countries, compares systems that differ profoundly in objectives, values, and organization. The American decentralization, lack of a national examination system, and values of egalitarianism, utilitarianism, and individualism work against the single-minded concentration on academic goals of other…

Books That Made a Difference.

ERIC Educational Resources Information Center

School Administrator, 1998

1998-01-01

Asked to identify one book that profoundly influenced their thinking, eight well-read superintendents recommended titles stressing learning and leadership themes. The list includes James Comer's "Waiting for a Miracle," Paulo Freire's "Pedagogy of the Oppressed," John Dewey's "Experience and Education," Antoine de…

Neuropsychological and SPECT scan findings during and after transient global amnesia: evidence for the differential impairment of remote episodic memory.

PubMed

Evans, J; Wilson, B; Wraight, E P; Hodges, J R

1993-11-01

A patient had neuropsychological testing during, and at two days and seven weeks after a transient global amnesia (TGA) attack. During the attack she exhibited a characteristically profound anterograde amnesia but a limited remote memory loss; the most striking impairment was a deficit in personal episodic memory revealed by her performance on the Autobiographical Memory Interview. Personal and general semantic information was less impaired although there were indications of a temporal gradient in the impairment. When tested after the attack, she demonstrated normal anterograde and retrograde memory. A SPECT scan performed during TGA showed a focal reduction in cerebral perfusion in the postero-medial temporal lobes bilaterally which had resolved after seven weeks.

Structural and Functional Consequences of Increased Tubulin Glycosylation in Diabetes Mellitus

NASA Astrophysics Data System (ADS)

Williams, Stuart K.; Howarth, Nancy L.; Devenny, James J.; Bitensky, Mark W.

1982-11-01

The extent of in vitro nonenzymatic glycosylation of purified rat brain tubulin was dependent on time and glucose concentration. Tubulin glycosylation profoundly inhibited GTP-dependent tubulin polymerization. Electron microscopy and NaDodSO4/polyacrylamide gel electrophoresis showed that glycosylated tubulin forms high molecular weight amorphous aggregates that are not disrupted by detergents or reducing agents. The amount of covalently bound NaB3H4-reducible sugars in tubulin recovered from brain of streptozotocin-induced diabetic rats was dramatically increased as compared with tubulin recovered from normal rat brain. Moreover, tubulin recovered from diabetic rat brain exhibited less GTP-induced polymerization than tubulin from nondiabetic controls. The possible implications of these data for diabetic neuropathy are discussed.

The dissociation of liquid silica at high pressure and temperature

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

Hicks, D; Boehly, T; Eggert, J

2005-11-17

Liquid silica at high pressure and temperature is shown to undergo significant structural modifications and profound changes in its electronic properties. Temperature measurements on shock waves in silica at 70-1000 GPa indicate that the specific heat of liquid SiO{sub 2} rises well above the Dulong-Petit limit, exhibiting a broad peak with temperature that is attributable to the growing structural disorder caused by bond-breaking in the melt. The simultaneous sharp rise in optical reflectivity of liquid SiO{sub 2} indicates that dissociation causes the electrical and therefore thermal conductivities of silica to attain metallic-like values of 1-5 x 10{sup 5} S/m andmore » 24-600 W/m.K respectively.« less

"The living picture": on the circulation of microscope-slide knowledge in 1903.

PubMed

Gaycken, Oliver

2013-01-01

Microscope slides allowed preparations to circulate among scientific and educational contexts. An extension of the circulation of microscope slides was how they became part of lantern exhibition culture. This article considers an early example of the adoption of microscope lantern show conventions by another medium, the cinema. E Martin Duncan, who was employed by Charles Urban to produce a series of popular-science films beginning in 1903, brought his experience with microphotography to bear on the challenge of adapting cinema to the purpose of public instruction. Duncan's first series of films, entitled "The Unseen World," demonstrated both profound links to the display tradition of the lantern lecture as well as the transformation of that tradition by the cinema's representational possibilities.

The Neuropeptides FLP-2 and PDF-1 Act in Concert To Arouse Caenorhabditis elegans Locomotion

PubMed Central

Chen, Didi; Taylor, Kelsey P.; Hall, Qi; Kaplan, Joshua M.

2016-01-01

During larval molts, Caenorhabditis elegans exhibits a sleep-like state (termed lethargus) that is characterized by the absence of feeding and profound locomotion quiescence. The rhythmic pattern of locomotion quiescence and arousal linked to the molting cycle is mediated by reciprocal changes in sensory responsiveness, whereby arousal is associated with increased responsiveness. Sensory neurons arouse locomotion via release of a neuropeptide (PDF-1) and glutamate. Here we identify a second arousing neuropeptide (FLP-2). We show that FLP-2 acts via an orexin-like receptor (FRPR-18), and that FLP-2 and PDF-1 secretion are regulated by reciprocal positive feedback. These results suggest that the aroused behavioral state is stabilized by positive feedback between two neuropeptides. PMID:27585848

Adaptation to high temperature mitigates the impact of water deficit during combined heat and drought stress in C3 sunflower and C4 maize varieties with contrasting drought tolerance.

PubMed

Killi, Dilek; Bussotti, Filippo; Raschi, Antonio; Haworth, Matthew

2017-02-01

Heat and drought stress frequently occur together, however, their impact on plant growth and photosynthesis (P N ) is unclear. The frequency, duration and severity of heat and drought stress events are predicted to increase in the future, having severe implications for agricultural productivity and food security. To assess the impact on plant gas exchange, physiology and morphology we grew drought tolerant and sensitive varieties of C3 sunflower (Helianthus annuus) and C4 maize (Zea mays) under conditions of elevated temperature for 4 weeks prior to the imposition of water deficit. The negative impact of temperature on P N was most apparent in sunflower. The drought tolerant sunflower retained ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) activity under heat stress to a greater extent than its drought sensitive counterpart. Maize exhibited no varietal difference in response to increased temperature. In contrast to previous studies, where a sudden rise in temperature induced an increase in stomatal conductance (G s ), we observed no change or a reduction in G s with elevated temperature, which alongside lower leaf area mitigated the impact of drought at the higher temperature. The drought tolerant sunflower and maize varieties exhibited greater investment in root-systems, allowing greater uptake of the available soil water. Elevated temperatures associated with heat-waves will have profound negative impacts on crop growth in both sunflower and maize, but the deleterious effect on P N was less apparent in the drought tolerant sunflower and both maize varieties. As C4 plants generally exhibit water use efficiency (WUE) and resistance to heat stress, selection on the basis of tolerance to heat and drought stress would be more beneficial to the yields of C3 crops cultivated in drought prone semi-arid regions. © 2016 Scandinavian Plant Physiology Society.

Chemo brain or tumor brain - that is the question: the presence of extracranial tumors profoundly affects molecular processes in the prefrontal cortex of TumorGraft mice

PubMed Central

Kovalchuk, Anna; Ilnytskyy, Yaroslav; Rodriguez-Juarez, Rocio; Shpyleva, Svitlana; Melnyk, Stepan; Pogribny, Igor; Katz, Amanda; Sidransky, David; Kovalchuk, Olga; Kolb, Bryan

2017-01-01

Cancer chemotherapy causes numerous persistent central nervous system complications. This condition is known as chemo brain. Cognitive impairments occur even before treatment, and hence are referred to as cancer associated cognitive changes, or tumor brain. There is much yet to be learned about the mechanisms of both chemo brain and tumor brain. The frequency and timing of chemo brain and tumor brain occurrence and persistence strongly suggest they may be epigenetic in nature and associated with altered gene expression. Here we used TumorGraftTM models wherein part of a patient's tumor is removed and grafted into immune-deficient mice and conducted global gene expression and DNA methylation analysis. We show that malignant non-central nervous system tumor growth causes profound molecular alterations in the brain. Mice harbouring triple negative or progesterone positive breast cancer TumorGrafts exhibited altered gene expression, decreased levels of DNA methylation, increased levels of DNA hydroxymethylation, and oxidative stress in the prefrontal cortex. Interestingly, chemotherapy did not have any additional synergistic effects on the analyzed processes. The molecular changes observed in this study are known signs of neurodegeneration and brain aging. This study provides an important roadmap for future large-scale analysis of the molecular and cellular mechanisms of tumor brain. PMID:28758896

Fatty acid modulated human serum albumin binding of the β-carboline alkaloids norharmane and harmane.

PubMed

Domonkos, Celesztina; Fitos, Ilona; Visy, Júlia; Zsila, Ferenc

2013-12-02

Harmane and norharmane are representative members of the large group of natural β-carboline alkaloids featured with diverse pharmacological activities. In blood, these agents are transported by human serum albumin (HSA) which has a profound impact on the pharmacokinetic and pharmacodynamic properties of many therapeutic drugs and xenobiotics. By combination of various spectroscopic methods, the present contribution is aimed to elucidate how nonesterified fatty acids (FAs), the primary endogenous ligands of HSA, affect the binding properties of harmane and norharmane. Analysis of induced circular dichroism (CD) and fluorescence spectroscopic data indicates the inclusion of the neutral form of both molecules into the binding pocket of subdomain IIIA, which hosts two FA binding sites, too. The induced CD and UV absorption spectra of harmane and norharmane exhibit peculiar changes upon addition of FAs, suggesting the formation of ternary complexes in which the lipid ligands significantly alter the binding mode of the alkaloids via cooperative allosteric mechanism. To our knowledge, it is the first instance of the demonstration of drug-FA cobinding at site IIIA. In line with these results, molecular docking calculations showed two distinct binding positions of norharmane within subdomain IIIA. The profound increase in the affinity constants of β-carbolines estimated in the presence of FAs predicts that the unbound, pharmacologically active serum fraction of these compounds strongly depends on the actual lipid binding profile of HSA.

The Effectiveness of Vowel Production Training with Real-Time Spectrographic Displays for Children with Profound Hearing Impairment.

NASA Astrophysics Data System (ADS)

Ertmer, David Joseph

1994-01-01

The effectiveness of vowel production training which incorporated direct instruction in combination with spectrographic models and feedback was assessed for two children who exhibited profound hearing impairment. A multiple-baseline design across behaviors, with replication across subjects was implemented to determine if vowel production accuracy improved following the introduction of treatment. Listener judgments of vowel correctness were obtained during the baseline, training, and follow-up phases of the study. Data were analyzed through visual inspection of changes in levels of accuracy, changes in trends of accuracy, and changes in variability of accuracy within and across phases. One subject showed significant improvement of all three trained vowel targets; the second subject for the first trained target only (Kolmogorov-Smirnov Two Sample Test). Performance trends during training sessions suggest that continued treatment would have resulted in further improvement for both subjects. Vowel duration, fundamental frequency, and the frequency locations of the first and second formants were measured before and after training. Acoustic analysis revealed highly individualized changes in the frequency locations of F1 and F2. Vowels which received the most training were maintained at higher levels than those which were introduced later in training, Some generalization of practiced vowel targets to untrained words was observed in both subjects. A bias towards judging productions as "correct" was observed for both subjects during self-evaluation tasks using spectrographic feedback.

Subunit stoichiometry of human muscle chloride channels.

PubMed

Fahlke, C; Knittle, T; Gurnett, C A; Campbell, K P; George, A L

1997-01-01

Voltage-gated Cl- channels belonging to the ClC family appear to function as homomultimers, but the number of subunits needed to form a functional channel is controversial. To determine subunit stoichiometry, we constructed dimeric human skeletal muscle Cl- channels in which one subunit was tagged by a mutation (D136G) that causes profound changes in voltage-dependent gating. Sucrose-density gradient centrifugation experiments indicate that both monomeric and dimeric hClC-1 channels in their native configurations exhibit similar sedimentation properties consistent with a multimeric complex having a molecular mass of a dimer. Expression of the heterodimeric channel in a mammalian cell line results in a homogenous population of Cl- channels exhibiting novel gating properties that are best explained by the formation of heteromultimeric channels with an even number of subunits. Heteromultimeric channels were not evident in cells cotransfected with homodimeric WT-WT and D136G-D136G constructs excluding the possibility that functional hClC-1 channels are assembled from more than two subunits. These results demonstrate that the functional hClC-1 unit consists of two subunits.

A mechanism by which dietary trans fats cause atherosclerosis.

PubMed

Chen, Chun-Lin; Tetri, Laura H; Neuschwander-Tetri, Brent A; Huang, Shuan Shian; Huang, Jung San

2011-07-01

Dietary trans fats (TFs) have been causally linked to atherosclerosis, but the mechanism by which they cause the disease remains elusive. Suppressed transforming growth factor (TGF)-β responsiveness in aortic endothelium has been shown to play an important role in the pathogenesis of atherosclerosis in animals with hypercholesterolemia. We investigated the effects of a high TF diet on TGF-β responsiveness in aortic endothelium and integration of cholesterol in tissues. Here, we show that normal mice fed a high TF diet for 24 weeks exhibit atherosclerotic lesions and suppressed TGF-β responsiveness in aortic endothelium. The suppressed TGF-β responsiveness is evidenced by markedly reduced expression of TGF-β type I and II receptors and profoundly decreased levels of phosphorylated Smad2, an important TGF-β response indicator, in aortic endothelium. These mice exhibit greatly increased integration of cholesterol into tissue plasma membranes. These results suggest that dietary TFs cause atherosclerosis, at least in part, by suppressing TGF-β responsiveness. This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia. Copyright © 2011 Elsevier Inc. All rights reserved.

Density Shock Waves in Confined Microswimmers

NASA Astrophysics Data System (ADS)

Tsang, Alan Cheng Hou; Kanso, Eva

2016-01-01

Motile and driven particles confined in microfluidic channels exhibit interesting emergent behavior, from propagating density bands to density shock waves. A deeper understanding of the physical mechanisms responsible for these emergent structures is relevant to a number of physical and biomedical applications. Here, we study the formation of density shock waves in the context of an idealized model of microswimmers confined in a narrow channel and subject to a uniform external flow. Interestingly, these density shock waves exhibit a transition from "subsonic" with compression at the back to "supersonic" with compression at the front of the population as the intensity of the external flow increases. This behavior is the result of a nontrivial interplay between hydrodynamic interactions and geometric confinement, and it is confirmed by a novel quasilinear wave model that properly captures the dependence of the shock formation on the external flow. These findings can be used to guide the development of novel mechanisms for controlling the emergent density distribution and the average population speed, with potentially profound implications on various processes in industry and biotechnology, such as the transport and sorting of cells in flow channels.

Myeloid cell recruitment versus local proliferation differentiates susceptibility from resistance to filarial infection

PubMed Central

Campbell, Sharon M; Knipper, Johanna A; Ruckerl, Dominik; Finlay, Conor M; Logan, Nicola; Minutti, Carlos M; Mack, Matthias; Jenkins, Stephen J; Taylor, Matthew D

2018-01-01

Both TH2-dependent helminth killing and suppression of the TH2 effector response have been attributed to macrophages (MΦ) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute to diverse infection outcomes, the MΦ compartment of susceptible BALB/c mice and more resistant C57BL/6 mice was profiled during infection of the pleural cavity with the filarial nematode, Litomosoides sigmodontis. C57BL/6 mice exhibited a profoundly expanded resident MΦ (resMΦ) population, which was gradually replenished from the bone marrow in an age-dependent manner. Infection status did not alter the bone-marrow derived contribution to the resMΦ population, confirming local proliferation as the driver of resMΦ expansion. Significantly less resMΦ expansion was observed in the susceptible BALB/c strain, which instead exhibited an influx of monocytes that assumed an immunosuppressive PD-L2+ phenotype. Inhibition of monocyte recruitment enhanced nematode killing. Thus, the balance of monocytic vs. resident M(IL-4) numbers varies between inbred mouse strains and impacts infection outcome. PMID:29299998

Developmental dyscalculia: a dysconnection syndrome?

PubMed

Kucian, Karin; Ashkenazi, Simone Schwizer; Hänggi, Jürgen; Rotzer, Stephanie; Jäncke, Lutz; Martin, Ernst; von Aster, Michael

2014-09-01

Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10 years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia.

ASXL1/EZH2 mutations promote clonal expansion of neoplastic HSC and impair erythropoiesis in PMF.

PubMed

Triviai, Ioanna; Zeschke, Silke; Rentel, Jan; Spanakis, Marios; Scherer, Theo; Gabdoulline, Razif; Panagiota, Victoria; Thol, Felicitas; Heuser, Michael; Stocking, Carol; Kröger, Nicolaus

2018-06-15

Primary myelofibrosis (PMF) is a hematopoietic stem cell (HSC) disease, characterized by aberrant differentiation of all myeloid lineages and profound disruption of the bone marrow niche. PMF samples carry several mutations, but their cell origin and hierarchy in regulating the different waves of clonal and aberrant myeloproliferation from the prime HSC compartment is poorly understood. Genotyping of >2000 colonies from CD133+HSC and progenitors from PMF patients confirmed the complex genetic heterogeneity within the neoplastic population. Notably, mutations in chromatin regulators ASXL1 and/or EZH2 were identified as the first genetic lesions, preceding both JAK2-V617F and CALR mutations, and are thus drivers of clonal myelopoiesis in a PMF subset. HSC from PMF patients with double ASXL1/EZH2 mutations exhibited significantly higher engraftment in immunodeficient mice than those from patients without histone modifier mutations. EZH2 mutations correlate with aberrant erythropoiesis in PMF patients, exemplified by impaired maturation and cell cycle arrest of erythroid progenitors. These data underscore the importance of post-transcriptional modifiers of histones in neoplastic stem cells, whose clonal growth sustains aberrant myelopoiesis and expansion of pre-leukemic clones in PMF.

Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2

PubMed Central

Liu, Beiying; Qin, Feng

2016-01-01

Thermal TRP channels mediate temperature transduction and pain sensation. The vanilloid receptor TRPV2 is involved in detection of noxious heat in a subpopulation of high-threshold nociceptors. It also plays a critical role in development of thermal hyperalgesia, but the underlying mechanism remains uncertain. Here we analyze the heat sensitivity of the TRPV2 channel. Heat activation of the channel exhibits strong use dependence. Prior heat activation can profoundly alter its subsequent temperature responsiveness, causing decreases in both temperature activation threshold and slope sensitivity of temperature dependence while accelerating activation time courses. Notably, heat and agonist activations differ in cross use-dependence. Prior heat stimulation can dramatically sensitize agonist responses, but not conversely. Quantitative analyses indicate that the use dependence in heat sensitivity is pertinent to the process of temperature sensing by the channel. The use dependence of TRPV2 reveals that the channel can have a dynamic temperature sensitivity. The temperature sensing structures within the channel have multiple conformations and the temperature activation pathway is separate from the agonist activation pathway. Physiologically, the use dependence of TRPV2 confers nociceptors with a hypersensitivity to heat and thus provides a mechanism for peripheral thermal hyperalgesia. PMID:27074678

Syntactic priming in American Sign Language.

PubMed

Hall, Matthew L; Ferreira, Victor S; Mayberry, Rachel I

2015-01-01

Psycholinguistic studies of sign language processing provide valuable opportunities to assess whether language phenomena, which are primarily studied in spoken language, are fundamentally shaped by peripheral biology. For example, we know that when given a choice between two syntactically permissible ways to express the same proposition, speakers tend to choose structures that were recently used, a phenomenon known as syntactic priming. Here, we report two experiments testing syntactic priming of a noun phrase construction in American Sign Language (ASL). Experiment 1 shows that second language (L2) signers with normal hearing exhibit syntactic priming in ASL and that priming is stronger when the head noun is repeated between prime and target (the lexical boost effect). Experiment 2 shows that syntactic priming is equally strong among deaf native L1 signers, deaf late L1 learners, and hearing L2 signers. Experiment 2 also tested for, but did not find evidence of, phonological or semantic boosts to syntactic priming in ASL. These results show that despite the profound differences between spoken and signed languages in terms of how they are produced and perceived, the psychological representation of sentence structure (as assessed by syntactic priming) operates similarly in sign and speech.

Sensorineural Deafness and Seizures in Mice Lacking Vesicular Glutamate Transporter 3

PubMed Central

Seal, Rebecca P.; Akil, Omar; Yi, Eunyoung; Weber, Christopher M.; Grant, Lisa; Yoo, Jong; Clause, Amanda; Kandler, Karl; Noebels, Jeffrey L; Glowatzki, Elisabeth; Lustig, Lawrence R.; Edwards, Robert H.

2008-01-01

Summary The expression of unconventional vesicular glutamate transporter VGLUT3 by neurons known to release a different classical transmitter has suggested novel roles for signaling by glutamate. However, this distribution, along with the localization of VGLUT3 to dendrites and its occurrence outside the nervous system, has raised questions about whether the protein actually contributes to glutamate release. We now report that mice lacking VGLUT3 are profoundly deaf due to the absence of glutamate release from hair cells at the first synapse in the auditory pathway. Inner hair cells of the cochlea start to express VGLUT3 shortly before birth, and the early degeneration of some cochlear ganglion neurons in knock-out mice indicates an important developmental role for the glutamate released by hair cells before the onset of hearing. In addition, the mice exhibit primary, generalized epilepsy that is accompanied by remarkably little or no change in ongoing motor behavior. VGLUT3 thus contributes to the exocytotic release of glutamate, and the glutamate released has an essential role in both function and development of the auditory pathway, as well as in the control of cortical excitability. PMID:18215623

Anisotropy of Single-Crystal Silicon in Nanometric Cutting.

PubMed

Wang, Zhiguo; Chen, Jiaxuan; Wang, Guilian; Bai, Qingshun; Liang, Yingchun

2017-12-01

The anisotropy exhibited by single-crystal silicon in nanometric cutting is very significant. In order to profoundly understand the effect of crystal anisotropy on cutting behaviors, a large-scale molecular dynamics model was conducted to simulate the nanometric cutting of single-crystal silicon in the (100)[0-10], (100)[0-1-1], (110)[-110], (110)[00-1], (111)[-101], and (111)[-12-1] crystal directions in this study. The simulation results show the variations of different degrees in chip, subsurface damage, cutting force, and friction coefficient with changes in crystal plane and crystal direction. Shear deformation is the formation mechanism of subsurface damage, and the direction and complexity it forms are the primary causes that result in the anisotropy of subsurface damage. Structurally, chips could be classified into completely amorphous ones and incompletely amorphous ones containing a few crystallites. The formation mechanism of the former is high-pressure phase transformation, while the latter is obtained under the combined action of high-pressure phase transformation and cleavage. Based on an analysis of the material removal mode, it can be found that compared with the other crystal direction on the same crystal plane, the (100)[0-10], (110)[-110], and (111)[-101] directions are more suitable for ductile cutting.

Tuning charge carrier transport and optical birefringence in liquid-crystalline thin films: A new design space for organic light-emitting diodes.

PubMed

Keum, Chang-Min; Liu, Shiyi; Al-Shadeedi, Akram; Kaphle, Vikash; Callens, Michiel Koen; Han, Lu; Neyts, Kristiaan; Zhao, Hongping; Gather, Malte C; Bunge, Scott D; Twieg, Robert J; Jakli, Antal; Lüssem, Björn

2018-01-15

Liquid-crystalline organic semiconductors exhibit unique properties that make them highly interesting for organic optoelectronic applications. Their optical and electrical anisotropies and the possibility to control the alignment of the liquid-crystalline semiconductor allow not only to optimize charge carrier transport, but to tune the optical property of organic thin-film devices as well. In this study, the molecular orientation in a liquid-crystalline semiconductor film is tuned by a novel blading process as well as by different annealing protocols. The altered alignment is verified by cross-polarized optical microscopy and spectroscopic ellipsometry. It is shown that a change in alignment of the liquid-crystalline semiconductor improves charge transport in single charge carrier devices profoundly. Comparing the current-voltage characteristics of single charge carrier devices with simulations shows an excellent agreement and from this an in-depth understanding of single charge carrier transport in two-terminal devices is obtained. Finally, p-i-n type organic light-emitting diodes (OLEDs) compatible with vacuum processing techniques used in state-of-the-art OLEDs are demonstrated employing liquid-crystalline host matrix in the emission layer.

Nanostructured porous Si optical biosensors: effect of thermal oxidation on their performance and properties.

PubMed

Shtenberg, Giorgi; Massad-Ivanir, Naama; Fruk, Ljiljana; Segal, Ester

2014-09-24

The influence of thermal oxidation conditions on the performance of porous Si optical biosensors used for label-free and real-time monitoring of enzymatic activity is studied. We compare three oxidation temperatures (400, 600, and 800 °C) and their effect on the enzyme immobilization efficiency and the intrinsic stability of the resulting oxidized porous Si (PSiO2), Fabry-Pérot thin films. Importantly, we show that the thermal oxidation profoundly affects the biosensing performance in terms of greater optical sensitivity, by monitoring the catalytic activity of horseradish peroxidase and trypsin-immobilized PSiO2. Despite the significant decrease in porous volume and specific surface area (confirmed by nitrogen gas adsorption-desorption studies) with elevating the oxidation temperature, higher content and surface coverage of the immobilized enzymes is attained. This in turn leads to greater optical stability and sensitivity of PSiO2 nanostructures. Specifically, films produced at 800 °C exhibit stable optical readout in aqueous buffers combined with superior biosensing performance. Thus, by proper control of the oxide layer formation, we can eliminate the aging effect, thus achieving efficient immobilization of different biomolecules, optical signal stability, and sensitivity.

Effect of manufacturing process sequence on the corrosion resistance characteristics of coated metallic bipolar plates

NASA Astrophysics Data System (ADS)

Dur, Ender; Cora, Ömer Necati; Koç, Muammer

2014-01-01

Metallic bipolar plate (BPP) with high corrosion and low contact resistance, durability, strength, low cost, volume, and weight requirements is one of the critical parts of the PEMFC. This study is dedicated to understand the effect of the process sequence (manufacturing then coating vs. coating then manufacturing) on the corrosion resistance of coated metallic bipolar plates. To this goal, three different PVD coatings (titanium nitride (TiN), chromium nitride (CrN), zirconium nitride (ZrN)), with three thicknesses, (0.1, 0.5, 1 μm) were applied on BPPs made of 316L stainless steel alloy before and after two types of manufacturing (i.e., stamping or hydroforming). Corrosion test results indicated that ZrN coating exhibited the best corrosion protection while the performance of TiN coating was the lowest among the tested coatings and thicknesses. For most of the cases tested, in which coating was applied before manufacturing, occurrence of corrosion was found to be more profound than the case where coating was applied after manufacturing. Increasing the coating thickness was found to improve the corrosion resistance. It was also revealed that hydroformed BPPs performed slightly better than stamped BPPs in terms of the corrosion behavior.

mTORC1-Independent Reduction of Retinal Protein Synthesis in Type 1 Diabetes

PubMed Central

Losiewicz, Mandy K.; Pennathur, Subramaniam; Jefferson, Leonard S.; Kimball, Scot R.; Abcouwer, Steven F.; Gardner, Thomas W.

2014-01-01

Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass resulting from a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes despite reduced Akt activity and increased rate of cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than in other insulin-sensitive tissues, such as skeletal muscle. Ins2Akita diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions in retinal protein synthesis matched by a concomitant reduction in retinal protein degradation associated with preserved retinal mass and protein content. The reduction in protein synthesis depended on both hyperglycemia and insulin deficiency, but protein degradation was only reversed by normalization of hyperglycemia. The reduction in protein synthesis was associated with diminished protein translation efficiency but, surprisingly, not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes induced a specific reduction of mTORC2 complex activity. These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared with muscle and liver that may provide a new means to ameliorate diabetic retinopathy. PMID:24740573

Atomically Thin Femtojoule Memristive Device

DOE PAGES

Zhao, Huan; Dong, Zhipeng; Tian, He; ...

2017-10-25

The morphology and dimension of the conductive filament formed in a memristive device are strongly influenced by the thickness of its switching medium layer. Aggressive scaling of this active layer thickness is critical toward reducing the operating current, voltage, and energy consumption in filamentary-type memristors. Previously, the thickness of this filament layer has been limited to above a few nanometers due to processing constraints, making it challenging to further suppress the on-state current and the switching voltage. In this paper, the formation of conductive filaments in a material medium with sub-nanometer thickness formed through the oxidation of atomically thin two-dimensionalmore » boron nitride is studied. The resulting memristive device exhibits sub-nanometer filamentary switching with sub-pA operation current and femtojoule per bit energy consumption. Furthermore, by confining the filament to the atomic scale, current switching characteristics are observed that are distinct from that in thicker medium due to the profoundly different atomic kinetics. The filament morphology in such an aggressively scaled memristive device is also theoretically explored. Finally, these ultralow energy devices are promising for realizing femtojoule and sub-femtojoule electronic computation, which can be attractive for applications in a wide range of electronics systems that desire ultralow power operation.« less

Effects of Preheating and Storage Temperatures on Aroma Profile and Physical Properties of Citrus-Oil Emulsions.

PubMed

Yang, Ying; Zhao, Chengying; Tian, Guifang; Lu, Chang; Zhao, Shaojie; Bao, Yuming; McClements, David Julian; Xiao, Hang; Zheng, Jinkai

2017-09-06

Citrus oils are used as good carrier oil for emulsion fabrication due to their special flavor and various health-promoting functions. In this study, the effects of preheating temperature (30, 40, 50, 60, and 70 °C) and storage temperature (4, 25, and 37 °C) on aroma profiles and physical properties of three citrus-oil (i.e., mandarin, sweet orange, and bergamot oils) emulsions were systematically investigated for the first time. The results demonstrated the significant impact of temperature on aroma profile and physical properties. The abundance of d-limonene was found to be the main factor determining the aroma of the three citrus-oil emulsions at different preheating and storage temperatures, while β-linalool and linalyl acetate were important for the aroma of bergamot oil emulsion. Preheating temperature showed a profound impact on the aroma of citrus-oil emulsions, and the aroma of different citrus oil emulsions showed different sensitivity to preheating temperature. Storage temperature was also able to alter the properties of citrus oil emulsions. The higher was the storage temperature, the more alteration of aroma and more instability of the emulsions there was, which could be attributed to the alteration of the oil components and the properties of emulsions. Among all three emulsions, bergamot-oil emulsion was the most stable and exhibited the most potent ability to preserve the aroma against high temperature. Our results would facilitate the application of citrus-oil emulsions in functional foods and beverages.

Metabolic profiles of triple-negative and luminal A breast cancer subtypes in African-American identify key metabolic differences.

PubMed

Tayyari, Fariba; Gowda, G A Nagana; Olopade, Olufunmilayo F; Berg, Richard; Yang, Howard H; Lee, Maxwell P; Ngwa, Wilfred F; Mittal, Suresh K; Raftery, Daniel; Mohammed, Sulma I

2018-02-20

Breast cancer, a heterogeneous disease with variable pathophysiology and biology, is classified into four major subtypes. While hormonal- and antibody-targeted therapies are effective in the patients with luminal and HER-2 subtypes, the patients with triple-negative breast cancer (TNBC) subtype do not benefit from these therapies. The incidence rates of TNBC subtype are higher in African-American women, and the evidence indicates that these women have worse prognosis compared to women of European descent. The reasons for this disparity remain unclear but are often attributed to TNBC biology. In this study, we performed metabolic analysis of breast tissues to identify how TNBC differs from luminal A breast cancer (LABC) subtypes within the African-American and Caucasian breast cancer patients, respectively. We used High-Resolution Magic Angle Spinning (HR-MAS) 1H Nuclear magnetic resonance (NMR) to perform the metabolomic analysis of breast cancer and adjacent normal tissues (total n=82 samples). TNBC and LABC subtypes in African American women exhibited different metabolic profiles. Metabolic profiles of these subtypes were also distinct from those revealed in Caucasian women. TNBC in African-American women expressed higher levels of glutathione, choline, and glutamine as well as profound metabolic alterations characterized by decreased mitochondrial respiration and increased glycolysis concomitant with decreased levels of ATP. TNBC in Caucasian women was associated with increased pyrimidine synthesis. These metabolic alterations could potentially be exploited as novel treatment targets for TNBC.

Metabolic profiles of triple-negative and luminal A breast cancer subtypes in African-American identify key metabolic differences

PubMed Central

Tayyari, Fariba; Gowda, G.A. Nagana; Olopade, Olufunmilayo F.; Berg, Richard; Yang, Howard H.; Lee, Maxwell P.; Ngwa, Wilfred F.; Mittal, Suresh K.; Raftery, Daniel; Mohammed, Sulma I.

2018-01-01

Breast cancer, a heterogeneous disease with variable pathophysiology and biology, is classified into four major subtypes. While hormonal- and antibody-targeted therapies are effective in the patients with luminal and HER-2 subtypes, the patients with triple-negative breast cancer (TNBC) subtype do not benefit from these therapies. The incidence rates of TNBC subtype are higher in African-American women, and the evidence indicates that these women have worse prognosis compared to women of European descent. The reasons for this disparity remain unclear but are often attributed to TNBC biology. In this study, we performed metabolic analysis of breast tissues to identify how TNBC differs from luminal A breast cancer (LABC) subtypes within the African-American and Caucasian breast cancer patients, respectively. We used High-Resolution Magic Angle Spinning (HR-MAS) 1H Nuclear magnetic resonance (NMR) to perform the metabolomic analysis of breast cancer and adjacent normal tissues (total n=82 samples). TNBC and LABC subtypes in African American women exhibited different metabolic profiles. Metabolic profiles of these subtypes were also distinct from those revealed in Caucasian women. TNBC in African-American women expressed higher levels of glutathione, choline, and glutamine as well as profound metabolic alterations characterized by decreased mitochondrial respiration and increased glycolysis concomitant with decreased levels of ATP. TNBC in Caucasian women was associated with increased pyrimidine synthesis. These metabolic alterations could potentially be exploited as novel treatment targets for TNBC. PMID:29545929

Bulk and interfacial structures of reline deep eutectic solvent: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Kaur, Supreet; Sharma, Shobha; Kashyap, Hemant K.

2017-11-01

We apply all-atom molecular dynamics simulations to describe the bulk morphology and interfacial structure of reline, a deep eutectic solvent comprising choline chloride and urea in 1:2 molar ratio, near neutral and charged graphene electrodes. For the bulk phase structural investigation, we analyze the simulated real-space radial distribution functions, X-ray/neutron scattering structure functions, and their partial components. Our study shows that both hydrogen-bonding and long-range correlations between different constituents of reline play a crucial role to lay out the bulk structure of reline. Further, we examine the variation of number density profiles, orientational order parameters, and electrostatic potentials near the neutral and charged graphene electrodes with varying electrode charge density. The present study reveals the presence of profound structural layering of not only the ionic components of reline but also urea near the electrodes. In addition, depending on the electrode charge density, the choline ions and urea molecules render different orientations near the electrodes. The simulated number density and electrostatic potential profiles for reline clearly show the presence of multilayer structures up to a distance of 1.2 nm from the respective electrodes. The observation of positive values of the surface potential at zero charge indicates the presence of significant nonelectrostatic attraction between the choline cation and graphene electrode. The computed differential capacitance (Cd) for reline exhibits an asymmetric bell-shaped curve, signifying different variation of Cd with positive and negative surface potentials.

Bulk and interfacial structures of reline deep eutectic solvent: A molecular dynamics study.

PubMed

Kaur, Supreet; Sharma, Shobha; Kashyap, Hemant K

2017-11-21

We apply all-atom molecular dynamics simulations to describe the bulk morphology and interfacial structure of reline, a deep eutectic solvent comprising choline chloride and urea in 1:2 molar ratio, near neutral and charged graphene electrodes. For the bulk phase structural investigation, we analyze the simulated real-space radial distribution functions, X-ray/neutron scattering structure functions, and their partial components. Our study shows that both hydrogen-bonding and long-range correlations between different constituents of reline play a crucial role to lay out the bulk structure of reline. Further, we examine the variation of number density profiles, orientational order parameters, and electrostatic potentials near the neutral and charged graphene electrodes with varying electrode charge density. The present study reveals the presence of profound structural layering of not only the ionic components of reline but also urea near the electrodes. In addition, depending on the electrode charge density, the choline ions and urea molecules render different orientations near the electrodes. The simulated number density and electrostatic potential profiles for reline clearly show the presence of multilayer structures up to a distance of 1.2 nm from the respective electrodes. The observation of positive values of the surface potential at zero charge indicates the presence of significant nonelectrostatic attraction between the choline cation and graphene electrode. The computed differential capacitance (C d ) for reline exhibits an asymmetric bell-shaped curve, signifying different variation of C d with positive and negative surface potentials.

Drosophila development, physiology, behavior, and lifespan are influenced by altered dietary composition

PubMed Central

Ormerod, Kiel G.; LePine, Olivia K.; Abbineni, Prabhodh S.; Bridgeman, Justin M.; Mercier, A. Joffre; Tattersall, Glenn J.

2017-01-01

ABSTRACT Diet profoundly influences the behavior of animals across many phyla. Despite this, most laboratories using model organisms, such as Drosophila, use multiple, different, commercial or custom-made media for rearing their animals. In addition to measuring growth, fecundity and longevity, we used several behavioral and physiological assays to determine if and how altering food media influence wild-type (Canton S) Drosophila melanogaster, at larval, pupal, and adult stages. Comparing 2 commonly used commercial food media we observed several key developmental and morphological differences. Third-instar larvae and pupae developmental timing, body weight and size, and even lifespan significantly differed between the 2 diets, and some of these differences persisted into adulthood. Diet was also found to produce significantly different thermal preference, locomotory capacity for geotaxis, feeding rates, and lower muscle response to hormonal stimulation. There were no differences, however, in adult thermal preferences, in the number or viability of eggs laid, or in olfactory learning and memory between the diets. We characterized the composition of the 2 diets and found particularly significant differences in cholesterol and (phospho)lipids between them. Notably, diacylglycerol (DAG) concentrations vary substantially between the 2 diets, and may contribute to key phenotypic differences, including lifespan. Overall, the data confirm that 2 different diets can profoundly influence the behavior, physiology, morphology and development of wild-type Drosophila, with greater behavioral and physiologic differences occurring during the larval stages. PMID:28277941

Astronomical and Cosmological Symbolism in Art Dedicated to Newton and Einstein

NASA Astrophysics Data System (ADS)

Sinclair, R.

2013-04-01

Separated by two and a half centuries, Isaac Newton (1642-1727) and Albert Einstein (1879-1955) had profound impacts on our understanding of the universe. Newton established our understanding of universal gravitation, which was recast almost beyond recognition by Einstein. Both discovered basic patterns behind astronomical phenomena and became the best-known scientists of their respective periods. I will describe here how artists of the 18th and 20th centuries represented the achievements of Newton and Einstein. Representations of Newton express reverence, almost an apotheosis, portraying him as the creator of the universe. Einstein, in a different age, is represented often as a comic figure, and only rarely do we find art that hints at the profound view of the universe he developed.

The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability.

PubMed

Dijkhuizen, Annemarie; Hilgenkamp, Thessa I M; Krijnen, Wim P; van der Schans, Cees P; Waninge, Aly

2016-01-01

The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and physical capacities. However, until recently, the impact of the significantly prevalent visual impairments on the performance of activities of daily living has not yet been revealed within this group. The purpose of this prospective cross-sectional study was to investigate the impact of visual impairment on the performance of activities of daily living for persons with a severe/profound intellectual disability. The Barthel Index (BI) and Comfortable Walking Speed (CWS) were used to measure the ability of performing activities of daily living (ADL) in 240 persons with severe/profound ID and having Gross Motor Functioning Classification System (GMFCS) levels I, II or III; this included 120 persons with visual impairment. The impact of visual impairment on ADL was analyzed with linear regression. The results of the study demonstrated that visual impairment slightly affects the ability of performing activities of daily living (BI) for persons experiencing a severe/profound intellectual disability. GMFCS Levels II or III, profound ID level, and visual impairment each have the effect of lowering BI scores. GMFCS Levels II or III, and profound ID level each have the effect of increasing CWS scores, which indicates a lower walking speed. A main effect of visual impairment is present on CWS, but our results do show a substantive interaction effect between GMFCS level III and visual impairment on Comfortable Walking Speed in persons with a severe/profound intellectual disability. Visual impairment has a slight effect on ability to perform ADL in persons experiencing severe/profound ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of ploidy on scale-cover pattern in linear ornamental (koi) common carp Cyprinus carpio.

PubMed

Gomelsky, B; Schneider, K J; Glennon, R P; Plouffe, D A

2012-09-01

The effect of ploidy on scale-cover pattern in linear ornamental (koi) common carp Cyprinus carpio was investigated. To obtain diploid and triploid linear fish, eggs taken from a leather C. carpio female (genotype ssNn) and sperm taken from a scaled C. carpio male (genotype SSnn) were used for the production of control (no shock) and heat-shocked progeny. In heat-shocked progeny, the 2 min heat shock (40° C) was applied 6 min after insemination. Diploid linear fish (genotype SsNn) demonstrated a scale-cover pattern typical for this category with one even row of scales along lateral line and few scales located near operculum and at bases of fins. The majority (97%) of triploid linear fish (genotype SssNnn) exhibited non-typical scale patterns which were characterized by the appearance of additional scales on the body. The extent of additional scales in triploid linear fish was variable; some fish had large scales, which covered almost the entire body. Apparently, the observed difference in scale-cover pattern between triploid and diploid linear fish was caused by different phenotypic expression of gene N/n. Due to incomplete dominance of allele N, triploids Nnn demonstrate less profound reduction of scale cover compared with diploids Nn. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

How the degree of instrumental practice in music increases perceptual sensitivity.

PubMed

Proverbio, Alice Mado; Bellini, Eleonora

2018-07-15

Literature has shown that playing a musical instrument is associated with the formation of multimodal audio visuomotor representations that are strongly instrument-specific. Here, we investigated the effect of increased motor practice on perceptual sensitivity in 32 professional musicians of comparable expertise but with different amounts of instrumental practice with piano (10,000 vs. 3000 estimated hours). Stimuli consisted of images of pianists' hands and piano arpeggio sounds. In half of the cases, the piano fingering and piano sounds were congruent, while they were incongruent in the other cases. ERPs were recorded from 128 sites while musicians performed a congruent vs. incongruent discrimination task. A fronto-central error-related negativity (ERN), mainly generated within the anterior cingulate cortex, was observed in response to incongruent videos only in pianists. Non-pianist musicians were able to carry out the task (with a worse performance) but exhibited a smaller response-related N400 to incongruent stimuli. Source reconstruction applied to ERP responses to incongruent stimuli indicated a less automatic mechanism for detecting sensory-motor deviance and a greater emphasis on visual rather than on acoustic features in non-pianists. Overall the data suggest a profound difference between the two populations of musicians and advise against considering "expert" populations to include those that undertook only a few weeks/months of training in a new discipline. Copyright © 2018 Elsevier B.V. All rights reserved.

Intra and Interspecific Variations of Gene Expression Levels in Yeast Are Largely Neutral: (Nei Lecture, SMBE 2016, Gold Coast).

PubMed

Yang, Jian-Rong; Maclean, Calum J; Park, Chungoo; Zhao, Huabin; Zhang, Jianzhi

2017-09-01

It is commonly, although not universally, accepted that most intra and interspecific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra and interspecific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Granger causality analysis reveals distinct spatio-temporal connectivity patterns in motor and perceptual visuo-spatial working memory.

PubMed

Protopapa, Foteini; Siettos, Constantinos I; Evdokimidis, Ioannis; Smyrnis, Nikolaos

2014-01-01

We employed spectral Granger causality analysis on a full set of 56 electroencephalographic recordings acquired during the execution of either a 2D movement pointing or a perceptual (yes/no) change detection task with memory and non-memory conditions. On the basis of network characteristics across frequency bands, we provide evidence for the full dissociation of the corresponding cognitive processes. Movement-memory trial types exhibited higher degree nodes during the first 2 s of the delay period, mainly at central, left frontal and right-parietal areas. Change detection-memory trial types resulted in a three-peak temporal pattern of the total degree with higher degree nodes emerging mainly at central, right frontal, and occipital areas. Functional connectivity networks resulting from non-memory trial types were characterized by more sparse structures for both tasks. The movement-memory trial types encompassed an apparent coarse flow from frontal to parietal areas while the opposite flow from occipital, parietal to central and frontal areas was evident for the change detection-memory trial types. The differences among tasks and conditions were more profound in α (8-12 Hz) and β (12-30 Hz) and less in γ (30-45 Hz) band. Our results favor the hypothesis which considers spatial working memory as a by-product of specific mental processes that engages common brain areas under different network organizations.

Triangulated Proxy Reporting: a technique for improving how communication partners come to know people with severe cognitive impairment.

PubMed

Lyons, Gordon; De Bortoli, Tania; Arthur-Kelly, Michael

2017-09-01

This paper explains and demonstrates the pilot application of Triangulated Proxy Reporting (TPR); a practical technique for enhancing communication around people who have severe cognitive impairment (SCI). An introduction explains SCI and how this impacts on communication; and consequently on quality of care and quality of life. This is followed by an explanation of TPR and its origins in triangulation research techniques. An illustrative vignette explicates its utility and value in a group home for a resident with profound multiple disabilities. The Discussion and Conclusion sections propose the wider application of TPR for different cohorts of people with SCIs, their communication partners and service providers. TPR presents as a practical technique for enhancing communication interactions with people who have SCI. The paper demonstrates the potential of the technique for improving engagement amongst those with profound multiple disabilities, severe acquired brain injury and advanced dementia and their partners in and across different care settings. Implications for Rehabilitation Triangulated Proxy Reporting (TPR) shows potential to improve communications between people with severe cognitive impairments and their communication partners. TPR can lead to improved quality of care and quality of life for people with profound multiple disabilities, very advanced dementia and severe acquired brain injury, who otherwise are very difficult to support. TPR is a relatively simple and inexpensive technique that service providers can incorporate into practice to improving communications between clients with severe cognitive impairments, their carers and other support professionals.

The Joint Operating Environment (JOE): Challenges and Implications for the Future Joint Force

DTIC Science & Technology

2008-11-25

the Nile and the Mesopotamian valleys were emerging. But those continuities and the cultural power of China’s civilization have...share a similar historical and cultural background, the mere fact of belligerence guarantees profound differences in attitudes, expectations...deep understanding of the enemy – his culture , history, geography, religious and ideological motivations, and particularly the huge differences

A Comparison of Multi-Age and Homogeneous Age Grouping in Early Childhood Centers.

ERIC Educational Resources Information Center

Freedman, Paula

Studies from several countries are described in this review of literature pertinent to assigning day care children to multi-age or homogeneous age groups. Three issues are discussed in this regard: (1) What difference does it make how one groups children? The answer is that a profound difference to children, staff, and parents may occur in terms…

The Deaf-Blind/Severely-Profoundly Handicapped: Proceedings from the 1978 Nebraska Statewide Conference, Nebraska Diagnostic Resource Center, Cozad, Nebraska.

ERIC Educational Resources Information Center

Clark, Douglas H., Ed.

The report presents the proceedings of a 1978 Nebraska statewide conference intitled "The Education and Training of the Deaf-Blind/Severely-Profoundly Handicapped." Titles and authors of the 13 papers presented include "Considerations for Full Educational Service for the Severely and Profoundly Handicapped" (N. Haring);…

An Examination of Specific Daily Living Skills Deficits in Adults with Profound Intellectual Disabilities

ERIC Educational Resources Information Center

Belva, Brian C.; Matson, Johnny L.

2013-01-01

While some researchers have investigated daily living skills deficits in individuals with intellectual disability (ID) as a whole, research on specific daily living skills in a profound ID population is limited. Two hundred and four adults with profound ID residing in two large developmental centers in the southeast portion of the United States…

Behavioral and Psychosocial Outcomes of a 16-Week Rebound Therapy-Based Exercise Program for People with Profound Intellectual Disabilities

ERIC Educational Resources Information Center

Jones, Martyn C.; Walley, Robert M.; Leech, Amanda; Paterson, Marion; Common, Stephanie; Metcalf, Charlotte

2007-01-01

People with profound intellectual disabilities rarely experience a physically active lifestyle, and their long-term physical inactivity likely contributes to poor health. The authors developed and implemented a pilot exercise program for persons with a profound intellectual disability and conducted a study to evaluate the effort. The development…

Sleep Studies of Adults with Severe or Profound Mental Retardation and Epilepsy.

ERIC Educational Resources Information Center

Espie, Colin A.; Paul, Audrey; McFie, Joyce; Amos, Pat; Hamilton, David; McColl, John H.; And Others

1998-01-01

A study of the sleep patterns of 28 people with severe or profound mental retardation and epilepsy found atypical sleep stages with significant depletion of REM sleep and a predominance of indiscriminate non-REM sleep. Sleep diaries completed by caregivers reveal lengthy sleep periods, especially among those with profound mental retardation.…

ProFound: Source Extraction and Application to Modern Survey Data

NASA Astrophysics Data System (ADS)

Robotham, A. S. G.

2018-04-01

ProFound detects sources in noisy images, generates segmentation maps identifying the pixels belonging to each source, and measures statistics like flux, size, and ellipticity. These inputs are key requirements of ProFit (ascl:1612.004), our galaxy profiling package; these two packages used in unison semi-automatically profile large samples of galaxies. The key novel feature introduced in ProFound is that all photometry is executed on dilated segmentation maps that fully contain the identifiable flux, rather than using more traditional circular or ellipse-based photometry. Also, to be less sensitive to pathological segmentation issues, the de-blending is made across saddle points in flux. ProFound offers good initial parameter estimation for ProFit, and also segmentation maps that follow the sometimes complex geometry of resolved sources, whilst capturing nearly all of the flux. A number of bulge-disc decomposition projects are already making use of the ProFound and ProFit pipeline.

Voices from the Unconscious

ERIC Educational Resources Information Center

Alper, Gerald

2005-01-01

The author, a Manhattan-based psychotherapist, contrasts the fascinating but profound differences between the autobiographical narratives of young college students and the free-associative unconscious voices of patients engaged in the process of psychotherapy. The author begins by recounting the immense impact of his own divorce upon his…

Societal Consequences of the g Factor in Employment.

ERIC Educational Resources Information Center

Gottfredson, Linda S.

1986-01-01

Reviews and rebuts seven common arguments that intelligence (g) is of little or no practical importance in employment. Illustrates in several ways the profound effect that differences in intelligence in a work force may have on the structure and functioning of whole societies. (Author/ABB)

Seeing Public Engagement Differently

ERIC Educational Resources Information Center

Willis, Jason

2010-01-01

The economic recession has had a profound effect on the ability of state and local governments to provide essential services to their communities--especially education. Stories about increased class sizes, personnel layoffs, and dwindling support for programs outside core classroom instruction have flooded newspapers around the country. Despite…

Which nature? A case study of Whitetop Mountain

Treesearch

David P. Robertson; R. Bruce Hull

2000-01-01

Nature is socially constructed and many different environmental conditions can be considered natural. These assertions have profound implications for landscape design, planning, and management. In our case study of Whitetop Mountain, we found four discrete but closely related natures - ecotourism, romanticism, pastoralism, and ecologism...

Injecting Cosmopolitanism into the Geography Classroom

ERIC Educational Resources Information Center

Warf, Barney

2015-01-01

Cosmopolitanism is an ethical, moral, and political philosophy with profound geographical implications. In extending circles of compassion to a worldwide scale, it encourages respect for difference, including the concerns of distant strangers. This essay outlines the precepts of cosmopolitanism, its historical development, and the challenges it…

The Australopithecus Afarensis (Lucy) of Higher Education.

ERIC Educational Resources Information Center

Gamble, John King

1999-01-01

Uses a fictitious character and story to express doubts about the use of business and marketing principles in American higher education. Asserts that higher education is profoundly different from other institutions, and that colleges and universities should be shielded from the vagaries of the market. (CAK)

Clinical-Physiological Considerations in Patients Undergoing Staged Palliation for a Functionally Single Ventricle.

PubMed

Penny, Daniel J; Krishnamurthy, Rajesh

2016-08-01

The objectives of this review are to discuss the pathophysiology of the circulation with a functionally univentricular heart, with a focus on the unique physiologic characteristics, which provide the underpinnings for the management of these complex patients. MEDLINE and PubMed. The circulation of the patient with a functionally univentricular heart displays unique physiologic characteristics, which are quite different from those of the normal biventricular circulation. There are profound differences within the heart itself in terms of ventricular function, interventricular interactions, and myocardial architecture, which are likely to have significant implications for the efficiency of ventricular ejection and metabolism. The coupling between the systemic ventricle and the aorta also displays unique features. The 3D orientation of the Fontan anastomosis itself can profoundly impact cardiac output, although the "portal" pulmonary arterial bed is a crucial determinant of overall cardiovascular function. As a result, disease-specific approaches to improve cardiovascular function are required at all stages during the care of these complex patients.

Transitioning hearing aid users with severe and profound loss to a new gain/frequency response: benefit, perception, and acceptance.

PubMed

Convery, Elizabeth; Keidser, Gitte

2011-03-01

Adults with severe and profound hearing loss tend to be long-term, full-time users of amplification who are highly reliant on their hearing aids. As a result of these characteristics, they are often reluctant to update their hearing aids when new features or signal-processing algorithms become available. Due to the electroacoustic constraints of older devices, many severely and profoundly hearing-impaired adults continue to wear hearing aids that provide more low- and mid-frequency gain and less high-frequency gain than would be prescribed by the National Acoustic Laboratories' revised formula with profound correction factor (NAL-RP). To investigate the effect of a gradual change in gain/frequency response on experienced hearing-aid wearers with moderately severe to profound hearing loss. Double-blind, randomized controlled trial. Twenty-three experienced adult hearing-aid users with severe and profound hearing loss participated in the study. Participants were selected for inclusion in the study if the gain/frequency response of their own hearing aids differed significantly from their NAL-RP prescription. Participants were assigned either to a control or to an experimental group balanced for aided ear three-frequency pure-tone average (PTA) and age. Participants were fitted with Siemens Artis 2 SP behind-the-ear (BTE) hearing aids that were matched to the gain/frequency response of their own hearing aids for a 65 dB SPL input level. The experimental group progressed incrementally to their NAL-RP targets over the course of 15 wk, while the control group maintained their initial settings throughout the study. Aided speech discrimination testing, loudness scaling, and structured questionnaires were completed at 3, 6, 9, 12, and 15 wk postfitting. A paired comparison between the old and new gain/frequency responses was completed at 1 and 15 wk postfitting. Statistical analysis was conducted to examine differences between the experimental and control groups and changes in objective performance and subjective perception over time. The results of the study showed that participants in the experimental group were subjectively accepting of the changes to their amplification characteristics, as evidenced by nonsignificant changes in the ratings of device performance over time. Perception of loudness, sound quality, speech intelligibility, and own voice volume did not change significantly throughout the study. Objectively, participants in the experimental group demonstrated poorer speech discrimination performance as the study progressed, although there was no change in objective loudness perception. According to the paired comparison, there was an overall subjective preference for the original gain/frequency response among all participants, although participants in the experimental group did show an increase in preference for the NAL-RP response by the end of the study. Based on the findings of this study, we suggest that undertaking a gradual change to a new gain/frequency response with severely and profoundly hearing-impaired adults is a feasible procedure. However, we recommend that clinicians select transition candidates carefully and initiate the procedure only if there is a clinical reason for doing so. A validated prescriptive formula should be used as a transition target, and speech discrimination performance should be monitored throughout the transition. American Academy of Audiology.

Domains of Quality of Life of People with Profound Multiple Disabilities: The Perspective of Parents and Direct Support Staff

ERIC Educational Resources Information Center

Petry, Katja; Maes, Bea; Vlaskamp, Carla

2005-01-01

Background: This study considered the general validity of the basic domains of quality of life that appear in theoretical models, in relation to people with profound multiple disabilities. The authors examined how parents and direct support staff operationalized these basic domains for people with profound multiple disabilities. They investigated…

Donald Campbell's doubt: cultural difference or failure of communication?

PubMed

Shweder, Richard A

2010-06-01

The objection, rightfully noted but then dismissed by Henrich et al., that the observed variation across populations "may be due to various methodological artifacts that arise from translating experiments across contexts" is a theoretically profound and potentially constructive criticism. It parallels Donald Campbell's concern that many cultural differences reported by psychologists "come from failures of communication misreported as differences." Ironically, Campbell's doubt is a good foundation for investigations in cultural psychology.

Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients

PubMed Central

Garçon, Loïc; Ge, Jingping; Manjunath, Shwetha H.; Mills, Jason A.; Apicella, Marisa; Parikh, Shefali; Sullivan, Lisa M.; Podsakoff, Gregory M.; Gadue, Paul; French, Deborah L.; Mason, Philip J.; Bessler, Monica

2013-01-01

Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the “safe harbor” AAVS1 locus alleviated abnormalities in ribosome biogenesis and hematopoiesis. Our studies show that pathological features of DBA are recapitulated by iPSCs, provide a renewable source of cells to model various tissue defects, and demonstrate proof of principle for genetic correction strategies in patient stem cells. PMID:23744582

Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients.

PubMed

Garçon, Loïc; Ge, Jingping; Manjunath, Shwetha H; Mills, Jason A; Apicella, Marisa; Parikh, Shefali; Sullivan, Lisa M; Podsakoff, Gregory M; Gadue, Paul; French, Deborah L; Mason, Philip J; Bessler, Monica; Weiss, Mitchell J

2013-08-08

Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the "safe harbor" AAVS1 locus alleviated abnormalities in ribosome biogenesis and hematopoiesis. Our studies show that pathological features of DBA are recapitulated by iPSCs, provide a renewable source of cells to model various tissue defects, and demonstrate proof of principle for genetic correction strategies in patient stem cells.

Rhythm Defects Caused by Newly Engineered Null Mutations in Drosophila's cryptochrome Gene

PubMed Central

Dolezelova, Eva; Dolezel, David; Hall, Jeffrey C.

2007-01-01

Much of the knowledge about cryptochrome function in Drosophila stems from analyzing the cryb mutant. Several features of this variant's light responsiveness imply either that CRYb retains circadian-photoreceptive capacities or that additional CRY-independent light-input routes subserve these processes. Potentially to resolve these issues, we generated cry knock-out mutants (cry0's) by gene replacement. They behaved in an anomalously rhythmic manner in constant light (LL). However, cry0 flies frequently exhibited two separate circadian components in LL, not observed in most previous cryb analyses. Temperature-dependent circadian phenotypes exhibited by cry0 flies suggest that CRY is involved in core pacemaking. Further locomotor experiments combined cry0 with an externally blinding mutation (norpAP24), which caused the most severe decrements of circadian photoreception observed so far. cryb cultures were shown previously to exhibit either aperiodic or rhythmic eclosion in separate studies. We found cry0 to eclose in a solidly periodic manner in light:dark cycles or constant darkness. Furthermore, both cry0 and cryb eclosed rhythmically in LL. These findings indicate that the novel cry0 type causes more profound defects than does the cryb mutation, implying that CRYb retains residual activity. Because some norpAP24 cry0 individuals can resynchronize to novel photic regimes, an as-yet undetermined light-input route exists in Drosophila. PMID:17720919

Lip-Reading by Deaf and Hearing Children

ERIC Educational Resources Information Center

Conradm, R.

1977-01-01

A group of profoundly deaf 15-year-old subjects with no other handicap and of average non-verbal intelligence were given a lip-reading test. The same test was given to comparable hearing subjects "deafened" by white noise masking. The difference between the groups was not significant. (Editor)

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements

EPA Science Inventory

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, ...

Pain Assessment in People with Profound Intellectual and Multiple Disabilities; a Pilot Study into the Use of the Pain Behaviour Checklist in Everyday Practice

ERIC Educational Resources Information Center

van der Putten, Annette; Vlaskamp, Carla

2011-01-01

Because of their physical and general health problems, people with a combination of profound intellectual and severe or profound motor disabilities (PIMD) are at risk of pain-related medical conditions. They are fully dependent on support professionals for the detection and accurate interpretation of nonverbal pain behaviour. These professionals…

The Neuropeptides FLP-2 and PDF-1 Act in Concert To Arouse Caenorhabditis elegans Locomotion.

PubMed

Chen, Didi; Taylor, Kelsey P; Hall, Qi; Kaplan, Joshua M

2016-11-01

During larval molts, Caenorhabditis elegans exhibits a sleep-like state (termed lethargus) that is characterized by the absence of feeding and profound locomotion quiescence. The rhythmic pattern of locomotion quiescence and arousal linked to the molting cycle is mediated by reciprocal changes in sensory responsiveness, whereby arousal is associated with increased responsiveness. Sensory neurons arouse locomotion via release of a neuropeptide (PDF-1) and glutamate. Here we identify a second arousing neuropeptide (FLP-2). We show that FLP-2 acts via an orexin-like receptor (FRPR-18), and that FLP-2 and PDF-1 secretion are regulated by reciprocal positive feedback. These results suggest that the aroused behavioral state is stabilized by positive feedback between two neuropeptides. Copyright © 2016 by the Genetics Society of America.

Peroxisome Proliferator-Activated Receptors (PPARs) as Potential Inducers of Antineoplastic Effects in CNS Tumors

PubMed Central

Tatenhorst, Lars; Hahnen, Eric; Heneka, Michael T.

2008-01-01

The peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS). The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy. PMID:18725982

Chimera states in multi-strain epidemic models with temporary immunity

NASA Astrophysics Data System (ADS)

Bauer, Larissa; Bassett, Jason; Hövel, Philipp; Kyrychko, Yuliya N.; Blyuss, Konstantin B.

2017-11-01

We investigate a time-delayed epidemic model for multi-strain diseases with temporary immunity. In the absence of cross-immunity between strains, dynamics of each individual strain exhibit emergence and annihilation of limit cycles due to a Hopf bifurcation of the endemic equilibrium, and a saddle-node bifurcation of limit cycles depending on the time delay associated with duration of temporary immunity. Effects of all-to-all and non-local coupling topologies are systematically investigated by means of numerical simulations, and they suggest that cross-immunity is able to induce a diverse range of complex dynamical behaviors and synchronization patterns, including discrete traveling waves, solitary states, and amplitude chimeras. Interestingly, chimera states are observed for narrower cross-immunity kernels, which can have profound implications for understanding the dynamics of multi-strain diseases.

Perk Gene Dosage Regulates Glucose Homeostasis by Modulating Pancreatic β-Cell Functions

PubMed Central

Wang, Rong; Munoz, Elyse E.; Zhu, Siying; McGrath, Barbara C.; Cavener, Douglas R.

2014-01-01

Background Insulin synthesis and cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in either aspect leads to development of diabetes. PERK (EIF2AK3) loss of function mutations in humans and mice exhibit permanent neonatal diabetes that is characterized by insufficient β-cell mass and reduced proinsulin trafficking and insulin secretion. Unexpectedly, we found that Perk heterozygous mice displayed lower blood glucose levels. Methodology Longitudinal studies were conducted to assess serum glucose and insulin, intracellular insulin synthesis and storage, insulin secretion, and β-cell proliferation in Perk heterozygous mice. In addition, modulation of Perk dosage specifically in β-cells showed that the glucose homeostasis phenotype of Perk heterozygous mice is determined by reduced expression of PERK in the β-cells. Principal Findings We found that Perk heterozygous mice first exhibited enhanced insulin synthesis and secretion during neonatal and juvenile development followed by enhanced β-cell proliferation and a substantial increase in β-cell mass at the adult stage. These differences are not likely to entail the well-known function of PERK to regulate the ER stress response in cultured cells as several markers for ER stress were not differentially expressed in Perk heterozygous mice. Conclusions In addition to the essential functions of PERK in β-cells as revealed by severely diabetic phenotype in humans and mice completely deficient for PERK, reducing Perk gene expression by half showed that intermediate levels of PERK have a profound impact on β-cell functions and glucose homeostasis. These results suggest that an optimal level of PERK expression is necessary to balance several parameters of β-cell function and growth in order to achieve normoglycemia. PMID:24915520

Hybrid marriages and phenotypic heterosis in offspring: Evidence from China.

PubMed

Zhu, Chen; Zhang, Xiaohui; Zhao, Qiran; Chen, Qihui

2018-05-01

In genetics, heterosis refers to the phenomenon that cross-breeding within species leads to offspring that are genetically fitter than their parents and exhibit improved phenotypic characteristics. Based on the theory of heterosis and existing genetic evidence, offspring of "hybrid" marriages (spouses originating from different states/provinces/countries/areas), though relatively rare due to physical boundaries, may exhibit greater genetic fitness in terms of intelligence, height, or physical attractiveness (the "distance-performance" hypothesis). This study explores whether heterosis is a contributing factor to offspring's educational attainment in China by applying a high-dimensional fixed effects (HDFE) modelling framework to the unique 0.1% micro-sample of the 2000 Chinese Population Census data. Concerning potential endogeneity of hybrid marriages, we conduct a series of robustness checks. Reassuringly, the estimated heterosis effect remains significantly positive across various measurements, after controlling for parental educational attainments/height, environmental influences, and over a thousand region and region-by-year fixed effects. The effects in male and higher-educated offspring are found to be stronger. Results are replicated when analyzing body height using data from the China Health and Nutrition Survey. Although endogeneity of "hybrid marriages" may not be completely ruled out, the current study sheds light on the potentially beneficial effects of interprovincial migration on population-level human capital accumulation, and we hope that this paper can intrigue future studies that further address endogeneity. The implied heterosis effect could, therefore, be profound for Homo sapiens as a species from an evolutionary point of view. An additional important implication is that the overall genetic influences of parents on offspring's performance may be further decomposed into a conventional heredity effect and a heterosis effect that has been neglected previously. Copyright © 2018 Elsevier B.V. All rights reserved.

Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep-Wake Physiology.

PubMed

Thomas, Alexia M; Schwartz, Michael D; Saxe, Michael D; Kilduff, Thomas S

2017-01-01

Although recent innovations have enabled modification of the rat genome, it is unclear whether enhanced utility of rodents as human disease models will result. We compared electroencephalogram (EEG) and behavioral phenotypes of rats and mice with homozygous deletion of Cntnap2, a gene associated with cortical dysplasia-focal epilepsy (CDFE) and autism spectrum disorders (ASD). Male contactin-associated protein-like 2 (Cntnap2) knockout (KO) and wild-type (WT) rats and male Cntnap2 KO and WT mice were implanted with telemeters to record EEG, electromyogram, body temperature, and locomotor activity. Animals were subjected to a test battery for ASD-related behaviors, followed by 24-hr EEG recordings that were analyzed for sleep-wake parameters and subjected to spectral analysis. Cntnap2 KO rats exhibited severe motor seizures, hyperactivity, and increased consolidation of wakefulness and REM sleep. By contrast, Cntnap2 KO mice demonstrated absence seizure-like events, hypoactivity, and wake fragmentation. Although seizures observed in Cntnap2 KO rats were more similar to those in CDFE patients than in KO mice, neither model fully recapitulated the full spectrum of disease symptoms. However, KOs in both species had reduced spectral power in the alpha (9-12 Hz) range during wake, suggesting a conserved EEG biomarker. Deletion of Cntnap2 impacts similar behaviors and EEG measures in rats and mice, but with profound differences in nature and phenotypic severity. These observations highlight the importance of cross-species comparisons to understand conserved gene functions and the limitations of single- species models to provide translational insights relevant to human diseases. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans

PubMed Central

Hall, Sarah E.; Chirn, Gung-Wei; Lau, Nelson C.; Sengupta, Piali

2013-01-01

Early environmental experiences profoundly influence adult phenotypes through complex mechanisms that are poorly understood. We previously showed that adult Caenorhabditis elegans that transiently passed through the stress-induced dauer larval stage (post-dauer adults) exhibit significant changes in gene expression profiles, chromatin states, and life history traits when compared with adults that bypassed the dauer stage (control adults). These wild-type, isogenic animals of equivalent developmental stages exhibit different signatures of molecular marks that reflect their distinct developmental trajectories. To gain insight into the mechanisms that contribute to these developmental history-dependent phenotypes, we profiled small RNAs from post-dauer and control adults by deep sequencing. RNA interference (RNAi) pathways are known to regulate genome-wide gene expression both at the chromatin and post-transcriptional level. By quantifying changes in endogenous small interfering RNA (endo-siRNA) levels in post-dauer as compared with control animals, our analyses identified a subset of genes that are likely targets of developmental history-dependent reprogramming through a complex RNAi-mediated mechanism. Mutations in specific endo-siRNA pathways affect expected gene expression and chromatin state changes for a subset of genes in post-dauer animals, as well as disrupt their increased brood size phenotype. We also find that both chromatin state and endo-siRNA distribution in dauers are unique, and suggest that remodeling in dauers provides a template for the subsequent establishment of adult post-dauer profiles. Our results indicate a role for endo-siRNA pathways as a contributing mechanism to early experience-dependent phenotypic plasticity in adults, and describe how developmental history can program adult physiology and behavior via epigenetic mechanisms. PMID:23329696

Temporal factors in the extinction of fear in inbred mouse strains differing in extinction efficacy.

PubMed

MacPherson, Kathryn; Whittle, Nigel; Camp, Marguerite; Gunduz-Cinar, Ozge; Singewald, Nicolas; Holmes, Andrew

2013-07-05

Various neuropsychiatric conditions, including posttraumatic stress disorder (PTSD), are characterized by deficient fear extinction, but individuals differ greatly in risk for these. While there is growing evidence that fear extinction is influenced by certain procedural variables, it is unclear how these influences might vary across individuals and subpopulations. To model individual differences in fear extinction, prior studies identified a strain of inbred mouse, 129S1/SvImJ (S1), which exhibits a profound deficit in fear extinction, as compared to other inbred strains, such as C57BL/6J (B6). Here, we assessed the effects of procedural variables on the impaired extinction phenotype of the S1 strain and, by comparison, the extinction-intact B6 strain. The variables studied were 1) the interval between conditioning and extinction, 2) the interval between cues during extinction training, 3) single-cue exposure before extinction training, and 4) extinction of a second-order conditioned cue. Conducting extinction training soon after ('immediately') conditioning attenuated fear retrieval in S1 mice and impaired extinction in B6 mice. Spacing cue presentations with long inter-trial intervals during extinction training augmented fear in S1 and B6 mice. The effect of spacing was lost with one-trial fear conditioning in B6, but not S1 mice. A single exposure to a conditioned cue before extinction training did not alter extinction retrieval, either in B6 or S1 mice. Both the S1 and B6 strains exhibited robust second-order fear conditioning, in which a cue associated with footshock was sufficient to serve as a conditioned exciter to condition a fear association to a second cue. B6 mice extinguished the fear response to the second-order conditioned cue, but S1 mice failed to do so. These data provide further evidence that fear extinction is strongly influenced by multiple procedural variables and is so in a highly strain-dependent manner. This suggests that the efficacy of extinction-based behavioral interventions, such as exposure therapy, for trauma-related anxiety disorders will be determined by the procedural parameters employed and the degree to which the patient can extinguish.

Why Learning Not Education?--Analysis of Transnational Education Policies in the Age of Globalization

ERIC Educational Resources Information Center

Mandal, Sayantan

2012-01-01

The profound influence of globalization seems helping outshine the concept of "education" with the more flexible notion of "learning" in the education policies of major transnational organizations. With considerable differences in concepts, all of them are promoting "learning", more specifically LLL (lifelong…

Classical Conditioning of Profoundly Retarded, Multiply Handicapped Children.

ERIC Educational Resources Information Center

Hogg, J.; And Others

1979-01-01

Conditioning was established for the two most developmentally advanced Ss, and the intermediate pair showed different patterns of orienting response to the conditioned stimulus but no evidence of conditioning. The fifth and most developmentally delayed child did not respond to the stimuli. Journal Availability: J. B. Lippincott Co., East…

Neural Correlates of Machiavellian Strategies in a Social Dilemma Task

ERIC Educational Resources Information Center

Bereczkei, Tamas; Deak, Anita; Papp, Peter; Perlaki, Gabor; Orsi, Gergely

2013-01-01

In spite of having deficits in various areas of social cognition, especially in mindreading, Machiavellian individuals are typically very successful in different tasks, including solving social dilemmas. We assume that a profound examination of neural structures associated with decision-making processes is needed to learn more about…

Effects Associated with Leadership Program Participation in International Students Compared to Domestic Students

ERIC Educational Resources Information Center

Collier, Daniel A.; Rosch, David M.

2016-01-01

International student enrollment in the U.S. higher education system has recently experienced profound growth. This research examines leadership-oriented differences between international and domestic students and focuses on their growth in capacity associated with participation in co-curricular leadership programs. Similarly-sized gains emerged…

Math in the Margins: Writing across Curricula into Community Heritage

ERIC Educational Resources Information Center

Sunstein, Bonnie S.; Liu, Rossina Zamora; Hunsicker, Arthur W.; Baker, Deidra F.

2012-01-01

Imagine two classfuls of American high school students, separated by 1,500 miles and profound differences in local cultures (East Coast urban and Midwestern rural) as they correspond and collaborate in writing between their geometry classes. Reading the students' observations, one sees authentic voice, specific detail, precise language, what…

Adult Education, Narratives and Cultural Values

ERIC Educational Resources Information Center

Barbosa, Fatima; Amaral, Maria do Rosario

2010-01-01

Nowadays we are experiencing profound economic and social changes, which cause new and different migratory fluxes in the search for better living conditions. In this manner, the human tissue that composes societies is getting diverse. Therefore we can now find new minorities originating from immigration, whose members possess ethnic, religious,…

MICROARRAY QUALITY CONTROL PROJECT: A COMPREHENSIVE GENE EXPRESSION TECHNOLOGY SURVEY DEMONSTRATES MEASURABLE CONSISTENCY AND CONCORDANT RESULTS BETWEEN PLATFORMS

EPA Science Inventory

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, h...

Environmental Design for a Structured Network Learning Society

ERIC Educational Resources Information Center

Chang, Ben; Cheng, Nien-Heng; Deng, Yi-Chan; Chan, Tak-Wai

2007-01-01

Social interactions profoundly impact the learning processes of learners in traditional societies. The rapid rise of the Internet using population has been the establishment of numerous different styles of network communities. Network societies form when more Internet communities are established, but the basic form of a network society, especially…

Contemporary Psychoanalytic Perspectives on Eating Disorders: A Case Illustration.

ERIC Educational Resources Information Center

Lerner, Howard D.

This paper examines recent formulations derived from different lines of conceptual development within psychoanalytic theory in relation to the anorexic and bulimic syndromes. The case history, clinical picture, and course of treatment of a bulimic adolescent girl are reviewed. This discussion illustrates the profound consequences upon cognition of…

What Are They Doing to Carl Rogers?

ERIC Educational Resources Information Center

Mader, Diane C.

1980-01-01

Notes that recent composition textbooks have classified Carl Rogers' work as a new rhetoric or as an alternative to classical argument. Demonstrates that to portray Rogers' method as a form of argument is to misunderstand his intent and that, while Rogers and Aristotle are similar superficially, their differences are profound. (FL)

Bidirectional Effects of Mother-Young Contact on the Maternal and Neonatal Brains.

PubMed

González-Mariscal, Gabriela; Melo, Angel I

2017-01-01

Adaptive plasticity occurs intensely during the early postnatal period through processes like proliferation, migration, differentiation, synaptogenesis, myelination and apoptosis. Exposure to particular stimuli during this critical period has long-lasting effects on cognition, stress reactivity and behavior. Maternal care is the main source of social, sensory and chemical stimulation to the young and is, therefore, critical to "fine-tune" the offspring's neural development. Mothers providing a low quantity or quality of stimulation produce offspring that will exhibit reduced cognitive performance, impaired social affiliation and increased agonistic behaviors. Transgenerational transmission of such traits occurs epigenetically, i.e., through mechanisms like DNA methylation and post-translational modification of nucleosomal histones, processes that silence or increase gene expression without affecting the DNA sequence. Reciprocally, providing maternal care profoundly affects the behavior, learning, memory and fine neuroanatomy of the adult female. Such effects are in many cases permanent and sometimes they involve the hormones of pregnancy and lactation. The above evidence supports the idea that the mother-young dyad exerts profound and permanent effects on the brains of both adult and developing organisms, respectively. Effects on the latter can be explained by the neural developmental processes taking place during the early postnatal period. In contrast, little is known about the mechanisms mediating the plasticity of the adult maternal brain. The bidirectional effects that mother and young exert on each other's brains exemplify a remarkable plasticity of this organ for organizing itself and provide an immense source of variability for adaptation and evolution in mammals.

[Etiological, clinical and neuroradiological investigation of deaf children with additional neuropsychiatric disabilities].

PubMed

Chilosi, A M; Scusa, M F; Comparini, A; Genovese, E; Forli, F; Berrettini, S; Cipriani, P

2012-04-01

Sensorineural hearing loss (SNHL) is complicated by additional disabilities in about 30% of cases, but the epidemiology of associated disorders, in terms of type, frequency and aetiology is still not clearly defined. Additional disabilities in a deaf child have important consequences in assessing and choosing a therapeutic treatment, in particular when considering cochlear implantation (CI) or hearing aids (HA). The aim of this paper was to evaluate frequency, type and severity of additional neurodevelopmental disabilities in children with profound bilateral sensorineural hearing loss and to investigate the relationship between disability and the etiology of deafness. Eighty children with profound bilateral sensorineural hearing loss (mean age 5.4 years) were investigated by means of a diagnostic protocol including clinical, neurodevelopmental, and audiological procedures together with genetic and neurometabolic tests and neuroradiological investigation by brain MRI. Fifty-five percent of the sample exhibited one or more disabilities in addition to deafness, with cognitive, behavioural-emotional and motor disorders being the most frequent. The risk of additional disabilities varied according to aetiology, with a higher incidence in hereditary syndromic deafness, in cases due to pre-perinatal pathology (in comparison to unknown and hereditary non syndromic forms) and in the presence of major brain abnormalities at MRI. Our results suggest that the aetiology of deafness may be a significant risk indicator for the presence of neuropsychiatric disorders. A multidimensional evaluation, including aetiological, neurodevelopmental and MRI investigation is needed for formulating prognosis and for planning therapeutic intervention, especially in those children candidated to cochlear implant.

Endogenous sterol biosynthesis is important for mitochondrial function and cell morphology in procyclic forms of Trypanosoma brucei.

PubMed

Pérez-Moreno, Guiomar; Sealey-Cardona, Marco; Rodrigues-Poveda, Carlos; Gelb, Michael H; Ruiz-Pérez, Luis Miguel; Castillo-Acosta, Víctor; Urbina, Julio A; González-Pacanowska, Dolores

2012-10-01

Sterol biosynthesis inhibitors are promising entities for the treatment of trypanosomal diseases. Insect forms of Trypanosoma brucei, the causative agent of sleeping sickness, synthesize ergosterol and other 24-alkylated sterols, yet also incorporate cholesterol from the medium. While sterol function has been investigated by pharmacological manipulation of sterol biosynthesis, molecular mechanisms by which endogenous sterols influence cellular processes remain largely unknown in trypanosomes. Here we analyse by RNA interference, the effects of a perturbation of three specific steps of endogenous sterol biosynthesis in order to dissect the role of specific intermediates in proliferation, mitochondrial function and cellular morphology in procyclic cells. A decrease in the levels of squalene synthase and squalene epoxidase resulted in a depletion of cellular sterol intermediates and end products, impaired cell growth and led to aberrant morphologies, DNA fragmentation and a profound modification of mitochondrial structure and function. In contrast, cells deficient in sterol methyl transferase, the enzyme involved in 24-alkylation, exhibited a normal growth phenotype in spite of a complete abolition of the synthesis and content of 24-alkyl sterols. Thus, the data provided indicates that while the depletion of squalene and post-squalene endogenous sterol metabolites results in profound cellular defects, bulk 24-alkyl sterols are not strictly required to support growth in insect forms of T. brucei in vitro. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Work preferences, life values, and personal views of top math/science graduate students and the profoundly gifted: Developmental changes and gender differences during emerging adulthood and parenthood.

PubMed

Ferriman, Kimberley; Lubinski, David; Benbow, Camilla P

2009-09-01

Work preferences, life values, and personal views of top math/science graduate students (275 men, 255 women) were assessed at ages 25 and 35 years. In Study 1, analyses of work preferences revealed developmental changes and gender differences in priorities: Some gender differences increased over time and increased more among parents than among childless participants, seemingly because the mothers' priorities changed. In Study 2, gender differences in the graduate students' life values and personal views at age 35 were compared with those of profoundly gifted participants (top 1 in 10,000, identified by age 13 and tracked for 20 years: 265 men, 84 women). Again, gender differences were larger among parents. Across both cohorts, men appeared to assume a more agentic, career-focused perspective than women did, placing more importance on creating high-impact products, receiving compensation, taking risks, and gaining recognition as the best in their fields. Women appeared to favor a more communal, holistic perspective, emphasizing community, family, friendships, and less time devoted to career. Gender differences in life priorities, which intensify during parenthood, anticipated differential male-female representation in high-level and time-intensive careers, even among talented men and women with similar profiles of abilities, vocational interests, and educational experiences. (c) 2009 APA, all rights reserved).

Unilateral Hearing Loss: Understanding Speech Recognition and Localization Variability-Implications for Cochlear Implant Candidacy.

PubMed

Firszt, Jill B; Reeder, Ruth M; Holden, Laura K

At a minimum, unilateral hearing loss (UHL) impairs sound localization ability and understanding speech in noisy environments, particularly if the loss is severe to profound. Accompanying the numerous negative consequences of UHL is considerable unexplained individual variability in the magnitude of its effects. Identification of covariables that affect outcome and contribute to variability in UHLs could augment counseling, treatment options, and rehabilitation. Cochlear implantation as a treatment for UHL is on the rise yet little is known about factors that could impact performance or whether there is a group at risk for poor cochlear implant outcomes when hearing is near-normal in one ear. The overall goal of our research is to investigate the range and source of variability in speech recognition in noise and localization among individuals with severe to profound UHL and thereby help determine factors relevant to decisions regarding cochlear implantation in this population. The present study evaluated adults with severe to profound UHL and adults with bilateral normal hearing. Measures included adaptive sentence understanding in diffuse restaurant noise, localization, roving-source speech recognition (words from 1 of 15 speakers in a 140° arc), and an adaptive speech-reception threshold psychoacoustic task with varied noise types and noise-source locations. There were three age-sex-matched groups: UHL (severe to profound hearing loss in one ear and normal hearing in the contralateral ear), normal hearing listening bilaterally, and normal hearing listening unilaterally. Although the normal-hearing-bilateral group scored significantly better and had less performance variability than UHLs on all measures, some UHL participants scored within the range of the normal-hearing-bilateral group on all measures. The normal-hearing participants listening unilaterally had better monosyllabic word understanding than UHLs for words presented on the blocked/deaf side but not the open/hearing side. In contrast, UHLs localized better than the normal-hearing unilateral listeners for stimuli on the open/hearing side but not the blocked/deaf side. This suggests that UHLs had learned strategies for improved localization on the side of the intact ear. The UHL and unilateral normal-hearing participant groups were not significantly different for speech in noise measures. UHL participants with childhood rather than recent hearing loss onset localized significantly better; however, these two groups did not differ for speech recognition in noise. Age at onset in UHL adults appears to affect localization ability differently than understanding speech in noise. Hearing thresholds were significantly correlated with speech recognition for UHL participants but not the other two groups. Auditory abilities of UHLs varied widely and could be explained only in part by hearing threshold levels. Age at onset and length of hearing loss influenced performance on some, but not all measures. Results support the need for a revised and diverse set of clinical measures, including sound localization, understanding speech in varied environments, and careful consideration of functional abilities as individuals with severe to profound UHL are being considered potential cochlear implant candidates.

Physical disturbance shapes vascular plant diversity more profoundly than fire in the sagebrush steppe of southeastern Idaho, U.S.A

PubMed Central

Lavin, Matt; Brummer, Tyler J; Quire, Ryan; Maxwell, Bruce D; Rew, Lisa J

2013-01-01

Fire is thought to profoundly change the ecology of the sagebrush steppe. The Idaho National Laboratory provides an ideal setting to compare the effects of fire and physical disturbance on plant diversity in high-native-cover sagebrush steppe. Seventy-eight 1-hectare transects were established along paved, green-striped, gravel, and two-track roads, in overgrazed rangeland, and within sagebrush steppe involving different fire histories. Transects were sampled for the diversity and abundance of all vascular plants. Alpha, beta, and phylogenetic beta diversity were analyzed as a response to fire and physical disturbance. Postfire vegetation readily rebounds to prefire levels of alpha plant diversity. Physical disturbance, in contrast, strongly shapes patterns of alpha, beta, and especially phylogenetic beta diversity much more profoundly than fire disturbance. If fire is a concern in the sagebrush steppe then the degree of physical-disturbance should be more so. This finding is probably not specific to the study area but applicable to the northern and eastern portions of the sagebrush biome, which is characterized by a pulse of spring moisture and cold mean minimum winter temperatures. The distinction of sagebrush steppe from Great Basin sagebrush should be revised especially with regard to reseeding efforts and the control of annual grasses. PMID:23789073

Physical disturbance shapes vascular plant diversity more profoundly than fire in the sagebrush steppe of southeastern Idaho, U.S.A.

PubMed

Lavin, Matt; Brummer, Tyler J; Quire, Ryan; Maxwell, Bruce D; Rew, Lisa J

2013-06-01

Fire is thought to profoundly change the ecology of the sagebrush steppe. The Idaho National Laboratory provides an ideal setting to compare the effects of fire and physical disturbance on plant diversity in high-native-cover sagebrush steppe. Seventy-eight 1-hectare transects were established along paved, green-striped, gravel, and two-track roads, in overgrazed rangeland, and within sagebrush steppe involving different fire histories. Transects were sampled for the diversity and abundance of all vascular plants. Alpha, beta, and phylogenetic beta diversity were analyzed as a response to fire and physical disturbance. Postfire vegetation readily rebounds to prefire levels of alpha plant diversity. Physical disturbance, in contrast, strongly shapes patterns of alpha, beta, and especially phylogenetic beta diversity much more profoundly than fire disturbance. If fire is a concern in the sagebrush steppe then the degree of physical-disturbance should be more so. This finding is probably not specific to the study area but applicable to the northern and eastern portions of the sagebrush biome, which is characterized by a pulse of spring moisture and cold mean minimum winter temperatures. The distinction of sagebrush steppe from Great Basin sagebrush should be revised especially with regard to reseeding efforts and the control of annual grasses.

P300 in individuals with sensorineural hearing loss.

PubMed

Reis, Ana Cláudia Mirandola Barbosa; Frizzo, Ana Claudia Figueiredo; Isaac, Myriam de Lima; Garcia, Cristiane Fregonesi Dutra; Funayama, Carolina Araújo Rodrigues; Iório, Maria Cecília Martinelli

2015-01-01

Behavioral and electrophysiological auditory evaluations contribute to the understanding of the auditory system and of the process of intervention. To study P300 in subjects with severe or profound sensorineural hearing loss. This was a descriptive cross-sectional prospective study. It included 29 individuals of both genders with severe or profound sensorineural hearing loss without other type of disorders, aged 11 to 42 years; all were assessed by behavioral audiological evaluation and auditory evoked potentials. A recording of the P3 wave was obtained in 17 individuals, with a mean latency of 326.97ms and mean amplitude of 3.76V. There were significant differences in latency in relation to age and in amplitude according to degree of hearing loss. There was a statistically significant association of the P300 results with the degrees of hearing loss (p=0.04), with the predominant auditory communication channels (p<0.0001), and with time of hearing loss. P300 can be recorded in individuals with severe and profound congenital sensorineural hearing loss; it may contribute to the understanding of cortical development and is a good predictor of the early intervention outcome. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Neuro-overprotection? A functional evaluation of clomethiazole-induced neuroprotection following hypoxic-ischemic injury.

PubMed

Gilby, K L; Kelly, M E; McIntyre, D C; Robertson, H A

2005-01-01

Hypoxic-ischemic (H-I) injury produces extensive damage to the hippocampus of young rats. We have recently shown that administration of 125 mg kg-1 clomethiazole (CMZ), a GABA(A)-agonist, provides complete histological protection against H-I injury if administered 3 h post-H-I (Brain Res 1035 (2005) 194). However, whether that histological protection translates into lasting functional preservation is unclear. To determine whether hippocampal-based circuits remain functionally intact in CMZ-protected H-I rats, we administered 125 mg kg-1 (high dose [CMZ-HD]) or 65 mg kg-1 (low dose [CMZ-LD]) CMZ, 3 h post-H-I, and examined numerous kindling parameters in the dorsal hippocampus 60 days following H-I. Kindling parameters included afterdischarge (AD) thresholds (ADTs), AD durations and kindling rates. Additional groups assessed included vehicle-injected H-I (VIH), hypoxic, ligated and naive rats. VIH, CMZ-HD, CMZ-LD and hypoxic rats all exhibited significantly faster kindling rates than naive rats. Thus, a previous traumatic event, even hypoxia alone, facilitated subsequent seizure propagation. Still, a significantly slower kindling rate was evident in CMZ-HD rats than in hypoxic, VIH or CMZ-LD rats. Moreover, while longer pre-kindling AD durations were observed in the damaged hippocampus of VIH compared with naive rats, this was not true for either CMZ-treated groups, hypoxic or ligated rats. Collectively, these findings suggest CMZ can suppress the epileptogenic effects of H-I. Surprisingly, however, both groups of CMZ-treated rats exhibited a four to nine times greater ADT than any other group and this effect was most profound in the CMZ-protected hippocampus. Thus, CMZ administration protected local neurons against terminal insult and left network excitability relatively normal with respect to seizure offset mechanisms but also caused profound elevation of local ADTs, which suggests a local hypoexcitability/increased inhibition. Finally, this study demonstrates, for the first time, that the kindling model can serve as a sensitive measure of function-related neuroprotective efficacy in animal models of ischemia.

Differences in mental health among young adults with borderline personality symptoms of various severities.

PubMed

Lu, Wei-Hsin; Wang, Peng-Wei; Ko, Chih-Hung; Hsiao, Ray C; Liu, Tai-Ling; Yen, Cheng-Fang

2018-04-01

This study examined the differences in mental health and behavioral problems among young adults with borderline personality symptoms of various severities. 500 college students participated in this study. Borderline personality symptoms were evaluated using the Taiwanese version of the Borderline Symptom List (BSL-23). Mental health problems were assessed using the Symptom Checklist-90-Revised Scale. Suicidality and other behavioral problems were assessed using questions from the epidemiological version of the Kiddie Schedule for Affective Disorders and Schizophrenia and BSL-23 Supplement. According to the distribution of BSL-23 scores at the 25th, 50th, and 75th percentiles, the participants were divided into 4 groups: No/Mild, Moderate, Severe, and Profound. Analysis of variance and the chi-square test were used to compare mental health and behavioral problems among the 4 groups. All mental health problems differed significantly among the 4 groups. The severity of nearly all mental health problems increased with that of borderline personality symptoms. The proportions of most behavioral problems differed significantly among the 4 groups. The Profound group was more likely to have behavioral problems than the other 3 groups. Young adults who had more severe borderline personality symptoms had more severe mental health and behavioral problems. Copyright © 2017. Published by Elsevier B.V.

Reproductive performance and gestational effort in relation to dietary fatty acids in guinea pigs.

PubMed

Nemeth, Matthias; Millesi, Eva; Siutz, Carina; Wagner, Karl-Heinz; Quint, Ruth; Wallner, Bernard

2017-01-01

Dietary saturated (SFAs) and polyunsaturated (PUFAs) fatty acids can highly affect reproductive functions by providing additional energy, modulating the biochemical properties of tissues, and hormone secretions. In precocial mammals such as domestic guinea pigs the offspring is born highly developed. Gestation might be the most critical reproductive period in this species and dietary fatty acids may profoundly influence the gestational effort. We therefore determined the hormonal status at conception, the reproductive success, and body mass changes during gestation in guinea pigs maintained on diets high in PUFAs or SFAs, or a control diet. The diets significantly affected the females' plasma fatty acid status at conception, while cortisol and estrogen levels did not differ among groups. SFA females exhibited a significantly lower body mass and litter size, while the individual birth mass of pups did not differ among groups and a general higher pup mortality rate in larger litters was diminished by PUFAs and SFAs. The gestational effort, determined by a mother's body mass gain during gestation, increased with total litter mass, whereas this increase was lowest in SFA and highest in PUFA individuals. The mother's body mass after parturition did not differ among groups and was positively affected by the total litter mass in PUFA females. While SFAs reduce the litter size, but also the gestational effort as a consequence, PUFA supplementation may contribute to an adjustment of energy accumulations to the total litter mass, which may both favor a mother's body condition at parturition and perhaps increase the offspring survival at birth.

Diverse Responses of Belowground Internal Nitrogen Cycling to Increasing Aridity

NASA Astrophysics Data System (ADS)

Kou, D.; Peng, Y.; Wang, G.; Ding, J.; Chen, Y.; Yang, G.; Fang, K.; Liu, L.; Zhang, B.; Müller, C.; Zhang, J.; Yang, Y.

2017-12-01

Belowground microbial nitrogen (N) dynamics play key roles in regulating structure and function of terrestrial ecosystems, however, our understanding on their responses to global change remains limited. This gap is particularly true for drylands, which constitute the largest biome in terrestrial ecosystems and are sensitive to predicted increase in aridity. Here, responding patterns and controls of six gross N transformation rates were explored along an aridity gradient in Tibetan drylands. Our results showed that gross N rates responded diversely to the changing aridity. Both mineralization (MN) and ammonium immobilization (INH4) declined as aridity increased. Aridity affected MN through its association with plant cover, clay content, soil organic matter (SOM), dissolved organic nitrogen (DON) and total microbial biomass, while regulated INH4 mainly through its effects on SOM and NH4+. Autotrophic nitrification (ONH4) exhibited a bell-shaped pattern along the gradient with a tipping point at aridity index = 0.47. Such a pattern was induced by aridity effects on the abundance of ammonia oxidizing archaea (AOA) and ammonia supplying capacity. Different from above N transformations, rates of nitrate immobilization (INO3) and dissimilatory nitrate reduction to ammonium (DNRA) had no responses to changing aridity, largely regulated by soil DON availability and clay content, respectively. Overall, these results suggest that predicted increase in aridity will exert different effects on various soil internal N cycling processes. The diverse patterns point to different responses of ecosystem N cycle with respect to aridity, and thus potentially have profound impact on structure and function of dryland ecosystems.

Analysis of common deafness gene mutations in deaf people from unique ethnic groups in Gansu Province, China.

PubMed

Xu, Bai-Cheng; Bian, Pan-Pan; Liu, Xiao-Wen; Zhu, Yi-Ming; Yang, Xiao-Long; Ma, Jian-Li; Chen, Xing-Jian; Wang, Yan-Li; Guo, Yu-Fen

2014-09-01

The GJB2 gene mutation characteristic of Dongxiang was the interaction result of ethnic background and geographical environment, and Yugur exhibited the typical founder effect. The SLC26A4 gene mutation characteristic of Dongxiang was related to caucasian backgrounds and selection of purpose exons, i.e. ethnic background and the penetrance of ethnic specificity caused the low mtDNA1555A>G mutation frequency in Dongxiang. To determine the prevalence of GJB2 and SLC26A4 genes and mtDNA1555A>G mutations and analyze the ethnic specificity in the non-syndromic sensorineural hearing loss (NSHL) of unique ethnic groups in Gansu Province. Peripheral blood samples were obtained from Dongxiang, Yugur, Bonan, and ethnic Han groups with moderately severe to profound NSHL in Gansu Province. Bidirectional sequencing (or enzyme digestion) was applied to identify the sequence variations. The pathogenic allele frequency of the three gene mutations was different. The frequency of the GJB2 gene among the Dongxiang, Yugur, Bonan, and ethnic Han groups was 9.03%, 12.5%, 5.88%, and 12.17%, respectively. No difference was found between the ethnic groups. The frequencies of the SLC26A4 genes were 3.23%, 8.33%, 0%, and 9.81%, respectively. The mutation frequency of mtDNA1555A>G was 0%, 0%, 0%, and 6.03%, respectively. No difference was found between the ethnic groups, except for the Dongxiang and ethnic Han groups, both in SLC26A4 gene and mtDNA1555A>G.

Insulin resistance in prepubertal obese children correlates with sex-dependent early onset metabolomic alterations.

PubMed

Mastrangelo, A; Martos-Moreno, G Á; García, A; Barrios, V; Rupérez, F J; Chowen, J A; Barbas, C; Argente, J

2016-10-01

Insulin resistance (IR) is usually the first metabolic alteration diagnosed in obese children and the key risk factor for development of comorbidities. The factors determining whether or not IR develops as a result of excess body mass index (BMI) are still not completely understood. This study aimed to elucidate the mechanisms underpinning the predisposition toward hyperinsulinemia-related complications in obese children by using a metabolomic strategy that allows a profound interpretation of metabolic profiles potentially affected by IR. Serum from 60 prepubertal obese children (30 girls/30 boys, 50% IR and 50% non-IR in each group, but with similar BMIs) were analyzed by using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry following an untargeted metabolomics approach. Validation was then performed on a group of 100 additional children with the same characteristics. When obese children with and without IR were compared, 47 metabolites out of 818 compounds (P<0.05) obtained after data pre-processing were found to be significantly different. Bile acids exhibit the greatest changes (that is, approximately a 90% increase in IR). The majority of metabolites differing between groups were lysophospholipids (15) and amino acids (17), indicating inflammation and central carbon metabolism as the most altered processes in impaired insulin signaling. Multivariate analysis (OPLS-DA models) showed subtle differences between groups that were magnified when females were analyzed alone. Inflammation and central carbon metabolism, together with the contribution of the gut microbiota, are the most altered processes in obese children with impaired insulin signaling in a sex-specific fashion despite their prepubertal status.

The "Cheshire Cat" escape strategy of the coccolithophore Emiliania huxleyi in response to viral infection.

PubMed

Frada, Miguel; Probert, Ian; Allen, Michael J; Wilson, William H; de Vargas, Colomban

2008-10-14

The coccolithophore Emiliania huxleyi is one of the most successful eukaryotes in modern oceans. The two phases in its haplodiploid life cycle exhibit radically different phenotypes. The diploid calcified phase forms extensive blooms, which profoundly impact global biogeochemical equilibria. By contrast, the ecological role of the noncalcified haploid phase has been completely overlooked. Giant phycodnaviruses (Emiliania huxleyi viruses, EhVs) have been shown to infect and lyse diploid-phase cells and to be heavily implicated in the regulation of populations and the termination of blooms. Here, we demonstrate that the haploid phase of E. huxleyi is unrecognizable and therefore resistant to EhVs that kill the diploid phase. We further show that exposure of diploid E. huxleyi to EhVs induces transition to the haploid phase. Thus we have clearly demonstrated a drastic difference in viral susceptibility between life cycle stages with different ploidy levels in a unicellular eukaryote. Resistance of the haploid phase of E. huxleyi provides an escape mechanism that involves separation of meiosis from sexual fusion in time, thus ensuring that genes of dominant diploid clones are passed on to the next generation in a virus-free environment. These "Cheshire Cat" ecological dynamics release host evolution from pathogen pressure and thus can be seen as an opposite force to a classic "Red Queen" coevolutionary arms race. In E. huxleyi, this phenomenon can account for the fact that the selective balance is tilted toward the boom-and-bust scenario of optimization of both growth rates of calcifying E. huxleyi cells and infectivity of EhVs.

The “Cheshire Cat” escape strategy of the coccolithophore Emiliania huxleyi in response to viral infection

PubMed Central

Frada, Miguel; Probert, Ian; Allen, Michael J.; Wilson, William H.; de Vargas, Colomban

2008-01-01

The coccolithophore Emiliania huxleyi is one of the most successful eukaryotes in modern oceans. The two phases in its haplodiploid life cycle exhibit radically different phenotypes. The diploid calcified phase forms extensive blooms, which profoundly impact global biogeochemical equilibria. By contrast, the ecological role of the noncalcified haploid phase has been completely overlooked. Giant phycodnaviruses (Emiliania huxleyi viruses, EhVs) have been shown to infect and lyse diploid-phase cells and to be heavily implicated in the regulation of populations and the termination of blooms. Here, we demonstrate that the haploid phase of E. huxleyi is unrecognizable and therefore resistant to EhVs that kill the diploid phase. We further show that exposure of diploid E. huxleyi to EhVs induces transition to the haploid phase. Thus we have clearly demonstrated a drastic difference in viral susceptibility between life cycle stages with different ploidy levels in a unicellular eukaryote. Resistance of the haploid phase of E. huxleyi provides an escape mechanism that involves separation of meiosis from sexual fusion in time, thus ensuring that genes of dominant diploid clones are passed on to the next generation in a virus-free environment. These “Cheshire Cat” ecological dynamics release host evolution from pathogen pressure and thus can be seen as an opposite force to a classic “Red Queen” coevolutionary arms race. In E. huxleyi, this phenomenon can account for the fact that the selective balance is tilted toward the boom-and-bust scenario of optimization of both growth rates of calcifying E. huxleyi cells and infectivity of EhVs. PMID:18824682

Dieckol, a phlorotannin isolated from a brown seaweed, Ecklonia cava, inhibits adipogenesis through AMP-activated protein kinase (AMPK) activation in 3T3-L1 preadipocytes.

PubMed

Ko, Seok-Chun; Lee, Myoungsook; Lee, Ji-Hyeok; Lee, Seung-Hong; Lim, Yunsook; Jeon, You-Jin

2013-11-01

In this study, we assessed the potential inhibitory effect of 5 species of brown seaweeds on adipogenesis the differentiation of 3T3-L1 preadipocytes into mature adipocytes by measuring Oil-Red O staining. The Ecklonia cava extract tested herein evidenced profound adipogenesis inhibitory effect, compared to that exhibited by the other four brown seaweed extracts. Thus, E. cava was selected for isolation of active compounds and finally the three polyphenol compounds of phlorotannins were obtained and their inhibitory effect on adipogenesis was observed. Among the phlorotannins, dieckol exhibited greatest potential adipogenesis inhibition and down-regulated the expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding proteins (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1) and fatty acid binding protein 4 (FABP4) in a dose-dependent manner. The specific mechanism mediating the effects of dieckol was confirmed by AMP-activated protein kinase (AMPK) activation. These results demonstrate inhibitory effect of dieckol compound on adipogenesis through the activation of the AMPK signal pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

Biomaterial associated impairment of local neutrophil function.

PubMed

Kaplan, S S; Basford, R E; Kormos, R L; Hardesty, R L; Simmons, R L; Mora, E M; Cardona, M; Griffith, B L

1990-01-01

The effect of biomaterials on neutrophil function was studied in vitro to determine if these materials activated neutrophils and to determine the subsequent response of these neutrophils to further stimulation. Two biomaterials--polyurethane, a commonly used substance, and Velcro pile (used in the Jarvik 7 heart)--were evaluated. Two control substances, polyethylene and serum-coated polystyrene, were used for comparison. Neutrophil superoxide release was measured following incubation with these materials for 10, 30, and 120 min in the absence of additional stimulation and after stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol myristate acetate (PMA). The authors observed that the incubation of neutrophils on both polyurethane and Velcro resulted in substantially increased superoxide release that was greater after the 10 min than after the 30 or 120 min association. These activated neutrophils exhibited a poor additional response to fMLP but responded well to PMA. The effect of implantation of the Novacor left ventricular assist device on peripheral blood neutrophil function was also evaluated. The peripheral blood neutrophils exhibited normal superoxide release and chemotaxis. These studies suggest that biomaterials may have a profound local effect on neutrophils, which may predispose the patient to periprosthetic infection, but that the reactivity of circulating neutrophils is unimpaired.

Intraoperative IR imaging in the cardiac operating room

NASA Astrophysics Data System (ADS)

Szabo, Tamas; Fazekas, Levente; Horkay, Ferenc; Geller, Laslu; Gyongy, Tibor; Juhasz-Nagy, Alexander

1999-07-01

The high blood flow rate and the considerable metabolic activity render the myocardium a possible candidate for IR imaging. The study was aimed to test cardiothermography in evaluating arterial bypass graft patency and in assessing myocardial protection during open-heart surgery. Ten patients underwent arterial bypass grafting. Thermograms were obtained immediately before and after opening the grafts. As the bypasses were opened in hypothermia the warmer blood coming from the extracorporeal circulation readily delineated graft and coronary anatomy. By the end of the 5 min observation period, the revascularized area exhibited a temperature increase of 5.9 +/- 0.7 degrees C. The affectivity of antegrade cardioplegia was monitored in 38 patients undergoing either valve implantations or aorto- coronary bypass surgery. Thermographic imags were taken after sternotomy, before aortic cross-clamping and after administrating the 4 degrees C cardioplegic solution. Most of the patients displayed adequate myocardial cooling, moreover the bypass-group exhibited a more profound temperature-decrease. In conclusion, cardiothermography can visualize arterial grafts, recipient coronaries and collaterals seconds after opening by bypass, thus it properly evaluated arterial bypass graft patency. The obtained images could easily be analyzed for qualitative flow- and quantitative temperature changes. Myocardial protection could also be safely assessed with thermography.

Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine▿ †‡

PubMed Central

Kumar, Sanjay; Das, Sajal Kumar; Dey, Sumanta; Maity, Pallab; Guha, Mithu; Choubey, Vinay; Panda, Gautam; Bandyopadhyay, Uday

2008-01-01

A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (KD = 12 to 20 μM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition of hemozoin formation may develop oxidative stress in Plasmodium falciparum due to the accumulation of free heme. Interestingly, AASMP developed oxidative stress in the parasite, as evident from the decreased level of glutathione and increased formation of lipid peroxide, H2O2, and hydroxyl radical (·OH) in P. falciparum. AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (ΔΨm) in malaria parasite, as measured by both flow cytometry and fluorescence microscopy. Furthermore, the generation of ·OH may be mainly responsible for the antimalarial effect of AASMP since ·OH scavengers such as mannitol, as well as spin trap α-phenyl-n-tertbutylnitrone, significantly protected P. falciparum from AASMP-mediated growth inhibition. Cytotoxicity testing of the active compounds showed selective activity against malaria parasite with selectivity indices greater than 100. AASMP also exhibited profound antimalarial activity in vivo against chloroquine resistant P. yoelii. Thus, AASMP represents a novel class of antimalarial. PMID:18025110

A case of butane hash oil (marijuana wax)-induced psychosis.

PubMed

Keller, Corey J; Chen, Evan C; Brodsky, Kimberly; Yoon, Jong H

2016-01-01

Marijuana is one of the most widely used controlled substances in the United States. Despite extensive research on smoked marijuana, little is known regarding the potential psychotropic effects of marijuana "wax," a high-potency form of marijuana that is gaining in popularity. The authors present a case of "Mr. B," a 34-year-old veteran who presented with profound psychosis in the setting of recent initiation of heavy, daily marijuana wax use. He exhibited incoherent speech and odd behaviors and appeared to be in a dream-like state with perseverating thoughts about his combat experience. His condition persisted despite treatment with risperidone 4 mg twice a day (BID), but improved dramatically on day 8 of hospitalization with the return of baseline mental function. Following discharge, Mr. B discontinued all marijuana use and did not exhibit the return of any psychotic symptoms. This study highlights the need for future research regarding the potential medical and psychiatric effects of new, high-potency forms of marijuana. Could cannabis have a dose-dependent impact on psychosis? What other potential psychiatric effects could emerge heretofore unseen in lower potency formulations? Given the recent legalization of marijuana, these questions merit timely exploration.

Autism in siblings with autosomal dominant nocturnal frontal lobe epilepsy.

PubMed

Miyajima, Tomoko; Kumada, Tomohiro; Saito, Keiko; Fujii, Tatsuya

2013-02-01

In 1999, Hirose et al. reported a Japanese family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) associated with a neuronal nicotinic acetylcholine receptor α4 subunit mutation (S252L). We followed the siblings of this family, and found that the elder brother had Asperger's disorder without mental retardation (MR) and the younger brother had autistic disorder with profound MR. The clinical epileptic features of the siblings were very similar, and both had deficits in socialization, but their cognitive development differed markedly. It thus seems that epilepsy is the direct phenotype of the S252L mutation, whereas other various factors modulate the cognitive and social development. No patients with ADNFLE have previously been reported to have autism spectrum disorder or profound MR. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Identification of methyl violet 2B as a novel blocker of focal adhesion kinase signaling pathway in cancer cells

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

Kim, Hwan; Translational Research Center for Protein Function Control; Kim, Nam Doo

2013-07-26

Highlights: •FAK signaling cascade in cancer cells is profoundly inhibited by methyl violet 2B. •Methyl violet 2B identified by virtual screening is a novel allosteric FAK inhibitor. •Methyl violet 2B possesses extremely high kinase selectivity. •Methyl violet 2B suppresses strongly the proliferation of cancer cells. •Methyl violet 2B inhibits focal adhesion, invasion and migration of cancer cells. -- Abstract: The focal adhesion kinase (FAK) signaling cascade in cancer cells was profoundly inhibited by methyl violet 2B identified with the structure-based virtual screening. Methyl violet 2B was shown to be a non-competitive inhibitor of full-length FAK enzyme vs. ATP. It turnedmore » out that methyl violet 2B possesses extremely high kinase selectivity in biochemical kinase profiling using a large panel of kinases. Anti-proliferative activity measurement against several different cancer cells and Western blot analysis showed that this substance is capable of suppressing significantly the proliferation of cancer cells and is able to strongly block FAK/AKT/MAPK signaling pathways in a dose dependent manner at low nanomolar concentration. Especially, phosphorylation of Tyr925-FAK that is required for full activation of FAK was nearly completely suppressed even with 1 nM of methyl violet 2B in A375P cancer cells. To the best of our knowledge, it has never been reported that methyl violet possesses anti-cancer effects. Moreover, methyl violet 2B significantly inhibited FER kinase phosphorylation that activates FAK in cell. In addition, methyl violet 2B was found to induce cell apoptosis and to exhibit strong inhibitory effects on the focal adhesion, invasion, and migration of A375P cancer cells at low nanomolar concentrations. Taken together, these results show that methyl violet 2B is a novel, potent and selective blocker of FAK signaling cascade, which displays strong anti-proliferative activities against a variety of human cancer cells and suppresses adhesion/migration/invasion of tumor cells.« less

Endothelial cells (ECs) for vascular tissue engineering: venous ECs are less thrombogenic than arterial ECs.

PubMed

Geenen, I L A; Molin, D G M; van den Akker, N M S; Jeukens, F; Spronk, H M; Schurink, G W H; Post, M J

2015-05-01

Primary endothelial cells (ECs) are the preferred cellular source for luminal seeding of tissue-engineered (TE) vascular grafts. Research into the potential of ECs for vascular TE has focused particularly on venous rather than arterial ECs. In this study we evaluated the functional characteristics of arterial and venous ECs, relevant for vascular TE. Porcine ECs were isolated from femoral artery (PFAECs) and vein (PFVECs). The proliferation rate was comparable for both EC sources, whereas migration, determined through a wound-healing assay, was less profound for PFVECs. EC adhesion was lower for PFVECs on collagen I, measured after 10 min of arterial shear stress. Gene expression was analysed by qRT-PCR for ECs cultured under static conditions and after exposure to arterial shear stress and revealed differences in gene expression, with lower expression of EphrinB2 and VCAM-1 and higher levels of vWF and COUP-TFII in PFVECs than in PFAECs. PFVECs exhibited diminished platelet adhesion under flow and cell-based thrombin generation was delayed for PFVECs, indicating diminished tissue factor (TF) activity. After stimulation, prostacyclin secretion, but not nitric oxide (NO), was lower in PFVECs. Our data support the use of venous ECs for TE because of their beneficial antithrombogenic profile. Copyright © 2012 John Wiley & Sons, Ltd.

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling

PubMed Central

Lu, Jinchang; Song, Guohui; Tang, Qinglian; Zou, Changye; Han, Feng; Zhao, Zhiqiang; Yong, Bicheng; Yin, Junqiang; Xu, Huaiyuan; Xie, Xianbiao; Kang, Tiebang; Lam, YingLee; Yang, Huiling; Shen, Jingnan; Wang, Jin

2015-01-01

Osteosarcoma is a common malignant bone tumor with a propensity to metastasize to the lungs. Epigenetic abnormalities have been demonstrated to underlie osteosarcoma development; however, the epigenetic mechanisms that are involved in metastasis are not yet clear. Here, we analyzed 2 syngeneic primary human osteosarcoma cell lines that exhibit disparate metastatic potential for differences in epigenetic modifications and expression. Using methylated DNA immunoprecipitation (MeDIP) and microarray expression analysis to screen for metastasis-associated genes, we identified Iroquois homeobox 1 (IRX1). In both human osteosarcoma cell lines and clinical osteosarcoma tissues, IRX1 overexpression was strongly associated with hypomethylation of its own promoter. Furthermore, experimental modulation of IRX1 in osteosarcoma cell lines profoundly altered metastatic activity, including migration, invasion, and resistance to anoikis in vitro, and influenced lung metastasis in murine models. These prometastatic effects of IRX1 were mediated by upregulation of CXCL14/NF-κB signaling. In serum from osteosarcoma patients, the presence of IRX1 hypomethylation in circulating tumor DNA reduced lung metastasis–free survival. Together, these results identify IRX1 as a prometastatic gene, implicate IRX1 hypomethylation as a potential molecular marker for lung metastasis, and suggest that epigenetic reversion of IRX1 activation may be beneficial for controlling osteosarcoma metastasis. PMID:25822025

Effects of alloy heat treatment on oxidation kinetics and scale morphology for Crofer 22 APU

NASA Astrophysics Data System (ADS)

Magdefrau, Neal J.; Chen, Lei; Sun, Ellen Y.; Aindow, Mark

2013-11-01

The effect of alloy heat treatment on the oxidation kinetics and oxide scale microstructure of Crofer 22 APU has been studied. Parabolic oxidation rate constants were measured for the as-received alloy and after pre-oxidation heat treatment in argon at 1050 °C for 1 and 4 h. The oxide scale microstructure was investigated using scanning electron microscopy, focused ion beam milling and transmission electron microscopy. It was found that the alloy forms a two-layer scale with a continuous chromia layer and a discontinuous MnCr2O4 overlayer. Two forms of internal oxides were also formed: subscale pockets of spinel and isolated TiOx precipitates in the underlying alloy. The pre-oxidation heat treatment had a profound effect on the grain size and morphology of the Cr2O3 and MnCr2O4 layers in the scale. The heat-treated samples exhibit a 3.5× lower parabolic oxidation rate constant than the as-received Crofer 22 APU. This improvement in oxidation resistance is attributed to the dramatic differences in the morphology of the oxide scale that forms during the earliest stages of oxidation (<5 h). The implications of these findings for oxidation mechanisms and long-term SOFC performance are discussed.

Ownership reform and the changing manufacturing landscape in Chinese cities: The case of Wuxi.

PubMed

Zhou, Lei; Yang, Shan; Wang, Shuguang; Xiong, Liyang

2017-01-01

Since the economic transition, manufacturing in China has undergone profound changes not only in number of enterprises, but also in ownership structure and intra-urban spatial distribution. Investigating the changing manufacturing landscape from the perspective of ownership structure is critical to a deep understanding of the changing role of market and government in re-shaping manufacturing location behavior. Through a case study of Wuxi, a city experiencing comprehensive ownership reform, this paper presents a detailed analysis of the intra-urban spatial shift of manufacturing, identifies the location discrepancies, and examines the underlying forces responsible for the geographical differentiations. Through zone- and district-based analysis, a distinctive trend of decentralization and suburbanization, as well as an uneven distribution of manufacturing, is unveiled. The results of Location Quotient analysis show that the distribution of manufacturing by ownership exhibits distinctive spatial patterns, which is characterized by a historically-based, market-led, and institutionally-created spatial variation. By employing Hot Spot analysis, the role of development zones in attracting manufacturing enterprises of different ownerships is established. Overall, the location behavior of the diversified manufacturing has been increasingly based on the forces of market since the land marketization began. A proactive role played by local governments has also guided the enterprise location decision through spatial planning and regulatory policies.

Titan Cells Confer Protection from Phagocytosis in Cryptococcus neoformans Infections

PubMed Central

Okagaki, Laura H.

2012-01-01

The human fungal pathogen Cryptococcus neoformans produces an enlarged “titan” cell morphology when exposed to the host pulmonary environment. Titan cells exhibit traits that promote survival in the host. Previous studies showed that titan cells are not phagocytosed and that increased titan cell production in the lungs results in reduced phagocytosis of cryptococcal cells by host immune cells. Here, the effect of titan cell production on host-pathogen interactions during early stages of pulmonary cryptococcosis was explored. The relationship between titan cell production and phagocytosis was found to be nonlinear; moderate increases in titan cell production resulted in profound decreases in phagocytosis, with significant differences occurring within the first 24 h of the infection. Not only were titan cells themselves protected from phagocytosis, but titan cell formation also conferred protection from phagocytosis to normal-size cryptococcal cells. Large particles introduced into the lungs were not phagocytosed, suggesting the large size of titan cells protects against phagocytosis. The presence of large particles was unable to protect smaller particles from phagocytosis, revealing that titan cell size alone is not sufficient to provide the observed cross-protection of normal-size cryptococcal cells. These data suggest that titan cells play a critical role in establishment of the pulmonary infection by promoting the survival of the entire population of cryptococcal cells. PMID:22544904

Titan cells confer protection from phagocytosis in Cryptococcus neoformans infections.

PubMed

Okagaki, Laura H; Nielsen, Kirsten

2012-06-01

The human fungal pathogen Cryptococcus neoformans produces an enlarged "titan" cell morphology when exposed to the host pulmonary environment. Titan cells exhibit traits that promote survival in the host. Previous studies showed that titan cells are not phagocytosed and that increased titan cell production in the lungs results in reduced phagocytosis of cryptococcal cells by host immune cells. Here, the effect of titan cell production on host-pathogen interactions during early stages of pulmonary cryptococcosis was explored. The relationship between titan cell production and phagocytosis was found to be nonlinear; moderate increases in titan cell production resulted in profound decreases in phagocytosis, with significant differences occurring within the first 24 h of the infection. Not only were titan cells themselves protected from phagocytosis, but titan cell formation also conferred protection from phagocytosis to normal-size cryptococcal cells. Large particles introduced into the lungs were not phagocytosed, suggesting the large size of titan cells protects against phagocytosis. The presence of large particles was unable to protect smaller particles from phagocytosis, revealing that titan cell size alone is not sufficient to provide the observed cross-protection of normal-size cryptococcal cells. These data suggest that titan cells play a critical role in establishment of the pulmonary infection by promoting the survival of the entire population of cryptococcal cells.

The Biogeochemical Response to Inter-decadal Atmospheric Forcing Across Watershed Scales in Canada's Subarctic

NASA Astrophysics Data System (ADS)

Spence, C.

2016-12-01

Rapid landscape changes in the circumpolar north have been documented, including degradation of permafrost and alteration of vegetation communities. These are widely expected to have profound impacts on the freshwater fluxes of solutes, carbon and nitrogen across the Arctic domain. However, there have been few attempts to document trends across the diversity of landscapes in the circumpolar north, mostly due to a dearth of long term data. Some of the fastest rates of warming over the last thirty years have occurred in Canada's Northwest Territories, so this region should already exhibit changes in aquatic chemistry. Observations of chemical loads in streams draining the ice-poor discontinuous permafrost subarctic Canadian Shield region were analyzed with the goal of determining how basins across scales have responded to changes in atmospheric forcing. Smaller streams, with much closer linkages to terrestrial processes, experienced a synchrony among hydrological and biogeochemical processes that enhanced chemical flux above that in their larger counterparts. This demonstrates that there are differences in resiliency and resistance across scales to climate change. These results highlight the importance of biogeochemical process understanding to properly explain and predict how chemical loading scales from headwaters to river mouths. This is important information if society is to properly adapt policies for effluent discharge, nearshore marine management, among others.

Ownership reform and the changing manufacturing landscape in Chinese cities: The case of Wuxi

PubMed Central

Zhou, Lei; Yang, Shan; Wang, Shuguang

2017-01-01

Since the economic transition, manufacturing in China has undergone profound changes not only in number of enterprises, but also in ownership structure and intra-urban spatial distribution. Investigating the changing manufacturing landscape from the perspective of ownership structure is critical to a deep understanding of the changing role of market and government in re-shaping manufacturing location behavior. Through a case study of Wuxi, a city experiencing comprehensive ownership reform, this paper presents a detailed analysis of the intra-urban spatial shift of manufacturing, identifies the location discrepancies, and examines the underlying forces responsible for the geographical differentiations. Through zone- and district-based analysis, a distinctive trend of decentralization and suburbanization, as well as an uneven distribution of manufacturing, is unveiled. The results of Location Quotient analysis show that the distribution of manufacturing by ownership exhibits distinctive spatial patterns, which is characterized by a historically-based, market-led, and institutionally-created spatial variation. By employing Hot Spot analysis, the role of development zones in attracting manufacturing enterprises of different ownerships is established. Overall, the location behavior of the diversified manufacturing has been increasingly based on the forces of market since the land marketization began. A proactive role played by local governments has also guided the enterprise location decision through spatial planning and regulatory policies. PMID:28278284

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies

PubMed Central

Szymańska, Emilia; Orłowski, Piotr; Tomaszewska, Emilia; Bąska, Piotr; Grobelny, Jarosław; Basa, Anna; Krzyżowska, Małgorzata

2018-01-01

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection. PMID:29382085

Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria.

PubMed

Bender, Aline; Hajieva, Parvana; Moosmann, Bernd

2008-10-28

Humans and most other animals use 2 different genetic codes to translate their hereditary information: the standard code for nuclear-encoded proteins and a modern variant of this code in mitochondria. Despite the pivotal role of the genetic code for cell biology, the functional significance of the deviant mitochondrial code has remained enigmatic since its first description in 1979. Here, we show that profound and functionally beneficial alterations on the encoded protein level were causative for the AUA codon reassignment from isoleucine to methionine observed in most mitochondrial lineages. We demonstrate that this codon reassignment leads to a massive accumulation of the easily oxidized amino acid methionine in the highly oxidative inner mitochondrial membrane. This apparently paradoxical outcome can yet be smoothly settled if the antioxidant surface chemistry of methionine is taken into account, and we present direct experimental evidence that intramembrane accumulation of methionine exhibits antioxidant and cytoprotective properties in living cells. Our results unveil that methionine is an evolutionarily selected antioxidant building block of respiratory chain complexes. Collective protein alterations can thus constitute the selective advantage behind codon reassignments, which authenticates the "ambiguous decoding" hypothesis of genetic code evolution. Oxidative stress has shaped the mitochondrial genetic code.

The marine mammal dive response is exercise modulated to maximize aerobic dive duration.

PubMed

Davis, Randall W; Williams, Terrie M

2012-08-01

When aquatically adapted mammals and birds swim submerged, they exhibit a dive response in which breathing ceases, heart rate slows, and blood flow to peripheral tissues and organs is reduced. The most intense dive response occurs during forced submersion which conserves blood oxygen for the brain and heart, thereby preventing asphyxiation. In free-diving animals, the dive response is less profound, and energy metabolism remains aerobic. However, even this relatively moderate bradycardia seems diametrically opposed to the normal cardiovascular response (i.e., tachycardia and peripheral vasodilation) during physical exertion. As a result, there has been a long-standing paradox regarding how aquatic mammals and birds exercise while submerged. We hypothesized based on cardiovascular modeling that heart rate must increase to ensure adequate oxygen delivery to active muscles. Here, we show that heart rate (HR) does indeed increase with flipper or fluke stroke frequency (SF) during voluntary, aerobic dives in Weddell seals (HR = 1.48SF - 8.87) and bottlenose dolphins (HR = 0.99SF + 2.46), respectively, two marine mammal species with different evolutionary lineages. These results support our hypothesis that marine mammals maintain aerobic muscle metabolism while swimming submerged by combining elements of both dive and exercise responses, with one or the other predominating depending on the level of exertion.

Misfit-guided self-organization of anticorrelated Ge quantum dot arrays on Si nanowires.

PubMed

Kwon, Soonshin; Chen, Zack C Y; Kim, Ji-Hun; Xiang, Jie

2012-09-12

Misfit-strain guided growth of periodic quantum dot (QD) arrays in planar thin film epitaxy has been a popular nanostructure fabrication method. Engineering misfit-guided QD growth on a nanoscale substrate such as the small curvature surface of a nanowire represents a new approach to self-organized nanostructure preparation. Perhaps more profoundly, the periodic stress underlying each QD and the resulting modulation of electro-optical properties inside the nanowire backbone promise to provide a new platform for novel mechano-electronic, thermoelectronic, and optoelectronic devices. Herein, we report a first experimental demonstration of self-organized and self-limited growth of coherent, periodic Ge QDs on a one-dimensional Si nanowire substrate. Systematic characterizations reveal several distinctively different modes of Ge QD ordering on the Si nanowire substrate depending on the core diameter. In particular, Ge QD arrays on Si nanowires of around 20 nm diameter predominantly exhibit an anticorrelated pattern whose wavelength agrees with theoretical predictions. The correlated pattern can be attributed to propagation and correlation of misfit strain across the diameter of the thin nanowire substrate. The QD array growth is self-limited as the wavelength of the QDs remains unchanged even after prolonged Ge deposition. Furthermore, we demonstrate a direct kinetic transformation from a uniform Ge shell layer to discrete QD arrays by a postgrowth annealing process.

The adipocyte as an important target cell for Trypanosoma cruzi infection.

PubMed

Combs, Terry P; Nagajyothi; Mukherjee, Shankar; de Almeida, Cecilia J G; Jelicks, Linda A; Schubert, William; Lin, Ying; Jayabalan, David S; Zhao, Dazhi; Braunstein, Vicki L; Landskroner-Eiger, Shira; Cordero, Aisha; Factor, Stephen M; Weiss, Louis M; Lisanti, Michael P; Tanowitz, Herbert B; Scherer, Philipp E

2005-06-24

Adipose tissue plays an active role in normal metabolic homeostasis as well as in the development of human disease. Beyond its obvious role as a depot for triglycerides, adipose tissue controls energy expenditure through secretion of several factors. Little attention has been given to the role of adipocytes in the pathogenesis of Chagas disease and the associated metabolic alterations. Our previous studies have indicated that hyperglycemia significantly increases parasitemia and mortality in mice infected with Trypanosoma cruzi. We determined the consequences of adipocyte infection in vitro and in vivo. Cultured 3T3-L1 adipocytes can be infected with high efficiency. Electron micrographs of infected cells revealed a large number of intracellular parasites that cluster around lipid droplets. Furthermore, infected adipocytes exhibited changes in expression levels of a number of different adipocyte-specific or adipocyte-enriched proteins. The adipocyte is therefore an important target cell during acute Chagas disease. Infection of adipocytes by T. cruzi profoundly influences the pattern of adipokines. During chronic infection, adipocytes may represent an important long-term reservoir for parasites from which relapse of infection can occur. We have demonstrated that acute infection has a unique metabolic profile with a high degree of local inflammation in adipose tissue, hypoadiponectinemia, hypoglycemia, and hypoinsulinemia but with relatively normal glucose disposal during an oral glucose tolerance test.

Functional nucleic acids as in vivo metabolite and ion biosensors.

PubMed

Alsaafin, Alaa; McKeague, Maureen

2017-08-15

Characterizing the role of metabolites, metals, and proteins is required to understand normal cell function, and ultimately, elucidate the mechanism of disease. Metabolite concentration and transformation results collected from cell lysates or fixed-cells conceal important dynamic information and differences between individual cells that often have profound functional consequences. Functional nucleic acid-based biosensors are emerging tools that are capable of monitoring ions and metabolites in cell populations or whole animals. Functional nucleic acids (FNAs) are a class of biomolecules that can exhibit either ligand binding or enzymatic activity. Unlike their protein analogues or the use of instrument-based analysis, FNA-based biosensors are capable of entering cells without disruption to the cellular environment and can report on the concentration, dynamics, and spatial localization of molecules in cells. Here, we review the types of FNAs that have been used as in vivo biosensors, and how FNAs can be coupled to transduction systems and delivered inside cells. We also provide examples from the literature that demonstrate their impact in practical applications. Finally, we comment on the critical limitations that need to be addressed to enable their use for single-cell dynamic tracking of metabolites and ions in vivo. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Effects of forest conversion on soil microbial communities depend on soil layer on the eastern Tibetan Plateau of China.

PubMed

He, Ruoyang; Yang, Kaijun; Li, Zhijie; Schädler, Martin; Yang, Wanqin; Wu, Fuzhong; Tan, Bo; Zhang, Li; Xu, Zhenfeng

2017-01-01

Forest land-use changes have long been suggested to profoundly affect soil microbial communities. However, how forest type conversion influences soil microbial properties remains unclear in Tibetan boreal forests. The aim of this study was to explore variations of soil microbial profiles in the surface organic layer and subsurface mineral soil among three contrasting forests (natural coniferous forest, NF; secondary birch forest, SF and spruce plantation, PT). Soil microbial biomass, activity and community structure of the two layers were investigated by chloroform fumigation, substrate respiration and phospholipid fatty acid analysis (PLFA), respectively. In the organic layer, both NF and SF exhibited higher soil nutrient levels (carbon, nitrogen and phosphorus), microbial biomass carbon and nitrogen, microbial respiration, PLFA contents as compared to PT. However, the measured parameters in the mineral soils often did not differ following forest type conversion. Irrespective of forest types, the microbial indexes generally were greater in the organic layer than in the mineral soil. PLFAs biomarkers were significantly correlated with soil substrate pools. Taken together, forest land-use change remarkably altered microbial community in the organic layer but often did not affect them in the mineral soil. The microbial responses to forest land-use change depend on soil layer, with organic horizons being more sensitive to forest conversion.

Ultrathin hexagonal MgO nanoflakes coated medical textiles and their enhanced antibacterial activity

NASA Astrophysics Data System (ADS)

Veeran Ponnuvelu, Dinesh; Selvaraj, Aravind; Prema Suriyaraj, Shanmugam; Selvakumar, Rajendran; Pulithadathail, Biji

2016-10-01

A facile hydrothermal method for development of ultrathin MgO nanoplates from different precursors and their enhanced antibacterial activity after coating onto medical textiles is reported. Ultrathin MgO nanoplates having hexagonal structure were characterized using UV-visible spectroscopy, atomic force microscopy, field emission scanning electron microscopy, x-ray diffraction and high resolution transmission electron microscopy. The formation of MgO nanoplates was found to exhibit profound anionic effect leading to ultrathin, planar structures with exposed MgO [111] facets, which may be responsible for enhanced antimicrobial activity. Medical fabrics (bleached 100% cotton) were coated with MgO nanoplates using pad-dry-cure method. The antibacterial activity of these fabrics was tested against Bacillus subtilis and Escherichia coli. The MgO nanoplates coated onto the fabric were found to have good adherence properties owing to their two-dimensional structure and were durable even after repeated washings without substantial reduction in the antimicrobial activity. The enhanced antibacterial activity may be attributed to the presence of oxygen vacancies, surface oxygen anions and hydroxyl groups on the surface of MgO nanoplates. This cost-effective functional finish (anti-microbial) to cotton fabric using MgO nanoplates may be suitable for many prospective medical applications and can serve as an alternative to the costlier silver based antimicrobial textiles.

Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2.

PubMed

Liu, Beiying; Qin, Feng

2016-04-12

Thermal TRP channels mediate temperature transduction and pain sensation. The vanilloid receptor TRPV2 is involved in detection of noxious heat in a subpopulation of high-threshold nociceptors. It also plays a critical role in development of thermal hyperalgesia, but the underlying mechanism remains uncertain. Here we analyze the heat sensitivity of the TRPV2 channel. Heat activation of the channel exhibits strong use dependence. Prior heat activation can profoundly alter its subsequent temperature responsiveness, causing decreases in both temperature activation threshold and slope sensitivity of temperature dependence while accelerating activation time courses. Notably, heat and agonist activations differ in cross use-dependence. Prior heat stimulation can dramatically sensitize agonist responses, but not conversely. Quantitative analyses indicate that the use dependence in heat sensitivity is pertinent to the process of temperature sensing by the channel. The use dependence of TRPV2 reveals that the channel can have a dynamic temperature sensitivity. The temperature sensing structures within the channel have multiple conformations and the temperature activation pathway is separate from the agonist activation pathway. Physiologically, the use dependence of TRPV2 confers nociceptors with a hypersensitivity to heat and thus provides a mechanism for peripheral thermal hyperalgesia. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Viral fusion efficacy of specific H3N2 influenza virus reassortant combinations at single-particle level

NASA Astrophysics Data System (ADS)

Hsu, Hung-Lun; Millet, Jean K.; Costello, Deirdre A.; Whittaker, Gary R.; Daniel, Susan

2016-10-01

Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs. We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings. Results illustrate that matching pseudoparticles behaved very similarly to native virus. Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates. Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles. An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression. Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses.

Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans

PubMed Central

Ow, Maria C.; Nichitean, Alexandra M.; Dorus, Steve; Hall, Sarah E.

2018-01-01

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite (“seesaw”) transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome. PMID:29447162

Comparative analysis of replication characteristics of BoHV-1 subtypes in bovine respiratory and genital mucosa explants: a phylogenetic enlightenment

PubMed Central

2011-01-01

In general, members of the Alphaherpesvirinae use the epithelium of the upper respiratory and/or genital tract as a preferential site for primary replication. Bovine herpesvirus type 1 (BoHV-1) may replicate at both sites and cause two major clinical entities designated as infectious bovine rhinotracheitis (IBR) and infectious pustular vulvovaginitis/balanoposthitis (IPV/IPB) in cattle. It has been hypothesized that subtype 1.1 invades preferentially the upper respiratory mucosa whereas subtype 1.2 favors replication at the peripheral genital tract. However, some studies are in contrast with this hypothesis. A thorough study of primary replication at both mucosae could elucidate whether or not different BoHV-1 subtypes show differences in mucosa tropism. We established bovine respiratory and genital organ cultures with emphasis on maintenance of tissue morphology and viability during in vitro culture. In a next step, bovine respiratory and genital mucosa explants of the same animals were inoculated with several BoHV-1 subtypes. A quantitative analysis of viral invasion in the mucosa was performed at 0 h, 24 h, 48 h and 72 h post inoculation (pi) by measuring plaque latitude and penetration depth underneath the basement membrane. All BoHV-1 subtypes exhibited a more profound invasion capacity in respiratory tissue compared to that in genital tissue at 24 h pi. However, at 24 h pi plaque latitude was found to be larger in genital tissue compared to respiratory tissue and this for all subtypes. These similar findings among the different subtypes take the edge off the belief of the existence of specific mucosa tropisms of different BoHV-1 subtypes. PMID:21324115

Prochlorococcus and Synechococcus have Evolved Different Adaptive Mechanisms to Cope with Light and UV Stress

PubMed Central

Mella-Flores, Daniella; Six, Christophe; Ratin, Morgane; Partensky, Frédéric; Boutte, Christophe; Le Corguillé, Gildas; Marie, Dominique; Blot, Nicolas; Gourvil, Priscillia; Kolowrat, Christian; Garczarek, Laurence

2012-01-01

Prochlorococcus and Synechococcus, which numerically dominate vast oceanic areas, are the two most abundant oxygenic phototrophs on Earth. Although they require solar energy for photosynthesis, excess light and associated high UV radiations can induce high levels of oxidative stress that may have deleterious effects on their growth and productivity. Here, we compared the photophysiologies of the model strains Prochlorococcus marinus PCC 9511 and Synechococcus sp. WH7803 grown under a bell-shaped light/dark cycle of high visible light supplemented or not with UV. Prochlorococcus exhibited a higher sensitivity to photoinactivation than Synechococcus under both conditions, as shown by a larger drop of photosystem II (PSII) quantum yield at noon and different diel patterns of the D1 protein pool. In the presence of UV, the PSII repair rate was significantly depressed at noon in Prochlorococcus compared to Synechococcus. Additionally, Prochlorococcus was more sensitive than Synechococcus to oxidative stress, as shown by the different degrees of PSII photoinactivation after addition of hydrogen peroxide. A transcriptional analysis also revealed dramatic discrepancies between the two organisms in the diel expression patterns of several genes involved notably in the biosynthesis and/or repair of photosystems, light-harvesting complexes, CO2 fixation as well as protection mechanisms against light, UV, and oxidative stress, which likely translate profound differences in their light-controlled regulation. Altogether our results suggest that while Synechococcus has developed efficient ways to cope with light and UV stress, Prochlorococcus cells seemingly survive stressful hours of the day by launching a minimal set of protection mechanisms and by temporarily bringing down several key metabolic processes. This study provides unprecedented insights into understanding the distinct depth distributions and dynamics of these two picocyanobacteria in the field. PMID:23024637

Prochlorococcus and Synechococcus have Evolved Different Adaptive Mechanisms to Cope with Light and UV Stress.

PubMed

Mella-Flores, Daniella; Six, Christophe; Ratin, Morgane; Partensky, Frédéric; Boutte, Christophe; Le Corguillé, Gildas; Marie, Dominique; Blot, Nicolas; Gourvil, Priscillia; Kolowrat, Christian; Garczarek, Laurence

2012-01-01

Prochlorococcus and Synechococcus, which numerically dominate vast oceanic areas, are the two most abundant oxygenic phototrophs on Earth. Although they require solar energy for photosynthesis, excess light and associated high UV radiations can induce high levels of oxidative stress that may have deleterious effects on their growth and productivity. Here, we compared the photophysiologies of the model strains Prochlorococcus marinus PCC 9511 and Synechococcus sp. WH7803 grown under a bell-shaped light/dark cycle of high visible light supplemented or not with UV. Prochlorococcus exhibited a higher sensitivity to photoinactivation than Synechococcus under both conditions, as shown by a larger drop of photosystem II (PSII) quantum yield at noon and different diel patterns of the D1 protein pool. In the presence of UV, the PSII repair rate was significantly depressed at noon in Prochlorococcus compared to Synechococcus. Additionally, Prochlorococcus was more sensitive than Synechococcus to oxidative stress, as shown by the different degrees of PSII photoinactivation after addition of hydrogen peroxide. A transcriptional analysis also revealed dramatic discrepancies between the two organisms in the diel expression patterns of several genes involved notably in the biosynthesis and/or repair of photosystems, light-harvesting complexes, CO(2) fixation as well as protection mechanisms against light, UV, and oxidative stress, which likely translate profound differences in their light-controlled regulation. Altogether our results suggest that while Synechococcus has developed efficient ways to cope with light and UV stress, Prochlorococcus cells seemingly survive stressful hours of the day by launching a minimal set of protection mechanisms and by temporarily bringing down several key metabolic processes. This study provides unprecedented insights into understanding the distinct depth distributions and dynamics of these two picocyanobacteria in the field.

ProFound: Source Extraction and Application to Modern Survey Data

NASA Astrophysics Data System (ADS)

Robotham, A. S. G.; Davies, L. J. M.; Driver, S. P.; Koushan, S.; Taranu, D. S.; Casura, S.; Liske, J.

2018-05-01

We introduce PROFOUND, a source finding and image analysis package. PROFOUND provides methods to detect sources in noisy images, generate segmentation maps identifying the pixels belonging to each source, and measure statistics like flux, size, and ellipticity. These inputs are key requirements of PROFIT, our recently released galaxy profiling package, where the design aim is that these two software packages will be used in unison to semi-automatically profile large samples of galaxies. The key novel feature introduced in PROFOUND is that all photometry is executed on dilated segmentation maps that fully contain the identifiable flux, rather than using more traditional circular or ellipse-based photometry. Also, to be less sensitive to pathological segmentation issues, the de-blending is made across saddle points in flux. We apply PROFOUND in a number of simulated and real-world cases, and demonstrate that it behaves reasonably given its stated design goals. In particular, it offers good initial parameter estimation for PROFIT, and also segmentation maps that follow the sometimes complex geometry of resolved sources, whilst capturing nearly all of the flux. A number of bulge-disc decomposition projects are already making use of the PROFOUND and PROFIT pipeline, and adoption is being encouraged by publicly releasing the software for the open source R data analysis platform under an LGPL-3 license on GitHub (github.com/asgr/ProFound).

Therapeutic effect of the natural compounds baicalein and baicalin on autoimmune diseases.

PubMed

Xu, Jian; Liu, Jinlong; Yue, Guolin; Sun, Mingqiang; Li, Jinliang; Xiu, Xia; Gao, Zhenzhong

2018-05-23

A series of natural compounds have been implicated to be useful in regulating the pathogenesis of various autoimmune diseases. The present study demonstrated that the Scutellariae radix compounds baicalein and baicalin may serve as drugs for the treatment of autoimmune diseases, including rheumatoid arthritis and inflammatory bowel disease. Following the administration of baicalein and baicalin in vivo, T cell‑mediated autoimmune diseases in the mouse model were profoundly ameliorated: In the collagen‑induced arthritis model (CIA), the severity of the disease was reduced by baicalein and, consistently, baicalein was demonstrated to suppress T cell proliferation in CIA mice. In the dextran sodium sulfate (DSS)‑induced colitis model, the disease was attenuated by baicalin, and baicalin promoted colon epithelial cell (CEC) proliferation in vitro. The present study further revealed that the mRNA expression of signal transducer and activator of transcription (STAT)3 and STAT4 in the tyrosine‑protein kinase JAK‑STAT signaling pathway in T cells was downregulated by baicalein, contributing to its regulation of T cell proliferation. However, in the DSS model, the STAT4 transcription in CECs, which are the target cells of activated T cells in the gut, was downregulated by baicalin, suggesting that baicalein and baicalin mediated similar STAT expression in different cell types in autoimmune diseases. In conclusion, the similarly structured compounds baicalein and baicalin selectively exhibited therapeutic effects on autoimmune diseases by regulating cell proliferation and STAT gene expression, albeit in different cell types.

Development of the Mental Synthesis Evaluation Checklist (MSEC): A Parent-Report Tool for Mental Synthesis Ability Assessment in Children with Language Delay

PubMed Central

Braverman, Julia; Dunn, Rita

2018-01-01

Mental synthesis is the conscious purposeful process of synthesizing novel mental images from objects stored in memory. Mental synthesis ability is essential for understanding complex syntax, spatial prepositions, and verb tenses. In typical children, the timeline of mental synthesis acquisition is highly correlated with an increasing vocabulary. Children with Autism Spectrum Disorder (ASD), on the other hand, may learn hundreds of words but never acquire mental synthesis. In these individuals, tests assessing vocabulary comprehension may fail to demonstrate the profound deficit in mental synthesis. We developed a parent-reported Mental Synthesis Evaluation Checklist (MSEC) designed to assess mental synthesis acquisition in ASD children. The psychometric quality of MSEC was tested with 3715 parents of ASD children. Internal reliability of the 20-item MSEC was good (Cronbach’s alpha >0.9). MSEC exhibited adequate test–retest reliability; good construct validity, supported by a positive correlation with the Autism Treatment Evaluation Checklist (ATEC) Communication subscale; and good known group validity reflected by the difference in MSEC scores for children of different ASD severity levels. The MSEC questionnaire is copyright-free and can be used by researchers as a complimentary subscale for the ATEC evaluation. We hope that the addition of MSEC will make the combined assessment more sensitive to small steps in a child’s development. As MSEC does not rely on productive language, it may be an especially useful tool for assessing the development of nonverbal and minimally verbal children. PMID:29783788

Muscle coordination in cycling: effect of surface incline and posture.

PubMed

Li, L; Caldwell, G E

1998-09-01

The purpose of the present study was to examine the neuromuscular modifications of cyclists to changes in grade and posture. Eight subjects were tested on a computerized ergometer under three conditions with the same work rate (250 W): pedaling on the level while seated, 8% uphill while seated, and 8% uphill while standing (ST). High-speed video was taken in conjunction with surface electromyography (EMG) of six lower extremity muscles. Results showed that rectus femoris, gluteus maximus (GM), and tibialis anterior had greater EMG magnitude in the ST condition. GM, rectus femoris, and the vastus lateralis demonstrated activity over a greater portion of the crank cycle in the ST condition. The muscle activities of gastrocnemius and biceps femoris did not exhibit profound differences among conditions. Overall, the change of cycling grade alone from 0 to 8% did not induce a significant change in neuromuscular coordination. However, the postural change from seated to ST pedaling at 8% uphill grade was accompanied by increased and/or prolonged muscle activity of hip and knee extensors. The observed EMG activity patterns were discussed with respect to lower extremity joint moments. Monoarticular extensor muscles (GM, vastus lateralis) demonstrated greater modifications in activity patterns with the change in posture compared with their biarticular counterparts. Furthermore, muscle coordination among antagonist pairs of mono- and biarticular muscles was altered in the ST condition; this finding provides support for the notion that muscles within these antagonist pairs have different functions.

The antisocial brain: psychopathy matters.

PubMed

Gregory, Sarah; ffytche, Dominic; Simmons, Andrew; Kumari, Veena; Howard, Matthew; Hodgins, Sheilagh; Blackwood, Nigel

2012-09-01

The population of men who display persistent antisocial and violent behavior is heterogeneous. Callous-unemotional traits in childhood and psychopathic traits in adulthood characterize a distinct subgroup. To identify structural gray matter (GM) differences between persistent violent offenders who meet criteria for antisocial personality disorder and the syndrome of psychopathy (ASPDP) and those meeting criteria only for ASPD (ASPD-P). Cross-sectional case-control structural magnetic resonance imaging study. Inner-city probation services and neuroimaging research unit in London, England. Sixty-six men, including 17 violent offenders with ASPDP, 27 violent offenders with ASPD-P, and 22 healthy nonoffenders participated in the study. Forensic clinicians assessed participants using the Structured Clinical Interview for DSM-IV and the Psychopathy Checklist-Revised. Gray matter volumes as assessed by structural magnetic resonance imaging and volumetric voxel-based morphometry analyses. Offenders with ASPDP displayed significantly reduced GM volumes bilaterally in the anterior rostral prefrontal cortex (Brodmann area 10) and temporal poles (Brodmann area 20/38) relative to offenders with ASPD-P and nonoffenders. These reductions were not attributable to substance use disorders. Offenders with ASPD-P exhibited GM volumes similar to the nonoffenders. Reduced GM volume within areas implicated in empathic processing, moral reasoning, and processing of prosocial emotions such as guilt and embarrassment may contribute to the profound abnormalities of social behavior observed in psychopathy. Evidence of robust structural brain differences between persistently violent men with and without psychopathy adds to the evidence that psychopathy represents a distinct phenotype. This knowledge may facilitate research into the etiology of persistent violent behavior.

Studies on Normal and Microgravity Annular Two Phase Flows

NASA Technical Reports Server (NTRS)

Balakotaiah, V.; Jayawardena, S. S.; Nguyen, L. T.

1999-01-01

Two-phase gas-liquid flows occur in a wide variety of situations. In addition to normal gravity applications, such flows may occur in space operations such as active thermal control systems, power cycles, and storage and transfer of cryogenic fluids. Various flow patterns exhibiting characteristic spatial and temporal distribution of the two phases are observed in two-phase flows. The magnitude and orientation of gravity with respect to the flow has a strong impact on the flow patterns observed and on their boundaries. The identification of the flow pattern of a flow is somewhat subjective. The same two-phase flow (especially near a flow pattern transition boundary) may be categorized differently by different researchers. Two-phase flow patterns are somewhat simplified in microgravity, where only three flow patterns (bubble, slug and annular) have been observed. Annular flow is obtained for a wide range of gas and liquid flow rates, and it is expected to occur in many situations under microgravity conditions. Slug flow needs to be avoided, because vibrations caused by slugs result in unwanted accelerations. Therefore, it is important to be able to accurately predict the flow pattern which exists under given operating conditions. It is known that the wavy liquid film in annular flow has a profound influence on the transfer of momentum and heat between the phases. Thus, an understanding of the characteristics of the wavy film is essential for developing accurate correlations. In this work, we review our recent results on flow pattern transitions and wavy films in microgravity.

Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus

PubMed Central

Kurioka, Takaomi; Lee, Min Young; Heeringa, Amarins N.; Beyer, Lisa A.; Swiderski, Donald L.; Kanicki, Ariane C.; Kabara, Lisa L.; Dolan, David F.; Shore, Susan E.; Raphael, Yehoash

2016-01-01

In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus. However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). We showed that DT-induced HC ablation has no significant impacts on the survival of auditory neurons, central synaptic terminals, and myelin, despite complete HC loss and profound deafness. In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and cochlear nucleus neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination. PMID:27403879

Precipitation-generated oscillations in open cellular cloud fields.

PubMed

Feingold, Graham; Koren, Ilan; Wang, Hailong; Xue, Huiwen; Brewer, Wm Alan

2010-08-12

Cloud fields adopt many different patterns that can have a profound effect on the amount of sunlight reflected back to space, with important implications for the Earth's climate. These cloud patterns can be observed in satellite images of the Earth and often exhibit distinct cell-like structures associated with organized convection at scales of tens of kilometres. Recent evidence has shown that atmospheric aerosol particles-through their influence on precipitation formation-help to determine whether cloud fields take on closed (more reflective) or open (less reflective) cellular patterns. The physical mechanisms controlling the formation and evolution of these cells, however, are still poorly understood, limiting our ability to simulate realistically the effects of clouds on global reflectance. Here we use satellite imagery and numerical models to show how precipitating clouds produce an open cellular cloud pattern that oscillates between different, weakly stable states. The oscillations are a result of precipitation causing downward motion and outflow from clouds that were previously positively buoyant. The evaporating precipitation drives air down to the Earth's surface, where it diverges and collides with the outflows of neighbouring precipitating cells. These colliding outflows form surface convergence zones and new cloud formation. In turn, the newly formed clouds produce precipitation and new colliding outflow patterns that are displaced from the previous ones. As successive cycles of this kind unfold, convergence zones alternate with divergence zones and new cloud patterns emerge to replace old ones. The result is an oscillating, self-organized system with a characteristic cell size and precipitation frequency.

Noonan Syndrome: An Underestimated Cause of Severe to Profound Sensorineural Hearing Impairment. Which Clues to Suspect the Diagnosis?

PubMed

Ziegler, Alban; Loundon, Natalie; Jonard, Laurence; Cavé, Hélène; Baujat, Geneviève; Gherbi, Souad; Couloigner, Vincent; Marlin, Sandrine

2017-09-01

To highlight Noonan syndrome as a clinically recognizable cause of severe to profound sensorineural hearing impairment. New clinical cases and review. Patients evaluated for etiological diagnosis by a medical geneticist in a reference center for hearing impairment. Five patients presenting with confirmed Noonan syndrome and profound sensorineural hearing impairment. Diagnostic and review of the literature. Five patients presented with profound sensorineural hearing impairment and molecularly confirmed Noonan syndrome. Sensorineural hearing impairment has been progressive for three patients. Cardiac echography identified pulmonary stenosis in two patients and was normal for the three other patients. Short stature was found in two patients. Mild intellectual disability was found in one patient. Inconspicuous clinical features as facial dysmorphism, cryptorchidism, or easy bruising were of peculiar interest to reach the diagnosis of Noonan syndrome. Profound sensorineural hearing impairment can be the main feature of Noonan syndrome. Associated features are highly variable; thus, detailed medical history and careful physical examination are mandatory to consider the diagnosis in case of a sensorineural hearing impairment.

Negative Affect Impairs Associative Memory but Not Item Memory

ERIC Educational Resources Information Center

Bisby, James A.; Burgess, Neil

2014-01-01

The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine…

The Beat of a Different Drummer: Essays on Educational Renewal in Honor of John I. Goodlad.

ERIC Educational Resources Information Center

Sirotnik, Kenneth A., Ed.; Soder, Roger, Ed.

This book contains essays by those who have been profoundly influenced by John Goodlad's research and scholarship on educational change and school improvement. The volume features 20 articles: "On Inquiry and Education," K. Sirotnik; "Invigorating Elementary Schooling: Savoring a Long-Term Partnership," R. Anderson;…

Teacher Education in Italy, Germany, England, Sweden and Finland

ERIC Educational Resources Information Center

Ostinelli, Giorgio

2009-01-01

This article presents a brief analysis of teacher education in five European countries: Italy, Germany, England, Sweden and Finland. In the post-industrial world, the sense of teaching has profoundly changed, influenced by a rapidly evolving socio-economic context. The responses given by each country are different, but two tendencies emerge: on…

On the Relationship of Multiple Intelligences with Listening Proficiency and Attitudes among Iranian TEFL University Students

ERIC Educational Resources Information Center

Naeini, Ma'ssoumeh Bemani; Pandian, Ambigapathy

2010-01-01

Gardner's (1983) Multiple Intelligences Theory (MIT) has been found to have profound implications in teaching English as a foreign language (TEFL) in that it provides a way for teachers to recognize learners' individual cognitive and affective differences by providing favorable motivational conditions for learning. However, little investigation…

Hot Brakes and Energy-Related Concepts: Is Energy Lost?

ERIC Educational Resources Information Center

Lopez, V.; Pinto, R.

2012-01-01

This paper describes a secondary school experience which is intended to help students to think profoundly about some energy-related concepts. It is quite different to other experiences of mechanics because the focus is not on the quantitative calculation of energy conservation but on the qualitative understanding of energy degradation. We first…

Feedback Provision in Mentoring Conversation--Differing Mentor and Student Perceptions

ERIC Educational Resources Information Center

Korver, Bettina; Tillema, Harm

2014-01-01

Diverging perceptions between a mentor and a mentee on the nature and content of feedback given in mentoring conversations may have a profound impact on the mentee's learning from conversation. This study gauges whether approaches to mentoring relate to establishing congruency in perceptions on provided feedback. The aim of this research is to…

The Construction of a Public Face as a School Principal

ERIC Educational Resources Information Center

Moller, Jorunn

2012-01-01

Purpose: The purpose of this paper is to examine how successful school leaders in Norway frame their public identity and how their narratives may be understood in relation to different discourses on leadership. Design/methodology/approach: The approach draws upon a theoretical perspective which asserts that there is a profound connection between…

Experimental fire in two different grassland ecosystems in the Southwestern United States

Treesearch

Paulette Ford; Laura Calabrese; Scott Collins; Don Kearney

2011-01-01

Over the last 150 years there have been profound changes in semiarid and aridland ecosystems, including overgrazing and shrub encroachment. Millions of dollars are spent annually for postfire rehabilitation and restoration activities, yet rehabilitation and restoration is often not successful. Although the re-establishment of periodic fire is fundamental to the...

Effective Partnership Working in Music Education: Principles and Practice

ERIC Educational Resources Information Center

Hallam, Richard

2011-01-01

Successful partnerships between policy makers and deliverers, providers and recipients can be both strategic and operational. Partnerships can operate in several different ways at the same time. Joint programmes achieve more than each organization or individual can achieve separately. The impact on children and young people can be profound if the…

The Revelation of Entrepreneurial Spirits on the Cultivation of College Students' Enterprise Qualities: A Case Study in Wenzhou

ERIC Educational Resources Information Center

Ma, Delong

2011-01-01

In Socialist market economy, the characteristics of economic development tend to vary in different regions. Accordingly, enterprise education on college students has to be combined with regional economic features, particularly with a profound knowledge about the characteristics of local entrepreneurs. Insufficient resources and inconvenient…

WAIS-R Verbal and Performance Profiles of Adolescents Referred for Atypical Learning Styles.

ERIC Educational Resources Information Center

Rush, Pamela; And Others

This study investigated Wechsler Adult Intelligence Scale-Revised (WAIS-R) profiles of deaf adolescents referred for academic difficulties. In addition, differences between referral deaf students and non-referral deaf peers were explored. The sample consisted of 28 severely-to-profoundly hearing impaired students enrolled in the School of…

An EUD Approach to the Design of Educational Games

ERIC Educational Resources Information Center

Ardito, Carmelo; Lanzilotti, Rosa

2011-01-01

Distance education has experienced profound changes due to the introduction of new technologies, especially mobile devices of different types. It is necessary to define new learning techniques which are able to capture students' attention and to engage them in their learning activities, reducing problems like distraction generated by the use of…

Organizing Language Intervention Relative to the Client's Personal Experience: A Clinical Case Study

ERIC Educational Resources Information Center

Chen, Liang; Whittington, Diane

2006-01-01

An analysis is presented of two different therapeutic activities designed for a profoundly deaf adult with cerebral palsy, DP. The study draws on techniques of qualitative methodology to identify elements that contribute to effective intervention practices for DP. Results indicate that therapeutic materials and activities must first of all be…

Early-Life Origins of Life-Cycle Well-Being: Research and Policy Implications

ERIC Educational Resources Information Center

Currie, Janet; Rossin-Slater, Maya

2015-01-01

Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population…

The Role of Sex and Gender Socialization in Stress Reactivity

ERIC Educational Resources Information Center

Dedovic, Katarina; Wadiwalla, Mehereen; Engert, Veronika; Pruessner, Jens C.

2009-01-01

Individual health is determined by a myriad of factors. Interestingly, simply being male or female is one such factor that carries profound implications for one's well-being. Intriguing differences between men and women have been observed with respect to vulnerability to and prevalence of particular illnesses. The activity of the major stress…

False Assumptions: The Challenges and Politics of Teaching in China

ERIC Educational Resources Information Center

Getty, Laura J.

2011-01-01

Teachers in American study-abroad programs usually receive little, if any, training before the trip, because "teaching is teaching". The cultural differences between Chinese and American university classrooms, however, affect the students' ability to learn and the teacher's ability to teach in profound ways. Foreign teachers in China require at…

Practicality in Curriculum Building: A Historical Perspective on the Mission of Chinese Education

ERIC Educational Resources Information Center

Bai, Limin

2013-01-01

This paper examines how the definition and interpretation of the concept gewu zhizhi ???? (investigating things and extending knowledge), evolved along with Chinese intellectual efforts to construct the framework for Chinese learning which, in turn, had a profound impact on the development of educational curricula in different historical periods.…

Face Recognition Is Shaped by the Use of Sign Language

ERIC Educational Resources Information Center

Stoll, Chloé; Palluel-Germain, Richard; Caldara, Roberto; Lao, Junpeng; Dye, Matthew W. G.; Aptel, Florent; Pascalis, Olivier

2018-01-01

Previous research has suggested that early deaf signers differ in face processing. Which aspects of face processing are changed and the role that sign language may have played in that change are however unclear. Here, we compared face categorization (human/non-human) and human face recognition performance in early profoundly deaf signers, hearing…

The subjective experience of solitude

Treesearch

Christopher Long; Thomas A. More; James R. Averill

2007-01-01

Solitude is a frequently cited motive for visiting parks, forests, and wilderness areas. But while visitors frequently say they achieve their solitude goals, most visit in groups of two or more, suggesting a conception that differs from the classical ideal of being profoundly alone with the universe. Moreover, solitude often can be experienced negatively, surrounded by...

Teacher Tenure: Fog Warning

ERIC Educational Resources Information Center

Goldhaber, Dan; Walch, Joe

2016-01-01

Debates over the efficacy of tenure are longstanding but tenure reform is now more prominent in the public eye given recent high-profile legislative battles in states like Ohio and Wisconsin. This focus on tenure also is a natural outgrowth of the large body of research showing that differences between individual teachers can have profound effects…

Why CCR: A conversation with Physician Assistant Julia Friend | Center for Cancer Research

Cancer.gov

"Where else can you make such a profound difference not only for the individual now, but for those who come in the future? It is hard work, good work and worth doing well.” Physician Assistant Julia Friend answers our questions about why she loves working for CCR. Read more...

Adaptive Force Control in Grasping as a Function of Level of Developmental Disability

ERIC Educational Resources Information Center

Sprague, R. L.; Deutsch, K. M.; Newell, K. M.

2009-01-01

Background: The adaptation to the task demands of grasping (grip mode and object mass) was investigated as a function of level of developmental disability. Methods: Subjects grasped objects of different grip widths and masses that were instrumented to record grip forces. Results: Proportionally, fewer participants from the profound compared with…

Automatic Word Sense Disambiguation of Acronyms and Abbreviations in Clinical Texts

ERIC Educational Resources Information Center

Moon, Sungrim

2012-01-01

The use of acronyms and abbreviations is increasing profoundly in the clinical domain in large part due to the greater adoption of electronic health record (EHR) systems and increased electronic documentation within healthcare. A single acronym or abbreviation may have multiple different meanings or senses. Comprehending the proper meaning of an…

Evaluation of Core Vocabulary Therapy for Deaf Children: Four Treatment Case Studies

ERIC Educational Resources Information Center

Herman, Rosalind; Ford, Katie; Thomas, Jane; Oyebade, Natalie; Bennett, Danita; Dodd, Barbara

2015-01-01

This study evaluated whether core vocabulary intervention (CVT) improved single word speech accuracy, consistency and intelligibility in four 9-11-year-old children with profound sensori-neural deafness fitted with cochlear implants and/or digital hearing aids. Their speech was characterized by inconsistent production of different error forms for…

Driving Change in Detroit: Libraries Innovating in Step with the Community

ERIC Educational Resources Information Center

Meyer, Jessica; Chang, Allister; Trujillo, Kat

2017-01-01

Often, the conversation about Detroit features the same words used over and over again: poor, broken, abandoned, blighted. But the authors' experiences in the Motor City have shown them something completely different--a community that, in the face of overwhelming challenges, maintains a profound commitment to making Detroit a better place. This…

Between Community and State: The Changing Role of the "Director De Escuela" in Postrevolutionary Mexico

ERIC Educational Resources Information Center

Rockwell, Elsie

2009-01-01

This article analyses the changing role of the principal in Mexico, during a period, 1921-1934, in which the configurations sustaining and surrounding schooling were profoundly transformed. It compares the experience of three "directores" working in towns that differed in their expectations and relationship to state and federal…

Oil and gas taxation in Algeria: exploration and production activities

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

Frilet, M.

1982-09-01

The Algerian taxation scheme for foreign companies involved in the petroleum sector is profoundly different depending on whether the company is directly involved in exploration and production or is merely acting as a service company or contractor. This article discusses Algerian taxation of foreign companies directly involved in production and exploration.

Darwin's mistake: explaining the discontinuity between human and nonhuman minds.

PubMed

Penn, Derek C; Holyoak, Keith J; Povinelli, Daniel J

2008-04-01

Over the last quarter century, the dominant tendency in comparative cognitive psychology has been to emphasize the similarities between human and nonhuman minds and to downplay the differences as "one of degree and not of kind" (Darwin 1871). In the present target article, we argue that Darwin was mistaken: the profound biological continuity between human and nonhuman animals masks an equally profound discontinuity between human and nonhuman minds. To wit, there is a significant discontinuity in the degree to which human and nonhuman animals are able to approximate the higher-order, systematic, relational capabilities of a physical symbol system (PSS) (Newell 1980). We show that this symbolic-relational discontinuity pervades nearly every domain of cognition and runs much deeper than even the spectacular scaffolding provided by language or culture alone can explain. We propose a representational-level specification as to where human and nonhuman animals' abilities to approximate a PSS are similar and where they differ. We conclude by suggesting that recent symbolic-connectionist models of cognition shed new light on the mechanisms that underlie the gap between human and nonhuman minds.

Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome.

PubMed

Ni, Christina; Zhang, Deming; Beyer, Lisa A; Halsey, Karin E; Fukui, Hideto; Raphael, Yehoash; Dolan, David F; Hornyak, Thomas J

2013-01-01

The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia-White (Mitf(Mi-wh) /+) mice were studied and hearing function of these mice characterized. Mitf(Mi-wh) /+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. Mitf(Mi-wh) /+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the Mitf(Mi-wh) /+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes. © 2012 John Wiley & Sons A/S.

Characterizing complex structural variation in germline and somatic genomes

PubMed Central

Quinlan, Aaron R.; Hall, Ira M.

2011-01-01

Genome structural variation (SV) is a major source of genetic diversity in mammals and a hallmark of cancer. While SV is typically defined by its canonical forms – duplication, deletion, insertion, inversion and translocation – recent breakpoint mapping studies have revealed a surprising number of “complex” variants that evade simple classification. Complex SVs are defined by clustered breakpoints that arose through a single mutation but cannot be explained by one simple end-joining or recombination event. Some complex variants exhibit profoundly complicated rearrangements between distinct loci from multiple chromosomes, while others involve more subtle alterations at a single locus. These diverse and unpredictable features present a challenge for SV mapping experiments. Here, we review current knowledge of complex SV in mammals, and outline techniques for identifying and characterizing complex variants using next-generation DNA sequencing. PMID:22094265

Equivalence relations in individuals with language limitations and mental retardation.

PubMed Central

O'Donnell, Jennifer; Saunders, Kathryn J

2003-01-01

The study of equivalence relations exhibited by individuals with mental retardation and language limitations holds the promise of providing information of both theoretical and practical significance. We reviewed the equivalence literature with this population, defined in terms of subjects having moderate, severe, or profound mental retardation. The literature includes 55 such individuals, most of whom showed positive outcomes on equivalence tests. The results to date suggest that naming skills are not necessary for positive equivalence test outcomes. Thus far, however, relatively few subjects with minimal language have been studied. Moreover, we suggest that the scientific contributions of studies in this area would be enhanced with better documentation of language skills and other subject characteristics. With recent advances in laboratory procedures for establishing the baseline performances necessary for equivalence tests, this research area is poised for rapid growth. PMID:13677612

A black hole nova obscured by an inner disk torus.

PubMed

Corral-Santana, J M; Casares, J; Muñoz-Darias, T; Rodríguez-Gil, P; Shahbaz, T; Torres, M A P; Zurita, C; Tyndall, A A

2013-03-01

Stellar-mass black holes (BHs) are mostly found in x-ray transients, a subclass of x-ray binaries that exhibit violent outbursts. None of the 50 galactic BHs known show eclipses, which is surprising for a random distribution of inclinations. Swift J1357.2-093313 is a very faint x-ray transient detected in 2011. On the basis of spectroscopic evidence, we show that it contains a BH in a 2.8-hour orbital period. Further, high-time-resolution optical light curves display profound dips without x-ray counterparts. The observed properties are best explained by the presence of an obscuring toroidal structure moving outward in the inner disk, seen at very high inclination. This observational feature should play a key role in models of inner accretion flows and jet collimation mechanisms in stellar-mass BHs.

Hippocampal damage impairs long-term spatial memory in rats: comparison between electrolytic and neurotoxic lesions.

PubMed

Ramos, Juan M J

2008-03-18

In previous studies we have suggested that the dorsal hippocampus is involved in spatial consolidation by showing that rats with electrolytic hippocampal lesions exhibit a profound deficit in the retention of an allocentric task 24 days after the acquisition. However, in various hippocampal-dependent tasks, several studies have shown an overestimation of the behavioral deficit when electrolytic versus axon-sparing cytotoxic lesions has been used. For this reason, in this report we compare the effects on spatial retention of electrolytic and neurotoxic lesions to the dorsal hippocampus. Results showed a similar deficit in spatial retention in both groups 24 days after acquisition. Thus, the hippocampus proper and not fibers of passage or extrahippocampal damage is directly responsible for the deficit in spatial retention seen in rats with electrolytic lesions.

Achieving profound anesthesia using the intraosseous technique.

PubMed

Coury, K A

1997-10-01

The intraosseous technique has been described as a useful adjunct to primary anesthetic administration. It has several advantages (Table 3) over other supplemental techniques in that it is relatively simple to implement into routine practice, it affords fast, predictable results, and it is relatively painless. The technique has been shown to be very successful in achieving profound pulpal anesthesia when administered as a supplement to the inferior alveolar nerve block and is effective in achieving profound anesthesia in irreversibly inflamed teeth, especially mandibular molars.

Vibrotactile Discrimination Training Affects Brain Connectivity in Profoundly Deaf Individuals

PubMed Central

González-Garrido, Andrés A.; Ruiz-Stovel, Vanessa D.; Gómez-Velázquez, Fabiola R.; Vélez-Pérez, Hugo; Romo-Vázquez, Rebeca; Salido-Ruiz, Ricardo A.; Espinoza-Valdez, Aurora; Campos, Luis R.

2017-01-01

Early auditory deprivation has serious neurodevelopmental and cognitive repercussions largely derived from impoverished and delayed language acquisition. These conditions may be associated with early changes in brain connectivity. Vibrotactile stimulation is a sensory substitution method that allows perception and discrimination of sound, and even speech. To clarify the efficacy of this approach, a vibrotactile oddball task with 700 and 900 Hz pure-tones as stimuli [counterbalanced as target (T: 20% of the total) and non-target (NT: 80%)] with simultaneous EEG recording was performed by 14 profoundly deaf and 14 normal-hearing (NH) subjects, before and after a short training period (five 1-h sessions; in 2.5–3 weeks). A small device worn on the right index finger delivered sound-wave stimuli. The training included discrimination of pure tone frequency and duration, and more complex natural sounds. A significant P300 amplitude increase and behavioral improvement was observed in both deaf and normal subjects, with no between group differences. However, a P3 with larger scalp distribution over parietal cortical areas and lateralized to the right was observed in the profoundly deaf. A graph theory analysis showed that brief training significantly increased fronto-central brain connectivity in deaf subjects, but not in NH subjects. Together, ERP tools and graph methods depicted the different functional brain dynamic in deaf and NH individuals, underlying the temporary engagement of the cognitive resources demanded by the task. Our findings showed that the index-fingertip somatosensory mechanoreceptors can discriminate sounds. Further studies are necessary to clarify brain connectivity dynamics associated with the performance of vibrotactile language-related discrimination tasks and the effect of lengthier training programs. PMID:28220063

Vibrotactile Discrimination Training Affects Brain Connectivity in Profoundly Deaf Individuals.

PubMed

González-Garrido, Andrés A; Ruiz-Stovel, Vanessa D; Gómez-Velázquez, Fabiola R; Vélez-Pérez, Hugo; Romo-Vázquez, Rebeca; Salido-Ruiz, Ricardo A; Espinoza-Valdez, Aurora; Campos, Luis R

2017-01-01

Early auditory deprivation has serious neurodevelopmental and cognitive repercussions largely derived from impoverished and delayed language acquisition. These conditions may be associated with early changes in brain connectivity. Vibrotactile stimulation is a sensory substitution method that allows perception and discrimination of sound, and even speech. To clarify the efficacy of this approach, a vibrotactile oddball task with 700 and 900 Hz pure-tones as stimuli [counterbalanced as target (T: 20% of the total) and non-target (NT: 80%)] with simultaneous EEG recording was performed by 14 profoundly deaf and 14 normal-hearing (NH) subjects, before and after a short training period (five 1-h sessions; in 2.5-3 weeks). A small device worn on the right index finger delivered sound-wave stimuli. The training included discrimination of pure tone frequency and duration, and more complex natural sounds. A significant P300 amplitude increase and behavioral improvement was observed in both deaf and normal subjects, with no between group differences. However, a P3 with larger scalp distribution over parietal cortical areas and lateralized to the right was observed in the profoundly deaf. A graph theory analysis showed that brief training significantly increased fronto-central brain connectivity in deaf subjects, but not in NH subjects. Together, ERP tools and graph methods depicted the different functional brain dynamic in deaf and NH individuals, underlying the temporary engagement of the cognitive resources demanded by the task. Our findings showed that the index-fingertip somatosensory mechanoreceptors can discriminate sounds. Further studies are necessary to clarify brain connectivity dynamics associated with the performance of vibrotactile language-related discrimination tasks and the effect of lengthier training programs.

Afferent Neural Feedback Overrides the Modulating Effects of Arousal, Hypercapnia and Hypoxemia on Neonatal Cardio-respiratory Control.

PubMed

Lumb, Kathleen J; Schneider, Jennifer M; Ibrahim, Thowfique; Rigaux, Anita; Hasan, Shabih U

2018-04-20

Evidence at whole animal, organ-system, and cellular and molecular levels suggests that afferent volume feedback is critical for establishment of adequate ventilation at birth. Due to the irreversible nature of vagal ablation studies to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control. During reversible perineural vagal block, profound apneas, and hypoxemia and hypercarbia were observed necessitating termination of perineural blockade. Respiratory depression and apneas were independent of the sleep states. We demonstrate that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life-threatening apneas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic-hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during early postnatal period. Seven lambs were instrumented during the first 48h of life to record/analyze sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Post-operatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30 minutes. Compared with baseline values, pHa, PaO 2 and SaO 2 decreased and PaCO 2 increased during perineural blockade (P < 0.05). Four of seven animals exhibited apneas of ≥20 sec requiring immediate termination of perineural blockade. Breathing rates decreased from the baseline value of 53 ± 12 to 24 ± 20 breaths/min during blockade despite an increased PaCO 2 (P < 0.001). Following blockade, breathing patterns returned to baseline values despite marked hypocapnia (PaCO 2 33 ± 3 torr; P = 0.03). Respiratory depression and apneas were independent of sleep states. This study provides the much needed physiologic evidence that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Rather, change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Fire Safety Training with Adults Who Are Profoundly Mentally Retarded.

ERIC Educational Resources Information Center

Rae, Rosamond; Roll, David

1985-01-01

An intensive fire safety training program for profoundly mentally retarded institutionalized persons resulted in a significant decrease in mean evacuation time and gradual substitution of verbal for physical prompts. (CL)

Unilateral Hearing Loss: Understanding Speech Recognition and Localization Variability - Implications for Cochlear Implant Candidacy

PubMed Central

Firszt, Jill B.; Reeder, Ruth M.; Holden, Laura K.

2016-01-01

Objectives At a minimum, unilateral hearing loss (UHL) impairs sound localization ability and understanding speech in noisy environments, particularly if the loss is severe to profound. Accompanying the numerous negative consequences of UHL is considerable unexplained individual variability in the magnitude of its effects. Identification of co-variables that affect outcome and contribute to variability in UHLs could augment counseling, treatment options, and rehabilitation. Cochlear implantation as a treatment for UHL is on the rise yet little is known about factors that could impact performance or whether there is a group at risk for poor cochlear implant outcomes when hearing is near-normal in one ear. The overall goal of our research is to investigate the range and source of variability in speech recognition in noise and localization among individuals with severe to profound UHL and thereby help determine factors relevant to decisions regarding cochlear implantation in this population. Design The present study evaluated adults with severe to profound UHL and adults with bilateral normal hearing. Measures included adaptive sentence understanding in diffuse restaurant noise, localization, roving-source speech recognition (words from 1 of 15 speakers in a 140° arc) and an adaptive speech-reception threshold psychoacoustic task with varied noise types and noise-source locations. There were three age-gender-matched groups: UHL (severe to profound hearing loss in one ear and normal hearing in the contralateral ear), normal hearing listening bilaterally, and normal hearing listening unilaterally. Results Although the normal-hearing-bilateral group scored significantly better and had less performance variability than UHLs on all measures, some UHL participants scored within the range of the normal-hearing-bilateral group on all measures. The normal-hearing participants listening unilaterally had better monosyllabic word understanding than UHLs for words presented on the blocked/deaf side but not the open/hearing side. In contrast, UHLs localized better than the normal hearing unilateral listeners for stimuli on the open/hearing side but not the blocked/deaf side. This suggests that UHLs had learned strategies for improved localization on the side of the intact ear. The UHL and unilateral normal hearing participant groups were not significantly different for speech-in-noise measures. UHL participants with childhood rather than recent hearing loss onset localized significantly better; however, these two groups did not differ for speech recognition in noise. Age at onset in UHL adults appears to affect localization ability differently than understanding speech in noise. Hearing thresholds were significantly correlated with speech recognition for UHL participants but not the other two groups. Conclusions Auditory abilities of UHLs varied widely and could be explained only in part by hearing threshold levels. Age at onset and length of hearing loss influenced performance on some, but not all measures. Results support the need for a revised and diverse set of clinical measures, including sound localization, understanding speech in varied environments and careful consideration of functional abilities as individuals with severe to profound UHL are being considered potential cochlear implant candidates. PMID:28067750

Peers Influence Prosocial Behavior in Adolescent Males with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Van Hoorn, Jorien; Van Dijk, Eric; Crone, Eveline A.; Stockmann, Lex; Rieffe, Carolien

2017-01-01

Peer influence has a profound impact on decision-making in typically developing adolescents. In this study, we examined to what extent adolescent males (age 11-17 years; N = 144) with and without autism (ASD) were influenced by peer feedback on prosocial behavior, and which factors were related to individual differences in peer feedback…

Marked Differences in Drug-Induced Methemoglobinemia in Sheep are not Due to RBC Glucose-6-Phosphate Dehydrogenase, Reduced Glutathione, or Methemoglobin Reductase Activity.

DTIC Science & Technology

Benzocaine is a commonly used topical anesthetic that is structurally similar to current candidates for cyanide prophylaxis. Benzocaine induces...profound methemoglobinemia in some sheep but not others. After topical benzocaine administration certain sheep respond to form MHb (elevated MHb 16-50

The Experiential Teaching of Berlin--Theoretical Reflections and Best Practices from a Study Abroad Site

ERIC Educational Resources Information Center

Wagenknecht, Thomas

2011-01-01

Creating first hand experiences of urban cultures that focus on reflection and leave profound impressions on students while providing the framing for future cycles of experiential learning is a complex and difficult dynamic to navigate. The way urban manifestations of a different culture are directly experienced varies depending on the…

Self-Harm among People with Intellectual Disabilities Living in Secure Service Provision: A Qualitative Exploration

ERIC Educational Resources Information Center

Brown, Jessica; Beail, Nigel

2009-01-01

Background: Research into self-harm among people with intellectual disabilities has focused predominantly on high frequency internally maladaptive behaviour among people whose disability is severe or profound. Research into different forms of self-harm, such as cutting or burning the skin, found in those with mild intellectual disabilities;…

Bringing fire back. The changing regimes of the Appalachian mixed-oak forest

Treesearch

Patrick Brose; Thomas Schuler; David Van Lear; John Berst

2001-01-01

Since vegetative associations stabilized about 4,000 years ago, the Appalachian mixed-oak forests have experienced three profoundly different fire regimes. Periodic, low-intensity surface fires lit by American Indians characterized the first regime, and this regime helped perpetuate oak as one of the dominant species groups. The Industrial Revolution led to high-...

Education in the Virtues: Tragic Emotions and the Artistic Imagination

ERIC Educational Resources Information Center

Penwell, Derek L.

2009-01-01

The profoundly thoughtful--not to mention extensive--character of the scholarship historically applied to the nature of the difference between Plato and Aristotle on the issue of the tragic emotions raises the obvious question: What new is there left to say? In this article, the author seeks to hold together two separate issues that have occupied…

Kocuria rosea, kocuria kristinae, leuconostoc mesenteroides as caries-causing representatives of oral microflora.

PubMed

Ananieva, Maiia M; Faustova, Mariia O; Basarab, Iaroslav O; Loban', Galina A

2017-01-01

Recently, opportunistic microflora are increasingly known to be involved in the development of pathological processes in various systems and organs. This situation promotes interest in their detailed study as causative agents of bacterial infections. To study the microbial species residing in carious cavities in acute profound caries. The study involved 14 people with a diagnosis of acute profound caries. Microbiological methods included determining species of microorganisms' cultures from carious cavities in acute profound caries. Final identification was carried out by automatic bacteriological analyzer Vitec-2compact bioMérieux. Among the bacteria isolated, Kocuria rosae, Kocuria kristinae, and Leuconostoc mesenteroides are the focus of the authors' attention due to their identification rate in the patients. These microbial species are little studied due to the lack of data on their cariogenic associations.The meticulous study of the microorganisms, isolated from carious cavities in patients with acute profound caries by automatic bacteriological analyzer Vitec-2 Systems bioMérieux, and findings on their biochemical properties allow us to conclude that Kocuria rosae, Kocuria kristinae, and Leuconostoc mesenteroides are among the microorganisms making up the microflora of carious cavities under acute profound caries and are involved in the development of the caries process.

The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers.

PubMed

Roseman, Leor; Leech, Robert; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

2014-01-01

Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template of different independent components analysis (ICA)-derived resting state networks (RSNs) under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.

Are hearing losses among young Maori different to those found in the young NZ European population?

PubMed

Digby, Janet E; Purdy, Suzanne C; Kelly, Andrea S; Welch, David; Thorne, Peter R

2014-07-18

This study was undertaken to determine if young Maori have more permanent bilateral hearing loss, or less severe and profound hearing loss than New Zealand (NZ) Europeans. Data include hearing-impaired children from birth to 19 years of age from the New Zealand Deafness Notification Database (DND) and covering the periods 1982-2005 and 2009-2013. These were retrospectively analysed, as was information on children and young people with cochlear implants. Young Maori are more likely to be diagnosed with permanent hearing loss greater than 26 dB HL, averaged across speech frequencies, with 39-43% of hearing loss notifications listed as Maori. Maori have a lower prevalence of severe/profound losses (n=1571, chi squared=22.08, p=0.01) but significantly more bilateral losses than their NZ European peers (n=595, Chi-squared=9.05, p=0.01). The difference in severity profile is supported by cochlear implant data showing Maori are less likely to receive a cochlear implant. There are significant differences in the proportion of bilateral (compared to unilateral) losses and in the rates and severity profile of hearing loss among young Maori when compared with their NZ European peers. This has implications for screening and other hearing services in NZ.

Life-History and Spatial Determinants of Somatic Growth Dynamics in Komodo Dragon Populations

PubMed Central

Laver, Rebecca J.; Purwandana, Deni; Ariefiandy, Achmad; Imansyah, Jeri; Forsyth, David; Ciofi, Claudio; Jessop, Tim S.

2012-01-01

Somatic growth patterns represent a major component of organismal fitness and may vary among sexes and populations due to genetic and environmental processes leading to profound differences in life-history and demography. This study considered the ontogenic, sex-specific and spatial dynamics of somatic growth patterns in ten populations of the world’s largest lizard the Komodo dragon (Varanus komodoensis). The growth of 400 individual Komodo dragons was measured in a capture-mark-recapture study at ten sites on four islands in eastern Indonesia, from 2002 to 2010. Generalized Additive Mixed Models (GAMMs) and information-theoretic methods were used to examine how growth rates varied with size, age and sex, and across and within islands in relation to site-specific prey availability, lizard population density and inbreeding coefficients. Growth trajectories differed significantly with size and between sexes, indicating different energy allocation tactics and overall costs associated with reproduction. This leads to disparities in maximum body sizes and longevity. Spatial variation in growth was strongly supported by a curvilinear density-dependent growth model with highest growth rates occurring at intermediate population densities. Sex-specific trade-offs in growth underpin key differences in Komodo dragon life-history including evidence for high costs of reproduction in females. Further, inverse density-dependent growth may have profound effects on individual and population level processes that influence the demography of this species. PMID:23028983

The dopant type and amount governs the electrochemical performance of graphene platforms for the antioxidant activity quantification

NASA Astrophysics Data System (ADS)

Hui, Kai Hwee; Ambrosi, Adriano; Sofer, Zdeněk; Pumera, Martin; Bonanni, Alessandra

2015-05-01

Graphene doped with heteroatoms can show new or improved properties as compared to the original undoped material. It has been reported that the type of heteroatoms and the doping conditions can have a strong influence on the electronic and electrochemical properties of the resulting material. Here, we wish to compare the electrochemical behavior of two n-type and two p-type doped graphenes, namely boron-doped graphenes and nitrogen-doped graphenes containing different amounts of heteroatoms. We show that the boron-doped graphene containing a higher amount of dopants provides the best electroanalytical performance in terms of calibration sensitivity, selectivity and linearity of response for the detection of gallic acid normally used as the standard probe for the quantification of antioxidant activity of food and beverages. Our findings demonstrate that the type and amount of heteroatoms used for the doping have a profound influence on the electrochemical detection of gallic acid rather than the structural properties of the materials such as amounts of defects, oxygen functionalities and surface area. This finding has a profound influence on the application of doped graphenes in the field of analytical chemistry.Graphene doped with heteroatoms can show new or improved properties as compared to the original undoped material. It has been reported that the type of heteroatoms and the doping conditions can have a strong influence on the electronic and electrochemical properties of the resulting material. Here, we wish to compare the electrochemical behavior of two n-type and two p-type doped graphenes, namely boron-doped graphenes and nitrogen-doped graphenes containing different amounts of heteroatoms. We show that the boron-doped graphene containing a higher amount of dopants provides the best electroanalytical performance in terms of calibration sensitivity, selectivity and linearity of response for the detection of gallic acid normally used as the standard probe for the quantification of antioxidant activity of food and beverages. Our findings demonstrate that the type and amount of heteroatoms used for the doping have a profound influence on the electrochemical detection of gallic acid rather than the structural properties of the materials such as amounts of defects, oxygen functionalities and surface area. This finding has a profound influence on the application of doped graphenes in the field of analytical chemistry. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01045d

Human dignity and the profoundly disabled: a theological perspective.

PubMed

Matthews, Pia

2011-01-01

One challenge to the concept of human dignity is that it is a rootless notion invoked simply to mask inequalities that inevitably exist between human beings. This privileging of humans is speciesist and its weak point is the profoundly disabled human being. This article argues that far from being a weak point, the profoundly disabled person is a source of strength and witness to the intrinsic dignity that all human beings have by virtue of being human. The disabled represent the reality of human existence that is both strong and fragile. Although human dignity can be understood philosophically its depth is rooted in Christian theological insights. The profoundly disabled occupy a privileged position and share in a theology of mission since they testify to the interdependence of every human being and human dependence on God to a myopic world that only values strength, autonomy and independence.

Host-specific parvovirus evolution in nature is recapitulated by in vitro adaptation to different carnivore species.

PubMed

Allison, Andrew B; Kohler, Dennis J; Ortega, Alicia; Hoover, Elizabeth A; Grove, Daniel M; Holmes, Edward C; Parrish, Colin R

2014-11-01

Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats and related carnivores. Although both viruses have wide host ranges, analysis of viral sequences recovered from different wild carnivore species, as shown here, demonstrated that>95% were derived from CPV-like viruses, suggesting that CPV is dominant in sylvatic cycles. Many viral sequences showed host-specific mutations in their capsid proteins, which were often close to sites known to control binding to the transferrin receptor (TfR), the host receptor for these carnivore parvoviruses, and which exhibited frequent parallel evolution. To further examine the process of host adaptation, we passaged parvoviruses with alternative backgrounds in cells from different carnivore hosts. Specific mutations were selected in several viruses and these differed depending on both the background of the virus and the host cells in which they were passaged. Strikingly, these in vitro mutations recapitulated many specific changes seen in viruses from natural populations, strongly suggesting they are host adaptive, and which were shown to result in fitness advantages over their parental virus. Comparison of the sequences of the transferrin receptors of the different carnivore species demonstrated that many mutations occurred in and around the apical domain where the virus binds, indicating that viral variants were likely selected through their fit to receptor structures. Some of the viruses accumulated high levels of variation upon passage in alternative hosts, while others could infect multiple different hosts with no or only a few additional mutations. Overall, these studies demonstrate that the evolutionary history of a virus, including how long it has been circulating and in which hosts, as well as its phylogenetic background, has a profound effect on determining viral host range.

Host-Specific Parvovirus Evolution in Nature Is Recapitulated by In Vitro Adaptation to Different Carnivore Species

PubMed Central

Allison, Andrew B.; Kohler, Dennis J.; Ortega, Alicia; Hoover, Elizabeth A.; Grove, Daniel M.; Holmes, Edward C.; Parrish, Colin R.

2014-01-01

Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats and related carnivores. Although both viruses have wide host ranges, analysis of viral sequences recovered from different wild carnivore species, as shown here, demonstrated that >95% were derived from CPV-like viruses, suggesting that CPV is dominant in sylvatic cycles. Many viral sequences showed host-specific mutations in their capsid proteins, which were often close to sites known to control binding to the transferrin receptor (TfR), the host receptor for these carnivore parvoviruses, and which exhibited frequent parallel evolution. To further examine the process of host adaptation, we passaged parvoviruses with alternative backgrounds in cells from different carnivore hosts. Specific mutations were selected in several viruses and these differed depending on both the background of the virus and the host cells in which they were passaged. Strikingly, these in vitro mutations recapitulated many specific changes seen in viruses from natural populations, strongly suggesting they are host adaptive, and which were shown to result in fitness advantages over their parental virus. Comparison of the sequences of the transferrin receptors of the different carnivore species demonstrated that many mutations occurred in and around the apical domain where the virus binds, indicating that viral variants were likely selected through their fit to receptor structures. Some of the viruses accumulated high levels of variation upon passage in alternative hosts, while others could infect multiple different hosts with no or only a few additional mutations. Overall, these studies demonstrate that the evolutionary history of a virus, including how long it has been circulating and in which hosts, as well as its phylogenetic background, has a profound effect on determining viral host range. PMID:25375184

Differences in bone structure between rheumatoid arthritis and psoriatic arthritis patients relative to autoantibody positivity.

PubMed

Kocijan, Roland; Finzel, Stephanie; Englbrecht, Matthias; Engelke, Klaus; Rech, Juergen; Schett, Georg

2014-11-01

To investigate whether trabecular and cortical bone structure differ between patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). So far, no study has performed a detailed comparative analysis of bone structure in patients with RA and PsA. 110 patients (60 RA, 50 PsA) received high-resolution peripheral quantitative CT of the distal radius. Demographic and disease-specific parameters including anti-rheumatic treatment, bone erosion status and previous fractures were recorded. RA and PsA patients were comparable in age, gender, body mass index, disease duration, disease activity, functional status, antirheumatic treatment and bone erosion status. No significant differences were found for volumetric bone mineral density (BMD), including total BMD (300±77 vs 316±62 mgHA/cm(3)), trabecular BMD (152±46 vs 165±40 mgHA/cm(3)) and cortical BMD (787±113 vs 818±76 mgHA/cm(3)) when comparing RA patients to PsA patients, respectively. However, in contrast to seronegative RA, seropositive RA showed significantly reduced trabecular BMD (p=0.007), bone volume per tissue volume (p=0.007) and trabecular number (p=0.044), as well as a strong trend towards higher trabecular inhomogeneity compared to PsA patients. In the regression analysis, higher age, female gender and presence of autoantibodies were independently associated with trabecular bone loss. Seropositive RA exhibits more profound changes in trabecular bone architecture than seronegative RA or PsA. The data support the concept that seropositive RA is a disease entity that is distinct from seronegative RA and PsA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Combined influence of adjuvant therapy and interval after surgery on peripheral CD4+ T lymphocytes in patients with esophageal squamous cell carcinoma

PubMed Central

LING, YANG; FAN, LIEYING; DONG, CHUNLEI; ZHU, JING; LIU, YONGPING; NI, YAN; ZHU, CHANGTAI; ZHANG, CHANGSONG

2010-01-01

The aim of this study was to investigate possible differences in cellular immunity between chemo- and/or radiotherapy groups during a long interval after surgery in esophageal squamous cell carcinoma (ESCC) patients. Cellular immunity was assessed as peripheral lymphocyte subsets in response to chemotherapy (CT), radiotherapy (RT) and CT+RT by flow cytometric analysis. There were 139 blood samples obtained at different time points relative to surgery from 73 patients with ESCC. The changes in the absolute and relative proportions of lymphocyte phenotypes were significant among the adjuvant therapy groups. There were significant differences in the absolute counts of CD4+ and CD8+ T cells among the interval groups, and a lower CD4/CD8 ratio was found in patients following a prolonged interval. RT alone had a profound effect on the absolute counts of CD3+, CD4+ and CD8+ T cells compared with the other groups. CD4+ T cells exhibited a decreasing trend during a long interval, leading to a prolonged T-cell imbalance after surgery. Univariate analysis revealed that the interaction of the type of adjuvant therapy and the interval after surgery was correlated only with the percentage of CD4+ T cells. The percentage of CD4+ T cells can be used as an indicator of the cellular immunity after surgery in ESCC patients. However, natural killer cells consistently remained suppressed in ESCC patients following adjuvant therapy after surgery. These findings confirm an interaction between adjuvant therapy and the interval after surgery on peripheral CD4+ T cells, and implies that adjuvant therapy may have selective influence on the cellular immunity of ESCC patients after surgery. PMID:23136603

Unravelling the Molecular Determinants of Bee Sensitivity to Neonicotinoid Insecticides.

PubMed

Manjon, Cristina; Troczka, Bartlomiej J; Zaworra, Marion; Beadle, Katherine; Randall, Emma; Hertlein, Gillian; Singh, Kumar Saurabh; Zimmer, Christoph T; Homem, Rafael A; Lueke, Bettina; Reid, Rebecca; Kor, Laura; Kohler, Maxie; Benting, Jürgen; Williamson, Martin S; Davies, T G Emyr; Field, Linda M; Bass, Chris; Nauen, Ralf

2018-04-02

The impact of neonicotinoid insecticides on the health of bee pollinators is a topic of intensive research and considerable current debate [1]. As insecticides, certain neonicotinoids, i.e., N-nitroguanidine compounds such as imidacloprid and thiamethoxam, are as intrinsically toxic to bees as to the insect pests they target. However, this is not the case for all neonicotinoids, with honeybees orders of magnitude less sensitive to N-cyanoamidine compounds such as thiacloprid [2]. Although previous work has suggested that this is due to rapid metabolism of these compounds [2-5], the specific gene(s) or enzyme(s) involved remain unknown. Here, we show that the sensitivity of the two most economically important bee species to neonicotinoids is determined by cytochrome P450s of the CYP9Q subfamily. Radioligand binding and inhibitor assays showed that variation in honeybee sensitivity to N-nitroguanidine and N-cyanoamidine neonicotinoids does not reside in differences in their affinity for the receptor but rather in divergent metabolism by P450s. Functional expression of the entire CYP3 clade of P450s from honeybees identified a single P450, CYP9Q3, that metabolizes thiacloprid with high efficiency but has little activity against imidacloprid. We demonstrate that bumble bees also exhibit profound differences in their sensitivity to different neonicotinoids, and we identify CYP9Q4 as a functional ortholog of honeybee CYP9Q3 and a key metabolic determinant of neonicotinoid sensitivity in this species. Our results demonstrate that bee pollinators are equipped with biochemical defense systems that define their sensitivity to insecticides and this knowledge can be leveraged to safeguard bee health. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Connections that Count: Brain-Computer Interface Enables the Profoundly Paralyzed to Communicate

MedlinePlus

... Home Current Issue Past Issues Connections that Count: Brain-Computer Interface Enables the Profoundly Paralyzed to Communicate ... of this page please turn Javascript on. A brain-computer interface (BCI) system This brain-computer interface ( ...

Breakdown of Universality for Unequal-Mass Fermi Gases with Infinite Scattering Length

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

Blume, D.; Daily, K. M.

We treat small trapped unequal-mass two-component Fermi gases at unitarity within a nonperturbative microscopic framework and investigate the system properties as functions of the mass ratio {kappa}, and the numbers N{sub 1} and N{sub 2} of heavy and light fermions. While equal-mass Fermi gases with infinitely large interspecies s-wave scattering length a{sub s} are universal, we find that unequal-mass Fermi gases are, for sufficiently large {kappa} and in the regime where Efimov physics is absent, not universal. In particular, the (N{sub 1},N{sub 2})=(2,1) and (3, 1) systems exhibit three-body and four-body resonances at {kappa}=12.314(2) and 10.4(2), respectively, as well asmore » surprisingly large finite-range effects. These findings have profound implications for ongoing experimental efforts and quantum simulation proposals that utilize unequal-mass atomic Fermi gases.« less

Cyclic lipopeptide biosurfactant from Bacillus tequilensis exhibits multifarious activity.

PubMed

Pradhan, Arun Kumar; Rath, Animesha; Pradhan, Nilotpala; Hazra, Rupenangshu Kumar; Nayak, Rati Ranjan; Kanjilal, Sanjit

2018-06-01

Bacillus tequilensis strain CH had been previously shown to produce a biosurfactant. In this study, chemical structure of the purified biosurfactant was determined by using high performance liquid chromatography and liquid chromatography-mass spectroscopy as a 10 amino acid cyclic lipopeptide (CL). The cyclic lipopeptide was found to be active against Anopheles culicifacies larvae with a LC 50 of 110 µg/ml in 2 days. 1 ppm cadmium (Cd) which had a profound mutagenic effect on the cell division of onion ( Allium cepa ) root tip cell resulting in abnormal metaphase, abnormal anaphase and nuclei elongation was partially reversed in the presence of 0.1 mg/ml of CL (52% cells dividing normally and 8% with abnormal division) and was comparable to control experiment where no Cd was present. Thus, the CL described in this report may have applications in eliminating larvae from water repository systems and in reversing the effects of cadmium pollution.

Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

PubMed Central

Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki; Hosaka, Kayoko; Seki, Takahiro; Andersson, Patrik; Lim, Sharon; Fischer, Carina; Nakamura, Masaki; Abe, Mitsuhiko; Cao, Renhai; Skov, Peter Vilhelm; Chen, Fang; Chen, Xiaoyun; Lu, Yongtian; Nie, Guohui; Cao, Yihai

2016-01-01

The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the ‘off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers. PMID:27580750

Earnings Management before Rights Issues and the Subsequent Cash Transfer in Chinese Firms

NASA Astrophysics Data System (ADS)

Tsai, Bi-Huei

2009-08-01

Unlike private enterprises in developed markets, political influence is profound upon Chinese state-dominated firms. Under this consideration, this paper demonstrates how political impact interferes in Chinese managers' decisions. State-assigned managers were found to deliberately transfer cash raised via rights issues from the public shareholders to the state by cash dividends in order to please Chinese politicians. Especially, to meet the regulatory requirement of rights issues, managers from firms which distributed more cash dividends in the same year of rights issues were more likely to inflate earnings before rights issues. The earnings inflation which managers use to boost firm's incomes is defined as "earnings management." Furthermore, the empirical results also exhibit that firm's close relationship with the state enables managers to obtain approvals of rights issues easily, which reduces the firm's earnings management tendency. The manager's incentives of earnings management is closely attributed to the political intervention.

Dynamics of cortical dendritic membrane potential and spikes in freely behaving rats.

PubMed

Moore, Jason J; Ravassard, Pascal M; Ho, David; Acharya, Lavanya; Kees, Ashley L; Vuong, Cliff; Mehta, Mayank R

2017-03-24

Neural activity in vivo is primarily measured using extracellular somatic spikes, which provide limited information about neural computation. Hence, it is necessary to record from neuronal dendrites, which can generate dendritic action potentials (DAPs) in vitro, which can profoundly influence neural computation and plasticity. We measured neocortical sub- and suprathreshold dendritic membrane potential (DMP) from putative distal-most dendrites using tetrodes in freely behaving rats over multiple days with a high degree of stability and submillisecond temporal resolution. DAP firing rates were several-fold larger than somatic rates. DAP rates were also modulated by subthreshold DMP fluctuations, which were far larger than DAP amplitude, indicating hybrid, analog-digital coding in the dendrites. Parietal DAP and DMP exhibited egocentric spatial maps comparable to pyramidal neurons. These results have important implications for neural coding and plasticity. Copyright © 2017, American Association for the Advancement of Science.

Family therapy with deaf persons: the systemic utilization of an interpreter.

PubMed

Harvey, M A

1984-06-01

This paper discusses the theory and practice of providing family therapy to families in which there are hearing parents and at least one Deaf child, particularly regarding the optimal utilization of an interpreter. The therapist must be knowledgeable about the psychosocial effects of deafness, the cultural aspects of deafness, and preferably be able to use American Sign Language and Signed English. The therapeutic benefit of utilizing an interpreter extends far beyond simply facilitating communication between each family member whose primary-language is either spoken English or Sign Language. The presence of an interpreter helps the therapist to modify family rules that deny the implications of deafness and prohibit the use of Sign Language, to modify the balance of power in the family, and to encourage participants to exhibit the ego defense mechanisms of projection and transference. The family therapist can utilize those subtle yet profound influences to therapeutic advantage.

Dispersive Stiffness of Dzyaloshinskii Domain Walls

NASA Astrophysics Data System (ADS)

Pellegren, J. P.; Lau, D.; Sokalski, V.

2017-07-01

It is well documented that subjecting perpendicular magnetic films that exhibit the interfacial Dzyaloshinskii-Moriya interaction to an in-plane magnetic field results in a domain wall (DW) energy σ , which is highly anisotropic with respect to the orientation of the DW in the film plane Θ . We demonstrate that this anisotropy has a profound impact on the elastic response of the DW as characterized by the surface stiffness σ ˜ (Θ )=σ (Θ )+σ''(Θ ) and evaluate its dependence on the length scale of deformation. The influence of stiffness on DW mobility in the creep regime is assessed, with analytic and numerical calculations showing trends in σ ˜ that better represent experimental measurements of domain wall velocity in magnetic thin films compared to σ alone. Our treatment provides experimental support for theoretical models of the mobility of anisotropic elastic manifolds and makes progress toward a more complete understanding of magnetic domain wall creep.

Phase stability and dynamics of entangled polymer-nanoparticle composites

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

Mangal, Rahul; Srivastava, Samanvaya; Archer, Lynden A.

Nanoparticle–polymer composites, or polymer–nanoparticle composites (PNCs), exhibit unusual mechanical and dynamical features when the particle size approaches the random coil dimensions of the host polymer. Here, we harness favourable enthalpic interactions between particle-tethered and free, host polymer chains to create model PNCs, in which spherical nanoparticles are uniformly dispersed in high molecular weight entangled polymers. Investigation of the mechanical properties of these model PNCs reveals that the nanoparticles have profound effects on the host polymer motions on all timescales. On short timescales, nanoparticles slow-down local dynamics of the host polymer segments and lower the glass transition temperature. On intermediate timescales,more » where polymer chain motion is typically constrained by entanglements with surrounding molecules, nanoparticles provide additional constraints, which lead to an early onset of entangled polymer dynamics. Finally, on long timescales, nanoparticles produce an apparent speeding up of relaxation of their polymer host.« less

Technological aids to support choice strategies by three girls with Rett syndrome.

PubMed

Stasolla, Fabrizio; Perilli, Viviana; Di Leone, Antonia; Damiani, Rita; Albano, Vincenza; Stella, Anna; Damato, Concetta

2015-01-01

This study was aimed at extending the use of assistive technology (i.e., photocells, interface and personal computer) to support choice strategies by three girls with Rett syndrome and severe to profound developmental disabilities. A second purpose of the study was to reduce stereotypic behaviors exhibited by the participants involved (i.e., body rocking, hand washing and hand mouthing). Finally, a third goal of the study was to monitor the effects of such program on the participants' indices of happiness. The study was carried out according to a multiple probe design across responses for each participant. Results showed that the three girls increased the adaptive responses and decreased the stereotyped behaviors during intervention phases compared to baseline. Moreover, during intervention phases, the indices of happiness augmented for each girl as well. Clinical, psychological and rehabilitative implications of the findings are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuroendocrine regulation of somatic growth in fishes.

PubMed

Dai, XiangYan; Zhang, Wei; Zhuo, ZiJian; He, JiangYan; Yin, Zhan

2015-02-01

Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth. Among the possible growth-regulating pathways in vertebrates, components of the somatotropic axis are thought to have the greatest influence. There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish. This includes research into growth hormone, upstream hypothalamic hormones, insulin-like growth factors, and downstream signaling molecules. Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism. Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo. In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis, including emerging research using genetic modified models. These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth.

Plasmonics of 2D Nanomaterials: Properties and Applications

PubMed Central

Li, Yu; Li, Ziwei; Chi, Cheng; Shan, Hangyong; Zheng, Liheng

2017-01-01

Plasmonics has developed for decades in the field of condensed matter physics and optics. Based on the classical Maxwell theory, collective excitations exhibit profound light‐matter interaction properties beyond classical physics in lots of material systems. With the development of nanofabrication and characterization technology, ultra‐thin two‐dimensional (2D) nanomaterials attract tremendous interest and show exceptional plasmonic properties. Here, we elaborate the advanced optical properties of 2D materials especially graphene and monolayer molybdenum disulfide (MoS2), review the plasmonic properties of graphene, and discuss the coupling effect in hybrid 2D nanomaterials. Then, the plasmonic tuning methods of 2D nanomaterials are presented from theoretical models to experimental investigations. Furthermore, we reveal the potential applications in photocatalysis, photovoltaics and photodetections, based on the development of 2D nanomaterials, we make a prospect for the future theoretical physics and practical applications. PMID:28852608

Inducing amnesia through systemic suppression

PubMed Central

Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

2016-01-01

Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

Goldstone mode and pair-breaking excitations in atomic Fermi superfluids

NASA Astrophysics Data System (ADS)

Hoinka, Sascha; Dyke, Paul; Lingham, Marcus G.; Kinnunen, Jami J.; Bruun, Georg M.; Vale, Chris J.

2017-10-01

Spontaneous symmetry breaking is a central paradigm of elementary particle physics, magnetism, superfluidity and superconductivity. According to Goldstone's theorem, phase transitions that break continuous symmetries lead to the existence of gapless excitations in the long-wavelength limit. These Goldstone modes can become the dominant low-energy excitation, showing that symmetry breaking has a profound impact on the physical properties of matter. Here, we present a comprehensive study of the elementary excitations in a homogeneous strongly interacting Fermi gas through the crossover from a Bardeen-Cooper-Schrieffer (BCS) superfluid to a Bose-Einstein condensate (BEC) of molecules using two-photon Bragg spectroscopy. The spectra exhibit a discrete Goldstone mode, associated with the broken-symmetry superfluid phase, as well as pair-breaking single-particle excitations. Our techniques yield a direct determination of the superfluid pairing gap and speed of sound in close agreement with strong-coupling theories.

Charophytes: Evolutionary Giants and Emerging Model Organisms

PubMed Central

Domozych, David S.; Popper, Zoë A.; Sørensen, Iben

2016-01-01

Charophytes are the group of green algae whose ancestral lineage gave rise to land plants in what resulted in a profoundly transformative event in the natural history of the planet. Extant charophytes exhibit many features that are similar to those found in land plants and their relatively simple phenotypes make them efficacious organisms for the study of many fundamental biological phenomena. Several taxa including Micrasterias, Penium, Chara, and Coleochaete are valuable model organisms for the study of cell biology, development, physiology and ecology of plants. New and rapidly expanding molecular studies are increasing the use of charophytes that in turn, will dramatically enhance our understanding of the evolution of plants and the adaptations that allowed for survival on land. The Frontiers in Plant Science series on “Charophytes” provides an assortment of new research reports and reviews on charophytes and their emerging significance as model plants. PMID:27777578

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers.

PubMed

Popovici-Muller, Janeta; Lemieux, René M; Artin, Erin; Saunders, Jeffrey O; Salituro, Francesco G; Travins, Jeremy; Cianchetta, Giovanni; Cai, Zhenwei; Zhou, Ding; Cui, Dawei; Chen, Ping; Straley, Kimberly; Tobin, Erica; Wang, Fang; David, Muriel D; Penard-Lacronique, Virginie; Quivoron, Cyril; Saada, Véronique; de Botton, Stéphane; Gross, Stefan; Dang, Lenny; Yang, Hua; Utley, Luke; Chen, Yue; Kim, Hyeryun; Jin, Shengfang; Gu, Zhiwei; Yao, Gui; Luo, Zhiyong; Lv, Xiaobing; Fang, Cheng; Yan, Liping; Olaharski, Andrew; Silverman, Lee; Biller, Scott; Su, Shin-San M; Yen, Katharine

2018-04-12

Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity.

Polysaccharides from Traditional Chinese Medicines: Extraction, Purification, Modification, and Biological Activity.

PubMed

Chen, Yun; Yao, Fangke; Ming, Ke; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo

2016-12-13

Traditional Chinese Medicine (TCM) has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development.

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers

PubMed Central

2018-01-01

Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity. PMID:29670690

Influence of Initial Vorticity Distribution on Axisymmetric Vortex Breakdown and Reconnection

NASA Technical Reports Server (NTRS)

Young, Larry A.

2007-01-01

An analytical treatment has been developed to study some of the axisymmetric vortex breakdown and reconnection fluid dynamic processes underlying body-vortex interactions that are frequently manifested in rotorcraft and propeller-driven fixed-wing aircraft wakes. In particular, the presence of negative vorticity in the inner core of a vortex filament (one example of which is examined in this paper) subsequent to "cutting" by a solid body has a profound influence on the vortex reconnection, leading to analog flow behavior similar to vortex breakdown phenomena described in the literature. Initial vorticity distributions (three specific examples which are examined) without an inner core of negative vorticity do not exhibit vortex breakdown and instead manifest diffusion-like properties while undergoing vortex reconnection. Though this work focuses on laminar vortical flow, this work is anticipated to provide valuable insight into rotary-wing aerodynamics as well as other types of vortical flow phenomena.

A year in the life of a thrombolite: comparative metatranscriptomics reveals dynamic metabolic changes over diel and seasonal cycles.

PubMed

Louyakis, Artemis S; Gourlé, Hadrien; Casaburi, Giorgio; Bonjawo, Rachelle M E; Duscher, Alexandrea A; Foster, Jamie S

2018-02-01

Microbialites are one of the oldest known ecosystems on Earth and the coordinated metabolisms and activities of these mineral-depositing communities have had a profound impact on the habitability of the planet. Despite efforts to understand the diversity and metabolic potential of these systems, there has not been a systematic molecular analysis of the transcriptional changes that occur within a living microbialite over time. In this study, we generated metatranscriptomic libraries from actively growing thrombolites, a type of microbialite, throughout diel and seasonal cycles and observed dynamic shifts in the population and metabolic transcriptional activity. The most transcribed genes in all seasons were associated with photosynthesis, but only transcripts associated with photosystem II exhibited diel cycling. Photosystem I transcripts were constitutively expressed at all time points including midnight and sunrise. Transcripts associated with nitrogen fixation, methanogenesis and dissimilatory sulfate reduction exhibited diel cycling, and variability between seasons. Networking analysis of the metatranscriptomes showed correlated expression patterns helping to elucidate how metabolic interactions are coordinated within the thrombolite community. These findings have identified distinctive temporal patterns within the thrombolites and will serve an important foundation to understand the mechanisms by which these communities form and respond to changes in their environment. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Transposable element evolution in Heliconius suggests genome diversity within Lepidoptera

PubMed Central

2013-01-01

Background Transposable elements (TEs) have the potential to impact genome structure, function and evolution in profound ways. In order to understand the contribution of transposable elements (TEs) to Heliconius melpomene, we queried the H. melpomene draft sequence to identify repetitive sequences. Results We determined that TEs comprise ~25% of the genome. The predominant class of TEs (~12% of the genome) was the non-long terminal repeat (non-LTR) retrotransposons, including a novel SINE family. However, this was only slightly higher than content derived from DNA transposons, which are diverse, with several families having mobilized in the recent past. Compared to the only other well-studied lepidopteran genome, Bombyx mori, H. melpomene exhibits a higher DNA transposon content and a distinct repertoire of retrotransposons. We also found that H. melpomene exhibits a high rate of TE turnover with few older elements accumulating in the genome. Conclusions Our analysis represents the first complete, de novo characterization of TE content in a butterfly genome and suggests that, while TEs are able to invade and multiply, TEs have an overall deleterious effect and/or that maintaining a small genome is advantageous. Our results also hint that analysis of additional lepidopteran genomes will reveal substantial TE diversity within the group. PMID:24088337

The Klebsiella pneumoniae YfgL (BamB) lipoprotein contributes to outer membrane protein biogenesis, type-1 fimbriae expression, anti-phagocytosis, and in vivo virulence

PubMed Central

Hsieh, Pei-Fang; Hsu, Chun-Ru; Chen, Chun-Tang; Lin, Tzu-Lung; Wang, Jin-Town

2016-01-01

ABSTRACT Klebsiella pneumoniae is an opportunistic pathogen that causes several kinds of infections, including pneumonia, bacteremia, urinary tract infection and community-acquired pyogenic liver abscess (PLA). Adhesion is the critical first step in the infection process. Our previous work demonstrated that the transcellular translocation is exploited by K. pneumoniae strains to migrate from the gut flora into other tissues, resulting in systemic infections. However, the initial stages of K. pneumoniae infection remain unclear. In this study, we demonstrated that a K. pneumoniae strain deleted for yfgL (bamB) exhibited reduced adherence to and invasion of host cells; changed biogenesis of major β-barrel outer membrane proteins; decreased transcriptional expression of type-1 fimbriae; and increased susceptibility to vancomycin and erythromycin. The yfgL deletion mutant also had reduced ability to against neutrophil phagocytosis; exhibited decreased induction of host IL-6 production; and was profoundly attenuated for virulence in a K. pneumoniae model of bacteremia. Thus, the K. pneumoniae YfgL lipoprotein mediates in outer membrane proteins biogenesis and is crucial for anti-phagocytosis and survival in vivo. These data provide a new insight for K. pneumoniae attachment and such knowledge could facilitate preventive therapies or alternative therapies against K. pneumoniae. PMID:27029012

Confinement-induced alterations in the evaporation dynamics of sessile droplets.

PubMed

Bansal, Lalit; Chakraborty, Suman; Basu, Saptarshi

2017-02-07

Evaporation of sessile droplets has been a topic of extensive research. However, the effect of confinement on the underlying dynamics has not been well explored. Here, we report the evaporation dynamics of a sessile droplet in a confined fluidic environment. Our findings reveal that an increase in the channel length delays the completion of the evaporation process and leads to unique spatio-temporal evaporation flux and internal flow. The evaporation modes (constant contact angle and constant contact radius) during the droplet lifetime however exhibit global similarity when normalized by appropriate length and timescales. These results are explained in light of an increase in vapor concentration inside the channel due to greater accumulation of water vapor on account of increased channel length. We have formulated a theoretical framework which introduces two key parameters namely an enhanced concentration of the vapor field in the vicinity of the confined droplet and a corresponding accumulation lengthscale over which the accumulated vapor relaxes to the ambient concentration. Using these two parameters and modified diffusion based evaporation we are able to show that confined droplets exhibit a universal behavior in terms of the temporal evolution of each evaporation mode irrespective of the channel length. These results may turn out to be of profound importance in a wide variety of applications, ranging from surface patterning to microfluidic technology.

Acquired aplastic anemia.

PubMed

Keohane, Elaine M

2004-01-01

Acquired aplastic anemia (AA) is a disorder characterized by a profound deficit of hematopoietic stem and progenitor cells, bone marrow hypocellularity, and peripheral blood pancytopenia. It primarily affects children, young adults, and those over 60 years of age. The majority of cases are idiopathic; however, idiosyncratic reactions to some drugs, chemicals, and viruses have been implicated in its etiology. An autoimmune T-cell reaction likely causes the stem cell depletion, but the precise mechanism, as well as the eliciting and target antigens, is unknown. Symptoms vary from severe life-threatening cytopenias to moderate or non-severe disease that does not require transfusion support. The peripheral blood typically exhibits pancytopenia, reticulocytopenia, and normocytic or macrocytic erythrocytes. The bone marrow is hypocellular and may exhibit dysplasia of the erythrocyte precursors. First line treatment for severe AA consists of hematopoietic stem cell transplantation in young patients with HLA identical siblings, while immunosuppression therapy is used for older patients and for those of any age who lack a HLA matched donor. Patients with AA have an increased risk of developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute leukemia. Further elucidation of the pathophysiology of this disease will result in a better understanding of the interrelationship among AA, PNH, and MDS, and may lead to novel targeted therapies.

Host behaviour and physiology underpin individual variation in avian influenza virus infection in migratory Bewick's swans.

PubMed

Hoye, Bethany J; Fouchier, Ron A M; Klaassen, Marcel

2012-02-07

Individual variation in infection modulates both the dynamics of pathogens and their impact on host populations. It is therefore crucial to identify differential patterns of infection and understand the mechanisms responsible. Yet our understanding of infection heterogeneity in wildlife is limited, even for important zoonotic host-pathogen systems, owing to the intractability of host status prior to infection. Using novel applications of stable isotope ecology and eco-immunology, we distinguish antecedent behavioural and physiological traits associated with avian influenza virus (AIV) infection in free-living Bewick's swans (Cygnus columbianus bewickii). Swans infected with AIV exhibited higher serum δ13C (-25.3±0.4) than their non-infected counterparts (-26.3±0.2). Thus, individuals preferentially foraging in aquatic rather than terrestrial habitats experienced a higher risk of infection, suggesting that the abiotic requirements of AIV give rise to heterogeneity in pathogen exposure. Juveniles were more likely to be infected (30.8% compared with 11.3% for adults), shed approximately 15-fold higher quantity of virus and exhibited a lower specific immune response than adults. Together, these results demonstrate the potential for heterogeneity in infection to have a profound influence on the dynamics of pathogens, with concomitant impacts on host habitat selection and fitness.

Defect and Ordered Tungsten Oxides Encapsulated Inside 2H-W X2( X=S and Se) Fullerene-Related Structures

NASA Astrophysics Data System (ADS)

Sloan, Jeremy; Hutchison, John L.; Tenne, Reshef; Feldman, Yishay; Tsirlina, Tatyana; Homyonfer, Moshe

1999-04-01

Complex tungsten oxides, consisting of nonstoichiometric oxides of the form WO3-xand stoichiometric lamellar oxides of the form {001}RWnO3n-1(n=3 to 6) have been observed incorporated within 2H-WX2(X=S or Se) inorganic fullerene-like (IF) structures by HRTEM. These encapsulates were formed from a gas-solid reaction between H2Xand disordered WO3-xprecursors exhibiting a range of particle sizes and morphologies. The microstructures of most of the encapsulated oxides could be described in terms of {hkl}Rcrystallographic shear (CS) structures formed relative to an ReO3-type (R) substructure. Smaller spheroidal WO3-xencapsulates were frequently found to exhibit random {103}RCS defects of the Wadsley type, while larger, needle encapsulates were found to form exclusively {001}RWnO3n-1type lamellar structures that were predominantely ordered. Spheriodal encapsulates with randomly spaced {001}RCS planes were also observed encapsulated inside 2H-WSe2IF structures. The growth and morphologies of the encapsulating 2H-WX2shells were profoundly influenced by those of the precursor oxides used in their formation. Ordering mechanisms were proposed with respect to the formation of the ordered encapsulated oxides from the disordered precursors.

Infrasound-induced changes on sexual behavior in male rats and some underlying mechanisms.

PubMed

Zhuang, Zhiqiang; Pei, Zhaohui; Chen, Jingzao

2007-01-01

To investigate some bioeffects of infrasound on copulation as well as underlying mechanisms, we inspected the changes of sexual behavior, serum testosterone concentration and mRNA expression levels of steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR) and cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) in testes of rats exposed to infrasound of 8Hz at 90 or 130dB for 1, 7, 14 and 21 days (2h/day), respectively. Rats exposed to 90dB exhibited significant decrement in sexual behavior, serum testosterone levels and mRNA expression levels of StAR and P450scc at the time point of 1 day but not at the rest time points, and no significantly change of SF-1 mRNA expression was observed over the period of 21 days in spite of mild fluctuation. Rats exposed to 130dB exhibited significant decrement in all aspects above, which became more profound with prolonged exposure. Our conclusion is that adverse bioeffects of infrasound on reproduction depend on some exposure parameters, the mechanism of which could involve in the decreased expression of some key enzymes or regulator for testosterone biosynthesis. Copyright © 2006. Published by Elsevier B.V.

Analysis of Phase Separation in Czochralski Grown Single Crystal Ilmenite

NASA Technical Reports Server (NTRS)

Wilkins, R.; Powell, Kirk St. A.; Loregnard, Kieron R.; Lin, Sy-Chyi; Muthusami, Jayakumar; Zhou, Feng; Pandey, R. K.; Brown, Geoff; Hawley, M. E.

1998-01-01

Ilmenite (FeTiOs) is a wide bandgap semiconductor with an energy gap of 2.58 eV. Ilmenite has properties suited for radiation tolerant applications, as well as a variety of other electronic applications. Single crystal ilmenite has been grown from the melt using the Czochralski method. Growth conditions have a profound effect on the microstructure of the samples. Here we present data from a variety of analytical techniques which indicate that some grown crystals exhibit distinct phase separation during growth. This phase separation is apparent for both post-growth annealed and unannealed samples. Under optical microscopy, there appear two distinct areas forming a matrix with an array of dots on order of 5 pm diameter. While appearing bright in the optical micrograph, atomic force microscope (AFM) shows the dots to be shallow pits on the surface. Magnetic force microscope (MFM) shows the dots to be magnetic. Phase identification via electron microprobe analysis (EMPA) indicates two major phases in the unannealed samples and four in the annealed samples, where the dots appear to be almost pure iron. This is consistent with micrographs taken with a scanning probe microscope used in the magnetic force mode. Samples that do not exhibit the phase separation have little or no discernible magnetic structure detectable by the MFM.

The Western States: Profound Diversity but Severe Segregation for Latino Students

ERIC Educational Resources Information Center

Kucsera, John; Flaxman, Greg

2012-01-01

The U.S. Western region and its public schools are in the midst of its largest racial and economic transformation, as the area witnesses a shrinking white majority, a surging Latino minority, and a growing class of poor. These groups, along with blacks and Asian, more often than not attend very different and segregated schools both in educational…

A Heart Rate Analysis of Developmental Change in Feedback Processing and Rule Shifting from Childhood to Early Adulthood

ERIC Educational Resources Information Center

Crone, Eveline A.; Somsen, Riek J. M.; Zanolie, Kiki; Van der Molen, Maurits W.

2006-01-01

Over the course of development, the ability to switch between different tasks on the basis of feedback cues increases profoundly, but the role of performance monitoring remains unclear. Heart rate indexes can provide critical information about how individuals monitor feedback cues indicating that performance should be adjusted. In this study,…

Organizational Culture in a Successful Primary School: An Ethnographic Case Study

ERIC Educational Resources Information Center

Negis-Isik, Ayse; Gursel, Musa

2013-01-01

Even though they are perceived similar from outside, all schools have distinct characteristics and a culture that differ them from other schools. School culture, is one of the important factors that play role in school efficiency and success. The purpose of this study was to examine the culture of a successful school profoundly. This study was a…

Teaching, Learning, Literacy in Our High-Risk High-Tech World: A Framework for Becoming Human

ERIC Educational Resources Information Center

Gee, James Paul

2017-01-01

This is a profound look at learning, language, and literacy. It is also about brains and bodies. And it is about talk, texts, media, and society. These topics, though usually studied in different narrow academic silos, are all part of one highly interactive process--human development. Gee argues that children will need to be resilient,…

Understanding Distress in People with Severe Communication Difficulties: Developing and Assessing the Disability Distress Assessment Tool (DisDAT)

ERIC Educational Resources Information Center

Regnard, C.; Reynolds, Joanna; Watson, Bill; Matthews, Dorothy; Gibson, Lynn; Clarke, Charlotte

2007-01-01

Background: Meaningful communication with people with profound communication difficulties depends on the ability of carers to recognize and translate many different verbal cues. Carers appear to be intuitively skilled at identifying distress cues, but have little confidence in their observations. To help in this process, a number of pain tools…

Do UOC Students Fit in the Net Generation Profile? An Approach to their Habits in ICT Use

ERIC Educational Resources Information Center

Romero, Marc; Guitert, Montse; Sangra, Albert; Bullen, Mark

2013-01-01

Some authors have stated that university students born after 1982 have been profoundly influenced by digital technologies, showing different characteristics when compared to previous generations. However, it is worth asking if that is a current observable phenomenon. Are those students born after the 80s really more familiar with ICT tools than…

E-Social Astuteness Skills for ICT-Supported Equitable Prosperity and a Capable Developmental State in South Africa

ERIC Educational Resources Information Center

Mitrovic, Zoran; Taylor, Wallace; Sharif, Mymoena; Claassen, Walter; Wesso, Harold

2013-01-01

Over 350 national and international delegates at the 2nd e-Skills Summit and the International Telecommunication Union (ITU) Global ICT Forum on Human Capital Development have agreed that the e-skilling agenda in South Africa is making a "profound difference" but still not sufficient to build a capable developmental state. The delegates…

From Capitol Hill to Dupont Circle and Beyond: The Influence of Policy Actors in the Federal Higher Education Rulemaking Process

ERIC Educational Resources Information Center

Natow, Rebecca S.

2015-01-01

The federal higher education rulemaking process develops policies that can profoundly affect college students, higher education institutions, and other actors in the higher education policy community. But little has been researched about the influence that different types of actors have on higher education rulemaking. By analyzing interviews with…

The effects of forest residual debris disposal on perennial grass emergence, growth, and survival in a ponderosa pine ecotone

Treesearch

Darin J. Law; Peter F. Kolb

2007-01-01

Soil surface conditions can have profound effects on plant seedling emergence and subsequent seedling survival. To test the hypothesis that different soil-surface treatments with logging residue affect range grass seedling emergence and survival, 6 alternative forest-residual treatments were established in the summer of 1998 following thinning of mature trees from...

The District and Charter Sectors of American K-12 Education: Pros and Cons

ERIC Educational Resources Information Center

Finn, Chester E., Jr.; Manno, Bruno V.; Wright, Brandon L.

2017-01-01

This article probes ways in which the school-choice marketplace as it developed via chartering has not worked as well in practice as many had hoped. It includes reflection on the profoundly different operating principles and theories of action that separate the district and charter sectors in their pure forms. It also offers market-strengthening…

The Effect of Modern Standard Arabic Orthography on Speech Production by Arab Children with Hearing Loss

ERIC Educational Resources Information Center

Most, Tova; Levin, Iris; Sarsour, Marwa

2008-01-01

This article examined the effect of Modern Standard Arabic orthography on speech production quality (syllable stress and vowels) by 23 Arabic-speaking children with severe or profound hearing loss aged 8-12 years. Children produced 15 one-syllable minimal pairs of words that differed in vowel length (short vs. long) and 20 two-syllable minimal…

Reflecting upon Researchers' and Policy-Makers' Tensions in the Collaborative Inquiry Process: "What Do Different Commonplaces Contribute to Curriculum Deliberation?"

ERIC Educational Resources Information Center

Tan, Yuen Sze Michelle; Atencio, Matthew

2017-01-01

This collaborative inquiry, as part of action research, is framed within the unique context of two researchers working closely alongside two policy-makers (research collaborators) to explore how teachers could enter more profoundly into a curriculum discourse. Drawing from Reid's concept of curriculum deliberation as located within institutional…

Gender Differences and the Risk of Falls in Individuals with Profound Vision Loss

ERIC Educational Resources Information Center

Ray, Christopher T.; Wolf, Steven L.

2010-01-01

Adults with visual impairments experience a loss of balance and mobility, which presents a barrier to independence and is associated with the fear of falling. The purpose of this study was to determine the extent to which visual status, age, gender, body mass index (BMI), and the strength of quadriceps and hamstrings contribute to compromised…

Looking Back, Looking Forward, Living in the Moment: Understanding the Individual Temporal Perspectives of Secondary School EFL Learners

ERIC Educational Resources Information Center

Begic, Ines; Mercer, Sarah

2017-01-01

Every individual has a different perspective on time, known as "temporal perspective". A person's orientation and attitude towards time can have a profound effect on their behaviour and motivation. In Second Language Acquisition, a variety of work has considered learners and their behaviours from various temporal perspectives. However,…

Social Skills Training for Students of Color with Disabilities through the Use of Social Networking

ERIC Educational Resources Information Center

Aldridge, Patricia R.; Jeffrey, Peter; Taylor, Gertrude; Barringer-Brown, Charletta H.

2017-01-01

The phenomenon of the use of cell phones as a primary source of communication among teens is having an impact on our society in profound ways. Children are creating and utilizing a different language and mechanism of communication--texting. The authors conducted research to determine if this cell phone phenomenon is as prevalent among students…

Deaf Children's Judgments on Conservation Problems of Liquid, Matter, Weight and Volume: A Pilot Study.

ERIC Educational Resources Information Center

Rittenhouse, Robert K.

Twenty-four profoundly deaf children (7 to 13 years old) from a residential school were presented with conservation problems of liquid, matter, weight, and volume. Analyses of variance showed that age was significant beyond the .01 level and type of task (conservation) at the .25 level. No significant sex effect was found. Differences among means…

Ethics roundtable debate: Child with severe brain damage and an underlying brain tumour

PubMed Central

Gunn, Scott; Hashimoto, Satoru; Karakozov, Michael; Marx, Thomas; Tan, Ian KS; Thompson, Dan R; Vincent, Jean-Louis

2004-01-01

A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches. PMID:15312199

Global climate change and vector-borne diseases

USGS Publications Warehouse

Ginsberg, H.S.

2002-01-01

Global warming will have different effects on different diseases because of the complex and idiosynchratic interactions between vectors, hosts, and pathogens that influence transmission dynamics of each pathogen. Human activities, including urbanization, rapid global travel, and vector management, have profound effects on disease transmission that can operate on more rapid time scales than does global climate change. The general concern about global warming encouraging the spread of tropical diseases is legitimate, but the effects vary among diseases, and the ecological implications are difficult to predict.

The Recourse to War: An Appraisal of the ’Weinberger Doctrine’

DTIC Science & Technology

1989-06-01

criteria adapted and clarified defense policies of a different time and a slower world to the exigencies of the present and the chaiienges of the future...coliapse in April 1975 were as profound a shock to the national psyche as any the republic had experienced since the Civil War. IMPACT OF VIETNAM AND...34 It is a historic document; it adapts and clarifies defense policies of a different time and slower world to the exigencies of the present and

A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.

PubMed

Kamada, Fumiaki; Kure, Shigeo; Kudo, Takayuki; Suzuki, Yoichi; Oshima, Takeshi; Ichinohe, Akiko; Kojima, Kanako; Niihori, Tetsuya; Kanno, Junko; Narumi, Yoko; Narisawa, Ayumi; Kato, Kumi; Aoki, Yoko; Ikeda, Katsuhisa; Kobayashi, Toshimitsu; Matsubara, Yoichi

2006-01-01

Autosomal-dominant, nonsyndromic hearing impairment is clinically and genetically heterogeneous. We encountered a large Japanese pedigree in which nonsyndromic hearing loss was inherited in an autosomal-dominant fashion. A genome-wide linkage study indicated linkage to the DFNA2 locus on chromosome 1p34. Mutational analysis of KCNQ4 encoding a potassium channel revealed a novel one-base deletion in exon 1, c.211delC, which generated a profoundly truncated protein without transmembrane domains (p.Q71fsX138). Previously, six missense mutations and one 13-base deletion, c.211_223del, had been reported in KCNQ4. Patients with the KCNQ4 missense mutations had younger-onset and more profound hearing loss than patients with the 211_223del mutation. In our current study, 12 individuals with the c.211delC mutation manifested late-onset and pure high-frequency hearing loss. Our results support the genotype-phenotype correlation that the KCNQ4 deletions are associated with later-onset and milder hearing impairment than the missense mutations. The phenotypic difference may be caused by the difference in pathogenic mechanisms: haploinsufficiency in deletions and dominant-negative effect in missense mutations.

Loudness judgment procedures for evaluating hearing aid preselection decisions for severely and profoundly hearing-impaired listeners.

PubMed

Gottermeier, L; De Filippo, C L; Block, M G

1991-08-01

Hearing aid fitting involves a two-phase process of preselection and evaluation (Seewald RC and Ross M. Amplification for the Hearing Impaired 1988:213-271). The purpose of the present study was to examine alternative procedures that clinicians might use in the evaluation phase to verify the adequacy of hearing aid preselection decisions for severely and profoundly hearing-impaired listeners. Bekesy tracking, loudness rating, and conventional bracketing procedures were used to determine threshold, most comfortable listening level, and uncomfortable listening level for 10 hearing-impaired young adults. Stimuli were pulsed pure tones of 500, 1000, and 2000 Hz and filtered words. Means and standard deviations of most comfortable listening levels and uncomfortable listening levels derived from loudness judgments of the 10 subjects showed only nominal differences across procedures. However, correlation analysis (Pearson r) indicated that individuals responded to the three procedures in varying ways, producing different loudness judgments and overall dynamic ranges. Thus, test procedure may influence the clinician's final evaluation of a preselected hearing aid. Initial work suggests that closed-set response categories such as loudness rating can limit measurement variability and potentially guide the clinician's evaluation of hearing aid preselection decisions.

Leaf hydraulic capacity in ferns, conifers and angiosperms: impacts on photosynthetic maxima.

PubMed

Brodribb, Tim J; Holbrook, N Michele; Zwieniecki, Maciej A; Palma, Beatriz

2005-03-01

* The hydraulic plumbing of vascular plant leaves varies considerably between major plant groups both in the spatial organization of veins, as well as their anatomical structure. * Five conifers, three ferns and 12 angiosperm trees were selected from tropical and temperate forests to investigate whether the profound differences in foliar morphology of these groups lead to correspondingly profound differences in leaf hydraulic efficiency. * We found that angiosperm leaves spanned a range of leaf hydraulic conductance from 3.9 to 36 mmol m2 s-1 MPa-1, whereas ferns (5.9-11.4 mmol m-2 s-1 MPa-1) and conifers (1.6-9.0 mmol m-2 s-1 MPa-1) were uniformly less conductive to liquid water. Leaf hydraulic conductance (Kleaf) correlated strongly with stomatal conductance indicating an internal leaf-level regulation of liquid and vapour conductances. Photosynthetic capacity also increased with Kleaf, however, it became saturated at values of Kleaf over 20 mmol m-2 s-1 MPa-1. * The data suggest that vessels in the leaves of the angiosperms studied provide them with the flexibility to produce highly conductive leaves with correspondingly high photosynthetic capacities relative to tracheid-bearing species.

Characteristics of an Appropriate Education for Severely and Profoundly Handicapped Students.

ERIC Educational Resources Information Center

Bates, Paul; And Others

1981-01-01

Twelve characteristics are important for an appropriate program for severely/profoundly handicapped (SPH) individuals: age appropriate curriculum, specific objectives, functional activities, consistent cue hierarchy, regular data collection, periodic individualized educational program revision, detailed classroom schedule, instruction outside the…

Delayed dyskinesia and prolonged psychosis in a patient presenting with profound hyponatraemia.

PubMed

John, Victoria; Evans, Philip; Kalhan, Atul

2017-01-01

A 65-year-old woman was admitted to the emergency unit with a 48 h history of generalised weakness and confusion. On examination, she had mild slurring of speech although there was no other focal neurological deficit. She had profound hyponatraemia (serum sodium level of 100 mmol/L) on admission with the rest of her metabolic parameters being within normal range. Subsequent investigations confirmed the diagnosis of small-cell lung cancer with paraneoplastic syndrome of inappropriate antidiuresis (SIAD). She was monitored closely in high-dependency unit with an attempt to cautiously correct her hyponatraemia to prevent sequelae associated with rapid correction. The patient developed prolonged psychosis (lasting over 2 weeks) and displayed delayed dyskinetic movements, even after a gradual increase in serum sodium levels close to 130 mmol/L. To our knowledge, delayed neurological recovery from profound hyponatraemia (without long-term neurological sequelae) has previously not been reported. This case should alert a clinician regarding the possibility of prolonged although reversible psychosis and dyskinetic movements in a patient presenting with profound symptomatic hyponatraemia. Patients with profound hyponatraemia may develop altered sensorium, dyskinesia and psychotic behaviour.Full recovery from psychotic symptoms and dyskinesia may be delayed despite cautious correction of serum sodium levels.Careful and close monitoring of such patients can help avoid long-term neurological sequelae.

Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration

PubMed Central

Shadmehr, Reza; Ohminami, Shinya; Tsutsumi, Ryosuke; Shirota, Yuichiro; Shimizu, Takahiro; Tanaka, Nobuyuki; Terao, Yasuo; Tsuji, Shoji; Ugawa, Yoshikazu; Uchimura, Motoaki; Inoue, Masato; Kitazawa, Shigeru

2015-01-01

Cerebellar damage can profoundly impair human motor adaptation. For example, if reaching movements are perturbed abruptly, cerebellar damage impairs the ability to learn from the perturbation-induced errors. Interestingly, if the perturbation is imposed gradually over many trials, people with cerebellar damage may exhibit improved adaptation. However, this result is controversial, since the differential effects of gradual vs. abrupt protocols have not been observed in all studies. To examine this question, we recruited patients with pure cerebellar ataxia due to cerebellar cortical atrophy (n = 13) and asked them to reach to a target while viewing the scene through wedge prisms. The prisms were computer controlled, making it possible to impose the full perturbation abruptly in one trial, or build up the perturbation gradually over many trials. To control visual feedback, we employed shutter glasses that removed visual feedback during the reach, allowing us to measure trial-by-trial learning from error (termed error-sensitivity), and trial-by-trial decay of motor memory (termed forgetting). We found that the patients benefited significantly from the gradual protocol, improving their performance with respect to the abrupt protocol by exhibiting smaller errors during the exposure block, and producing larger aftereffects during the postexposure block. Trial-by-trial analysis suggested that this improvement was due to increased error-sensitivity in the gradual protocol. Therefore, cerebellar patients exhibited an improved ability to learn from error if they experienced those errors gradually. This improvement coincided with increased error-sensitivity and was present in both groups of subjects, suggesting that control of error-sensitivity may be spared despite cerebellar damage. PMID:26311179

Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

PubMed Central

Rao, Sambasiva P.; Sancho, Jose; Campos-Rivera, Juanita; Boutin, Paula M.; Severy, Peter B.; Weeden, Timothy; Shankara, Srinivas; Roberts, Bruce L.; Kaplan, Johanne M.

2012-01-01

Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact. PMID:22761788

Role of Detergents in Conformational Exchange of a G Protein-coupled Receptor*

PubMed Central

Chung, Ka Young; Kim, Tae Hun; Manglik, Aashish; Alvares, Rohan; Kobilka, Brian K.; Prosser, R. Scott

2012-01-01

The G protein-coupled β2-adrenoreceptor (β2AR) signals through the heterotrimeric G proteins Gs and Gi and β-arrestin. As such, the energy landscape of β2AR-excited state conformers is expected to be complex. Upon tagging Cys-265 of β2AR with a trifluoromethyl probe, 19F NMR was used to assess conformations and possible equilibria between states. Here, we report key differences in β2AR conformational dynamics associated with the detergents used to stabilize the receptor. In dodecyl maltoside (DDM) micelles, the spectra are well represented by a single Lorentzian line that shifts progressively downfield with activation by appropriate ligand. The results are consistent with interconversion between two or more states on a time scale faster than the greatest difference in ligand-dependent chemical shift (i.e. >100 Hz). Given that high detergent off-rates of DDM monomers may facilitate conformational exchange between functional states of β2AR, we utilized the recently developed maltose-neopentyl glycol (MNG-3) diacyl detergent. In MNG-3 micelles, spectra indicated at least three distinct states, the relative populations of which depended on ligand, whereas no ligand-dependent shifts were observed, consistent with the slow exchange limit. Thus, detergent has a profound effect on the equilibrium kinetics between functional states. MNG-3, which has a critical micelle concentration in the nanomolar regime, exhibits an off-rate that is 4 orders of magnitude lower than that of DDM. High detergent off-rates are more likely to facilitate conformational exchange between distinct functional states associated with the G protein-coupled receptor. PMID:22893704

Effects of point defect concentrations of the reactive element oxides on the oxidation kinetics of pure Ni and Ni-Cr alloys

NASA Astrophysics Data System (ADS)

Yan, Ruey-Fong

The addition of some reactive element oxides, e.g. Ysb2Osb3 or ZrOsb2, has significant effects, e.g. improvement in scale adhesion and reduction in oxidation rate, on the oxidation behavior of chromia and alumina scale forming alloys at high temperatures. However, there is little agreement about how a small addition of an oxygen-active element can cause such profound effects. It was the goal of this project to study the growth kinetics of an oxide scale when different reactive-element oxides were added to pure Ni and Ni-Cr alloys and, consequently, to aid in clarifying the mechanism of reactive element effects. The oxidation kinetics were measured using a thermogravimetric analysis (TGA) method and the material characterization of oxide scale was conducted. The relationship between point defect structures and oxidation kinetics was discussed. The results in this research showed that Ysb2Osb3 and ZrOsb2 exhibited the reactive element effects on the oxidation behaviors of Ni and Ni-Cr alloys. In addition, the point defect concentrations of the reactive element oxide, Ysb2Osb3, were changed by doping of different valent oxides. The modification of point defect concentrations of the reactive element oxide dispersed phases did change the oxidation kinetics of the pure Ni and Ni-Cr alloys containing Ysb2Osb3. These results indicate that the transport properties of the reactive element oxide dispersed phases are one of the important factors in determining the growth rate of an oxide scale.

Muscle coordination during breaststroke swimming: Comparison between elite swimmers and beginners.

PubMed

Vaz, João R; Olstad, Bjørn Harald; Cabri, Jan; Kjendlie, Per-Ludvik; Pezarat-Correia, Pedro; Hug, François

2016-10-01

The present study aimed to compare muscle coordination strategies of the upper and lower limb muscles between beginners and elite breaststroke swimmers. Surface electromyography (EMG) of eight muscles was recorded in 16 swimmers (8 elite, 8 beginners) during a 25 m swimming breaststroke at 100% of maximal effort. A decomposition algorithm was used to identify the muscle synergies that represent the temporal and spatial organisation of muscle coordination. Between-groups indices of similarity and lag times were calculated. Individual muscle patterns were moderately to highly similar between groups (between-group indices range: 0.61 to 0.84). Significant differences were found in terms of lag time for pectoralis major (P < 0.05), biceps brachii, rectus femoris and tibialis anterior (P < 0.01), indicating an earlier activation for these muscles in beginners compared to elites (range: -13.2 to -3.8% of the swimming cycle). Three muscle synergies were identified for both beginners and elites. Although their composition was similar between populations, the third synergy exhibited a high within-group variability. Moderate to high indices of similarity were found for the shape of synergy activation coefficients (range: 0.63 to 0.88) but there was a significant backward shift (-8.4% of the swimming cycle) in synergy #2 for beginners compared to elites. This time shift suggested differences in the global arm-to-leg coordination. These results indicate that the synergistic organisation of muscle coordination during breaststroke swimming is not profoundly affected by expertise. However, specific timing adjustments were observed between lower and upper limbs.

Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers.

PubMed

Ornstein, T J; Iddon, J L; Baldacchino, A M; Sahakian, B J; London, M; Everitt, B J; Robbins, T W

2000-08-01

Groups of subjects whose primary drug of abuse was amphetamine or heroin were compared, together with age- and IQ-matched control subjects. The study consisted of a neuropsychological test battery which included both conventional tests and also computerised tests of recognition memory, spatial working memory, planning, sequence generation, visual discrimination learning, and attentional set-shifting. Many of these tests have previously been shown to be sensitive to cortical damage (including selective lesions of the temporal or frontal lobes) and to cognitive deficits in dementia, basal ganglia disease, and neuropsychiatric disorder. Qualitative differences, as well as some commonalities, were found in the profile of cognitive impairment between the two groups. The chronic amphetamine abusers were significantly impaired in performance on the extra-dimensional shift task (a core component of the Wisconsin Card Sort Test) whereas in contrast, the heroin abusers were impaired in learning the normally easier intra-dimensional shift component. Both groups were impaired in some of tests of spatial working memory. However, the amphetamine group, unlike the heroin group, were not deficient in an index of strategic performance on this test. The heroin group failed to show significant improvement between two blocks of a sequence generation task after training and additionally exhibited more perseverative behavior on this task. The two groups were profoundly, but equivalently impaired on a test of pattern recognition memory sensitive to temporal lobe dysfunction. These results indicate that chronic drug use may lead to distinct patterns of cognitive impairment that may be associated with dysfunction of different components of cortico-striatal circuitry.

Characterization of microRNAs Expressed during Secondary Wall Biosynthesis in Acacia mangium

PubMed Central

Ong, Seong Siang; Wickneswari, Ratnam

2012-01-01

MicroRNAs (miRNAs) play critical regulatory roles by acting as sequence specific guide during secondary wall formation in woody and non-woody species. Although thousands of plant miRNAs have been sequenced, there is no comprehensive view of miRNA mediated gene regulatory network to provide profound biological insights into the regulation of xylem development. Herein, we report the involvement of six highly conserved amg-miRNA families (amg-miR166, amg-miR172, amg-miR168, amg-miR159, amg-miR394, and amg-miR156) as the potential regulatory sequences of secondary cell wall biosynthesis. Within this highly conserved amg-miRNA family, only amg-miR166 exhibited strong differences in expression between phloem and xylem tissue. The functional characterization of amg-miR166 targets in various tissues revealed three groups of HD-ZIP III: ATHB8, ATHB15, and REVOLUTA which play pivotal roles in xylem development. Although these three groups vary in their functions, -psRNA target analysis indicated that miRNA target sequences of the nine different members of HD-ZIP III are always conserved. We found that precursor structures of amg-miR166 undergo exhaustive sequence variation even within members of the same family. Gene expression analysis showed three key lignin pathway genes: C4H, CAD, and CCoAOMT were upregulated in compression wood where a cascade of miRNAs was downregulated. This study offers a comprehensive analysis on the involvement of highly conserved miRNAs implicated in the secondary wall formation of woody plants. PMID:23251324

Non-equivalent contributions of maternal and paternal genomes to early plant embryogenesis.

PubMed

Del Toro-De León, Gerardo; García-Aguilar, Marcelina; Gillmor, C Stewart

2014-10-30

Zygotic genome activation in metazoans typically occurs several hours to a day after fertilization, and thus maternal RNAs and proteins drive early animal embryo development. In plants, despite several molecular studies of post-fertilization transcriptional activation, the timing of zygotic genome activation remains a matter of debate. For example, two recent reports that used different hybrid ecotype combinations for RNA sequence profiling of early Arabidopsis embryo transcriptomes came to divergent conclusions. One identified paternal contributions that varied by gene, but with overall maternal dominance, while the other found that the maternal and paternal genomes are transcriptionally equivalent. Here we assess paternal gene activation functionally in an isogenic background, by performing a large-scale genetic analysis of 49 EMBRYO DEFECTIVE genes and testing the ability of wild-type paternal alleles to complement phenotypes conditioned by mutant maternal alleles. Our results demonstrate that wild-type paternal alleles for nine of these genes are completely functional 2 days after pollination, with the remaining 40 genes showing partial activity beginning at 2, 3 or 5 days after pollination. Using our functional assay, we also demonstrate that different hybrid combinations exhibit significant variation in paternal allele activation, reconciling the apparently contradictory results of previous transcriptional studies. The variation in timing of gene function that we observe confirms that paternal genome activation does not occur in one early discrete step, provides large-scale functional evidence that maternal and paternal genomes make non-equivalent contributions to early plant embryogenesis, and uncovers an unexpectedly profound effect of hybrid genetic backgrounds on paternal gene activity.

Effects of the hippopotamus on the chemistry and ecology of a changing watershed.

PubMed

Stears, Keenan; McCauley, Douglas J; Finlay, Jacques C; Mpemba, James; Warrington, Ian T; Mutayoba, Benezeth M; Power, Mary E; Dawson, Todd E; Brashares, Justin S

2018-05-29

Cross-boundary transfers of nutrients can profoundly shape the ecology of recipient systems. The common hippopotamus, Hippopotamus amphibius , is a significant vector of such subsidies from terrestrial to river ecosystems. We compared river pools with high and low densities of H. amphibius to determine how H. amphibius subsidies shape the chemistry and ecology of aquatic communities. Our study watershed, like many in sub-Saharan Africa, has been severely impacted by anthropogenic water abstraction reducing dry-season flow to zero. We conducted observations for multiple years over wet and dry seasons to identify how hydrological variability influences the impacts of H. amphibius During the wet season, when the river was flowing, we detected no differences in water chemistry and nutrient parameters between pools with high and low densities of H. amphibius Likewise, the diversity and abundance of fish and aquatic insect communities were indistinguishable. During the dry season, however, high-density H. amphibiu s pools differed drastically in almost all measured attributes of water chemistry and exhibited depressed fish and insect diversity and fish abundance compared with low-density H. amphibius pools. Scaled up to the entire watershed, we estimate that H. amphibius in this hydrologically altered watershed reduces dry-season fish abundance and indices of gamma-level diversity by 41% and 16%, respectively, but appears to promote aquatic invertebrate diversity. Widespread human-driven shifts in hydrology appear to redefine the role of H. amphibius , altering their influence on ecosystem diversity and functioning in a fashion that may be more severe than presently appreciated.

Role of detergents in conformational exchange of a G protein-coupled receptor.

PubMed

Chung, Ka Young; Kim, Tae Hun; Manglik, Aashish; Alvares, Rohan; Kobilka, Brian K; Prosser, R Scott

2012-10-19

The G protein-coupled β(2)-adrenoreceptor (β(2)AR) signals through the heterotrimeric G proteins G(s) and G(i) and β-arrestin. As such, the energy landscape of β(2)AR-excited state conformers is expected to be complex. Upon tagging Cys-265 of β(2)AR with a trifluoromethyl probe, (19)F NMR was used to assess conformations and possible equilibria between states. Here, we report key differences in β(2)AR conformational dynamics associated with the detergents used to stabilize the receptor. In dodecyl maltoside (DDM) micelles, the spectra are well represented by a single Lorentzian line that shifts progressively downfield with activation by appropriate ligand. The results are consistent with interconversion between two or more states on a time scale faster than the greatest difference in ligand-dependent chemical shift (i.e. >100 Hz). Given that high detergent off-rates of DDM monomers may facilitate conformational exchange between functional states of β(2)AR, we utilized the recently developed maltose-neopentyl glycol (MNG-3) diacyl detergent. In MNG-3 micelles, spectra indicated at least three distinct states, the relative populations of which depended on ligand, whereas no ligand-dependent shifts were observed, consistent with the slow exchange limit. Thus, detergent has a profound effect on the equilibrium kinetics between functional states. MNG-3, which has a critical micelle concentration in the nanomolar regime, exhibits an off-rate that is 4 orders of magnitude lower than that of DDM. High detergent off-rates are more likely to facilitate conformational exchange between distinct functional states associated with the G protein-coupled receptor.

In vitro and in vivo drug disposition of cilengitide in animals and human.

PubMed

Dolgos, Hugues; Freisleben, Achim; Wimmer, Elmar; Scheible, Holger; Krätzer, Friedrich; Yamagata, Tetsuo; Gallemann, Dieter; Fluck, Markus

2016-04-01

Cilengitide is very low permeable (1.0 nm/sec) stable cyclic pentapeptide containing an Arg-Gly-Asp motif responsible for selective binding to αvβ3 and αvβ5 integrins administered intravenously (i.v.). In vivo studies in the mouse and Cynomolgus monkeys showed the major component in plasma was unchanged drug (>85%). These results, together with the absence of metabolism in vitro and in animals, indicate minimal metabolism in both species. The excretion of [(14)C]-cilengitide showed profound species differences, with a high renal excretion of the parent drug observed in Cynomolgus monkey (50% dose), but not in mouse (7 and 28%: m/f). Consistently fecal (biliary) secretion was high in mouse (87 and 66% dose: m/f) but low in Cynomolgus monkey (36.5%). Human volunteers administrated with [(14)C]-cilengitide showed that most of the dose was recovered in urine as unchanged drug (77.5%, referred to Becker et al. 2015), indicating that the Cynomolgus monkey was the closer species to human. In order to better understand the species difference between human and mouse, the hepatobiliary disposition of [(14)C]-cilengitide was determined in sandwich-cultured hepatocytes. Cilengitide exhibited modest biliary efflux (30-40%) in mouse, while in human hepatocytes this was negligible. Furthermore, it was confirmed that the uptake of cilengitide into human hepatocytes was minor and appeared to be passive. In summary, the extent of renal and biliary secretion of cilengitide appears to be highly species specific and is qualitatively well explained using sandwich hepatocyte culture models.

Let's Get Fit!: Fitness Activities for Children with Severe/Profound Disabilities.

ERIC Educational Resources Information Center

Modell, Scott J.; Cox, Thomas Alan

1999-01-01

Guidelines for developing a physical activity program for students with severe/profound disabilities address medical clearance; levels of participation; staffing; equipment; and program components, including warm-up, range of motion/flexibility activities, aerobics, resistance training, and cool-down. (DB)

22 CFR 95.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... administration or application, of mind altering substances or other procedures calculated to disrupt profoundly... application of mind altering substances or other procedures calculated to disrupt profoundly the senses or... custody or physical control. (5) The term “acquiescence” as used in this definition requires that the...

An Annotated Bibliography on the Severely and Profoundly Mentally Retarded.

ERIC Educational Resources Information Center

Cass, Michael, Comp.; Schilit, Jeffrey, Comp.

Presented is an annotated bibliography with approximately 250 entries relating to the severely and profoundly retarded. Citations are listed alphabetically by author under the following categories: assessments, measurements, evaluations; associations; attending behavior; behavior modification; books; classical conditioning; cognitive development;…

Temporal factors in the extinction of fear in inbred mouse strains differing in extinction efficacy

PubMed Central

2013-01-01

Background Various neuropsychiatric conditions, including posttraumatic stress disorder (PTSD), are characterized by deficient fear extinction, but individuals differ greatly in risk for these. While there is growing evidence that fear extinction is influenced by certain procedural variables, it is unclear how these influences might vary across individuals and subpopulations. To model individual differences in fear extinction, prior studies identified a strain of inbred mouse, 129S1/SvImJ (S1), which exhibits a profound deficit in fear extinction, as compared to other inbred strains, such as C57BL/6J (B6). Methods Here, we assessed the effects of procedural variables on the impaired extinction phenotype of the S1 strain and, by comparison, the extinction-intact B6 strain. The variables studied were 1) the interval between conditioning and extinction, 2) the interval between cues during extinction training, 3) single-cue exposure before extinction training, and 4) extinction of a second-order conditioned cue. Results Conducting extinction training soon after (‘immediately’) conditioning attenuated fear retrieval in S1 mice and impaired extinction in B6 mice. Spacing cue presentations with long inter-trial intervals during extinction training augmented fear in S1 and B6 mice. The effect of spacing was lost with one-trial fear conditioning in B6, but not S1 mice. A single exposure to a conditioned cue before extinction training did not alter extinction retrieval, either in B6 or S1 mice. Both the S1 and B6 strains exhibited robust second-order fear conditioning, in which a cue associated with footshock was sufficient to serve as a conditioned exciter to condition a fear association to a second cue. B6 mice extinguished the fear response to the second-order conditioned cue, but S1 mice failed to do so. Conclusions These data provide further evidence that fear extinction is strongly influenced by multiple procedural variables and is so in a highly strain-dependent manner. This suggests that the efficacy of extinction-based behavioral interventions, such as exposure therapy, for trauma-related anxiety disorders will be determined by the procedural parameters employed and the degree to which the patient can extinguish. PMID:23830244

Familial auditory neuropathy.

PubMed

Wang, Qiuju; Gu, Rui; Han, Dongyi; Yang, Weiyan

2003-09-01

Auditory neuropathy is a sensorineural hearing disorder characterized by absent or abnormal auditory brainstem responses and normal cochlear outer hair cell function as measured by otoacoustic emission recordings. Many risk factors are thought to be involved in its etiology and pathophysiology. Four Chinese pedigrees with familial auditory neuropathy were presented to demonstrate involvement of genetic factors in the etiology of auditory neuropathy. Probands of the above-mentioned pedigrees, who had been diagnosed with auditory neuropathy, were evaluated and followed in the Department of Otolaryngology-Head and Neck Surgery, China People Liberation Army General Hospital (Beijing, China). Their family members were studied, and the pedigree maps established. History of illness, physical examination, pure-tone audiometry, acoustic reflex, auditory brainstem responses, and transient evoked and distortion-product otoacoustic emissions were obtained from members of these families. Some subjects received vestibular caloric testing, computed tomography scan of the temporal bone, and electrocardiography to exclude other possible neuropathic disorders. In most affected patients, hearing loss of various degrees and speech discrimination difficulties started at 10 to 16 years of age. Their audiological evaluation showed absence of acoustic reflex and auditory brainstem responses. As expected in auditory neuropathy, these patients exhibited near-normal cochlear outer hair cell function as shown in distortion product otoacoustic emission recordings. Pure-tone audiometry revealed hearing loss ranging from mild to profound in these patients. Different inheritance patterns were observed in the four families. In Pedigree I, 7 male patients were identified among 43 family members, exhibiting an X-linked recessive pattern. Affected brothers were found in Pedigrees II and III, whereas in pedigree IV, two sisters were affected. All the patients were otherwise normal without evidence of peripheral neuropathy at the time of writing. Patients with characteristics of nonsyndromic hereditary auditory neuropathy were identified in one large and three smaller Chinese families. Pedigree analysis suggested an X-linked, recessive hereditary pattern in one pedigree and autosomal recessive inheritances in the other three pedigrees. The phenotypes in the study were typical of auditory neuropathy; they were transmitted in different inheritance patterns, indicating clinical and genetic heterogeneity of this disorder. The observed inheritance and clinical audiological findings are different from those previously described for nonsyndromic low-frequency sensorineural hearing loss. This information should facilitate future molecular linkage analyses and positional cloning for the relative genes contributing to auditory neuropathy.

Effects of forest conversion on soil microbial communities depend on soil layer on the eastern Tibetan Plateau of China

PubMed Central

He, Ruoyang; Yang, Kaijun; Li, Zhijie; Schädler, Martin; Yang, Wanqin; Wu, Fuzhong; Tan, Bo; Zhang, Li

2017-01-01

Forest land-use changes have long been suggested to profoundly affect soil microbial communities. However, how forest type conversion influences soil microbial properties remains unclear in Tibetan boreal forests. The aim of this study was to explore variations of soil microbial profiles in the surface organic layer and subsurface mineral soil among three contrasting forests (natural coniferous forest, NF; secondary birch forest, SF and spruce plantation, PT). Soil microbial biomass, activity and community structure of the two layers were investigated by chloroform fumigation, substrate respiration and phospholipid fatty acid analysis (PLFA), respectively. In the organic layer, both NF and SF exhibited higher soil nutrient levels (carbon, nitrogen and phosphorus), microbial biomass carbon and nitrogen, microbial respiration, PLFA contents as compared to PT. However, the measured parameters in the mineral soils often did not differ following forest type conversion. Irrespective of forest types, the microbial indexes generally were greater in the organic layer than in the mineral soil. PLFAs biomarkers were significantly correlated with soil substrate pools. Taken together, forest land-use change remarkably altered microbial community in the organic layer but often did not affect them in the mineral soil. The microbial responses to forest land-use change depend on soil layer, with organic horizons being more sensitive to forest conversion. PMID:28982191

Neuroimmune mechanisms of stress: sex differences, developmental plasticity, and implications for pharmacotherapy of stress-related disease

PubMed Central

Deak, Terrence; Quinn, Matt; Cidlowski, John A.; Victoria, Nicole C.; Murphy, Anne Z.; Sheridan, John F.

2016-01-01

The last decade has witnessed profound growth in studies examining the role of fundamental neuroimmune processes as key mechanisms that might form a natural bridge between normal physiology and pathological outcomes. Rooted in core concepts from psychoneuroimmunology, this review utilizes a succinct, exemplar-driven approach of several model systems that contribute significantly to our knowledge of the mechanisms by which neuroimmune processes interact with stress physiology. Specifically, we review recent evidence showing that (i) stress challenges produce time-dependent and stressor-specific patterns of cytokine/chemokine expression in the CNS; (ii) inflammation-related genes exhibit unique expression profiles in males and females depending upon individual, cooperative, or antagonistic interactions between steroid hormone receptors (Estrogen and Glucocorticoid receptors); (iii) adverse social experiences incurred through repeated social defeat engage a dynamic process of immune cell migration from the bone marrow to brain and prime neuroimmune function; and (iv) early developmental exposure to an inflammatory stimulus (carageenin injection into the hindpaw) has a lasting influence on stress reactivity across the lifespan. As such, the present review provides a theoretical framework for understanding the role that neuroimmune mechanisms might play in stress plasticity and pathological outcomes, while at the same time pointing toward features of the individual (sex, developmental experience, stress history) that might ultimately be used for the development of personalized strategies for therapeutic intervention in stress-related pathologies. PMID:26176590

Conformational analyses of 2,3-dihydroxypropanoic acid as a function of solvent and ionization state as determined by NMR spectroscopy.

PubMed

Drake, Michael D; Harsha, Alex K; Terterov, Sergei; Roberts, John D

2006-03-01

Vicinal (1)H--(1)H coupling constants were used to determine the conformational preferences of 2,3-dihydroxypropanoic acid (1) (DL-glyceric acid) in various solvents and its different carboxyl ionization states. The stereospecific assignments of J(12) and J(13) were confirmed through the point-group substitution of the C-3 hydrogen with deuterium, yielding rac-(2SR,3RS)-[3-(2)H]-1, and the observation of only J(13) in the (1)H NMR spectra. While hydrogen bonding and steric strain may be expected to drive the conformational equilibrium, their role is overshadowed by a profound gauche effect between the vicinal hydroxyl groups that mimics other substituted ethanes, such as 1,2-ethanediol and 1,2-difluoroethane. At low pH, the conformational equilibrium is heavily weighted toward the gauche-hydroxyl rotamers with a range of 81% in DMSO-d(6) to 92% in tert-butyl alcohol-d(10). At high pH, the equilibrium exhibits a larger dependence upon the polarity and solvating capability of the medium, although the gauche effect still dominates in D(2)O, 1,4-dioxane-d(8), methanol-d(4), and ethanol-d(6) (96, 89, 85, and 83% gauche-hydroxyls respectively). The observed preference for the gauche-hydroxyl rotamers is believed to stem primarily from hyperconjugative sigma(C--H) --> sigma*(C--OH) interactions.

Neuroimmune mechanisms of stress: sex differences, developmental plasticity, and implications for pharmacotherapy of stress-related disease.

PubMed

Deak, Terrence; Quinn, Matt; Cidlowski, John A; Victoria, Nicole C; Murphy, Anne Z; Sheridan, John F

2015-01-01

The last decade has witnessed profound growth in studies examining the role of fundamental neuroimmune processes as key mechanisms that might form a natural bridge between normal physiology and pathological outcomes. Rooted in core concepts from psychoneuroimmunology, this review utilizes a succinct, exemplar-driven approach of several model systems that contribute significantly to our knowledge of the mechanisms by which neuroimmune processes interact with stress physiology. Specifically, we review recent evidence showing that (i) stress challenges produce time-dependent and stressor-specific patterns of cytokine/chemokine expression in the CNS; (ii) inflammation-related genes exhibit unique expression profiles in males and females depending upon individual, cooperative or antagonistic interactions between steroid hormone receptors (estrogen and glucocorticoid receptors); (iii) adverse social experiences incurred through repeated social defeat engage a dynamic process of immune cell migration from the bone marrow to brain and prime neuroimmune function and (iv) early developmental exposure to an inflammatory stimulus (carageenin injection into the hindpaw) has a lasting influence on stress reactivity across the lifespan. As such, the present review provides a theoretical framework for understanding the role that neuroimmune mechanisms might play in stress plasticity and pathological outcomes, while at the same time pointing toward features of the individual (sex, developmental experience, stress history) that might ultimately be used for the development of personalized strategies for therapeutic intervention in stress-related pathologies.

Viral fusion efficacy of specific H3N2 influenza virus reassortant combinations at single-particle level

PubMed Central

Hsu, Hung-Lun; Millet, Jean K.; Costello, Deirdre A.; Whittaker, Gary R.; Daniel, Susan

2016-01-01

Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs. We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings. Results illustrate that matching pseudoparticles behaved very similarly to native virus. Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates. Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles. An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression. Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses. PMID:27752100

Peripheral Leukocyte Migration in Ferrets in Response to Infection with Seasonal Influenza Virus

PubMed Central

Kim, Jin Hyang; York, Ian A.

2016-01-01

In order to better understand inflammation associated with influenza virus infection, we measured cell trafficking, via flow cytometry, to various tissues in the ferret model following infection with an A(H3N2) human seasonal influenza virus (A/Perth/16/2009). Changes in immune cells were observed in the blood, bronchoalveolar lavage fluid, and spleen, as well as lymph nodes associated with the site of infection or distant from the respiratory system. Nevertheless clinical symptoms were mild, with circulating leukocytes exhibiting rapid, dynamic, and profound changes in response to infection. Each of the biological compartments examined responded differently to influenza infection. Two days after infection, when infected ferrets showed peak fever, a marked, transient lymphopenia and granulocytosis were apparent in all infected animals. Both draining and distal lymph nodes demonstrated significant accumulation of T cells, B cells, and granulocytes at days 2 and 5 post-infection. CD8+ T cells significantly increased in spleen at days 2 and 5 post-infection; CD4+ T cells, B cells and granulocytes significantly increased at day 5. We interpret our findings as showing that lymphocytes exit the peripheral blood and differentially home to lymph nodes and tissues based on cell type and proximity to the site of infection. Monitoring leukocyte homing and trafficking will aid in providing a more detailed view of the inflammatory impact of influenza virus infection. PMID:27315117

Peripheral Leukocyte Migration in Ferrets in Response to Infection with Seasonal Influenza Virus.

PubMed

Music, Nedzad; Reber, Adrian J; Kim, Jin Hyang; York, Ian A

2016-01-01

In order to better understand inflammation associated with influenza virus infection, we measured cell trafficking, via flow cytometry, to various tissues in the ferret model following infection with an A(H3N2) human seasonal influenza virus (A/Perth/16/2009). Changes in immune cells were observed in the blood, bronchoalveolar lavage fluid, and spleen, as well as lymph nodes associated with the site of infection or distant from the respiratory system. Nevertheless clinical symptoms were mild, with circulating leukocytes exhibiting rapid, dynamic, and profound changes in response to infection. Each of the biological compartments examined responded differently to influenza infection. Two days after infection, when infected ferrets showed peak fever, a marked, transient lymphopenia and granulocytosis were apparent in all infected animals. Both draining and distal lymph nodes demonstrated significant accumulation of T cells, B cells, and granulocytes at days 2 and 5 post-infection. CD8+ T cells significantly increased in spleen at days 2 and 5 post-infection; CD4+ T cells, B cells and granulocytes significantly increased at day 5. We interpret our findings as showing that lymphocytes exit the peripheral blood and differentially home to lymph nodes and tissues based on cell type and proximity to the site of infection. Monitoring leukocyte homing and trafficking will aid in providing a more detailed view of the inflammatory impact of influenza virus infection.

Misfit-guided self-organization of anti-correlated Ge quantum dot arrays on Si nanowires

PubMed Central

Kwon, Soonshin; Chen, Zack C.Y.; Kim, Ji-Hun; Xiang, Jie

2012-01-01

Misfit-strain guided growth of periodic quantum dot (QD) arrays in planar thin film epitaxy has been a popular nanostructure fabrication method. Engineering misfit-guided QD growth on a nanoscale substrate such as the small curvature surface of a nanowire represents a new approach to self-organized nanostructure preparation. Perhaps more profoundly, the periodic stress underlying each QD and the resulting modulation of electro-optical properties inside the nanowire backbone promise to provide a new platform for novel mechano-electronic, thermoelectronic, and optoelectronic devices. Herein, we report a first experimental demonstration of self-organized and self-limited growth of coherent, periodic Ge QDs on a one dimensional Si nanowire substrate. Systematic characterizations reveal several distinctively different modes of Ge QD ordering on the Si nanowire substrate depending on the core diameter. In particular, Ge QD arrays on Si nanowires of around 20 nm diameter predominantly exhibit an anti-correlated pattern whose wavelength agrees with theoretical predictions. The correlated pattern can be attributed to propagation and correlation of misfit strain across the diameter of the thin nanowire substrate. The QD array growth is self-limited as the wavelength of the QDs remains unchanged even after prolonged Ge deposition. Furthermore, we demonstrate a direct kinetic transformation from a uniform Ge shell layer to discrete QD arrays by a post-growth annealing process. PMID:22889063

Binaural pitch fusion: Comparison of normal-hearing and hearing-impaired listenersa)

PubMed Central

Reiss, Lina A. J.; Shayman, Corey S.; Walker, Emily P.; Bennett, Keri O.; Fowler, Jennifer R.; Hartling, Curtis L.; Glickman, Bess; Lasarev, Michael R.; Oh, Yonghee

2017-01-01

Binaural pitch fusion is the fusion of dichotically presented tones that evoke different pitches between the ears. In normal-hearing (NH) listeners, the frequency range over which binaural pitch fusion occurs is usually <0.2 octaves. Recently, broad fusion ranges of 1–4 octaves were demonstrated in bimodal cochlear implant users. In the current study, it was hypothesized that hearing aid (HA) users would also exhibit broad fusion. Fusion ranges were measured in both NH and hearing-impaired (HI) listeners with hearing losses ranging from mild-moderate to severe-profound, and relationships of fusion range with demographic factors and with diplacusis were examined. Fusion ranges of NH and HI listeners averaged 0.17 ± 0.13 octaves and 1.7 ± 1.5 octaves, respectively. In HI listeners, fusion ranges were positively correlated with a principal component measure of the covarying factors of young age, early age of hearing loss onset, and long durations of hearing loss and HA use, but not with hearing threshold, amplification level, or diplacusis. In NH listeners, no correlations were observed with age, hearing threshold, or diplacusis. The association of broad fusion with early onset, long duration of hearing loss suggests a possible role of long-term experience with hearing loss and amplification in the development of broad fusion. PMID:28372056

Brown spider monkeys (Ateles hybridus): a model for differentiating the role of social networks and physical contact on parasite transmission dynamics

PubMed Central

Rimbach, Rebecca; Bisanzio, Donal; Galvis, Nelson; Link, Andrés; Di Fiore, Anthony; Gillespie, Thomas R.

2015-01-01

Elevated risk of disease transmission is considered a major cost of sociality, although empirical evidence supporting this idea remains scant. Variation in spatial cohesion and the occurrence of social interactions may have profound implications for patterns of interindividual parasite transmission. We used a social network approach to shed light on the importance of different aspects of group-living (i.e. within-group associations versus physical contact) on patterns of parasitism in a neotropical primate, the brown spider monkey (Ateles hybridus), which exhibits a high degree of fission–fusion subgrouping. We used daily subgroup composition records to create a ‘proximity’ network, and built a separate ‘contact’ network using social interactions involving physical contact. In the proximity network, connectivity between individuals was homogeneous, whereas the contact network highlighted high between-individual variation in the extent to which animals had physical contact with others, which correlated with an individual's age and sex. The gastrointestinal parasite species richness of highly connected individuals was greater than that of less connected individuals in the contact network, but not in the proximity network. Our findings suggest that among brown spider monkeys, physical contact impacts the spread of several common parasites and supports the idea that pathogen transmission is one cost associated with social contact. PMID:25870396

Brown spider monkeys (Ateles hybridus): a model for differentiating the role of social networks and physical contact on parasite transmission dynamics.

PubMed

Rimbach, Rebecca; Bisanzio, Donal; Galvis, Nelson; Link, Andrés; Di Fiore, Anthony; Gillespie, Thomas R

2015-05-26

Elevated risk of disease transmission is considered a major cost of sociality, although empirical evidence supporting this idea remains scant. Variation in spatial cohesion and the occurrence of social interactions may have profound implications for patterns of interindividual parasite transmission. We used a social network approach to shed light on the importance of different aspects of group-living (i.e. within-group associations versus physical contact) on patterns of parasitism in a neotropical primate, the brown spider monkey (Ateles hybridus), which exhibits a high degree of fission-fusion subgrouping. We used daily subgroup composition records to create a 'proximity' network, and built a separate 'contact' network using social interactions involving physical contact. In the proximity network, connectivity between individuals was homogeneous, whereas the contact network highlighted high between-individual variation in the extent to which animals had physical contact with others, which correlated with an individual's age and sex. The gastrointestinal parasite species richness of highly connected individuals was greater than that of less connected individuals in the contact network, but not in the proximity network. Our findings suggest that among brown spider monkeys, physical contact impacts the spread of several common parasites and supports the idea that pathogen transmission is one cost associated with social contact. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Mutations in the Circadian Gene period Alter Behavioral and Biochemical Responses to Ethanol in Drosophila

PubMed Central

Liao, Jennifer; Seggio, Joseph A.; Ahmad, S. Tariq

2016-01-01

Clock genes, such as period, which maintain an organism’s circadian rhythm, can have profound effects on metabolic activity, including ethanol metabolism. In turn, ethanol exposure has been shown in Drosophila and mammals to cause disruptions of the circadian rhythm. Previous studies from our labs have shown that larval ethanol exposure disrupted the free-running period and period expression of Drosophila. In addition, a recent study has shown that arrhythmic flies show no tolerance to ethanol exposure. As such, Drosophila period mutants, which have either a shorter than wild-type free-running period (perS) or a longer one (perL), may also exhibit altered responses to ethanol due to their intrinsic circadian differences. In this study, we tested the initial sensitivity and tolerance of ethanol exposure on Canton-S, perS, and perL, and then measured their Alcohol Dehydrogenase (ADH) and body ethanol levels. We showed that perL flies had slower sedation rate, longer recovery from ethanol sedation, and generated higher tolerance for sedation upon repeated ethanol exposure compared to Canton-S wild-type flies. Furthermore, perL flies had lower ADH activity and had a slower ethanol clearance compared to wild-type flies. The findings of this study suggest that period mutations influence ethanol induced behavior and ethanol metabolism in Drosophila and that flies with longer circadian periods are more sensitive to ethanol exposure. PMID:26802726

Pathological and behavioral manifestations of the “Cayuga syndrome,” a thiamine deficiency in larval landlocked Atlantic salmon

USGS Publications Warehouse

Fisher, Jeffrey P.; Spitsbergen, Jan M.; Iamonte, Tina; Little, Edward E.; DeLonay, Aaron

1995-01-01

The “Cayuga syndrome” is a maternally transmitted, naturally occurring thiamine deficiency that causes 100% mortality of larval landlocked Atlantic salmon Salmo salar in several of New York's Finger Lakes, Results of multiyear studies to qualify and quantify the neurobehavioral and gross pathological signs of this condition are described, Affected sac fry became weak and ataxic and responded atypically to stimuli 1–2 weeks before death. Quantitative assays of stimulus-provoked swimming revealed a significant neuropathy whereby the sac fry exhibited abnormal thigmotactic and phototactic behaviors. Gross lesions observed in Cayuga sac fry included yolk-sac opacities, subcutaneous edema, vitelline hemorrhage or congestion, pericardial edema, retrobulbar edema, branchial congestion, foreshortened maxillae, hydrocephalus, and occasional caudal fin deformities, Lesion frequency in progeny differed significantly between dam source. Yolk conversion efficiency was decreased at least 1 week before death, suggesting that the bioenergetics of the fish was compromised and thereby supporting the thiamine residue and treatment data reported elsewhere, Comparisons with coagulated-yolk, blue-sac and swim-up syndromes are presented, The pathological signs of the Cayuga syndrome represent a unique departure from the lesions induced by toxicants or pathogens in other piscine models, and for the first time profile the profound effects of thiamine deficiency on cardiovascular and neurological systems of larval fish.

Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation.

PubMed

Reinisch, Andreas; Etchart, Nathalie; Thomas, Daniel; Hofmann, Nicole A; Fruehwirth, Margareta; Sinha, Subarna; Chan, Charles K; Senarath-Yapa, Kshemendra; Seo, Eun-Young; Wearda, Taylor; Hartwig, Udo F; Beham-Schmid, Christine; Trajanoski, Slave; Lin, Qiong; Wagner, Wolfgang; Dullin, Christian; Alves, Frauke; Andreeff, Michael; Weissman, Irving L; Longaker, Michael T; Schallmoser, Katharina; Majeti, Ravindra; Strunk, Dirk

2015-01-08

In the last decade there has been a rapid expansion in clinical trials using mesenchymal stromal cells (MSCs) from a variety of tissues. However, despite similarities in morphology, immunophenotype, and differentiation behavior in vitro, MSCs sourced from distinct tissues do not necessarily have equivalent biological properties. We performed a genome-wide methylation, transcription, and in vivo evaluation of MSCs from human bone marrow (BM), white adipose tissue, umbilical cord, and skin cultured in humanized media. Surprisingly, only BM-derived MSCs spontaneously formed a BM cavity through a vascularized cartilage intermediate in vivo that was progressively replaced by hematopoietic tissue and bone. Only BM-derived MSCs exhibited a chondrogenic transcriptional program with hypomethylation and increased expression of RUNX3, RUNX2, BGLAP, MMP13, and ITGA10 consistent with a latent and primed skeletal developmental potential. The humanized MSC-derived microenvironment permitted homing and maintenance of long-term murine SLAM(+) hematopoietic stem cells (HSCs), as well as human CD34(+)/CD38(-)/CD90(+)/CD45RA(+) HSCs after cord blood transplantation. These studies underscore the profound differences in developmental potential between MSC sources independent of donor age, with implications for their clinical use. We also demonstrate a tractable human niche model for studying homing and engraftment of human hematopoietic cells in normal and neoplastic states. © 2015 by The American Society of Hematology.

Thermochemically evolved nanoplatelets of bismuth selenide with enhanced thermoelectric figure of merit

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

Ali, Zulfiqar; Cao, Chuanbao, E-mail: cbcao@bit.edu.cn; Butt, Faheem K.

We firstly present a simple thermochemical method to fabricate high-quality Bi{sub 2}Se{sub 3} nanoplatelets with enhanced figure of merit using elemental bismuth and selenium powders as precursors. The crystal structure of as synthesized products is characterized via X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and high resolution transmission electron microscopy (HRTEM) measurements. Morphological and chemical synthetic parameters are investigated through a series of experiments; thickness and composition of the platelets are well controlled in large scale production. Subsequently spark plasma sintering (SPS) is performed to fabricate n-type nanostructured bulk thermoelectric materials. Raman Spectroscopy of the two selected samples with approximatelymore » of 50 and 100 nm thicknesses shows three vibrational modes. The lower thickness sample exhibits the maximum red shift of about 2.17 cm{sup -1} and maximum broadening of about 10 cm{sup -1} by in-plane vibrational mode E{sup 2}{sub g}. The enhanced value of figure of merit ∼0.41 is obtained for pure phase bismuth selenide to the best of our knowledge. We observe metallic conduction behavior while semiconducting behavior for nanostructured bismuth selenide is reported elsewhere which could be due to different synthetic techniques adopted. These results clearly suggest that our adopted synthetic technique has profound effect on the electronic and thermoelectric transport properties of this material.« less

mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes.

PubMed

Fort, Patrice E; Losiewicz, Mandy K; Pennathur, Subramaniam; Jefferson, Leonard S; Kimball, Scot R; Abcouwer, Steven F; Gardner, Thomas W

2014-09-01

Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass resulting from a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes despite reduced Akt activity and increased rate of cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than in other insulin-sensitive tissues, such as skeletal muscle. Ins2(Akita) diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions in retinal protein synthesis matched by a concomitant reduction in retinal protein degradation associated with preserved retinal mass and protein content. The reduction in protein synthesis depended on both hyperglycemia and insulin deficiency, but protein degradation was only reversed by normalization of hyperglycemia. The reduction in protein synthesis was associated with diminished protein translation efficiency but, surprisingly, not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes induced a specific reduction of mTORC2 complex activity. These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared with muscle and liver that may provide a new means to ameliorate diabetic retinopathy. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Report: Bioconversion of agriculture waste to lysine with UV mutated strain of brevibacterium flavum and its biological evaluation in broiler chicks.

PubMed

Tabassum, Alia; Hashmi, Abu Saeed; Masood, Faiza; Iqbal, Muhammad Aamir; Tayyab, Muhammad; Nawab, Amber; Nadeem, Asif; Sadeghi, Zahra; Mahmood, Adeel

2015-07-01

Lysine executes imperative structural and functional roles in body and its supplementation in diet beneficial to prevent the escalating threat of protein deficiency. The physical mutagenesis offers new fascinating avenues of research for overproduction of lysine through surplus carbohydrate containing agriculture waste especially in developing countries. The current study was aimed to investigate the potential of UV mutated strain of Brevibacterium flavum at 254 nm for lysine production. The physical and nutritional parameters were optimized and maximum lysine production was observed with molasses (4% substrate water ratio). Moreover, supplementation of culture medium with metal cations (i.e. 0.4% CaSO₄, 0.3% NaCl, 0.3% KH₂PO₄, 0.4% MgSO₄, and 0.2% (NH₄) ₂SO₄w/v) together with 0.75% v/v corn steep liquor significantly enhanced the lysine production up to 26.71 ± 0.31 g/L. Though, concentrations of urea, ammonium nitrate and yeast sludge did not exhibit any profound effect on lysine production. Biological evaluation of lysine enriched biomass in terms of weight gain and feed conversion ratio reflected non-significant difference for experimental and control (+ve) groups. Conclusively, lysine produced in the form of biomass was compatible to market lysine in its effectiveness and have potential to utilize at commercial scale.

Effects of the Amino Acid Linkers on the Melanoma-Targeting and Pharmacokinetic Properties of Indium-111-labeled Lactam Bridge-Cyclized α-MSH Peptides

PubMed Central

Guo, Haixun; Yang, Jianquan; Gallazzi, Fabio; Miao, Yubin

2011-01-01

The purpose of this study was to examine the profound effects of the amino acid linkers on the melanoma targeting and pharmacokinetic properties of novel 111In-labeled lactam bridge-cyclized DOTA-[X]-CycMSHhex {1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid-[X]-c[Asp-His-dPhe-Arg-Trp-Lys]-CONH2, X=GlyGlyNle, GlyGluNle or NleGlyGlu} peptides. Methods Three novel DOTA-GGNle-CycMSHhex, DOTA-GENle-CycMSHhex and DOTA-NleGE-CycMSHhex peptides were designed and synthesized. The melanocortin-1 (MC1) receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The melanoma targeting and pharmacokinetic properties of 111In-DOTA-GGNle-CycMSHhex and 111In-DOTA-GENle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice. Results DOTA-GGNle-CycMSHhex and DOTA-GENle-CycMSHhex displayed 2.1 and 11.5 nM MC1 receptor binding affinities, whereas DOTA-NleGE-CycMSHhex showed 873.4 nM MC1 receptor binding affinity. The introduction of the -GlyGly- linker maintained high melanoma uptake while decreased the renal and liver uptakes of 111In-DOTA-GlyGlyNle-CycMSHhex. The tumor uptake values of 111In-DOTA-GGNle-CycMSHhex were 19.05 ± 5.04 and 18.6 ± 3.56 % injected dose/gram (%ID/g) at 2 and 4 h post-injection. 111In-DOTA-GGNle-CycMSHhex exhibited 28, 32 and 42% less renal uptake values than 111In-DOTA-Nle-CycMSHhex we reported previously, and 61, 65 and 68% less liver uptake values than 111In-DOTA-Nle-CycMSHhex at 2, 4 and 24 h post-injection, respectively. Conclusion The amino acid linkers exhibited the profound effects on the melanoma targeting and pharmacokinetic properties of the 111In-labeled lactam bridge-cyclized α-MSH peptides. Introduction of the -GlyGly- linker maintained high melanoma uptake while reducing the renal and liver uptakes of 111In-DOTA-GlyGlyNle-CycMSHhex, highlighting its potential as an effective imaging probe for melanoma detection, as well as a therapeutic peptide for melanoma treatment when labeled with a therapeutic radionuclide. PMID:21421725

Effects of the amino acid linkers on the melanoma-targeting and pharmacokinetic properties of 111In-labeled lactam bridge-cyclized alpha-MSH peptides.

PubMed

Guo, Haixun; Yang, Jianquan; Gallazzi, Fabio; Miao, Yubin

2011-04-01

The purpose of this study was to examine the profound effects of the amino acid linkers on the melanoma-targeting and pharmacokinetic properties of (111)In-labeled lactam bridge-cyclized DOTA-[X]-CycMSH(hex) {1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[X]-c[Asp-His-dPhe-Arg-Trp-Lys]-CONH(2); X = GGNle, GENle, or NleGE; GG = -Gly-Gly- and GE = -Gly-Glu-} peptides. Three novel peptides (DOTA-GGNle-CycMSH(hex), DOTA-GENle-CycMSH(hex), and DOTA-NleGE-CycMSH(hex)) were designed and synthesized. The melanocortin-1 (MC1) receptor-binding affinities of the peptides were determined in B16/F1 melanoma cells. The melanoma-targeting and pharmacokinetic properties of (111)In-DOTA-GGNle-CycMSH(hex) and (111)In-DOTA-GENle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice. DOTA-GGNle-CycMSH(hex) and DOTA-GENle-CycMSH(hex) displayed 2.1 and 11.5 nM MC1 receptor-binding affinities, whereas DOTA-NleGE-CycMSH(hex) showed 873.4 nM MC1 receptor-binding affinity. The introduction of the -GG- linker maintained high melanoma uptake while decreasing kidney and liver uptake of (111)In-DOTA-GGNle-CycMSH(hex). The tumor uptake of (111)In-DOTA-GGNle-CycMSH(hex) was 19.05 ± 5.04 and 18.6 ± 3.56 percentage injected dose per gram at 2 and 4 h after injection, respectively. (111)In-DOTA-GGNle-CycMSH(hex) exhibited 28%, 32%, and 42% less kidney uptake than (111)In-DOTA-Nle-CycMSH(hex) we reported previously, and 61%, 65%, and 68% less liver uptake than (111)In-DOTA-Nle-CycMSH(hex) at 2, 4, and 24 h after injection, respectively. The amino acid linkers exhibited profound effects on the melanoma-targeting and pharmacokinetic properties of the (111)In-labeled lactam bridge-cyclized α-melanocyte-stimulating hormone peptides. Introduction of the -GG- linker maintained high melanoma uptake while reducing kidney and liver uptake of (111)In-DOTA-GGNle-CycMSH(hex), highlighting its potential as an effective imaging probe for melanoma detection, as well as a therapeutic peptide for melanoma treatment when labeled with a therapeutic radionuclide.

Synergistic effects of the xid gene in X chromosome congenic mice. I. Inability of C3.CBA/N mice to respond to thymus-dependent antigens in adoptive transfer assays.

PubMed

Kenny, J J; Guelde, G; Hansen, C; Mond, J J

1987-03-01

The xid gene, which causes a B lymphocyte immune defect in CBA/N mice, has been bred onto the C3H/HeN background. The resulting X chromosome congenic mice (C3.CBA/N) exhibit immunologic defects that are much more profound than the defect exhibited by CBA/N mice; thus, the B cells from C3.CBA/N mice not only fail to respond to thymus-independent (TI) type 2 antigens such as TNP-Ficoll, but they fail to respond in vitro to TI-type 1 antigens such as TNP-Brucella abortus (BA) and B cell mitogens such as LPS and Nocardia water-soluble mitogen. In this paper we show that the synergistic defect seen in C3.CBA/N B cells is also elicited in adoptive transfer assays to thymus-dependent (TD) antigens such as TNP-KLH and PC-KLH, antigens to which both parental strains respond. Thus, the secondary adoptive transfer response of C3.CBA/N spleen cells is generally less than 5% of the immune response produced by CBA/N or C3H/HeN spleen cells. This synergistic defect is restricted to the C3.CBA/N B cells, since C3.CBA/N T cells can provide help to CBA/N B cells that is equivalent to the help obtained with CBA/N T cells. The low responsiveness of C3.CBA/N spleen cells to TD antigens, which is elicited in adoptive transfer assays, is not seen when the intact animal is immunized with antigen in CFA; this, intact C3.CBA/N mice produce anti-PC-KLH and anti-TNP-KLH responses only slightly lower than the responses of CBA/N mice to these same antigens. In contrast, when these mice are immunized with phenol-extracted LPS, a TI-type 1 antigen, their antibody responses are severely depressed. These data suggest that under conditions in which T cell help may be limiting or in which the intact physiology of the T and B cells has been disrupted, C3.CBA/N B cells demonstrate profound immunologic impairment; however, when adequate T cell help is available and the splenic architecture is not disrupted, their immune responses appear to progress in a normal fashion.

An atypical case of successful resuscitation of an accidental profound hypothermia patient, occurring in a temperate climate.

PubMed

Coleman, E; Doddakula, K; Meeke, R; Marshall, C; Jahangir, S; Hinchion, J

2010-03-01

Cases of accidental profound hypothermia occur most frequently in cold, northern climates. We describe an atypical case, occurring in a temperate climate, where a hypothermic cardiac-arrested patient was successfully resuscitated using extracorporeal circulation (ECC).

Intellectual Prosthesis: Reality or Dream for the Severely/Profoundly Retarded Person.

ERIC Educational Resources Information Center

Lent, James R.

1982-01-01

Developments in artificial intelligence have relevance for the education of severely/profoundly retarded persons by enhancing the learning of facts, principles, skills and concepts and by providing opportunities (via more portable equipment) for applications in a wide variety of settings. (CL)

Attuning: A Communication Process between People with Severe and Profound Intellectual Disability and Their Interaction Partners.

PubMed

Griffiths, Colin; Smith, Martine

2016-03-01

People with severe and profound intellectual disability typically demonstrate a limited ability to communicate effectively. Most of their communications are non-verbal, often idiosyncratic and ambiguous. This article aims to identify the process that regulates communications of this group of people with others and to describe the methodological approach that was used to achieve this. In this qualitative study, two dyads consisting of a person with severe or profound intellectual and multiple disability and a teacher or carer were filmed as they engaged in school-based activities. Two 1-hour videotapes were transcribed and analysed using grounded theory. Attuning was identified within the theory proposed here as a central process that calibrates and regulates communication. Attuning is conceptualized as a bidirectional, dyadic communication process. Understanding this process may support more effective communication between people with severe or profound intellectual and multiple disability and their interaction partners. © 2015 John Wiley & Sons Ltd.

Various Strategies for Pain-Free Root Canal Treatment

PubMed Central

Parirokh, Masoud; V. Abbott, Paul

2014-01-01

Introduction: Achieving successful anesthesia and performing pain-free root canal treatment are important aims in dentistry. This is not always achievable and therefore, practitioners are constantly seeking newer techniques, equipments, and anesthetic solutions for this very purpose. The aim of this review is to introduce strategies to achieve profound anesthesia particularly in difficult cases. Materials and Methods: A review of the literature was performed by electronic and hand searching methods for anesthetic agents, techniques, and equipment. The highest level of evidence based investigations with rigorous methods and materials were selected for discussion. Results: Numerous studies investigated to pain management during root canal treatment; however, there is still no single technique that will predictably provide profound pulp anesthesia. One of the most challenging issues in endodontic practice is achieving a profound anesthesia for teeth with irreversible pulpitis especially in mandibular posterior region. Conclusion: According to most investigations, achieving a successful anesthesia is not always possible with a single technique and practitioners should be aware of all possible alternatives for profound anesthesia. PMID:24396370

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

PubMed

Gordon, K A; Papsin, B C; Harrison, R V

2007-08-01

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy.

PubMed

Löscher, Wolfgang; Ferland, Russell J; Ferraro, Thomas N

2017-08-01

It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals' performance in behavioral tests that often accompany acute and chronic seizure testing. Copyright © 2017 Elsevier Inc. All rights reserved.

The Prevalence of Boredom Proneness and Depression among Profoundly Deaf Residential School Adolescents.

ERIC Educational Resources Information Center

Watt, John D.; Davis, Faith E.

1991-01-01

Fifty profoundly deaf residential school adolescents were administered the Boredom Proneness scale and a modified version of the Beck Depression Inventory. Deaf students had a significantly higher incidence of depression and were more boredom prone than were hearing subjects. (Author/JDD)

Foundation Care: A Treatment Model for Nonambulatory Profoundly Mentally Retarded Persons.

ERIC Educational Resources Information Center

LaMendola, Walter F.; And Others

1987-01-01

Two institutional treatment models--Intermediate Care Facilities and Foundation Care--were compared with 30 profoundly mentally retarded adults. The Foundation Care model (which emphasized habilitation through health, nurturance, stimulation, and play) demonstrated more resident-oriented management practices and used more tactile modalities and…

Training Eye-Pointing Behavior in a Nonabulatory Profoundly Mentally Retarded Child Using Contingent Vibratory Stimulation.

ERIC Educational Resources Information Center

Zucker, Stanley H.; And Others

1980-01-01

Contingent vibration was used to train a precommunication response in a spastic/quadriplegic profoundly mentally retarded boy (age 11). The results indicated an increase in the S's eye pointing behavior subsequent to the administration of response contingent vibration. (Author)

JPRS Report, West Europe

DTIC Science & Technology

1987-06-02

Hiding Profound Difficulties (A.J.R. Soares de Mello; SEMANARIO, 28 Mar 87) 112 c MILITARY FEDERAL REPUBLIC OF GERMANY Air Force Looks To...ever to the fight against unemployment Happart- De Cross: Same Fight? There are few differences also regarding the notoriety of politicians, with a...traditional practices? De Croo has had very good results in the southern and central regions of the country, probably because the very human and

F-16 Instructional Sequencing Plan Report.

DTIC Science & Technology

1981-03-01

information). 2. Interference (learning of some tasks interferes with the learning of other tasks when they possess similar but confusing differences ...profound effect on the total training expense. This increases the desirability of systematic, precise methods of syllabus generation. Inherent in a given...the expensive to acquire. resource. Least cost The syllabus must Select sequences which provide a least total make maximum use of cost method of

Consciousness and values in the quantum universe

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

Stapp, H.P.

1985-01-01

Application of quantum mechanical description to neurophysiological processes appears to provide for a natural unification of the physical and humanistic sciences. The categories of thought used to represent physical and psychical processes become united, and the mechanical conception of man created by classical physics is replaced by a profoundly different quantum conception. This revised image of man allows human values to be rooted in contemporary science.

Create the Plan, Work the Plan: A Look at Why the Independent Business Owner Has Trouble Calling a Franchisee a True Entrepreneur

ERIC Educational Resources Information Center

Buzza, John; Mosca, Joseph B.

2009-01-01

Our complex and intricate economic system is comprised of many different types and sizes of businesses, ranging from big corporations to small individually owned entities. The genre of business is and can be profoundly complex. Independence can vary from small single person mom and pops to consortiums of multiple partners, silent partners and…

Compositional changes of soil organic matter with cropping time were more profound in subsoils and distinct between Phaeozem and Chernozem in Northeast China

USDA-ARS?s Scientific Manuscript database

Soil organic matter (SOM) contributes to soil processes and is found both in shallow and deep soil layers. Its activity can be affected by its chemical composition, yet knowledge is incomplete of how land use alters the structural composition of SOM throughout the profiles of different soil types. T...

Making a difference? A comparison between multi-sensory and regular storytelling for persons with profound intellectual and multiple disabilities.

PubMed

Ten Brug, A; Van der Putten, A A J; Penne, A; Maes, B; Vlaskamp, C

2016-11-01

Multi-sensory storytelling (MSST) was developed to include persons with profound intellectual and multiple disabilities in storytelling culture. In order to increase the listeners' attention, MSST stories are individualised and use multiple sensory stimuli to support the verbal text. In order to determine the value of MSST, this study compared listeners' attention under two conditions: (1) being read MSST books and (2) being read regular stories. A non-randomised control study was executed in which the intervention group read MSST books (n = 45) and a comparison group (n = 31) read regular books. Books were read 10 times during a 5-week period. The 1st, 5th and 10th storytelling sessions were recorded on video in both groups, and the percentage of attention directed to the book and/or stimuli and to the storyteller was scored by a trained and independent rater. Two repeated measure analyses (with the storytelling condition as a between-subject factor and the three measurements as factor) were performed to determine the difference between the groups in terms of attention directed to the book/stimuli (first analysis) and storyteller (second analysis). A further analysis established whether the level of attention changed between the reading sessions and whether there was an interaction effect between the repetition of the book and the storytelling condition. The attention directed to the book and/or the stimuli was significantly higher in the MSST group than in the comparison group. No significant difference between the two groups was found in the attention directed to the storyteller. For MSST stories, most attention was observed during the fifth reading session, while for regular stories, the fifth session gained least attentiveness from the listener. The persons with profound intellectual and multiple disabilities paid more attention to the book and/or stimuli in the MSST condition compared with the regular story telling group. Being more attentive towards the book and stimuli might give persons with PIMD the opportunity to apprehend the story and to be included in storytelling culture. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Hearing Loss in Stranded Odontocete Dolphins and Whales

PubMed Central

Mann, David; Hill-Cook, Mandy; Manire, Charles; Greenhow, Danielle; Montie, Eric; Powell, Jessica; Wells, Randall; Bauer, Gordon; Cunningham-Smith, Petra; Lingenfelser, Robert; DiGiovanni, Robert; Stone, Abigale; Brodsky, Micah; Stevens, Robert; Kieffer, George; Hoetjes, Paul

2010-01-01

The causes of dolphin and whale stranding can often be difficult to determine. Because toothed whales rely on echolocation for orientation and feeding, hearing deficits could lead to stranding. We report on the results of auditory evoked potential measurements from eight species of odontocete cetaceans that were found stranded or severely entangled in fishing gear during the period 2004 through 2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed dolphins had significant hearing deficits with a reduction in sensitivity equivalent to severe (70–90 dB) or profound (>90 dB) hearing loss in humans. The only stranded short-finned pilot whale examined had profound hearing loss. No impairments were detected in seven Risso's dolphins from three different stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could play a significant role in some cetacean stranding events, and the hearing of all cetaceans in rehabilitation should be tested. PMID:21072206

Pioneering figures in medicine: Albert Bruce Sabin--inventor of the oral polio vaccine.

PubMed

Smith, Derek R; Leggat, Peter A

2005-01-01

Over ten years after his death, the Sabin oral vaccine continues its profound influence on public health throughout the world. The annual incidence of polio has fallen dramatically since its introduction, with more than 300,000 lives being spared each year and an annual global saving in excess of 1 billion US dollars. In many ways, the development of an effective oral vaccine and its subsequent regulation by the World Health Organization can serve as a model for medical researchers. Our review describes the contribution of Albert Sabin as a medical researcher, and how his vaccine had a profound impact on the global reduction of polio infections. As many different factors influenced health-care last century, we describe Sabin's involvement with respect to prevailing scientific paradigms and public health issues of the time. Our paper also outlines the basic epidemiology of poliovirus and the historical development of an effective vaccine, both with and without Albert Sabin.

Hearing loss in stranded odontocete dolphins and whales.

PubMed

Mann, David; Hill-Cook, Mandy; Manire, Charles; Greenhow, Danielle; Montie, Eric; Powell, Jessica; Wells, Randall; Bauer, Gordon; Cunningham-Smith, Petra; Lingenfelser, Robert; DiGiovanni, Robert; Stone, Abigale; Brodsky, Micah; Stevens, Robert; Kieffer, George; Hoetjes, Paul

2010-11-03

The causes of dolphin and whale stranding can often be difficult to determine. Because toothed whales rely on echolocation for orientation and feeding, hearing deficits could lead to stranding. We report on the results of auditory evoked potential measurements from eight species of odontocete cetaceans that were found stranded or severely entangled in fishing gear during the period 2004 through 2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed dolphins had significant hearing deficits with a reduction in sensitivity equivalent to severe (70-90 dB) or profound (>90 dB) hearing loss in humans. The only stranded short-finned pilot whale examined had profound hearing loss. No impairments were detected in seven Risso's dolphins from three different stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could play a significant role in some cetacean stranding events, and the hearing of all cetaceans in rehabilitation should be tested.

The demand for speech pathology services for children: Do we need more or just different?

PubMed

Reilly, Sheena; Harper, Megan; Goldfeld, Sharon

2016-12-01

An inability or difficulty communicating can have a profound impact on a child's future ability to participate in society as a productive adult. Over the past few years the number of interventions for children with speech and language problems has almost doubled; the majority are targeted interventions delivered by speech pathologists. In this paper we examine the distribution of speech pathology services in metropolitan Melbourne and how these are aligned with need as defined by vulnerability in language and social disadvantage. We identified three times as many private sector services compared to public services for the 0-5 year age group. Overall there was poorer availability of services in some of the most vulnerable areas. The profound and long-term impact of impoverished childhood language, coupled with the considerable limitations on public spending, provide a strong impetus to deliver more equitably distributed speech pathology services. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Over-dose insulin and stable gastric pentadecapeptide BPC 157. Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats.

PubMed

Ilic, S; Brcic, I; Mester, M; Filipovic, M; Sever, M; Klicek, R; Barisic, I; Radic, B; Zoricic, Z; Bilic, V; Berkopic, L; Brcic, L; Kolenc, D; Romic, Z; Pazanin, L; Seiwerth, S; Sikiric, P

2009-12-01

We focused on over-dose insulin (250 IU/kg i.p.) induced gastric ulcers and then on other disturbances that were concomitantly induced in rats, seizures (eventually fatal), severely damaged neurons in cerebral cortex and hippocampus, hepatomegaly, fatty liver, increased AST, ALT and amylase serum values, breakdown of liver glycogen with profound hypoglycemia and calcification development. Calcium deposits were present in the blood vessel walls, hepatocytes surrounding blood vessels and sometimes even in parenchyma of the liver mainly as linear and only occasionally as granular accumulation. As an antidote after insulin, we applied the stable gastric pentadecapeptide BPC 157 (10 microg/kg) given (i) intraperitoneally or (ii) intragastrically immediately after insulin. Controls received simultaneously an equivolume of saline (5 ml/kg). Those rats that survived till the 180 minutes after over-dose application were further assessed. Interestingly, pentadecapeptide BPC 157, as an antiulcer peptide, may besides stomach ulcer consistently counteract all insulin disturbances and fatal outcome. BPC 157 rats showed no fatal outcome, they were mostly without hypoglycemic seizures with apparently higher blood glucose levels (glycogen was still present in hepatocytes), less liver pathology (i.e., normal liver weight, less fatty liver), decreased ALT, AST and amylase serum values, markedly less damaged neurons in brain and they only occasionally had small gastric lesions. BPC 157 rats exhibited mostly only dot-like calcium presentation. In conclusion, the success of BPC 157 therapy may indicate a likely role of BPC 157 in insulin controlling and BPC 157 may influence one or more causative process(es) after excessive insulin application.

Profound Amplification of Pathogenic Murine Polytropic Retrovirus Release from Coinfected Cells

PubMed Central

Rosenke, Kyle; Lavignon, Marc; Malik, Frank; Kolokithas, Angelo; Hendrick, Duncan; Virtaneva, Kimmo; Peterson, Karin

2012-01-01

Previous studies indicate that mice infected with mixtures of mouse retroviruses (murine leukemia viruses [MuLVs]) exhibit dramatically altered pathology compared to mice infected with individual viruses of the mixture. Coinoculation of the ecotropic virus Friend MuLV (F-MuLV) with Fr98, a polytropic MuLV, induced a rapidly fatal neurological disease that was not observed in infections with either virus alone. The polytropic virus load in coinoculated mice was markedly enhanced, while the ecotropic F-MuLV load was unchanged. Furthermore, pseudotyping of the polytropic MuLV genome within ecotropic virions was nearly complete in coinoculated mice. In an effort to better understand these phenomena, we examined mixed retrovirus infections by utilizing in vitro cell lines. Similar to in vivo mixed infections, the polytropic MuLV genome was extensively pseudotyped within ecotropic virions; polytropic virus release was profoundly elevated in coinfected cells, and the ecotropic virus release was unchanged. A reduced level of polytropic SU protein on the surfaces of coinfected cells was observed and correlated with a reduced level of nonpseudotyped polytropic virion release. Marked amplification and pseudotyping of the polytropic MuLV were also observed in mixed Fr98–F-MuLV infections of cell lines derived from the central nervous system (CNS), the target for Fr98 pathogenesis. Additional experiments indicated that pseudotyping contributed to the elevated polytropic virus titer by increasing the efficiency of packaging and release of the polytropic genomes within ecotropic virions. Mixed infections are the rule rather than the exception in retroviral infection, and the ability to examine them in vitro should facilitate a more thorough understanding of retroviral interactions in general. PMID:22514353

Consistent platelet inhibition during long-term maintenance-dose clopidogrel therapy among 359 compliant outpatients with documented vascular disease.

PubMed

Serebruany, Victor L; Malinin, Alex I; Atar, Dan; Hanley, Dan F

2007-03-01

Numerous reports have dichotomized responses after clopidogrel therapy using varying definitions and platelet tests in patients immediately after acute vascular events; however, no large study has assessed platelet characteristics in outpatients receiving long-term treatment for more than 30 days with the maintenance dose (75 mg/d) of clopidogrel. The aim of this study was to describe the responses of ex vivo measures of platelet aggregation and activation to long-term clopidogrel therapy in a large population of outpatients after coronary stenting or ischemic stroke. We conducted a secondary post hoc analysis of a data set represented by presumably compliant patients after coronary stenting (n = 237) or a documented ischemic stroke (n = 122) treated with clopidogrel-and-aspirin combination antiplatelet therapy. The mean duration of treatment was 5.8 months (range 1-21 months). Every patient exhibited a significant inhibition of adenosine diphosphate-induced platelet aggregation (mean 52.9%, range 36%-70%) as compared with the preclopidogrel measures. Inhibition of aggregation strongly correlated with a diminished expression of PECAM-1 (platelet/endothelial cell adhesion molecule 1, r = 0.75), glycoprotein IIb/IIIa (r = 0.62), and PAR-1 (protease-activated receptor 1, r = 0.71). None of the patients developed hyporesponsiveness (reduction from the baseline <15%) or profound inhibition (residual platelet activity <10%). In contrast to the wide variability of responses that exists in the acute setting, long-term therapy with clopidogrel leads to consistent and much less variable platelet inhibition. Lack of nonresponse and profound inhibition with clopidogrel allow for the maintenance of a delicate balance between proven efficacy and acceptable bleeding risks for long-term secondary prevention in outpatients after acute vascular events.

Critical Slowing Down Governs the Transition to Neuron Spiking

PubMed Central

Meisel, Christian; Klaus, Andreas; Kuehn, Christian; Plenz, Dietmar

2015-01-01

Many complex systems have been found to exhibit critical transitions, or so-called tipping points, which are sudden changes to a qualitatively different system state. These changes can profoundly impact the functioning of a system ranging from controlled state switching to a catastrophic break-down; signals that predict critical transitions are therefore highly desirable. To this end, research efforts have focused on utilizing qualitative changes in markers related to a system’s tendency to recover more slowly from a perturbation the closer it gets to the transition—a phenomenon called critical slowing down. The recently studied scaling of critical slowing down offers a refined path to understand critical transitions: to identify the transition mechanism and improve transition prediction using scaling laws. Here, we outline and apply this strategy for the first time in a real-world system by studying the transition to spiking in neurons of the mammalian cortex. The dynamical system approach has identified two robust mechanisms for the transition from subthreshold activity to spiking, saddle-node and Hopf bifurcation. Although theory provides precise predictions on signatures of critical slowing down near the bifurcation to spiking, quantitative experimental evidence has been lacking. Using whole-cell patch-clamp recordings from pyramidal neurons and fast-spiking interneurons, we show that 1) the transition to spiking dynamically corresponds to a critical transition exhibiting slowing down, 2) the scaling laws suggest a saddle-node bifurcation governing slowing down, and 3) these precise scaling laws can be used to predict the bifurcation point from a limited window of observation. To our knowledge this is the first report of scaling laws of critical slowing down in an experiment. They present a missing link for a broad class of neuroscience modeling and suggest improved estimation of tipping points by incorporating scaling laws of critical slowing down as a strategy applicable to other complex systems. PMID:25706912

Home Range Utilisation and Long-Range Movement of Estuarine Crocodiles during the Breeding and Nesting Season

PubMed Central

Campbell, Hamish A.; Dwyer, Ross G.; Irwin, Terri R.; Franklin, Craig E.

2013-01-01

The estuarine crocodile (Crocodylus porosus) is the apex-predator in waterways and coastlines throughout south-east Asia and Australasia. C. porosus pose a potential risk to humans, and management strategies are implemented to control their movement and distribution. Here we used GPS-based telemetry to accurately record geographical location of adult C. porosus during the breeding and nesting season. The purpose of the study was to assess how C. porosus movement and distribution may be influenced by localised social conditions. During breeding, the females (2.92±0.013 metres total length (TL), mean ± S.E., n = 4) occupied an area<1 km length of river, but to nest they travelled up to 54 km away from the breeding area. All tagged male C. porosus sustained high rates of movement (6.49±0.9 km d−1; n = 8) during the breeding and nesting period. The orientation of the daily movements differed between individuals revealing two discontinuous behavioural strategies. Five tagged male C. porosus (4.17±0.14 m TL) exhibited a ‘site-fidelic’ strategy and moved within well-defined zones around the female home range areas. In contrast, three males (3.81±0.08 m TL) exhibited ‘nomadic’ behaviour where they travelled continually throughout hundreds of kilometres of waterway. We argue that the ‘site-fidelic’ males patrolled territories around the female home ranges to maximise reproductive success, whilst the ‘nomadic’ males were subordinate animals that were forced to range over a far greater area in search of unguarded females. We conclude that C. porosus are highly mobile animals existing within a complex social system, and mate/con-specific interactions are likely to have a profound effect upon population density and distribution, and an individual's travel potential. We recommend that impacts on socio-spatial behaviour are considered prior to the implementation of management interventions. PMID:23650510

Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) alpha knock-out mice. Evidence for compensatory regulation by PPAR delta.

PubMed

Muoio, Deborah M; MacLean, Paul S; Lang, David B; Li, Shi; Houmard, Joseph A; Way, James M; Winegar, Deborah A; Corton, J Christopher; Dohm, G Lynis; Kraus, William E

2002-07-19

Ablation of peroxisome proliferator activated receptor (PPAR) alpha, a lipid-activated transcription factor that regulates expression of beta-oxidative genes, results in profound metabolic abnormalities in liver and heart. In the present study we used PPAR alpha knockout (KO) mice to determine whether this transcription factor is essential for regulating fuel metabolism in skeletal muscle. When animals were challenged with exhaustive exercise or starvation, KO mice exhibited lower serum levels of glucose, lactate, and ketones and higher nonesterified fatty acids than wild type (WT) littermates. During exercise, KO mice exhausted earlier than WT and exhibited greater rates of glycogen depletion in liver but not skeletal muscle. Fatty acid oxidative capacity was similar between muscles of WT and KO when animals were fed and only 28% lower in KO muscles when animals were starved. Exercise-induced regulation and starvation-induced regulation of pyruvate-dehydrogenase kinase 4 and uncoupling protein 3, two classical and robustly responsive PPAR alpha target genes, were similar between WT and KO in skeletal muscle but markedly different between genotypes in heart. Real time quantitative PCR analyses showed that unlike in liver and heart, in mouse skeletal muscle PPAR delta is severalfold more abundant than either PPAR alpha or PPAR gamma. In both human and rodent myocytes, the highly selective PPAR delta agonist GW742 increased fatty acid oxidation about 2-fold and induced expression of several lipid regulatory genes, including pyruvate-dehydrogenase kinase 4 and uncoupling protein 3, responses that were similar to those elicited by the PPAR alpha agonist GW647. These results show redundancy in the functions of PPARs alpha and delta as transcriptional regulators of fatty acid homeostasis and suggest that in skeletal muscle high levels of the delta-subtype can compensate for deficiency of PPAR alpha.

Unexpected Long-Term Protection of Adult Offspring Born to High-Fat Fed Dams against Obesity Induced by a Sucrose-Rich Diet

PubMed Central

Couvreur, Odile; Ferezou, Jacqueline; Gripois, Daniel; Serougne, Colette; Crépin, Delphine; Aubourg, Alain; Gertler, Arieh; Vacher, Claire-Marie; Taouis, Mohammed

2011-01-01

Background Metabolic and endocrine environment during early life is crucial for metabolic imprinting. When dams were fed a high fat diet (HF diet), rat offspring developed hypothalamic leptin resistance with lean phenotype when weaned on a normal diet. Interestingly, when grown on the HF diet, they appeared to be protected against the effects of HF diet as compared to offspring of normally fed dams. The mechanisms involved in the protective effect of maternal HF diet are unclear. Methodology/Principal Findings We thus investigated the impact of maternal high fat diet on offspring subjected to normal or high palatable diet (P diet) on metabolic and endocrine parameters. We compared offspring born to dams fed P or HF diet. Offspring born to dams fed control or P diet, when fed P diet exhibited a higher body weight, altered hypothalamic leptin sensitivity and metabolic parameters suggesting that maternal P diet has no protective effect on offspring. Whereas, maternal HF diet reduces body weight gain and circulating triglycerides, and ameliorates corpulence index of offspring, even when subjected to P diet. Interestingly, this protective effect is differently expressed in male and female offspring. Male offspring exhibited higher energy expenditure as mirrored by increased hypothalamic UCP-2 and liver AdipoR1/R2 expression, and a profound change in the arcuate nucleus astrocytic organization. In female offspring, the most striking impact of maternal HF diet is the reduced hypothalamic expression of NPY and POMC. Conclusions/Significance HF diet given during gestation and lactation protects, at least partially, offspring from excessive weight gain through several mechanisms depending upon gender including changes in arcuate nucleus astrocytic organization and increased hypothalamic UCP-2 and liver AdipoR1/2 expression in males and reduced hypothalamic expression of NPY and POMC in females. Taken together our results reveal new mechanisms involved in the protective effect of maternal HF diet. PMID:21464991

Polythiol-containing, recombinant mannosylated-albumin is a superior CD68+/CD206+ Kupffer cell-targeted nanoantioxidant for treatment of two acute hepatitis models.

PubMed

Maeda, Hitoshi; Hirata, Kenshiro; Watanabe, Hiroshi; Ishima, Yu; Chuang, Victor Tuan Giam; Taguchi, Kazuaki; Inatsu, Akihito; Kinoshita, Manabu; Tanaka, Motohiko; Sasaki, Yutaka; Otagiri, Masaki; Maruyama, Toru

2015-02-01

Since reactive oxygen species (ROS) derived from Kupffer cells (KC), especially CD68(+) KC, play a key role in the induction of hepatic oxidative stress and injuries, we developed a polythiolated- and mannosylated human serum albumin (SH-Man-HSA), which functions as a novel nanoantioxidant for delivering thiol to CD68(+) KC. In vitro electron paramagnetic resonance coupled with pharmacokinetics and immunohistochemical studies showed that SH-Man-HSA possessed powerful radical-scavenging activity and rapidly and selectively delivered thiols to the liver via mannose receptor (CD206) on CD68(+) cells. SH-Man-HSA significantly improved the survival rate of concanavalin-A (Con-A)-treated mice. Moreover, SH-Man-HSA exhibited excellent hepatoprotective functions, not by decreasing tumor necrosis factor or interferon-γ production that is closely associated with Con-A-induced hepatitis, but by suppressing ROS production. Interestingly, the protective effect of SH-Man-HSA was superior to N-acetyl cysteine (NAC). This could be attributed to the difference in the inhibition of hepatic oxidative stress between the two antioxidants depending on their potential for thiol delivery to the liver. Similar results were also observed for acetaminophen (APAP)-induced hepatopathy models. Flow cytometric data further confirmed that an increase in F4/80(+)/ROS(+) cells was dramatically decreased by SH-Man-HSA. The administration of SH-Man-HSA at 4 hours following a Con-A or APAP injection also exhibited a profound hepatoprotective action against these hepatitis models, whereas this was not observed for NAC. It can be concluded therefore that SH-Man-HSA has great potential for use in a rescue therapy for hepatopathy as a nanoantioxidant because of its ability to efficiently and rapidly deliver thiols to CD68(+)/CD206(+) KC. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Aerobic Fitness for the Severely and Profoundly Mentally Retarded.

ERIC Educational Resources Information Center

Bauer, Dan

1981-01-01

The booklet discusses the aerobic fitness capacities of severely/profoundly retarded students and discusses approaches for improving their fitness. An initial section describes a method for determining the student's present fitness level on the basis of computations of height, weight, blood pressure, resting pulse, and Barach Index and Crampton…

Discovering Indices of Contingency Awareness in Adults with Multiple Profound Disabilities

ERIC Educational Resources Information Center

Saunders, Richard R.; Saunders, Muriel D.; Struve, Brittany; Munce, Abbie L.; Olswang, Lesley B.; Dowden, Patricia A.; Klasner, Estelle R.

2007-01-01

Two studies were conducted to examine parameters of social attention in contingency awareness training using switch activation with individuals who had multiple profound disabilities. Study 1 compared leisure devices and social attention as reinforcing stimuli with 5 individuals. Results indicated the reinforcing qualities of social attention over…

Self-Concept of Severely to Profoundly Hearing-Impaired Children.

ERIC Educational Resources Information Center

Warren, Charlotte; Hasenstab, Suzanne

1986-01-01

A study examined demographic, impairment-related, and parental variables that best predicted self-concept among 49 severely to profoundly hearing-impaired 5- to 11-year-olds. A strong relationship was observed between self-concept and parental indulgence, parental rejection, parental protection, parental discipline, and extent of language…

Identifying Reinforcers for Persons with Profound Handicaps: Staff Opinion versus Systematic Assessment of Preferences.

ERIC Educational Resources Information Center

Green, Carolyn W.; And Others

1988-01-01

A systematic assessment procedure successfully identified stimulus preferences of seven profoundly and multiply handicapped individuals (ages 12-34). Preference rankings based on caregiver opinion did not consistently coincide with these results. Systematically assessed student preferences were a likely, though not certain, source of reinforcing…

The False-Friend Effect in Three Profoundly Deaf Learners of French: Disentangling Morphology, Phonology and Orthography

ERIC Educational Resources Information Center

Janke, Vikki; Kolokonte, Marina

2015-01-01

Three profoundly deaf individuals undertook a low-frequency backward lexical translation task (French/English), where morphological structure was manipulated and orthographic distance between test items was measured. Conditions included monomorphemic items (simplex), polymorphemic items (complex), items whose French morphological structure…

Learners with Profound and Complex Needs in Scotland's Colleges

ERIC Educational Resources Information Center

Her Majesty's Inspectorate of Education, 2009

2009-01-01

The Scottish Further and Higher Education Funding Council's (SFC) Corporate Plan (2009-12) makes clear its commitment to learners with profound and complex needs. Under "Outcome 2 Access, Inclusion and Progression" it states: "we will work with the Scottish Government, colleges and other stakeholders to ensure that appropriate…

Developing Skills in Severely and Profoundly Handicapped Children.

ERIC Educational Resources Information Center

Thomas, M. Angele, Ed.

Included in the publication are 10 articles on developing basic skills in severely and profoundly handicapped children. The first paper focuses on the development of object permanence, a basic cognitive skill, while the second and third review procedures for developing self care skills (toileting and eating). A fourth paper discusses an…

Social Peer Interactions in Persons with Profound Intellectual and Multiple Disabilities: A Literature Review

ERIC Educational Resources Information Center

Nijs, Sara; Maes, Bea

2014-01-01

Social interactions may positively influence developmental and quality of life outcomes. Research in persons with profound intellectual and multiple disabilities (PIMD) mostly investigated interactions with caregivers. This literature review focuses on peer interactions of persons with PIMD. A computerized literature search of three databases was…