Sample records for absent calcemic activity

  1. Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia

    PubMed Central

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

    2013-01-01

    Familial dysautonomia (Riley–Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement. PMID:23165765

  2. Absent Apologies

    ERIC Educational Resources Information Center

    Drew, Paul; Hepburn, Alexa

    2016-01-01

    Absent apologies--apologies that were expected but are not forthcoming--are quite frequently identified and commented on, for instance in the media. In this article we discuss two kinds of evidence that apologies can be "noticeably" absent for participants in ordinary interactions. The first kind is the delays that can occur in the…

  3. Disneyland Dads, Disneyland Moms? How Nonresident Parents Spend Time with Absent Children.

    ERIC Educational Resources Information Center

    Stewart, Susan D.

    1999-01-01

    Examines gender differences in how nonresident parents spend time with their absent children. Results suggest that nonresident mothers and fathers exhibit a similar pattern of participation in activities with their absent children. Most nonresident parents either engage in only leisure activities with their children or have no contact. (Author/MKA)

  4. "Absent Data, Absent Women": Gender and Higher Education Leadership

    ERIC Educational Resources Information Center

    Aiston, Sarah Jane; Yang, Zi

    2017-01-01

    The study of the position, status and experience of women academics has in recent decades attracted a great deal of scholarly attention. The literature is characterized by what might be referred to as the "absent women" discourse, namely the underrepresentation of women in the highest positions in the sector, and is dominated by research…

  5. Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails.

    PubMed

    Kariminejad, Ariana; Ajeawung, Norbert Fonya; Bozorgmehr, Bita; Dionne-Laporte, Alexandre; Molidperee, Sirinart; Najafi, Kimia; Gibbs, Richard A; Lee, Brendan H; Hennekam, Raoul C; Campeau, Philippe M

    2017-04-01

    Kaufman oculo-cerebro-facial syndrome (KOS) is caused by recessive UBE3B mutations and presents with microcephaly, ocular abnormalities, distinctive facial morphology, low cholesterol levels and intellectual disability. We describe a child with microcephaly, brachycephaly, hearing loss, ptosis, blepharophimosis, hypertelorism, cleft palate, multiple renal cysts, absent nails, small or absent terminal phalanges, absent speech and intellectual disability. Syndromes that were initially considered include DOORS syndrome, Coffin-Siris syndrome and Dubowitz syndrome. Clinical investigations coupled with karyotype analysis, array-comparative genomic hybridization, exome and Sanger sequencing were performed to characterize the condition in this child. Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM_183415:c.3139_3141del, p.1047_1047del) located within the terminal portion of the HECT domain. This finding coupled with the presence of characteristic features such as brachycephaly, ptosis, blepharophimosis, hypertelorism, short palpebral fissures, cleft palate and developmental delay allowed us to make a diagnosis of KOS. In conclusion, our findings highlight the importance of considering KOS as a differential diagnosis for patients under evaluation for DOORS syndrome and expand the phenotype of KOS to include small or absent terminal phalanges, nails, and the presence of hallux varus and multicystic dysplastic kidneys.

  6. Communication about absent entities in great apes and human infants.

    PubMed

    Bohn, Manuel; Call, Josep; Tomasello, Michael

    2015-12-01

    There is currently debate about the extent to which non-linguistic beings such as human infants and great apes are capable of absent reference. In a series of experiments we investigated the flexibility and specificity of great apes' (N=36) and 12 month-old infants' (N=40) requests for absent entities. Subjects had the choice between requesting visible objects directly and using the former location of a depleted option to request more of these now-absent entities. Importantly, we systematically varied the quality of the present and absent options. We found that great apes as well as human infants flexibly adjusted their requests for absent entities to these contextual variations and only requested absent entities when the visible option was of lower quality than the absent option. These results suggest that the most basic cognitive capacities for absent reference do not depend on language and are shared by humans and their closest living relatives. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Congenitally absent lumbar pedicle: a reappraisal

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

    Wortzman, G.; Steinhardt, M.I.

    1984-09-01

    Three patients who had a diagnosis of congenitally absent lumbar pedicle underwent CT examination. Findings showed that each patient had an aberrant hypoplastic pedicle plus a retroisthmic defect in their ipsilateral lamina rather than an absent pedicle. Axial CT was the diagnostic modality of choice; reformated images were of little value. The differential diagnosis to be considered from the findings of plain film radiography includes pediculate thinning, neoplastic disease, neurofibroma, mesodermal dysplasia associated with neurofibromatosis, and vascular anomalies.

  8. Congenital hypogonadotropic hypogonadism: implications of absent mini-puberty.

    PubMed

    Dwyer, Andrew A; Jayasena, Channa N; Quinton, Richard

    2016-06-01

    The phenomenon known as "mini-puberty" refers to activation of the neonatal hypothalamo-pituitary axis causing serum concentrations of gonadotrophins and testosterone (T) to approach adult male levels. This early neonatal period is a key proliferative window for testicular germ cells and immature Sertoli cells. Although failure to spontaneously initiate (adolescent) puberty is the most evident consequence of a defective gonadotropin-releasing hormone (GnRH) neurosecretory network, absent mini-puberty is also likely to have a major impact on the reproductive phenotype of men with congenital hypogonadotrophic hypogonadism (CHH). Furthermore, the phase of male mini-puberty represents a key window-of-opportunity to identify congenital GnRH deficiency (either isolated CHH, or as part of combined pituitary hormone deficiency) in childhood. Among male neonates exhibiting "red flag" indicators for CHH (i.e. maldescended testes with or without cryptorchidism) a single serum sample (between 4-8 weeks of life) can pinpoint congenital GnRH deficiency far more rapidly and with much greater accuracy than dynamic tests performed in later childhood or adolescence. Potential consequences for missing absent mini-puberty in a male neonate include the lack of monitoring of pubertal progression/lack of progression, and the missed opportunity for early therapeutic intervention. This article will review our current understanding of the mechanisms and clinical consequences of mini-puberty. Furthermore, evidence for the optimal clinical management of patients with absent mini-puberty will be discussed.

  9. A new documentation system for congenital absent digits.

    PubMed

    Jones, Neil F; Kaplan, Jesse

    2012-12-01

    Congenital absent digits continue to be described by many confusing terms and are currently classified in categories I, V, and VI of the International Federation of Societies for Surgery of the Hand classification and seven subclassification systems. Very few classification systems provide any logical basis for surgical reconstruction. The purpose of this study was to develop a simple alphanumerical documentation system to reproducibly describe the morphological or radiographic appearance of congenital absent digits and facilitate communication of these childrens' hand anomalies from one hand surgeon to another. Dorsal and palmar photographs and PA radiographs of 235 hands in 204 children born with congenital absent digits over a 15-year period were analyzed to determine which digital rays were missing and their level of absence. Each hand can be described by three letters, R (radial), C (central), and U (ulnar), as well as numbers 1-5. The first letter and number designate which rays are missing and the second and third letters and numbers designate which rays remain present. There are 15 morphological phenotypes of congenital absent digits. The three most common phenotypes are U4R1 (a thumb but absence of all four fingers), R1U4 (absent thumb), and R5 (aplastic hand). This new documentation system allows hand surgeons to describe the simple morphological or radiographic appearance of congenital absent digits; incorporates all the previous subclassification systems that have attempted to describe congenital absent digits in radial, central, and ulnar deficiencies, symbrachydactyly, and congenital constriction ring syndrome; and has subsequently allowed the development of an algorithm which predicts whether conventional or microsurgical reconstruction is indicated for each specific phenotype.

  10. Minimal Absent Words in Four Human Genome Assemblies

    PubMed Central

    Garcia, Sara P.; Pinho, Armando J.

    2011-01-01

    Minimal absent words have been computed in genomes of organisms from all domains of life. Here, we aim to contribute to the catalogue of human genomic variation by investigating the variation in number and content of minimal absent words within a species, using four human genome assemblies. We compare the reference human genome GRCh37 assembly, the HuRef assembly of the genome of Craig Venter, the NA12878 assembly from cell line GM12878, and the YH assembly of the genome of a Han Chinese individual. We find the variation in number and content of minimal absent words between assemblies more significant for large and very large minimal absent words, where the biases of sequencing and assembly methodologies become more pronounced. Moreover, we find generally greater similarity between the human genome assemblies sequenced with capillary-based technologies (GRCh37 and HuRef) than between the human genome assemblies sequenced with massively parallel technologies (NA12878 and YH). Finally, as expected, we find the overall variation in number and content of minimal absent words within a species to be generally smaller than the variation between species. PMID:22220210

  11. 46 CFR 502.243 - Participation of absent Commissioner.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AND PROCEDURE Oral Argument; Submission for Final Decision § 502.243 Participation of absent... participate in a decision shall participate in making that decision after reading the transcript of oral... 46 Shipping 9 2010-10-01 2010-10-01 false Participation of absent Commissioner. 502.243 Section...

  12. TEI-A00114: a new vitamin D3 analogue that inhibits neutrophil recruitment in an acute lung injury hamster model while showing reduced hypercalcemic activity.

    PubMed

    Takano, Yasuhiro; Mitsuhashi, Hiroaki; Ishizuka, Seiichi; Takahashi, Katsushi; Chokki, Manabu; Takenouchi, Kazuya; Gao, Qingzhi; Tanaka, Hiroko; Hazato, Atsushi; Tabe, Masayasu; Furuya, Minoru; Manabe, Kenji; Ueno, Koichi

    2012-12-01

    While searching for vitamin D(3) analogues which inhibit neutrophil recruitment in the lung without elevating plasma calcium level, we found that (5Z,7E)-(1S,3R)-20(R)-[(5E)-(2S)-2-hydroxy-2-methyl-cyclopentanone-5-ylidene]methyl-9,10-secopregna-5,7,10(19)-triene-1,3-diol (TEI-A00114) had the best efficacy and calcemic action. TEI-A00114 has a vitamin D receptor affinity 2.5-fold weaker and a vitamin D binding protein affinity 330.9-fold weaker than those of 1α,25(OH)(2)D(3). The estimated effective doses for 40% inhibition (ED(40)) via peroral and intratracheal administration are 7.6 and 0.4 μg/kg, respectively. TEI-A00114 was also tested by inhaled administration, and its ED(40) was calculated as 0.2 μg/kg. The estimated 40% inhibitory concentration (IC(40)) of TEI-A00114 on interleukin (IL)-8 production induced by lipopolysaccharide and on IL-1β in human whole blood cells in vitro were 9.8 × 10(-8) or 1.8 × 10(-9)M, respectively. These levels of TEI-A00114's activities are equal to those of 1α,25(OH)(2)D(3). On the other hand, the calcemic action of TEI-A00114, which was evaluated at day 14 after sequential peroral quaque die administration, was 89-fold weaker (molar ratio) than that of 1α,25(OH)(2)D(3). These results indicate that TEI-A00114 has a dissociated profile between inhibition of neutrophil recruitment in the lung and calcemic action, suggesting its suitability over 1α,25(OH)(2)D(3) as a candidate for the treatment of acute lung injury. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. The role of within-compound associations in learning about absent cues.

    PubMed

    Witnauer, James E; Miller, Ralph R

    2011-05-01

    When two cues are reinforced together (in compound), most associative models assume that animals learn an associative network that includes direct cue-outcome associations and a within-compound association. All models of associative learning subscribe to the importance of cue-outcome associations, but most models assume that within-compound associations are irrelevant to each cue's subsequent behavioral control. In the present article, we present an extension of Van Hamme and Wasserman's (Learning and Motivation 25:127-151, 1994) model of retrospective revaluation based on learning about absent cues that are retrieved through within-compound associations. The model was compared with a model lacking retrieval through within-compound associations. Simulations showed that within-compound associations are necessary for the model to explain higher-order retrospective revaluation and the observed greater retrospective revaluation after partial reinforcement than after continuous reinforcement alone. These simulations suggest that the associability of an absent stimulus is determined by the extent to which the stimulus is activated through the within-compound association.

  14. Mands for Information Using "How" Under EO-Absent and EO-Present Conditions.

    PubMed

    Shillingsburg, M Alice; Bowen, Crystal N; Valentino, Amber L

    2014-06-01

    The present study replicates and extends previous research on teaching "How?" mands for information to children with autism. The experimental preparation involved mand training in the context of completing preferred activities and included training and testing under conditions when the establishing operation (EO) was present and absent. Results show that two children with autism acquired mands for information using How? only in situations where information was valuable (i.e., the EO was present); they then consistently made use of the information provided in activity completion. Generalization to novel, untaught situations was assessed.

  15. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  16. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  17. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  18. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  19. 42 CFR 410.175 - Alien absent from the United States.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Alien absent from the United States. 410.175... Alien absent from the United States. (a) Medicare does not pay Part B benefits for services furnished to... during the first full calendar month the alien is back in the United States. [53 FR 6634, Mar. 2, 1988] ...

  20. Cervical Fusion for Absent Pedicle Syndrome Manifesting with Myelopathy.

    PubMed

    Goodwin, C Rory; Desai, Atman; Khattab, Mohamed H; Elder, Benjamin D; Bydon, Ali; Wolinsky, Jean-Paul

    2016-02-01

    Absent congenital pedicle syndrome is a posterior arch defect characterized by numerous congenital and mechanical abnormalities that result from disconnection of the anterior and posterior columns of the spinal canal. Absent congenital pedicle syndrome is a rare anomaly that is most commonly diagnosed incidentally, after evaluation of minor trauma, or after complaints of chronic neck pain. We report a case of absent congenital pedicle syndrome in a patient who presented with myelopathy and lower extremity weakness and review the literature on the surgical management of this entity. A 32-year-old woman with a history of systemic lupus erythematosus presented to the Neurosurgery Service with progressive weakness in her upper and lower extremities, clonus, and hyperreflexia. Magnetic resonance imaging revealed congenital absence of the pedicles of C2, C3, C4, C5, and C6 with a congenitally narrow canal at C4-5. The patient underwent a staged anterior and posterior cervical decompression and fusion. She was placed in a halo after surgery; at the 1-year follow-up, she was ambulatory with demonstrated improvement in weakness and fusion of her cervical spine. Absent congenital pedicle syndrome is rare, and most reported cases were treated conservatively. Surgical management is reserved for patients with myelopathy or instability. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The role of within-compound associations in learning about absent cues

    PubMed Central

    Witnauer, James E.

    2011-01-01

    When two cues are reinforced together (in compound), most associative models assume that animals learn an associative network that includes direct cue–outcome associations and a within-compound association. All models of associative learning subscribe to the importance of cue–outcome associations, but most models assume that within-compound associations are irrelevant to each cue's subsequent behavioral control. In the present article, we present an extension of Van Hamme and Wasserman's (Learning and Motivation 25:127–151, 1994) model of retrospective revaluation based on learning about absent cues that are retrieved through within-compound associations. The model was compared with a model lacking retrieval through within-compound associations. Simulations showed that within-compound associations are necessary for the model to explain higher-order retrospective revaluation and the observed greater retrospective revaluation after partial reinforcement than after continuous reinforcement alone. These simulations suggest that the associability of an absent stimulus is determined by the extent to which the stimulus is activated through the within-compound association. PMID:21264569

  2. The target of daptomycin is absent from Escherichia coli and other gram-negative pathogens.

    PubMed

    Randall, Christopher P; Mariner, Katherine R; Chopra, Ian; O'Neill, Alex J

    2013-01-01

    Antistaphylococcal agents commonly lack activity against Gram-negative bacteria like Escherichia coli owing to the permeability barrier presented by the outer membrane and/or the action of efflux transporters. When these intrinsic resistance mechanisms are artificially compromised, such agents almost invariably demonstrate antibacterial activity against Gram negatives. Here we show that this is not the case for the antibiotic daptomycin, whose target appears to be absent from E. coli and other Gram-negative pathogens.

  3. Absent right common carotid artery associated with aberrant right subclavian artery.

    PubMed

    Uchino, Akira; Uwabe, Kazuhiko; Osawa, Iichiro

    2018-06-01

    Rarely, the external and internal carotid arteries arise separately from the brachiocephalic trunk and right subclavian artery (SA) or the aortic arch and reflect the absence of a common carotid artery (CCA). We report a 45-year-old man with absent right CCA associated with aberrant right SA, an extremely rare combination, diagnosed by computed tomography (CT) angiography during follow-up for postoperative aortic dissection. Retrospective careful observation of preoperative postcontrast CT revealed the absent right CCA. Previously reported arch variations associated with absent CCA include cervical aortic arch, double aortic arch, and right aortic arch.

  4. Causal Attributions as Predictors of Academic Achievement in Father-Absent Children.

    ERIC Educational Resources Information Center

    Salzman, Stephanie A.

    The purpose of this study was to examine the potential impact of maternal attributions and self-attributions on the academic achievement of father-absent children in comparison to commonly identified family interaction and demographic variables. Subjects included 33 male and 34 female father-absent sixth graders (mean age of 11.6 years) and their…

  5. Role of "Sural Sparing" Pattern (Absent/Abnormal Median and Ulnar with Present Sural SNAP) Compared to Absent/Abnormal Median or Ulnar with Normal Sural SNAP in Acute Inflammatory Demyelinating Polyneuropathy.

    PubMed

    Surpur, Spurthi Sunil; Govindarajan, Raghav

    2017-01-01

    Sural sparing defined as absent/abnormal median sensory nerve action potential (SNAP) amplitude or absent/abnormal ulnar SNAP amplitude with a normal sural SNAP amplitude is thought to be a marker for inflammatory demyelinating polyneuropathies. If sural sparing pattern specifically defined as absent/abnormal median and ulnar SNAP amplitude with normal sural SNAP amplitude (AMUNS) is sensitive and specific when compared with either absent/abnormal median and normal sural (AMNS) or absent/abnormal ulnar and normal sural (AUNS) for acute inflammatory demyelinating polyneuropathy (AIDP), chronic inflammatory demyelinating polyneuropathy (CIDP), select non-diabetic axonopathies (AXPs), and diabetic neuropathies (DNs). Retrospective analysis from 2001 to 2010 on all newly diagnosed AIDP, CIDP, select non-diabetic AXP, and DN. There were 20 AIDP and 23 CIDP. Twenty AXP and 50 DN patients between 2009 and 2010 were included as controls. AMUNS was seen in 65% of AIDP, 39% CIDP compared with 10% of AXP and 6% for DN with sensitivity of 51%, specificity of 92%, whereas the specificity of AMNS/AUNS was 73% and its sensitivity was 58%. If a patient has AMUNS they are >12 times more likely to have AIDP ( p  < 0.001). Sural sparing is highly specific but not sensitive when compared with either AMNS or AUNS in AIDP but does not add to sensitivity or specificity in CIDP.

  6. Absent and Accounted For: Absenteeism and Cooperative Learning

    ERIC Educational Resources Information Center

    Koppenhaver, G. D.

    2006-01-01

    In a small section collaborative learning environment where student work teams promote mutual learning about investments, students limit the opportunity to learn from other students if they are absent from class. Absenteeism not only denies the student the opportunity to learn from others but also denies other members of the student's work team…

  7. Absent circle of Willis with vascular pollarding in an adult with colpocephaly: A developmental perspective

    PubMed Central

    Verghese, Renjan; Paul, Divyan

    2015-01-01

    Absent circle of Willis (COW) has been described in cases of severe forms of cerebral developmental anomalies such as alobar prosencephaly. However, there are no reports of absent COW in patients with a milder form of cerebral abnormality such as colpocephaly. We report a unique case of an adult with colpocephaly and absent COW and discuss their association from a developmental perspective. PMID:26443299

  8. 15 CFR 0.735-47 - Decision absent a hearing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Decision absent a hearing. 0.735-47 Section 0.735-47 Commerce and Foreign Trade Office of the Secretary of Commerce EMPLOYEE RESPONSIBILITIES AND CONDUCT Disciplinary Actions Concerning Post-Employment Conflict of Interest Violations § 0.735-47...

  9. The Production of Present and Absent Presences in Education

    ERIC Educational Resources Information Center

    Frelin, Anneli; Grannäs, Jan

    2013-01-01

    Drawing on the distinction between absent and present presences, this article contributes to our understanding of how new managerial and performative discourses are played out in a secondary school context in Sweden. The consequences of numerous educational reforms during the last 20 years include a surge of new independent schools and increased…

  10. Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

    PubMed

    Laique, Sobia; Singh, Tavankit; Dornblaser, David; Gadre, Abhishek; Rangan, Vikram; Fass, Ronnie; Kirby, Donald; Chatterjee, Soumya; Gabbard, Scott

    2018-01-19

    This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

  11. Vampire Selfie: A Curious Case of an Absent Reflection

    ERIC Educational Resources Information Center

    Grossman, Joshua M.

    2014-01-01

    This article presents a puzzle for the optics section of an introductory course on reflections. A teacher could ask students to explain the phenomenon of the "vampire selfie" or the absent reflection. How could that be? What physics caused this curious phenomenon? The article explains light refraction and its effect on what we see and…

  12. The social-cognitive basis of infants' reference to absent entities.

    PubMed

    Bohn, Manuel; Zimmermann, Luise; Call, Josep; Tomasello, Michael

    2018-04-06

    Recent evidence suggests that infants as young as 12 month of age use pointing to communicate about absent entities. The tacit assumption underlying these studies is that infants do so based on tracking what their interlocutor experienced in a previous shared interaction. The present study addresses this assumption empirically. In three experiments, 12-month-old infants could request additional desired objects by pointing to the location in which these objects were previously located. We systematically varied whether the adult from whom infants were requesting had previously experienced the former content of the location with the infant. Infants systematically adjusted their pointing to the now empty location to what they experienced with the adult previously. These results suggest that infants' ability to communicate about absent referents is based on an incipient form of common ground. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. A review of supernumerary and absent limbs and digits of the upper limb.

    PubMed

    Klaassen, Zachary; Choi, Monica; Musselman, Ruth; Eapen, Deborah; Tubbs, R Shane; Loukas, Marios

    2012-03-01

    For years people have been enamored by anomalies of the human limbs, particularly supernumerary and absent limbs and digits. Historically, there are a number of examples of such anomalies, including royal families of ancient Chaldea, tribes from Arabia, and examples from across nineteenth century Europe. The development of the upper limbs in a growing embryo is still being elucidated with the recent advent of homeobox genes, but researchers agree that upper limbs develop between stages 12-23 through a complex embryological process. Maternal thalidomide intake during limb development is known to cause limb reduction and subsequent amelia or phocomelia. Additionally, a number of clinical reports have illustrated different limb anomaly cases, with each situation unique in phenotype and developmental abnormality. Supernumerary and absent limbs and digits are not unique to humans, and a number of animal cases have also been reported. This review of the literature illustrates the historical, anatomical, and clinical aspects of supernumerary and absent limbs and digits for the upper limb.

  14. Differences in sexual attitudes and likeliness of sexual behaviors of black lower-socioeconomic father-present vs. father-absent female adolescents.

    PubMed

    Eberhardt, C A; Schill, T

    1984-01-01

    This study compared sexual permissiveness attitudes and likely behaviors of father-absent vs. father-present black, lower-socioeconomic female adolescents. Father-absent subjects were not found to be more sexually permissive in reported likely behavior or attitude than father-present subjects. However, the father-absent group was found to have significantly greater inconsistency between behavioral and attitudinal scores in which the reported behavior was more permissive than the reported attitude. Finally, within the father-absent group, those subjects whose fathers became absent before they were five years old, were found to have a significantly higher need for social approval than subjects whose fathers became absent after they were five years old. The implications of these results are discussed.

  15. Successful Black Men from Absent-Father Homes and Their Resilient Single Mothers: A Phenomenological Study

    ERIC Educational Resources Information Center

    Wilson, Angie D.; Henriksen, Richard C.; Bustamante, Rebecca; Irby, Beverly

    2016-01-01

    The phenomenon of absent fathers is a common occurrence in today's homes that appears to be escalating, especially in Black households across the United States. The purpose of this study was to describe the lived experiences of successful Black men who were raised in absent-father homes as well as the lived experiences of their resilient single…

  16. Fourteen-Month-Olds' Decontextualized Understanding of Words for Absent Objects

    ERIC Educational Resources Information Center

    Hendrickson, Kristi; Sundara, Megha

    2017-01-01

    The majority of research examining infants' decontextualized word knowledge comes from studies in which words and pictures are presented simultaneously. However, comprehending utterances about unseen objects is a hallmark of language. Do infants demonstrate decontextualized absent object knowledge early in the second year of life? Further, to what…

  17. Conceptually new deltanoids (vitamin D analogs) inhibit multistage skin tumorigenesis.

    PubMed

    Kensler, T W; Dolan, P M; Gange, S J; Lee, J K; Wang, Q; Posner, G H

    2000-07-01

    Development of vitamin D analogs (deltanoids) as chemopreventive agents requires separation of desirable antiproliferative and pro-differentiating activities from the undesirable calcemic activity also found in the hormone calcitriol (1 alpha, 25-dihydroxyvitamin D(3)). Therefore, several conceptually new deltanoids were synthesized with modifications to the 1alpha- and/or 25-hydroxyl groups, positions traditionally considered essential for stimulating biological responses. In this study, 1 beta-hydroxymethyl-3-epi-25-hydroxyvitamin D(3), a non-calcemic CH(2) homolog of the natural hormone with antiproliferative activity in vitro, was ineffective as an inhibitor of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced induction of ornithine decarboxylase activity in mouse epidermis. However, a hybrid analog incorporating not only the calcemia-ablating 1 beta-hydroxymethyl alteration, but potentiating C,D ring 16-unsaturation and side chain 24,24-fluorination and 26, 27-homologation was found to be as effective as calcitriol. Several non-calcemic 24- or 25-t-butyl sulfones, some containing side chain fluorination but all lacking the 25-hydroxyl group, were also shown to be active in this assay. Three sulfones and the 1 beta-hydroxymethyl hybrid were evaluated as inhibitors of multistage carcinogenesis in mouse skin. Female CD-1 mice were initiated with a single dose of 7,12-dimethylbenz[a]anthracene and then promoted twice weekly for 20 weeks with TPA. Deltanoids were applied topically 30 min before TPA. Unlike calcitriol, none of the atypical deltanoids affected body weight gain in these animals. Minimal effects on urinary calcium excretion were observed following chronic treatment with these analogs. All deltanoids inhibited the incidence and multiplicity of papilloma formation, with the hybrid analog showing the greatest efficacy. With this deltanoid, tumor incidence was significantly reduced by 28% and tumor multiplicity by 63%. These results, coupled with the rich

  18. The differential influence of absent and harsh fathers on juvenile delinquency.

    PubMed

    Simmons, Cortney; Steinberg, Laurence; Frick, Paul J; Cauffman, Elizabeth

    2018-01-01

    Researchers have identified father absence as a contributor to juvenile delinquency. Consequently, politicians and community leaders are making efforts to re-engage fathers. However, it is possible that the presence of fathers is not, in itself, a substantial protective factor and, in some cases, can even be more detrimental than father absence. Employing a diverse sample of male juvenile offenders in the U.S. (ages 13-17), the present study examined the differential effects of absent fathers and harsh fathers on delinquency. Results indicated that youth in the harsh-father group engaged in more offending behaviors and used more substances than youth in the absent-father group. This difference remained even after controlling for the mother-child relationship. Implications of these findings for future research and delinquency prevention programs are discussed. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  19. Allograft replacement for absent native tissue.

    PubMed

    Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J; Warren, Russell F; Doyle, Maureen; Rodeo, Scott A

    2013-03-01

    Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs.

  20. Allograft Replacement for Absent Native Tissue

    PubMed Central

    Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J.; Warren, Russell F.; Doyle, Maureen; Rodeo, Scott A.

    2013-01-01

    Context: Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. Objective: This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs. PMID:24427387

  1. Case report: absent C6 cervical pedicle in a collegiate football player.

    PubMed

    Fowler, John R; Moyer, Ray A

    2010-06-01

    Congenital absence of a cervical pedicle is a rare clinical finding with only 70 reported cases in the literature from 1946 until present. The congenitally absent pedicle has clinical importance owing to the frequency of misdiagnosis and inappropriate invasive treatments. We present the case of a 21-year-old college football player who experienced neck and shoulder pain after violent twisting of his neck by the face mask. The player walked off the field under his own power. He was sent to the locker room, where he underwent right shoulder and cervical spine radiographs. Initial review of the radiographs raised concern for a jumped right C6 facet. The patient then underwent CT and MRI of the cervical spine, confirming the diagnosis of an absent cervical pedicle. He was treated nonoperatively for a short time and completed the season. He had no symptoms at last followup at 8 months. The most frequent location of the absent cervical pedicle is at the C6 level, and the next most common is at the C5 level. Neural compression or instability is uncommon and nonsurgical treatment is the mainstay of treatment. Misdiagnosis can lead to inappropriate treatment such as halo or tong application with traction, which occurred in seven of 57 cases in one series, and exploratory surgery, which occurred in four of 57 cases.

  2. Absent without leave; a neuroenergetic theory of mind wandering

    PubMed Central

    Killeen, Peter R.

    2013-01-01

    Absent minded people are not under the control of task-relevant stimuli. According to the Neuroenergetics Theory of attention (NeT), this lack of control is often due to fatigue of the relevant processing units in the brain caused by insufficient resupply of the neuron's preferred fuel, lactate, from nearby astrocytes. A simple drift model of information processing accounts for response-time statistics in a paradigm often used to study inattention, the Sustained Attention to Response Task (SART). It is suggested that errors and slowing in this fast-paced, response-engaging task may have little to due with inattention. Slower-paced and less response-demanding tasks give greater license for inattention—aka absent-mindedness, mind-wandering. The basic NeT is therefore extended with an ancillary model of attentional drift and recapture. This Markov model, called NEMA, assumes probability λ of lapses of attention from 1 s to the next, and probability α of drifting back to the attentional state. These parameters measure the strength of attraction back to the task (α), or away to competing mental states or action patterns (λ); their proportion determines the probability of the individual being inattentive at any point in time over the long run. Their values are affected by the fatigue of the brain units they traffic between. The deployment of the model is demonstrated with a data set involving paced responding. PMID:23847559

  3. Absent Audiovisual Integration Elicited by Peripheral Stimuli in Parkinson's Disease.

    PubMed

    Ren, Yanna; Suzuki, Keisuke; Yang, Weiping; Ren, Yanling; Wu, Fengxia; Yang, Jiajia; Takahashi, Satoshi; Ejima, Yoshimichi; Wu, Jinglong; Hirata, Koichi

    2018-01-01

    The basal ganglia, which have been shown to be a significant multisensory hub, are disordered in Parkinson's disease (PD). This study was to investigate the audiovisual integration of peripheral stimuli in PD patients with/without sleep disturbances. Thirty-six age-matched normal controls (NC) and 30 PD patients were recruited for an auditory/visual discrimination experiment. The mean response times for each participant were analyzed using repeated measures ANOVA and race model. The results showed that the response to all stimuli was significantly delayed for PD compared to NC (all p < 0.01). The response to audiovisual stimuli was significantly faster than that to unimodal stimuli in both NC and PD ( p < 0.001). Additionally, audiovisual integration was absent in PD; however, it did occur in NC. Further analysis showed that there was no significant audiovisual integration in PD with/without cognitive impairment or in PD with/without sleep disturbances. Furthermore, audiovisual facilitation was not associated with Hoehn and Yahr stage, disease duration, or the presence of sleep disturbances (all p > 0.05). The current results showed that audiovisual multisensory integration for peripheral stimuli is absent in PD regardless of sleep disturbances and further suggested the abnormal audiovisual integration might be a potential early manifestation of PD.

  4. Absent Audiovisual Integration Elicited by Peripheral Stimuli in Parkinson's Disease

    PubMed Central

    Yang, Weiping; Ren, Yanling; Yang, Jiajia; Takahashi, Satoshi; Ejima, Yoshimichi

    2018-01-01

    The basal ganglia, which have been shown to be a significant multisensory hub, are disordered in Parkinson's disease (PD). This study was to investigate the audiovisual integration of peripheral stimuli in PD patients with/without sleep disturbances. Thirty-six age-matched normal controls (NC) and 30 PD patients were recruited for an auditory/visual discrimination experiment. The mean response times for each participant were analyzed using repeated measures ANOVA and race model. The results showed that the response to all stimuli was significantly delayed for PD compared to NC (all p < 0.01). The response to audiovisual stimuli was significantly faster than that to unimodal stimuli in both NC and PD (p < 0.001). Additionally, audiovisual integration was absent in PD; however, it did occur in NC. Further analysis showed that there was no significant audiovisual integration in PD with/without cognitive impairment or in PD with/without sleep disturbances. Furthermore, audiovisual facilitation was not associated with Hoehn and Yahr stage, disease duration, or the presence of sleep disturbances (all p > 0.05). The current results showed that audiovisual multisensory integration for peripheral stimuli is absent in PD regardless of sleep disturbances and further suggested the abnormal audiovisual integration might be a potential early manifestation of PD. PMID:29850014

  5. Mayer Rokitansky Kuster Hauser (MRKH) syndrome with absent thumbs and big toes.

    PubMed

    Yunus, Mahira

    2014-01-01

    Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare developmental failure of Müllerian ducts. Principle clinical features of MRKH syndrome are primary amenorrhoea associated with congenital absence of vagina, uterine anomalies, normal ovaries, 46 XX karyotype with normal female secondary sexual characteristics and frequent association with renal, skeletal, and other congenital anomalies. A case of a 3-year-old child with congenitally absent thumbs and big toes is reported herein; she was brought in with complaints of urinary incontinence. Radiological investigation (ultrasound and magnetic resonance imaging (MRI) scan) revealed absent uterus and vagina while both ovaries were normal. Intravenous urography (IVU) study showed bifid pelvicalyceal systems bilaterally. Karyotyping revealed a 46 XX female phenotype. Laparoscopy confirmed normal ovaries bilaterally and small unfused uterine buds lying beside both ovaries on each side of pelvis. Early diagnosis of MRKH syndrome is essential for timely planning of vaginal and (if possible) uterine reconstructive surgeries.

  6. The absent bow tie sign in bucket-handle tears of the menisci in the knee.

    PubMed

    Helms, C A; Laorr, A; Cannon, W D

    1998-01-01

    Bucket-handle tears of the menisci are one of the most frequently missed diagnoses in MR examinations of the knee. This article describes the "absent bow tie sign," which can be used to identify bucket-handle tears on routine MR examinations of the knee. The arthroscopic surgical reports (n = 350) from a single orthopedic surgeon's practice during a 24-month period were examined for patients who had a diagnosis of bucket-handle tear and who underwent MR imaging before surgery (n = 32). The MR examinations were retrospectively evaluated for the presence of a bow tie sign. The bow tie sign was considered normal when two sagittal images showed the body segment (a bow tie appearance). The bow tie sign was considered abnormal, consistent with a bucket-handle tear, when only one or no body segment was seen (the absent bow tie sign). Coronal images were evaluated for a truncated meniscus. Also, each MR examination was scrutinized for a displaced fragment and a double posterior cruciate ligament (PCL) sign. Thirty-three bucket-handle tears were found at arthroscopy in 32 patients. One patient had tears of the medial and lateral menisci. The absent bow tie sign was seen in 32 of the 33 cases (sensitivity, 97%) and correlated with the medial or lateral meniscus that was reported torn at arthroscopy. The single false-negative result occurred in a patient with a nondisplaced bucket-handle tear. The findings in 31 contralateral normal menisci were all negative for an absent bow tie sign (specificity, 100%). A displaced fragment was found in 30 (94%) of 32 cases. The coronal images showed a truncated meniscus in 21 (64%) of 33 cases. A double PCL sign was seen in 10 (30%) of 33 cases. The absent bow tie sign is an easily applied finding that can be used with good sensitivity to diagnose bucket-handle tears of the menisci on MR imaging. This sign has a higher accuracy rate than other findings common with bucket-handle tears, such as displaced fragments, a truncated appearance of

  7. Exploring What’s Missing: What Do Target Absent Trials Reveal About Autism Search Superiority?

    PubMed Central

    Keehn, Brandon; Joseph, Robert M.

    2016-01-01

    We used eye-tracking to investigate the roles of enhanced discrimination and peripheral selection in superior visual search in autism spectrum disorder (ASD). Children with ASD were faster at visual search than their typically developing peers. However, group differences in performance and eye-movements did not vary with the level of difficulty of discrimination or selection. Rather, consistent with prior ASD research, group differences were mainly the effect of faster performance on target-absent trials. Eye-tracking revealed a lack of left-visual-field search asymmetry in ASD, which may confer an additional advantage when the target is absent. Lastly, ASD symptomatology was positively associated with search superiority, the mechanisms of which may shed light on the atypical brain organization that underlies social-communicative impairment in ASD. PMID:26762114

  8. Differences in Sexual Attitudes and Likeliness of Sexual Behaviors of Black Lower-Socioeconomic Father-Present vs. Father-Absent Female Adolescents.

    ERIC Educational Resources Information Center

    Eberhardt, Carolyn A.; Schill, Thomas

    1984-01-01

    Compared sexual permissiveness attitudes and likely behaviors of father-absent vs. father-present Black, lower-socioeconomic female adolescents (N=100). Father-absent subjects were not found to be more sexually permissive, but had significantly greater inconsistency between behavioral and attitudinal scores in which the reported behavior was more…

  9. Comparison of Smoking, Drinking, and Marijuana Use between Students Present or Absent on the Day of a School-Based Survey

    ERIC Educational Resources Information Center

    Bovet, Pascal; Viswanathan, Bharathi; Faeh, David; Warren, Wick

    2006-01-01

    The aim of this population-based survey was to compare the prevalence of selected risk behaviors between students present or absent on the day of a school-based survey. The study population was a representative sample of all students of secondary schools in the Seychelles (Indian Ocean). Students absent on the day of the survey were traced and…

  10. Design, Synthesis and Biological Activities of Novel Gemini 20S-Hydroxyvitamin D3 Analogs

    PubMed Central

    LIN, ZONGTAO; MAREPALLY, SRINIVASA R.; KIM, TAE-KANG; JANJETOVIC, ZORICA; OAK, ALLEN SW.; POSTLETHWAITE, ARNOLD E.; MYERS, LINDA K.; TUCKEY, ROBERT C.; SLOMINSKI, ANDRZEJ T.; MILLER, DUANE D.; LI, WEI

    2017-01-01

    Vitamin D3 (D3) can be metabolized by cytochrome P450scc (CYP11A1) into 20S-hydroxyvitamin D3 (20D3) as a major metabolite. This bioactive metabolite has shown strong antiproliferative, antifibrotic, pro-differentiation and anti-inflammatory effects while being non-toxic (non-calcemic) at high concentrations. Since D3 analogs with two symmetric side chains (Gemini analogs) result in potent activation of the vitamin D receptor (VDR), we hypothesized that the chain length and composition of these types of analogs also containing a 20-hydroxyl group would affect their biological activities. In this study, we designed and synthesized a series of Gemini 20D3 analogs. Biological tests showed that some of these analogs are partial VDR activators and can significantly stimulate the expression of mRNA for VDR and VDR-regulated genes including CYP24A1 and transient receptor potential cation channel V6 (TRPV6). These analogs inhibited the proliferation of melanoma cells with potency comparable to that of 1α,25-dihydroxyvitamin D3. Moreover, these analogs reduced the level of interferon γ and up-regulated the expression of leukocyte associated immunoglobulin-like receptor 1 in splenocytes, indicating that they have potent anti-inflammatory activities. There are no clear correlations between the Gemini chain length and their VDR activation or biological activities, consistent with the high flexibility of the ligand-binding pocket of the VDR. PMID:26976974

  11. Histone H3 is absent from organelle nucleoids in BY-2 cultured tobacco cells.

    PubMed

    Takusagawa, Mari; Tamotsu, Satoshi; Sakai, Atsushi

    2013-07-01

    The core histone proteins (H2A, H2B, H3 and H4) are nuclear-localised proteins that play a central role in the formation of nucleosome structure. They have long been considered to be absent from extra-nuclear, DNA-containing organelles; that is plastids and mitochondria. Recently, however, the targeting of core histone H3 to mitochondria, and the presence of nucleosome-like structures in mitochondrial nucleoids, were proposed in cauliflower and tobacco respectively. Thus, we examined whether histone H3 was present in plant organelles and participated in the organisation of nucleoid structure, using highly purified organelles and organelle nucleoids isolated from BY-2 cultured tobacco cells. Immunofluorescence microscopic observations and Western blotting analyses demonstrated that histone H3 was absent from organelles and organelle nucleoids, consistent with the historical hypothesis. Thus, the organisation of organelle nucleoids, including putative nucleosome-like repetitive structures, should be constructed and maintained without participation of histone H3. © 2013 International Federation for Cell Biology.

  12. Paricalcitol, a Vitamin D Receptor Activator, Inhibits Tumor Formation in a Murine Model of Uterine Fibroids

    PubMed Central

    Halder, Sunil K.; Sharan, Chakradhari; Al-Hendy, Omar

    2014-01-01

    We examined the antitumor and therapeutic potentials of paricalcitol, an analog of 1,25-dihydroxyvitamin D3 with lower calcemic activity, against uterine fibroids using in vitro and in vivo evaluations in appropriate uterine fibroid cells and animal models. We found that paricalcitol has potential to reduce the proliferation of the immortalized human uterine fibroid cells. For the in vivo study, we generated subcutaneous tumors by injecting the Eker rat-derived uterine leiomyoma cell line (ELT-3) rat uterine fibroid-derived cell line in athymic nude mice supplemented with estrogen pellets. These mice were administered with vehicle versus paricalcitol (300 ng/kg/d) or 1,25-dihydroxyvitamin D3 (500 ng/kg/d) for 4 consecutive weeks, and the data were analyzed. We found that while both paricalcitol and 1,25-dihydroxyvitamin D3 significantly reduced fibroid tumor size, the shrinkage was slightly higher in the paricalcitol-treated group. Together, our results suggest that paricalcitol may be a potential candidate for effective, safe, and noninvasive medical treatment option for uterine fibroids. PMID:24925855

  13. Tetralogy of Fallot with absent pulmonary valve syndrome; appropriate surgical strategies.

    PubMed

    Shahid, Fatima; Siddiqui, Maria Tariq; Amanullah, Muhammad Muneer

    2015-05-01

    To evaluate patients presenting with Tetralogy of Fallot with absent pulmonary valve syndrome to a tertiary care hospital and their surgical management. The retrospective study was conducted at Congenital Cardiac Services, Aga Khan University Hospital, Karachi, Pakistan, and comprised data of Tetralogy of Fallot patients between April 2007 and June 2012. Data was analysed together with follow-up echocardiography. Variables assessed included demographics, imaging, operative technique, complications, post-operative recovery and follow-up echocardiography. SPSS 17 was used for statistical analysis. Of the 204 patients, 6 (3%) had undergone surgical correction for Tetralogy of Fallot with absent pulmonary valve syndrome. All 6(100%) patients underwent complete repair. Median age for surgery was 8.5 years (range: 0.5-29 years). Of the different surgical strategies used, Contegra and Bioprosthetic valve placement had satisfactory outcome with minimal gradient at Right Ventricular Outflow Tract, good ventricular function and mild valvular regurgitation. One (16.6%) patient with Trans Annular Patch developed post-operative Right Ventricle Outflow Tract gradient of 80mmHg with moderate pulmonary regurgitation. One (16.6%) patient with monocusp valve developed free pulmonary regurgitation at 6 months. The other 4(66.6%) patients are currently free from any complications or re-intervention. Early surgery is preferred in symptomatic patients. The repair depends upon achieving integrity of pulmonary circulation which is best achieved by using right ventricle to pulmonary artery conduit or inserting a pulmonary valve.

  14. Creating insight when the literature is absent: the circle of advisors.

    PubMed

    Batcheller, Joyce; Yoder-Wise, Patricia S

    2011-01-01

    When changes happen as rapidly as they do today, the literature is often absent. Although related literature may be available to substantiate a direction to take when faced with some issue to resolve, that literature may be vague in terms of its applicability within health care. The idea of a circle of advisors was instituted to gain insight from experts who had faced similar challenges and often had extensive networks of shared experiences. The use of a sequential dialog identified specific talents to be developed in a chief nurse executive enculturation program.

  15. Equality, Difference and the Absent Presence of "Race" in Citizenship Education in the UK

    ERIC Educational Resources Information Center

    Garratt, Dean

    2011-01-01

    This paper examines the political and historical antecedents of the absent presence of "race" in successive policies for citizenship education in contemporary Britain. It questions the possibility of embracing an emerging cosmopolitanism and politics of difference, within the limiting frame of the nation state and its overarching appeal…

  16. Adulthood depression, anxiety, and trauma symptoms: a comparison of women with nonabusive, abusive, and absent father figures in childhood.

    PubMed

    Downs, William R; Rindels, Barb

    2004-12-01

    We collected data from 447 women (aged 18 or higher) from seven domestic violence programs and five substance use disorder treatment programs in a midwestern state. Women who reported a nonabusive natural/adoptive father or stepfather (N=185), abusive natural/adoptive father or stepfather (N=200), or absent father figure (N=40) were compared on a series of mental health measures with multivariate analysis of variance and pairwise post hoc comparisons using the Bonferroni test. Women with absent father figures were found to have significantly lower mean scores on the Beck Anxiety Inventory, Beck Depression Inventory, and Trauma Symptom Checklist-40 (TSC-40) than women with abusive fathers. There were no significant differences between women with absent father figures and women with nonabusive father figures on the Beck Anxiety Inventory, Beck Depression Inventory, and TSC-40. Implications for research, practice, and policy are discussed.

  17. Does Research on Children Reared in Father-absent Families Yield Information on Father Influences?

    ERIC Educational Resources Information Center

    Pedersen, Frank A.

    1976-01-01

    The most frequently employed research design for studying paternal influences on child development has been to compare children reared in father-absent families to those reared in father-present families. Research should be directed to the study and conceptualization of the more specific components of experience in the father-child and…

  18. Interventions for replacing missing teeth: partially absent dentition.

    PubMed

    Abt, Elliot; Carr, Alan B; Worthington, Helen V

    2012-02-15

    Management of individuals presenting with partial loss of teeth is a common task for dentists. Outcomes important to the management of missing teeth in the partially absent dentition should be systematically summarized. This review recognizes both the challenges associated with such a summarization and the critical nature of the information for patients. To assess the effects of different prostheses for the treatment of partially absent dentition in terms of the following outcomes: long-term success, function, morbidity and patient satisfaction. We searched the Cochrane Oral Health Group's Trials Register (to 21 March 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to March 2011) and EMBASE via OVID (1980 to March 2011). There were no restrictions regarding language or date of publication. We contacted several authors to identify non-published trials. Randomized controlled trials (RCTs) comparing different methods (including the design and materials used) of treating partial edentulism, with clinically relevant outcomes, were included in this review. Trials reporting only surrogate outcomes, such as plaque accumulation or gingival volume, were excluded from this review. Two review authors independently carried out the screening of eligible studies, assessment of dimensions of quality of trials, and data extraction. Results were expressed as mean differences for continuous data, risk ratios for dichotomous outcomes, and hazard ratios with 95% confidence intervals for time-to-event data. Twenty-one trials met the inclusion criteria for this review. Twenty-four per cent of these were assessed as being at high risk of bias and the remainder were at unclear risk of bias. The clinical heterogeneity among the included studies precluded any attempt at meta-analysis. There was insufficient evidence to determine whether one type of removable dental prosthesis (RDP) was better or worse than

  19. Effect of daily sildenafil on patients with absent nocturnal erections due to pelvic fracture urethral disruption: a single-centre experience.

    PubMed

    Peng, J; Zhang, Z; Gao, B; Yuan, Y; Cui, W; Tang, Y; Song, W; Xin, Z

    2016-12-01

    Erectile dysfunction (ED) is a common sequel of pelvic fracture urethral disruption. Those patients with nocturnal erections may respond favourably to sildenafil; however, little is known about the response to sildenafil in patients with absent nocturnal erections. The aim was to evaluate the response to the treatment of sildenafil 50 mg taken once daily in the patients with absent nocturnal erections. From January 2008 to December 2011, a total of 28 patients with absent nocturnal erections were evaluated. We recorded nocturnal penile tumescence and rigidity with an erectometer. If nocturnal erections were absent for three nights, patients were administrated sildenafil 100 mg at bedtime and tested again at the fourth night. Penile duplex ultrasound with intracavernous injection was performed to define the cause of ED. All patients received a daily dose of sildenafil 50 mg for 12 weeks. Response to sildenafil treatment was defined as sustained erections allowing vaginal penetration and intercourse. Twenty-three (78%) patients completed the daily sildenafil treatment, and follow-up was available. The nocturnal erections at the fourth night in 13 patients (46.4%) were improved. About 61.5% (8/13) reported effective response to daily sildenafil. The improvement of nocturnal erections induced by sildenafil taken at bedtime might predict the response to sildenafil taken daily. © 2016 Blackwell Verlag GmbH.

  20. When Familiar Is Not Better: 12-Month-Old Infants Respond to Talk about Absent Objects

    ERIC Educational Resources Information Center

    Osina, Maria A.; Saylor, Megan M.; Ganea, Patricia A.

    2013-01-01

    Three experiments that demonstrate a novel constraint on infants' language skills are described. Across the experiments it is shown that as babies near their 1st birthday, their ability to respond to talk about an absent object is influenced by a referent's spatiotemporal history: familiarizing infants with an object in 1 or several nontest…

  1. Therapeutic uses of vitamin D analogues.

    PubMed

    Brown, A J

    2001-11-01

    The vitamin D endocrine system has been implicated in numerous biological activities throughout the body. The breadth and magnitude of vitamin D activity suggest potential therapeutic applications for the treatment of several diseases and disorders, including hyperproliferative diseases, immune dysfunction, endocrine disorders, and metabolic bone diseases. However, therapy using natural vitamin D hormone, 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) has been precluded in most cases because of the potent calcemic activity shown by this hormone. Newly developed vitamin D analogues with lower calcemic activity have been shown to retain many therapeutic properties of 1,25(OH)(2)D(3). Molecular studies discussed in this article provide insights into the unique target cell specificity afforded by these analogues. In particular, the importance of the nuclear vitamin D receptor (VDR), serum vitamin D-binding protein, 24-hydroxylase, and membrane receptor is noted because analogue selectivity, specificity, and potency are afforded through their molecular interactions. The nuclear VDR has been isolated from a variety of target cells and tissues, suggesting that vitamin D compounds may have therapeutic potential throughout several body systems. Five vitamin D analogues have been approved for use in patients: calcipotriol (Dovonex; Leo Pharmaceuticals, Copenhagen, Denmark) for the treatment of psoriasis, 19-nor-1,25(OH)(2)D(2) (Zemplar; Abbott Laboratories, Abbott Park, IL) for secondary hyperparathyroidism, doxercalciferol (Hectorol; Bone Care Int, Madison, WI) for reduction of elevated parathyroid hormone levels, 22-oxacalcitriol (Maxacalcitol; Chugai Pharmaceuticals, Tokyo, Japan), and alfacalcidol. Several other analogues are currently being tested in preclinical and clinical trials for the treatment of various types of cancer and osteoporosis, as well as immunosuppression. Understanding how analogues exert their selective actions may allow for the design of more effective

  2. The confidence-accuracy relationship in eyewitness identification: effects of lineup instructions, foil similarity, and target-absent base rates.

    PubMed

    Brewer, Neil; Wells, Gary L

    2006-03-01

    Discriminating accurate from mistaken eyewitness identifications is a major issue facing criminal justice systems. This study examined whether eyewitness confidence assists such decisions under a variety of conditions using a confidence-accuracy (CA) calibration approach. Participants (N = 1,200) viewed a simulated crime and attempted 2 separate identifications from 8-person target-present or target-absent lineups. Confidence and accuracy were calibrated for choosers (but not nonchoosers) for both targets under all conditions. Lower overconfidence was associated with higher diagnosticity, lower target-absent base rates, and shorter identification latencies. Although researchers agree that courtroom expressions of confidence are uninformative, our findings indicate that confidence assessments obtained immediately after a positive identification can provide a useful guide for investigators about the likely accuracy of an identification.

  3. MAPK Target Sites of Eyes Absent Are Not Required for Eye Development or Survival in Drosophila

    PubMed Central

    Jusiak, Barbara; Abulimiti, Abuduaini; Haelterman, Nele; Chen, Rui; Mardon, Graeme

    2012-01-01

    Eyes absent (Eya) is a highly conserved transcription cofactor and protein phosphatase that plays an essential role in eye development and survival in Drosophila. Ectopic eye induction assays using cDNA transgenes have suggested that mitogen activated protein kinase (MAPK) activates Eya by phosphorylating it on two consensus target sites, S402 and S407, and that this activation potentiates the ability of Eya to drive eye formation. However, this mechanism has never been tested in normal eye development. In the current study, we generated a series of genomic rescue transgenes to investigate how loss- and gain-of-function mutations at these two MAPK target sites within Eya affect Drosophila survival and normal eye formation: eya+GR, the wild-type control; eyaSAGR, which lacks phosphorylation at the two target residues; and eyaSDEGR, which contains phosphomimetic amino acids at the same two residues. Contrary to the previous studies in ectopic eye development, all eya genomic transgenes tested rescue both eye formation and survival equally effectively. We conclude that, in contrast to ectopic eye formation, MAPK-mediated phosphorylation of Eya on S402 and S407 does not play a role in normal development. This is the first study in Drosophila to evaluate the difference in outcomes between genomic rescue and ectopic cDNA-based overexpression of the same gene. These findings indicate similar genomic rescue strategies may prove useful for re-evaluating other long-standing Drosophila developmental models. PMID:23251383

  4. Absent 99mTc-MIBI Uptake in the Thyroid Gland during Early Phase of Parathyroid Scintigraphy in Patients with Primary and Secondary Hyperparathyroidism.

    PubMed

    Jovanovska, Anamarija; Stoilovska, Bojana; Mileva, Magdalena; Miladinova, Daniela; Majstorov, Venjamin; Ugrinska, Ana

    2018-05-20

    Thyroid uptake of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) during parathyroid scintigraphy can be affected by various conditions. To evaluate the frequency of absent 99m Tc-MIBI uptake by the thyroid gland in the early phase of dual-phase parathyroid scintigraphy. The early planar images of dual phase Tc 99m MIBI parathyroid scintigraphy from 217 patients performed between 2014 and 2017 were retrospectively analysed. Patients were divided into two groups. The first group included 147 patients with primary hyperparathyroidism and the second group included 70 patients with chronic renal failure. Patient records, laboratory and ultrasonographic data were analysed in all patients. Descriptive statistic was used for data analysis. Out of all patients in the first group, 18 patients (12.24%) showed absent thyroid uptake. Thyroidectomy was performed in 44.4% of these patients, and the rest of them had some thyroid disease. Only one patient had no thyroid or another chronic disease. In the second group, 8 patients (11.42%) presented with absent thyroid uptake of MIBI. Among them, 5 patients had no history of thyroid disease and had been on hemodialysis programme, and 3 patients had hypothyroidism. Absent 99m Tc-MIBI uptake in the thyroid during the early phase of parathyroid scintigraphy is most frequently related to thyroid disease. A small proportion of patients with chronic renal failure can present with absent 99m Tc-MIBI uptake in the thyroid as well. The mechanism for this alteration is still unclear and needs further investigation.

  5. Discovery of common sequences absent in the human reference genome using pooled samples from next generation sequencing.

    PubMed

    Liu, Yu; Koyutürk, Mehmet; Maxwell, Sean; Xiang, Min; Veigl, Martina; Cooper, Richard S; Tayo, Bamidele O; Li, Li; LaFramboise, Thomas; Wang, Zhenghe; Zhu, Xiaofeng; Chance, Mark R

    2014-08-16

    Sequences up to several megabases in length have been found to be present in individual genomes but absent in the human reference genome. These sequences may be common in populations, and their absence in the reference genome may indicate rare variants in the genomes of individuals who served as donors for the human genome project. As the reference genome is used in probe design for microarray technology and mapping short reads in next generation sequencing (NGS), this missing sequence could be a source of bias in functional genomic studies and variant analysis. One End Anchor (OEA) and/or orphan reads from paired-end sequencing have been used to identify novel sequences that are absent in reference genome. However, there is no study to investigate the distribution, evolution and functionality of those sequences in human populations. To systematically identify and study the missing common sequences (micSeqs), we extended the previous method by pooling OEA reads from large number of individuals and applying strict filtering methods to remove false sequences. The pipeline was applied to data from phase 1 of the 1000 Genomes Project. We identified 309 micSeqs that are present in at least 1% of the human population, but absent in the reference genome. We confirmed 76% of these 309 micSeqs by comparison to other primate genomes, individual human genomes, and gene expression data. Furthermore, we randomly selected fifteen micSeqs and confirmed their presence using PCR validation in 38 additional individuals. Functional analysis using published RNA-seq and ChIP-seq data showed that eleven micSeqs are highly expressed in human brain and three micSeqs contain transcription factor (TF) binding regions, suggesting they are functional elements. In addition, the identified micSeqs are absent in non-primates and show dynamic acquisition during primate evolution culminating with most micSeqs being present in Africans, suggesting some micSeqs may be important sources of human

  6. Mismatch negativity of sad syllables is absent in patients with major depressive disorder.

    PubMed

    Pang, Xiaomei; Xu, Jing; Chang, Yi; Tang, Di; Zheng, Ya; Liu, Yanhua; Sun, Yiming

    2014-01-01

    Major depressive disorder (MDD) is an important and highly prevalent mental disorder characterized by anhedonia and a lack of interest in everyday activities. Additionally, patients with MDD appear to have deficits in various cognitive abilities. Although a number of studies investigating the central auditory processing of low-level sound features in patients with MDD have demonstrated that this population exhibits impairments in automatic processing, the influence of emotional voice processing has yet to be addressed. To explore the automatic processing of emotional prosodies in patients with MDD, we analyzed the ability to detect automatic changes using event-related potentials (ERPs). This study included 18 patients with MDD and 22 age- and sex-matched healthy controls. Subjects were instructed to watch a silent movie but to ignore the afferent acoustic emotional prosodies presented to both ears while continuous electroencephalographic activity was synchronously recorded. Prosodies included meaningless syllables, such as "dada" spoken with happy, angry, sad, or neutral tones. The mean amplitudes of the ERPs elicited by emotional stimuli and the peak latency of the emotional differential waveforms were analyzed. The sad MMN was absent in patients with MDD, whereas the happy and angry MMN components were similar across groups. The abnormal sad emotional MMN component was not significantly correlated with the HRSD-17 and HAMA scores, respectively. The data indicate that patients with MDD are impaired in their ability to automatically process sad prosody, whereas their ability to process happy and angry prosodies remains normal. The dysfunctional sad emotion-related MMN in patients with MDD were not correlated with depression symptoms. The blunted MMN of sad prosodies could be considered a trait of MDD.

  7. Irregular or absent periods--what can an ultrasound scan tell you?

    PubMed

    Khalid, Asma

    2004-02-01

    Transvaginal ultrasonography has increased our appreciation of the physiological changes in the ovary and endometrium that occur during the normal menstrual cycle. It has become a primary investigative tool in women with irregular or absent periods. Its usefulness in cases of primary amenorrhoea to assess anatomy is also undisputed although it may have limitations in terms of its specificity. However, the interpretation of ultrasound images in women with irregular menses or secondary amenorrhoea is not entirely straightforward. This is particularly true in the diagnosis of polycystic ovary syndrome, a condition of uncertain aetiology, which may present with oligoamenorrhoea. This chapter aims to discuss the benefits and limitations of ultrasound while taking into account the broad overlap between normal and abnormal physiology, some of which has still to be elucidated.

  8. Quantifying kinematics of purposeful movements to real, imagined, or absent functional objects: implications for modelling trajectories for robot-assisted ADL tasks.

    PubMed

    Wisneski, Kimberly J; Johnson, Michelle J

    2007-03-23

    Robotic therapy is at the forefront of stroke rehabilitation. The Activities of Daily Living Exercise Robot (ADLER) was developed to improve carryover of gains after training by combining the benefits of Activities of Daily Living (ADL) training (motivation and functional task practice with real objects), with the benefits of robot mediated therapy (repeatability and reliability). In combining these two therapy techniques, we seek to develop a new model for trajectory generation that will support functional movements to real objects during robot training. We studied natural movements to real objects and report on how initial reaching movements are affected by real objects and how these movements deviate from the straight line paths predicted by the minimum jerk model, typically used to generate trajectories in robot training environments. We highlight key issues that to be considered in modelling natural trajectories. Movement data was collected as eight normal subjects completed ADLs such as drinking and eating. Three conditions were considered: object absent, imagined, and present. This data was compared to predicted trajectories generated from implementing the minimum jerk model. The deviations in both the plane of the table (XY) and the sagittal plane of torso (XZ) were examined for both reaches to a cup and to a spoon. Velocity profiles and curvature were also quantified for all trajectories. We hypothesized that movements performed with functional task constraints and objects would deviate from the minimum jerk trajectory model more than those performed under imaginary or object absent conditions. Trajectory deviations from the predicted minimum jerk model for these reaches were shown to depend on three variables: object presence, object orientation, and plane of movement. When subjects completed the cup reach their movements were more curved than for the spoon reach. The object present condition for the cup reach showed more curvature than in the object

  9. On avoided words, absent words, and their application to biological sequence analysis.

    PubMed

    Almirantis, Yannis; Charalampopoulos, Panagiotis; Gao, Jia; Iliopoulos, Costas S; Mohamed, Manal; Pissis, Solon P; Polychronopoulos, Dimitris

    2017-01-01

    The deviation of the observed frequency of a word w from its expected frequency in a given sequence x is used to determine whether or not the word is avoided . This concept is particularly useful in DNA linguistic analysis. The value of the deviation of w , denoted by [Formula: see text], effectively characterises the extent of a word by its edge contrast in the context in which it occurs. A word w of length [Formula: see text] is a [Formula: see text]-avoided word in x if [Formula: see text], for a given threshold [Formula: see text]. Notice that such a word may be completely absent from x . Hence, computing all such words naïvely can be a very time-consuming procedure, in particular for large k . In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length k in a given sequence of length n over a fixed-sized alphabet. We also present a time-optimal [Formula: see text]-time algorithm to compute all [Formula: see text]-avoided words (of any length) in a sequence of length n over an integer alphabet of size [Formula: see text]. In addition, we provide a tight asymptotic upper bound for the number of [Formula: see text]-avoided words over an integer alphabet and the expected length of the longest one. We make available an implementation of our algorithm. Experimental results, using both real and synthetic data, show the efficiency and applicability of our implementation in biological sequence analysis. The systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x . We suggest a modification to this algorithm so that it computes all avoided words of x , irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words.

  10. Profuse congenital familial milia with absent dermatoglyphics (Basan's Syndrome): description of a new family.

    PubMed

    Luna, Paula Carolina; Larralde, Margarita

    2012-01-01

    Milia are common, small, keratin-containing cysts frequently seen in all age groups. They may arise spontaneously or develop after a variety of stimuli. They can be found alone or as part of syndromes. We present a female neonate born not only with profuse facial milia, but also with acral bullae and absent dermatoglyphics. Similar features were seen in several members of her family. These findings correspond to the syndrome known as Basan's syndrome, a rare autosomal-dominant inherited dermatosis characterized by profuse congenital milia, transient neonatal acral bullae, and absence of dermatoglyphics. © 2011 Wiley Periodicals, Inc.

  11. Sleep and eyewitness memory: Fewer false identifications after sleep when the target is absent from the lineup.

    PubMed

    Stepan, Michelle E; Dehnke, Taylor M; Fenn, Kimberly M

    2017-01-01

    Inaccurate eyewitness identifications are the leading cause of known false convictions in the United States. Moreover, improving eyewitness memory is difficult and often unsuccessful. Sleep consistently strengthens and protects memory from interference, particularly when a recall test is used. However, the effect of sleep on recognition memory is more equivocal. Eyewitness identification tests are often recognition based, thus leaving open the question of how sleep affects recognition performance in an eyewitness context. In the current study, we investigated the effect of sleep on eyewitness memory. Participants watched a video of a mock-crime and attempted to identify the perpetrator from a simultaneous lineup after a 12-hour retention interval that either spanned a waking day or night of sleep. In Experiment 1, we used a target-present lineup and, in Experiment 2, we used a target-absent lineup in order to investigate correct and false identifications, respectively. Sleep reduced false identifications in the target-absent lineup (Experiment 2) but had no effect on correct identifications in the target-present lineup (Experiment 1). These results are discussed with respect to memory strength and decision making strategies.

  12. Sleep and eyewitness memory: Fewer false identifications after sleep when the target is absent from the lineup

    PubMed Central

    Dehnke, Taylor M.; Fenn, Kimberly M.

    2017-01-01

    Inaccurate eyewitness identifications are the leading cause of known false convictions in the United States. Moreover, improving eyewitness memory is difficult and often unsuccessful. Sleep consistently strengthens and protects memory from interference, particularly when a recall test is used. However, the effect of sleep on recognition memory is more equivocal. Eyewitness identification tests are often recognition based, thus leaving open the question of how sleep affects recognition performance in an eyewitness context. In the current study, we investigated the effect of sleep on eyewitness memory. Participants watched a video of a mock-crime and attempted to identify the perpetrator from a simultaneous lineup after a 12-hour retention interval that either spanned a waking day or night of sleep. In Experiment 1, we used a target-present lineup and, in Experiment 2, we used a target-absent lineup in order to investigate correct and false identifications, respectively. Sleep reduced false identifications in the target-absent lineup (Experiment 2) but had no effect on correct identifications in the target-present lineup (Experiment 1). These results are discussed with respect to memory strength and decision making strategies. PMID:28877169

  13. Deficits of Semantic Control Produce Absent or Reverse Frequency Effects in Comprehension: Evidence from Neuropsychology and Dual Task Methodology

    ERIC Educational Resources Information Center

    Almaghyuli, Azizah; Thompson, Hannah; Lambon Ralph, Matthew A.; Jefferies, Elizabeth

    2012-01-01

    Patients with multimodal semantic impairment following stroke (referred to here as "semantic aphasia" or SA) fail to show the standard effects of frequency in comprehension tasks. Instead, they show absent or even "reverse" frequency effects: i.e., better understanding of less common words. In addition, SA is associated with poor regulatory…

  14. The role of past interactions in great apes' communication about absent entities.

    PubMed

    Bohn, Manuel; Call, Josep; Tomasello, Michael

    2016-11-01

    Recent evidence suggests that great apes can use the former location of an entity to communicate about it. In this study we built on these findings to investigate the social-cognitive foundations of great apes' communicative abilities. We tested whether great apes (n = 35) would adjust their requests for absent entities to previous interactions they had with their interlocutor. We manipulated the apes' experience with respect to the interlocutor's knowledge about the previous content of the now-empty location as well as their experience with the interlocutor's competence to provide additional food items. We found that apes adjusted their requests to both of these aspects but failed to integrate them with one another. These results demonstrate a surprising amount of flexibility in great apes' communicative abilities while at the same time suggesting some important limitations in their social communicative skills. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  15. Revealing the protein propionylation activity of the histone acetyltransferase MOF (males absent on the first).

    PubMed

    Han, Zhen; Wu, Hong; Kim, Sunjoo; Yang, Xiangkun; Li, Qianjin; Huang, He; Cai, Houjian; Bartlett, Michael G; Dong, Aiping; Zeng, Hong; Brown, Peter J; Yang, Xiang-Jiao; Arrowsmith, Cheryl H; Zhao, Yingming; Zheng, Y George

    2018-03-02

    Short-chain acylation of lysine residues has recently emerged as a group of reversible posttranslational modifications in mammalian cells. The diversity of acylation further broadens the landscape and complexity of the proteome. Identification of regulatory enzymes and effector proteins for lysine acylation is critical to understand functions of these novel modifications at the molecular level. Here, we report that the MYST family of lysine acetyltransferases (KATs) possesses strong propionyltransferase activity both in vitro and in cellulo Particularly, the propionyltransferase activity of MOF, MOZ, and HBO1 is as strong as their acetyltransferase activity. Overexpression of MOF in human embryonic kidney 293T cells induced significantly increased propionylation in multiple histone and non-histone proteins, which shows that the function of MOF goes far beyond its canonical histone H4 lysine 16 acetylation. We also resolved the X-ray co-crystal structure of MOF bound with propionyl-coenzyme A, which provides a direct structural basis for the propionyltransferase activity of the MYST KATs. Our data together define a novel function for the MYST KATs as lysine propionyltransferases and suggest much broader physiological impacts for this family of enzymes. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Finding the Two-Way Street: Women from Mother-Present/Father-Absent Homes and Their Ability to Make Close Female Friendships

    ERIC Educational Resources Information Center

    Marote, Melissa A.

    2011-01-01

    This heuristic study involving seven coresearchers, which included the author, explores the experiences of women from mother-present/father-absent homes and their ability to form and maintain close female friendships. The heuristic research model was chosen to provide the opportunity to conduct research in a very personalized, collaborative way…

  17. Cigarette smoke–induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD

    PubMed Central

    Dove, Rosamund E.; Leong-Smith, Pheneatia; Roos-Engstrand, Ester; Pourazar, Jamshid; Shah, Mittal; Behndig, Annelie F.; Mudway, Ian S.; Blomberg, Anders

    2015-01-01

    Background Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke. Methods Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13). Results Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers. Conclusions We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke–induced increase in intra-cellular antioxidant enzyme activities only within the smokers with

  18. Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    PubMed

    Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

    2016-04-01

    The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

  19. Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089

    NASA Technical Reports Server (NTRS)

    Narayanan, R.; Smith, C. L.; Weigel, N. L.

    2002-01-01

    Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect. Copyright 2002 Elsevier Science Inc.

  20. Neural processes mediating the preparation and release of focal motor output are suppressed or absent during imagined movement

    PubMed Central

    Eagles, Jeremy S.; Carlsen, Anthony N.

    2016-01-01

    Movements that are executed or imagined activate a similar subset of cortical regions, but the extent to which this activity represents functionally equivalent neural processes is unclear. During preparation for an executed movement, presentation of a startling acoustic stimulus (SAS) evokes a premature release of the planned movement with the spatial and temporal features of the tasks essentially intact. If imagined movement incorporates the same preparatory processes as executed movement, then a SAS should release the planned movement during preparation. This hypothesis was tested using an instructed-delay cueing paradigm during which subjects were required to rapidly release a handheld weight while maintaining the posture of the arm or to perform first-person imagery of the same task while holding the weight. In a subset of trials, a SAS was presented at 1500, 500, or 200 ms prior to the release cue. Task-appropriate preparation during executed and imagined movements was confirmed by electroencephalographic recording of a contingent negative variation waveform. During preparation for executed movement, a SAS often resulted in premature release of the weight with the probability of release progressively increasing from 24 % at −1500 ms to 80 % at −200 ms. In contrast, the SAS rarely (<2 % of trials) triggered a release of the weight during imagined movement. However, the SAS frequently evoked the planned postural response (suppression of bicep brachii muscle activity) irrespective of the task or timing of stimulation (even during periods of postural hold without preparation). These findings provide evidence that neural processes mediating the preparation and release of the focal motor task (release of the weight) are markedly attenuated or absent during imagined movement and that postural and focal components of the task are prepared independently. PMID:25744055

  1. Expression of the Na+/l- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus

    PubMed Central

    Altorjay, Áron; Dohán, Orsolya; Szilágyi, Anna; Paroder, Monika; Wapnir, Irene L; Carrasco, Nancy

    2007-01-01

    Background The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. Methods Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. Results Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. Conclusion That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease. PMID:17214887

  2. Absent end diastolic flow of umbilical artery Doppler: pregnancy outcome in 62 cases.

    PubMed

    Poulain, P; Palaric, J C; Milon, J; Betremieux, P; Proudhon, J F; Signorelli, D; Grall, J Y; Giraud, J R

    1994-02-01

    We retrospectively studied the outcome of pregnancy in 62 cases of absent end diastolic flow (AEDF) of umbilical artery Doppler flow velocity waveform. The history of pregnancies revealed that nearly all were of high risk. Many cases presented cerebral (65%) or uterine (55.5%) Doppler flow abnormalities, or both (38%). We noted 10 fetal deaths and decided 7 pregnancy terminations. Malformation and chromosomal defect rate was 16%. We noted 44 (71%) live-births, a very high rate of cesarean section (86%), prematurity (75%), small for gestational age (39%). Forty-five percent of the neonates had a 1-min Apgar score under 7, which dropped to 27% at 5 min. Neonate mortality rate was 6.9% and the total mortality rate was 34% (21/62). Morbidity was significant (7 cases with severe morbidity, 2 cases with chromosomal abnormality of poor prognosis). We compared different sub-groups with a view to looking for some prenatal factors which predict poor neonatal outcome in case of AEDF.

  3. When Absence of Evidence Is Evidence of Absence: Rational Inferences From Absent Data.

    PubMed

    Hsu, Anne S; Horng, Andy; Griffiths, Thomas L; Chater, Nick

    2017-05-01

    Identifying patterns in the world requires noticing not only unusual occurrences, but also unusual absences. We examined how people learn from absences, manipulating the extent to which an absence is expected. People can make two types of inferences from the absence of an event: either the event is possible but has not yet occurred, or the event never occurs. A rational analysis using Bayesian inference predicts that inferences from absent data should depend on how much the absence is expected to occur, with less probable absences being more salient. We tested this prediction in two experiments in which we elicited people's judgments about patterns in the data as a function of absence salience. We found that people were able to decide that absences either were mere coincidences or were indicative of a significant pattern in the data in a manner that was consistent with predictions of a simple Bayesian model. Copyright © 2016 Cognitive Science Society, Inc.

  4. Absent husbands, single wives: success, domesticity, and seminuclear families in the nineteenth-century Great Lakes world.

    PubMed

    Nutting, P Bradley

    2010-01-01

    The industrial and transportation revolutions of nineteenth-century America separated work from home (at least for the growing middle class) and intensified the development of masculine and feminine spheres devoted to success and domesticity, respectively. This development tended to reduce the husband's traditional patriarchal roles to that of provider only, while leaving the wife and mother with enhanced authority over household management and child rearing, a development with consequences for feminism. This article examines two extreme cases of separation of work from home: absent husbands, respected professional men, who left their wives alone for months or years and, while they provided financial support, surrendered all household authority to "single" wives.

  5. Expression of beta-dystroglycan is reduced or absent in many human carcinomas.

    PubMed

    Cross, S S; Lippitt, J; Mitchell, A; Hollingsbury, F; Balasubramanian, S P; Reed, M W R; Eaton, C; Catto, J W; Hamdy, F; Winder, S J

    2008-11-01

    Dystroglycan is an important structural and signalling protein that is expressed in most human cells. alpha-Dystroglycan has been investigated and found to be reduced in human cancers, but there is only one published study on the expression of beta-dystroglycan in human cancer and that was only on small numbers of breast and prostatic cancers. The aim was to conduct a comprehensive immunohistochemical survey of the expression of beta-dystroglycan in normal human tissues and common cancers. Triplicate tissue microarrays of 681 samples of normal human tissues and common cancers were stained using an antibody directed against the cytoplasmic component of beta-dystroglycan. beta-Dystroglycan was strongly expressed at the intercellular junctions and basement membranes of all normal human epithelia. Expression of beta-dystroglycan was absent or markedly reduced in 100% of oesophageal adenocarcinomas, 97% of colonic cancers, 100% of transitional cell carcinomas of the urothelium and 94% of breast cancers. In the breast cancers, the only tumours that showed any retention of beta-dystroglycan expression were small low-grade oestrogen receptor-positive tumours. The only cancers that showed retention of beta-dystroglycan expression were cutaneous basal cell carcinomas. There is loss or marked reduction of beta-dystroglycan expression (by immunohistochemistry) in the vast majority of human cancers surveyed. Since beta-dystroglycan is postulated to have a tumour suppressor effect, this loss may have important functional significance.

  6. Lack of muco-cutaneous signs of toxic shock syndrome when T cells are absent: S.aureus shock in immunodeficient adults with multiple myeloma

    PubMed Central

    KAMEL, N S; BANKS, M C; DOSIK, A; URSEA, D; YARILINA, A A; POSNETT, D N

    2002-01-01

    Staphylococcal toxic shock syndrome (TSS) is an acute life threatening disease. The diagnosis can be made clinically based on diagnostic criteria. The clinical manifestations are caused in large part by the release of high levels of T-cell-derived cytokines as a result of potent toxins, also called superantigens (SAg), produced by Staphylococcus aureus, but it is not clear which clinical symptoms/signs are strictly T-cell dependent. Here, we report on three adults with multiple myeloma (MM) presenting with S. aureus sepsis/shock, and two patients with typical TSS. The MM patients had compromised humoral immunity because of depression of normal immunoglobulin (Ig) levels at the expense of the M protein. In addition, their T cells were absent due to high dose chemotherapy initiated for bone marrow transplantation. The MM cases lacked mucosal hyperemia, erythroderma and desquamation, but were otherwise indistinguishable from the TSS cases. All patients grew S. aureus and in each case, SAg genes were detected by PCR. In several cases, the plasma contained biological SAg activity resulting in Vβ specific proliferation of indicator T cells in vitro. The same specific activity was observed with the supernatant fluids of S. aureus broth cultures from the respective bacterial isolates. This confirms the presence of bio-active toxins in the plasma but did not lead to full blown TSS when T cells were lacking. Thus, S.aureus sepsis/shock can be clinically distinguished from typical TSS, and we suggest that muco-cutaneous manifestations of TSS are the most telling signs of massive T-cell-dependent cytokine release. PMID:12033193

  7. Dissociation of Active Working Memory and Passive Recognition in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Basile, Benjamin M.; Hampton, Robert R.

    2013-01-01

    Active cognitive control of working memory is central in most human memory models, but behavioral evidence for such control in nonhuman primates is absent and neurophysiological evidence, while suggestive, is indirect. We present behavioral evidence that monkey memory for familiar images is under active cognitive control. Concurrent cognitive…

  8. Risk of fetal death in growth-restricted fetuses with umbilical and/or ductus venosus absent or reversed end-diastolic velocities before 34 weeks of gestation: a systematic review and meta-analysis.

    PubMed

    Caradeux, J; Martinez-Portilla, R J; Basuki, T R; Kiserud, T; Figueras, F

    2018-02-01

    The objective of the study was to establish the risk of fetal death in early-onset growth-restricted fetuses with absent or reversed end-diastolic velocities in the umbilical artery or ductus venosus. A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, or German using the databases PubMed, ISI Web of Science, and SCOPUS, without publication time restrictions. The study criteria included observational cohort studies and randomized controlled trials of early-onset growth-restricted fetuses (diagnosed before 34 weeks of gestation), with information on the rate of fetal death occurring before 34 weeks of gestation and absent or reversed end-diastolic velocities in the umbilical artery and/or ductus venosus. For quality assessment, 2 reviewers independently assessed the risk of bias using the Newcastle-Ottawa Scale for observational studies and the Cochrane Collaboration's tool for randomized trials. For the meta-analysis, odds ratio for both fixed and random-effects models (weighting by inverse of variance) were used. Heterogeneity between studies was assessed using tau 2 , χ2 (Cochrane Q), and I 2 statistics. Publication bias was assessed by a funnel plot for meta-analyses and quantified by the Egger method. A total of 31 studies were included in this meta-analysis. The odds ratios for fetal death (random-effects models) were 3.59 (95% confidence interval, 2.3-5.6), 7.27 (95% confidence interval, 4.6-11.4), and 11.6 (95% confidence interval, 6.3-19.7) for growth-restricted fetuses with umbilical artery absent end-diastolic velocities, umbilical artery reversed end-diastolic velocities, and ductus venosus absent or reversed end-diastolic velocities, respectively. There was no substantial heterogeneity among studies for any of the analyses. Early-onset growth-restricted fetuses with either umbilical artery or ductus venosus absent or reserved end-diastolic velocities are at a substantially increased risk for

  9. Normal Range of Fetal Nasal Bone Length during the Second Trimester in an Afro-Caribbean Population and Likelihood Ratio for Trisomy 21 of Absent or Hypoplastic Nasal Bone.

    PubMed

    Gautier, Manuella; Gueneret, Michèle; Plavonil, Corinne; Jolivet, Eugénie; Schaub, Bruno

    2017-01-01

    To establish the normal reference range of fetal nasal bone length (NBL) during the second trimester in an Afro-Caribbean population and the likelihood ratio (LR) for fetal trisomy 21. Prenatal records of euploid, non-malformed singleton fetuses who underwent second-trimester ultrasonographic scans at 20-24 weeks of gestation were retrospectively analyzed for NBL and gestational age (GA). Only Afro-Caribbean couples were selected. The relationship between fetal NBL and GA was determined. The data of all fetuses with Down syndrome were provided by the French West Indies Register of Congenital Malformations (REMALAN). There was a significant linear association between fetal NBL and GA (R2 = 0. 354). The 50th percentile for NBL increased from 5.0 to 7.0 mm from week 20 to 24 of gestation. The nasal bone (NB) was absent or hypoplastic in 8.6% of the euploid fetuses and in 69.2% of the trisomy 21 fetuses. The LR for trisomy 21 of absent or hypoplastic NB in an Afro-Caribbean population was 8.02, but only 2.32 when this sign was isolated. The reference range for fetal NBL at 20-24 weeks of gestation in an Afro-Caribbean population and the LR for trisomy 21 of absent or hypoplastic NB differed from the other populations. © 2016 S. Karger AG, Basel.

  10. Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors with activating KIRs reduces nonrelapse mortality.

    PubMed

    Mancusi, Antonella; Ruggeri, Loredana; Urbani, Elena; Pierini, Antonio; Massei, Maria Speranza; Carotti, Alessandra; Terenzi, Adelmo; Falzetti, Franca; Tosti, Antonella; Topini, Fabiana; Bozza, Silvia; Romani, Luigina; Tognellini, Rita; Stern, Martin; Aversa, Franco; Martelli, Massimo F; Velardi, Andrea

    2015-05-14

    Because activating killer cell immunoglobulinlike receptors (KIRs) are heterogeneously expressed in the population, we investigated the role of donor activating KIRs in haploidentical hematopoietic transplants for acute leukemia. Transplants were grouped according to presence vs absence of KIR-ligand mismatches in the graft-vs-host direction (ie, of donor-vs-recipient natural killer [NK]-cell alloreactivity). In the absence of donor-vs-recipient NK-cell alloreactivity, donor activating KIRs had no effects on outcomes. In the 69 transplant pairs with donor-vs-recipient NK-cell alloreactivity, transplantation from donors with KIR2DS1 and/or KIR3DS1 was associated with reduced risk of nonrelapse mortality, largely infection related (KIR2DS1 present vs absent: hazard ratio [HR], 0.25; P = .01; KIR3DS1 present vs absent: HR, 0.18; P = .006), and better event-free survival (KIR2DS1 present vs absent: HR, 0.31; P = .011; KIR3DS1 present vs absent: HR, 0.30; P = .008). Transplantation from donors with KIR2DS1 and/or KIR3DS1 was also associated with a 50% reduction in infection rate (P = .003). In vitro analyses showed that KIR2DS1 binding to its HLA-C2 ligand upregulated inflammatory cytokine production by alloreactive NK cells in response to infectious challenges. Because ∼40% of donors able to exert donor-vs-recipient NK-cell alloreactivity carry KIR2DS1 and/or KIR3DS1, searching for them may become a feasible, additional criterion in donor selection. © 2015 by The American Society of Hematology.

  11. Anophthalmia, cleft lip/palate, absent vomer bone, nystagmus, and mental-motor retardation: a new syndrome or Fryns "anophthalmia-plus" syndrome?

    PubMed

    Ozçelik, Derya; Sağlam, Ibrahim; SIlan, Fatma; Sezen, Gülbin; Unveren, Toygar

    2008-05-01

    We report that a 4-year-old boy presented with right unilateral complete cleft lip and palate, right anophthalmos, left congenital nystagmus, absence of the vomer bone, mental-motor retardation, and normal lymphocyte karyotype (46, XY). For reconstruction of the deformities, we performed cleft lip repair by Millard's rotation-advancement technique and planned cleft palate repair. This combination of cleft lip and palate, anophthalmos, congenital nystagmus, absent vomer bone, and mental-motor retardation has not, to our knowledge, previously been described. We suggest that this represents either another case of the rare Fryns "anophthalmia-plus" syndrome or a new syndrome.

  12. Nocturnal polyuria is related to absent circadian rhythm of glomerular filtration rate.

    PubMed

    De Guchtenaere, A; Vande Walle, C; Van Sintjan, P; Raes, A; Donckerwolcke, R; Van Laecke, E; Hoebeke, P; Vande Walle, J

    2007-12-01

    Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria. We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria. Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate. Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

  13. Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome.

    PubMed

    Manukjan, Georgi; Bösing, Hendrik; Schmugge, Markus; Strauß, Gabriele; Schulze, Harald

    2017-11-01

    Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' untranslated region (5'UTR) or within the first intron of RBM8A. Although phenotypically readily diagnosed after birth, the genetic determination of particular SNPs in TAR syndrome harbours valuable information to evaluate disease severity and treatment decisions. Here, we present clinical data in a cohort of 38 patients and observed that platelet counts in individuals with 5'UTR SNP are significantly lower compared to patients bearing the SNP in intron 1. Moreover, elevated haemoglobin values could only be assessed in patients with 5'UTR SNP whereas white blood cell count is unaffected, indicating that frequently observed anaemia in TAR patients could also be SNP-dependent whereas leucocytosis does not correlate with genetic background. However, this report on a large cohort provides an overview of important haematological characteristics in TAR patients, facilitating evaluation of the various traits in this disease and indicating the importance of genetic validation for TAR syndrome. © 2017 John Wiley & Sons Ltd.

  14. Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells.

    PubMed

    Tada, Hiroyuki; Shimizu, Takamitsu; Nagaoka, Isao; Takada, Haruhiko

    2016-01-01

    Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D3 and D2. Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D3.

  15. [Right branch pulmonary artery stenosis with supravalvar aortic stenosis as a complication of Lecompte maneuver for tetralogy of Fallot associated with absent pulmonary valve].

    PubMed

    Honda, Yoshihiro; Suzuki, Shoji; Kaga, Shigeaki; Yoshida, Yukiyo; Kimura, Mitsuhiro; Kamiya, Kentaro; Sakakibara, Kenji; Katsu, Masatake

    2015-05-01

    The patient was diagnosed with tetralogy of Fallot associated with absent pulmonary valve syndrome and a low birth weight of 1,912 g. He suffered from respiratory distress on day 14 and received non-invasive positive pressure ventilation. At 5 months of age and 4.1 kg, he underwent intracardiac repair including right ventricular outflow repair with a monocusp patch, patch closure of the ventricular septum defect and right pulmonary transposition to the anterior of the ascending aorta following the Lecompte maneuver for airway decompression. He was subsequently discharged to home and exhibited an uneventful clinical course with non-invasive positive pressure ventilation for 5 months postoperatively. However, right pulmonary artery and supra-aortic stenosis was noted 2 years after the operation. Computed tomography (CT) and angiography showed ascending aorta strangulation by the right pulmonary artery with right ventricular outflow regurgitation. Right pulmonary artery reconstruction using polytetrafluoroethylene graft interposition and repeat right ventricular outflow repair with bicuspid hand-sewn valves was therefore performed;the postoperative course was uneventful. Pre- and post-operative management using non-invasive positive pressure ventilation and airway decompression with pulmonary artery translocation is a useful strategy in patients exhibiting symptomatic tetralogy of Fallot associated with absent pulmonary valve syndrome in the neonatal period.

  16. High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pediatric and adult CNS tumors.

    PubMed

    Hughes, Julie A I; Cooke-Yarborough, Claire M; Chadwick, Nigel C; Schevzov, Galina; Arbuckle, Susan M; Gunning, Peter; Weinberger, Ron P

    2003-04-01

    Tropomyosin has been implicated in the control of actin filament dynamics during cell migration, morphogenesis, and cytokinesis. In order to gain insight into the role of tropomyosins in cell division, we examined their expression in developing and neoplastic brain tissue. We found that the high-molecular-weight tropomyosins are downregulated at birth, which correlates with glial cell differentiation and withdrawal of most cells from the cell cycle. Expression of these isoforms was restricted to proliferative areas in the embryonic brain and was absent from the adult, where the majority of cells are quiescent. However, they were induced under conditions where glial cells became proliferative in response to injury. During cytokinesis, these tropomyosin isoforms were associated with the contractile ring. We also investigated tropomyosin expression in neoplastic CNS tissues. Low-grade astrocytic tumors expressed high-molecular-weight tropomyosins, while highly malignant CNS tumors of diverse origin did not (P absent from the contractile ring in highly malignant astrocytoma cells. Our findings suggest a role for high-molecular-weight tropomyosins in astrocyte cytokinesis, although highly malignant CNS tumors are still able to undergo cell division in their absence. Additionally, the correlation between high-molecular-weight tropomyosin expression and tumor grade suggests that tropomyosins are potentially useful as indicators of CNS tumor grade. Copyright 2003 Wiley-Liss, Inc.

  17. Sweating - absent

    MedlinePlus

    ... page, please enable JavaScript. An abnormal lack of sweat in response to heat may be harmful, because ... diseases or scarring of the skin that block sweat glands Trauma to sweat glands Use of certain ...

  18. D-seco-Vitamin D analogs having reversed configurations at C-13 and C-14: Synthesis, docking studies and biological evaluation.

    PubMed

    Szybinski, Marcin; Sokolowska, Katarzyna; Sicinski, Rafal R; Plum, Lori A; DeLuca, Hector F

    2017-10-01

    Prompted by results of molecular modeling performed on the seco-d-ring-vitamins D, we turned our attention to such analogs, having reversed configurations at C-13 and C-14, as the next goals of our studies on the structure-activity relationship for vitamin D compounds. First, we developed an efficient total synthesis of the "upper" C/seco-d-ring fragment with a 7-carbon side chain. Then, we coupled it with A-ring fragments using Sonogashira or Wittig-Horner protocol, providing the targeted D-seco analogs of 1α,25-dihydroxyvitamin D 3 and 1α,25-dihydroxy-19-norvitamin D 3 possessing a vinyl substituent at C-14 and a double bond between C-17 and C-20. The affinities of the synthesized vitamin D analogs to the full-length recombinant rat VDR were examined, as well as their differentiating and transcriptional activities. In these in vitro tests, they were significantly less active compared to 1α,25-(OH) 2 D 3 . Moreover, it was established that the analogs tested in vivo in rats showed no calcemic potency. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Retinal Expression of the Drosophila eyes absent Gene Is Controlled by Several Cooperatively Acting Cis-regulatory Elements

    PubMed Central

    Neuman, Sarah D.; Bashirullah, Arash; Kumar, Justin P.

    2016-01-01

    The eyes absent (eya) gene of the fruit fly, Drosophila melanogaster, is a member of an evolutionarily conserved gene regulatory network that controls eye formation in all seeing animals. The loss of eya leads to the complete elimination of the compound eye while forced expression of eya in non-retinal tissues is sufficient to induce ectopic eye formation. Within the developing retina eya is expressed in a dynamic pattern and is involved in tissue specification/determination, cell proliferation, apoptosis, and cell fate choice. In this report we explore the mechanisms by which eya expression is spatially and temporally governed in the developing eye. We demonstrate that multiple cis-regulatory elements function cooperatively to control eya transcription and that spacing between a pair of enhancer elements is important for maintaining correct gene expression. Lastly, we show that the loss of eya expression in sine oculis (so) mutants is the result of massive cell death and a progressive homeotic transformation of retinal progenitor cells into head epidermis. PMID:27930646

  20. [History of the development of new vitamin D analogs for the treatment of renal failure, and future aspects].

    PubMed

    Nishii, Yasuho

    2002-06-01

    In 1981, Suda and colleagues reported the new activity of calcitriol namely its ability to differentiate the myeloid leukemia cells into monocyte-macrophages. Several companies and organic chemists initiated the synthesis of vitamin D analogs with the aim to separate the calcemic actions of calcitriol from its actions on regulating the cell growth and differentiation. The group of Chugai company succeeded in marketing OCT, Oxarol, as a therapeutic agent for secondary hyperparathyroidism and psoriasis, and Leo company, MC903, Dovonex, as a drug for psoriasis. The work on OCT and MC903 vigorously stimulated research world-wide in the development of vitamin D analogs into pharmaceutical products. More new impressive vitamin D analogs are being developed. I am convinced that various vitamin D analogs will become highly effective therapeutic agents at the clinical level in the new century, and also that a new theory on the mechanism of vitamin D action will be generated.

  1. Attenuated or absent HRV response to postural change in subjects with primary insomnia.

    PubMed

    Jiang, Xiao-ling; Zhang, Zheng-gang; Ye, Cui-ping; Lei, Ying; Wu, Lei; Zhang, Ying; Chen, Yuan-yuan; Xiao, Zhong-ju

    2015-03-01

    Previous studies have compared rest heart rate variability (HRV) between insomniacs and good sleepers, but the results have not been consistent. The altered HRV behavior in response to postural change was considered useful as another sensitive measure for evaluating the autonomic nervous function, however, to our knowledge, no study was found using HRV response to postural change in primary insomnia. Our study aimed to examine HRV response to postural change maneuver (PCM) in both primary insomniacs and controls between 22 and 39 years of age to gain insights into the characteristics of the autonomic nervous system (ANS) function in primary insomnia subjects. HRV was recorded for 5 min at seated rest, and then, the subjects quickly stood up from a seated position in up to 3s and remained standing for 15 min. HRV was recorded at the following times: seated rest and 0-5 min, 5-10 min and 10-15 min in the standing position. In primary insomnia subjects, attenuated or absent HRV response to postural change was identified, the increase in LF/HF ratio and the decrease in HF and SD1 from seated to standing were much slower than in the normal controls. In conclusion, this study provided evidence of the possible bi-directional relationship between insomnia and autonomic nervous system (ANS) function, which will move us closer to developing a new sensitive method for measuring autonomic impairment and early sympathetic damage in primary insomnia subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Management of small-for-gestational-age twins with absent/reversed end diastolic flow in the umbilical artery: outcome of a policy of daily biophysical profile (BPP).

    PubMed

    Kennelly, Máiréad M; Sturgiss, Stephen N

    2007-01-01

    To evaluate a strategy of daily biophysical profile (BPP) for pregnancies with small-for-gestational-age twins and with absent or reversed end diastolic flow (AREDF) in the umbilical artery of one twin and to assess the latency interval between detection and delivery in monochorionic (MC) and dichorionic (DC) twin pregnancy. A search of the Fetal Medicine Database was carried out between 2000 and 2005 at a single tertiary centre to identify all cases with AREDF in the umbilical artery with one small-for-gestational-age twin. Active monitoring with daily BPP was undertaken, once the estimated fetal weights (EFW) was >or= 500 g and at a gestational age of >or= 24 weeks in both twins. Delivery was timed on the basis of an abnormal BPP, two equivocal BPP within 12 h or gestational age of >or= 32(+0) weeks. Twenty-two MC and 17 DC twin pregnancies were identified. There were no fetal losses in the viable actively monitored MC (19) and DC (13) twins. There was a longer latency interval in the MC group at 21.7 days versus 14.4 days in the DC group (p = 0.13). Delivery was indicated for an abnormal BPP (57.8% MC vs 30.8% DC). A strategy of daily BPP can be used to monitor preterm twin fetuses with AREDF, prolonging pregnancy with an acceptable perinatal outcome. Copyright 2007 John Wiley & Sons, Ltd.

  3. Bilateral Malar Reconstruction Using Patient-Specific Polyether Ether Ketone Implants in Treacher-Collins Syndrome Patients With Absent Zygomas.

    PubMed

    Sainsbury, David C G; George, Alan; Forrest, Christopher R; Phillips, John H

    2017-03-01

    The authors performed bilateral malar reconstruction using polyether ether ketone implants in 3 patients with Treacher-Collins syndrome with absent, as opposed to hypoplastic, zygomata. These patient-specific implants were fabricated using computed-aided design software reformatted from three-dimensional bony preoperative computed tomography images. The first time the authors performed this procedure the implant compressed the globe resulting in temporary anisocoria that was quickly recognized intraoperatively. The implant was immediately removed and the patient made a full-recovery with no ocular disturbance. The computer-aided design and manufacturing process was adjusted to include periorbital soft-tissue boundaries to aid in contouring the new implants. The same patient, and 2 further patients, subsequently underwent malar reconstruction using this soft tissue periorbital boundary fabrication process with an additional 2 mm relief removed from the implant's orbital surface. These subsequent procedures were performed without complication and with pleasing aesthetic results. The authors describe their experience and the salutary lessons learnt.

  4. From Absent to Active Voices: Securing Disability Equality within Higher Education

    ERIC Educational Resources Information Center

    Beauchamp-Pryor, Karen

    2012-01-01

    This article discusses the representation and participation of disabled students in the development of higher education policy and provision within the UK, at both a national and institutional level. Findings are drawn from a doctoral study, which identified the importance of student participation in securing equality and inclusion. Power…

  5. Characterization of the first intragenic SATB2 duplication in a girl with intellectual disability, nearly absent speech and suspected hypodontia.

    PubMed

    Kaiser, Ann-Sophie; Maas, Bianca; Wolff, Anna; Sutter, Christian; Janssen, Johannes W G; Hinderhofer, Katrin; Moog, Ute

    2015-05-01

    SATB2, a gene encoding a highly conserved DNA-binding protein, is known to have an important role in craniofacial and neuronal development. Only a few patients with SATB2 variants have been described so far. Recently, Döcker et al provided a summary of these patients and delineated the SAS (SATB2-associated syndrome). We here report on a girl with intellectual disability, nearly absent speech and suspected hypodontia who was shown to carry an intragenic SATB2 tandem duplication hypothesized to lead to haploinsufficiency of SATB2. Preliminary information on this patient had already been included in the article by Döcker et al. We want to give a detailed description of the patient's phenotype and genotype, providing further insight into the spectrum of the molecular mechanisms leading to SAS.

  6. A Report to the President of the United States [from the] Intergovernmental Advisory Council on Education, National Networking Conference [on] The Absent Parent (Washington, D.C. May 9-10, 1988).

    ERIC Educational Resources Information Center

    Intergovernmental Advisory Council on Education (ED), Washington, DC.

    This report on child care and the Federal government's role in child care is based on the National Networking Conference on the Absent Parent which was held May 9-10, 1988 under the sponsorship of the President's Intergovernmental Advisory Council on Education (IACE). The report begins with 12 recommendations concerning day care and latchkey…

  7. IMPORTANCE OF GLUTATHIONE IN THE ACQUISITION AND MAINTENANCE OF SPERM NUCLEAR DECONDENSING ACTIVITY IN MATURING HAMSTER OOCYTES

    EPA Science Inventory

    Sperm nuclear decondensing activity in mammalian oocytes is dependent upon the maturational state of the oocyte. It is maximal in mature, metaphase II oocytes and minimal or absent in immature germinal vesicle (GV) and fertilized pronuclear oocytes. Previous studies suggested tha...

  8. A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia

    PubMed Central

    Na, Songqing; Ma, Yanfei; Zhao, Jingyong; Schmidt, Clint; Zeng, Qing Q.; Chandrasekhar, Srinivasan; Chin, William W.; Nagpal, Sunil

    2011-01-01

    Vitamin D receptor (VDR) agonists are currently the agents of choice for the treatment of psoriasis, a skin inflammatory indication that is believed to involve an autoimmune component. 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D, has shown efficacy in animal autoimmune disease models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type I diabetes. However, the side effect of 1,25-(OH)2D3 and its synthetic secosteroidal analogs is hypercalcemia, which is a major impediment in their clinical development for autoimmune diseases. Hypercalcemia develops as a result of the action of VDR agonists on the intestine. Here, we describe the identification of a VDR modulator (VDRM) compound A that was transcriptionally less active in intestinal cells and as a result exhibited less calcemic activity in vivo than 1,25-(OH)2D3. Cytokine analysis indicated that the VDRM not only modulated the T-helper cell balance from Th1 to Th2 effector function but also inhibited Th17 differentiation. Finally, we demonstrate that the oral administration of compound A inhibited the induction and progress of experimental autoimmune encephalomyelitis in mice without causing hypercalcemia. PMID:21318047

  9. Differential effects of absent visual feedback control on gait variability during different locomotion speeds.

    PubMed

    Wuehr, M; Schniepp, R; Pradhan, C; Ilmberger, J; Strupp, M; Brandt, T; Jahn, K

    2013-01-01

    Healthy persons exhibit relatively small temporal and spatial gait variability when walking unimpeded. In contrast, patients with a sensory deficit (e.g., polyneuropathy) show an increased gait variability that depends on speed and is associated with an increased fall risk. The purpose of this study was to investigate the role of vision in gait stabilization by determining the effects of withdrawing visual information (eyes closed) on gait variability at different locomotion speeds. Ten healthy subjects (32.2 ± 7.9 years, 5 women) walked on a treadmill for 5-min periods at their preferred walking speed and at 20, 40, 70, and 80 % of maximal walking speed during the conditions of walking with eyes open (EO) and with eyes closed (EC). The coefficient of variation (CV) and fractal dimension (α) of the fluctuations in stride time, stride length, and base width were computed and analyzed. Withdrawing visual information increased the base width CV for all walking velocities (p < 0.001). The effects of absent visual information on CV and α of stride time and stride length were most pronounced during slow locomotion (p < 0.001) and declined during fast walking speeds. The results indicate that visual feedback control is used to stabilize the medio-lateral (i.e., base width) gait parameters at all speed sections. In contrast, sensory feedback control in the fore-aft direction (i.e., stride time and stride length) depends on speed. Sensory feedback contributes most to fore-aft gait stabilization during slow locomotion, whereas passive biomechanical mechanisms and an automated central pattern generation appear to control fast locomotion.

  10. New findings and concepts about the G-spot in normal and absent vagina: precautions possibly needed for preservation of the G-spot and sexuality during surgery.

    PubMed

    Thabet, Saeed Mohamad Ahmad

    2013-08-01

    The aim of this study was to extend the clinicohistological study to involve the whole normal and absent vagina for confirming the presence of the G-spot and its relation to the surrounding organs and sexuality and to identify certain precautions for its preservation during surgery. This study was a descriptive randomized prospective study conducted at Kasr El Aini School of Medicine, Cairo University, Egypt. The G-spot was examined in 1500 women, 500 of them having vaginal and vulval surgery done for gynecological reasons. The G-spot was examined for its clinical and histological features and for determining the effect of surgery on its state and function. The G-spot was found to be present in all women. It was a localized spot in 58% and diffuse in 42% of cases. Associated ejaculation was reported in all cases of the localized type and in 24.5% of the diffuse types. Clinical examination was found to be associated with certain local response in 52.7% of the local types. The G-spot was also found to be connected to the hymen in 100%, the urethra in 52.7%, the vulva in 82.2% and the cervix in 10.8% of cases. The mean of the sex scores and sexuality were significantly decreased in surgery involving the G-spot area. Recorded figures were 93.6 ± 3.4 and 88.2 ± 3.3 before and after surgery, respectively. The corresponding figures in the cases having a general spot were 86.4 ± 4.4 and 84.5 ± 2.4, respectively. The G-spot was found in cases of absent vagina to be localized in 59%, generalized in 28.2% and absent in 12.8% of cases. The G-spot is actually present in all women. It is originally related to the lower urinary tract and it is connected to different parts of the genital tract. It may be localized or generalized. Its integrity is essential for obtaining normal physiological sexuality. Surgery may affect the integrity of the G-spot, so surgical precautions must be carried out to maintain the integrity of this spot and the patient's sexuality.

  11. Absent pulmonary valve

    MedlinePlus

    ... Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, ... Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, ...

  12. CD18 activation epitopes induced by leukocyte activation.

    PubMed

    Beals, C R; Edwards, A C; Gottschalk, R J; Kuijpers, T W; Staunton, D E

    2001-12-01

    The cell surface adhesion molecule LFA-1 coordinates leukocyte trafficking and is a costimulatory molecule for T cell activation. We developed a panel of mAbs that recognize activation epitopes on the CD18 subunit, and show that stimulation of T lymphocytes appears to be accompanied by a conformational change in a subpopulation of LFA-1 that does not require ligand binding. Activation epitope up-regulation requires divalent cations, is sensitive to cellular signal transduction events, and correlates with cell adhesion. In addition, the stimulated appearance of these activation epitopes is absent in cell lines from patients with leukocyte adhesion deficiency-1/variant that has previously been shown to be defective in LFA-1 activation. Thus, these activation epitope Abs can be used to dissect signal transmission to CD18. Evidence suggests that these CD18 activation epitopes are induced early in cellular activation and are independent of actin rearrangement necessary for avid adhesion. We have also determined that function-blocking CD18 Abs inhibit the induction of activation epitopes. One activation epitope Ab binds to a site on CD18 distinct from that of the blocking Abs, indicating that the blocking Abs suppress a conformational change in LFA-1. We also find that these neoepitopes are present on rLFA-1 with high affinity for ICAM-1 and their binding is modulated in parallel with the affinity of LFA-1 for ICAM-1. Collectively, these neoepitope Abs identify a subpopulation of LFA-1 most likely with high affinity for ICAM-1 and necessary for LFA-1 function.

  13. Antitumor properties of (5E,7E) analogs of vitamin D3.

    PubMed

    Filip, B; Milczarek, M; Wietrzyk, J; Chodyński, M; Kutner, A

    2010-07-01

    Geometric isomers (5E,7E) of major active metabolites of vitamin D3 [1alpha,25(OH)2D3 and (24R)-1,24(OH)2D3] were synthesized by a new convenient procedure. Vitamin D triene system of the metabolites was first derivatized as a Diels-Alder adduct. Removal of the triene protecting group, in a key synthetic step, yielded the title compounds PRI-2208 and PRI-2209, respectively. The analogs were examined for their antiproliferative activity in vitro against human breast cancer cells (MCF-7) and promyelocytic leukemia (HL-60) cells. The activity was compared with one of the parent compounds. Both analogs examined revealed similar or higher antiproliferative activity compared to 1alpha,25(OH)2D3 or to (24R)-1,24(OH)2D3. The studies of calcemic activity in vivo showed that analogs PRI-2208 and PRI-2209 did not influence the serum calcium level in doses, in which 1alpha,25(OH)2D3 or (24R)-1,24(OH)2D3 significantly increased this level. The antitumor activity of these analogs in the LLC mice tumor model was studied. Analog PRI-2208 was found to be more active in inhibiting LLC tumor growth than 1alpha,25(OH)2D3, as well as than PRI-2191 and PRI-2209. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  14. Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice

    PubMed Central

    Higa, K. K.; Grim, A.; Kamenski, M. E.; van Enkhuizen, J.; Zhou, X.; Li, K.; Naviaux, J. C.; Wang, L.; Naviaux, R. K.; Geyer, M. A.; Markou, A.; Young, J. W.

    2017-01-01

    Rationale Smoking is the leading cause of preventable death in the U.S., but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. Objectives We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the 5-choice continuous performance test (5C-CPT). Methods Mice were trained in the 5C-CPT prior to osmotic minipump implantation containing saline or nicotine. Experiment 1 used 40 mg/kg/day nicotine treatment and tested C57BL/6 mice 4, 28, and 52 h after pump removal. Experiment 2 used 14 and 40 mg/kg/day nicotine treatment in α7 nAChR knockout (KO) and wildtype (WT) littermates tested 4 h after pump removal. Subsets of WT mice were sacrificed before and after pump removal to assess changes in receptor expression associated with nicotine administration and withdrawal. Results Nicotine withdrawal impaired attention in the 5C-CPT, driven by response inhibition and target detection deficits. The overall attentional deficit was absent in α7 nAChR KO mice despite response disinhibition in these mice. Synaptosomal glutamate mGluR5 and dopamine D4 receptor expression were reduced during chronic nicotine but increased during withdrawal, potentially contributing to cognitive deficits. Conclusions The α7 nAChR may underlie nicotine withdrawal-induced deficits in target detection but is not required for response disinhibition deficits. Alterations to the glutamatergic and dopaminergic pathways may also contribute to withdrawal-induced attentional deficits, providing novel targets to alleviate the cognitive symptoms of withdrawal during quit attempts. PMID:28243714

  15. The investigation of solar activity signals by analyzing of tree ring chronological scales

    NASA Astrophysics Data System (ADS)

    Nickiforov, M. G.

    2017-07-01

    The present study examines the ability of detecting short-cycles and global minima of solar activity by analyzing dendrochronologies. Starting with the study of Douglass, which was devoted to the question of climatic cycles and the growth of trees, it is believed that the analysis of dendrochronologies allows to detect the cycle of Wolf-Schwabe. According to his results, the cycle was absent during Maunder's minimum and appeared after its completion. Having checked Douglass's conclusions by using 10 dendrochronologies of yellow pines from Arizona, which cover the time period from 1600 to 1900, we have come to the opposite results. The verification shows that: a) none of the considered dendroscale allows to detect an 11-year cycle; 2) the behaviour of a short peroid-signal does not undergo significant changes before, during or after Maunder's minimum. A similar attempt to detect global minima of solar activity by using five dendrochronologies from different areas has not led to positive results. On the one hand, the signal of global extremum is not always recorded in dendrochronology, on the other hand, the deep depression of annual rings allows to suppose the existence of a global minimum of solar activity, which is actually absent.

  16. Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity.

    PubMed

    Jones, Scott L; To, Minh-Son; Stuart, Greg J

    2017-10-23

    Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.

  17. In Vitro Activities of 35 Double Combinations of Antifungal Agents against Scedosporium apiospermum and Scedosporium prolificans▿

    PubMed Central

    Cuenca-Estrella, Manuel; Alastruey-Izquierdo, Ana; Alcazar-Fuoli, Laura; Bernal-Martinez, Leticia; Gomez-Lopez, Alicia; Buitrago, Maria J.; Mellado, Emilia; Rodriguez-Tudela, Juan L.

    2008-01-01

    Activities of 35 combinations of antifungal agents against Scedosporium spp. were analyzed by a checkerboard microdilution design and the summation of fractional concentration index. An average indifferent effect was detected apart from combinations of azole agents and echinocandins against Scedosporium apiospermum. Antagonism was absent for all antifungal combinations against both species. PMID:18195067

  18. GW501516 acts as an efficient PPARα activator in the mouse liver.

    PubMed

    Terada, M; Araki, M; Ashibe, B; Motojima, K

    2011-08-01

    The peroxisome proliferator-activated receptor (PPAR) subtype specificity of GW501516, a well-known PPARδ-specific agonist, was studied by examining its effects on the expression of endogenous genes in primary hepatocytes and the liver of wild-type and PPARα-null mice. GW501516, like the PPARα-specific agonist Wy14,643, induced the expression of several PPAR target genes in a dose-dependent manner but this action was mostly absent in the cells and liver of PPARα-null mice. Results indicated that GW501516 acts as an efficient PPARα activator in the mouse liver.

  19. Amine templating effect absent in uranyl sulfates synthesized with 1,4-n-butyldiamine

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

    Jouffret, Laurent J., E-mail: ljouffret@nd.edu; Wylie, Ernest M.; Burns, Peter C.

    2013-01-15

    Two new uranyl sulfates, (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2}){sub 2}(SO{sub 4}){sub 3}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS2) and (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2})(SO{sub 4}){sub 2}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS3), were synthesized and their crystal structures determined. NDUS2 was obtained in highly acidic media heat-treated at 373 K and subsequently maintained at 278 K until crystals formed after two months. NDUS3 results from the degradation of NDUS2 over the course of a few days. NDUS2 and NDUS3 crystallize in the monoclinic space group P2{sub 1}/n, a=10.9075(4) A, b=10.4513(4) A, c=17.7881(7) A, {beta}=97.908(2) Degree-Sign , V=2008.52(13) A{sup 3}, Z=4, at 140 K and a=8.8570(4) A,more » b=7.3299(3) A, c=20.4260(9) A, {beta}=95.140(2) Degree-Sign , V=1320.74(10) A{sup 3}, Z=4, at 140 K, respectively. The compounds contain interlayer 1,4-n-butyldiammonium cations that charge-balance the anionic structural units. - Graphical abstract: Amine templating effect absent in uranyl sulfates synthesized with 1,4-diaminobutane, as shown by the synthesis of two new uranyl sulfates, (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2}){sub 2}(SO{sub 4}){sub 3}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS2) and (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2})(SO{sub 4}){sub 2}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS3). Highlights: Black-Right-Pointing-Pointer Two layered uranyl sulfates were synthesized. Black-Right-Pointing-Pointer Amine molecules are located in the interlayers of the compounds. Black-Right-Pointing-Pointer No templating effect of the amine was observed. Black-Right-Pointing-Pointer Amine molecules are only charge balancing cations in the structures.« less

  20. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27.

    PubMed

    Gan, Nanqin; Wu, Yu-Chieh; Brunet, Mathilde; Garrido, Carmen; Chung, Fung-Lung; Dai, Chengkai; Mi, Lixin

    2010-11-12

    It is conceivable that stimulating proteasome activity for rapid removal of misfolded and oxidized proteins is a promising strategy to prevent and alleviate aging-related diseases. Sulforaphane (SFN), an effective cancer preventive agent derived from cruciferous vegetables, has been shown to enhance proteasome activities in mammalian cells and to reduce the level of oxidized proteins and amyloid β-induced cytotoxicity. Here, we report that SFN activates heat shock transcription factor 1-mediated heat shock response. Specifically, SFN-induced expression of heat shock protein 27 (Hsp27) underlies SFN-stimulated proteasome activity. SFN-induced proteasome activity was significantly enhanced in Hsp27-overexpressing cells but absent in Hsp27-silenced cells. The role of Hsp27 in regulating proteasome activity was further confirmed in isogenic REG cells, in which SFN-induced proteasome activation was only observed in cells stably overexpressing Hsp27, but not in the Hsp27-free parental cells. Finally, we demonstrated that phosphorylation of Hsp27 is irrelevant to SFN-induced proteasome activation. This study provides a novel mechanism underlying SFN-induced proteasome activity. This is the first report to show that heat shock response by SFN, in addition to the antioxidant response mediated by the Keap1-Nrf2 pathway, may contribute to cytoprotection.

  1. Potent 19-norvitamin D analogs for prostate and liver cancer therapy

    PubMed Central

    Kittaka, Atsushi; Yoshida, Akihiro; Chiang, Kun-Chun; Takano, Masashi; Sawada, Daisuke; Sakaki, Toshiyuki; Chen, Tai C

    2013-01-01

    The active form of vitamin D3, 1α,25(OH)2D3 or calcitriol, is known to inhibit the proliferation and invasiveness of many types of cancer cells, including prostate and liver cancer cells. These findings support the use of 1α,25(OH)2D3 for prostate and liver cancer therapy. However, 1α,25(OH)2D3 can cause hypercalcemia, thus, analogs of 1α,25(OH)2D3 that are less calcemic but exhibit potent antiproliferative activity would be attractive as therapeutic agents. We have developed 2α-functional group substituted 19-norvitamin D3 analogs with and without 14-epimerization. Among them, 2α- and 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3 (MART-10 and -11, respectively) and 14-epi-2α- and 14-epi-2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3 (14-epi-MART-10 and 14-epi-MART-11, respectively) were found to be the most promising. In this review, we discuss the synthesis of this unique class of vitamin D analogs, the molecular mechanism of anticancer actions of vitamin D, and the biological evaluation of these analogs for potential application to the prevention and treatment of prostate and liver cancer. PMID:23157238

  2. Memory-induced mechanism for self-sustaining activity in networks

    NASA Astrophysics Data System (ADS)

    Allahverdyan, A. E.; Steeg, G. Ver; Galstyan, A.

    2015-12-01

    We study a mechanism of activity sustaining on networks inspired by a well-known model of neuronal dynamics. Our primary focus is the emergence of self-sustaining collective activity patterns, where no single node can stay active by itself, but the activity provided initially is sustained within the collective of interacting agents. In contrast to existing models of self-sustaining activity that are caused by (long) loops present in the network, here we focus on treelike structures and examine activation mechanisms that are due to temporal memory of the nodes. This approach is motivated by applications in social media, where long network loops are rare or absent. Our results suggest that under a weak behavioral noise, the nodes robustly split into several clusters, with partial synchronization of nodes within each cluster. We also study the randomly weighted version of the models where the nodes are allowed to change their connection strength (this can model attention redistribution) and show that it does facilitate the self-sustained activity.

  3. Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics

    PubMed Central

    Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen; Christensen, Sune M.; Abel, Steven M.; Iwig, Jeff; Wu, Hung-Jen; Gureasko, Jodi; Rhodes, Christopher; Petit, Rebecca S.; Hansen, Scott D.; Thill, Peter; Yu, Cheng-Han; Stamou, Dimitrios; Chakraborty, Arup K.; Kuriyan, John; Groves, Jay T.

    2014-01-01

    Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras–guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average. PMID:24994643

  4. Absent Inferior Vena Cava Leading to Recurrent Lower Extremity Deep Vein Thrombosis in a United States Marine.

    PubMed

    Kim, Sang; Kunkel, Scott; Browske, Kristin

    2018-01-01

    Anomalies of the inferior vena cava (AIVC) are rare but well-recognized anatomic abnormalities that can lead to clinically significant deep vein thrombosis (DVT) in a subset of otherwise healthy patients. This report illustrates an uncommon congenital anomaly that military clinicians should consider when evaluating unprovoked DVT in young patients. Single case report and literature review. We describe a case of a 24-yr-old United States Marine who presented with abdominal pain for 2 wk. After conservative therapy failed, a contrast-enhanced abdominal computed tomography (CT) scan was performed. The CT scan revealed an absent inferior vena cava with evidence of right venous thrombophlebitis. We include four contrast-enhanced helical CT scans that illustrate this phenomenon. Due to the lack of available studies and data, we do not know the relative risk of DVT in patients with AIVC. However, the literature review suggests that there is a pro-thrombogenic effect of this congenital anomaly. Clinicians should include AIVC in their differential when treating young, otherwise healthy patients with unprovoked DVT. This population is much more likely to have an AIVC than the general population. In addition to thrombophilia markers, a contrast-enhanced CT scan should be considered as part of the initial workup. Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  5. The functional architecture of the human body: assessing body representation by sorting body parts and activities.

    PubMed

    Bläsing, Bettina; Schack, Thomas; Brugger, Peter

    2010-05-01

    We investigated mental representations of body parts and body-related activities in two subjects with congenitally absent limbs (one with, the other without phantom sensations), a wheelchair sports group of paraplegic participants, and two groups of participants with intact limbs. To analyse mental representation structures, we applied Structure Dimensional Analysis. Verbal labels indicating body parts and related activities were presented in randomized lists that had to be sorted according to a hierarchical splitting paradigm. Participants were required to group the items according to whether or not they were considered related, based on their own body perception. Results of the groups of physically intact and paraplegic participants revealed separate clusters for the lower body, upper body, fingers and head. The participant with congenital phantom limbs also showed a clear separation between upper and lower body (but not between fingers and hands). In the participant without phantom sensations of the absent arms, no such modularity emerged, but the specific practice of his right foot in communication and daily routines was reflected. Sorting verbal labels of body parts and activities appears a useful method to assess body representation in individuals with special body anatomy or function and leads to conclusions largely compatible with other assessment procedures.

  6. It only takes once: The absent-exempt heuristic and reactions to comparison-based sexual risk information.

    PubMed

    Stock, Michelle L; Gibbons, Frederick X; Beekman, Janine B; Gerrard, Meg

    2015-07-01

    Three studies (N = 545) investigated the effects of social comparison on the "absent-exempt" (AE) heuristic (feeling exempt from future risk). Study 1 examined how comparison with an infected peer (comparison target) who was similar or nonsimilar in terms of sexual risk (number of partners, lack of condom use), influenced willingness and intentions to engage in sex without a condom, and conditional perceived vulnerability to an STD. Participants generally reported lower willingness and higher conditional vulnerability if they compared with a similar-risk level target. However, high-risk students who compared with a low-risk target engaged in what appeared to be AE thinking, reporting the highest willingness and lowest conditional vulnerability. Intentions to have sex without a condom were not influenced. Study 2 included a direct measure of AE thinking and compared the impact of a low-risk comparison target with a Public Service Announcement (PSA) stating that negative outcomes (STDs) can happen even to low-risk targets. Among high-risk participants, comparing with the low-risk target increased AE thinking. The effects in Studies 1 and 2 were strongest among participants high in tendencies to socially compare. Study 3 explored whether AE thinking could be decreased by encouraging more reasoned processing. Results indicated that asking participants to think about the illogicality of AE thinking reduces AE endorsement and increases STD testing intentions. Findings suggest that comparison-based information can have a stronger influence on health cognitions than analytic-based information (e.g., most PSAs). Implications for dual-processing models of decision-making and their applicability to health messages are discussed. (c) 2015 APA, all rights reserved).

  7. A chromogranin A ELISA absent of an apparent high-dose hook effect observed in other chromogranin A ELISAs.

    PubMed

    Erickson, J Alan; Grenache, David G

    2016-01-15

    Routine testing for chromogranin A (CgA) using an established commercial ELISA revealed an apparent high-dose hook effect in approximately 15% of specimens. Investigations found the same effect in two additional ELISAs. We hypothesized that a CgA derived peptide(s) at high concentrations was responsible but experiments were inconclusive. Here we describe the analytical performance characteristics of the Chromoa™ CgA ELISA that did not display the apparent high-dose hook effect. Performance characteristics of the Chromoa ELISA were assessed. The reference interval was established utilizing healthy volunteers. Specimens producing the apparent high-dose hook effect in other assays were evaluated using the Chromoa ELISA. The limit of detection was 8ng/ml. Linearity was acceptable (slope=1.04, intercept=18.1 and r(2)=0.997). CVs were ≤4.6 and ≤9.3% for repeatability and within-laboratory imprecision, respectively. CgA was stable at ambient and refrigerated temperatures for a minimum of two and 14days, respectively. An upper reference interval limit of 95ng/ml was established. Specimens demonstrating the apparent high-dose hook effect in other ELISAs did not exhibit the phenomenon using the Chromoa ELISA. The Chromoa ELISA demonstrates acceptable performance for quantifying serum CgA. The apparent high-dose hook effect exhibited in other ELISAs was absent using the Chromoa assay. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Absent movement-related cortical potentials in children with primary motor stereotypies.

    PubMed

    Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A; Vorbach, Sherry; Singer, Harvey S; Hallett, Mark

    2014-08-01

    The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown, with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about 1 second before the onset of a voluntary movement. Early MRCPs preceded self-paced arm movements in 8 of 10 children with motor stereotypies and in 6 of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. © 2013 International Parkinson and Movement Disorder Society.

  9. Absent movement-related cortical potentials in children with primary motor stereotypies

    PubMed Central

    Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A.; Vorbach, Sherry; Singer, Harvey S.; Hallett, Mark

    2013-01-01

    Background The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Methods Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about one second before the onset of a voluntary movement. Results Early MRCPs preceded self-paced arm movements in 8 out of 10 children with motor stereotypies and in 6 out of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Conclusions Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. PMID:24259275

  10. Edge instability in incompressible planar active fluids

    NASA Astrophysics Data System (ADS)

    Nesbitt, David; Pruessner, Gunnar; Lee, Chiu Fan

    2017-12-01

    Interfacial instability is highly relevant to many important biological processes. A key example arises in wound healing experiments, which observe that an epithelial layer with an initially straight edge does not heal uniformly. We consider the phenomenon in the context of active fluids. Improving upon the approximation used by Zimmermann, Basan, and Levine [Eur. Phys. J.: Spec. Top. 223, 1259 (2014), 10.1140/epjst/e2014-02189-7], we perform a linear stability analysis on a two-dimensional incompressible hydrodynamic model of an active fluid with an open interface. We categorize the stability of the model and find that for experimentally relevant parameters, fingering instability is always absent in this minimal model. Our results point to the crucial role of density variation in the fingering instability in tissue regeneration.

  11. TRPV3 channels mediate strontium-induced mouse egg activation

    PubMed Central

    Carvacho, Ingrid; Lee, Hoi Chang; Fissore, Rafael A.; Clapham, David E.

    2014-01-01

    SUMMARY In mammals, calcium influx is required for oocyte maturation and egg activation. The molecular identities of the calcium-permeant channels that underlie the initiation of embryonic development are not established. Here, we describe a Transient Receptor Potential (TRP) ion channel current activated by TRP agonists that is absent in TrpV3−/− eggs. TRPV3 current is differentially expressed during oocyte maturation, reaching a peak of maximum density and activity at metaphase of meiosis II (MII), the stage of fertilization. Selective activation of TRPV3 channels provokes egg activation by mediating massive calcium entry. Widely used to activate eggs, strontium application is known to yield normal offspring in combination with somatic cell nuclear transfer. We show that TRPV3 is required for strontium influx, as TrpV3−/− eggs failed to permeate Sr2+ or undergo strontium-induced activation. We propose that TRPV3 is the major mediator of calcium influx in mouse eggs and is a putative target for artificial egg activation. PMID:24316078

  12. Physical activity promotion for people with spinal cord injury: physiotherapists' beliefs and actions.

    PubMed

    Williams, Toni L; Smith, Brett; Papathomas, Anthony

    2018-01-01

    It is vital that people with spinal cord injury (SCI) lead a physically active lifestyle to promote long term health and well-being. Yet within rehabilitation and upon discharge into the community, people with SCI are largely inactive. Physiotherapists are well placed to promote a physically active lifestyle and are valued and trusted messengers of physical activity (PA) by people with SCI. Therefore this study aimed to explore the perceptions of physiotherapists in SCI rehabilitation on PA for people with SCI, and what is done to promote PA. Semi-structured interviews were completed with 18 neurological physiotherapists (2-22 years experience) from SCI centres in the United Kingdom and Ireland. Framed by interpretivism, an inductive thematic analysis was conducted. Three themes were identified: (1) perceived importance of PA; (2) inconsistent PA promotion efforts; and (3) concern regarding community PA. This article makes a significant contribution to the literature by identifying that although physiotherapists value PA, active promotion of PA remains largely absent from their practice. To enable physiotherapists to promote and prescribe PA as a structured and integral component of their practice, effective knowledge strategies need designing and implementing at the macro, meso, and micro levels of healthcare. Implications for Rehabilitation Physiotherapists are well placed to promote a physically active lifestyle and are perceived as valued and trusted messengers of physical activity (PA). The importance of PA for patients with spinal cord injury (SCI) is valued by physiotherapists yet PA promotion is largely absent from their practice. Physiotherapists lack specific education and training on PA and SCI and hold certain beliefs which restrict their promotion of PA. Knowledge translation across the macro, meso, and micro levels of healthcare are essential to facilitate effective PA promotion.

  13. It only takes once: The absent-exempt heuristic and reactions to comparison-based sexual risk information

    PubMed Central

    Stock, Michelle L.; Gibbons, Frederick X.; Beekman, Janine B.; Gerrard, Meg

    2015-01-01

    Three studies (N = 545) investigated the effects of social comparison on a type of heuristic called “absent-exempt” (AE; feeling exempt from future risk). Study 1 examined how comparison with an infected peer (comparison target) who was similar or non-similar in terms of sexual risk (number of partners, lack of condom use), influenced willingness and intentions to engage in sex without a condom and conditional perceived vulnerability to a sexually transmitted disease (STD). Participants generally reported lower willingness and higher conditional vulnerability if they compared with a similar-risk level target. However, high-risk students who compared with a low-risk comparison target engaged in what appeared to be AE thinking, reporting the highest willingness and lowest conditional vulnerability. Intentions to have sex without a condom were not influenced. Study 2 included a direct measure of AE thinking, and compared the impact of a low-risk comparison target with a Public Service Announcement (PSA) stating that negative outcomes (e.g., STDs) can happen even to low-risk targets. Among high-risk participants, comparing with the low-risk target led to an increase in AE thinking. As expected, the effects in Studies 1 and 2 were strongest among participants high in tendencies to socially compare. Study 3 explored whether AE thinking could be decreased by encouraging more reasoned processing. Results indicated that asking participants to think about the illogicality of AE thinking reduces AE endorsement and increases STD testing intentions. Findings suggest that comparison-based information can have a stronger influence on health cognitions than analytic-based information (e.g., most PSAs). Implications for dual-processing models of decision-making and their applicability to interventions and health messages are discussed. PMID:26098587

  14. Absent menstrual periods - primary

    MedlinePlus

    ... Either of these problems may be due to: Anorexia (loss of appetite) Chronic or long-term illnesses, ... to begin. If the cause is the bulimia , anorexia or too much exercise, periods will often begin ...

  15. Absent menstrual periods - secondary

    MedlinePlus

    ... example, from strict or extreme diets or after gastric bypass surgery ) Other causes include: Brain (pituitary) tumors Drugs for cancer treatment Drugs to treat schizophrenia or psychosis Overactive ...

  16. BCL10 aberations and NF-kappa B activation involving p65 are absent or rare in primary gastric MALT lymphoma.

    PubMed

    Hajder, Jelena; Marisavljević, Dragomir; Stanisavljević, Natasa; Mihaljević, Biljana; Kovcin, Vladimir; Marković, Olivera; Zivković, Radmila

    2014-11-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 5-17% non-Hodgkin lymphomas (NHL). The molecular pathogenesis of MALT lymphomas is not well-established. The aim of this study was to evaluate immunohistochemically determined nuclear coexpression of BCL10 and NF-kappaB (NF-kappaB) in tumor cells of gastric MALT lymphoma and its impact on the patogenesis and outcome of the disease. Medical records of 35 patients with newly diagnosed gastric MALT lymphoma were analyzed and biopsy specimens were immunostained for BCL10 and NF-kappaB expression (p65 subunit). The median age of 35 patients diagnosed with gastric MALT lymphoma was 63.5 years (male/female = 21/14). Symptoms were present in 23/35 (65.7%) patients with the weight loss as the most common symptom. Gastric MALT lymphomas were usually localized in the stomach corpus and corpus and antrum (45.7% and 31.2%, respectively). H. pylon infection was confirmed in 20 out of 30 (66.7%) patients. Treatment options were as follows: immunochemotherapy in 10 (28.5%) patients, surgery in 9 (25.8%) patients, combined surgery and chemotherapy in 14 (40%) patients and supportive measures in 2 (5.7%) patients. Complete remission was achieved in 13 (37.10/) patients and partial remission in two (5.7%/) patients. Sixteen (45.7%/) patients had disease progression (p < 0.001). Cytoplasmatic expression of BCL10 in tumor cells was detected in 19 (54.3%) specimens. Nuclear expression was detected in no specimen. Cytoplasmic expression of NF-kappaB was present in 22 (65.7%) specimens, but nuclear expression was not detected in any specimens. Nuclear expressions (activation)of NF-kappaB p65 subunit and BCL10 were not detected in specimens of gastric MALT lymphoma. The correlation of nuclear coexpression of BCL10 and NF-kappaB in gastric MALT lymphoma was not established. These results indicate that other mechanisms and signal pathways are active in lymphogenesis of gastric MALT lymphoma, as that apoptotic inhibition is not

  17. Focal versus distributed temporal cortex activity for speech sound category assignment

    PubMed Central

    Bouton, Sophie; Chambon, Valérian; Tyrand, Rémi; Seeck, Margitta; Karkar, Sami; van de Ville, Dimitri; Giraud, Anne-Lise

    2018-01-01

    Percepts and words can be decoded from distributed neural activity measures. However, the existence of widespread representations might conflict with the more classical notions of hierarchical processing and efficient coding, which are especially relevant in speech processing. Using fMRI and magnetoencephalography during syllable identification, we show that sensory and decisional activity colocalize to a restricted part of the posterior superior temporal gyrus (pSTG). Next, using intracortical recordings, we demonstrate that early and focal neural activity in this region distinguishes correct from incorrect decisions and can be machine-decoded to classify syllables. Crucially, significant machine decoding was possible from neuronal activity sampled across different regions of the temporal and frontal lobes, despite weak or absent sensory or decision-related responses. These findings show that speech-sound categorization relies on an efficient readout of focal pSTG neural activity, while more distributed activity patterns, although classifiable by machine learning, instead reflect collateral processes of sensory perception and decision. PMID:29363598

  18. Two Major Medicinal Honeys Have Different Mechanisms of Bactericidal Activity

    PubMed Central

    Kwakman, Paulus H. S.; te Velde, Anje A.; de Boer, Leonie; Vandenbroucke-Grauls, Christina M. J. E.; Zaat, Sebastian A. J.

    2011-01-01

    Honey is increasingly valued for its antibacterial activity, but knowledge regarding the mechanism of action is still incomplete. We assessed the bactericidal activity and mechanism of action of Revamil® source (RS) honey and manuka honey, the sources of two major medical-grade honeys. RS honey killed Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa within 2 hours, whereas manuka honey had such rapid activity only against B. subtilis. After 24 hours of incubation, both honeys killed all tested bacteria, including methicillin-resistant Staphylococcus aureus, but manuka honey retained activity up to higher dilutions than RS honey. Bee defensin-1 and H2O2 were the major factors involved in rapid bactericidal activity of RS honey. These factors were absent in manuka honey, but this honey contained 44-fold higher concentrations of methylglyoxal than RS honey. Methylglyoxal was a major bactericidal factor in manuka honey, but after neutralization of this compound manuka honey retained bactericidal activity due to several unknown factors. RS and manuka honey have highly distinct compositions of bactericidal factors, resulting in large differences in bactericidal activity. PMID:21394213

  19. Adenosine triphosphatase activity of cutaneous nerve fibers.

    PubMed

    Idé, C; Saito, T

    1980-02-01

    The histochemical study of Mg++-activated adenosine triphosphatase (Mg++-ATPase) activity was carried out on the peripheral nerves of mouse digital skin by light and electron microscopy. Under the light microscope, the ATPase activity was clearly demonstrated on the nerve fibers as a fine network in the subepidermal regions. Under the electron microscope, the reaction product of enzyme activity was located in the interspace between axolemma and the surrounding Schwann cells of the unmyelinated nerve fibers. No reaction product was observed in the space between the axolemma and the Schwann cells associated with myelinated nerve fibers. Demonstrable activity was absent at the nodes of Ranvier as well as on the para- and internodal regions of these myelinated axons. The part of the axolemma lacking a Schwann cell sheath failed to show a reaction product. The perineural epithelial cells surrounding the nerve fibers displayed reaction product in the caveolae. These results suggest a functional difference in the axon-Schwann interface of myelinated as compared to unmyelinated nerve fibers. The function of the perineural epithelial cell would be expected to be a regulatory one in transferring materials across the epithelium to keep the proper humoral environment around nerve fibers.

  20. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

    PubMed

    Altieri, Barbara; Muscogiuri, Giovanna; Barrea, Luigi; Mathieu, Chantal; Vallone, Carla V; Mascitelli, Luca; Bizzaro, Giorgia; Altieri, Vincenzo M; Tirabassi, Giacomo; Balercia, Giancarlo; Savastano, Silvia; Bizzaro, Nicola; Ronchi, Cristina L; Colao, Annamaria; Pontecorvi, Alfredo; Della Casa, Silvia

    2017-09-01

    In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

  1. Visual attention modulates brain activation to angry voices.

    PubMed

    Mothes-Lasch, Martin; Mentzel, Hans-Joachim; Miltner, Wolfgang H R; Straube, Thomas

    2011-06-29

    In accordance with influential models proposing prioritized processing of threat, previous studies have shown automatic brain responses to angry prosody in the amygdala and the auditory cortex under auditory distraction conditions. However, it is unknown whether the automatic processing of angry prosody is also observed during cross-modal distraction. The current fMRI study investigated brain responses to angry versus neutral prosodic stimuli during visual distraction. During scanning, participants were exposed to angry or neutral prosodic stimuli while visual symbols were displayed simultaneously. By means of task requirements, participants either attended to the voices or to the visual stimuli. While the auditory task revealed pronounced activation in the auditory cortex and amygdala to angry versus neutral prosody, this effect was absent during the visual task. Thus, our results show a limitation of the automaticity of the activation of the amygdala and auditory cortex to angry prosody. The activation of these areas to threat-related voices depends on modality-specific attention.

  2. Molecular kinetics. Ras activation by SOS: allosteric regulation by altered fluctuation dynamics.

    PubMed

    Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen; Christensen, Sune M; Abel, Steven M; Iwig, Jeff; Wu, Hung-Jen; Gureasko, Jodi; Rhodes, Christopher; Petit, Rebecca S; Hansen, Scott D; Thill, Peter; Yu, Cheng-Han; Stamou, Dimitrios; Chakraborty, Arup K; Kuriyan, John; Groves, Jay T

    2014-07-04

    Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras-guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average. Copyright © 2014, American Association for the Advancement of Science.

  3. Anticipatory Postural Activity During Long-Duration Space Flight

    NASA Technical Reports Server (NTRS)

    Layne, C. S.; Mulavara, A. P.; McDonald, P. V.; Pruett, C. J.; Koslovskaya, B.; Bloomberg, J. J.

    1999-01-01

    Somatosensory input has been used to modify motor output in many contexts. During space flight, the use of the lower limb musculature is much less than during activities in 1g. Consequently the neuromuscular activity of the legs is also reduced during space flight. This decrease in muscle activity contributes to muscle atrophy. Furthermore, adaptations to weightlessness contribute to posture and locomotion problems upon the return to Earth. Providing techniques to counter the negative effects of weightlessness on the neuromuscular system is an important goal, particularly during a long-duration mission. Previous work by our group has shown that lower limb neuromuscular activation that normally precedes arm movements in 1g is absent or greatly reduced during similar movements made while freefloating. However, preliminary evidence indicates that applying pressure to the feet results in enhanced neuromuscular activation during rapid arm movements performed while freefloating. This finding suggests that sensory input can be used to "drive" the motor system to increase neuromuscular functioning throughout a mission. The purpose of this investigation was to quantify the increase in neuromuscular activation resulting from the application of pressure to the feet.

  4. NMDA-receptor dependent synaptic activation of TRPC channels in olfactory bulb granule cells

    PubMed Central

    Stroh, Olga; Freichel, Marc; Kretz, Oliver; Birnbaumer, Lutz; Hartmann, Jana; Egger, Veronica

    2012-01-01

    TRPC channels are widely expressed throughout the nervous system including the olfactory bulb where their function is largely unknown. Here we describe their contribution to central synaptic processing at the reciprocal mitral and tufted cell - granule cell microcircuit, the most abundant synapse of the mammalian olfactory bulb. Suprathreshold activation of the synapse causes sodium action potentials in mouse granule cells and a subsequent long-lasting depolarization (LLD) linked to a global dendritic postsynaptic calcium signal recorded with two-photon laser scanning microscopy. These signals are not observed after action potentials evoked by current injection in the same cells. The LLD persists in the presence of group I metabotropic glutamate receptor antagonists but is entirely absent from granule cells deficient for the NMDA receptor subunit NR1. Moreover, both depolarization and Ca2+ rise are sensitive to the blockade of NMDA receptors. The LLD and the accompanying Ca2+ rise are also absent in granule cells from mice deficient for both TRPC channel subtypes 1 and 4, whereas the deletion of either TRPC1 or TRPC4 results in only a partial reduction of the LLD. Recordings from mitral cells in the absence of both subunits reveal a reduction of asynchronous neurotransmitter release from the granule cells during recurrent inhibition. We conclude that TRPC1 and TRPC4 can be activated downstream of NMDA receptor activation and contribute to slow synaptic transmission in the olfactory bulb, including the calcium dynamics required for asynchronous release from the granule cell spine. PMID:22539836

  5. The temporal relationship between non-respiratory burst activity of expiratory laryngeal motoneurons and phrenic apnoea during stimulation of the superior laryngeal nerve in rat

    PubMed Central

    Sun, Qi-Jian; Bautista, Tara G; Berkowitz, Robert G; Zhao, Wen-Jing; Pilowsky, Paul M

    2011-01-01

    Abstract A striking effect of stimulating the superior laryngeal nerve (SLN) is its ability to inhibit central inspiratory activity (cause ‘phrenic apnoea’), but the mechanism underlying this inhibition remains unclear. Here we demonstrate, by stimulating the SLN at varying frequencies, that the evoked non-respiratory burst activity recorded from expiratory laryngeal motoneurons (ELMs) has an intimate temporal relationship with phrenic apnoea. During 1–5 Hz SLN stimulation, occasional absences of phrenic nerve discharge (PND) occurred such that every absent PND was preceded by an ELM burst activity. During 10–20 Hz SLN stimulation, more bursts were evoked together with more absent PNDs, leading eventually to phrenic apnoea. Interestingly, subsequent microinjections of isoguvacine (10 mm, 20–40 nl) into ipsilateral Bötzinger complex (BötC) and contralateral nucleus tractus solitarii (NTS) significantly attenuated the apnoeic response but not the ELM burst activity. Our results suggest a bifurcating projection from NTS to both the caudal nucleus ambiguus and BötC, which mediates the closely related ELM burst and apnoeic response, respectively. We believe that such an intimate timing between laryngeal behaviour and breathing is crucial for the effective elaboration of the different airway protective behaviours elicited following SLN stimulation, including the laryngeal adductor reflex, swallowing and cough. PMID:21320890

  6. Leisure-time physical activity and direct cost of short-term sickness absence among Finnish municipal employees.

    PubMed

    Tolonen, Anu; Rahkonen, Ossi; Lahti, Jouni

    2017-03-04

    We aimed to examine the direct costs of short-term (1-14 days) sickness absence and the effect of employees' physical activity on the costs. The Finnish Helsinki Health Study survey (2007) was used in the analysis (n = 3,935). Physical activity was classified into inactive, moderately active, and vigorously active. Sickness absence (3 years follow-up) and salary data were derived from the employer's registers. On average, an employee was absent 6 days a year due to short-term sickness absence, with a production loss of 2,350 EUR during the 3 years. The vigorously active had less sickness absence than those less active. The direct cost of sickness absence of a vigorously active employee was 404 EUR less than that of an inactive employee. Promoting physical activity among employees may decrease direct cost of short-term sickness absence.

  7. Regulated expression of telomerase activity in human T lymphocyte development and activation

    PubMed Central

    1996-01-01

    Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation required RNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of S pi protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion. PMID:8676067

  8. Chromatin as active matter

    NASA Astrophysics Data System (ADS)

    Agrawal, Ankit; Ganai, Nirmalendu; Sengupta, Surajit; Menon, Gautam I.

    2017-01-01

    Active matter models describe a number of biophysical phenomena at the cell and tissue scale. Such models explore the macroscopic consequences of driving specific soft condensed matter systems of biological relevance out of equilibrium through ‘active’ processes. Here, we describe how active matter models can be used to study the large-scale properties of chromosomes contained within the nuclei of human cells in interphase. We show that polymer models for chromosomes that incorporate inhomogeneous activity reproduce many general, yet little understood, features of large-scale nuclear architecture. These include: (i) the spatial separation of gene-rich, low-density euchromatin, predominantly found towards the centre of the nucleus, vis a vis. gene-poor, denser heterochromatin, typically enriched in proximity to the nuclear periphery, (ii) the differential positioning of individual gene-rich and gene-poor chromosomes, (iii) the formation of chromosome territories, as well as (iv), the weak size-dependence of the positions of individual chromosome centres-of-mass relative to the nuclear centre that is seen in some cell types. Such structuring is induced purely by the combination of activity and confinement and is absent in thermal equilibrium. We systematically explore active matter models for chromosomes, discussing how our model can be generalized to study variations in chromosome positioning across different cell types. The approach and model we outline here represent a preliminary attempt towards a quantitative, first-principles description of the large-scale architecture of the cell nucleus.

  9. Accuracy of increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection for diagnosing hyperthyroidism in cats.

    PubMed

    Page, Richard B; Scrivani, Peter V; Dykes, Nathan L; Erb, Hollis N; Hobbs, Jeff M

    2006-01-01

    Our purpose was to determine the accuracy of increased thyroid activity for diagnosing hyperthyroidism in cats suspected of having that disease during pertechnetate scintigraphy using subcutaneous rather than intravenous radioisotope administration. Increased thyroid activity was determined by two methods: the thyroid:salivary ratio (T:S) and visual inspection. These assessments were made on the ventral scintigram of the head and neck. Scintigraphy was performed by injecting sodium pertechnetate (111 MBq, SQ) in the right-dorsal-lumbar region; static-acquisition images were obtained 20 min after injection. We used 49 cats; 34 (69%) had hyperthyroidism based on serum-chemistry analysis. Using a Wilcoxon's rank-sum test, a significant difference (P < 0.0001) was detected in the T:S between cats with and without hyperthyroidism. Using a decision criterion of 2.0 for the T:S, the test accurately predicted hyperthyroidism in 32/34 cats (sensitivity, 94%; 95% confidence interval (CI), 85-100%) and correctly predicted that hyperthyroidism was absent in 15/15 cats (specificity, 100%; CI, 97-100%). Using visual inspection, the test accurately predicted hyperthyroidism in 34/34 cats (sensitivity, 100%; CI, 99-100%) and correctly predicted that hyperthyroidism was absent in 12/15 cats (specificity, 80%; CI, 56-100%). The positive and negative predictive values were high for a wide range of prevalence of hyperthyroidism. And, the test had excellent agreement within and between examiners. Therefore, detecting increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection is an accurate and reproducible test for feline hyperthyroidism.

  10. Triclosan Antagonizes Fluconazole Activity against Candida albicans

    PubMed Central

    Higgins, J.; Pinjon, E.; Oltean, H.N.; White, T.C.; Kelly, S.L.; Martel, C.M.; Sullivan, D.J.; Coleman, D.C.; Moran, G.P.

    2012-01-01

    Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg/L. However, at subinhibitory concentrations (0.5-2 mg/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Δ strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes. PMID:21972257

  11. Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation.

    PubMed

    Dang, Eric V; McDonald, Jeffrey G; Russell, David W; Cyster, Jason G

    2017-11-16

    Type I interferon restrains interleukin-1β (IL-1β)-driven inflammation in macrophages by upregulating cholesterol-25-hydroxylase (Ch25h) and repressing SREBP transcription factors. However, the molecular links between lipid metabolism and IL-1β production remain obscure. Here, we demonstrate that production of 25-hydroxycholesterol (25-HC) by macrophages is required to prevent inflammasome activation by the DNA sensor protein absent in melanoma 2 (AIM2). We find that in response to bacterial infection or lipopolysaccharide (LPS) stimulation, macrophages upregulate Ch25h to maintain repression of SREBP2 activation and cholesterol synthesis. Increasing macrophage cholesterol content is sufficient to trigger IL-1β release in a crystal-independent but AIM2-dependent manner. Ch25h deficiency results in cholesterol-dependent reduced mitochondrial respiratory capacity and release of mitochondrial DNA into the cytosol. AIM2 deficiency rescues the increased inflammasome activity observed in Ch25h -/- . Therefore, activated macrophages utilize 25-HC in an anti-inflammatory circuit that maintains mitochondrial integrity and prevents spurious AIM2 inflammasome activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. THE LOCALIZATION OF MYOFIBRILLAR ATPASE ACTIVITY IN THE FLIGHT MUSCLES OF THE BLOWFLY, CALLIPHORA ERYTHROCEPHALA

    PubMed Central

    Tice, Lois W.; Smith, David S.

    1965-01-01

    The distribution of ATPase activity in the asynchronous flight muscles of Calliphora erythrocephala (Diptera) was studied at a fine structural level, using preparations of teased fibers, both unfixed and after brief fixation in hydroxyadipaldehyde, incubated in a medium for the histochemical demonstration of myosin or actomyosin ATPase. In relaxed fibrils, activity was found confined to the A bands and was absent from the H zones as well as from the Z and I band regions. At high magnification, deposits of final product, lead phosphate, appeared primarily related to the thick filaments, or to short lateral extensions from them. Evidence was gathered which indicated that this enzyme activity was that of a triphosphatase which did not act on dinucleoside or non-nucleoside substrates. PMID:4221034

  13. C—H Oxidation of Ingenanes Enables Potent and Selective Protein Kinase C Isoform Activation

    PubMed Central

    Jin, Yehua; Yeh, Chien‐Hung; Kuttruff, Christian A.; Jørgensen, Lars; Dünstl, Georg; Felding, Jakob; Natarajan, Swaminathan R.

    2015-01-01

    Abstract Ingenol derivatives with varying degrees of oxidation were prepared by two‐phase terpene synthesis. This strategy has allowed access to analogues that cannot be prepared by semisynthesis from natural ingenol. Complex ingenanes resulting from divergent C—H oxidation of a common intermediate were found to interact with protein kinase C in a manner that correlates well with the oxidation state of the ingenane core. Even though previous work on ingenanes has suggested a strong correlation between potential to activate PKCδ and induction of neutrophil oxidative burst, the current study shows that the potential to activate PKCβII is of key importance while interaction with PKCδ is dispensable. Thus, key modifications of the ingenane core allowed PKC isoform selectivity wherein PKCδ‐driven activation of keratinocytes is strongly reduced or even absent while PKCβII‐driven activation of neutrophils is retained. PMID:26418078

  14. Activation of the AMP-Activated Protein Kinase by Eicosapentaenoic Acid (EPA, 20:5 n-3) Improves Endothelial Function In Vivo

    PubMed Central

    Wu, Yong; Zhang, Cheng; Dong, Yunzhou; Wang, Shuangxi; Song, Ping; Viollet, Benoit; Zou, Ming-Hui

    2012-01-01

    The aim of the present study was to test the hypothesis that the cardiovascular-protective effects of eicosapentaenoic acid (EPA) may be due, in part, to its ability to stimulate the AMP-activated protein kinase (AMPK)-induced endothelial nitric oxide synthase (eNOS) activation. The role of AMPK in EPA-induced eNOS phosphorylation was investigated in bovine aortic endothelial cells (BAEC), in mice deficient of either AMPKα1 or AMPKα2, in eNOS knockout (KO) mice, or in Apo-E/AMPKα1 dual KO mice. EPA-treatment of BAEC increased both AMPK-Thr172 phosphorylation and AMPK activity, which was accompanied by increased eNOS phosphorylation, NO release, and upregulation of mitochondrial uncoupling protein-2 (UCP-2). Pharmacologic or genetic inhibition of AMPK abolished EPA-enhanced NO release and eNOS phosphorylation in HUVEC. This effect of EPA was absent in the aortas isolated from either eNOS KO mice or AMPKα1 KO mice fed a high-fat, high-cholesterol (HFHC) diet. EPA via upregulation of UCP-2 activates AMPKα1 resulting in increased eNOS phosphorylation and consequent improvement of endothelial function in vivo. PMID:22532857

  15. Cytosine DNA Methylation Is Found in Drosophila melanogaster but Absent in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Other Yeast Species

    PubMed Central

    2014-01-01

    The methylation of cytosine to 5-methylcytosine (5-meC) is an important epigenetic DNA modification in many bacteria, plants, and mammals, but its relevance for important model organisms, including Caenorhabditis elegans and Drosophila melanogaster, is still equivocal. By reporting the presence of 5-meC in a broad variety of wild, laboratory, and industrial yeasts, a recent study also challenged the dogma about the absence of DNA methylation in yeast species. We would like to bring to attention that the protocol used for gas chromatography/mass spectrometry involved hydrolysis of the DNA preparations. As this process separates cytosine and 5-meC from the sugar phosphate backbone, this method is unable to distinguish DNA- from RNA-derived 5-meC. We employed an alternative LC–MS/MS protocol where by targeting 5-methyldeoxycytidine moieties after enzymatic digestion, only 5-meC specifically derived from DNA is quantified. This technique unambiguously identified cytosine DNA methylation in Arabidopsis thaliana (14.0% of cytosines methylated), Mus musculus (7.6%), and Escherichia coli (2.3%). Despite achieving a detection limit at 250 attomoles (corresponding to <0.00002 methylated cytosines per nonmethylated cytosine), we could not confirm any cytosine DNA methylation in laboratory and industrial strains of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Saccharomyces boulardii, Saccharomyces paradoxus, or Pichia pastoris. The protocol however unequivocally confirmed DNA methylation in adult Drosophila melanogaster at a value (0.034%) that is up to 2 orders of magnitude below the detection limit of bisulphite sequencing. Thus, 5-meC is a rare DNA modification in drosophila but absent in yeast. PMID:24640988

  16. Analysis of the crystal structure of an active MCM hexamer.

    PubMed

    Miller, Justin M; Arachea, Buenafe T; Epling, Leslie B; Enemark, Eric J

    2014-09-29

    In a previous Research article (Froelich et al., 2014), we suggested an MCM helicase activation mechanism, but were limited in discussing the ATPase domain because it was absent from the crystal structure. Here we present the crystal structure of a nearly full-length MCM hexamer that is helicase-active and thus has all features essential for unwinding DNA. The structure is a chimera of Sulfolobus solfataricus N-terminal domain and Pyrococcus furiosus ATPase domain. We discuss three major findings: 1) a novel conformation for the A-subdomain that could play a role in MCM regulation; 2) interaction of a universally conserved glutamine in the N-terminal Allosteric Communication Loop with the AAA+ domain helix-2-insert (h2i); and 3) a recessed binding pocket for the MCM ssDNA-binding motif influenced by the h2i. We suggest that during helicase activation, the h2i clamps down on the leading strand to facilitate strand retention and regulate ATP hydrolysis.

  17. Odor-mediated taste learning requires dorsal hippocampus, but not basolateral amygdala activity

    PubMed Central

    Wheeler, Daniel S.; Chang, Stephen E.; Holland, Peter C.

    2013-01-01

    Mediated learning is a unique cognitive phenomenon in which mental representations of physically absent stimuli enter into associations with directly-activated representations of physically present stimuli. Three experiments investigated the functional physiology of mediated learning involving the use of odor-taste associations. In Experiments 1a and 1b, basolateral amygdala lesions failed to attenuate mediated taste aversion learning. In Experiment 2, dorsal hippocampus inactivation impaired mediated learning, but left direct learning intact. Considered with past studies, the results implicate the dorsal hippocampus in mediated learning generally, and suggest a limit on the importance of the basolateral amygdala. PMID:23274135

  18. The perceptions of caregivers toward physical activity and health in youth with congenital heart disease.

    PubMed

    Moola, Fiona; Fusco, Caroline; Kirsh, Joel A

    2011-02-01

    Medical advances have reduced mortality in youth with congenital heart disease (CHD). Although physical activity is associated with enhanced quality of life, most patients are inactive. By addressing medical and psychological barriers, previous literature has reproduced discourses of individualism which position cardiac youth as personally responsible for physical inactivity. Few sociological investigations have sought to address the influence of social barriers to physical activity, and the insights of caregivers are absent from the literature. In this study, caregiver perceptions toward physical activity for youth with CHD were investigated at a Canadian hospital. Media representations, school liability, and parental overprotection construct cardiac youth as "at risk" during physical activity, and position their health precariously. Indeed, from the perspective of hospital staff, the findings indicate the centrality of sociological factors to the physical activity experiences of youth with CHD, and the importance of attending to the contextual barriers that constrain their health and physical activity.

  19. Complement, Kinins, and Hereditary Angioedema: Mechanisms of Plasma Instability when C1 Inhibitor is Absent.

    PubMed

    Kaplan, Allen P; Joseph, Kusumam

    2016-10-01

    Plasma of patients with types I and II hereditary angioedema is unstable if incubated in a plastic (i.e., inert) vessel at 37 °C manifested by progressively increasing formation of bradykinin. There is also a persistent low level of C4 in 95 % of patients even when they are symptomatic. These phenomena are due to the properties of the C1r subcomponent of C1, factor XII, and the bimolecular complex of prekallikrein with high molecular weight kininogen (HK). Purified C1r auto-activates in physiologic buffers, activates C1s, which in turn depletes C4. This occurs when C1 inhibitor is deficient. The complex of prekallikrein-HK acquires an inducible active site not present in prekallikrein which in Tris-type buffers cleaves HK stoichiometrically to release bradykinin, or in phosphate buffer auto-activates to generate kallikrein and bradykinin. Thus immunologic depletion of C1 inhibitor from factor XII-deficient plasma (phosphate is the natural buffer) auto-activates on incubation to release bradykinin. Normal C1 inhibitor prevents this from occurring. During attacks of angioedema, if factor XII auto-activates on surfaces, the initial factor XIIa formed converts prekallikrein to kallikrein, and kallikrein cleaves HK to release bradykinin. Kallikrein also rapidly activates most remaining factor XII to factor XIIa. Additional cleavages convert factor XIIa to factor XIIf and factor XIIf activates C1r enzymatically so that C4 levels approach zero, and C2 is depleted. There is also a possibility that kallikrein is generated first as a result of activation of the prekallikrein-HK complex by heat shock protein 90 released from endothelial cells, followed by kallikrein activation of factor XII.

  20. Free energy landscape of activation in a signaling protein at atomic resolution

    PubMed Central

    Pontiggia, F.; Pachov, D.V.; Clarkson, M.W.; Villali, J.; Hagan, M.F.; Pande, V.S.; Kern, D.

    2015-01-01

    The interconversion between inactive and active protein states, traditionally described by two static structures, is at the heart of signaling. However, how folded states interconvert is largely unknown due to the inability to experimentally observe transition pathways. Here we explore the free energy landscape of the bacterial response regulator NtrC by combining computation and NMR, and discover unexpected features underlying efficient signaling. We find that functional states are defined purely in kinetic and not structural terms. The need of a well-defined conformer, crucial to the active state, is absent in the inactive state, which comprises a heterogeneous collection of conformers. The transition between active and inactive states occurs through multiple pathways, facilitated by a number of nonnative transient hydrogen bonds, thus lowering the transition barrier through both entropic and enthalpic contributions. These findings may represent general features for functional conformational transitions within the folded state. PMID:26073309

  1. Abandoned babies and absent policies.

    PubMed

    Mueller, Joanne; Sherr, Lorraine

    2009-12-01

    Although infant abandonment is a historical problem, we know remarkably little about the conditions or effects of abandonment to guide evidence driven policies. This paper briefly reviews the existing international evidence base with reference to potential mental health considerations before mapping current UK guidelines and procedures, and available incidence data. Limitations arising from these findings are discussed with reference to international practice, and interpreted in terms of future pathways for UK policy. A systematic approach was utilized to gather available data on policy information and statistics on abandoned babies in the UK. A review of the limited literature indicates that baby abandonment continues to occur, with potentially wide-ranging mental health ramifications for those involved. However, research into such consequences is lacking, and evidence with which to understand risk factors or motives for abandonment is scarce. International approaches to the issue remain controversial with outcomes unclear. Our systematic search identified that no specific UK policy relating to baby abandonment exists, either nationally or institutionally. This is compounded by a lack of accurate of UK abandonment statistics. Data that does exist is not comprehensive and sources are incompatible, resulting in an ambiguous picture of UK baby abandonment. Available literature indicates an absence of clear provision, policy and research on baby abandonment. Based on current understanding of maternal and child mental health issues likely to be involved in abandonment, existing UK strategy could be easily adapted to avoid the 'learning from scratch' approach. National policies on recording and handling of baby abandonments are urgently needed, and future efforts should be concentrated on establishing clear data collection frameworks to inform understanding, guide competent practice and enable successfully targeted interventions.

  2. Tooth formation - delayed or absent

    MedlinePlus

    ... missing teeth they never developed. Cosmetic or orthodontic dentistry can correct this problem. Causes Specific diseases can ... process. In: Dean JA, ed. McDonald and Avery's Dentistry for the Child and Adolescent . 10th ed. St. ...

  3. Absent pedicles in campomelic dysplasia.

    PubMed

    McDowell, Michael M; Dede, Ozgur; Bosch, Patrick; Tyler-Kabara, Elizabeth C

    2017-06-01

    The objective of the present study is to report a case of campomelic dysplasia illustrating the absence of cervical and thoracic pedicles. This report reiterates the importance of this clinical peculiarity in the setting of spine instrumentation. A 10-year-old female patient with campomelic dysplasia presented with progressive kyphoscoliosis and signs of neural compromise. Imaging studies confirmed thoracic level stenosis and demonstrated absence of multiple pedicles in cervical and thoracic spine. The patient underwent decompression and instrumentation/fusion for her spinal deformity. The patient was instrumented between C2 and L4 with pedicle screws and sublaminar cables. However, pedicle fixation was not possible for the lower cervical and upper-mid thoracic spine. Also, floating posterior elements precluded the use of laminar fixation in the lower cervical spine. Cervicothoracic lumbosacral orthosis (CTLSO) was used for external immobilization to supplement the tenuous fixation in the cervicothoracic area. The patient improved neurologically with no signs of implant failure at the 2-year follow-up. Absence of pedicles and floating posterior elements present a challenge during spine surgery in campomelic dysplasia. Surgeons should prepare for alternative fixation methods and external immobilization when planning on spinal instrumentation in affected patients. Level IV Case Report.

  4. Calling for the absent male.

    PubMed

    Edgar, D

    1999-08-01

    This is an edited version of a keynote address given by Dr Don Edgar at both the VicHealth Conference on 'Healthy Relationships in the Workplace' held in August 1998 and the Tasmanian Men's Health Conference held in Launceston in November 1998. Men's lack of communication skills and emotional intelligence has serious negative consequences for their own physical and mental health, the wellbeing of their families and for the quality of their performance in the workplace.

  5. Mesenchymal stem cells reside in a vascular niche in the decidua basalis and are absent in remodelled spiral arterioles.

    PubMed

    Kusuma, G D; Manuelpillai, U; Abumaree, M H; Pertile, M D; Brennecke, S P; Kalionis, B

    2015-03-01

    Maternal decidua basalis tissue attached to the placenta following delivery is a source of decidual mesenchymal stem cells (DMSCs). The in vitro characteristics of DMSCs have been partly defined but their in vivo function(s) are poorly understood. The anatomic location, or niche, provides clues regarding potential in vivo function(s) of DMSCs, but the niche has not been described. Cells were isolated from the decidua basalis and flow cytometric analyses showed the expected phenotypic profile for MSC cell surface markers. In vitro, the cells differentiated into adipocytes, osteocytes, and chondrocytes. DMSCs were then stained with antibodies by immunofluorescence detection. Immunocytochemistry revealed that DMSCs were positive for FZD-9, STRO-1, 3G5, and α-SMA as expected and lacked expression of vWF and Ck7. Fluorescence in situ hybridization analysis showed the cultured cells were of maternal origin. Immunofluorescence was carried out on placental bed biopsies using the FZD-9, STRO-1, 3G5, and α-SMA antibodies. DMSCs were located in the vascular niche in decidua basalis. Immunofluorescence with antibodies to FZD-9, Ck7 and vWF revealed DMSCs in the vascular niche surrounding intact non-transformed spiral arterioles but DMSCs were absent in fully transformed spiral arterioles. Spiral arteriole remodelling is a critical feature of human pregnancy. The DMSC niche was investigated in fully transformed and non-transformed spiral arterioles. DMSCs have not been previously implicated in spiral arteriole remodelling. The absence of DMSCs around fully transformed spiral arterioles suggests they are a target for replacement or destruction by invading placental extravillous trophoblast cells, which carry out spiral arteriole remodelling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. [Increased content of nucleotide sequences in transcriptionally active DNA and poly(A)+-mRNA of the rat liver and a rise in its translation activity as affected by inducers].

    PubMed

    Dashkevich, V S; Vishnivetskiĭ, S N; Skobel'tsina, L M; Luk'ianchikova, N L; Kaledin, V I

    1986-12-01

    Cortisol and 3'-methyl-4-dimethyl-amino-azobenzene induce an increase in the content of repeated sequences (RS) in transcriptionally active (TA) DNA, while the content of respective RS in potentially active DNA fractions enriched with regulatory regions of the genome decreases. RS content in induced poly A+-mRNA also rises, as determined by the nature of hybridization of respective c DNA with total DNA. The translation of induced poly A+-mRNA rises essentially, with the qualitative distinctions in in vitro synthesized protein product spectrum being absent. Inducible RS with unstable chromatine conformation are thought to provide a universal system of rapid response of the genetic apparatus to extreme situations, serving as transcription intensifiers in TA DNA and as translation intensifiers in induced poly A+-mRNA.

  7. Role of support afferentation in control of the tonic muscle activity

    NASA Astrophysics Data System (ADS)

    Kozlovskaya, I. B.; Sayenko, I. V.; Sayenko, D. G.; Miller, T. F.; Khusnutdinova, D. R.; Melnik, K. A.

    2007-02-01

    The paper summarizes the results of experimental studies advocating for the leading role of support afferentation in control of the functional organization of the tonic muscle system. It is shown that transition to supportless conditions is followed by a significant decline of transverse stiffness and maximal voluntary force of postural (extensor) muscles limiting their participation in locomotion and increasing involvement of phasic muscles. Mechanical stimulation of the support zones of the soles under the supportless conditions eliminates all the above-mentioned effects, including changes in transverse stiffness and maximal voluntary forces of postural muscles, and consequent loss of influence of postural muscles in the locomotor activity. It is suggested that support afferentation, facilitating (support is present) or suppressing (support is absent) the tonic motor units (MUs) activities, defines the coordination patterns of postural synergies, and ensures the optimal strategy of corrective postural responses.

  8. Exploring the limits of sequence and structure in a variant βγ-crystallin domain of the protein absent in melanoma-1 (AIM1)

    PubMed Central

    Aravind, Penmatsa; Wistow, Graeme; Sharma, Yogendra; Sankaranarayanan, Rajan

    2008-01-01

    βγ-Crystallins belong to a superfamily of proteins in prokaryotes and eukaryotes that are based on duplications of a characteristic, highly conserved Greek Key motif. Most members of the superfamily in vertebrates are structural proteins of the eye lens that contain four motifs arranged as two structural domains. Absent in melanoma-1 (AIM1), an unusual member of the superfamily whose expression is associated with suppression of malignancy in melanoma, contains 12 βγ-crystallin motifs in six domains. Some of these motifs diverge considerably from the canonical motif sequence. AIM1g1, the first βγ-crystallin domain of AIM1, is the most variant of βγ-crystallin domains currently known. In order to understand the limits of sequence variation on the structure, we report the crystal structure of AIM1g1 at 1.9Å resolution. In spite of having changes in key residues, the domain retains the overall βγ-crystallin fold. The domain also contains an unusual extended surface loop that significantly alters the shape of the domain and its charge profile. This structure illustrates the resilience of the βγ fold to considerable sequence changes and its remarkable ability to adapt for novel functions. PMID:18582473

  9. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota.

    PubMed

    Hehemann, Jan-Hendrik; Correc, Gaëlle; Barbeyron, Tristan; Helbert, William; Czjzek, Mirjam; Michel, Gurvan

    2010-04-08

    Gut microbes supply the human body with energy from dietary polysaccharides through carbohydrate active enzymes, or CAZymes, which are absent in the human genome. These enzymes target polysaccharides from terrestrial plants that dominated diet throughout human evolution. The array of CAZymes in gut microbes is highly diverse, exemplified by the human gut symbiont Bacteroides thetaiotaomicron, which contains 261 glycoside hydrolases and polysaccharide lyases, as well as 208 homologues of susC and susD-genes coding for two outer membrane proteins involved in starch utilization. A fundamental question that, to our knowledge, has yet to be addressed is how this diversity evolved by acquiring new genes from microbes living outside the gut. Here we characterize the first porphyranases from a member of the marine Bacteroidetes, Zobellia galactanivorans, active on the sulphated polysaccharide porphyran from marine red algae of the genus Porphyra. Furthermore, we show that genes coding for these porphyranases, agarases and associated proteins have been transferred to the gut bacterium Bacteroides plebeius isolated from Japanese individuals. Our comparative gut metagenome analyses show that porphyranases and agarases are frequent in the Japanese population and that they are absent in metagenome data from North American individuals. Seaweeds make an important contribution to the daily diet in Japan (14.2 g per person per day), and Porphyra spp. (nori) is the most important nutritional seaweed, traditionally used to prepare sushi. This indicates that seaweeds with associated marine bacteria may have been the route by which these novel CAZymes were acquired in human gut bacteria, and that contact with non-sterile food may be a general factor in CAZyme diversity in human gut microbes.

  10. Effect of atmospheric pressure dielectric barrier discharge plasma on the biological activity of naringin.

    PubMed

    Kim, Hyun-Joo; Yong, Hae In; Park, Sanghoo; Kim, Kijung; Kim, Tae Hoon; Choe, Wonho; Jo, Cheorun

    2014-10-01

    The biological activity of naringin treated with atmospheric pressure plasma was evaluated to investigate whether exposure to plasma can be used as a method to improve the biological activity of natural materials. Naringin was dissolved in methanol (at 500 ppm) and transferred to a container. A dielectric barrier discharge (DBD) (250 W, 15 kHz, ambient air) was then generated. Treatment with the plasma for 20 min increased the radical-scavenging activity, FRAP value, and the total phenolic compound content of naringin from 1.45% to 38.20%, from 27.78 to 207.78 μM/g, and from 172.50 to 225.83 ppm, respectively. Moreover, the tyrosinase-inhibition effect of naringin increased from 6.12% to 83.30% upon plasma treatment. Naringin treated with plasma exhibited antimicrobial activity against foodborne pathogens, especially Salmonella Typhimurium; an activity that was absent before plasma treatment. Structural modifications induced in the naringin molecule by plasma might be responsible for improving the biological activity of naringin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Novel Keto-phospholipids Are Generated by Monocytes and Macrophages, Detected in Cystic Fibrosis, and Activate Peroxisome Proliferator-activated Receptor-γ*

    PubMed Central

    Hammond, Victoria J.; Morgan, Alwena H.; Lauder, Sarah; Thomas, Christopher P.; Brown, Sarah; Freeman, Bruce A.; Lloyd, Clare M.; Davies, Jane; Bush, Andrew; Levonen, Anna-Liisa; Kansanen, Emilia; Villacorta, Luis; Chen, Y. Eugene; Porter, Ned; Garcia-Diaz, Yoel M.; Schopfer, Francisco J.; O'Donnell, Valerie B.

    2012-01-01

    12/15-Lipoxygenases (LOXs) in monocytes and macrophages generate novel phospholipid-esterified eicosanoids. Here, we report the generation of two additional families of related lipids comprising 15-ketoeicosatetraenoic acid (KETE) attached to four phosphatidylethanolamines (PEs). The lipids are generated basally by 15-LOX in IL-4-stimulated monocytes, are elevated on calcium mobilization, and are detected at increased levels in bronchoalveolar lavage fluid from cystic fibrosis patients (3.6 ng/ml of lavage). Murine peritoneal macrophages generate 12-KETE-PEs, which are absent in 12/15-LOX-deficient mice. Inhibition of 15-prostaglandin dehydrogenase prevents their formation from exogenous 15-hydroxyeicosatetraenoic acid-PE in human monocytes. Both human and murine cells also generated analogous hydroperoxyeicosatetraenoic acid-PEs. The electrophilic reactivity of KETE-PEs is shown by their Michael addition to glutathione and cysteine. Lastly, both 15-hydroxyeicosatetraenoic acid-PE and 15-KETE-PE activated peroxisome proliferator-activated receptor-γ reporter activity in macrophages in a dose-dependent manner. In summary, we demonstrate novel peroxisome proliferator-activated receptor-γ-activating oxidized phospholipids generated enzymatically by LOX and 15-prostaglandin dehydrogenase in primary monocytic cells and in a human Th2-related lung disease. The lipids are a new family of bioactive mediators from the 12/15-LOX pathway that may contribute to its known anti-inflammatory actions in vivo. PMID:23060450

  12. Novel keto-phospholipids are generated by monocytes and macrophages, detected in cystic fibrosis, and activate peroxisome proliferator-activated receptor-γ.

    PubMed

    Hammond, Victoria J; Morgan, Alwena H; Lauder, Sarah; Thomas, Christopher P; Brown, Sarah; Freeman, Bruce A; Lloyd, Clare M; Davies, Jane; Bush, Andrew; Levonen, Anna-Liisa; Kansanen, Emilia; Villacorta, Luis; Chen, Y Eugene; Porter, Ned; Garcia-Diaz, Yoel M; Schopfer, Francisco J; O'Donnell, Valerie B

    2012-12-07

    12/15-Lipoxygenases (LOXs) in monocytes and macrophages generate novel phospholipid-esterified eicosanoids. Here, we report the generation of two additional families of related lipids comprising 15-ketoeicosatetraenoic acid (KETE) attached to four phosphatidylethanolamines (PEs). The lipids are generated basally by 15-LOX in IL-4-stimulated monocytes, are elevated on calcium mobilization, and are detected at increased levels in bronchoalveolar lavage fluid from cystic fibrosis patients (3.6 ng/ml of lavage). Murine peritoneal macrophages generate 12-KETE-PEs, which are absent in 12/15-LOX-deficient mice. Inhibition of 15-prostaglandin dehydrogenase prevents their formation from exogenous 15-hydroxyeicosatetraenoic acid-PE in human monocytes. Both human and murine cells also generated analogous hydroperoxyeicosatetraenoic acid-PEs. The electrophilic reactivity of KETE-PEs is shown by their Michael addition to glutathione and cysteine. Lastly, both 15-hydroxyeicosatetraenoic acid-PE and 15-KETE-PE activated peroxisome proliferator-activated receptor-γ reporter activity in macrophages in a dose-dependent manner. In summary, we demonstrate novel peroxisome proliferator-activated receptor-γ-activating oxidized phospholipids generated enzymatically by LOX and 15-prostaglandin dehydrogenase in primary monocytic cells and in a human Th2-related lung disease. The lipids are a new family of bioactive mediators from the 12/15-LOX pathway that may contribute to its known anti-inflammatory actions in vivo.

  13. Short-term psychosocial stress protects photoreceptors from damage via corticosterone-mediated activation of the AKT pathway.

    PubMed

    Forkwa, Tembei K; Neumann, Inga D; Tamm, Ernst R; Ohlmann, Andreas; Reber, Stefan O

    2014-02-01

    Apoptotic death of photoreceptors in hereditary retinal degenerations can be prevented by neuroprotective molecules. Here, we report that adrenal glucocorticoids (GC) released during psychosocial stress protect photoreceptors from apoptosis after light damage. Psychosocial stress is known to be the main type of stressor humans are exposed to and was induced here in mice by 10h of chronic subordinate colony housing (CSC). Photoreceptor damage was generated by subsequent exposure to white light. Short-term psychosocial stress prior to illumination significantly reduced the number of apoptotic photoreceptors, an effect that was absent in adrenalectomized (ADX) mice. The neuroprotective effect was completely restored in ADX mice substituted with GC. Moreover, phosphorylation of retinal AKT increased following CSC or exogenous GC treatment, an effect that was again absent in ADX mice exposed to CSC. Finally, inhibition of AKT signaling with triciribine blocked the stress- and GC-mediated neuroprotective effects on photoreceptors. In summary, we provide evidence that 1) short-term psychosocial stress protects photoreceptors from light-induced damage and 2) the protective effect is most likely mediated by GC-induced activation of the AKT signaling pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Does processing a shallow and a deep orthography produce different brain activity patterns? An ERP study conducted in Hebrew.

    PubMed

    Bar-Kochva, Irit

    2011-01-01

    Orthographies range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Two forms of script transcribe the Hebrew language: the shallow pointed script (with diacritics) and the deep unpointed script (without diacritics). This study was set out to examine whether the reading of these scripts evokes distinct brain activity. Preliminary results indicate distinct Event-related-potentials (ERPs). As an equivalent finding was absent when ERPs of non-orthographic stimuli with and without meaningless diacritics were compared, the results imply that print-specific aspects of processing account for the distinct activity elicited by the pointed and unpointed scripts.

  15. The absent discourse of communication: understanding ethics of provider-patient relationship in six hospitals in urban India

    PubMed Central

    Ghoshal, Rakhi; Madhiwalla, Neha; Jesani, Amar; Samant, Padmaja; Badhwar, Vijaya; Surve, Sweta

    2013-01-01

    Understanding the complexities of a provider-patient relationship is considered to be of critical importance especially in medical ethics. It is important to understand this relation from the perspectives of all stakeholders. This article derives from a qualitative study conducted across six obstetric care providing institutions in the cities of Mumbai and Navi Mumbai, India, over a period of 10 months. Thirty obstetricians were interviewed in-depth to understand what they perceived as the most important aspect in developing a good provider-patient relationship. The study found that while most providers highlighted the point of communication as the most critical part of the provider-patient relationship, they admitted that they could not engage in communication with the patients for various reasons. Obstetric consultants and residents said that they were too overburdened to spend time communicating with patients; providers working in public hospitals added that the lack of education of their patients posed a hindrance in effective communication. However, providers practicing in private institutions explained that they faced a challenge in communicating with patients because their patients came from educated families who tended to trust the provider less and were generally more critical of the provider’s clinical judgement. The article shows how provider-patient communication exists as an idea among medical providers but is absent in daily clinical practice. This gives rise to a discourse shaped around an absence. The authors conclude by decoding the term ‘communication’ – they read the word against the context of its use in the interviews, and argue that for the providers ‘communication’ was not intended to be a trope towards setting up a dialogue-based, egalitarian provider-patient relationship. Providers used the word in lieu of ‘counselling’, ‘guiding’, ‘talking to’. It concludes that, despite the providers’ insisting on the

  16. Long-term outcome of cataract surgery in patients with idiopathic hypoparathyroidism and its relationship with their calcemic status.

    PubMed

    Saha, Soma; Gantyala, Shiva Prasad; Aggarwal, Sameer; Sreenivas, Vishnubhatla; Tandon, Radhika; Goswami, Ravinder

    2017-07-01

    Cataract is a cardinal manifestation of hypoparathyroidism. Although patients with hypoparathyroidism require cataract surgery at a younger age than individuals without hypoparathyroidism, there is limited information on the outcome of this surgery. We assessed long-term complications of cataract surgery in patients with idiopathic hypoparathyroidism (IH) and its relationship with their clinical and biochemical parameters. Twenty-seven patients with IH and 25 nonhypoparathyroid controls with a minimum follow-up of 2 years after cataract surgery were assessed for visual acuity, intraocular pressure, lens centricity, Nd:YAG laser capsulotomy, and the severity of posterior capsular opacification (PCO) and anterior capsular opacification. High-resolution optical slit-lamp images were analyzed by an ophthalmologist. Patients with IH had cataract surgery at a younger age than controls (34.0 ± 16.4 years vs 58.0 ± 11.2 years, P < 0.001). A higher proportion of IH patients had dense white PCO (75.0 % vs 39.4 %, P = 0.004), Nd:YAG laser capsulotomy (44.2 % vs 10.0 %, P = 0.001), anterior capsular opacification (97.7 % vs 84.2 %, P = 0.03), and a decentric lens (28.3% vs 2.6 %, P = 0.001) at a comparable time after surgery (8.6 ± 6.1 years vs 8.7 ± 6.8 years, P = 0.85). On regression analysis, the severity of PCO in IH correlated only with male sex and not with other factors, including serum total calcium and inorganic phosphorus levels at the baseline and during follow-up. To conclude, patients with IH are likelier than individuals without IH to develop PCO and to require Nd:YAG laser capsulotomy after cataract surgery. Proper precautions should be taken during surgery to minimize this complication in IH.

  17. Release phenomena and iterative activities in psychiatric geriatric patients

    PubMed Central

    Villeneuve, A.; Turcotte, J.; Bouchard, M.; Côté, J. M.; Jus, A.

    1974-01-01

    This survey was undertaken to assess the frequency of some of the so-called release phenomena and iterative activities in an aged psychiatric population. Three groups of geriatric psychiatric patients with diagnoses of (I) organic brain syndrome, including senile dementia (56), (II) functional psychoses, predominantly schizophrenia (51) and (III) chronic schizophrenia never treated by neuroleptics or other biologic agents (16), were compared with (IV) a control group of 32 elderly people in good physical and mental health. In general, for the manifestations studied, the geriatric psychiatric patients suffering from an organic brain syndrome and treated with neuroleptics differed notably from the control group. This latter group, although older, had few neurological signs of senescence and the spontaneous oral movements usually associated with the use of neuroleptics were absent. Release phenomena such as the grasp and pouting reflexes, as well as the stereotyped activities, were encountered significantly more frequently in patients with an organic brain syndrome than in the two other groups of patients. Our survey has yielded limited results with regard to the possible influence of type of illness and neuroleptic treatment on the incidence of release phenomena and iterative activities. PMID:4810188

  18. Species-specific calls evoke asymmetric activity in the monkey's temporal poles.

    PubMed

    Poremba, Amy; Malloy, Megan; Saunders, Richard C; Carson, Richard E; Herscovitch, Peter; Mishkin, Mortimer

    2004-01-29

    It has often been proposed that the vocal calls of monkeys are precursors of human speech, in part because they provide critical information to other members of the species who rely on them for survival and social interactions. Both behavioural and lesion studies suggest that monkeys, like humans, use the auditory system of the left hemisphere preferentially to process vocalizations. To investigate the pattern of neural activity that might underlie this particular form of functional asymmetry in monkeys, we measured local cerebral metabolic activity while the animals listened passively to species-specific calls compared with a variety of other classes of sound. Within the superior temporal gyrus, significantly greater metabolic activity occurred on the left side than on the right, only in the region of the temporal pole and only in response to monkey calls. This functional asymmetry was absent when these regions were separated by forebrain commissurotomy, suggesting that the perception of vocalizations elicits concurrent interhemispheric interactions that focus the auditory processing within a specialized area of one hemisphere.

  19. Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size.

    PubMed

    Li, Junhui; Li, Shan; Yan, Lufeng; Ding, Tian; Linhardt, Robert J; Yu, Yanlei; Liu, Xinyue; Liu, Donghong; Ye, Xingqian; Chen, Shiguo

    2017-10-20

    Fucosylated chondroitin sulfates (fCSs) are structurally unusual glycosaminoglycans isolated from sea cucumbers that exhibit potent anticoagulant activity. These fCSs were isolated from sea cucumber, Isostichopus badionotus and Pearsonothuria graeffei. Fenton reaction followed by gel filtration chromatography afforded fCS oligosaccharides, with different sulfation patterns identified by mass and NMR spectroscopy, and these were used to clarify the relationship between the structures and the anticoagulant activities of fCSs. In vitro activities were measured by activated partial thromboplastin time (APTT), thrombin time (TT), thrombin and factor Xa inhibition, and activation of FXII. The results showed that free radicals preferentially acted on GlcA residues affording oligosaccharides that were purified from both fCSs. The inhibition of thrombin and factor X activities, mediated through antithrombin III and heparin cofactor II of fCSs oligosaccharides were affected by their molecular weight and fucose branches. Oligosaccharides with different sulfation patterns of the fucose branching had a similar ability to inhibit the FXa by the intrinsic factor Xase (factor IXa-VIIIa complex). Oligosaccharides with 2,4-O-sulfo fucose branches from fCS-Ib showed higher activities than ones with 3,4-O-disulfo branches obtained from fCS-Pg. Furthermore, a heptasaccharide is the minimum size oligosaccharide required for anticoagulation and FXII activation. This activity was absent for fCS oligosaccharides smaller than nonasaccharides. Molecular size and fucose branch sulfation are important for anticoagulant activity and reduction of size can reverse the activation of FXII caused by native fCSs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Recent Uptrend in Whole-Grain Intake Is Absent for Low-Income Adolescents, National Health and Nutrition Examination Survey, 2005-2012.

    PubMed

    Tester, June M; Leung, Cindy W; Leak, Tashara M; Laraia, Barbara A

    2017-07-06

    Whole-grain consumption reduces risk of chronic disease, yet adolescents consume suboptimal amounts. It is unclear whether trends in consumption of whole grains have been positive among adolescents, and research assessing disparities by socioeconomic status is limited. The objective of our study was to evaluate recent trends in whole-grain consumption by US adolescents. We examined data on 3,265 adolescents aged 13 to18 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2012. Intake of whole and refined grains was analyzed by using generalized linear models, and odds of no whole-grain intake were examined with logistic regression, adjusting for socioeconomic and demographic factors. We evaluated trends and examined heterogeneity of trends with respect to annual household income. Daily whole-grain consumption among adolescents increased overall by about a quarter-ounce-equivalent per day (oz-eq/d) (P trend <.001). We found a significant relationship between whole-grain intake and income. Daily whole grains (recommended as ≥3 oz-eq/d), increased (0.6 to 1.0 oz-eq/d) among high-income adolescents (P trend < .001) but remained at 0.5 oz-eq/d for low-income adolescents. The ratio of whole grains to total grains (recommended to be at least 50%) rose from 7.6% to 14.2% for high-income adolescents (P trend < .001), with no significant trend for the low-income group. Consumption of refined grains did not change. Odds of having no whole grains trended downward, but only for the high-income adolescents (P trend = .01). These data show significant (albeit modest) trends toward increased intake of whole grains among high-income adolescents nationwide that are absent among low-income peers. Future interventions and policies should address barriers to whole-grain consumption among this vulnerable group.

  1. Synergistic Antileukemic Activity of Carnosic Acid-Rich Rosemary Extract and the 19-nor Gemini Vitamin D Analogue in a Mouse Model of Systemic Acute Myeloid Leukemia

    PubMed Central

    Shabtay, Ayelet; Sharabani, Hagar; Barvish, Zeev; Kafka, Michael; Amichay, Doron; Levy, Joseph; Sharoni, Yoav; Uskokovic, Milan R.; Studzinski, George P.; Danilenko, Michael

    2008-01-01

    Objective Differentiation therapy with the hormonal form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), is a promising approach to treatment of acute myeloid leukemia (AML); however, 1,25D3 induces hypercalcemia at pharmacologically active doses. We investigated the in vitro and in vivoantileukemic efficacy of combined treatment with non-toxic doses of a low-calcemic 1,25D3 analogue, 1,25-dihydroxy-21(3-hydroxy-3-methyl-butyl)-19-nor-cholecalciferol (19-nor-Gemini; Ro27-5646), and rosemary plant agents in a mouse model of AML. Methods Proliferation and differentiation of WEHI-3B D– (WEHI) murine myelomonocytic leukemia cellsin vitro were determined by standard assays. Reactive oxygen species, glutathione and protein expression levels were measured by flow cytometry, enzymatic assay and Western blotting, respectively. Systemic AML was developed by intravenous injection of WEHI cells in syngeneic Balb/c mice. Results 19-nor-Gemini had a higher potency than its parent compounds, Gemini (Ro27-2310) and 1,25D3, in the induction of differentiation (EC50 = 0.059 ± 0.011, 0.275 ± 0.093 and 0.652 ± 0.085 nM, respectively) and growth arrest (IC50 = 0.072 ± 0.018, 0.165 ± 0.061 and 0.895 ± 0.144 nM, respectively) in WEHI cells in vitro, and lower in vivo toxicity. Combined treatment of leukemia-bearing mice with 19-nor-Gemini (injected intraperitoneally) and standardized rosemary extract (mixed with food) resulted in a synergistic increase in survival (from 42.2 ± 2.5 days in untreated mice to 66.5 ± 4.2 days, n = 3) and normalization of white blood cell and differential counts. This was consistent with strong cooperative antiproliferative and differentiation effects of low concentrations of 19-nor-Gemini or 1,25D3 combined with rosemary extract or its major polyphenolic component, carnosic acid, as well as with the antioxidant action of rosemary agents and vitamin D derivatives in WEHI cell cultures. Conclusion Combined effectiveness of 1,25D3 analogues and

  2. Counseling activity in single-session online counseling with adolescents: an adherence study.

    PubMed

    Chardon, Lydia; Bagraith, Karl S; King, Robert John

    2011-09-01

    While online counseling is increasingly utilized, little is known about what counseling work takes place in the online environment. The aim of this study was to quantify online counseling activity by determining counselors' adherence to the widely used model in which they had been trained. Transcripts (n=85) of online counseling with adolescents were evaluated, using a standardized and psychometrically sound instrument. We found that, while counseling in 53% of transcripts progressed through each of the key stages of counseling, the focus of most sessions was information gathering; and goal exploration and action planning were typically superficial and often absent. Possible reasons for low counseling depth are discussed and recommendations made for the further development of online counseling.

  3. Activation of multiple pH-regulatory pathways in granulocytes by a phosphotyrosine phosphatase antagonist.

    PubMed Central

    Bianchini, L; Nanda, A; Wasan, S; Grinstein, S

    1994-01-01

    Activated phagocytes undergo a massive burst of metabolic acid generation, yet must be able to maintain their cytosolic pH (pHi) within physiological limits. Peroxides of vanadate (V(4+)-OOH), potent inhibitors of phosphotyrosine phosphatases, have recently been shown to produce activation of the respiratory burst in HL60 granulocytes. We therefore investigated the effects of V(4+)-OOH on pHi homoeostasis in HL60 granulocytes, using a pH-sensitive fluorescent dye. V(4+)-OOH stimulation induced a biphasic pH change: a transient cytosolic acidification followed by a significant alkalinization. The initial acidification was prevented by inhibition of the NADPH oxidase and was absent in undifferentiated cells lacking oxidase activity. Analysis of the alkalinization phase demonstrated the involvement of the Na+/H+ antiporter, and also provided evidence for activation of two alternative H(+)-extrusion pathways: a bafilomycin-sensitive component, likely reflecting vacuolar-type H(+)-ATPase activity, and a Zn(2+)-sensitive H(+)-conductive pathway. Our results indicate that V(4+)-OOH stimulation not only activated the NADPH oxidase but concomitantly stimulated H(+)-extrusion pathways, enabling the cells to compensate for the massive production of intracellular H+ associated with the respiratory burst. PMID:8043000

  4. Periosteal BMP2 activity drives bone graft healing.

    PubMed

    Chappuis, Vivianne; Gamer, Laura; Cox, Karen; Lowery, Jonathan W; Bosshardt, Dieter D; Rosen, Vicki

    2012-10-01

    Bone graft incorporation depends on the orchestrated activation of numerous growth factors and cytokines in both the host and the graft. Prominent in this signaling cascade is BMP2. Although BMP2 is dispensable for bone formation, it is required for the initiation of bone repair; thus understanding the cellular mechanisms underlying bone regeneration driven by BMP2 is essential for improving bone graft therapies. In the present study, we assessed the role of Bmp2 in bone graft incorporation using mice in which Bmp2 has been removed from the limb prior to skeletal formation (Bmp2(cKO)). When autograft transplantations were performed in Bmp2cKO mice, callus formation and bone healing were absent. Transplantation of either a vital wild type (WT) bone graft into a Bmp2(cKO) host or a vital Bmp2(cKO) graft into a WT host also resulted in the inhibition of bone graft incorporation. Histological analyses of these transplants show that in the absence of BMP2, periosteal progenitors remain quiescent and healing is not initiated. When we analyzed the expression of Sox9, a marker of chondrogenesis, on the graft surface, we found it significantly reduced when BMP2 was absent in either the graft itself or the host, suggesting that local BMP2 levels drive periosteal cell condensation and subsequent callus cell differentiation. The lack of integrated healing in the absence of BMP2 was not due to the inability of periosteal cells to respond to BMP2. Healing was achieved when grafts were pre-soaked in rhBMP2 protein, indicating that periosteal progenitors remain responsive in the absence of BMP2. In contrast to the requirement for BMP2 in periosteal progenitor activation in vital bone grafts, we found that bone matrix-derived BMP2 does not significantly enhance bone graft incorporation. Taken together, our data show that BMP2 signaling is not essential for the maintenance of periosteal progenitors, but is required for the activation of these progenitors and their subsequent

  5. Absent mandibular gap in the retronasal triangle view: a clue to the diagnosis of micrognathia in the first trimester.

    PubMed

    Sepulveda, W; Wong, A E; Viñals, F; Andreeva, E; Adzehova, N; Martinez-Ten, P

    2012-02-01

    To describe a new ultrasound technique that may be useful for the diagnosis of micrognathia in the first trimester of pregnancy. The retronasal triangle (RNT) view is a technique that captures the coronal plane of the face in which the primary palate and the frontal processes of the maxilla are visualized simultaneously. Normal first-trimester fetuses display a characteristic gap between the right and left body of the mandible in this view (the 'mandibular gap'). The presence or absence of this gap was evaluated and measured prospectively during real-time scanning (n = 154) and retrospectively by analyzing three-dimensional (3D) datasets (n = 50) in normal first-trimester fetuses undergoing screening for aneuploidy at 11-13 weeks' gestation. 3D datasets from 12 fetuses with suspected micrognathia were also collected and examined retrospectively for the same features. The mandibular gap was identified in all 204 normal fetuses and increased linearly with increasing crown-rump length (y = 0.033x + 0.435; R(2) = 0.316), with no statistically significant differences between measurements obtained by two-dimensional ultrasound and 3D offline analysis. Among fetuses with suspected micrognathia, three 3D datasets were excluded from analysis because of poor image quality in one and the diagnosis of a normal chin in two. In the remaining nine fetuses, the mandibular gap was absent and was replaced by a bony structure representing the receding chin in seven (77.8%) cases and was not visualized due to severe retrognathia in the remaining two (22.2%) cases. All fetuses with micrognathia had associated anomalies, including seven with aneuploidy and two with skeletal dysplasia. The RNT view may be a helpful technique for detecting micrognathia in the first trimester. The absence of the mandibular gap or failure to identify the mandible in this view is highly suggestive of micrognathia and should prompt a targeted ultrasound scan to assess for other anomalies. Further research is

  6. What Makes Red Giants Tick? Linking Tidal Forces, Activity, and Solar-Like Oscillations via Eclipsing Binaries

    NASA Astrophysics Data System (ADS)

    Rawls, Meredith L.; Gaulme, Patrick; McKeever, Jean; Jackiewicz, Jason

    2016-01-01

    Thanks to advances in asteroseismology, red giants have become astrophysical laboratories for studying stellar evolution and probing the Milky Way. However, not all red giants show solar-like oscillations. It has been proposed that stronger tidal interactions from short-period binaries and increased magnetic activity on spotty giants are linked to absent or damped solar-like oscillations, yet each star tells a nuanced story. In this work, we characterize a subset of red giants in eclipsing binaries observed by Kepler. The binaries exhibit a range of orbital periods, solar-like oscillation behavior, and stellar activity. We use orbital solutions together with a suite of modeling tools to combine photometry and spectroscopy in a detailed analysis of tidal synchronization timescales, star spot activity, and stellar evolution histories. These red giants offer an unprecedented opportunity to test stellar physics and are important benchmarks for ensemble asteroseismology.

  7. Expression of Active Notch1 in Avian Coronary Development

    PubMed Central

    Yang, Ke; Doughman, Yong-Qiu; Karunamuni, Ganga; Gu, Shi; Yang, Yu-Chung; Bader, David M.; Watanabe, Michiko

    2010-01-01

    Notch1 is an important regulator of intercellular interactions in cardiovascular development. We show that the nuclear-localized, cleaved and active form of Notch1, the Notch1 intracellular domain (N1ICD), appeared in mesothelial cells of the pro-epicardium during epicardial formation at looped heart stages. N1ICD was also present in mesothelial cells and mesenchymal cells specifically within the epicardium at sulcus regions. N1ICD-positive endothelial cells were detected within the nascent vessel plexus at the atrio-ventricular junction and within the compact myocardium (HH25-30). The endothelial cells expressing N1ICD were surrounded by N1ICD positive smooth muscle cells after coronary orifice formation (HH32-35), while N1ICD expression was absent in the mesenchymal and mesothelial cells surrounding mature coronary vessels. We propose that differential activation of the hypoxia/HIF1-VEGF-Notch pathway may play a role in epicardial cell interactions that promote epicardial EMT and coronary progenitor cell differentiation during epicardial development and coronary vasculogenesis in particularly hypoxic sulcus regions. PMID:19097050

  8. Impact of definition and procedures used for absent blood culture data on the rate of intravascular catheter infection during parenteral nutrition.

    PubMed

    Austin, P D; Hand, K S; Elia, M

    2016-06-01

    Diagnosis of intravascular catheter infection may be affected by the definition and procedures applied in the absence of blood culture data. To examine the extent to which different definitions of catheter infection and procedures for handling absent blood culture data can affect reported catheter infection rates. Catheter infection rates were established in a cohort of hospitalized patients administered parenteral nutrition according to three clinical and four published definitions. Paired and unpaired comparisons were made using available case analyses, sensitivity analyses and intention-to-categorize analyses. Complete data were available for each clinical definition (N = 193), and there were missing data (4.1-26.9%) for the published definitions. In an available case analysis, the catheter infection rate was 13.0-36.8% for the clinical definitions and 2.1-12.4% for the published definitions. For the published definitions, the rate was 1.6-32.1% in a sensitivity analysis and 11.4-16.9% in an intention-to-categorize analysis, with suggestion of bias towards a higher catheter infection rate in those with missing data, in keeping with the analyses of the clinical definitions. For paired comparisons, the strength of agreement between definitions varied from 'poor' (Cohen's kappa <0.21) to 'very good' (Cohen's kappa ≥0.81). The use of different definitions of catheter infection and procedures applied in the absence of blood culture data produced widely different catheter infection rates, which could compromise measurements or comparisons of service quality or study outcome. As such, there is a need to establish and use a valid, consistent and practical definition. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  9. [Exaggerated somatomedin activity in the Beckwith-Wiedemann syndrome (author's transl)].

    PubMed

    Schabel, F; Frisch, H

    1979-01-01

    Beckwith and Wiedemann described the syndrome of exomphalos, macroglossia and gigantism with hypoglycemia and visceral organ hyperplasias. In some cases of severe hypoglycemias hyperplasia of beta cells of the pancreas was found. Hyperinsulinism, which has to date rarely been investigated, reacts strongly to beta cell stimulation and can hardly be suppressed. The cause of gigantism and organ hyperplasias is still unknown. After a short description of a case of hypoglycemias in the first two weeks of life a long-term profile of the endocrinologic abnormalities and carbohydrate metabolism is given. Growth hormone response to insulin is normal, tolbutamide is followed by severe hypoglycemias without an increase in the immunoreactive insulin levels; the activity of somatomedin is excessively increased. The high activity of somatomedin explains the high potency of growth in the different tissues and the hypoglycemic reactions and it seems reasonable to assume that somatomedin could create nesidioblastosis of the pancreas with hyperinsulinism and severe hypoglycemias. It is likely that the Beckwith-Wiedemann syndrome and the Laron type familial dwarfism with high plasma growth hormone, absent activity of somatomedin, and disorders in carbohydrate metabolism represent complementary diseases.

  10. Aberrant promoter hypermethylation of PBRM1, BAP1, SETD2, KDM6A and other chromatin-modifying genes is absent or rare in clear cell RCC

    PubMed Central

    Ibragimova, Ilsiya; Maradeo, Marie E.; Dulaimi, Essel; Cairns, Paul

    2013-01-01

    Recent sequencing studies of clear cell (conventional) renal cell carcinoma (ccRCC) have identified inactivating point mutations in the chromatin-modifying genes PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2 and BAP1. To investigate whether aberrant hypermethylation is a mechanism of inactivation of these tumor suppressor genes in ccRCC, we sequenced the promoter region within a bona fide CpG island of PBRM1, KDM6A, SETD2 and BAP1 in bisulfite-modified DNA of a representative series of 50 primary ccRCC, 4 normal renal parenchyma specimens and 5 RCC cell lines. We also interrogated the promoter methylation status of KDM5C and ARID1A in the Cancer Genome Atlas (TCGA) ccRCC Infinium data set. PBRM1, KDM6A, SETD2 and BAP1 were unmethylated in all tumor and normal specimens. KDM5C and ARID1A were unmethylated in the TCGA 219 ccRCC and 119 adjacent normal specimens. Aberrant promoter hypermethylation of PBRM1, BAP1 and the other chromatin-modifying genes examined here is therefore absent or rare in ccRCC. PMID:23644518

  11. Toward understanding the active SETI debate: Insights from risk communication and perception

    NASA Astrophysics Data System (ADS)

    Korbitz, Adam

    2014-12-01

    Insights from the robust field of risk communication and perception have to date been almost totally absent from the policy debate regarding the relative risks and merits of Active SETI or Messaging to Extraterrestrial Intelligence (METI). For many years, the practice (or proposed practice) of Active SETI has generated a vigorous and sometimes heated policy debate within the scientific community. There have also been some negative reactions in the media toward the activities of those engaged in Active SETI. Risk communication is a scientific approach to communication regarding situations involving potentially sensitive or controversial situations in which there may be high public concern and low public trust. The discipline has found wide acceptance and utility in fields such as public health, industrial regulation and environmental protection. Insights from the scientific field of risk communication (such as omission bias, loss aversion, the availability heuristic, probability neglect, and the general human preference for voluntary over involuntary risks) may help those who have participated in either side of the debate over Active SETI to better understand why the debate has taken on this posture. Principles of risk communication and risk perception may also help those engaged in Active SETI to communicate more effectively with other scientists, the public, with the media, and with policy makers regarding their activities and to better understand and respond to concerns expressed regarding the activity.

  12. Activated Rho Kinase Mediates Diabetes-Induced Elevation of Vascular Arginase Activation and Contributes to Impaired Corpora Cavernosa Relaxation: Possible Involvement of p38 MAPK Activation

    PubMed Central

    Nunes, Kenia P.; Yao, Lin; Liao, James K.; Webb, R. Clinton; Caldwell, Ruth B.; Caldwell, R. William

    2013-01-01

    Introduction Activated RhoA/Rho kinase (ROCK) has been implicated in diabetes-induced erectile dysfunction. Earlier studies have demonstrated involvement of ROCK pathway in the activation of arginase in endothelial cells. However, signaling pathways activated by ROCK in the penis remain unclear. Aim We tested whether ROCK and p38 MAPK are involved in the elevation of arginase activity and subsequent impairment of corpora cavernosal (CC) relaxation in diabetes. Methods Eight weeks after streptozotocin-induced diabetes, vascular functional studies, arginase activity assay, and protein expression of RhoA, ROCK, phospho-p38 MAPK, p38 MAPK, phospho-MYPT-1Thr850, MYPT-1 and arginase levels were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT + D), partial ROCK 2+/− knockout (KO), and ROCK 2+/− KO + D mice. Main Outcome Measures The expression of RhoA, ROCK 1 and 2, phosphorylation of MYPT-1Thr850 and p38 MAPK, arginase activity/expression, endothelial- and nitrergic-dependent relaxation of CC was assayed. Results Diabetes significantly reduced maximum relaxation (Emax) to both endothelium-dependent acetylcholine (WT + D: Emax; 61 ± 4% vs. WT: Emax; 75 ± 2%) and nitrergic nerve stimulation. These effects were associated with increased expression of active RhoA, ROCK 2, phospho-MYPT-1Thr850, phospho-p38 MAPK, arginase II, and activity of corporal arginase (1.6-fold) in WT diabetic CC. However, this impairment in CC of WT + D mice was absent in heterozygous ROCK 2+/− KO + D mice for acetylcholine (Emax: 80 ± 5%) and attenuated for nitrergic nerve-induced relaxation. CC of ROCK 2+/− KO + D mice showed much less ROCK activity, did not exhibit p38 MAPK activation, and had reduced arginase activity and arginase II expression. These findings indicate that ROCK 2 mediates diabetes-induced elevation of arginase activity. Additionally, pretreatment of WT diabetic CC with inhibitors of arginase (ABH) or p38 MAPK (SB203580) partially prevented

  13. Purkinje cell-specific males absent on the first (mMof) gene deletion results in an ataxia-telangiectasia-like neurological phenotype and backward walking in mice

    PubMed Central

    Kumar, Rakesh; Hunt, Clayton R.; Gupta, Arun; Nannepaga, Suraj; Pandita, Raj K.; Shay, Jerry W.; Bachoo, Robert; Ludwig, Thomas; Burns, Dennis K.; Pandita, Tej K.

    2011-01-01

    The brains of ataxia telangiectasia (AT) patients display an aberrant loss of Purkinje cells (PCs) that is postulated to contribute to the observed deficits in motor coordination as well as in learning and cognitive function. AT patients have mutations in the ataxia telangiectasia mutated (ATM) gene [Savitsky et al. (1995) Science 268:1749–1753]. However, in Atm-deficient mice, the neurological defects are limited, and the PCs are not deformed or lost as observed in AT patients [Barlow et al. (1996) Cell 86:159–171]. Here we report that PC-specific deletion of the mouse males absent on the first (mMof) gene (Cre−), which encodes a protein that specifically acetylates histone H4 at lysine 16 (H4K16ac) and influences ATM function, is critical for PC longevity. Mice deficient for PC-specific Mof display impaired motor coordination, ataxia, a backward-walking phenotype, and a reduced life span. Treatment of MofF/F/Pcp2-Cre+ mice with histone deacetylase inhibitors modestly prolongs PC survival and delays death. Therefore, Mof expression and H4K16 acetylation are essential for PC survival and function, and their absence leads to PC loss and cerebellar dysfunction similar to that observed in AT patients. PMID:21321203

  14. P-glycoprotein ATPase activity requires lipids to activate a switch at the first transmission interface.

    PubMed

    Loo, Tip W; Clarke, David M

    2016-04-01

    P-glycoprotein (P-gp) is an ABC (ATP-Binding Cassette) drug pump. A common feature of ABC proteins is that they are organized into two wings. Each wing contains a transmembrane domain (TMD) and a nucleotide-binding domain (NBD). Drug substrates and ATP bind at the interface between the TMDs and NBDs, respectively. Drug transport involves ATP-dependent conformational changes between inward- (open, NBDs far apart) and outward-facing (closed, NBDs close together) conformations. P-gps crystallized in the presence of detergent show an open structure. Human P-gp is inactive in detergent but basal ATPase activity is restored upon addition of lipids. The lipids might cause closure of the wings to bring the NBDs close together to allow ATP hydrolysis. We show however, that cross-linking the wings together did not activate ATPase activity when lipids were absent suggesting that lipids may induce other structural changes required for ATPase activity. We then tested the effect of lipids on disulfide cross-linking of mutants at the first transmission interface between intracellular loop 4 (TMD2) and NBD1. Mutants L443C/S909C and L443C/R905C but not G471C/S909C and V472C/S909C were cross-linked with oxidant when in membranes. The mutants were then purified and cross-linked with or without lipids. Mutants G471C/S909C and V472C/S909C cross-linked only in the absence of lipids whereas mutants L443C/S909C and L443C/R905C were cross-linked only in the presence of lipids. The results suggest that lipids activate a switch at the first transmission interface and that the structure of P-gp is different in detergents and lipids. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Increased osteoblastic activity and expression of receptor activator of NF-kappaB ligand in nonuremic nephrotic syndrome.

    PubMed

    Freundlich, Michael; Alonzo, Evelyn; Bellorin-Font, Ezequiel; Weisinger, Jose R

    2005-07-01

    Patients with nephrotic syndrome (NS), even with normal GFR, often display altered mineral homeostasis and abnormal bone histology. However, the latter, mostly osteomalacia and increased bone resorption, cannot be readily explained by the prevalent concentrations of parathyroid hormone and vitamin D metabolites. The transmembrane receptor activator of NF-kappaB ligand (RANKL) of osteoblasts is essential for osteoclast formation and differentiation. Osteoblasts activity and the expression of RANKL were tested in cultures of normal human osteoblasts with sera obtained from patients with NS and normal GFR (129 +/- 26 ml/min per 1.73 m2) during relapse and remission of their NS. Osteoblasts that were cultured in vitro with sera during relapse displayed elevated concentrations of alkaline phosphatase (AP) and increased expression of RANKL. By contrast, during remission, AP concentrations were significantly lower (P < 0.05) and RANKL expression notably attenuated or absent. AP correlated with the proteinuria (r = 0.5, P < 0.05) and was not significantly affected by the therapeutic administration of corticosteroids. Whereas parathyroid hormone levels were normal (35 +/- 21 pg/ml), the serum markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) were lower during relapse compared with remission. Thus, sera from patients with NS and normal GFR stimulate the activity of osteoblasts and upregulate their expression of RANKL. These alterations, more prominent during clinically active NS, are transient and reversible upon remission. These disturbances of bone biology may play an important pathogenic role in the abnormal bone histology observed in patients with NS even before a decline in GFR occurs.

  16. EVOKED CAVERNOUS ACTIVITY: NEUROANATOMIC IMPLICATIONS

    PubMed Central

    Yilmaz, Ugur; Vicars, Brenda; Yang, Claire C.

    2013-01-01

    We investigated the autonomic innervation of the penis by using evoked cavernous activity (ECA). We recruited 7 males with thoracic spinal cord injury (SCI) and sexual dysfunction and 6 males who were scheduled to have pelvic surgery (PS), specifically non-nerve-sparing radical cystoprostatectomy. In the PS subjects, ECA was performed both pre- and postoperatively. The left median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into the right and left cavernous bodies. We simultaneously recorded hand and foot sympathetic skin responses (SSRs) as controls. In the SCI group, all but one subject had reproducible hand SSRs. None of these subjects had ECA or foot SSRs. All the PS subjects had reproducible ECA and SSRs, both preoperatively and postoperatively. There was no difference in the latency and amplitude measurements of ECA and SSRs in the postoperative compared to the preoperative period (p>0.05). In conclusion, ECA is absent in men with SCI above the sympathetic outflow to the genitalia. In men following radical pelvic surgery, ECA is preserved, indicating the preservation of sympathetic fibers. PMID:19609298

  17. Comparison of developmental gradients for growth, ATPase, and fusicoccin-binding activity in mung bean hypocotyls

    NASA Technical Reports Server (NTRS)

    Basel, L. E.; Cleland, R. E.

    1992-01-01

    A comparison has been made of the developmental gradients along a mung bean (Vigna radiata L.) hypocotyl of the growth rate, plasma membrane ATPase, and fusicoccin-binding protein (FCBP) activity to determine whether they are interrelated. The hook and four sequential 7.5 millimeter segments of the hypocotyl below the hook were cut. A plasma membrane-enriched fraction was isolated from each section by aqueous two-phase partitioning and assayed for vanadate-sensitive ATPase and FCBP activity. Each gradient had a distinctive and different pattern. Endogenous growth rate was maximal in the second section and much lower in the others. Vanadate-sensitive ATPase activity was maximal in the third section, but remained high in the older sections. Amounts of ATPase protein, shown by specific antibody binding, did not correlate with the amount of vanadate-sensitive ATPase activity in the three youngest sections. FCBP activity was almost absent in the first section, then increased to a maximum in the oldest sections. These data show that the growth rate is not determined by the ATPase activity, and that there are no fixed ratios between the ATPase and FCBP.

  18. Infant Development in Father-Absent Families.

    ERIC Educational Resources Information Center

    Pedersen, Frank A.; And Others

    1979-01-01

    Father role in infancy was examined through a comparison of the stimulus responses of 27 infants reared by their mothers in single-parent families with the stimulus responses of 28 infants in father-present families. (CM)

  19. Absent virtues: the poacher becomes gamekeeper.

    PubMed

    Koch, T

    2003-12-01

    Since its inception, bioethics' principled stance has been to argue against paternalism and elitism, and for an inclusive ethical perspective. But at least in North America, the growth of bioethics as a special area of applied ethics has created conflicts within the field itself. Those who, a generation earlier, argued against paternalism and for both professional and public accountability in medical decision making are now part of the decision making process. Too often, it is argued in this paper, their allegiance is to the employer, or to a view of medicine that is institutionally based. As a result, it is suggested by this review, medical ethicists have adopted the perspective that, in the early 1970s, they most criticised. The answer, it is argued here, is to revisit a lexicographical ordering of responsibility in bioethics, one that recognises professionals as individuals with responsibilities, as citizens with a public posture, and finally, as professionals involved in the process of medical decision making.

  20. Absent virtues: the poacher becomes gamekeeper

    PubMed Central

    Koch, T

    2003-01-01

    Since its inception, bioethics' principled stance has been to argue against paternalism and elitism, and for an inclusive ethical perspective. But at least in North America, the growth of bioethics as a special area of applied ethics has created conflicts within the field itself. Those who, a generation earlier, argued against paternalism and for both professional and public accountability in medical decision making are now part of the decision making process. Too often, it is argued in this paper, their allegiance is to the employer, or to a view of medicine that is institutionally based. As a result, it is suggested by this review, medical ethicists have adopted the perspective that, in the early 1970s, they most criticised. The answer, it is argued here, is to revisit a lexicographical ordering of responsibility in bioethics, one that recognises professionals as individuals with responsibilities, as citizens with a public posture, and finally, as professionals involved in the process of medical decision making. PMID:14662812

  1. Fluid-absent metamorphism in the Adirondacks

    NASA Technical Reports Server (NTRS)

    Valley, J. W.

    1986-01-01

    Results on late Proterozoic metamorphism of granulite in the Adirondacks are presented. There more than 20,000 sq km of rock are at granulite facies. Low water fugacites are implied by orthopyroxene bearing assemblages and by stability of k'spar-plag-quartz assemblages. After mentioning the popular concept of infiltration of carbon dioxide into Precambrian rocks and attendent generation of granulite facies assemblages, several features of Adirondack rocks pertinent to carbon dioxide and water during their metamorphism are summarized: wollastonite occurs in the western lowlands; contact metamorphism by anorthosite preceeding granulite metamorphism is indicated by oxygen isotopes. Oxygen fugacity lies below that of the QFM buffer; total P sub water + P sub carbon dioxide determined from monticellite bearing assemblages are much less than P sub total (7 to 7.6 kb). These and other features indicate close spatial association of high- and low-P sub carbon dioxide assemblages and that a vapor phase was not present during metamorphism. Thus Adirondack rocks were not infiltrated by carbon dioxide vapor. Their metamorphism, at 625 to 775 C, occurred either when the protoliths were relatively dry or after dessication occurred by removal of a partial melt phase.

  2. Soil Compaction Absent in Plantation Thinning

    Treesearch

    Tony King; Sharon Haines

    1979-01-01

    We examine the effects on soil bulk density by using a TH-105 Thinner Harvester and two forwarders in a mechanically thinned slash pine (Pinus elliottii Engelm.) plantation. Points in the machine tracks were sampled before and after harvesting at depths of 5 and 10 cm (2 and 4 in) for moisture and bulk density. Both the standard gravimetric method...

  3. The Importance of Purkinje Activation in Long Duration Ventricular Fibrillation

    PubMed Central

    Huang, Jian; Dosdall, Derek J.; Cheng, Kang‐An; Li, Li; Rogers, Jack M.; Ideker, Raymond E.

    2014-01-01

    Background The mechanisms that maintain long duration ventricular fibrillation (LDVF) are unclear. The difference in distribution of the Purkinje system in dogs and pigs was explored to determine if Purkinje activation propagates to stimulate working myocardium (WM) during LDVF and WM pacing. Methods and Results In‐vivo extracellular recordings were made from 1044 intramural plunge and epicardial plaque electrodes in 6 pig and 6 dog hearts. Sinus activation propagated sequentially from the endocardium to the epicardium in dogs but not pigs. During epicardial pacing, activation propagated along the endocardium and traversed the LV wall almost parallel to the epicardium in dogs, but in pigs propagated away from the pacing site approximately perpendicular to the epicardium. After 1 minute of VF, activation rate near the endocardium was significantly faster than near the epicardium in dogs (P<0.01) but not pigs (P>0.05). From 2 to 10 minutes of LDVF, recordings exhibiting Purkinje activations were near the endocardium in dogs (P<0.01) but were scattered transmurally in pigs, and the WM activation rate in recordings in which Purkinje activations were present was significantly faster than the WM activation rate in recordings in which Purkinje activations were absent (P<0.01). In 10 isolated perfused dog hearts, the LV endocardium was exposed and 2 microelectrodes were inserted into Purkinje and adjacent myocardial cells. After 5 minutes of LDVF, mean Purkinje activation rate was significantly faster than mean WM activation rate (P<0.01). Conclusion These extracellular and intracellular findings about activation support the hypothesis that Purkinje activation propagates to stimulate WM during sinus rhythm, pacing, and LDVF. PMID:24584738

  4. Multimodal recording of brain activity in term newborns during photic stimulation by near-infrared spectroscopy and electroencephalography

    NASA Astrophysics Data System (ADS)

    Biallas, Martin; Trajkovic, Ivo; Hagmann, Cornelia; Scholkmann, Felix; Jenny, Carmen; Holper, Lisa; Beck, Andreas; Wolf, Martin

    2012-08-01

    In this study 14 healthy term newborns (postnatal mean age 2.1 days) underwent photic stimulation during sleep on two different days. Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) was acquired simultaneously. The aims of the study were: to determine (i) the sensitivity and (ii) the repeatability of NIRS to detect the hemodynamic response, (iii) the sensitivity and (iv) the repeatability of EEG to detect a visual evoked potential (VEP), (v) to analyze optical data for the optical neuronal signal, and (vi) to test whether inadequate stimulation could be reason for absent hemodynamic responses. The results of the study were as follows. (i) Sensitivity of NIRS was 61.5% to detect hemodynamic responses; (ii) their reproducibility was 41.7%. A VEP was detected (iii) in 96.3% of all subjects with (iv) a reproducibility of 92.3%. (v) In two measurements data met the criteria for an optical neuronal signal. The noise level was 9.6.10-5% change in optical density. (vi) Insufficient stimulation was excluded as reason for absent hemodynamic responses. We conclude that NIRS is an promising tool to study cognitive activation and development of the brain. For clinical application, however, the sensitivity and reproducibility on an individual level needs to be improved.

  5. Role of activator protein-1 on the effect of arginine-glycine-aspartic acid containing peptides on transforming growth factor-beta1 promoter activity.

    PubMed

    Ruiz-Torres, M P; Perez-Rivero, G; Diez-Marques, M L; Griera, M; Ortega, R; Rodriguez-Puyol, M; Rodríguez-Puyol, D

    2007-01-01

    While arginine-glycine-aspartic acid-based peptidomimetics have been employed for the treatment of cardiovascular disorders and cancer, their use in other contexts remains to be explored. Arginine-glycine-aspartic acid-serine induces Transforming growth factor-beta1 transcription in human mesangial cells, but the molecular mechanisms involved have not been studied extensively. We explored whether this effect could be due to Activator protein-1 activation and studied the potential pathways involved. Addition of arginine-glycine-aspartic acid-serine promoted Activator protein-1 binding to its cognate sequence within the Transforming growth factor-beta1 promoter as well as c-jun and c-fos protein abundance. Moreover, this effect was suppressed by curcumin, a c-Jun N terminal kinase inhibitor, and was absent when the Activator protein-1 cis-regulatory element was deleted. Activator protein-1 binding was dependent on the activity of integrin linked kinase, as transfection with a dominant negative mutant suppressed both Activator protein-1 binding and c-jun and c-fos protein increment. Integrin linked kinase was, in turn, dependent on Phosphoinositol-3 kinase activity. Arginine-glycine-aspartic acid-serine stimulated Phosphoinositol-3 kinase activity, and Transforming growth factor-beta1 promoter activation was abrogated by the use of Phosphoinositol-3 kinase specific inhibitors. In summary, we propose that arginine-glycine-aspartic acid-serine activates Integrin linked kinase via the Phosphoinositol-3 kinase pathway and this leads to activation of c-jun and c-fos and increased Activator protein-1 binding and Transforming growth factor-beta1 promoter activity. These data may contribute to understand the molecular mechanisms involved in the cellular actions of arginine-glycine-aspartic acid-related peptides and enhance their relevance as these products evolve into clinical therapeutic use.

  6. Facilitative glucose transporter Glut1 is actively excluded from rod outer segments.

    PubMed

    Gospe, Sidney M; Baker, Sheila A; Arshavsky, Vadim Y

    2010-11-01

    Photoreceptors are among the most metabolically active cells in the body, relying on both oxidative phosphorylation and glycolysis to satisfy their high energy needs. Local glycolysis is thought to be particularly crucial in supporting the function of the photoreceptor's light-sensitive outer segment compartment, which is devoid of mitochondria. Accordingly, it has been commonly accepted that the facilitative glucose transporter Glut1 responsible for glucose entry into photoreceptors is localized in part to the outer segment plasma membrane. However, we now demonstrate that Glut1 is entirely absent from the rod outer segment and is actively excluded from this compartment by targeting information present in its cytosolic C-terminal tail. Our data indicate that glucose metabolized in the outer segment must first enter through other parts of the photoreceptor cell. Consequently, the entire energy supply of the outer segment is dependent on diffusion of energy-rich substrates through the thin connecting cilium that links this compartment to the rest of the cell.

  7. Pharmacogenetic research activity in Central America and the Caribbean: a systematic review

    PubMed Central

    Céspedes-Garro, Carolina; Naranjo, María-Eugenia G; Rodrigues-Soares, Fernanda; LLerena, Adrián; Duconge, Jorge; Montané-Jaime, Lazara K; Roblejo, Hilda; Fariñas, Humberto; Campos, María de los A; Ramírez, Ronald; Serrano, Víctor; Villagrán, Carmen I; Peñas-LLedó, Eva M

    2016-01-01

    Aim: The present review was aimed at analyzing the pharmacogenetic scientific activity in Central America and the Caribbean. Materials & methods: A literature search for pharmacogenetic studies in each country of the region was conducted on three databases using a list of the most relevant pharmacogenetic biomarkers including ‘phenotyping probe drugs’ for major drug metabolizing enzymes. The review included 132 papers involving 47 biomarkers and 35,079 subjects (11,129 healthy volunteers and 23,950 patients). Results: The country with the most intensive pharmacogenetic research was Costa Rica. The most studied medical therapeutic area was oncology, and the most investigated biomarkers were CYP2D6 and HLA-A/B. Conclusion: Research activity on pharmacogenetics in Central American and the Caribbean populations is limited or absent. Therefore, strategies to promote effective collaborations, and foster interregional initiatives and research efforts among countries from the region could help for the rational clinical implementation of pharmacogenetics and personalized medicine. PMID:27633613

  8. Motivators and barriers for physical activity in the oldest old: a systematic review.

    PubMed

    Baert, Veerle; Gorus, Ellen; Mets, Tony; Geerts, Christel; Bautmans, Ivan

    2011-09-01

    Worldwide, people engage insufficiently in physical activity, particularly subjects aged 80 years and over. For optimal life-style campaigns, knowledge of motivators and barriers for physical activity is mandatory. Given their specific needs, it is conceivable that these would be different for the oldest old compared to younger subjects. Pubmed, Web of Science and Psychinfo were systematically screened for articles reporting motivators and barriers for physical activity. Papers were excluded if data regarding elderly aged >79 years were absent. Forty-four relevant articles were included, involving a total of 28,583 subjects. Sixty one motivators and 59 barriers for physical activity in the elderly were identified, including those who are relevant for persons aged 80 years and over. Based on the results of our literature review, we recommend that when promoting physical activity in the oldest old, special attention is paid to the health benefits of physical activity, to the subject's fears, individual preferences and social support, and to constraints related to the physical environment. However, no studies were found exclusively describing people aged 80 years and over, and future research is necessary to differentiate the barriers or motivators that are specific for the oldest old from those of younger elderly. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Impact of Procyanidins from Different Berries on Caspase 8 Activation in Colon Cancer.

    PubMed

    Minker, Carole; Duban, Livine; Karas, Daniel; Järvinen, Päivi; Lobstein, Annelise; Muller, Christian D

    2015-01-01

    The aim of this work is to identify which proapoptotic pathway is induced in human colon cancer cell lines, in contact with proanthocyanidins extracted from various berries. Proanthocyanidins (Pcys) extracted from 11 berry species are monitored for proapoptotic activities on two related human colon cancer cell lines: SW480-TRAIL-sensitive and SW620-TRAIL-resistant. Apoptosis induction is monitored by cell surface phosphatidylserine (PS) detection. Lowbush blueberry extract triggers the strongest activity. When tested on the human monocytic cell line THP-1, blueberry Pcys are less effective for PS externalisation and DNA fragmentation is absent, highlighting a specificity of apoptosis induction in gut cells. In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells. We highlight here that berries Pcys, especially lowbush blueberry Pcys, are of putative interest for nutritional chemoprevention of colorectal cancer in view of their apoptosis induction in a human colorectal cancer cell lines.

  10. [Tissue collagenase MMP-14 and endogenous regulators of its activity in the corpus uteri in squamous cell carcinoma of the cervix].

    PubMed

    Timoshenko, O S; Gureeva, T A; Kugaevskaya, E V; Zavalishina, L E; Andreeva, Yu Yu; Solovyeva, N I

    to investigate the expression of the membrane-bound matrix metalloproteinase MT1-MMP (MMP-14), its tissue inhibitor TIMP-2, and the proMMP-14 activator furin in the corpus uteri from the vaginal wall to the bottom of the uterine cavity in squamous cell carcinoma of the cervix (SCCC). Hysterectomy material was examined in patients with SCCC. Reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and enzyme assays were used. In SCCC, higher levels of MMP-14 expression were established in tumor cells, as evidenced by IHC (+3) and RT-PCR. IHC showed that the expression of MMP-14 was absent or insignificant in the normal uterine endometrial and myometrial tissues. However, that of MMP-14 mRNA was also found in the normal tissues to the bottom of the uterine cavity. Furin activity in the tumor was much higher than that in normal tissues. IHC indicated that TIMP-2 expression was low or absent in both the tumor and normal tissues. The expression of TIMP-2 mRNA was sufficiently obvious in both the tumor and normal tissues to the bottom of the uterine cavity. In SCCC, MMP-14 expression was substantially increased in tumors. The expression of MMP-14 and regulators of its activity is aimed at enhancing the tumor destructive (invasive) potential in the pericellular space and can occur (be induced) in the morphologically normal uterine tissue apparently with involvement of signaling through the epithelial-mesenchymal interaction. Data are important for understanding the role of MMP-14 in the development of a multistage process of carcinogenesis and may have prognostic value and an impact on therapeutic strategy for the patient.

  11. Recent Uptrend in Whole-Grain Intake Is Absent for Low-Income Adolescents, National Health and Nutrition Examination Survey, 2005–2012

    PubMed Central

    Leung, Cindy W.; Leak, Tashara M.; Laraia, Barbara A.

    2017-01-01

    Introduction Whole-grain consumption reduces risk of chronic disease, yet adolescents consume suboptimal amounts. It is unclear whether trends in consumption of whole grains have been positive among adolescents, and research assessing disparities by socioeconomic status is limited. The objective of our study was to evaluate recent trends in whole-grain consumption by US adolescents. Methods We examined data on 3,265 adolescents aged 13 to18 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2012. Intake of whole and refined grains was analyzed by using generalized linear models, and odds of no whole-grain intake were examined with logistic regression, adjusting for socioeconomic and demographic factors. We evaluated trends and examined heterogeneity of trends with respect to annual household income. Results Daily whole-grain consumption among adolescents increased overall by about a quarter-ounce–equivalent per day (oz-eq/d) (P trend <.001). We found a significant relationship between whole-grain intake and income. Daily whole grains (recommended as ≥3 oz-eq/d), increased (0.6 to 1.0 oz-eq/d) among high-income adolescents (P trend < .001) but remained at 0.5 oz-eq/d for low-income adolescents. The ratio of whole grains to total grains (recommended to be at least 50%) rose from 7.6% to 14.2% for high-income adolescents (P trend < .001), with no significant trend for the low-income group. Consumption of refined grains did not change. Odds of having no whole grains trended downward, but only for the high-income adolescents (P trend = .01). Conclusion These data show significant (albeit modest) trends toward increased intake of whole grains among high-income adolescents nationwide that are absent among low-income peers. Future interventions and policies should address barriers to whole-grain consumption among this vulnerable group. PMID:28682743

  12. Urtica spp.: Phenolic composition, safety, antioxidant and anti-inflammatory activities.

    PubMed

    Carvalho, Ana Rita; Costa, Gustavo; Figueirinha, Artur; Liberal, Joana; Prior, João A V; Lopes, Maria Celeste; Cruz, Maria Teresa; Batista, Maria Teresa

    2017-09-01

    Urtica dioica and other less studied Urtica species (Urticaceae) are often used as a food ingredient. Fifteen hydroxycinnamic acid derivatives and sixteen flavonoids, flavone and flavonol-type glycosides were identified in hydroalcoholic extracts from aerial parts of Urtica dioica L., Urtica urens L. and Urtica membranacea using HPLC-PDA-ESI/MS n . Among them, the 4-caffeoyl-5-p-coumaroylquinic acid and three statin-like 3-hydroxy-3-methylglutaroyl flavone derivatives were identified for the first time in Urtica urens and U. membranacea respectively. Urtica membranacea showed the higher content of flavonoids, mainly luteolin and apigenin C-glycosides, which are almost absent in the other species studied. In vitro, Urtica dioica exhibited greater antioxidant activity but Urtica urens exhibited stronger anti-inflammatory potential. Interestingly, statin-like compounds detected in Urtica membranacea have been associated with hypocholesterolemic activity making this plant interesting for future investigations. None of the extracts were cytotoxic to macrophages and hepatocytes in bioactive concentrations (200 and 350μg/mL), suggesting their safety use in food applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Real-Time Observation of Human LINE-1 Retrotransposon Activity in Bacteria

    NASA Astrophysics Data System (ADS)

    Kaur, Davneet; Kuhlman, Thomas; Kuhlman Team; Nigel Goldenfeld Collaboration

    Transposable elements (TEs) are fundamental building blocks of all genomes. Retrotransposable elements (RTEs) are one of the two primary classes of TEs that are ubiquitous in eukaryotes. They propagate through a copy-and-paste mechanism utilizing reverse-transcribed mRNA intermediates. This leads to disruption and dispersal of coding and control elements throughout the genome, and consequently TEs are thought to be a major driving force behind diversification. However, RTEs are absent in most prokaryotes including E. coli. and the reason for this remains an open question. Despite their prevalence, there still remain many unanswered questions about how `hot' or active L1 RTEs (L1Hs) function. In particular, their rates of activity and their effects upon their host are currently poorly understood and only roughly estimated within the limitations of available technology. To address these unanswered questions, we have constructed and released an L1H element in E. coli to quantify its rates of activity and physiological effects on its host. To overcome the technical limitations, we've designed fluorescent visualization and quantification techniques that make real time high resolution observations of retrotransposition events as they occur in living cells.

  14. Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation

    PubMed Central

    Kaushal, V; Dye, R; Pakavathkumar, P; Foveau, B; Flores, J; Hyman, B; Ghetti, B; Koller, B H; LeBlanc, A C

    2015-01-01

    Neuronal active Caspase-6 (Casp6) is associated with Alzheimer disease (AD), cognitive impairment, and axonal degeneration. Caspase-1 (Casp1) can activate Casp6 but the expression and functionality of Casp1-activating inflammasomes has not been well-defined in human neurons. Here, we show that primary cultures of human CNS neurons expressed functional Nod-like receptor protein 1 (NLRP1), absent in melanoma 2, and ICE protease activating factor, but not the NLRP3, inflammasome receptor components. NLRP1 neutralizing antibodies in a cell-free system, and NLRP1 siRNAs in neurons hampered stress-induced Casp1 activation. NLRP1 and Casp1 siRNAs also abolished stress-induced Casp6 activation in neurons. The functionality of the NLRP1 inflammasome in serum-deprived neurons was also demonstrated by NLRP1 siRNA-mediated inhibition of speck formation of the apoptosis-associated speck-like protein containing a caspase recruitment domain conjugated to green fluorescent protein. These results indicated a novel stress-induced intraneuronal NLRP1/Casp1/Casp6 pathway. Lipopolysaccharide induced Casp1 and Casp6 activation in wild-type mice brain cortex, but not in that of Nlrp1−/− and Casp1−/− mice. NLRP1 immunopositive neurons were increased 25- to 30-fold in AD brains compared with non-AD brains. NLRP1 immunoreactivity in these neurons co-localized with Casp6 activity. Furthermore, the NLRP1/Casp1/Casp6 pathway increased amyloid beta peptide 42 ratio in serum-deprived neurons. Therefore, CNS human neurons express functional NLRP1 inflammasomes, which activate Casp1 and subsequently Casp6, thus revealing a fundamental mechanism linking intraneuronal inflammasome activation to Casp1-generated interleukin-1-β-mediated neuroinflammation and Casp6-mediated axonal degeneration. PMID:25744023

  15. Loss of Ca2+-mediated ion transport during colitis correlates with reduced ion transport responses to a Ca2+-activated K+ channel opener

    PubMed Central

    Hirota, Christina L; McKay, Derek M

    2009-01-01

    Background and purpose: Epithelial surface hydration is critical for proper gut function. However, colonic tissues from individuals with inflammatory bowel disease or animals with colitis are hyporesponsive to Cl− secretagogues. The Cl− secretory responses to the muscarinic receptor agonist bethanechol are virtually absent in colons of mice with dextran sodium sulphate (DSS)-induced colitis. Our aim was to define the mechanism underlying this cholinergic hyporesponsiveness. Experimental approach: Colitis was induced by 4% DSS water, given orally. Epithelial ion transport was measured in Ussing chambers. Colonic crypts were isolated and processed for mRNA expression via RT-PCR and protein expression via immunoblotting and immunolocalization. Key results: Expression of muscarinic M3 receptors in colonic epithelium was not decreased during colitis. Short-circuit current (ISC) responses to other Ca2+-dependent secretagogues (histamine, thapsigargin, cyclopiazonic acid and calcium ionophore) were either absent or severely attenuated in colonic tissue from DSS-treated mice. mRNA levels of several ion transport molecules (a Ca2+-regulated Cl− channel, the intermediate-conductance Ca2+-activated K+ channel, the cystic fibrosis transmembrane conductance regulator, the Na+/K+-ATPase pump or the Na+/K+/2Cl− co-transporter) were not reduced in colonic crypts from DSS-treated mice. However, protein expression of Na+/K+-ATPase α1 subunits was decreased twofold during colitis. Activation of Ca2+-activated K+ channels increased ISC significantly less in DSS colons compared with control, as did the protein kinase C activator, phorbol 12-myristate 13-acetate. Conclusions and implications: Decreased Na+/K+-ATPase expression probably contributes to overall epithelial hyporesponsiveness during colitis, while dysfunctional K+ channels may account, at least partially, for lack of epithelial secretory responses to Ca2+-mediated secretagogues. PMID:19298254

  16. RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL.

    PubMed

    Lawlor, Kate E; Khan, Nufail; Mildenhall, Alison; Gerlic, Motti; Croker, Ben A; D'Cruz, Akshay A; Hall, Cathrine; Kaur Spall, Sukhdeep; Anderton, Holly; Masters, Seth L; Rashidi, Maryam; Wicks, Ian P; Alexander, Warren S; Mitsuuchi, Yasuhiro; Benetatos, Christopher A; Condon, Stephen M; Wong, W Wei-Lynn; Silke, John; Vaux, David L; Vince, James E

    2015-02-18

    RIPK3 and its substrate MLKL are essential for necroptosis, a lytic cell death proposed to cause inflammation via the release of intracellular molecules. Whether and how RIPK3 might drive inflammation in a manner independent of MLKL and cell lysis remains unclear. Here we show that following LPS treatment, or LPS-induced necroptosis, the TLR adaptor protein TRIF and inhibitor of apoptosis proteins (IAPs: X-linked IAP, cellular IAP1 and IAP2) regulate RIPK3 and MLKL ubiquitylation. Hence, when IAPs are absent, LPS triggers RIPK3 to activate caspase-8, promoting apoptosis and NLRP3-caspase-1 activation, independent of RIPK3 kinase activity and MLKL. In contrast, in the absence of both IAPs and caspase-8, RIPK3 kinase activity and MLKL are essential for TLR-induced NLRP3 activation. Consistent with in vitro experiments, interleukin-1 (IL-1)-dependent autoantibody-mediated arthritis is exacerbated in mice lacking IAPs, and is reduced by deletion of RIPK3, but not MLKL. Therefore RIPK3 can promote NLRP3 inflammasome and IL-1β inflammatory responses independent of MLKL and necroptotic cell death.

  17. Increased brain lysosomal pepstatin-insensitive proteinase activity in patients with neurodegenerative diseases.

    PubMed

    Junaid, M A; Pullarkat, R K

    1999-04-02

    A recent study has shown mutations in CLN2 gene, that encodes a novel lysosomal pepstatin-insensitive proteinase (LPIP), in the pathophysiology of late-infantile neuronal ceroid lipofuscinosis (LINCL). We have measured the LPIP activities in brains from various forms of human neuronal ceroid lipofuscinoses (NCL), canine ceroid lipofuscinosis and other neurodegenerative disorders with a highly sensitive assay using a tetrapeptide Gly-Phe-Phe-Leu-amino-trifluoromethyl coumarin (AFC) as substrate. Brain LPIP has a pH optimum of 3.5 and an apparent km of 100 microM for the crude enzyme. The enzyme activity is totally absent in LINCL patients. Pronounced increase in the LPIP activity was seen in patients suffering from infantile (INCL), juvenile (JNCL) and adult (ANCL) forms of neuronal ceroid lipofuscinoses. LPIP activity was also found to be increased about two-fold in Alzheimer's disease when compared with normal or age-matched controls, while in globoidal-cell leukodystrophy (Krabbe's disease) it was similar to the normal controls. Although mannose-6-phosphorylated LPIP is increased 13-fold in brains of patients with JNCL, this form of LPIP did not have any enzyme activity. The mechanism by which LPIP activities are increased in a wide range of neurodegenerative diseases is unknown, although neuronal loss, followed by gliosis are common characteristics of these diseases.

  18. Why Teachers Are Absent: An Examination of Teacher Absences in Broward County Public Schools.

    ERIC Educational Resources Information Center

    Green, Laura R.; Blasik, Katherine A.; Varela-Russo, Carmen

    1999-01-01

    An absenteeism study found that the largest percentage of teacher absences was due to professional development activities, illness, and vacant positions. High schools had lower absence rates than elementary and middle schools and centers. Absenteeism was also related to number of kids eligible for free-lunch programs. (Contains 20 references.)…

  19. Recreational physical activity and the risk of preeclampsia: a prospective cohort of Norwegian women.

    PubMed

    Magnus, Per; Trogstad, Lill; Owe, Katrine M; Olsen, Sjurdur F; Nystad, Wenche

    2008-10-15

    Previous case-control studies suggest that recreational physical activity protects against preeclampsia. Using a prospective design, the authors estimated the risk of preeclampsia for pregnant women according to level of physical activity, taking other variables that influence risk into consideration. The data set comprised 59,573 pregnancies from the Norwegian Mother and Child Cohort Study (1999-2006). Information on physical activity and other exposures was extracted from questionnaire responses given in pregnancy weeks 14-22, whereas diagnosis of preeclampsia was retrieved from the Medical Birth Registry of Norway. Estimation and confounder control was performed with multiple logistic regression. About 24% of pregnant women reported no physical activity, and 7% reported more than 25 such activities per month. The adjusted odds ratio was 0.79 (95% confidence interval: 0.65, 0.96) for preeclampsia when comparing women who exercised 25 times or more per month with inactive women. The association appeared strongest among women whose body mass index was less than 25 kg/m(2) and was absent among women whose body mass index was higher than 30 kg/m(2). These results suggest that the preventive effect of recreational physical activity during pregnancy may be more limited than has been shown in case-control studies and may apply to nonobese women only.

  20. Cooperative Dynamics of AR and ER Activity in Breast Cancer

    PubMed Central

    D’Amato, Nicholas C.; Gordon, Michael A.; Babbs, Beatrice L.; Spoelstra, Nicole S.; Carson Butterfield, Kiel T.; Torkko, Kathleen C.; Phan, Vernon T.; Barton, Valerie N.; Rogers, Thomas J.; Sartorius, Carol A; Elias, Anthony D.; Gertz, Jason; Jacobsen, Britta M.; Richer, Jennifer K.

    2016-01-01

    Androgen receptor (AR) is expressed in 90% of estrogen receptor alpha positive (ER+) breast tumors, but its role in tumor growth and progression remains controversial. Use of two anti-androgens that inhibit AR nuclear localization, enzalutamide and MJC13, revealed that AR is required for maximum ER genomic binding. Here, a novel global examination of AR chromatin binding found that estradiol induced AR binding at unique sites compared to dihydrotestosterone (DHT). Estradiol-induced AR binding sites were enriched for estrogen response elements and had significant overlap with ER binding sites. Furthermore, AR inhibition reduced baseline and estradiol-mediated proliferation in multiple ER+/AR+ breast cancer cell lines, and synergized with tamoxifen and fulvestrant. In vivo, enzalutamide significantly reduced viability of tamoxifen-resistant MCF7 xenograft tumors and an ER+/AR+ patient-derived model. Enzalutamide also reduced metastatic burden following cardiac injection. Lastly, in a comparison of ER+/AR+ primary tumors versus patient-matched local recurrences or distant metastases, AR expression was often maintained even when ER was reduced or absent. These data provide pre-clinical evidence that anti-androgens that inhibit AR nuclear localization affect both AR and ER, and are effective in combination with current breast cancer therapies. In addition, single agent efficacy may be possible in tumors resistant to traditional endocrine therapy, since clinical specimens of recurrent disease demonstrate AR expression in tumors with absent or refractory ER. Implications This study suggests that AR plays a previously-unrecognized role in supporting E2-mediated ER activity in ER+/AR+ breast cancer cells, and that enzalutamide may be an effective therapeutic in ER+/AR+ breast cancers. PMID:27565181

  1. Challenging the present definition of "normal" vitamin D levels obtained by a single blood test. Can we develop a formula to predict vitamin D levels in the 4 seasons from a single season's measure?

    PubMed

    Tandeter, Howard

    2014-08-01

    Publications on the health effects of vitamin D (25(OH) D) had almost triplicate in the last 10years, not only for its known "calcemic effects" (calcium, phosphor, PTH), but for the more recent findings on its "non-calcemic effects" (all-cause and cardiovascular mortality, and relation with certain types of cancer). Part of these publications deal with the definition of what is a "normal" circulating level of 25(OH) D that may distinguish between health and disease. The literature also deals with seasonal variations of vitamin D, showing levels that rise in summer and fall in winter and with DBP phenotypes and geographical location that affect seasonality of 25(OH) D measurements. Despite the knowledge of the existence of these phenomena many studies on vitamin D fail to acknowledge the time of the year the blood sample was extracted. Thus, when we compare results from different studies without defining the season that the samples were drawn, we compare incomparable figures. Furthermore, it is quite absurd to define "normal levels" as a static measure (over or under a certain value) using a single blood test when the value measured is known to change with seasons. Knowing that people have different vitamin D levels in different seasons of the year, we should ask ourselves which of these measurements should be used to define a "real" or "normal" level? Is it the lower one? Is there a "mean measure" that should be used for this matter? If yes, how do we obtain it? Do we have to make 4 seasonal measurements in each patient? Alternatively, might there be a possibility of developing a formula to help us obtain the mean from a single season's measure or one season's prediction from another season's measurement? And knowing that DBP phenotypes and geographical location affect seasonality of 25(OH) D measurements; shouldn't we include this in the equation? In this article I will discuss the hypothetical existence of an Individual Mean Annual vitamin D level that I will

  2. Bioflocculation of mesophilic and thermophilic activated sludge.

    PubMed

    Vogelaar, J C T; De Keizer, A; Spijker, S; Lettinga, G

    2005-01-01

    Thermophilic activated sludge treatment is often hampered by a turbid effluent. Reasons for this phenomenon are so far unknown. Here, the hypothesis of the temperature dependency of the hydrophobic interaction as a possible cause for diminished thermophilic activated sludge bioflocculation was tested. Adsorption of wastewater colloidal particles was monitored on different flat surfaces as a function of temperature. Adsorption on a hydrophobic surface varied with temperature between 20 and 60 degrees C and no upward or downward trend could be observed. This makes the hydrophobic interaction hypothesis unlikely in explaining the differences in mesophilic and thermophilic activated sludge bioflocculation. Both mesophilic and thermophilic biomass did not flocculate with wastewater colloidal particles under anaerobic conditions. Only in the presence of oxygen, with biologically active bacteria, the differences in bioflocculation behavior became evident. Bioflocculation was shown only to occur with the combination of wastewater and viable mesophilic biomass at 30 degrees C, in the presence of oxygen. Bioflocculation did not occur in case the biomass was inactivated or when oxygen was absent. Thermophilic activated sludge hardly showed any bioflocculation, also under mesophilic conditions. Despite the differences in bioflocculation behavior, sludge hydrophobicity and sludge zetapotentials were almost similar. Theoretical calculations using the DLVO (Derjaguin, Landau, Verweij and Overbeek) theory showed that flocculation is unlikely in all cases due to long-range electrostatic forces. These calculations, combined with the fact that bioflocculation actually did occur at 30 degrees C and the unlikelyness of the hydrophobic interaction, point in the direction of bacterial exo-polymers governing bridging flocculation. Polymer interactions are not included in the DLVO theory and may vary as a function of temperature.

  3. Learning-induced Dependence of Neuronal Activity in Primary Motor Cortex on Motor Task Condition.

    PubMed

    Cai, X; Shimansky, Y; He, Jiping

    2005-01-01

    A brain-computer interface (BCI) system such as a cortically controlled robotic arm must have a capacity of adjusting its function to a specific environmental condition. We studied this capacity in non-human primates based on chronic multi-electrode recording from the primary motor cortex of a monkey during the animal's performance of a center-out 3D reaching task and adaptation to external force perturbations. The main condition-related feature of motor cortical activity observed before the onset of force perturbation was a phasic raise of activity immediately before the perturbation onset. This feature was observed during a series of perturbation trials, but were absent under no perturbations. After adaptation has been completed, it usually was taking the subject only one trial to recognize a change in the condition to switch the neuronal activity accordingly. These condition-dependent features of neuronal activity can be used by a BCI for recognizing a change in the environmental condition and making corresponding adjustments, which requires that the BCI-based control system possess such advanced properties of the neural motor control system as capacity to learn and adapt.

  4. Recycling Endosomes of Polarized Epithelial Cells Actively Sort Apical and Basolateral Cargos into Separate Subdomains

    PubMed Central

    Thompson, Anthony; Nessler, Randy; Wisco, Dolora; Anderson, Eric; Winckler, Bettina

    2007-01-01

    The plasma membranes of epithelial cells plasma membranes contain distinct apical and basolateral domains that are critical for their polarized functions. However, both domains are continuously internalized, with proteins and lipids from each intermixing in supranuclear recycling endosomes (REs). To maintain polarity, REs must faithfully recycle membrane proteins back to the correct plasma membrane domains. We examined sorting within REs and found that apical and basolateral proteins were laterally segregated into subdomains of individual REs. Subdomains were absent in unpolarized cells and developed along with polarization. Subdomains were formed by an active sorting process within REs, which precedes the formation of AP-1B–dependent basolateral transport vesicles. Both the formation of subdomains and the fidelity of basolateral trafficking were dependent on PI3 kinase activity. This suggests that subdomain and transport vesicle formation occur as separate sorting steps and that both processes may contribute to sorting fidelity. PMID:17494872

  5. Treatment of actinic cheilitis by photodynamic therapy with 5-aminolevulinic acid and blue light activation.

    PubMed

    Zaiac, Martin; Clement, Annabelle

    2011-11-01

    Actinic cheilitis (AC), a common disorder of the lower lip, should be treated early to prevent progression to invasive squamous cell carcinoma. This study evaluated the safety and efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) activated by blue light for the treatment of AC. Fifteen patients with clinically evident or biopsy-proven AC received two treatments with ALA PDT with blue light activation. Treatments were spaced three to five weeks apart. Most patients achieved 65% to 75% clearance three to five weeks after the first treatment and all achieved more than 75% clearance one month after the second treatment. Three patients achieved complete clearance. Pain and burning during irradiation were absent or mild. All patients said they would repeat the procedure. ALA PDT with 417 nm blue light is a promising option for the treatment of AC of the lower lip.

  6. Obstacle stepping involves spinal anticipatory activity associated with quadrupedal limb coordination.

    PubMed

    Michel, J; van Hedel, H J A; Dietz, V

    2008-04-01

    Obstacle avoidance steps are associated with a facilitation of spinal reflexes in leg muscles. Here we have examined the involvement of both leg and arm muscles. Subjects walking with reduced vision on a treadmill were acoustically informed about an approaching obstacle and received feedback about task performance. Reflex responses evoked by tibial nerve stimulation were observed in all arm and leg muscles examined in this study. They were enhanced before the execution of obstacle avoidance compared with normal steps and showed an exponential adaptation in contralateral arm flexor muscles corresponding to the improvement of task performance. This enhancement was absent when the body was partially supported during the task. During the execution of obstacle steps, electromyographic activity in the arm muscles mimicked the preceding reflex behaviour with respect to enhancement and adaptation. Our results demonstrate an anticipatory quadrupedal limb coordination with an involvement of proximal arm muscles in the acquisition and performance of this precision locomotor task. This is presumably achieved by an up-regulated activity of coupled cervico-thoracal interneuronal circuits.

  7. Giant spin splitting in optically active ZnMnTe/ZnMgTe core/shell nanowires.

    PubMed

    Wojnar, Piotr; Janik, Elżbieta; Baczewski, Lech T; Kret, Sławomir; Dynowska, Elżbieta; Wojciechowski, Tomasz; Suffczyński, Jan; Papierska, Joanna; Kossacki, Piotr; Karczewski, Grzegorz; Kossut, Jacek; Wojtowicz, Tomasz

    2012-07-11

    An enhancement of the Zeeman splitting as a result of the incorporation of paramagnetic Mn ions in ZnMnTe/ZnMgTe core/shell nanowires is reported. The studied structures are grown by gold-catalyst assisted molecular beam epitaxy. The near band edge emission of these structures, conspicuously absent in the case of uncoated ZnMnTe nanowires, is activated by the presence of ZnMgTe coating. Giant Zeeman splitting of this emission is studied in ensembles of nanowires with various average Mn concentrations of the order of a few percent, as well as in individual nanowires. Thus, we show convincingly that a strong spin sp-d coupling is indeed present in these structures.

  8. Fibrinogen adsorption, platelet adhesion and activation on mixed hydroxyl-/methyl-terminated self-assembled monolayers.

    PubMed

    Rodrigues, Sofia N; Gonçalves, Inês C; Martins, M C L; Barbosa, Mário A; Ratner, Buddy D

    2006-11-01

    The effect of surface wettability on fibrinogen adsorption, platelet adhesion and platelet activation was investigated using self-assembled monolayers (SAMs) containing different ratios of longer chain methyl- and shorter chain hydroxyl-terminated alkanethiols (C15CH3 vs. C11OH) on gold. Protein adsorption studies were performed using radiolabeled human fibrinogen (HFG). Platelet adhesion and activation studies with and without pre-adsorbed fibrinogen, albumin and plasma were assessed using scanning electron microscopy (SEM) and a glutaraldehyde-induced fluorescence technique (GIFT). Results demonstrated a linear decrease of HFG adsorption with the increase of OH groups on the monolayer (increase of the hydrophilicity). Platelet adhesion and activation also decrease with increase of hydrophilicity of surface. Concerning SAMs pre-immersed in proteins, fibrinogen adsorption was related with high platelet adhesion and activation. The passivant effect of albumin on platelet adhesion and activation was only demonstrated on SAMs contained C11OH. When all the blood proteins are present (plasma) platelet adhesion was almost absent on SAMs with 65% and 100% C11OH. This could be explained by the higher albumin affinity of the SAMs with 65% C11OH and the lower total protein adsorption associated with SAMs with 100% C11OH.

  9. Activation of Gαq subunits up-regulates the expression of the tumor suppressor Fhit.

    PubMed

    Zuo, Hao; Chan, Anthony S L; Ammer, Hermann; Wong, Yung H

    2013-12-01

    The tumor suppressor Fhit protein is defective or absent in many tumor cells due to methylation, mutation or deletion of the FHIT gene. Despite numerous attempts to unravel the functions of Fhit, the mechanisms by which the function and expression of Fhit are regulated remain poorly understood. We have recently shown that activated Gαq subunits interact directly with Fhit and enhance its inhibitory effect on cell growth. Here we investigated the regulation of Fhit expression by Gq. Our results showed that Fhit was up-regulated specifically by activating Gα subunits of the Gq subfamily but not by those of the other G protein subfamilies. This up-regulation effect was mediated by a PKC/MEK pathway independent of Src-mediated Fhit Tyr(114) phosphorylation. We further demonstrated that elevated Fhit expression was due to the specific regulation of Fhit protein synthesis in the ribosome by activated Gαq, where the regulations of cap-dependent protein synthesis were apparently not required. Moreover, we showed that activated Gαq could increase cell-cell adhesion through Fhit. These findings provide a possible handle to modulate the level of the Fhit tumor suppressor by manipulating the activity of Gq-coupled receptors. © 2013. Published by Elsevier Inc. All rights reserved.

  10. Isolation, activity and immunological characterisation of a secreted aspartic protease, CtsD, from Aspergillus fumigatus.

    PubMed

    Vickers, Imelda; Reeves, Emer P; Kavanagh, Kevin A; Doyle, Sean

    2007-05-01

    Aspergillus fumigatus is an opportunistic fungal pathogen that infects immunocompromised patients. A putative aspartic protease gene (ctsD; 1425 bp; intron-free) was identified and cloned. CtsD is evolutionarily distinct from all previously identified A. fumigatus aspartic proteases. Recombinant CtsD was expressed in inclusion bodies in Escherichia coli (0.2mg/g cells) and subjected to extensive proteolysis in the baculovirus expression system. Activation studies performed on purified, refolded, recombinant CtsD resulted in protease activation with a pH(opt)4.0 and specific activity=10 U/mg. Pepstatin A also inhibited recombinant CtsD activity by up to 72% thereby confirming classification as an aspartic protease. Native CtsD was also immunologically identified in culture supernatants and purified from fungal cultures using pepstatin-agarose affinity chromatography (7.8 microg CtsD/g mycelia). In A. fumigatus, semi-quantitative RT-PCR analysis revealed expression of ctsD in minimal and proteinaceous media only. Expression of ctsD was absent under nutrient-rich conditions. Expression of ctsD was also detected, in vivo, in the Galleria mellonella virulence model following A. fumigatus infection.

  11. Abnormal Complex Auditory Pattern Analysis in Schizophrenia Reflected in an Absent Missing Stimulus Mismatch Negativity.

    PubMed

    Salisbury, Dean F; McCathern, Alexis G

    2016-11-01

    The simple mismatch negativity (MMN) to tones deviating physically (in pitch, loudness, duration, etc.) from repeated standard tones is robustly reduced in schizophrenia. Although generally interpreted to reflect memory or cognitive processes, simple MMN likely contains some activity from non-adapted sensory cells, clouding what process is affected in schizophrenia. Research in healthy participants has demonstrated that MMN can be elicited by deviations from abstract auditory patterns and complex rules that do not cause sensory adaptation. Whether persons with schizophrenia show abnormalities in the complex MMN is unknown. Fourteen schizophrenia participants and 16 matched healthy underwent EEG recording while listening to 400 groups of 6 tones 330 ms apart, separated by 800 ms. Occasional deviant groups were missing the 4th or 6th tone (50 groups each). Healthy participants generated a robust response to a missing but expected tone. The schizophrenia group was significantly impaired in activating the missing stimulus MMN, generating no significant activity at all. Schizophrenia affects the ability of "primitive sensory intelligence" and pre-attentive perceptual mechanisms to form implicit groups in the auditory environment. Importantly, this deficit must relate to abnormalities in abstract complex pattern analysis rather than sensory problems in the disorder. The results indicate a deficit in parsing of the complex auditory scene which likely impacts negatively on successful social navigation in schizophrenia. Knowledge of the location and circuit architecture underlying the true novelty-related MMN and its pathophysiology in schizophrenia will help target future interventions.

  12. Rodent ultrasonic vocalizations are bound to active sniffing behavior

    PubMed Central

    Sirotin, Yevgeniy B.; Costa, Martín Elias; Laplagne, Diego A.

    2014-01-01

    During rodent active behavior, multiple orofacial sensorimotor behaviors, including sniffing and whisking, display rhythmicity in the theta range (~5–10 Hz). During specific behaviors, these rhythmic patterns interlock, such that execution of individual motor programs becomes dependent on the state of the others. Here we performed simultaneous recordings of the respiratory cycle and ultrasonic vocalization emission by adult rats and mice in social settings. We used automated analysis to examine the relationship between breathing patterns and vocalization over long time periods. Rat ultrasonic vocalizations (USVs, “50 kHz”) were emitted within stretches of active sniffing (5–10 Hz) and were largely absent during periods of passive breathing (1–4 Hz). Because ultrasound was tightly linked to the exhalation phase, the sniffing cycle segmented vocal production into discrete calls and imposed its theta rhythmicity on their timing. In turn, calls briefly prolonged exhalations, causing an immediate drop in sniffing rate. Similar results were obtained in mice. Our results show that ultrasonic vocalizations are an integral part of the rhythmic orofacial behavioral ensemble. This complex behavioral program is thus involved not only in active sensing but also in the temporal structuring of social communication signals. Many other social signals of mammals, including monkey calls and human speech, show structure in the theta range. Our work points to a mechanism for such structuring in rodent ultrasonic vocalizations. PMID:25477796

  13. An fMRI Study of Nicotine-Deprived Smokers' Reactivity to Smoking Cues during Novel/Exciting Activity

    PubMed Central

    Xu, Xiaomeng; Aron, Arthur; Westmaas, J. Lee; Wang, Jin; Sweet, Lawrence H.

    2014-01-01

    Engaging in novel/exciting (“self-expanding”) activities activates the mesolimbic dopamine pathway, a brain reward pathway also associated with the rewarding effects of nicotine. This suggests that self-expanding activities can potentially substitute for the reward from nicotine. We tested this model among nicotine-deprived smokers who, during fMRI scanning, played a series of two-player cooperative games with a relationship partner. Games were randomized in a 2 (self-expanding vs. not) x 2 (cigarette cue present vs. absent) design. Self-expansion conditions yielded significantly greater activation in a reward region (caudate) than did non-self-expansion conditions. Moreover, when exposed to smoking cues during the self-expanding versus the non-self-expanding cooperative games, smokers showed less activation in a cigarette cue-reactivity region, a priori defined [temporo-parietal junction (TPJ)] from a recent meta-analysis of cue-reactivity. In smoking cue conditions, increases in excitement associated with the self-expanding condition (versus the non-self-expanding condition) were also negatively correlated with TPJ activation. These results support the idea that a self-expanding activity promoting reward activation attenuates cigarette cue-reactivity among nicotine-deprived smokers. Future research could focus on the parameters of self-expanding activities that produce this effect, as well as test the utility of self-expansion in clinical interventions for smoking cessation. PMID:24727905

  14. Impact of Procyanidins from Different Berries on Caspase 8 Activation in Colon Cancer

    PubMed Central

    Minker, Carole; Duban, Livine; Karas, Daniel; Järvinen, Päivi; Lobstein, Annelise; Muller, Christian D.

    2015-01-01

    Scope. The aim of this work is to identify which proapoptotic pathway is induced in human colon cancer cell lines, in contact with proanthocyanidins extracted from various berries. Methods and Results. Proanthocyanidins (Pcys) extracted from 11 berry species are monitored for proapoptotic activities on two related human colon cancer cell lines: SW480-TRAIL-sensitive and SW620-TRAIL-resistant. Apoptosis induction is monitored by cell surface phosphatidylserine (PS) detection. Lowbush blueberry extract triggers the strongest activity. When tested on the human monocytic cell line THP-1, blueberry Pcys are less effective for PS externalisation and DNA fragmentation is absent, highlighting a specificity of apoptosis induction in gut cells. In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells. Conclusion. We highlight here that berries Pcys, especially lowbush blueberry Pcys, are of putative interest for nutritional chemoprevention of colorectal cancer in view of their apoptosis induction in a human colorectal cancer cell lines. PMID:26180579

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

    PubMed

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

    2012-11-13

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

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

    PubMed Central

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

    2012-01-01

    The general transcription factor TFIID comprises the TATA-box-binding protein (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find, unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all TAFs are expressed. Directed and global chromatin immunoprecipitation analyses reveal an unprecedented promoter occupancy pattern: most active genes are bound by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a previously undescribed complex comprising TAFs 2, 6, 7, 11 and TBP. Altering the composition of hESC TAFs, either by depleting TAFs that are present or ectopically expressing TAFs that are absent, results in misregulated expression of pluripotency genes and induction of differentiation. Thus, the selective expression and use of TAFs underlies the ability of hESCs to self-renew. DOI: http://dx.doi.org/10.7554/eLife.00068.001 PMID:23150797

  17. [Cellular mechanism of the generation of spontaneous activity in gastric muscle].

    PubMed

    Nakamura, Eri; Kito, Yoshihiko; Fukuta, Hiroyasu; Yanai, Yoshimasa; Hashitani, Hikaru; Yamamoto, Yoshimichi; Suzuki, Hikaru

    2004-03-01

    In gastric smooth muscles, interstitial cells of Cajal (ICC) might be the pacemaker cells of spontaneous activities since ICC are rich in mitochondria and are connected with smooth muscle cells via gap junctions. Several types of ICC are distributed widely in the stomach wall. A group of ICC distributed in the myenteric layer (ICC-MY) were the pacemaker cells of gastrointestinal smooth muscles. Pacemaker potentials were generated in ICC-MY, and the potentials were conducted to circular smooth muscles to trigger slow waves and also conducted to longitudinal muscles to form follower potentials. In circular muscle preparations, interstitial cells distributed within muscle bundles (ICC-IM) produced unitary potentials, which were conducted to circular muscles to form slow potentials by summation. In mutant mice lacking inositol trisphosphate (IP(3)) receptor, slow waves were absent in gastric smooth muscles. The generation of spontaneous activity was impaired by the inhibition of Ca(2+)-release from internal stores through IP(3) receptors, inhibition of mitochondrial Ca(2+)-handling with proton pump inhibitors, and inhibition of ATP-sensitive K(+)-channels at the mitochondrial inner membrane. These results suggested that mitochondrial Ca(2+)-handling causes the generation of spontaneous activity in pacemaker cells. Possible involvement of protein kinase C (PKC) in the Ca(2+) signaling system was also suggested.

  18. Disruption of the Crithidia fasciculata RNH1 gene results in the loss of two active forms of ribonuclease H.

    PubMed Central

    Ray, D S; Hines, J C

    1995-01-01

    Both prokaryotic and eukaryotic cells contain multiple forms of ribonuclease H, a ribonuclease that specifically degrades the RNA strand of RNA-DNA hybrids and which has been implicated in the processing of initiator RNAs and in the removal of RNA primers from Okazaki fragments. The Crithidia fasciculata RNH1 gene encodes an RNase H and was shown to be a single-copy gene in this diploid trypanosomatid. The RNH1 gene has been disrupted by targeted gene disruption using hygromycin or G418 drug-resistance cassettes. Major active forms of RNase H (38 and 45 kDa) were observed on activity gels of extracts of wild-type cells or cells in which one allele of RNH1 was disrupted. Both the 38 and 45 kDa activities were absent in extracts of cells in which both alleles of RNH1 were disrupted indicating that both forms of the C.fasciculata RNase H are encoded by the RNH1 gene. Images PMID:7630731

  19. Recreational Physical Activity and the Risk of Preeclampsia: A Prospective Cohort of Norwegian Women

    PubMed Central

    Trogstad, Lill; Owe, Katrine M.; Olsen, Sjurdur F.; Nystad, Wenche

    2008-01-01

    Previous case-control studies suggest that recreational physical activity protects against preeclampsia. Using a prospective design, the authors estimated the risk of preeclampsia for pregnant women according to level of physical activity, taking other variables that influence risk into consideration. The data set comprised 59,573 pregnancies from the Norwegian Mother and Child Cohort Study (1999–2006). Information on physical activity and other exposures was extracted from questionnaire responses given in pregnancy weeks 14–22, whereas diagnosis of preeclampsia was retrieved from the Medical Birth Registry of Norway. Estimation and confounder control was performed with multiple logistic regression. About 24% of pregnant women reported no physical activity, and 7% reported more than 25 such activities per month. The adjusted odds ratio was 0.79 (95% confidence interval: 0.65, 0.96) for preeclampsia when comparing women who exercised 25 times or more per month with inactive women. The association appeared strongest among women whose body mass index was less than 25 kg/m2 and was absent among women whose body mass index was higher than 30 kg/m2. These results suggest that the preventive effect of recreational physical activity during pregnancy may be more limited than has been shown in case-control studies and may apply to nonobese women only. PMID:18701444

  20. Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways

    PubMed Central

    Slominski, Andrzej T.; Zmijewski, Michal A.; Semak, Igor; Zbytek, Blazej; Pisarchik, Alexander; Li, Wei; Zjawiony, Jordan; Tuckey, Robert C.

    2013-01-01

    Skin is the largest body organ forming a metabolically active barrier between external and internal environments. The metabolic barrier is composed of cytochromes P450 (CYPs) that regulate its homeostasis through activation or inactivation of biologically relevant molecules. In this review we focus our attention on local steroidogenic and secosteroidogenic systems in relation to skin cancer, e.g., prevention, attenuation of tumor progression and therapy. The local steroidogenic system is composed of locally expressed CYPs involved in local production of androgens, estrogens, gluco- and mineralo-corticosteroids from cholesterol (initiated by CYP11A1) or from steroid precursors delivered to the skin, and of their metabolism and/or inactivation. Cutaneous 7-hydroxylases (CYP7A1, CYP7B1 and CYP39) potentially can produce 7-hydroxy/oxy-steroids/sterols with modifying effects on local tumorigenesis. CYP11A1 also transforms 7-dehydrocholesterol (7DHC)→22(OH)7DHC→20,22(OH)2-7DHC→7-dehydropregnenolone, which can be further metabolized to other 5,7-steroidal dienes. These 5,7-dienal intermediates are converted by ultraviolet radiation B (UVB) into secosteroids which show pro-differentiation and anti-cancer properties. Finally, the skin is the site of activation of vitamin D3 through two alternative pathways. The classical one involves sequential hydroxylation at positions 25 and 1 to produce active 1,25(OH)2D3, which is further inactivated through hydroxylation at C24. The novel pathway is initiated by CYP11A1 with predominant production of 20(OH)D3 which is further metabolized to biologically active but non-calcemic D3-hydroxyderivatives. Classical and non-classical (novel) vitamin D analogs show pro-differentiation, anti-proliferative and anticancer properties. In addition, melatonin is metabolized by local CYPs. In conclusion cutaneously expressed CYPs have significant effects on skin physiology and pathology trough regulation of its chemical milieu. PMID:23869782

  1. No Sun-like dynamo on the active star ζ Andromedae from starspot asymmetry.

    PubMed

    Roettenbacher, R M; Monnier, J D; Korhonen, H; Aarnio, A N; Baron, F; Che, X; Harmon, R O; Kővári, Zs; Kraus, S; Schaefer, G H; Torres, G; Zhao, M; ten Brummelaar, T A; Sturmann, J; Sturmann, L

    2016-05-12

    Sunspots are cool areas caused by strong surface magnetic fields that inhibit convection. Moreover, strong magnetic fields can alter the average atmospheric structure, degrading our ability to measure stellar masses and ages. Stars that are more active than the Sun have more and stronger dark spots than does the Sun, including on the rotational pole. Doppler imaging, which has so far produced the most detailed images of surface structures on other stars, cannot always distinguish the hemisphere in which the starspots are located, especially in the equatorial region and if the data quality is not optimal. This leads to problems in investigating the north-south distribution of starspot active latitudes (those latitudes with more starspot activity); this distribution is a crucial constraint of dynamo theory. Polar spots, whose existence is inferred from Doppler tomography, could plausibly be observational artefacts. Here we report imaging of the old, magnetically active star ζ Andromedae using long-baseline infrared interferometry. In our data, a dark polar spot is seen in each of two observation epochs, whereas lower-latitude spot structures in both hemispheres do not persist between observations, revealing global starspot asymmetries. The north-south symmetry of active latitudes observed on the Sun is absent on ζ And, which hosts global spot patterns that cannot be produced by solar-type dynamos.

  2. Electron cyclotron heating can drastically alter reversed shear Alfvén eigenmode activity in DIII-D through finite pressure effects

    NASA Astrophysics Data System (ADS)

    Van Zeeland, M. A.; Heidbrink, W. W.; Sharapov, S. E.; Spong, D.; Cappa, A.; Chen, Xi; Collins, C.; García-Muñoz, M.; Gorelenkov, N. N.; Kramer, G. J.; Lauber, P.; Lin, Z.; Petty, C.

    2016-11-01

    A recent DIII-D experiment investigating the impact of electron cyclotron heating (ECH) on neutral beam driven reversed shear Alfvén eigenmode (RSAE) activity is presented. The experiment includes variations of ECH injection location and timing, current ramp rate, beam injection geometry (on/off-axis), and neutral beam power. Essentially all variations carried out in this experiment were observed to change the impact of ECH on AE activity significantly. In some cases, RSAEs were observed to be enhanced with ECH near the off-axis minimum in magnetic safety factor ({{q}\\min} ), in contrast to the original DIII-D experiments where the modes were absent when ECH was deposited near {{q}\\min} . It is found that during intervals when the geodesic acoustic mode (GAM) frequency at {{q}\\min} is elevated and the calculated RSAE minimum frequency, including contributions from thermal plasma gradients, is very near or above the nominal TAE frequency (f TAE), RSAE activity is not observed or RSAEs with a much reduced frequency sweep range are found. This condition is primarily brought about by ECH modification of the local electron temperature (T e) which can raise both the local T e at {{q}\\min} as well as its gradient. A q-evolution model that incorporates this reduction in RSAE frequency sweep range is in agreement with the observed spectra and appears to capture the relative balance of TAE or RSAE-like modes throughout the current ramp phase of over 38 DIII-D discharges. Detailed ideal MHD calculations using the NOVA code show both modification of plasma pressure and pressure gradient at {{q}\\min} play an important role in modifying the RSAE activity. Analysis of the ECH injection near the {{q}\\min} case where no frequency sweeping RSAEs are observed shows the typical RSAE is no longer an eigenmode of the system. What remains is an eigenmode with poloidal harmonic content reminiscent of the standard RSAE, but absent of the typical frequency sweeping behavior. The

  3. Electron cyclotron heating can drastically alter reversed shear Alfvén eigenmode activity in DIII-D through finite pressure effects

    DOE PAGES

    Van Zeeland, M. A.; Heidbrink, W. W.; Sharapov, S. E.; ...

    2016-07-22

    Here, a recent DIII-D experiment investigating the impact of electron cyclotron heating (ECH) on neutral beam driven reversed shear Alfvén eigenmode (RSAE) activity is presented. The experiment includes variations of ECH injection location and timing, current ramp rate, beam injection geometry (on/off-axis), and neutral beam power. Essentially all variations carried out in this experiment were observed to change the impact of ECH on AE activity significantly. In some cases, RSAEs were observed to be enhanced with ECH near the off-axis minimum in magnetic safety factor (more » $${{q}_{\\min}}$$ ), in contrast to the original DIII-D experiments where the modes were absent when ECH was deposited near $${{q}_{\\min}}$$ . It is found that during intervals when the geodesic acoustic mode (GAM) frequency at $${{q}_{\\min}}$$ is elevated and the calculated RSAE minimum frequency, including contributions from thermal plasma gradients, is very near or above the nominal TAE frequency (f TAE), RSAE activity is not observed or RSAEs with a much reduced frequency sweep range are found. This condition is primarily brought about by ECH modification of the local electron temperature (T e) which can raise both the local T e at $${{q}_{\\min}}$$ as well as its gradient. A q-evolution model that incorporates this reduction in RSAE frequency sweep range is in agreement with the observed spectra and appears to capture the relative balance of TAE or RSAE-like modes throughout the current ramp phase of over 38 DIII-D discharges. Detailed ideal MHD calculations using the NOVA code show both modification of plasma pressure and pressure gradient at $${{q}_{\\min}}$$ play an important role in modifying the RSAE activity. Analysis of the ECH injection near the $${{q}_{\\min}}$$ case where no frequency sweeping RSAEs are observed shows the typical RSAE is no longer an eigenmode of the system. What remains is an eigenmode with poloidal harmonic content reminiscent of the standard RSAE, but

  4. The DNA Helicase Activity of BLM Is Necessary for the Correction of the Genomic Instability of Bloom Syndrome Cells

    PubMed Central

    Neff, Norma F.; Ellis, Nathan A.; Ye, Tian Zhang; Noonan, James; Huang, Kelly; Sanz, Maureen; Proytcheva, Maria

    1999-01-01

    Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by growth deficiency, immunodeficiency, genomic instability, and the early development of cancers of many types. BLM, the protein encoded by BLM, the gene mutated in BS, is localized in nuclear foci and absent from BS cells. BLM encodes a DNA helicase, and proteins from three missense alleles lack displacement activity. BLM transfected into BS cells reduces the frequency of sister chromatid exchanges and restores BLM in the nucleus. Missense alleles fail to reduce the sister chromatid exchanges in transfected BS cells or restore the normal nuclear pattern. BLM complements a phenotype of a Saccharomyces cerevisiae sgs1 top3 strain, and the missense alleles do not. This work demonstrates the importance of the enzymatic activity of BLM for its function and nuclear localization pattern. PMID:10069810

  5. Spontaneous default network activity reflects behavioral variability independent of mind-wandering.

    PubMed

    Kucyi, Aaron; Esterman, Michael; Riley, Clay S; Valera, Eve M

    2016-11-29

    The brain's default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain-behavior-experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report.

  6. Spontaneous default network activity reflects behavioral variability independent of mind-wandering

    PubMed Central

    Kucyi, Aaron; Esterman, Michael; Riley, Clay S.; Valera, Eve M.

    2016-01-01

    The brain’s default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain–behavior–experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report. PMID:27856733

  7. Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence.

    PubMed Central

    Katiyar, S K; Gordon, V R; McLaughlin, G L; Edlind, T D

    1994-01-01

    Benzimidazoles have been widely used since the 1960s as anthelmintic agents in veterinary and human medicine and as antifungal agents in agriculture. More recently, selected benzimidazole derivatives were shown to be active in vitro against two protozoan parasites, Trichomonas vaginalis and Giardia lamblia, and clinical studies with AIDS patients have suggested that microsporidia are susceptible as well. Here, we first present in vitro susceptibility data for T. vaginalis and G. lamblia using an expanded set of benzimidazole derivatives. Both parasites were highly susceptible to four derivatives, including mebendazole, flubendazole, and fenbendazole (50% inhibitory concentrations of 0.005 to 0.16 microgram/ml). These derivatives also had lethal activity that was time dependent: 90% of T. vaginalis cells failed to recover following a 20-h exposure to mebendazole at 0.17 microgram/ml. G. lamblia, but not T. vaginalis, was highly susceptible to five additional derivatives. Next, we examined in vitro activity of benzimidazoles against additional protozoan parasites: little or no activity was observed against Entamoeba histolytica, Leishmania major, and Acanthamoeba polyphaga. Since the microtubule protein beta-tubulin has been identified as the benzimidazole target in helminths and fungi, potential correlations between benzimidazole activity and beta-tubulin sequence were examined. This analysis included partial sequences (residues 108 to 259) from the organisms mentioned above, as well as the microsporidia Encephalitozoon hellem and Encephalitozoon cuniculi and the sporozoan Cryptosporidium parvum. beta-tubulin residues Glu-198 and, in particular, Phe-200 are strong predictors of benzimidazole susceptibility; both are present in Encephalitozoon spp. but absent in C. parvum. PMID:7811023

  8. Fructose 6-phosphate phosphoketolase activity in wild-type strains of Lactobacillus, isolated from the intestinal tract of pigs.

    PubMed

    Bolado-Martínez, E; Acedo-Félix, E; Peregrino-Uriarte, A B; Yepiz-Plascencia, G

    2012-01-01

    Phosphoketolases are key enzymes of the phosphoketolase pathway of heterofermentative lactic acid bacteria, which include lactobacilli. In heterofermentative lactobacilli xylulose 5-phosphate phosphoketolase (X5PPK) is the main enzyme of the phosphoketolase pathway. However, activity of fructose 6-phosphate phosphoketolase (F6PPK) has always been considered absent in lactic acid bacteria. In this study, the F6PPK activity was detected in 24 porcine wild-type strains of Lactobacillus reuteri and Lactobacillus mucosae, but not in the Lactobacillus salivarius or in L. reuteri ATCC strains. The activity of F6PPK increased after treatment of the culture at low-pH and diminished after porcine bile-salts stress conditions in wild-type strains of L. reuteri. Colorimetric quantification at 505 nm allowed to differentiate between microbial strains with low activity and without the activity of F6PPK. Additionally, activity of F6PPK and the X5PPK gene expression levels were evaluated by real time PCR, under stress and nonstress conditions, in 3 L. reuteri strains. Although an exact correlation, between enzyme activity and gene expression was not obtained, it remains possible that the xpk gene codes for a phosphoketolase with dual substrate, at least in the analyzed strains of L. reuteri.

  9. A common active site of polyhydroxyalkanoate synthase from Bacillus cereus YB-4 is involved in polymerization and alcoholysis reactions.

    PubMed

    Hyakutake, Manami; Tomizawa, Satoshi; Mizuno, Kouhei; Hisano, Tamao; Abe, Hideki; Tsuge, Takeharu

    2015-06-01

    Polyhydroxyalkanoate (PHA) synthase from Bacillus cereus YB-4 (PhaRCYB4) catalyzes not only PHA polymerization but also alcoholytic cleavage of PHA chains. The alcoholysis activity of PhaRCYB4 is expressed when a hydroxyacyl-CoA monomer is absent but an alcohol compound is present. In this study, we performed alanine mutagenesis of the putative catalytic triad (Cys(151), Asp(306), and His(335)) in the PhaCYB4 subunit to identify the active site residues for polymerization and alcoholysis activities. Individual substitution of each triad residue with alanine resulted in loss of both polymerization and alcoholysis activities, suggesting that these residues are commonly shared between polymerization and alcoholysis reactions. The loss of activity was also observed following mutagenesis of the triad to other amino acids, except for one PhaRCYB4 mutant with a C151S substitution, which lost polymerization activity but still possessed cleavage activity towards PHA chains. The low-molecular-weight PHA isolated from the PhaRCYB4(C151S)-expressing strain showed a lower ratio of alcohol capping at the P(3HB) carboxy terminus than did that from the wild-type-expressing strain. This observation implies that hydrolysis activity of PhaRCYB4 might be elicited by the C151S mutation.

  10. Gamma band activity and the P3 reflect post-perceptual processes, not visual awareness

    PubMed Central

    Pitts, Michael A.; Padwal, Jennifer; Fennelly, Daniel; Martínez, Antígona; Hillyard, Steven A.

    2014-01-01

    A primary goal in cognitive neuroscience is to identify neural correlates of conscious perception (NCC). By contrasting conditions in which subjects are aware versus unaware of identical visual stimuli, a number of candidate NCCs have emerged, among them induced gamma band activity in the EEG and the P3 event-related potential. In most previous studies, however, the critical stimuli were always directly relevant to the subjects’ task, such that aware versus unaware contrasts may well have included differences in post-perceptual processing in addition to differences in conscious perception per se. Here, in a series of EEG experiments, visual awareness and task relevance were manipulated independently. Induced gamma activity and the P3 were absent for task-irrelevant stimuli regardless of whether subjects were aware of such stimuli. For task-relevant stimuli, gamma and the P3 were robust and dissociable, indicating that each reflects distinct post-perceptual processes necessary for carrying-out the task but not for consciously perceiving the stimuli. Overall, this pattern of results challenges a number of previous proposals linking gamma band activity and the P3 to conscious perception. PMID:25063731

  11. Persistent suppression of subthalamic beta-band activity during rhythmic finger tapping in Parkinson's disease.

    PubMed

    Joundi, Raed A; Brittain, John-Stuart; Green, Alex L; Aziz, Tipu Z; Brown, Peter; Jenkinson, Ned

    2013-03-01

    The function of synchronous oscillatory activity at beta band (15-30Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement. We recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson's disease during a synchronized tapping task at three different externally cued rates. Beta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate. Our results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping, These findings implicate consistent beta suppression in the facilitation of continuous movement sequences. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Pit-1 inhibits BRCA1 and sensitizes human breast tumors to cisplatin and vitamin D treatment

    PubMed Central

    Seoane, Samuel; Arias, Efigenia; Sigueiro, Rita; Sendon-Lago, Juan; Martinez-Ordoñez, Anxo; Castelao, Esteban; Eiró, Noemí; Garcia-Caballero, Tomás; Macia, Manuel; Lopez-Lopez, Rafael; Maestro, Miguel; Vizoso, Francisco; Mouriño, Antonio; Perez-Fernandez, Roman

    2015-01-01

    The POU class 1 homeobox 1 (POU1F1, also known as Pit-1), pertaining to the Pit-Oct-Unc (POU) family of transcription factors, has been related to tumor growth and metastasis in breast. However, its role in response to breast cancer therapy is unknown. We found that Pit-1 down-regulated DNA-damage and repair genes, and specifically inhibited BRCA1 gene expression, sensitizing breast cancer cells to DNA-damage agents. Administration of 1α, 25-dihydroxy-3-epi-vitamin D3 (3-Epi, an endogenous low calcemic vitamin D metabolite) reduced Pit-1 expression, and synergized with cisplatin, thus, decreasing cell proliferation and apoptosis in vitro, and reducing tumor growth in vivo. In addition, fifteen primary cultures of human breast tumors showed significantly decreased proliferation when treated with 3-Epi+cisplatin, compared to cisplatin alone. This response positively correlated with Pit-1 levels. Our findings demonstrate that high levels of Pit-1 and reduced BRCA1 levels increase breast cancer cell susceptibility to 3-Epi+cisplatin therapy. PMID:25992773

  13. [Genealogy of the Books of Practica medicinae in Europe before the End of 18th Century: From the Origin to the Disappearance].

    PubMed

    Sakai, Tatsuo

    2015-09-01

    The Practica medicinae represented the books written in Europe before the end of 18th century that dealt with individual deseases. In total, 100 Practica books, written by 95 authors, were collected and divided into four periods from the early 11th to the end of 18th century. The first Practica book was written at the Salernitan medical school on the basis of ancient medical books in the basic style, dealing with regional deseases arranged in "a capite ad calcem" manner, as well as with the fevers. The basic style comprised a majority in the first period and decreased gradually, becoming a minority in the 3rd and 4th periods. Sennert's practica was the largest and it elaborated with precise construction. The additional categories, such as female, children, and surgical deseases increased in the later periods. Those written in non-basic style based on pathogenesis or in alphabetical order also increased in the later periods. The practica books changed slightly and gradually, indicating the essential consistency of the concepts of diseases in these periods.

  14. Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

    PubMed

    Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2017-07-01

    Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p < .001). Elevated caudate activation was associated with robust improvement for methylphenidate and little improvement for atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p < .001). Enhanced caudate activation for response inhibition may be a candidate biomarker of superior response to methylphenidate over atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American

  15. A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence.

    PubMed

    Lou, Haiyi; Lu, Yan; Lu, Dongsheng; Fu, Ruiqing; Wang, Xiaoji; Feng, Qidi; Wu, Sijie; Yang, Yajun; Li, Shilin; Kang, Longli; Guan, Yaqun; Hoh, Boon-Peng; Chung, Yeun-Jun; Jin, Li; Su, Bing; Xu, Shuhua

    2015-07-02

    Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10(-15)). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276-46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r(2) = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Inhibitory Phenotype of HBV-Specific CD4+ T-Cells Is Characterized by High PD-1 Expression but Absent Coregulation of Multiple Inhibitory Molecules

    PubMed Central

    Kurktschiev, Peter; Schraut, Winfried; Zachoval, Reinhart; Wendtner, Clemens; Wächtler, Martin; Spannagl, Michael; Denk, Gerald; Ulsenheimer, Axel; Bengsch, Bertram; Pircher, Hanspeter; Diepolder, Helmut M.; Grüner, Norbert H.; Jung, Maria-Christina

    2014-01-01

    Background T-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB) infection and the role of inhibitory molecules such as programmed death 1 (PD-1) for CD4+ T-cell failure. Methods The expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer. Effects of in vitro PD-L1/2 blockade were defined by investigating changes in CD4+ T-cell proliferation and cytokine production. Results CD4+ T-cell responses during chronic HBV infection was characterized by reduced Tetramer+CD4+ T-cell frequencies, effector memory phenotype, sustained PD-1 but low levels of CTLA-4, TIM-3, KLRG1 and CD244 expression. PD-1 blockade revealed individualized patterns of in vitro responsiveness with partly increased IFN-γ, IL-2 and TNF-α secretion as well as enhanced CD4+ T-cell expansion almost in treated patients with viral control. Conclusion HBV-specific CD4+ T-cells are reliably detectable during different courses of HBV infection by MHC class II Tetramer technology. CD4+ T-cell dysfunction during chronic HBV is basically linked to strong PD-1 upregulation but absent coregulation of multiple inhibitory receptors. PD-L1/2 neutralization partly leads to enhanced CD4+ T-cell functionality with heterogeneous patterns of CD4+ T-cell rejunivation. PMID:25144233

  17. A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence

    PubMed Central

    Lou, Haiyi; Lu, Yan; Lu, Dongsheng; Fu, Ruiqing; Wang, Xiaoji; Feng, Qidi; Wu, Sijie; Yang, Yajun; Li, Shilin; Kang, Longli; Guan, Yaqun; Hoh, Boon-Peng; Chung, Yeun-Jun; Jin, Li; Su, Bing; Xu, Shuhua

    2015-01-01

    Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10−15). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276–46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r2 = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075–14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1. PMID:26073780

  18. A mechanical stretch induces contractile activation in unstimulated developing rat skeletal muscle in vitro

    PubMed Central

    Mutungi, Gabriel; Edman, K A P; Ranatunga, K W

    2003-01-01

    The effects of a stretch-release cycle (≈25 % of the resting muscle fibre length, Lo) on both tension and [Ca2+]i in small, unstimulated, intact muscle fibre bundles isolated from adult and neonatal rats were investigated at 20 °C. The results show that the effects of the length change depended on the age of the rats. Thus, the length change produced three effects in the neonatal rat muscle fibre bundles, but only a single effect in the adult ones. In the neonatal fibre bundles, the length change led to an increase in resting muscle tension and to a transient increase in [Ca2+]i. The stretch-release cycle was then followed by a twitch-like tension response. In the adult fibre bundles, only the increase in resting tension was seen and both the transient increase in [Ca2+]i and the stretch-induced twitch-like tension response were absent. The amplitude of the twitch-like tension response was affected by both 2,3-butanedione monoxime and sarcomere length in the same manner as active twitch tension, suggesting that it arose from actively cycling crossbridges. It was also reversibly abolished by 25 mM K+, 1 μM tetrodotoxin and 1.5 mM lidocaine (lignocaine), and was significantly depressed (P < 0.001) by lowering [Ca2+]o. These findings suggest that a rapid stretch in neonatal rats induces a propagated impulse that leads to an increase in [Ca2+]i, and that abolishing the action potential abolishes the stretch-induced twitch-like tension response. In 5- to 7-day-old rats, the twitch-like tension response was ≈50 % of the isometric twitch. It then decreased progressively with age and was virtually absent by the time the rats were 21 days old. Interestingly, this is the same period over which rat muscles differentiate from their neonatal to their adult types. PMID:12813148

  19. Analysis of phytochemical constituents of Eucalyptus citriodora L. responsible for antifungal activity against post-harvest fungi.

    PubMed

    Javed, S; Shoaib, A; Mahmood, Z; Mushtaq, S; Iftikhar, S

    2012-01-01

    In vitro antifungal activity and phytochemical constituents of essential oil, aqueous, methanol and chloroform extract of Eucalyptus citriodora Hook leaves were investigated. A qualitative phytochemical analysis was performed for the detection of alkaloids, cardiac glycosides, flavonoids, saponins, sterols, tannins and phenols. Methanolic extract holds all identified biochemical constituents except for the tannin. While these biochemical constituents were found to be absent in essential oil, aqueous and chloroform extracts with the exception of sterols, cardiac glycosides and phenols in essential oil and sterols and phenols in aqueous and chloroform extracts. Antimycotic activity of four fractions of E. citriodora was investigated through agar-well diffusion method against four post-harvest fungi, namely, Aspergillus flavus Link ex Gray, Aspergillus fumigatus Fres., Aspergillus nidulans Eidam ex Win and Aspergillus terreus Thom. The results revealed maximum fungal growth inhibition by methanolic extract (14.5%) followed by essential oil (12.9%), chloroform extract (10.15%) and aqueous extract (10%).

  20. Role of Prefrontal Persistent Activity in Working Memory

    PubMed Central

    Riley, Mitchell R.; Constantinidis, Christos

    2016-01-01

    The prefrontal cortex is activated during working memory, as evidenced by fMRI results in human studies and neurophysiological recordings in animal models. Persistent activity during the delay period of working memory tasks, after the offset of stimuli that subjects are required to remember, has traditionally been thought of as the neural correlate of working memory. In the last few years several findings have cast doubt on the role of this activity. By some accounts, activity in other brain areas, such as the primary visual and posterior parietal cortex, is a better predictor of information maintained in visual working memory and working memory performance; dynamic patterns of activity may convey information without requiring persistent activity at all; and prefrontal neurons may be ill-suited to represent non-spatial information about the features and identity of remembered stimuli. Alternative interpretations about the role of the prefrontal cortex have thus been suggested, such as that it provides a top-down control of information represented in other brain areas, rather than maintaining a working memory trace itself. Here we review evidence for and against the role of prefrontal persistent activity, with a focus on visual neurophysiology. We show that persistent activity predicts behavioral parameters precisely in working memory tasks. We illustrate that prefrontal cortex represents features of stimuli other than their spatial location, and that this information is largely absent from early cortical areas during working memory. We examine memory models not dependent on persistent activity, and conclude that each of those models could mediate only a limited range of memory-dependent behaviors. We review activity decoded from brain areas other than the prefrontal cortex during working memory and demonstrate that these areas alone cannot mediate working memory maintenance, particularly in the presence of distractors. We finally discuss the discrepancy between

  1. Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha.

    PubMed

    Li, Guolin; Brocker, Chad N; Yan, Tingting; Xie, Cen; Krausz, Kristopher W; Xiang, Rong; Gonzalez, Frank J

    2018-01-01

    Peroxisome proliferator-activated receptor alpha (PPARA) is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF) has not been investigated. Mice were pre-conditioned using either a diet containing the potent PPARA agonist Wy-14643 or an EODF regimen prior to acute fasting. Ppara-null mice were used to assess the contribution of PPARA activation during the metabolic response to EODF. Livers were collected for histological, biochemical, qRT-PCR, and Western blot analysis. Acute fasting activated PPARA and led to steatosis, whereas EODF protected against fasting-induced hepatic steatosis without affecting PPARA signaling. In contrast, pretreatment with Wy-14,643 did activate PPARA signaling but did not ameliorate acute fasting-induced steatosis and unexpectedly promoted liver injury. Ppara ablation exacerbated acute fasting-induced hypoglycemia, hepatic steatosis, and liver injury in mice, whereas these detrimental effects were absent in response to EODF, which promoted PPARA-independent fatty acid metabolism and normalized serum lipids. These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis. Published by Elsevier GmbH.

  2. Proteinuria and lipoprotein lipase activity in Miniature schnauzer dogs with and without hypertriglyceridemia

    PubMed Central

    Furrow, E.; Jaeger, J.Q.; Parker, V.J.; Hinchcliff, K.W.; Johnson, S.E.; Murdoch, S.J.; de Boer, I.H.; Sherding, R.G.; Brunzell, J.D.

    2016-01-01

    Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature shnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77–0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required. PMID:27256031

  3. A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis.

    PubMed

    Kumar, Anuradha; Casey, Allen; Odingo, Joshua; Kesicki, Edward A; Abrahams, Garth; Vieth, Michal; Masquelin, Thierry; Mizrahi, Valerie; Hipskind, Philip A; Sherman, David R; Parish, Tanya

    2013-01-01

    The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis. It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed.

  4. The microsomal mixed function oxidase system of amphibians and reptiles: components, activities and induction.

    PubMed

    Ertl, R P; Winston, G W

    1998-11-01

    This article reviews current research in amphibian and reptilian cytochromes P450, important to the overall understanding of xenobiotic metabolism in the ecosystem and the evolution of P450s. Amphibians and reptilians contain the normal mixed function oxidase system (MFO). In general the MFO content and activities are less than those found in mammals, but only a few of the known activities have been examined in these vertebrate classes. Research to date has focused on two families of cytochromes P450, CYP1 and 2. The isoforms examined catalyze the classic activities but there have been notable absences. The total number of isoforms present and the breadth of substrates metabolized are yet unknown. Induction by foreign compounds (xenobiotics) is lengthier and yields lower levels of induced activity than is typically found in mammals. When these animals are pretreated with 3-methylcholanthrene (3MC) and beta-naphthaflavone (BNF), which are known to induce the same isoform in mammals, multiple isoforms are induced with different activities. Phenobarbital-pretreatment in turtles and alligators induces cytochromes P450 and suggestive data indicates induction in the lizard Agama lizard and the newt Pleurodeles waltl. In amphibians and reptiles a CYP2B protein does appear to be present along with constitutive activities associated with the 2 family of cytochromes P450. The markedly different response to classic inducers combined with lower or absent activities alters the view of how amphibians and reptilians respond to xenobiotic challenges.

  5. Graded activity for low back pain in occupational health care: a randomized, controlled trial.

    PubMed

    Staal, J Bart; Hlobil, Hynek; Twisk, Jos W R; Smid, Tjabe; Köke, Albère J A; van Mechelen, Willem

    2004-01-20

    Low back pain is a common medical and social problem frequently associated with disability and absence from work. However, data on effective return to work after interventions for low back pain are scarce. To determine the effectiveness of a behavior-oriented graded activity program compared with usual care. Randomized, controlled trial. Occupational health services department of an airline company in the Netherlands. 134 workers who were absent from work because of low back pain were randomly assigned to either graded activity (n = 67) or usual care (n = 67). Graded activity, a physical exercise program based on operant-conditioning behavioral principles, to stimulate a rapid return to work. Outcomes were the number of days of absence from work because of low back pain, functional status (Roland Disability Questionnaire), and severity of pain (11-point numerical scale). The median number of days of absence from work over 6 months of follow-up was 58 days in the graded activity group and 87 days in the usual care group. From randomization onward, graded activity was effective after 50 days of absence from work (hazard ratio, 1.9 [95% CI, 1.2 to 3.2]; P = 0.009). The graded activity group was more effective in improving functional status and pain than the usual care group. The effects, however, were small and not statistically significant. Graded activity was more effective than usual care in reducing the number of days of absence from work because of low back pain.

  6. Stability and activity modulation of chymotrypsins in AOT reversed micelles by protein-interface interaction: interaction of alpha-chymotrypsin with a negative interface leads to a cooperative breakage of a salt bridge that keeps the catalytic active conformation (Ile16-Asp194).

    PubMed

    Almeida, F C; Valente, A P; Chaimovich, H

    1998-08-05

    The stability of alpha-chymotrypsin and delta-chymotrypsin was studied in reversed micelles of sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane. alpha-Chymotrypsin is inactivated at the interface and at the water pool, while delta-chymotrypsin is inactivated only at the water pool. The mechanism of inactivation at the interface is related to the interaction of N-terminal group alanine 149 (absent in delta-chymotrypsin) with the negative interface. The dependence of enzyme activity on water content of these two enzymes in reversed micelles of AOT is also related with the interface interaction, since delta-chymotrypsin does not have a bell-shaped curve as observed for alpha-chymotrypsin. Copyright 1998 John Wiley & Sons, Inc.

  7. Endo-β-Glucosidase Tag Allows Dual Detection of Fusion Proteins by Fluorescent Mechanism-Based Probes and Activity Measurement.

    PubMed

    Kallemeijn, Wouter W; Scheij, Saskia; Voorn-Brouwer, Tineke M; Witte, Martin D; Verhoek, Marri; Overkleeft, Hermen S; Boot, Rolf G; Aerts, Johannes M F G

    2016-09-15

    β-Glucoside-configured cyclophellitols are activity-based probes (ABPs) that allow sensitive detection of β-glucosidases. Their applicability to detect proteins fused with β-glucosidase was investigated in the cellular context. The tag was Rhodococcus sp. M-777 endoglycoceramidase II (EGCaseII), based on its lack of glycans and ability to hydrolyze fluorogenic 4-methylumbelliferyl β-d-lactoside (an activity absent in mammalian cells). Specific dual detection of fusion proteins was possible in vitro and in situ by using fluorescent ABPs and a fluorogenic substrate. Pre-blocking with conduritol β-epoxide (a poor inhibitor of EGCaseII) eliminated ABP labeling of endogenous β-glucosidases. ABPs equipped with biotin allowed convenient purification of the fusion proteins. Diversification of ABPs (distinct fluorophores, fluorogenic high-resolution detection moieties) should assist further research in living cells and organisms. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Being accountable for care of the poor. CHA's social accountability budget helps facilities keep track of charitable activity.

    PubMed

    Trocchio, J; Eckels, T

    1989-06-01

    The Catholic Health Association's social accountability budget is a set of tools to help Catholic healthcare facilities plan for, administer, and report benefits provided to their communities, especially the poor. It defines a full roster of community benefits that a healthcare organization may provide. The benefits fall into three major categories: activities and services, policies and procedures, and community leadership. The social accountability budget also presents guidelines for assessing the facility's existing services, activities, policies, and procedures and discusses how the facility can conduct or be part of a community needs assessment. Information collected through this assessment is used in the planning and budgeting processes. This ensures that uncompensated care and charitable services receive consideration along with traditional planning and budgeting items. Additional guidelines show the facility how to track and measure its services to the community. The final step, often absent from Catholic healthcare facilities' programs, is reporting community benefits.

  9. Stress-induced activation of the immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is restricted to telencephalic areas in the rat brain: relationship to c-fos mRNA.

    PubMed

    Ons, Sheila; Martí, Octavi; Armario, Antonio

    2004-06-01

    Arc is an effector immediate early gene whose expression is induced in situations of increased neuronal activity. However, there is no report on the influence of stress on Arc expression. Here, we compared the induction of both c-fos and Arc mRNAs in the brain of rats exposed to one of three different stressful situations: novel environment, forced swimming and immobilization. An absent or weak c-fos mRNA signal was observed in control rats, whereas those exposed to one of three stressors showed enhanced c-fos expression in a wide range of brain areas. Constitutive Arc expression was observed in some areas such as cortex, striatum, hippocampus, reticular thalamic nucleus and cerebellar cortex. In response to stressors, a strong induction of Arc was observed, but the pattern was different from that of c-fos. For instance, activation of Arc but not c-fos was observed in the nucleus accumbens after immobilization and in the hippocampus after novel environment. No Arc induction was observed in diencephalic and brainstem areas. The present data show that Arc has a neuroanatomically restricted pattern of induction in the brain after emotional stress. Telencephalic activation suggests that a more intense induction of synaptic plasticity is occurring in this area after exposure to emotional stressors.

  10. Genetics Home Reference: thrombocytopenia-absent radius syndrome

    MedlinePlus

    ... half of affected individuals have allergic reactions to cow's milk that may worsen the thrombocytopenia associated with ... Central Mokha J, Serrano M. Thrombocytopenia associated with cow's milk protein allergy: a case report. Clin Pediatr ( ...

  11. An Absent Body in a Present Landscape

    ERIC Educational Resources Information Center

    Marcussen, Jens

    2012-01-01

    The wilderness expedition experience will always be a confluence of emotional, cognitive and bodily processes. The author wants to show that the body is an important but often forgotten part of the wilderness expedition experience. In society, the focus on the body is often polarised. Sometimes, there is an extreme focus on the thin and fit body…

  12. [Influence of the activator of transcription GAL4 on growth and development of embryos and embryonic cells in primary cultures of sand dollar].

    PubMed

    Odintsova, N A; Kiselev, K V; Bulgakov, V P; Kol'tsova, E A; Iakovlev, K V

    2003-01-01

    In order to solve many tasks of biotechnology, constant lines of the cells of marine invertebrates with a high growth potential are required, which are absent at present. We used the universal activator of transcription gal4 to change the degree of expression of genes of growth factors in embryonic sea urchin cells and, thereby, increase their proliferative activity. The fertilized sea urchin eggs and dissociated embryonic cells at the blastula stage were treated with plasmids containing both the functional gene gal4 and the gene devoid of the regions encoding the activator domain. The transfection of embryonic sea urchin eggs with the functional gene led to cell dedifferentiation and formation of tumor-like structures in the embryos or increased number of embryonic cells in culture. In the cells obtained from the transfected embryos, the pigments were found within two months of cultivation, whose absorption spectrum coincided with that of echinochrome.

  13. In vitro biological activity and essential oil composition of four indigenous South African Helichrysum species.

    PubMed

    Lourens, A C U; Reddy, D; Başer, K H C; Viljoen, A M; Van Vuuren, S F

    2004-12-01

    Helichrysum species are used widely to treat various medical conditions. In this study, the anti-microbial, anti-oxidant (DPPH assay) and anti-inflammatory activity (5-lipoxygenase assay) of Helichrysum dasyanthum, Helichrysum felinum, Helichrysum excisum and Helichrysum petiolare were investigated. The essential oil compositions of these species were determined. The acetone and methanol extracts as well as the essential oils exhibited activity against Gram-positive bacteria, while both the methanol and acetone extracts of all four species were active in the anti-oxidant assay. The essential oils, on the other hand, displayed activity in the 5-lipoxygenase assay, which was used as an indication of anti-inflammatory activity. Two extracts exhibited promising activity in the anti-microbial assay, the acetone extract of Helichrysum dasyanthum with a MIC value of 15.63 microg/ml and the methanol extract of Helichrysum excisum with a MIC value of 62.5 microg/ml. The acetone extract of Helichrysum dasyanthum was the most active free radical scavenger in the DPPH assay (IC(50) of 9.53 microg/ml) while values for the anti-inflammatory activity of the essential oils ranged between 25 and 32 microg/ml. The essential oil compositions of three species (Helichrysum dasyanthum, Helichrysum excisum and Helichrysum petiolare) were dominated by the presence of monoterpenes such as alpha-pinene, 1,8-cineole and p-cymene. In the oil of Helichrysum felinum, monoterpenes were largely absent. Its profile consisted of a variety of sesquiterpenes in low concentrations with beta-caryophyllene dominating.

  14. In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling.

    PubMed

    Becker, John V W; van der Merwe, Marina M; van Brummelen, Anna C; Pillay, Pamisha; Crampton, Bridget G; Mmutlane, Edwin M; Parkinson, Chris; van Heerden, Fanie R; Crouch, Neil R; Smith, Peter J; Mancama, Dalu T; Maharaj, Vinesh J

    2011-10-11

    Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile. Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis. The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that

  15. Evaluation of long term solar activity effects on GPS derived TEC

    NASA Astrophysics Data System (ADS)

    Mansoori, Azad A.; Khan, Parvaiz A.; Ahmad, Rafi; Atulkar, Roshni; M, Aslam A.; Bhardwaj, Shivangi; Malvi, Bhupendra; Purohit, P. K.; Gwal, A. K.

    2016-10-01

    The solar activity hence the solar radiance follows a long term periodic variability with eleven years periodicity, known as solar cycle. This drives the long term variability of the ionosphere. In the present problem we investigate the long term behaviour of the ionosphere with the eleven year cyclic solar activity. Under the present study we characterize the ionospheric variability by Total Electron Content (TEC) using measurements made by Global Positioning System (GPS) and solar cycle variability by various solar activity indices. We make use of five solar activity indices viz. sunspot number (Rz), solar radio Flux (F10.7 cm), EUV Flux (26-34 nm), flare index and CME occurrences. The long term variability of these solar activity indices were then compared and correlated with the variability of ionospheric TEC, at a mid latitude station, Usuda (36.13N, 138.36E), of Japan, during the solar cycle 23 and ascending phase of cycle 24. From our study, we found that long term changes in the ionospheric TEC vary synchronously with corresponding changes in the solar activity indices. The correlation analysis shows that all the solar activity indices exhibit a very strong correlation with TEC (R =0.76 -0.99). Moreover the correlation between the two is stronger in the descending phase of the solar cycle. The correlation is found to be remarkably strongest during the deep minimum of the solar cycle 24 i.e. between 2007- 2009. Also we noticed a hysteresis effect exists with solar radio flux (F10.7 cm) and solar EUV flux (26-34 nm). This effect is absent with other parameters.

  16. The effectiveness of graded activity for low back pain in occupational healthcare.

    PubMed

    Steenstra, I A; Anema, J R; Bongers, P M; de Vet, H C W; Knol, D L; van Mechelen, W

    2006-11-01

    Low back pain is a common medical and social problem associated with disability and absence from work. Knowledge on effective return to work (RTW) interventions is scarce. To determine the effectiveness of graded activity as part of a multistage RTW programme. Randomised controlled trial. Occupational healthcare. 112 workers absent from work for more than eight weeks due to low back pain were randomised to either graded activity (n = 55) or usual care (n = 57). Graded activity, a physical exercise programme aimed at RTW based on operant-conditioning behavioural principles. The number of days off work until first RTW for more then 28 days, total number of days on sick leave during follow up, functional status, and severity of pain. Follow up was 26 weeks. Graded activity prolonged RTW. Median time until RTW was equal to the total number of days on sick leave and was 139 (IQR = 69) days in the graded activity group and 111 (IQR = 76) days in the usual care group (hazard ratio = 0.52, 95% CI 0.32 to 0.86). An interaction between a prior workplace intervention and graded activity, together with a delay in the start of the graded activity intervention, explained most of the delay in RTW (hazard ratio = 0.86, 95% CI 0.40 to 1.84 without prior intervention and 0.39, 95% CI 0.19 to 0.81 with prior intervention). Graded activity did not improve pain or functional status clinically significantly. Graded activity was not effective for any of the outcome measures. Different interventions combined can lead to a delay in RTW. Delay in referral to graded activity delays RTW. In implementing graded activity special attention should be paid to the structure and process of care.

  17. Tight coupling of astrocyte energy metabolism to synaptic activity revealed by genetically encoded FRET nanosensors in hippocampal tissue.

    PubMed

    Ruminot, Iván; Schmälzle, Jana; Leyton, Belén; Barros, L Felipe; Deitmer, Joachim W

    2017-01-01

    The potassium ion, K + , a neuronal signal that is released during excitatory synaptic activity, produces acute activation of glucose consumption in cultured astrocytes, a phenomenon mediated by the sodium bicarbonate cotransporter NBCe1 ( SLC4A4). We have explored here the relevance of this mechanism in brain tissue by imaging the effect of neuronal activity on pH, glucose, pyruvate and lactate dynamics in hippocampal astrocytes using BCECF and FRET nanosensors. Electrical stimulation of Schaffer collaterals produced fast activation of glucose consumption in astrocytes with a parallel increase in intracellular pyruvate and biphasic changes in lactate . These responses were blocked by TTX and were absent in tissue slices prepared from NBCe1-KO mice. Direct depolarization of astrocytes with elevated extracellular K + or Ba 2+ mimicked the metabolic effects of electrical stimulation. We conclude that the glycolytic pathway of astrocytes in situ is acutely sensitive to neuronal activity, and that extracellular K + and the NBCe1 cotransporter are involved in metabolic crosstalk between neurons and astrocytes. Glycolytic activation of astrocytes in response to neuronal K + helps to provide an adequate supply of lactate, a metabolite that is released by astrocytes and which acts as neuronal fuel and an intercellular signal.

  18. Characterization of AQX-1125, a small-molecule SHIP1 activator

    PubMed Central

    Stenton, Grant R; Mackenzie, Patrick Tam, Lloyd F; Cross, Jennifer L; Harwig, Curtis; Raymond, Jeffrey; Toews, Judy; Wu, Joyce; Ogden, Nancy; MacRury, Thomas; Szabo, Csaba

    2013-01-01

    Background The SH2-containing inositol-5′-phosphatase 1 (SHIP1) metabolizes PI(3,4,5)P3 to PI(3,4)P2. SHIP1-deficient mice exhibit progressive inflammation. Pharmacological activation of SHIP1 is emerging as a potential therapy for pulmonary inflammatory diseases. Here we characterize the efficacy of AQX-1125, a small-molecule SHIP1 activator currently in clinical development. Experimental Approach The effects of AQX-1125 were tested in several in vitro assays: on enzyme catalytic activity utilizing recombinant human SHIP1, on Akt phosphorylation in SHIP1-proficient and SHIP1-deficient cell lines, on cytokine release in murine splenocytes, on human leukocyte chemotaxis using modified Boyden chambers and on β-hexosaminidase release from murine mast cells. In addition, pharmacokinetic and drug distribution studies were performed in rats and dogs. Results AQX-1125 increased the catalytic activity of human recombinant SHIP1, an effect, which was absent after deletion of the C2 region. AQX-1125 inhibited Akt phosphorylation in SHIP1-proficient but not in SHIP1-deficient cells, reduced cytokine production in splenocytes, inhibited the activation of mast cells and inhibited human leukocyte chemotaxis. In vivo, AQX-1125 exhibited >80% oral bioavailability and >5 h terminal half-life. Conclusions Consistent with the role of SHIP1 in cell activation and chemotaxis, the SHIP1 activator AQX-1125 inhibits Akt phosphorylation, inflammatory mediator production and leukocyte chemotaxis in vitro. The in vitro effects and the pharmacokinetic properties of the compound make it a suitable candidate for in vivo testing in various models of inflammation. Linked Article This article is accompanied by Stenton et al., pp. 1519–1529 of this issue. To view this article visit http://dx.doi.org/10.1111/bph.12038 PMID:23121445

  19. Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci

    PubMed Central

    Philippe, Claude; Vargas-Landin, Dulce B; Doucet, Aurélien J; van Essen, Dominic; Vera-Otarola, Jorge; Kuciak, Monika; Corbin, Antoine; Nigumann, Pilvi; Cristofari, Gaël

    2016-01-01

    LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants. DOI: http://dx.doi.org/10.7554/eLife.13926.001 PMID:27016617

  20. Impact of Stainless Steel Exposure on the Oxidation of Polysorbate 80 in Histidine Placebo and Active Monoclonal Antibody Formulation.

    PubMed

    Gopalrathnam, Ganapathy; Sharma, Anant Navanithan; Dodd, Steven Witt; Huang, Lihua

    2018-01-01

    Rapid oxidation of polysorbate 80 in histidine buffer was observed upon brief exposure to stainless steel. Liquid chromatography-mass spectrometry analysis indicates degradation of both polyoxyethylene sorbitan and polyoxyethylene head groups and unsaturated fatty acid chains, with further confirmation by reversed-phase high-performance liquid chromatography data. Both Fe 2+ and Fe 3+ were shown to induce polysorbate 80 oxidation. The degree of oxidation in polysorbate 20 and polysorbate 80 are comparable for the head groups and saturated fatty acid esters. However, the same phenomenon was not observed with placebo or monoclonal antibody at a threshold protein concentration, formulated in sodium citrate, in combination with histidine and sodium citrate, or with Na 2 ethylenediaminetetraacetic acid (EDTA). Further, polysorbate 80 oxidation was not observed with Lilly's antibody containing the active ingredient LY2951742, at or above a threshold concentration. Finally, no major polysorbate 80 degradation was observed in histidine buffer, with or without protein, in containers composed of glass or plastic, or when stainless steel exposure was otherwise completely absent. Finally, the 2-oxo oxidation form of histidine was not observed, but the other oxidation products and modifications of histidine were identified. LAY ABSTRACT: Rapid oxidation of polysorbate 80 in histidine buffer was observed upon brief exposure to stainless steel. The degree of oxidation in polysorbate 80 and polysorbate 20 were comparable. However, the same phenomenon was not observed with placebo when formulated in sodium citrate, in combination with histidine and sodium citrate, or with Na 2 ethylenediaminetetraacetic acid (EDTA). Polysorbate 80 oxidation was not observed with Lilly's antibody containing the active ingredient, LY2951742, at or above a threshold concentration. No major polysorbate 80 degradation in histidine buffer was observed when stainless steel contact was completely absent.

  1. Removal of a putative inhibitory element reduces the calcium-dependent calmodulin activation of neuronal nitric-oxide synthase.

    PubMed

    Montgomery, H J; Romanov, V; Guillemette, J G

    2000-02-18

    Neuronal nitric-oxide synthase (NOS) and endothelial NOS are constitutive NOS isoforms that are activated by binding calmodulin in response to elevated intracellular calcium. In contrast, the inducible NOS isoform binds calmodulin at low basal levels of calcium in resting cells. Primary sequence comparisons show that each constitutive NOS isozyme contains a polypeptide segment within its reductase domain, which is absent in the inducible NOS enzyme. To study a possible link between the presence of these additional polypeptide segments in constitutive NOS enzymes and their calcium-dependent calmodulin activation, three deletion mutants were created. The putative inhibitory insert was removed from the FMN binding regions of the neuronal NOS holoenzyme and from two truncated neuronal NOS reductase enzymes in which the calmodulin binding region was either included or deleted. All three mutant enzymes showed reduced incorporation of FMN and required reconstitution with exogenous FMN for activity. The combined removal of both the calmodulin binding domain and the putative inhibitory insert did not result in a calmodulin-independent neuronal NOS reductase. Thus, although the putative inhibitory element has an effect on the calcium-dependent calmodulin activation of neuronal NOS, it does not have the properties of the typical autoinhibitory domain found in calmodulin-activated enzymes.

  2. Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women.

    PubMed

    Blitz, Sandra; Baxter, Joanna; Raboud, Janet; Walmsley, Sharon; Rachlis, Anita; Smaill, Fiona; Ferenczy, Alex; Coutlée, François; Hankins, Catherine; Money, Deborah

    2013-08-01

    The Canadian Women's HIV Study (CWHS) enrolled human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women in a longitudinal cohort. This analysis considered the effects of HIV and highly active antiretroviral therapy (HAART) on HPV persistence and cervical squamous intraepithelial lesions (SILs). Longitudinal cytopathologic and HPV DNA results were analyzed using multistate models. States of cervical SIL were defined as absent, present, and treatment; HPV states were defined as negative or positive. Demographic variables and markers of sexual activity were considered predictors. Results were calculated on the basis of transition probabilities and reported as hazard ratios (HRs). The CWHS followed 750 HIV-positive and 323 HIV-negative women during 1993-2002. A total of 467 and 456 women were included in the longitudinal cervical cytopathologic and HPV DNA analyses, respectively. HIV-positive women had increased prevalence (46.6% vs 28.7%; P < .0001), increased acquisition (HR, 2.3; P = .03), and decreased clearance (HR, 0.4; P < .001) of oncogenic HPV as compared to HIV-negative women. Oncogenic HPV infection predicted progression of cervical dysplasia from normal to abnormal SIL (HR, 2.8; P = .002). Among HIV-positive participants, HAART increased the likelihood of regression (from present to absent) of cervical SIL (HR, 3.3; P = .02) and increased the clearance of oncogenic HPV types other than HPV-16 or HPV-18 (HR, 2.2; P = .01). This analysis demonstrated beneficial effects of HAART on cervical SIL in HIV-positive women.

  3. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice.

    PubMed

    Luo, Zhidan; Ma, Liqun; Zhao, Zhigang; He, Hongbo; Yang, Dachun; Feng, Xiaoli; Ma, Shuangtao; Chen, Xiaoping; Zhu, Tianqi; Cao, Tingbing; Liu, Daoyan; Nilius, Bernd; Huang, Yu; Yan, Zhencheng; Zhu, Zhiming

    2012-03-01

    Impaired aerobic exercise capacity and skeletal muscle dysfunction are associated with cardiometabolic diseases. Acute administration of capsaicin enhances exercise endurance in rodents, but the long-term effect of dietary capsaicin is unknown. The capsaicin receptor, the transient receptor potential vanilloid 1 (TRPV1) cation channel has been detected in skeletal muscle, the role of which remains unclear. Here we report the function of TRPV1 in cultured C2C12 myocytes and the effect of TRPV1 activation by dietary capsaicin on energy metabolism and exercise endurance of skeletal muscles in mice. In vitro, capsaicin increased cytosolic free calcium and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in C2C12 myotubes through activating TRPV1. In vivo, PGC-1α in skeletal muscle was upregulated by capsaicin-induced TRPV1 activation or genetic overexpression of TRPV1 in mice. TRPV1 activation increased the expression of genes involved in fatty acid oxidation and mitochondrial respiration, promoted mitochondrial biogenesis, increased oxidative fibers, enhanced exercise endurance and prevented high-fat diet-induced metabolic disorders. Importantly, these effects of capsaicin were absent in TRPV1-deficient mice. We conclude that TRPV1 activation by dietary capsaicin improves energy metabolism and exercise endurance by upregulating PGC-1α in skeletal muscles. The present results indicate a novel therapeutic strategy for managing metabolic diseases and improving exercise endurance.

  4. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry

    PubMed Central

    Kluk, Michael J.; Ashworth, Todd; Wang, Hongfang; Knoechel, Birgit; Mason, Emily F.; Morgan, Elizabeth A.; Dorfman, David; Pinkus, Geraldine; Weigert, Oliver; Hornick, Jason L.; Chirieac, Lucian R.; Hirsch, Michelle; Oh, David J.; South, Andrew P.; Leigh, Irene M.; Pourreyron, Celine; Cassidy, Andrew J.; DeAngelo, Daniel J.; Weinstock, David M.; Krop, Ian E.; Dillon, Deborah; Brock, Jane E.; Lazar, Alexander J. F.; Peto, Myron; Cho, Raymond J.; Stoeck, Alexander; Haines, Brian B.; Sathayanrayanan, Sriram; Rodig, Scott; Aster, Jon C.

    2013-01-01

    Fixed, paraffin-embedded (FPE) tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1) in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC) stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors), but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of patients for clinical

  5. Cocaine locomotor activation, sensitization and place preference in six inbred strains of mice

    PubMed Central

    2011-01-01

    Background The expanding set of genomics tools available for inbred mouse strains has renewed interest in phenotyping larger sets of strains. The present study aims to explore phenotypic variability among six commonly-used inbred mouse strains to both the rewarding and locomotor stimulating effects of cocaine in a place conditioning task, including several strains or substrains that have not yet been characterized for some or all of these behaviors. Methods C57BL/6J (B6), BALB/cJ (BALB), C3H/HeJ (C3H), DBA/2J (D2), FVB/NJ (FVB) and 129S1/SvImJ (129) mice were tested for conditioned place preference to 20 mg/kg cocaine. Results Place preference was observed in most strains with the exception of D2 and 129. All strains showed a marked increase in locomotor activity in response to cocaine. In BALB mice, however, locomotor activation was context-dependent. Locomotor sensitization to repeated exposure to cocaine was most significant in 129 and D2 mice but was absent in FVB mice. Conclusions Genetic correlations suggest that no significant correlation between conditioned place preference, acute locomotor activation, and locomotor sensitization exists among these strains indicating that separate mechanisms underlie the psychomotor and rewarding effects of cocaine. PMID:21806802

  6. Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis.

    PubMed

    Siler, Ulrich; Romao, Susana; Tejera, Emilio; Pastukhov, Oleksandr; Kuzmenko, Elena; Valencia, Rocio G; Meda Spaccamela, Virginia; Belohradsky, Bernd H; Speer, Oliver; Schmugge, Markus; Kohne, Elisabeth; Hoenig, Manfred; Freihorst, Joachim; Schulz, Ansgar S; Reichenbach, Janine

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells in human subjects, causing hemolytic anemia linked to impaired nicotinamide adenine dinucleotide phosphate (NADPH) production and imbalanced redox homeostasis in erythrocytes. Because G6PD is expressed by a variety of hematologic and nonhematologic cells, a broader clinical phenotype could be postulated in G6PD-deficient patients. We describe 3 brothers with severe G6PD deficiency and susceptibility to bacterial infection. We sought to study the molecular pathophysiology leading to susceptibility to infection in 3 siblings with severe G6PD deficiency. Blood samples of 3 patients with severe G6PD deficiency were analyzed for G6PD enzyme activity, cellular oxidized nicotinamide adenine dinucleotide phosphate/NADPH levels, phagocytic reactive oxygen species production, neutrophil extracellular trap (NET) formation, and neutrophil elastase translocation. In these 3 brothers strongly reduced NADPH oxidase function was found in granulocytes, leading to impaired NET formation. Defective NET formation has thus far been only observed in patients with the NADPH oxidase deficiency chronic granulomatous disease, who require antibiotic and antimycotic prophylaxis to prevent life-threatening bacterial and fungal infections. Because severe G6PD deficiency can be a phenocopy of chronic granulomatous disease with regard to the cellular and clinical phenotype, careful evaluation of neutrophil function seems mandatory in these patients to decide on appropriate anti-infective preventive measures. Determining the level of G6PD enzyme activity should be followed by analysis of reactive oxygen species production and NET formation to decide on required antibiotic and antimycotic prophylaxis. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Increased experience amplifies the activation of task-irrelevant category representations.

    PubMed

    Wu, Rachel; Pruitt, Zoe; Zinszer, Benjamin D; Cheung, Olivia S

    2017-02-01

    Prior research has demonstrated the benefits (i.e., task-relevant attentional selection) and costs (i.e., task-irrelevant attentional capture) of prior knowledge on search for an individual target or multiple targets from a category. This study investigated whether the level of experience with particular categories predicts the degree of task-relevant and task-irrelevant activation of item and category representations. Adults with varying levels of dieting experience (measured via 3 subscales of Disinhibition, Restraint, Hunger; Stunkard & Messick, Journal of Psychosomatic Research, 29(1), 71-83, 1985) searched for targets defined as either a specific food item (e.g., carrots), or a category (i.e., any healthy or unhealthy food item). Apart from the target-present trials, in the target-absent "foil" trials, when searching for a specific item (e.g., carrots), irrelevant items from the target's category (e.g., squash) were presented. The ERP (N2pc) results revealed that the activation of task-relevant representations (measured via Exemplar and Category N2pc amplitudes) did not differ based on the degree of experience. Critically, however, increased dieting experience, as revealed by lower Disinhibition scores, predicted activation of task-irrelevant representations (i.e., attentional capture of foils from the target item category). Our results suggest that increased experience with particular categories encourages the rapid activation of category representations even when category information is task irrelevant, and that the N2pc in foil trials could potentially serve as an indication of experience level in future studies on categorization.

  8. Na+/H+ exchange activity in the plasma membrane of Arabidopsis.

    PubMed

    Qiu, Quan-Sheng; Barkla, Bronwyn J; Vera-Estrella, Rosario; Zhu, Jian-Kang; Schumaker, Karen S

    2003-06-01

    In plants, Na+/H+ exchangers in the plasma membrane are critical for growth in high levels of salt, removing toxic Na+ from the cytoplasm by transport out of the cell. The molecular identity of a plasma membrane Na+/H+ exchanger in Arabidopsis (SOS1) has recently been determined. In this study, immunological analysis provided evidence that SOS1 localizes to the plasma membrane of leaves and roots. To characterize the transport activity of this protein, purified plasma membrane vesicles were isolated from leaves of Arabidopsis. Na+/H+ exchange activity, monitored as the ability of Na to dissipate an established pH gradient, was absent in plants grown without salt. However, exchange activity was induced when plants were grown in 250 mm NaCl and increased with prolonged salt exposure up to 8 d. H+-coupled exchange was specific for Na, because chloride salts of other monovalent cations did not dissipate the pH gradient. Na+/H+ exchange activity was dependent on Na (substrate) concentration, and kinetic analysis indicated that the affinity (apparent Km) of the transporter for Na+ is 22.8 mm. Data from two experimental approaches supports electroneutral exchange (one Na+ exchanged for one proton): (a) no change in membrane potential was measured during the exchange reaction, and (b) Na+/H+ exchange was unaffected by the presence or absence of a membrane potential. Results from this research provide a framework for future studies into the regulation of the plant plasma membrane Na+/H+ exchanger and its relative contribution to the maintenance of cellular Na+ homeostasis during plant growth in salt.

  9. Zoanthid mucus as new source of useful biologically active proteins.

    PubMed

    Guarnieri, Míriam Camargo; de Albuquerque Modesto, Jeanne Claíne; Pérez, Carlos Daniel; Ottaiano, Tatiana Fontes; Ferreira, Rodrigo da Silva; Batista, Fabrício Pereira; de Brito, Marlon Vilela; Campos, Ikaro Henrique Mendes Pinto; Oliva, Maria Luiza Vilela

    2018-03-01

    Palythoa caribaeorum is a very common colonial zoanthid in the coastal reefs of Brazil. It is known for its massive production of mucus, which is traditionally used in folk medicine by fishermen in northeastern Brazil. This study identified biologically active compounds in P. caribaerum mucus. Crude mucus was collected during low tides by the manual scraping of colonies; samples were maintained in an ice bath, homogenized, and centrifuged at 16,000 g for 1 h at 4 °C; the supernatant (mucus) was kept at -80 °C until use. The enzymatic (proteolytic and phospholipase A 2 ), inhibitory (metallo, cysteine and serine proteases), and hemagglutinating (human erythrocyte) activities were determined. The results showed high levels of cysteine and metallo proteases, intermediate levels of phosholipase A 2 , low levels of trypsin, and no elastase and chymotrypsin like activities. The mucus showed potent inhibitory activity on snake venom metalloproteases and cysteine proteinase papain. In addition, it showed agglutinating activity towards O + , B + , and A + erythrocyte types. The hemostatic results showed that the mucus prolongs the aPTT and PT, and strongly inhibited platelet aggregation induced by arachidonic acid, collagen, epinephrine, ADP, and thrombin. The antimicrobial activity was tested on 15 strains of bacteria and fungi through the radial diffusion assay in agar, and no activity was observed. Compounds in P. caribaeorum mucus were analyzed for the first time in this study, and our results show potential pharmacological activities in these compounds, which are relevant for use in physiopathological investigations. However, the demonstration of these activities indicates caution in the use of crude mucus in folk medicine. Furthermore, the present or absent activities identified in this mucus suggest that the studied P. caribaeorum colonies were in thermal stress conditions at the time of sample collection; these conditions may precede the bleaching

  10. Effect of prophylactic oral calcium supplementation on postpartum mineral status and markers of energy balance of multiparous Jersey cows.

    PubMed

    Valldecabres, A; Pires, J A A; Silva-Del-Río, N

    2018-05-01

    The effects of prophylactic oral Ca supplementation on blood mineral status and markers of energy balance were evaluated on 205 multiparous Jersey cows at a commercial dairy. Postpartum, cows were systematically assigned to control (n = 105) or oral Ca supplementation (CaOS; 50 to 60 g of Ca as boluses; n = 100) at 0 and 1 d in milk (DIM). Blood samples for analysis of serum minerals (Ca, P, Mg, K, Na, Fe, Zn, and Cu) were collected before and 1 h after treatment at 0 and 1 DIM, and at 2 DIM. Urine pH was measured immediately before and 1 h after treatment administration (n = 96). A subset of 74 cows was evaluated for plasma glucose and fatty acid concentrations at 0, 1, and 2 DIM. Cows were classified according to their initial calcemic status (Ca status) as normocalcemic (NC; serum Ca >2.12 mmol/L) or subclinically hypocalcemic (SCH; serum Ca ≤2.12 mmol/L). Average serum Ca concentration was higher in CaOS than control cows (2.12 vs. 2.06 mmol/L); this treatment effect was higher for SCH [CaOS (2.03 mmol/L); control (1.89 mmol/L)] than NC cows [CaOS (2.22 mmol/L); control (2.22 mmol/L)]. The incidence of subclinical hypocalcemia was lower for CaOS than control cows (53 vs. 65%); however, at 2 DIM the prevalence of subclinical hypocalcemia tended to be higher for CaOS cows, mostly because it was higher for CaOS-NC than control-NC cows (70 vs. 25%). Urine pH was lower for CaOS than control cows (6.10 vs. 7.04). Lower serum Mg concentration was detected for CaOS-SCH (1.06 mmol/L) than for control-SCH (1.10 mmol/L) cows. Cows in the CaOS group had higher serum K (4.68 vs. 4.53 mmol/L), lower plasma glucose (2.97 vs. 3.10 mmol/L), and at 2 DIM higher plasma fatty acid concentrations (0.43 vs. 0.35 mmol/L) than control cows. Our results showed that postpartum serum Ca concentration increases with oral Ca supplementation, but calcemic status influenced treatment response. Future studies should evaluate the long-term implications on production and reproduction of oral

  11. Alternative activation of STAT1 and STAT3 in response to interferon-gamma.

    PubMed

    Qing, Yulan; Stark, George R

    2004-10-01

    Interferon-gamma (IFNgamma) is a pluripotent cytokine whose major biological effects are mediated through a pathway in which STAT1 is the predominant and essential transcription factor. STAT3 can also be activated weakly by IFNgamma, but the mechanism of activation and function of STAT3 as a part of the interferon response are not known. Here we show that STAT3 activation is much stronger and more prolonged in STAT1-null mouse embryo fibroblasts than in wild-type cells. In response to IFNgamma, SRC-family kinases are required to activate STAT3 (but not STAT1) through tyrosine phosphorylation, whereas the receptor-bound kinases JAK1 and JAK2 are required to activate both STATs. Tyrosine 419 of the IFNgamma receptor subunit 1 (IFNGR1) is required to activate both STATs, suggesting that STAT1 and STAT3 compete with each other for the same receptor phosphotyrosine motif. Activated STAT3 can replace STAT1 in STAT1-null cells to drive the transcription of certain genes, for example, socs-3 and c/ebpdelta, which have gamma-activated sequence motifs in their promoters. Work from Ian Kerr's laboratory reveals that the gp130-linked interleukin-6 receptor, which usually activates STAT3 predominantly, activates STAT1 efficiently when STAT3 is absent. Because STAT1 and STAT3 have opposing biological effects (STAT3 is an oncogene, and STAT1 is a tumor suppressor), the reciprocal activation of these two transcription factors in response to IFNgamma or interleukin-6 suggests that their relative abundance, which may vary substantially in different normal cell types, under different conditions or in tumors is likely to have a major impact on how cells behave in response to different cytokines.

  12. Altered medial temporal activation related to local glutamate levels in subjects with prodromal signs of psychosis.

    PubMed

    Valli, Isabel; Stone, James; Mechelli, Andrea; Bhattacharyya, Sagnik; Raffin, Marie; Allen, Paul; Fusar-Poli, Paolo; Lythgoe, David; O'Gorman, Ruth; Seal, Marc; McGuire, Philip

    2011-01-01

    Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated. We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers. We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent. In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Differential skeletal responses of hindlimb unloaded rats on a vitamin D-deficient diet to 1,25-dihydroxyvitamin D3 and its analog, seocalcitol (EB1089)

    NASA Technical Reports Server (NTRS)

    Narayanan, Ramesh; Allen, Matthew R.; Gaddy, Dana; Bloomfield, Susan A.; Smith, Carolyn L.; Weigel, Nancy L.

    2004-01-01

    Conditions of disuse in bed rest patients, as well as microgravity experienced by astronauts are accompanied by reduced mechanical loading, reduced calcium absorption, and lower serum levels of 1,25(OH)2D3 (1,25-D), the active metabolite of vitamin D, all contributing to bone loss. To determine whether 1,25-D or a less calcemic analog, Seocalcitol or EB1089 (1 alpha,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin D3) can alleviate bone loss in a rat hindlimb unloading model of disuse osteopenia, mature male rats originally on a vitamin D replete diet containing 1.01% calcium were transferred to a vitamin D-deficient diet containing 0.48% calcium and then tail suspended and treated for 28 days with vehicle, 0.05 microg/kg 1,25-D, or 0.05 microg/kg EB1089. The vitamin D-deficient diet caused a substantial decrease in bone mineral density (-8%), which may be compounded by hindlimb unloading (-10%). Exogenous 1,25-D not only prevented the bone loss but also increased the bone mineral density to greater than the baseline level (+7%). EB1089 was less effective in preventing bone loss. Analysis of site and cell-specific effects of 1,25-D and EB1089 revealed that 1,25-D was more active than EB1089 in the intestine, the site of calcium absorption, and in inducing osteoclastogenesis and bone resorption whereas EB1089 was more effective in inducing osteoblast differentiation. These studies suggest that elevating circulating 1,25-D levels presumably increasing calcium absorption can counteract bone loss induced by disuse or microgravity with its associated reductions in circulating 1,25-D and decreased calcium absorption.

  14. The activity of superoxide dismutase in animal liver and erythrocyte at Sea Area nearby Dayawan Nuclear Power Station

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

    Cheng, Ge; Cai, Yana; Chen, Huizhen

    1995-11-01

    Many tests, the effect of ionizing radiation on SOD in vivo and vitro, had proved that the irradiation can cause the SOD activity to decrease with the increase of irradiation dose, change some physicochemical properties and structure. This artical was to study the activity of SOD in Fish (Thearpon jorbua) and Toad(Bufo melanostictus) liver erythrocyte at sea area nearby Dayawan Nuclear Power Station (Nps). We found that the SOD activity in fish liver, after NPS revolved one year, was higher than that of before revoling (7.30 {plus_minus} 1.35U/mg protein, 5.49 {plus_minus}1.56 U/mg protein respectively). The SOD activity in the toadmore » liver at NPS revolving one year after was decreased (4.54 {plus_minus} 0.75 U/mg protein 5.68{plus_minus} 1.49U/mg protein P < 0.001) but in erythrocyte increased (2.32 {plus_minus} 0.75 U/mg Hb, 0.70 {plus_minus} 0.33 U/mg Hb P < 0.001). These results indicated that the SOD activity was changed in different with the animal variety. The effect of irradiation on fish at present was absent, on toad need to research in the future.« less

  15. A strong electro-optically active lead-free ferroelectric integrated on silicon

    NASA Astrophysics Data System (ADS)

    Abel, Stefan; Stöferle, Thilo; Marchiori, Chiara; Rossel, Christophe; Rossell, Marta D.; Erni, Rolf; Caimi, Daniele; Sousa, Marilyne; Chelnokov, Alexei; Offrein, Bert J.; Fompeyrine, Jean

    2013-04-01

    The development of silicon photonics could greatly benefit from the linear electro-optical properties, absent in bulk silicon, of ferroelectric oxides, as a novel way to seamlessly connect the electrical and optical domain. Of all oxides, barium titanate exhibits one of the largest linear electro-optical coefficients, which has however not yet been explored for thin films on silicon. Here we report on the electro-optical properties of thin barium titanate films epitaxially grown on silicon substrates. We extract a large effective Pockels coefficient of reff=148 pm V-1, which is five times larger than in the current standard material for electro-optical devices, lithium niobate. We also reveal the tensor nature of the electro-optical properties, as necessary for properly designing future devices, and furthermore unambiguously demonstrate the presence of ferroelectricity. The integration of electro-optical active films on silicon could pave the way towards power-efficient, ultra-compact integrated devices, such as modulators, tuning elements and bistable switches.

  16. Physical activity and exercise promotion and prescription in undergraduate physiotherapy education: content analysis of Irish curricula.

    PubMed

    O'Donoghue, Grainne; Doody, Catherine; Cusack, Tara

    2011-06-01

    Overwhelming evidence shows that physical activity and exercise promotion and prescription are effective in preventing and managing numerous chronic conditions. With physiotherapists commonly referred to as 'exercise prescription experts', an in-depth knowledge of exercise promotion and prescription is assumed. However, to date, no information exists about what is or should be included in terms of undergraduate physiotherapy physical activity and exercise education, nor whether the content prepares graduates to be exercise experts for contemporary practice. To provide an accurate, contemporary picture of physical activity and exercise promotion and prescription content within Irish undergraduate physiotherapy curricula. Content analysis was used to explore physical activity and exercise inclusion within four of the five programmes in Ireland. Seven categories were generated. Frequency analysis for each category was used to provide a guide to the extensiveness of physical activity and exercise promotion and prescription content. All curricula included varying quantities of basic exercise science and exercise testing and prescription. Physical activity and exercise promotion and prescription for conditions routinely referred to physiotherapy, such as cardio respiratory disease, were well represented. Three key areas were identified as being absent or needing further emphasis: physical activity/exercise for public health, strategies for changing physical activity behaviour, and physical activity/exercise for lifestyle-related diseases. Results indicate a strong need for re-evaluation of physical activity and exercise education in Irish physiotherapy curricula. There is a lack of explicit exercise content in relation to public health and lifestyle-related disease. Copyright © 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  17. Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia.

    PubMed

    Furrow, E; Jaeger, J Q; Parker, V J; Hinchcliff, K W; Johnson, S E; Murdoch, S J; de Boer, I H; Sherding, R G; Brunzell, J D

    2016-06-01

    Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Antibacterial Activities of Jatropha curcas (LINN) on Coliforms Isolated from Surface Waters in Akure, Nigeria

    PubMed Central

    Dada, E. O.; Ekundayo, F. O.; Makanjuola, O. O.

    2014-01-01

    This study investigated the antibacterial activities of hot water, ethanol and acetone extracts of Jatropha curcas (LINN) leaves on coliforms isolated from surface waters using growth inhibition indices based on agar plate technique. The percentage recovery of the extracts was 19.17%, 18.10% and 18.80% for hot water, ethanol and acetone respectively. Phytochemical screening of the extracts was also determined. Qualitative phytochemical screening showed that the plant extracts contained steroids, tannins, flavonoids and cardiac glycosides, while alkaloids, phlobatannin, terpenoids and anthraquinones were absent. Only ethanolic extract did not possess saponins. Aqueous extracts of J. curcas compared most favourably with the standard antibiotics (gentamycin) on all the coliform bacteria except on K. pneumoniae and E. coli likely due to a measurably higher antibacterial activity compared to the organic extracts. The minimum inhibitory concentration of the aqueous extract ranged from 3.00 to 7.00 mg/L while minimum bactericidal concentration ranged from 4.00 to 10.00 mg/L. Aqueous extract of J. curcas could be used as antibacterial agents against diseases caused by coliforms. PMID:24711746

  19. Persistent complement activation on tumor cells in breast cancer.

    PubMed Central

    Niculescu, F.; Rus, H. G.; Retegan, M.; Vlaicu, R.

    1992-01-01

    The neoantigens of the C5b-9 complement complex, IgG, C3, C4, S-protein/vitronectin, fibronectin, and macrophages were localized on 17 samples of breast cancer and on 6 samples of benign breast tumors using polyclonal or monoclonal antibodies and the streptavidin-biotin-peroxidase technique. All the tissue samples with carcinoma in each the TNM stages presented C5b-9 deposits on the membranes of tumor cells, thin granules on cell remnants, and diffuse deposits in the necrotic areas. When chemotherapy and radiation therapy preceded surgery, C5b-9 deposits were more intense and extended. The C5b-9 deposits were absent in all the samples with benign lesions. S-protein/vitronectin was present as fibrillar deposits in the connective tissue matrix and as diffuse deposits around the tumor cells, less intense and extended than fibronectin. IgG, C3, and C4 deposits were present only in carcinoma samples. The presence of C5b-9 deposits is indicative of complement activation and its subsequent pathogenetic effects in breast cancer. Images Figure 1 PMID:1374587

  20. Signal transducer and activator of transcription 5B (STAT5B) modulates adipocyte differentiation via MOF.

    PubMed

    Gao, Peng; Zhang, Yuchao; Liu, Yuantao; Chen, Jicui; Zong, Chen; Yu, Cong; Cui, Shang; Gao, Weina; Qin, Dandan; Sun, Wenchuan; Li, Xia; Wang, Xiangdong

    2015-12-01

    The role and mechanism of signal transducer and activator of transcription 5B (STAT5B) in adipogenesis remain unclear. In this study, our data showed that Males absent on the first (MOF) protein expression was increased during 3 T3-L1 preadipocytes differentiation accompanied with STAT5B expression increasing. Over-expression STAT5B enhanced MOF promoter trans-activation in HeLa cells. Mutagenesis assay and ChIP analysis exhibited that STAT5B was able to bind MOF promoter. Knocking-down STAT5B in 3 T3-L1 preadipocytes led to decreased expression of MOF, but resulted in increased expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid-binding protein 4 (Fabp4), which were important factors or enzymes for adipogenesis. We also found that knocking-down MOF in 3 T3-L1 preadipocytes resulted in increased expression of PPARγ, C/EBPα and Fabp4, which was in the same trend as STAT5B knocking-down. Over-expression MOF resulted in reduced promoter trans-activation activity of C/EBPα. These results suggest that STAT5B and MOF work as negative regulators in adipogenesis, and STAT5B modulates preadipocytes differentiation partially by regulating MOF expression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Degree Of Diminution In Vagal-Cardiac Activity Predicts Sudden Death In Familial Dysautonomia When Resting Tachycardia Is Absent

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Marthol, H.; Bucchner, S.; Tutaj, M.; Berlin, D.; Axelrod, F. B.; Hilz, M. J.

    2004-01-01

    Patients with familial dysautonomia (FD) have an increased risk of sudden death, but sensitive and specific predictors of sudden death in FD are lacking. Methods. We recorded 10-min resting high-fidelity 12-lead ECGs in 14 FD patients and in 14 age/gender-matched healthy subjects and studied 25+ different heart rate variability (HRV) indices for their ability to predict sudden death in the FD patients. Indices studied included those from 4 "nonlinear" HRV techniques (detrended fluctuation analysis, approximate entropy, correlation dimension, and PoincarC analyses). The predictive value of PR, QRS, QTc and JTc intervals, QT dispersion (QTd), beat-to-beat QT and PR interval variability indices (QTVI and PRVI) and 12- lead high frequency QRS ECG (150-250 Hz) were also studied. FD patients and controls (C) differed (Pless than 0.0l) with respect to 20+ of the HRV indices (FD less than C) and with respect to QTVI and PRVI (FDBC) and HF QRS- related root mean squared voltages (FDBC) and reduced amplitude zone counts (FD less than C). They differed less with respect to PR intervals (FD less than C) and JTc intervals (FD greater than C) (P less than 0.05 for both) and did not differ at all with respect to QRS and QTc intervals and to QTd. Within 12 months after study, 2 of the 14 patients succumbed to sudden cardiac arrest. The best predictor of sudden death was the degree of diminution in HRV vagal-cardiac (parasympathetic) parameters such as RMSSD, the SDl of Poincare plots, and HF spectral power. Excluding the two FD patients who had resting tachycardia (HR greater than 100, which confounds traditional HRV analyses), the following criteria were independently 100% sensitive and 100% specific for predicting sudden death in the remaining 12 FD patients during spontaneous breathing: RMSSD less than 13 ms and/or PoincarC SD1 less than 9 ms. In FD patients without supine tachycardia, the degree of diminution in parasympathetic HRV parameters (by high-fidelity ECG) predicts incipient death.

  2. Plasma B-esterase activities in European raptors.

    PubMed

    Roy, Claudie; Grolleau, Gérard; Chamoulaud, Serge; Rivière, Jean-Louis

    2005-01-01

    Strigidae families were characterized by a BChE contribution that dominated the total ChE activity, while in the species of the Falconidae family, AChE activity dominated. With the exception of the barn owl, CbE activity (eserine-insensitive alpha-naphthyl acetate esterase [alpha-NAE] activity) in all species was almost absent or very low. The values obtained in this study for ChE, AChE, and BChE activities and the AChE:BChE ratios for buzzard, kestrel, barn owl, and tawny owl provide a good estimate of the normal values in free-living individuals of these European species. They can be used as a baseline to evaluate the effect of anticholinesterase insecticides in the field.

  3. Seasonal and Diel Activity Patterns of Eight Sympatric Mammals in Northern Japan Revealed by an Intensive Camera-Trap Survey.

    PubMed

    Ikeda, Takashi; Uchida, Kenta; Matsuura, Yukiko; Takahashi, Hiroshi; Yoshida, Tsuyoshi; Kaji, Koichi; Koizumi, Itsuro

    2016-01-01

    The activity patterns of mammals are generally categorized as nocturnal, diurnal, crepuscular (active at twilight), and cathemeral (active throughout the day). These patterns are highly variable across regions and seasons even within the same species. However, quantitative data is still lacking, particularly for sympatric species. We monitored the seasonal and diel activity patterns of terrestrial mammals in Hokkaido, Japan. Through an intensive camera-trap survey a total of 13,279 capture events were recorded from eight mammals over 20,344 camera-trap days, i.e., two years. Diel activity patterns were clearly divided into four categories: diurnal (Eurasian red squirrels), nocturnal (raccoon dogs and raccoons), crepuscular (sika deer and mountain hares), and cathemeral (Japanese martens, red foxes, and brown bears). Some crepuscular and cathemeral mammals shifted activity peaks across seasons. Particularly, sika deer changed peaks from twilight during spring-autumn to day-time in winter, possibly because of thermal constraints. Japanese martens were cathemeral during winter-summer, but nocturnal in autumn. We found no clear indication of predator-prey and competitive interactions, suggesting that animal densities are not very high or temporal niche partitioning is absent among the target species. This long-term camera-trap survey was highly cost-effective and provided one of the most detailed seasonal and diel activity patterns in multiple sympatric mammals under natural conditions.

  4. Na+/H+ Exchange Activity in the Plasma Membrane of Arabidopsis1

    PubMed Central

    Qiu, Quan-Sheng; Barkla, Bronwyn J.; Vera-Estrella, Rosario; Zhu, Jian-Kang; Schumaker, Karen S.

    2003-01-01

    In plants, Na+/H+ exchangers in the plasma membrane are critical for growth in high levels of salt, removing toxic Na+ from the cytoplasm by transport out of the cell. The molecular identity of a plasma membrane Na+/H+ exchanger in Arabidopsis (SOS1) has recently been determined. In this study, immunological analysis provided evidence that SOS1 localizes to the plasma membrane of leaves and roots. To characterize the transport activity of this protein, purified plasma membrane vesicles were isolated from leaves of Arabidopsis. Na+/H+ exchange activity, monitored as the ability of Na to dissipate an established pH gradient, was absent in plants grown without salt. However, exchange activity was induced when plants were grown in 250 mm NaCl and increased with prolonged salt exposure up to 8 d. H+-coupled exchange was specific for Na, because chloride salts of other monovalent cations did not dissipate the pH gradient. Na+/H+ exchange activity was dependent on Na (substrate) concentration, and kinetic analysis indicated that the affinity (apparent Km) of the transporter for Na+ is 22.8 mm. Data from two experimental approaches supports electroneutral exchange (one Na+ exchanged for one proton): (a) no change in membrane potential was measured during the exchange reaction, and (b) Na+/H+ exchange was unaffected by the presence or absence of a membrane potential. Results from this research provide a framework for future studies into the regulation of the plant plasma membrane Na+/H+ exchanger and its relative contribution to the maintenance of cellular Na+ homeostasis during plant growth in salt. PMID:12805632

  5. Repeated psychosocial stress at night affects the circadian activity rhythm of male mice.

    PubMed

    Bartlang, Manuela S; Oster, Henrik; Helfrich-Förster, Charlotte

    2015-06-01

    We have recently shown that molecular rhythms in the murine suprachiasmatic nucleus (SCN) are affected by repeated social defeat (SD) during the dark/active phase (social defeat dark [SDD]), while repeated SD during the light/inactive phase (social defeat light [SDL]) had no influence on PERIOD2::LUCIFERASE explant rhythms in the SCN. Here we assessed the effects of the same stress paradigm by in vivo biotelemetry on 2 output rhythms of the circadian clock (i.e., activity and core body temperature) in wild-type (WT) and clock-deficient Period (Per)1/2 double-mutant mice during and following repeated SDL and SDD. In general, stress had more pronounced effects on activity compared to body temperature rhythms. Throughout the SD procedure, activity and body temperature were markedly increased during the 2 h of stressor exposure at zeitgeber time (ZT) 1 to ZT3 (SDL mice) and ZT13 to ZT15 (SDD mice), which was compensated by decreased activity during the remaining dark phase (SDL and SDD mice) and light phase (SDL mice) in both genotypes. Considerable differences in the activity between SDL and SDD mice were seen in the poststress period. SDD mice exhibited a reduced first activity bout at ZT13, delayed activity onset, and, consequently, a more narrow activity bandwidth compared with single-housed control (SHC) and SDL mice. Given that this effect was absent in Per1/2 mutant SDD mice and persisted under constant darkness conditions in SDD WT mice, it suggests an involvement of the endogenous clock. Taken together, the present findings demonstrate that SDD has long-lasting consequences for the functional output of the biological clock that, at least in part, appear to depend on the clock genes Per1 and Per2. © 2015 The Author(s).

  6. The auditory P50 component to onset and offset of sound

    PubMed Central

    Pratt, Hillel; Starr, Arnold; Michalewski, Henry J.; Bleich, Naomi; Mittelman, Nomi

    2008-01-01

    Objective: The auditory Event-Related Potentials (ERP) component P50 to sound onset and offset have been reported to be similar, but their magnetic homologue has been reported absent to sound offset. We compared the spatio-temporal distribution of cortical activity during P50 to sound onset and offset, without confounds of spectral change. Methods: ERPs were recorded in response to onsets and offsets of silent intervals of 0.5 s (gaps) appearing randomly in otherwise continuous white noise and compared to ERPs to randomly distributed click pairs with half second separation presented in silence. Subjects were awake and distracted from the stimuli by reading a complicated text. Measures of P50 included peak latency and amplitude, as well as source current density estimates to the clicks and sound onsets and offsets. Results P50 occurred in response to noise onsets and to clicks, while to noise offset it was absent. Latency of P50 was similar to noise onset (56 msec) and to clicks (53 msec). Sources of P50 to noise onsets and clicks included bilateral superior parietal areas. In contrast, noise offsets activated left inferior temporal and occipital areas at the time of P50. Source current density was significantly higher to noise onset than offset in the vicinity of the temporo-parietal junction. Conclusions: P50 to sound offset is absent compared to the distinct P50 to sound onset and to clicks, at different intracranial sources. P50 to stimulus onset and to clicks appears to reflect preattentive arousal by a new sound in the scene. Sound offset does not involve a new sound and hence the absent P50. Significance: Stimulus onset activates distinct early cortical processes that are absent to offset. PMID:18055255

  7. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

    PubMed Central

    Luo, Zhidan; Ma, Liqun; Zhao, Zhigang; He, Hongbo; Yang, Dachun; Feng, Xiaoli; Ma, Shuangtao; Chen, Xiaoping; Zhu, Tianqi; Cao, Tingbing; Liu, Daoyan; Nilius, Bernd; Huang, Yu; Yan, Zhencheng; Zhu, Zhiming

    2012-01-01

    Impaired aerobic exercise capacity and skeletal muscle dysfunction are associated with cardiometabolic diseases. Acute administration of capsaicin enhances exercise endurance in rodents, but the long-term effect of dietary capsaicin is unknown. The capsaicin receptor, the transient receptor potential vanilloid 1 (TRPV1) cation channel has been detected in skeletal muscle, the role of which remains unclear. Here we report the function of TRPV1 in cultured C2C12 myocytes and the effect of TRPV1 activation by dietary capsaicin on energy metabolism and exercise endurance of skeletal muscles in mice. In vitro, capsaicin increased cytosolic free calcium and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in C2C12 myotubes through activating TRPV1. In vivo, PGC-1α in skeletal muscle was upregulated by capsaicin-induced TRPV1 activation or genetic overexpression of TRPV1 in mice. TRPV1 activation increased the expression of genes involved in fatty acid oxidation and mitochondrial respiration, promoted mitochondrial biogenesis, increased oxidative fibers, enhanced exercise endurance and prevented high-fat diet-induced metabolic disorders. Importantly, these effects of capsaicin were absent in TRPV1-deficient mice. We conclude that TRPV1 activation by dietary capsaicin improves energy metabolism and exercise endurance by upregulating PGC-1α in skeletal muscles. The present results indicate a novel therapeutic strategy for managing metabolic diseases and improving exercise endurance. PMID:22184011

  8. PHARMACOLOGICAL SIRT1 ACTIVATION IMPROVES MORTALITY AND MARKEDLY ALTERS TRANSCRIPTIONAL PROFILES THAT ACCOMPANY EXPERIMENTAL SEPSIS.

    PubMed

    Opal, Steven M; Ellis, James L; Suri, Vipin; Freudenberg, Johannes M; Vlasuk, George P; Li, Yong; Chahin, Abdullah B; Palardy, John E; Parejo, Nicholas; Yamamoto, Michelle; Chahin, Abdulrahman; Kessimian, Noubar

    2016-04-01

    The sirtuin family consists of seven NAD+-dependent enzymes affecting a broad array of regulatory protein networks by primarily catalyzing the deacetylation of key lysine residues in regulatory proteins. The enzymatic activity of SIRT1 can be enhanced by small molecule activators known as SIRT1 activator compounds (STACs). We tested the therapeutic potential of the STAC SRT3025 in two preclinical models of severe infection, the murine cecal ligation and puncture (CLP) model to induce peritonitis and intratracheal installation of Streptococcus pneumoniae to induce severe bacterial pneumonia. SRT3025 provided significant survival benefits over vehicle control in both the peritonitis and pneumococcal pneumonia models when administered with appropriate antimicrobial agents. The survival benefit of SRT3025 in the CLP model was absent in SIRT1 knockout showing the SIRT1 dependency of SRT3025's effects. SRT3025 administration promoted bacterial clearance and significantly reduced inflammatory cytokines from the lungs of animals challenged with S. pneumoniae. SRT3025 treatment was also accompanied by striking changes in the transcription profiles in multiple inflammatory and metabolic pathways in liver, spleen, small bowel, and lung tissue. Remarkably, these organ-specific changes in the transcriptome analyses were similar following CLP or pneumococcal challenge despite different sets of pathogens at disparate sites of infection. Pharmacologic activation of SIRT1 modulates the innate host response and could represent a novel treatment strategy for severe infection.

  9. Alcohol interactions with channel activation and desensitization at 5-HT[sub 3] and GABA[sub A] receptors

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

    Lovinger, D.M.; Zhou, O.

    1992-01-01

    Ethanol (EtOH) and trichloroethanol (TCEt) potentiate 5-HT[sub 3] receptor-mediated ion current in NCB-20 neuroblastoma cells and nodose ganglion neurons. TCEt potentiates GABA[sub A] receptor-mediated current in dorsal root ganglion neurons. Whole-cell patch-clamp recording was used to examine the interactions of alcohols with current activation and receptor desensitization. Alcohols increased the potency of 5-HT, consistent with an increase in channel activation rate. Current decay rate increased in the presence of alcohols such that potentiation decreased with time following in onset of agonist + alcohol treatment. Potentiation of 5-HT-activated current by EtOH was 61 [plus minus] 17% above control at the startmore » of application but was absent 10 sec after current onset. Agonist pretreatment decreased potentiation by subsequent agonist + alcohol application. Potentiation by TCEt of 5-HT-activated current decreased from 96% above control with simultaneous application of 5-HT + TCEt to 44% after a 30 sec 5-HT treatment. This agonist- and time-dependent loss of potentiation was observed prior to the onset of current decay when low agonist concentrations were used. Agonist pretreatment appears to drive the channel into an alcohol-insensitive. Current activated by GABA + TCEt recovers from desensitization produced by GABA alone more slowly than recovery tested in the absence of TCEt.« less

  10. Prolonged activation EEG differentiates dementia with and without delirium in frail elderly patients.

    PubMed

    Thomas, C; Hestermann, U; Walther, S; Pfueller, U; Hack, M; Oster, P; Mundt, C; Weisbrod, M

    2008-02-01

    Delirium in the elderly results in increased morbidity, mortality and functional decline. Delirium is underdiagnosed, particularly in dementia. To increase diagnostic accuracy, we investigated whether maintenance of activation assessed by EEG discriminates delirium in association with dementia (D+D) from dementia without delirium (DP) and cognitively unimpaired elderly subjects (CU). Routine and quantitative EEG (rEEG/qEEG) with additional prolonged activation (3 min eyes open period) were evaluated in hospitalised elderly patients with acute geriatric disease. Patients were assigned post hoc to three comparable groups (D+D/DP/CU) by expert consensus based on DSM-IV criteria. Dementia diagnosis was confirmed using cognitive and functional tests and caregiver rating (IQCODE, Informed Questionnaire of Cognitive Decline in the Elderly). While rEEG at rest showed low accuracy for a diagnosis of delirium, qEEG in DP and CU revealed a specific activation pattern of high significance found to be absent in the D+D group. Stepwise logistic regression confirmed that differentiation of D+D from DP was best resolved using activated upper alpha and delta power density which, compared with rEEG, enabled an 11% increase in diagnostic correctness to 83%, resulting in 67% sensitivity and 91% specificity. Among frail CU and D+D subjects, almost 90% were correctly classified. Dementia associated with delirium can be discriminated reliably from dementia alone in a meaningful clinical setting. Thus EEG evaluation in chronic encephalopathy should be optimised by a simple activation task and spectral analysis, particularly in the elderly with dementia.

  11. Clinical application of a rapid method using agarose gel electrophoresis and Western blotting to evaluate von Willebrand factor protease activity.

    PubMed

    Kirzek, D M; Rick, M E

    2001-03-01

    A method for evaluating the activity of the von Willebrand factor (vWF) protease is described, and a clinical application is illustrated. The procedure utilizes gel electrophoresis, Western blotting, and luminographic detection methods to evaluate the distribution of vWF multimers before and after incubation of clinical samples under conditions that favor proteolysis by this enzyme. Physiologically, the high-molecular-weight multimers of vWF are cleaved by the vWF protease under conditions of high shear stress in parts of the arterial circulation; cleavage of vWF multimers is also observed after exposure of vWF to denaturing agents in vitro and thus can serve as a laboratory test for the activity of the protease. vWF protease activity is decreased or absent in patients with thrombotic thrombocytopenic purpura due to an inhibiting autoantibody, and this leads to high levels of noncleaved vWF and to life-threatening thrombosis, thrombocytopenia and anemia. The assay evaluates the activity of the protease by assessing the cleavage of vWF multimers after patient plasmas are incubated in vitro under denaturing conditions. With the use of these electrophoresis and Western blotting techniques, patient plasmas can be rapidly assessed for the activity of the vWF protease which may aid in the treatment strategy for these patients.

  12. Pyrrole Alkaloids with Potential Cancer Chemopreventive Activity Isolated from a Goji Berry-Contaminated Commercial Sample of African Mango

    PubMed Central

    2015-01-01

    Bioassay-guided fractionation of a commercial sample of African mango (Irvingia gabonensis) that was later shown to be contaminated with goji berry (Lycium sp.) led to the isolation of a new pyrrole alkaloid, methyl 2-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]propanoate, 1, along with seven known compounds, 2–8. The structures of the isolated compounds were established by analysis of their spectroscopic data. The new compound 1g showed hydroxyl radical-scavenging activity with an ED50 value of 16.7 μM, whereas 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (2) was active in both the hydroxyl radical-scavenging (ED50 11.9 μM) and quinone reductase-induction [CD (concentration required to double QR activity) 2.4 μM)] assays used. The isolated compounds were shown to be absent in a taxonomically authenticated African mango sample but present in three separate authentic samples of goji berry (Lycium barbarum) using LC-MS and 1H NMR fingerprinting analysis, including one sample that previously showed inhibitory activity in vivo in a rat esophageal cancer model induced with N-nitrosomethylbenzylamine. Additionally, microscopic features characteristic of goji berry were observed in the commercial African mango sample. PMID:24792835

  13. A Multi-center, Double-blind, Randomized Study, Comparing Clindamycin Phosphate Vaginal Cream 2% (Watson Laboratories, Inc.) to Clindesse® (Ther-Rx™, Clindamyin Phosphate Vaginal Cream 2%) and Both Active Treatments to a Placebo Control in the Treatment of Bacterial Vaginosis in Non-pregnant Women

    ClinicalTrials.gov

    2015-03-18

    BACTERIAL VAGINOSIS; Signs and Symptoms to be Evaluated and Recorded Include:; Vaginal Discharge: Color, Odor, and Consistency;; Vulvovaginal Itching and Irritation (Subjective): Absent, Mild, Moderate, or Severe; Vulvovaginal Inflammation (Objective): Absent, Mild, Moderate, or Severe.

  14. Specific Activation of the Plant P-type Plasma Membrane H+-ATPase by Lysophospholipids Depends on the Autoinhibitory N- and C-terminal Domains.

    PubMed

    Wielandt, Alex Green; Pedersen, Jesper Torbøl; Falhof, Janus; Kemmer, Gerdi Christine; Lund, Anette; Ekberg, Kira; Fuglsang, Anja Thoe; Pomorski, Thomas Günther; Buch-Pedersen, Morten Jeppe; Palmgren, Michael

    2015-06-26

    Eukaryotic P-type plasma membrane H(+)-ATPases are primary active transport systems that are regulated at the post-translation level by cis-acting autoinhibitory domains, which can be relieved by protein kinase-mediated phosphorylation or binding of specific lipid species. Here we show that lysophospholipids specifically activate a plant plasma membrane H(+)-ATPase (Arabidopsis thaliana AHA2) by a mechanism that involves both cytoplasmic terminal domains of AHA2, whereas they have no effect on the fungal counterpart (Saccharomyces cerevisiae Pma1p). The activation was dependent on the glycerol backbone of the lysophospholipid and increased with acyl chain length, whereas the headgroup had little effect on activation. Activation of the plant pump by lysophospholipids did not involve the penultimate residue, Thr-947, which is known to be phosphorylated as part of a binding site for activating 14-3-3 protein, but was critically dependent on a single autoinhibitory residue (Leu-919) upstream of the C-terminal cytoplasmic domain in AHA2. A corresponding residue is absent in the fungal counterpart. These data indicate that plant plasma membrane H(+)-ATPases evolved as specific receptors for lysophospholipids and support the hypothesis that lysophospholipids are important plant signaling molecules. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Correlation between active layer thickness and ambient gas stability in IGZO thin-film transistors

    NASA Astrophysics Data System (ADS)

    Gao, Xu; Lin, Meng-Fang; Mao, Bao-Hua; Shimizu, Maki; Mitoma, Nobuhiko; Kizu, Takio; Ou-Yang, Wei; Nabatame, Toshihide; Liu, Zhi; Tsukagoshi, Kazuhito; Wang, Sui-Dong

    2017-01-01

    Decreasing the active layer thickness has been recently reported as an alternative way to achieve fully depleted oxide thin-film transistors for the realization of low-voltage operations. However, the correlation between the active layer thickness and device resistivity to environmental changes is still unclear, which is important for the optimized design of oxide thin-film transistors. In this work, the ambient gas stability of IGZO thin-film transistors is found to be strongly correlated to the IGZO thickness. The TFT with the thinnest IGZO layer shows the highest intrinsic electron mobility in a vacuum, which is greatly reduced after exposure to O2/air. The device with a thick IGZO layer shows similar electron mobility in O2/air, whereas the mobility variation measured in the vacuum is absent. The thickness dependent ambient gas stability is attributed to a high-mobility region in the IGZO surface vicinity with less sputtering-induced damage, which will become electron depleted in O2/air due to the electron transfer to adsorbed gas molecules. The O2 adsorption and deduced IGZO surface band bending is demonstrated by the ambient-pressure x-ray photoemission spectroscopy results.

  16. Cortical activation patterns to spatially presented pure tone stimuli with different intensities measured by functional near-infrared spectroscopy.

    PubMed

    Bauernfeind, Günther; Wriessnegger, Selina C; Haumann, Sabine; Lenarz, Thomas

    2018-03-08

    Functional near-infrared spectroscopy (fNIRS) is an emerging technique for the assessment of functional activity of the cerebral cortex. Recently fNIRS was also envisaged as a novel neuroimaging approach for measuring the auditory cortex activity in the field of in auditory diagnostics. This study aimed to investigate differences in brain activity related to spatially presented sounds with different intensities in 10 subjects by means of functional near-infrared spectroscopy (fNIRS). We found pronounced cortical activation patterns in the temporal and frontal regions of both hemispheres. In contrast to these activation patterns, we found deactivation patterns in central and parietal regions of both hemispheres. Furthermore our results showed an influence of spatial presentation and intensity of the presented sounds on brain activity in related regions of interest. These findings are in line with previous fMRI studies which also reported systematic changes of activation in temporal and frontal areas with increasing sound intensity. Although clear evidence for contralaterality effects and hemispheric asymmetries were absent in the group data, these effects were partially visible on the single subject level. Concluding, fNIRS is sensitive enough to capture differences in brain responses during the spatial presentation of sounds with different intensities in several cortical regions. Our results may serve as a valuable contribution for further basic research and the future use of fNIRS in the area of central auditory diagnostics. © 2018 Wiley Periodicals, Inc.

  17. Measurements of fast ion spatial dynamics during magnetic activity in the RFP

    NASA Astrophysics Data System (ADS)

    Goetz, J. A.; Anderson, J. K.; Bonofiglo, P.; Kim, J.; McConnell, R.; Magee, R. M.

    2017-10-01

    Fast ions in the RFP are only weakly affected by a stochastic magnetic field and behave nearly classically in concentration too low to excite Alfvenic activity. At high fast ion concentration sourced by H-NBI in 300kA RFP discharges, a substantial drop in core-localized high pitch fast ions is observed during bursts of coupled EPM and IAE (magnetic island-induced Alfven eigenmode) activity (100-200kHz) through neutral particle analysis. Sourcing instead fast deuterium with NBI, the DD fusion products can measure the dynamics of the fast ion density profile. Both a collimated neutron detector and a new 3MeV fusion proton detector loaned by TriAlpha Energy measure the fast ion density profile with 5cm spatial resolution and 100 μs temporal resolution. In D-NBI, the bursting EPM is excited at slightly lower frequency and the IAE activity is nearly absent, likely due to an isotope effect and loss of wave-particle interaction. In these cases, neutral particle analysis shows little change in the core-localized high pitch fast ion content, and the fusion product profile indicates little change in the fast ion density profile, leaving unexplained the mechanism removing EPM drive. We measure a substantial redistribution of the fast ion profile due to strong lower-frequency ( 30kHz) MHD activity that accompanies the current profile relaxation in the RFP. Profile flattening is strongest in low bulk density discharges, which often occur with a total increase in global neutron flux from acceleration of the beam ions. Work supported by US DoE.

  18. Rat and mouse CD94 associate directly with the activating transmembrane adaptor proteins DAP12 and DAP10 and activate NK cell cytotoxicity.

    PubMed

    Saether, Per C; Hoelsbrekken, Sigurd E; Fossum, Sigbjørn; Dissen, Erik

    2011-12-15

    Signaling by the CD94/NKG2 heterodimeric NK cell receptor family has been well characterized in the human but has remained unclear in the mouse and rat. In the human, the activating receptor CD94/NKG2C associates with DAP12 by an ionic bond between oppositely charged residues within the transmembrane regions of NKG2C and DAP12. The lysine residue responsible for DAP12 association is absent in rat and mouse NKG2C and -E, raising questions about signaling mechanisms in these species. As a possible substitute, rat and mouse NKG2C and -E contain an arginine residue in the transition between the transmembrane and stalk regions. In this article, we demonstrate that, similar to their human orthologs, NKG2A inhibits, whereas NKG2C activates, rat NK cells. Redirected lysis assays using NK cells transfected with a mutated NKG2C construct indicated that the activating function of CD94/NKG2C did not depend on the transmembrane/stalk region arginine residue. Flow cytometry and biochemical analysis demonstrated that both DAP12 and DAP10 can associate with rat CD94/NKG2C. Surprisingly, DAP12 and DAP10 did not associate with NKG2C but instead with CD94. These associations depended on a transmembrane lysine residue in CD94 that is unique to rodents. Thus, in the mouse and rat, the ability to bind activating adaptor proteins has been transferred from NKG2C/E to the CD94 chain as a result of mutation events in both chains. Remarkable from a phylogenetic perspective, this sheds new light on the evolution and function of the CD94/NKG2 receptor family.

  19. Temporal variability of local abundance, sex ratio and activity in the Sardinian chalk hill blue butterfly

    USGS Publications Warehouse

    Casula, P.; Nichols, J.D.

    2003-01-01

    When capturing and marking of individuals is possible, the application of newly developed capture-recapture models can remove several sources of bias in the estimation of population parameters such as local abundance and sex ratio. For example, observation of distorted sex ratios in counts or captures can reflect either different abundances of the sexes or different sex-specific capture probabilities, and capture-recapture models can help distinguish between these two possibilities. Robust design models and a model selection procedure based on information-theoretic methods were applied to study the local population structure of the endemic Sardinian chalk hill blue butterfly, Polyommatus coridon gennargenti. Seasonal variations of abundance, plus daily and weather-related variations of active populations of males and females were investigated. Evidence was found of protandry and male pioneering of the breeding space. Temporary emigration probability, which describes the proportion of the population not exposed to capture (e.g. absent from the study area) during the sampling process, was estimated, differed between sexes, and was related to temperature, a factor known to influence animal activity. The correlation between temporary emigration and average daily temperature suggested interpreting temporary emigration as inactivity of animals. Robust design models were used successfully to provide a detailed description of the population structure and activity in this butterfly and are recommended for studies of local abundance and animal activity in the field.

  20. Abrupt changes in the patterns and complexity of anterior cingulate cortex activity when food is introduced into an environment

    PubMed Central

    Caracheo, Barak F.; Emberly, Eldon; Hadizadeh, Shirin; Hyman, James M.; Seamans, Jeremy K.

    2013-01-01

    Foraging typically involves two distinct phases, an exploration phase where an organism explores its local environment in search of needed resources and an exploitation phase where a discovered resource is consumed. The behavior and cognitive requirements of exploration and exploitation are quite different and yet organisms can quickly and efficiently switch between them many times during a foraging bout. The present study investigated neural activity state dynamics in the anterior cingulate sub-region of the rat medial prefrontal cortex (mPFC) when a reliable food source was introduced into an environment. Distinct and largely independent states were detected using a Hidden Markov Model (HMM) when food was present or absent in the environment. Measures of neural entropy or complexity decreased when rats went from exploring the environment to exploiting a reliable food source. Exploration in the absence of food was associated with many weak activity states, while bouts of food consumption were characterized by fewer stronger states. Widespread activity state changes in the mPFC may help to inform foraging decisions and focus behavior on what is currently most prominent or valuable in the environment. PMID:23745102

  1. Effects of Exergaming and Message Framing in School Environments on Physical Activity Attitudes and Intentions of Children and Adolescents.

    PubMed

    Lwin, May O; Ho, Shirley S; Younbo, Jung; Leng, Theng Yin; Wardoyo, Reidinar J; Jung, Kim Hyo

    2016-09-01

    Although interventions targeting the health of students in schools are becoming common, few studies have examined how health messages operate at the group level in school environments. This study examines the effects of message-based health interventions (extrinsic vs. intrinsic goal framing) in group environments (exergame competitive vs. exergame noncompetitive) on eliciting attitudes and intentions toward physical activity among children and adolescents. We conducted a 7-week school-based intervention program involving 336 children and 259 adolescents in Singapore in which pre- and post-intervention responses were recorded. Our findings revealed the difference in responses between child and adolescent groups. Children who participated in noncompetitive exergames with extrinsically framed health messages and those who participated in competitive exergames with intrinsically framed health messages demonstrated more favorable attitudes toward physical activity. However, the same effects were absent in our adolescent group. These findings suggest that the integration of exergames into competitive and noncompetitive environments can serve as a gateway to traditional physical activity in schools when strategically combined with intrinsically and extrinsically framed messages. Practical and theoretical implications for schools and health educators are discussed.

  2. A Natural Chimeric Pseudomonas Bacteriocin with Novel Pore-Forming Activity Parasitizes the Ferrichrome Transporter

    PubMed Central

    Kemland, Lieselore; Anoz-Carbonell, Ernesto; Buchanan, Susan K.; De Mot, René

    2017-01-01

    ABSTRACT Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently inhibit the toxin’s activity through formation of bacteriocin-immunity complexes or by insertion in the inner membrane, depending on the type of toxin module. We demonstrate strain-specific inhibitory activity for PmnH, a Pseudomonas bacteriocin with an unprecedented dual-toxin architecture, hosting both a colicin M domain, potentially interfering with peptidoglycan synthesis, and a novel colicin N-type domain, a pore-forming module distinct from the colicin Ia-type domain in Pseudomonas aeruginosa pyocin S5. A downstream-linked gene product confers PmnH immunity upon susceptible strains. This protein, ImnH, has a transmembrane topology similar to that of Pseudomonas colicin M-like and pore-forming immunity proteins, although homology with either of these is essentially absent. The enhanced killing activity of PmnH under iron-limited growth conditions reflects parasitism of the ferrichrome-type transporter for entry into target cells, a strategy shown here to be used as well by monodomain colicin M-like bacteriocins from pseudomonads. The integration of a second type of toxin module in a bacteriocin gene could offer a competitive advantage against bacteria displaying immunity against only one of both toxic activities. PMID:28223456

  3. Top-down controlled alpha band activity in somatosensory areas determines behavioral performance in a discrimination task.

    PubMed

    Haegens, Saskia; Händel, Barbara F; Jensen, Ole

    2011-04-06

    The brain receives a rich flow of information which must be processed according to behavioral relevance. How is the state of the sensory system adjusted to up- or downregulate processing according to anticipation? We used magnetoencephalography to investigate whether prestimulus alpha band activity (8-14 Hz) reflects allocation of attentional resources in the human somatosensory system. Subjects performed a tactile discrimination task where a visual cue directed attention to their right or left hand. The strength of attentional modulation was controlled by varying the reliability of the cue in three experimental blocks (100%, 75%, or 50% valid cueing). While somatosensory prestimulus alpha power lateralized strongly with a fully predictive cue (100%), lateralization was decreased with lower cue reliability (75%) and virtually absent if the cue had no predictive value at all (50%). Importantly, alpha lateralization influenced the subjects' behavioral performance positively: both accuracy and speed of response improved with the degree of alpha lateralization. This study demonstrates that prestimulus alpha lateralization in the somatosensory system behaves similarly to posterior alpha activity observed in visual attention tasks. Our findings extend the notion that alpha band activity is involved in shaping the functional architecture of the working brain by determining both the engagement and disengagement of specific regions: the degree of anticipation modulates the alpha activity in sensory regions in a graded manner. Thus, the alpha activity is under top-down control and seems to play an important role for setting the state of sensory regions to optimize processing.

  4. Sialidase activities of cultured human fibroblasts and the metabolism of GM3 ganglioside

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

    Usuki, S.; Lyu, S.C.; Sweeley, C.C.

    1988-05-15

    Free sialic acid has been found in the cell-conditioned medium of human foreskin fibroblasts. It is proposed that the accumulation of extracellular sialic acid may result from the hydrolysis of GM3 ganglioside on the cell surface of these fibroblasts. Sialidase activities with GM3 ganglioside and sialyllactitol as substrates were demonstrated in cell-conditioned medium, and the levels of their activities correlated positively with cell density. The GM3 sialidase activity at pH 4.5 was 4.1 and 38 pmol/h/ml of medium at sparse and confluent densities, respectively; the corresponding activities with sialyllactitol as the substrate were 12 and 75 pmol/h/ml of medium (pHmore » 4.5). The pH versus activity profiles with GM3 as the substrate suggested the presence of a second sialidase with an optimal activity at pH 6.5 in the conditioned medium of preconfluent cells. This activity was virtually absent in the medium of contact-inhibited cells and could not be assayed with sialyllactitol as the substrate. The turnover of cell surface GM3 was assessed by pulse labeling human foreskin fibroblasts with a radioactive precursor of sialic acid ((1-14C)N-acetylmannosamine) and a radioactive precursor of ceramide ((3,3-3H2)serine). During a chase period of 24 h turnover of the doubly labeled cellular GM3 was observed; there was a loss of about 35% of the 14C-labeled sialic acid without any measureable loss of 3H-labeled ceramide from GM3. We have speculated that the enzyme-catalyzed removal of sialic acid from the GM3 ganglioside on the extracellular aspect of the plasma membrane may be a necessary event involved in the modulation of cell growth.« less

  5. LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism.

    PubMed

    Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco

    2014-11-01

    Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. The (Absent) Politics of Neo-Liberal Education Policy

    ERIC Educational Resources Information Center

    Clarke, Matthew

    2012-01-01

    Despite its ideological saturation, recent neo-liberal education policy has been deeply depoliticising in the sense of reducing properly political concerns to matters of technical efficiency. This depoliticisation is reflected in the hegemony of a managerial discourse and the decontestation of terms like "quality" and…

  7. A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease.

    PubMed

    Ivanov, Yury V; Shariat, Nikki; Register, Karen B; Linz, Bodo; Rivera, Israel; Hu, Kai; Dudley, Edward G; Harvill, Eric T

    2015-10-26

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (cas) are widely distributed among bacteria. These systems provide adaptive immunity against mobile genetic elements specified by the spacer sequences stored within the CRISPR. The CRISPR-Cas system has been identified using Basic Local Alignment Search Tool (BLAST) against other sequenced and annotated genomes and confirmed via CRISPRfinder program. Using Polymerase Chain Reactions (PCR) and Sanger DNA sequencing, we discovered CRISPRs in additional bacterial isolates of the same species of Bordetella. Transcriptional activity and processing of the CRISPR have been assessed via RT-PCR. Here we describe a novel Type II-C CRISPR and its associated genes-cas1, cas2, and cas9-in several isolates of a newly discovered Bordetella species. The CRISPR-cas locus, which is absent in all other Bordetella species, has a significantly lower GC-content than the genome-wide average, suggesting acquisition of this locus via horizontal gene transfer from a currently unknown source. The CRISPR array is transcribed and processed into mature CRISPR RNAs (crRNA), some of which have homology to prophages found in closely related species B. hinzii. Expression of the CRISPR-Cas system and processing of crRNAs with perfect homology to prophages present in closely related species, but absent in that containing this CRISPR-Cas system, suggest it provides protection against phage predation. The 3,117-bp cas9 endonuclease gene from this novel CRISPR-Cas system is 990 bp smaller than that of Streptococcus pyogenes, the 4,017-bp allele currently used for genome editing, and which may make it a useful tool in various CRISPR-Cas technologies.

  8. Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers.

    PubMed

    Gu, Xiaosi; Lohrenz, Terry; Salas, Ramiro; Baldwin, Philip R; Soltani, Alireza; Kirk, Ulrich; Cinciripini, Paul M; Montague, P Read

    2016-01-01

    Little is known about the specific neural mechanisms through which cognitive factors influence craving and associated brain responses, despite the initial success of cognitive therapies in treating drug addiction. In this study, we investigated how cognitive factors such as beliefs influence subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told "nicotine" vs. told "no nicotine") with the nicotine content in a cigarette (nicotine vs. placebo) which participants smoked immediately before performing a fMRI task involving reward learning. Subjects' reported craving was measured both before smoking and after the fMRI session. We found that first, in the presence of nicotine, smokers demonstrated significantly reduced craving after smoking when told "nicotine in cigarette" but showed no change in craving when told "no nicotine." Second, neural activity in the insular cortex related to craving was only significant when smokers were told "nicotine" but not when told "no nicotine." Both effects were absent in the placebo condition. Third, insula activation related to computational learning signals was modulated by belief about nicotine regardless of nicotine's presence. These results suggest that belief about nicotine has a strong impact on subjective craving and insula responses related to both craving and learning in deprived smokers, providing insights into the complex nature of belief-drug interactions.

  9. Self-reported physical activity in patients on chronic hemodialysis: correlates and barriers.

    PubMed

    Bossola, Maurizio; Pellu, Valentina; Di Stasio, Enrico; Tazza, Luigi; Giungi, Stefania; Nebiolo, Pier Eugenio

    2014-01-01

    The knowledge of the barriers that are associated with decreased physical activity (PA) in patients on chronic hemodialysis (PCH) may be of primary importance for the nephrologists. Thus, we aimed to assess the barriers associated with the absent or reduced PA in PCH of a Mediterranean country. Patients were invited to answer the question 'How often do you exercise during your leisure time?'. Also, patients included in the study were asked to answer questions regarding barriers to physical activity lower than desired. We studied 105 patients. Forty (38.1%) patients reported to never exercise, 6 (5.7%) reported to exercise less than once/week, 4 (3.8%) once/week, 23 (21.9%) two to three times/week, 12 (11.4%) four to five times/week and 20 (19%) daily. Overall, 46 (43.8%) patients never exercised or exercised less than once/week ('inactive') and 59 (56.2%) did exercise more often ('active'). At the multivariate analysis, reduced walking ability, fatigue on the non-dialysis days, and shortness of breath were independently and negatively associated with PA. The same results were found when the reduced model of the multivariate logistic backward regression was built introducing in the model also clinical and laboratory variables. In PCH, fatigue on the non-dialysis days, reduced walking ability, and shortness of breath are barriers independently associated to decreased PA. Knowledge about the causes and mechanisms that generate these barriers has to be acquired. © 2014 S. Karger AG, Basel.

  10. Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression

    PubMed Central

    Beer, Philip A.; Knapp, David J. H. F.; Miller, Paul H.; Kannan, Nagarajan; Sloma, Ivan; Heel, Kathy; Babovic, Sonja; Bulaeva, Elizabeth; Rabu, Gabrielle; Terry, Jefferson; Druker, Brian J.; Loriaux, Marc M.; Loeb, Keith R.; Radich, Jerald P.; Erber, Wendy N.

    2015-01-01

    Without effective therapy, chronic-phase chronic myeloid leukemia (CP-CML) evolves into an acute leukemia (blast crisis [BC]) that displays either myeloid or B-lymphoid characteristics. This transition is often preceded by a clinically recognized, but biologically poorly characterized, accelerated phase (AP). Here, we report that IKAROS protein is absent or reduced in bone marrow blasts from most CML patients with advanced myeloid disease (AP or BC). This contrasts with primitive CP-CML cells and BCR-ABL1–negative acute myeloid leukemia blasts, which express readily detectable IKAROS. To investigate whether loss of IKAROS contributes to myeloid disease progression in CP-CML, we examined the effects of forced expression of a dominant-negative isoform of IKAROS (IK6) in CP-CML patients’ CD34+ cells. We confirmed that IK6 disrupts IKAROS activity in transduced CP-CML cells and showed that it confers on them features of AP-CML, including a prolonged increased output in vitro and in xenografted mice of primitive cells with an enhanced ability to differentiate into basophils. Expression of IK6 in CD34+ CP-CML cells also led to activation of signal transducer and activator of transcription 5 and transcriptional repression of its negative regulators. These findings implicate loss of IKAROS as a frequent step and potential diagnostic harbinger of progressive myeloid disease in CML patients. PMID:25370416

  11. Spatio-temporal accumulation and activity of calcium-dependent protein kinases during embryogenesis, seed development, and germination in sandalwood.

    PubMed

    Anil, V S; Harmon, A C; Rao, K S

    2000-04-01

    Western-blot analysis and protein kinase assays identified two Ca(2+)-dependent protein kinases (CDPKs) of 55 to 60 kD in soluble protein extracts of embryogenic cultures of sandalwood (Santalum album L.). However, these sandalwood CDPKs (swCDPKs) were absent in plantlets regenerated from somatic embryos. swCDPKs exhibited differential expression (monitored at the level of the protein) and activity in different developmental stages. Zygotic embryos, seedlings, and endosperm showed high accumulation of swCDPK, but the enzyme was not detected in the soluble proteins of shoots and flowers. swCDPK exhibited a temporal pattern of expression in endosperm, showing high accumulation and activity in mature fruit and germinating stages; the enzyme was localized strongly in the storage bodies of the endosperm cells. The study also reports for the first time to our knowledge a post-translational inhibition/inactivation of swCDPK in zygotic embryos during seed dormancy and early stages of germination. The temporal expression of swCDPK during somatic/zygotic embryogenesis, seed maturation, and germination suggests involvement of the enzyme in these developmental processes.

  12. Turning Virtual Reality into Reality: A Checklist to Ensure Virtual Reality Studies of Eating Behavior and Physical Activity Parallel the Real World

    PubMed Central

    Tal, Aner; Wansink, Brian

    2011-01-01

    Virtual reality (VR) provides a potentially powerful tool for researchers seeking to investigate eating and physical activity. Some unique conditions are necessary to ensure that the psychological processes that influence real eating behavior also influence behavior in VR environments. Accounting for these conditions is critical if VR-assisted research is to accurately reflect real-world situations. The current work discusses key considerations VR researchers must take into account to ensure similar psychological functioning in virtual and actual reality and does so by focusing on the process of spontaneous mental simulation. Spontaneous mental simulation is prevalent under real-world conditions but may be absent under VR conditions, potentially leading to differences in judgment and behavior between virtual and actual reality. For simulation to occur, the virtual environment must be perceived as being available for action. A useful chart is supplied as a reference to help researchers to investigate eating and physical activity more effectively. PMID:21527088

  13. Turning virtual reality into reality: a checklist to ensure virtual reality studies of eating behavior and physical activity parallel the real world.

    PubMed

    Tal, Aner; Wansink, Brian

    2011-03-01

    Virtual reality (VR) provides a potentially powerful tool for researchers seeking to investigate eating and physical activity. Some unique conditions are necessary to ensure that the psychological processes that influence real eating behavior also influence behavior in VR environments. Accounting for these conditions is critical if VR-assisted research is to accurately reflect real-world situations. The current work discusses key considerations VR researchers must take into account to ensure similar psychological functioning in virtual and actual reality and does so by focusing on the process of spontaneous mental simulation. Spontaneous mental simulation is prevalent under real-world conditions but may be absent under VR conditions, potentially leading to differences in judgment and behavior between virtual and actual reality. For simulation to occur, the virtual environment must be perceived as being available for action. A useful chart is supplied as a reference to help researchers to investigate eating and physical activity more effectively. © 2011 Diabetes Technology Society.

  14. Activation of bean (Phaseolus vulgaris) [alpha]-amylase inhibitor requires proteolytic processing of the proprotein

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

    Pueyo, J.J.; Hunt, D.C.; Chrispeels, M.J.

    Seeds of the common bean (Phaseolus vulgaris) contain a plant defense protein that inhibits the [alpha]-amylases of mammals and insects. This [alpha]-amylase inhibitor ([alpha]Al) is synthesized as a proprotein on the endoplasmic reticulum and is proteolytically processed after arrival in the protein storage vacuoles to polypeptides of relative molecular weight (M[sub r]) 15,000 to 18,000. The authors report two types of evidence that proteolytic processing is linked to activation of the inhibitory activity. First, by surveying seed extracts of wild accessions of P. vulgaris and other species in the genus Phaseolus, they found that antibodies to [alpha]Al recognize large (M[submore » r] 30,000-35,000) polypeptides as well as typical [alpha]Al processing products (M[sub r] 15,000-18,000). [alpha]Al activity was found in all extracts that had the typical [alpha]Al processed polypeptides, but was absent from seed extracts that lacked such polypeptides. Second, they made a mutant [alpha]Al in which asparagine-77 is changed to aspartic acid-77. This mutation slows down the proteolytic processing of pro-[alpha]Al when the gene is expressed in tobacco. When pro-[alpha]Al was separated from mature [alpha]Al by gel filtration, pro-[alpha]Al was found not to have [alpha]-amylase inhibitory activity. The authors interpret these results to mean that formation of the active inhibitor is causally related to proteolytic processing of the proprotein. They suggest that the polypeptide cleavage removes a conformation constraint on the precursor to produce the biochemically active molecule. 43 refs., 5 figs., 1 tab.« less

  15. The importance of delineating networks by activity type in bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida.

    PubMed

    Gazda, Stefanie; Iyer, Swami; Killingback, Timothy; Connor, Richard; Brault, Solange

    2015-03-01

    Network analysis has proved to be a valuable tool for studying the behavioural patterns of complex social animals. Often such studies either do not distinguish between different behavioural states of the organisms or simply focus attention on a single behavioural state to the exclusion of all others. In either of these approaches it is impossible to ascertain how the behavioural patterns of individuals depend on the type of activity they are engaged in. Here we report on a network-based analysis of the behavioural associations in a population of bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida. We consider three distinct behavioural states-socializing, travelling and foraging-and analyse the association networks corresponding to each activity. Moreover, in constructing the different activity networks we do not simply record a spatial association between two individuals as being either present or absent, but rather quantify the degree of any association, thus allowing us to construct weighted networks describing each activity. The results of these weighted activity networks indicate that networks can reveal detailed patterns of bottlenose dolphins at the population level; dolphins socialize in large groups with preferential associations; travel in small groups with preferential associates; and spread out to forage in very small, weakly connected groups. There is some overlap in the socialize and travel networks but little overlap between the forage and other networks. This indicates that the social bonds maintained in other activities are less important as they forage on dispersed, solitary prey. The overall network, not sorted by activity, does not accurately represent any of these patterns.

  16. The importance of delineating networks by activity type in bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida

    PubMed Central

    Gazda, Stefanie; Iyer, Swami; Killingback, Timothy; Connor, Richard; Brault, Solange

    2015-01-01

    Network analysis has proved to be a valuable tool for studying the behavioural patterns of complex social animals. Often such studies either do not distinguish between different behavioural states of the organisms or simply focus attention on a single behavioural state to the exclusion of all others. In either of these approaches it is impossible to ascertain how the behavioural patterns of individuals depend on the type of activity they are engaged in. Here we report on a network-based analysis of the behavioural associations in a population of bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida. We consider three distinct behavioural states—socializing, travelling and foraging—and analyse the association networks corresponding to each activity. Moreover, in constructing the different activity networks we do not simply record a spatial association between two individuals as being either present or absent, but rather quantify the degree of any association, thus allowing us to construct weighted networks describing each activity. The results of these weighted activity networks indicate that networks can reveal detailed patterns of bottlenose dolphins at the population level; dolphins socialize in large groups with preferential associations; travel in small groups with preferential associates; and spread out to forage in very small, weakly connected groups. There is some overlap in the socialize and travel networks but little overlap between the forage and other networks. This indicates that the social bonds maintained in other activities are less important as they forage on dispersed, solitary prey. The overall network, not sorted by activity, does not accurately represent any of these patterns. PMID:26064611

  17. Loosenin, a novel protein with cellulose-disrupting activity from Bjerkandera adusta.

    PubMed

    Quiroz-Castañeda, Rosa E; Martínez-Anaya, Claudia; Cuervo-Soto, Laura I; Segovia, Lorenzo; Folch-Mallol, Jorge L

    2011-02-11

    Expansins and expansin-like proteins loosen cellulose microfibrils, possibly through the rupture of intramolecular hydrogen bonds. Together with the use of lignocellulolytic enzymes, these proteins are potential molecular tools to treat plant biomass to improve saccharification yields. Here we describe a new type of expansin-related fungal protein that we have called loosenin. Its corresponding gene, loos1, from the basidiomycete Bjerkandera adusta, was cloned and heterologously expressed in Saccharomyces cerevisiae. LOOS1 is distantly related to plant expansins through the shared presence of a DPBB domain, however domain II found in plant expansins is absent. LOOS1 binds tightly to cellulose and chitin, and we demonstrate that cotton fibers become susceptible to the action of a commercial cellulase following treatment with LOOS1. Natural fibers of Agave tequilana also become susceptible to hydrolysis by cellulases after loosenin treatment. LOOS1 is a new type of protein with disrupting activity on cellulose. LOOS1 binds polysaccharides, and given its enhancing properties on the action of hydrolytic enzymes, LOOS1 represents a potential additive in the production of fermentable sugars from lignocellulose.

  18. BIOCHEMICAL AND ULTRASTRUCTURAL PROPERTIES OF A MITOCHONDRIAL INNER MEMBRANE FRACTION DEFICIENT IN OUTER MEMBRANE AND MATRIX ACTIVITIES

    PubMed Central

    Chan, T. L.; Greenawalt, John W.; Pedersen, Peter L.

    1970-01-01

    Treatment of the inner membrane matrix fraction of rat liver mitochondria with the nonionic detergent Lubrol WX solubilized about 70% of the total protein and 90% or more of the following matrix activities: malate dehydrogenase, glutamate dehydrogenase, and isocitrate dehydrogenase (NADP). The Lubrol-insoluble fraction was enriched in cytochromes, phospholipids, and a Mg++-stimulated ATPase activity. Less than 2% of the total mitochondrial activity of monoamine oxidase, an outer membrane marker, or adenylate kinase, an intracristal space marker could be detected in this inner membrane fraction. Electron micrographs of negatively stained preparations showed vesicles (≤0.4 µ diameter) literally saturated on the periphery with the 90 A ATPase particles. These inner membrane vesicles, which appeared for the most part to be inverted with respect to the normal inner membrane configuration in intact mitochondria, retained the succinicoxidase portion of the electron-transport chain, an intact phosphorylation site II with a high affinity for ADP, and the capacity to accumulate Ca++. A number of biochemical properties characteristic of intact mitochondria and the inner membrane matrix fraction, however, were either absent or markedly deficient in the inner membrane vesicles. These included stimulation of respiration by either ADP or 2,4-dinitrophenol, oligomycin-sensitive ADP-ATP exchange activity, atractyloside sensitivity of adenine nucleotide requiring reactions, and a stimulation of the Mg++-ATPase by 2,4-dinitrophenol. PMID:4254678

  19. Relation between cooperative molecular motors and active Brownian particles.

    PubMed

    Touya, Clément; Schwalger, Tilo; Lindner, Benjamin

    2011-05-01

    Active Brownian particles (ABPs), obeying a nonlinear Langevin equation with speed-dependent drift and noise amplitude, are well-known models used to describe self-propelled motion in biology. In this paper we study a model describing the stochastic dynamics of a group of coupled molecular motors (CMMs). Using two independent numerical methods, one based on the stationary velocity distribution of the motors and the other one on the local increments (also known as the Kramers-Moyal coefficients) of the velocity, we establish a connection between the CMM and the ABP models. The parameters extracted for the ABP via the two methods show good agreement for both symmetric and asymmetric cases and are independent of N, the number of motors, provided that N is not too small. This indicates that one can indeed describe the CMM problem with a simpler ABP model. However, the power spectrum of velocity fluctuations in the CMM model reveals a peak at a finite frequency, a peak which is absent in the velocity spectrum of the ABP model. This implies richer dynamic features of the CMM model which cannot be captured by an ABP model.

  20. Fluorogen-Activating-Proteins as Universal Affinity Biosensors for Immunodetection

    PubMed Central

    Gallo, Eugenio; Vasilev, Kalin V.; Jarvik, Jonathan

    2014-01-01

    Fluorogen-activating-proteins (FAPs) are a novel platform of fluorescence biosensors utilized for protein discovery. The technology currently demands molecular manipulation methods that limit its application and adaptability. Here, we highlight an alternative approach based on universal affinity reagents for protein detection. The affinity reagents were engineered as bi-partite fusion proteins, where the specificity moiety is derived from IgG-binding proteins –Protein-A or Protein-G – and the signaling element is a FAP. In this manner, primary antibodies provide the antigenic selectivity against a desired protein in biological samples, while FAP affinity reagents target the constant region (Fc) of antibodies and provide the biosensor component of detection. Fluorescence results using various techniques indicate minimal background and high target specificity for exogenous and endogenous proteins in mammalian cells. Additionally, FAP-based affinity reagents provide enhanced properties of detection previously absent using conventional affinity systems. Distinct features explored in this report include: (1) unfixed signal wavelengths (excitation and emission) determined by the particular fluorogen chosen, (2) real-time user controlled fluorescence on-set and off-set, (3) signal wavelength substitution while performing live analysis, and (4) enhanced resistance to photobleaching. PMID:24122476

  1. Relation between cooperative molecular motors and active Brownian particles

    NASA Astrophysics Data System (ADS)

    Touya, Clément; Schwalger, Tilo; Lindner, Benjamin

    2011-05-01

    Active Brownian particles (ABPs), obeying a nonlinear Langevin equation with speed-dependent drift and noise amplitude, are well-known models used to describe self-propelled motion in biology. In this paper we study a model describing the stochastic dynamics of a group of coupled molecular motors (CMMs). Using two independent numerical methods, one based on the stationary velocity distribution of the motors and the other one on the local increments (also known as the Kramers-Moyal coefficients) of the velocity, we establish a connection between the CMM and the ABP models. The parameters extracted for the ABP via the two methods show good agreement for both symmetric and asymmetric cases and are independent of N, the number of motors, provided that N is not too small. This indicates that one can indeed describe the CMM problem with a simpler ABP model. However, the power spectrum of velocity fluctuations in the CMM model reveals a peak at a finite frequency, a peak which is absent in the velocity spectrum of the ABP model. This implies richer dynamic features of the CMM model which cannot be captured by an ABP model.

  2. Water in the Active Site of Ketosteroid Isomerase

    PubMed Central

    Hanoian, Philip; Hammes-Schiffer, Sharon

    2011-01-01

    Classical molecular dynamics simulations were utilized to investigate the structural and dynamical properties of water in the active site of ketosteroid isomerase (KSI) to provide insight into the role of these water molecules in the enzyme-catalyzed reaction. This reaction is thought to proceed via a dienolate intermediate that is stabilized by hydrogen bonding with residues Tyr16 and Asp103. A comparative study was performed for the wild-type (WT) KSI and the Y16F, Y16S, and Y16F/Y32F/Y57F (FFF) mutants. These systems were studied with three different bound ligands: equilenin, which is an intermediate analog, and the intermediate states of two steroid substrates. Several distinct water occupation sites were identified in the active site of KSI for the WT and mutant systems. Three additional sites were identified in the Y16S mutant that were not occupied in WT KSI or the other mutants studied. The number of water molecules directly hydrogen bonded to the ligand oxygen was approximately two waters in the Y16S mutant, one water in the Y16F and FFF mutants, and intermittent hydrogen bonding of one water molecule in WT KSI. The molecular dynamics trajectories of the Y16F and FFF mutants reproduced the small conformational changes of residue 16 observed in the crystal structures of these two mutants. Quantum mechanical/molecular mechanical calculations of 1H NMR chemical shifts of the protons in the active site hydrogen-bonding network suggest that the presence of water in the active site does not prevent the formation of short hydrogen bonds with far-downfield chemical shifts. The molecular dynamics simulations indicate that the active site water molecules exchange much more frequently for WT KSI and the FFF mutant than for the Y16F and Y16S mutants. This difference is most likely due to the hydrogen-bonding interaction between Tyr57 and an active site water molecule that is persistent in the Y16F and Y16S mutants but absent in the FFF mutant and significantly less

  3. Water in the active site of ketosteroid isomerase.

    PubMed

    Hanoian, Philip; Hammes-Schiffer, Sharon

    2011-08-09

    Classical molecular dynamics simulations were utilized to investigate the structural and dynamical properties of water in the active site of ketosteroid isomerase (KSI) to provide insight into the role of these water molecules in the enzyme-catalyzed reaction. This reaction is thought to proceed via a dienolate intermediate that is stabilized by hydrogen bonding with residues Tyr16 and Asp103. A comparative study was performed for the wild-type (WT) KSI and the Y16F, Y16S, and Y16F/Y32F/Y57F (FFF) mutants. These systems were studied with three different bound ligands: equilenin, which is an intermediate analog, and the intermediate states of two steroid substrates. Several distinct water occupation sites were identified in the active site of KSI for the WT and mutant systems. Three additional sites were identified in the Y16S mutant that were not occupied in WT KSI or the other mutants studied. The number of water molecules directly hydrogen bonded to the ligand oxygen was approximately two in the Y16S mutant and one in the Y16F and FFF mutants, with intermittent hydrogen bonding of one water molecule in WT KSI. The molecular dynamics trajectories of the Y16F and FFF mutants reproduced the small conformational changes of residue 16 observed in the crystal structures of these two mutants. Quantum mechanical/molecular mechanical calculations of (1)H NMR chemical shifts of the protons in the active site hydrogen-bonding network suggest that the presence of water in the active site does not prevent the formation of short hydrogen bonds with far-downfield chemical shifts. The molecular dynamics simulations indicate that the active site water molecules exchange much more frequently for WT KSI and the FFF mutant than for the Y16F and Y16S mutants. This difference is most likely due to the hydrogen-bonding interaction between Tyr57 and an active site water molecule that is persistent in the Y16F and Y16S mutants but absent in the FFF mutant and significantly less probable

  4. Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women.

    PubMed

    Vessby, B; Ahrén, B; Warensjö, E; Lindgärde, F

    2012-03-01

    Two Amerindian populations--Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. Fasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women. The high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation. Copyright © 2010. Published by Elsevier B.V.

  5. Different responses of spontaneous and stimulus-related alpha activity to ambient luminance changes.

    PubMed

    Benedetto, Alessandro; Lozano-Soldevilla, Diego; VanRullen, Rufin

    2017-12-04

    Alpha oscillations are particularly important in determining our percepts and have been implicated in fundamental brain functions. Oscillatory activity can be spontaneous or stimulus-related. Furthermore, stimulus-related responses can be phase- or non-phase-locked to the stimulus. Non-phase-locked (induced) activity can be identified as the average amplitude changes in response to a stimulation, while phase-locked activity can be measured via reverse-correlation techniques (echo function). However, the mechanisms and the functional roles of these oscillations are far from clear. Here, we investigated the effect of ambient luminance changes, known to dramatically modulate neural oscillations, on spontaneous and stimulus-related alpha. We investigated the effect of ambient luminance on EEG alpha during spontaneous human brain activity at rest (experiment 1) and during visual stimulation (experiment 2). Results show that spontaneous alpha amplitude increased by decreasing ambient luminance, while alpha frequency remained unaffected. In the second experiment, we found that under low-luminance viewing, the stimulus-related alpha amplitude was lower, and its frequency was slightly faster. These effects were evident in the phase-locked part of the alpha response (echo function), but weaker or absent in the induced (non-phase-locked) alpha responses. Finally, we explored the possible behavioural correlates of these modulations in a monocular critical flicker frequency task (experiment 3), finding that dark adaptation in the left eye decreased the temporal threshold of the right eye. Overall, we found that ambient luminance changes impact differently on spontaneous and stimulus-related alpha expression. We suggest that stimulus-related alpha activity is crucial in determining human temporal segmentation abilities. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. Relevance of rhodopsin studies for GPCR activation.

    PubMed

    Deupi, Xavier

    2014-05-01

    Rhodopsin, the dim-light photoreceptor present in the rod cells of the retina, is both a retinal-binding protein and a G protein-coupled receptor (GPCR). Due to this conjunction, it benefits from an arsenal of spectroscopy techniques that can be used for its characterization, while being a model system for the important family of Class A (also referred to as "rhodopsin-like") GPCRs. For instance, rhodopsin has been a crucial player in the field of GPCR structural biology. Until 2007, it was the only GPCR for which a high-resolution crystal structure was available, so all structure-activity analyses on GPCRs, from structure-based drug discovery to studies of structural changes upon activation, were based on rhodopsin. At present, about a third of currently available GPCR structures are still from rhodopsin. In this review, I show some examples of how these structures can still be used to gain insight into general aspects of GPCR activation. First, the analysis of the third intracellular loop in rhodopsin structures allows us to gain an understanding of the structural and dynamic properties of this region, which is absent (due to protein engineering or poor electron density) in most of the currently available GPCR structures. Second, a detailed analysis of the structure of the transmembrane domains in inactive, intermediate and active rhodopsin structures allows us to detect early conformational changes in the process of ligand-induced GPCR activation. Finally, the analysis of a conserved ligand-activated transmission switch in the transmembrane bundle of GPCRs in the context of the rhodopsin activation cycle, allows us to suggest that the structures of many of the currently available agonist-bound GPCRs may correspond to intermediate active states. While the focus in GPCR structural biology is inevitably moving away from rhodopsin, in other aspects rhodopsin is still at the forefront. For instance, the first studies of the structural basis of disease mutants in

  7. Plasmid linkage of the D-tagatose 6-phosphate pathway in Streptococcus lactis: effect on lactose and galactose metabolism.

    PubMed Central

    Crow, V L; Davey, G P; Pearce, L E; Thomas, T D

    1983-01-01

    The three enzymes of the D-tagatose 6-phosphate pathway (galactose 6-phosphate isomerase, D-tagatose 6-phosphate kinase, and tagatose 1,6-diphosphate aldolase) were absent in lactose-negative (Lac-) derivatives of Streptococcus lactis C10, H1, and 133 grown on galactose. The lactose phosphoenolpyruvate-dependent phosphotransferase system and phospho-beta-galactosidase activities were also absent in Lac- derivatives of strains H1 and 133 and were low (possibly absent) in C10 Lac-. In all three Lac- derivatives, low galactose phosphotransferase system activity was found. On galactose, Lac- derivatives grew more slowly (presumably using the Leloir pathway) than the wild-type strains and accumulated high intracellular concentrations of galactose 6-phosphate (up to 49 mM); no intracellular tagatose 1,6-diphosphate was detected. The data suggest that the Lac phenotype is plasmid linked in the three strains studied, with the evidence being more substantial for strain H1. A Lac- derivative of H1 contained a single plasmid (33 megadaltons) which was absent from the Lac- mutant. We suggest that the genes linked to the lactose plasmid in S. lactis are more numerous than previously envisaged, coding for all of the enzymes involved in lactose metabolism from initial transport to the formation of triose phosphates via the D-tagatose 6-phosphate pathway. Images PMID:6294064

  8. Motives and activities for continuing professional development: An exploration of their relationships by integrating literature and interview data.

    PubMed

    Pool, Inge A; Poell, Rob F; Berings, Marjolein G M C; Ten Cate, Olle

    2016-03-01

    To effectively enhance professional development, it is important to understand the motivational factors behind nurses' engagement in particular types of learning activities. Nurses have various motives for professional development and utilise different learning activities. Not much is known about how these relate. The aim of this study was to explore the relationship between nurses' motives and activities for continuing professional development, by examining in which types of learning activities nurses engage, with which motives, and whether certain motives are associated with certain learning activities. A qualitative study using semi-structured interviews. Twenty-one nurses in academic and general Dutch hospitals participated. Interview data on nurses' learning biographies were analysed using a literature-based framework on motives and learning activities for continuing professional development. As recent classifications of nurses' motives for professional development were absent, the literature was reviewed for motives, using three databases. The interview transcripts were analysed for motives, learning activities and their relationships. Nine motives and four categories of learning activities for continuing professional development were delineated. Increasing competence was the primary motive that stimulated nurses to engage in self-directed learning during work, and in formal learning activities. To comply with requirements, they engaged in mandatory courses. To deepen knowledge, they registered for conferences. To develop their careers, they enrolled in postgraduate education. Five other motives were not mentioned as frequently. Specific motives were found to be related to engagement in particular learning activities. Nurses could use these findings to increase their awareness of why and how they develop professionally, and managers and human resource development professionals could develop approaches that would better suit nurses' needs. Copyright © 2016

  9. Spatio-Temporal Accumulation and Activity of Calcium-Dependent Protein Kinases during Embryogenesis, Seed Development, and Germination in Sandalwood1

    PubMed Central

    Anil, Veena S.; Harmon, Alice C.; Rao, K. Sankara

    2000-01-01

    Western-blot analysis and protein kinase assays identified two Ca2+-dependent protein kinases (CDPKs) of 55 to 60 kD in soluble protein extracts of embryogenic cultures of sandalwood (Santalum album L.). However, these sandalwood CDPKs (swCDPKs) were absent in plantlets regenerated from somatic embryos. swCDPKs exhibited differential expression (monitored at the level of the protein) and activity in different developmental stages. Zygotic embryos, seedlings, and endosperm showed high accumulation of swCDPK, but the enzyme was not detected in the soluble proteins of shoots and flowers. swCDPK exhibited a temporal pattern of expression in endosperm, showing high accumulation and activity in mature fruit and germinating stages; the enzyme was localized strongly in the storage bodies of the endosperm cells. The study also reports for the first time to our knowledge a post-translational inhibition/inactivation of swCDPK in zygotic embryos during seed dormancy and early stages of germination. The temporal expression of swCDPK during somatic/zygotic embryogenesis, seed maturation, and germination suggests involvement of the enzyme in these developmental processes. PMID:10759499

  10. Impaired mitochondrial Fe-S cluster biogenesis activates the DNA damage response through different signaling mediators.

    PubMed

    Pijuan, Jordi; María, Carlos; Herrero, Enrique; Bellí, Gemma

    2015-12-15

    Fe-S cluster biogenesis machinery is required for multiple DNA metabolism processes. In this work, we show that, in Saccharomyces cerevisiae, defects at different stages of the mitochondrial Fe-S cluster assembly machinery (ISC) result in increased spontaneous mutation rate and hyper-recombination, accompanied by an increment in Rad52-associated DNA repair foci and a higher phosphorylated state of γH2A histone, altogether supporting the presence of constitutive DNA lesions. Furthermore, ISC assembly machinery deficiency elicits a DNA damage response that upregulates ribonucleotide reductase activity by promoting the reduction of Sml1 levels and the cytosolic redistribution of Rnr2 and Rnr4 enzyme subunits. Depending on the impaired stage of the ISC machinery, different signaling pathway mediators contribute to such a response, converging on Dun1. Thus, cells lacking the glutaredoxin Grx5, which are compromised at the core ISC system, show Mec1- and Rad53-independent Dun1 activation, whereas both Mec1 and Chk1 are required when the non-core ISC member Iba57 is absent. Grx5-null cells exhibit a strong dependence on the error-free post-replication repair and the homologous recombination pathways, demonstrating that a DNA damage response needs to be activated upon ISC impairment to preserve cell viability. © 2015. Published by The Company of Biologists Ltd.

  11. Analysis of Antibacterial Activity and Bioactive Compounds of the Giant Mushroom, Macrocybe gigantea (Agaricomycetes), from India.

    PubMed

    Gaur, Tanvi; Rao, P B

    2017-01-01

    The antibacterial activity, phenolic profile, and bioactive compounds of fruiting bodies from 2 strains (MA1 and MA2) of the giant mushroom Macrocybe gigantea were evaluated to access their nutraceutical efficacy. The antibacterial activity was higher in MA2 against all selected pathogenic bacteria. Selected phenolics were analyzed by high-performance liquid chromatography coupled with ultraviolet-visible detection. Gallic acid, ferulic acid, quercetin, p-hydroxy benzoic acid, cinnamic acid, and rutin contents (micrograms per gram dry weight) were quantified. Quercetin and rutin were absent in both strains of M. gigantea. M. gigantea MA2 showed relatively higher phenolic content (915.8 μg/g dry weight) than M. gigantea MA1 (854.4 μg/g dry weight). Among the phenolics, gallic acid is found in the largest amount; in M. gigantea MA2, it was 847.9 ± 2.67 μg/g dry weight. Gas chromatography-mass spectrometry analysis showed the presence of bioactive compounds in both strains; most compounds were antibacterial. Thus, the selected strains of M. gigantea can combat oxidative damage and can be used in foods, pharmaceuticals, and cosmetics because of their antioxidant potential.

  12. Structural elucidation and antioxidant activity of lignin isolated from rice straw and alkali‑oxygen black liquor.

    PubMed

    Jiang, Bo; Zhang, Yu; Gu, Lihui; Wu, Wenjuan; Zhao, Huifang; Jin, Yongcan

    2018-05-17

    Alkali‑oxygen cooking of lignocellulose offers lignin many structural properties and bioactivities for biorefinery. In this work, milled wood lignin (MWL) and alkali‑oxygen lignin (AOL) were isolated from rice straw and alkali‑oxygen black liquor, respectively. The lignin structure was characterized by spectroscopy and wet chemistry. Antioxidant activity of lignins was assessed by DPPH·and ABTS scavenging ability assay. Results showed the oxidization and condensation of lignin occurred during alkali‑oxygen cooking. The p-hydroxyphenyl was more easily removed from rice straw than guaiacyl and syringyl units. The ester or ether linkages derived from hydroxycynnamic acids, and the main interunit linkages, i.e. β-O-4' bonds, were mostly cleaved. Lignin-xylan complex had high reactivity under alkali‑oxygen condition. Tricin, incorporated into lignin, was detected in MWL but was absent in AOL. Nitrobenzene oxidation showed MWL can well represent the protolignin of rice straw, and the products yield decreased dramatically after alkali‑oxygen cooking. AOL had higher radical scavenging ability than MWL indicating alkali‑oxygen cooking was an effective pathway for the enhancement of antioxidant activity of lignin. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Memory-driven attentional capture reveals the waxing and waning of working memory activation due to dual-task interference.

    PubMed

    Sasin, Edyta; Nieuwenstein, Mark

    2016-12-01

    Previous studies have shown that information held in working memory (WM) actively or as a residue of previous processing can lead to attentional capture by corresponding stimuli in the environment. Here, we compared attentional capture by goal-driven and residual WM activation and examined how these effects are affected by dual-task interference. In two experiments, participants performed an animacy judgment task for a word that they did or did not have to remember for a later recognition test. The word was followed in half of the trials by an arithmetic task that served to disrupt the WM activation of the previously processed word. Subsequently, WM-driven capture was assessed by having participants perform a single-target rapid serial visual presentation task in which a line drawing corresponding to the word was presented shortly before a target. The results showed that the line drawing captured attention irrespective of the presence of the arithmetic task when the word had to be remembered. In comparison, the animacy judgment alone resulted in capture only when the arithmetic task was absent, and this effect was equally strong as the capture effect caused by a to-be-remembered word. Taken together, these findings show that although residual and goal-driven WM activation may be equally potent in guiding attentional selection, these two forms of WM activation differ in that residual activation is overwritten by an attention-demanding task, whereas goal-driven WM activation can lead to the reinstatement of a stimulus after performing such a task.

  14. Graded activity for workers with low back pain: who benefits most and how does it work?

    PubMed

    Staal, J Bart; Hlobil, Hynek; Köke, Albère J A; Twisk, Jos W R; Smid, Tjabe; van Mechelen, Willem

    2008-05-15

    To identify subgroups of workers absent from work due to low back pain who are more or less likely to return to work earlier as a result of a graded activity intervention, and to investigate whether this intervention is effective in reducing pain-related fears and if so, whether these reductions in pain-related fears mediate return to work. A subgroup analysis was conducted on data from a previous randomized controlled trial of 134 Dutch airline workers, which found that a behaviorally-oriented graded activity intervention was more effective than usual care in stimulating return to work. The subgroup analyses added interaction terms to a Cox regression model that described the relationship between treatment allocation and return to work over 12 months of followup. Furthermore, we studied the effects of graded activity on pain-related fears and added variables indicating a reduction in pain-related fears to the model in order to investigate their influence on return to work. Statistically significant interactions were found for disability, fear-avoidance beliefs about physical activity, and fear-avoidance beliefs about work. No indication was found that the reduction in pain-related fears in the graded activity group mediated more favorable return-to-work results in this group. Workers who perceive their disability to be moderate and workers with moderate scores for fear-avoidance beliefs return to work more rapidly as a result of the graded activity intervention than workers with higher scores. The return to work of workers receiving the graded activity intervention is possibly independent from the reductions in pain-related fears caused by this intervention.

  15. Human Temporal Cortical Single Neuron Activity During Working Memory Maintenance

    PubMed Central

    Zamora, Leona; Corina, David; Ojemann, George

    2016-01-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  16. The fibrate gemfibrozil is a NO- and haem-independent activator of soluble guanylyl cyclase: in vitro studies

    PubMed Central

    Sharina, I G; Sobolevsky, M; Papakyriakou, A; Rukoyatkina, N; Spyroulias, G A; Gambaryan, S; Martin, E

    2015-01-01

    Background and Purpose Fibrates are a class of drugs widely used to treat dyslipidaemias. They regulate lipid metabolism and act as PPARα agonists. Clinical trials demonstrate that besides changes in lipid profiles, fibrates decrease the incidence of cardiovascular events, with gemfibrozil exhibiting the most pronounced benefit. This study aims to characterize the effect of gemfibrozil on the activity and function of soluble guanylyl cyclase (sGC), the key mediator of NO signalling. Experimental Approach High-throughput screening of a drug library identified gemfibrozil as a direct sGC activator. Activation of sGC is unique to gemfibrozil and is not shared by other fibrates. Key Results Gemfibrozil activated purified sGC, induced endothelium-independent relaxation of aortic rings and inhibited platelet aggregation. Gemfibrozil-dependent activation was absent when the sGC haem domain was deleted, but was significantly enhanced when sGC haem was lacking or oxidized. Oxidation of sGC haem enhanced the vasoactive and anti-platelet effects of gemfibrozil. Gemfibrozil competed with the haem-independent sGC activators ataciguat and cinaciguat. Computational modelling predicted that gemfibrozil occupies the space of the haem group and interacts with residues crucial for haem stabilization. This is consistent with structure-activity data which revealed an absolute requirement for gemfibrozil's carboxyl group. Conclusions and Implications These data suggest that in addition to altered lipid and lipoprotein state, the cardiovascular preventive benefits of gemfibrozil may derive from direct activation and protection of sGC function. A sGC-directed action may explain the more pronounced cardiovascular benefit of gemfibrozil observed over other fibrates and some of the described side effects of gemfibrozil. PMID:25536881

  17. The fibrate gemfibrozil is a NO- and haem-independent activator of soluble guanylyl cyclase: in vitro studies.

    PubMed

    Sharina, I G; Sobolevsky, M; Papakyriakou, A; Rukoyatkina, N; Spyroulias, G A; Gambaryan, S; Martin, E

    2015-05-01

    Fibrates are a class of drugs widely used to treat dyslipidaemias. They regulate lipid metabolism and act as PPARα agonists. Clinical trials demonstrate that besides changes in lipid profiles, fibrates decrease the incidence of cardiovascular events, with gemfibrozil exhibiting the most pronounced benefit. This study aims to characterize the effect of gemfibrozil on the activity and function of soluble guanylyl cyclase (sGC), the key mediator of NO signalling. High-throughput screening of a drug library identified gemfibrozil as a direct sGC activator. Activation of sGC is unique to gemfibrozil and is not shared by other fibrates. Gemfibrozil activated purified sGC, induced endothelium-independent relaxation of aortic rings and inhibited platelet aggregation. Gemfibrozil-dependent activation was absent when the sGC haem domain was deleted, but was significantly enhanced when sGC haem was lacking or oxidized. Oxidation of sGC haem enhanced the vasoactive and anti-platelet effects of gemfibrozil. Gemfibrozil competed with the haem-independent sGC activators ataciguat and cinaciguat. Computational modelling predicted that gemfibrozil occupies the space of the haem group and interacts with residues crucial for haem stabilization. This is consistent with structure-activity data which revealed an absolute requirement for gemfibrozil's carboxyl group. These data suggest that in addition to altered lipid and lipoprotein state, the cardiovascular preventive benefits of gemfibrozil may derive from direct activation and protection of sGC function. A sGC-directed action may explain the more pronounced cardiovascular benefit of gemfibrozil observed over other fibrates and some of the described side effects of gemfibrozil. © 2014 The British Pharmacological Society.

  18. Btk levels set the threshold for B-cell activation and negative selection of autoreactive B cells in mice.

    PubMed

    Kil, Laurens P; de Bruijn, Marjolein J W; van Nimwegen, Menno; Corneth, Odilia B J; van Hamburg, Jan Piet; Dingjan, Gemma M; Thaiss, Friedrich; Rimmelzwaan, Guus F; Elewaut, Dirk; Delsing, Dianne; van Loo, Pieter Fokko; Hendriks, Rudi W

    2012-04-19

    On antigen binding by the B-cell receptor (BCR), B cells up-regulate protein expression of the key downstream signaling molecule Bruton tyrosine kinase (Btk), but the effects of Btk up-regulation on B-cell function are unknown. Here, we show that transgenic mice overexpressing Btk specifically in B cells spontaneously formed germinal centers and manifested increased plasma cell numbers, leading to antinuclear autoantibody production and systemic lupus erythematosus (SLE)-like autoimmune pathology affecting kidneys, lungs, and salivary glands. Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant. B cells overexpressing wild-type Btk were selectively hyperresponsive to BCR stimulation and showed enhanced Ca(2+) influx, nuclear factor (NF)-κB activation, resistance to Fas-mediated apoptosis, and defective elimination of selfreactive B cells in vivo. These findings unravel a crucial role for Btk in setting the threshold for B-cell activation and counterselection of autoreactive B cells, making Btk an attractive therapeutic target in systemic autoimmune disease such as SLE. The finding of in vivo pathology associated with Btk overexpression may have important implications for the development of gene therapy strategies for X-linked agammaglobulinemia, the immunodeficiency associated with mutations in BTK.

  19. Gamma Activation in Young People with Autism Spectrum Disorders and Typically-Developing Controls When Viewing Emotions on Faces

    PubMed Central

    Wright, Barry; Alderson-Day, Ben; Prendergast, Garreth; Bennett, Sophie; Jordan, Jo; Whitton, Clare; Gouws, Andre; Jones, Nick; Attur, Ram; Tomlinson, Heather; Green, Gary

    2012-01-01

    Background Behavioural studies have highlighted irregularities in recognition of facial affect in children and young people with autism spectrum disorders (ASDs). Recent findings from studies utilising electroencephalography (EEG) and magnetoencephalography (MEG) have identified abnormal activation and irregular maintenance of gamma (>30 Hz) range oscillations when ASD individuals attempt basic visual and auditory tasks. Methodology/Principal Fndings The pilot study reported here is the first study to use spatial filtering techniques in MEG to explore face processing in children with ASD. We set out to examine theoretical suggestions that gamma activation underlying face processing may be different in a group of children and young people with ASD (n = 13) compared to typically developing (TD) age, gender and IQ matched controls. Beamforming and virtual electrode techniques were used to assess spatially localised induced and evoked activity. While lower-band (3–30 Hz) responses to faces were similar between groups, the ASD gamma response in occipital areas was observed to be largely absent when viewing emotions on faces. Virtual electrode analysis indicated the presence of intact evoked responses but abnormal induced activity in ASD participants. Conclusions/Significance These findings lend weight to previous suggestions that specific components of the early visual response to emotional faces is abnormal in ASD. Elucidation of the nature and specificity of these findings is worthy of further research. PMID:22859975

  20. Active Mobility and Environment: A Pilot Qualitative Study for the Design of a New Questionnaire

    PubMed Central

    Salze, Paul; Weber, Christiane; Feuillet, Thierry; Charreire, Hélène; Menai, Mehdi; Perchoux, Camille; Nazare, Julie-Anne; Simon, Chantal; Oppert, Jean-Michel

    2017-01-01

    It is generally accepted that active mobility, mainly walking and cycling, contributes to people’s physical and mental health. One of the current challenges is to improve our understanding of this type of behaviour. This study aims to identify factors from the daily-life environment that may be related to active mobility behaviours, in order to design a new questionnaire for a quantitative study of a large adult population. The new questionnaire obtained through this pilot study combines information from interviews with existing questionnaires materials in order to introduce new factors while retaining the factors already assessed. This approach comprises three stages. The first was a content analysis (Reinert method) of interviews with a sample of participants about daily living activities as well as mobility. This stage led to a typology of factors suggested by interviews. The second was a scoping review of the literature in order to identify the active mobility questionnaires currently used in international literature. The last stage was a cross-tabulation of the factors resulting from the written interviews and the questionnaires. A table of the inter-relationships between the interview-based typology and the questionnaires shows discrepancies between factors considered by the existing questionnaires, and factors coming from individual interviews. Independent factors which were ignored in or absent from the questionnaires are the housing situation within the urban structure, overall consideration of the activity space beyond the limits of the residential neighbourhood, the perception of all the transportation modes, and the time scheduling impacting the modes actually used. Our new questionnaire integrates both the usual factors and the new factors that may be related to active mobility behaviours. PMID:28052086

  1. Active Mobility and Environment: A Pilot Qualitative Study for the Design of a New Questionnaire.

    PubMed

    Hess, Franck; Salze, Paul; Weber, Christiane; Feuillet, Thierry; Charreire, Hélène; Menai, Mehdi; Perchoux, Camille; Nazare, Julie-Anne; Simon, Chantal; Oppert, Jean-Michel; Enaux, Christophe

    2017-01-01

    It is generally accepted that active mobility, mainly walking and cycling, contributes to people's physical and mental health. One of the current challenges is to improve our understanding of this type of behaviour. This study aims to identify factors from the daily-life environment that may be related to active mobility behaviours, in order to design a new questionnaire for a quantitative study of a large adult population. The new questionnaire obtained through this pilot study combines information from interviews with existing questionnaires materials in order to introduce new factors while retaining the factors already assessed. This approach comprises three stages. The first was a content analysis (Reinert method) of interviews with a sample of participants about daily living activities as well as mobility. This stage led to a typology of factors suggested by interviews. The second was a scoping review of the literature in order to identify the active mobility questionnaires currently used in international literature. The last stage was a cross-tabulation of the factors resulting from the written interviews and the questionnaires. A table of the inter-relationships between the interview-based typology and the questionnaires shows discrepancies between factors considered by the existing questionnaires, and factors coming from individual interviews. Independent factors which were ignored in or absent from the questionnaires are the housing situation within the urban structure, overall consideration of the activity space beyond the limits of the residential neighbourhood, the perception of all the transportation modes, and the time scheduling impacting the modes actually used. Our new questionnaire integrates both the usual factors and the new factors that may be related to active mobility behaviours.

  2. Controlled and reversible induction of differentiation and activation of adult human hepatocytes by a biphasic culture technique

    PubMed Central

    Auth, Marcus K.H.; Boost, Kim A.; Leckel, Kerstin; Beecken, Wolf-Dietrich; Engl, Tobias; Jonas, Dietger; Oppermann, Elsie; Hilgard, Philip; Markus, Bernd H.; Bechstein, Wolf-Otto; Blaheta, Roman A.

    2005-01-01

    AIM: Clinical application of human hepatocytes (HC) is hampered by the progressive loss of growth and differentiation in vitro. The object of the study was to evaluate the effect of a biphasic culture technique on expression and activation of growth factor receptors and differentiation of human adult HC. METHODS: Isolated HC were sequentially cultured in a hormone enriched differentiation medium (DM) containing nicotinamide, insulin, transferrin, selenium, and dexame-thasone or activation medium (AM) containing hepatocyte growth factor (HGF), epidermal growth factor (EGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Expression, distribution and activation of the HC receptors (MET and EGFR) and the pattern of characteristic cytokeratin (CK) filaments were measured by fluorometry, confocal microscopy and Western blotting. RESULTS: In the biphasic culture system, HC underwent repeated cycles of activation (characterized by expression and activation of growth factor receptors) and re-differentiation (illustrated by distribution of typical filaments CK-18 but low or absent expression of CK-19). In AM increased expression of MET and EGFR was associated with receptor translocation into the cytoplasm and induction of atypical CK-19. In DM low expression of MET and EGFR was localized on the cell membrane and CK-19 was reduced. Receptor phosphorylation required embedding of HC in collagen type I gel. CONCLUSION: Control and reversible modulation of growth factor receptor activation of mature human HC can be accomplished in vitro, when defined signals from the extracellular matrix and sequential growth stimuli are provided. The biphasic technique helps overcome de-differentiation, which occurs during continuous stimulation by means of growth factors. PMID:15810072

  3. Controlled and reversible induction of differentiation and activation of adult human hepatocytes by a biphasic culture technique.

    PubMed

    Auth, Marcus-K H; Boost, Kim A; Leckel, Kerstin; Beecken, Wolf-Dietrich; Engl, Tobias; Jonas, Dietger; Oppermann, Elsie; Hilgard, Philip; Markus, Bernd H; Bechstein, Wolf-Otto; Blaheta, Roman A

    2005-04-14

    Clinical application of human hepatocytes (HC) is hampered by the progressive loss of growth and differentiation in vitro. The object of the study was to evaluate the effect of a biphasic culture technique on expression and activation of growth factor receptors and differentiation of human adult HC. Isolated HC were sequentially cultured in a hormone enriched differentiation medium (DM) containing nicotinamide, insulin, transferrin, selenium, and dexame-thasone or activation medium (AM) containing hepatocyte growth factor (HGF), epidermal growth factor (EGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Expression, distribution and activation of the HC receptors (MET and EGFR) and the pattern of characteristic cytokeratin (CK) filaments were measured by fluorometry, confocal microscopy and Western blotting. In the biphasic culture system, HC underwent repeated cycles of activation (characterized by expression and activation of growth factor receptors) and re-differentiation (illustrated by distribution of typical filaments CK-18 but low or absent expression of CK-19). In AM increased expression of MET and EGFR was associated with receptor translocation into the cytoplasm and induction of atypical CK-19. In DM low expression of MET and EGFR was localized on the cell membrane and CK-19 was reduced. Receptor phosphorylation required embedding of HC in collagen type I gel. Control and reversible modulation of growth factor receptor activation of mature human HC can be accomplished in vitro, when defined signals from the extracellular matrix and sequential growth stimuli are provided. The biphasic technique helps overcome de-differentiation, which occurs during continuous stimulation by means of growth factors.

  4. Activation of the Cystic Fibrosis Transmembrane Conductance Regulator by the Flavonoid Quercetin

    PubMed Central

    Pyle, Louise C.; Fulton, Jennifer C.; Sloane, Peter A.; Backer, Kyle; Mazur, Marina; Prasain, Jeevan; Barnes, Stephen; Clancy, J. P.; Rowe, Steven M.

    2010-01-01

    Therapies to correct the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) folding defect require sensitive methods to detect channel activity in vivo. The β2 adrenergic receptor agonists, which provide the CFTR stimuli commonly used in nasal potential difference assays, may not overcome the channel gating defects seen in ΔF508 CFTR after plasma membrane localization. In this study, we identify an agent, quercetin, that enhances the detection of surface ΔF508 CFTR, and is suitable for nasal perfusion. A screen of flavonoids in CFBE41o− cells stably transduced with ΔF508 CFTR, corrected to the cell surface with low temperature growth, revealed that quercetin stimulated an increase in the short-circuit current. This increase was dose-dependent in both Fisher rat thyroid and CFBE41o− cells. High concentrations inhibited Cl− conductance. In CFBE41o− airway cells, quercetin (20 μg/ml) activated ΔF508 CFTR, whereas the β2 adrenergic receptor agonist isoproterenol did not. Quercetin had limited effects on cAMP levels, but did not produce detectable phosphorylation of the isolated CFTR R-domain, suggesting an activation independent of channel phosphorylation. When perfused in the nares of Cftr+ mice, quercetin (20 μg/ml) produced a hyperpolarization of the potential difference that was absent in Cftr−/− mice. Finally, quercetin-induced, dose-dependent hyperpolarization of the nasal potential difference was also seen in normal human subjects. Quercetin activates CFTR-mediated anion transport in respiratory epithelia in vitro and in vivo, and may be useful in studies intended to detect the rescue of ΔF508 CFTR by nasal potential difference. PMID:20042712

  5. Characteristics and physiological role of hyperpolarization activated currents in mouse cold thermoreceptors

    PubMed Central

    Orio, Patricio; Madrid, Rodolfo; de la Peña, Elvira; Parra, Andrés; Meseguer, Víctor; Bayliss, Douglas A; Belmonte, Carlos; Viana, Félix

    2009-01-01

    Hyperpolarization-activated currents (Ih) are mediated by the expression of combinations of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel subunits (HCN1–4). These cation currents are key regulators of cellular excitability in the heart and many neurons in the nervous system. Subunit composition determines the gating properties and cAMP sensitivity of native Ih currents. We investigated the functional properties of Ih in adult mouse cold thermoreceptor neurons from the trigeminal ganglion, identified by their high sensitivity to moderate cooling and responsiveness to menthol. All cultured cold-sensitive (CS) neurons expressed a fast activating Ih, which was fully blocked by extracellular Cs+ or ZD7288 and had biophysical properties consistent with those of heteromeric HCN1–HCN2 channels. In CS neurons from HCN1(−/−) animals, Ih was greatly reduced but not abolished. We find that Ih activity is not essential for the transduction of cold stimuli in CS neurons. Nevertheless, Ih has the potential to shape the excitability of CS neurons. First, Ih blockade caused a membrane hyperpolarization in CS neurons of about 5 mV. Furthermore, impedance power analysis showed that all CS neurons had a prominent subthreshold membrane resonance in the 5–7 Hz range, completely abolished upon blockade of Ih and absent in HCN1 null mice. This frequency range matches the spontaneous firing frequency of cold thermoreceptor terminals in vivo. Behavioural responses to cooling were reduced in HCN1 null mice and after peripheral pharmacological blockade of Ih with ZD7288, suggesting that Ih plays an important role in peripheral sensitivity to cold. PMID:19273581

  6. Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice.

    PubMed

    Lorenz, Viola; Ramsey, Haley; Liu, Zhi-Jian; Italiano, Joseph; Hoffmeister, Karin; Bihorel, Sihem; Mager, Donald; Hu, Zhongbo; Slayton, William B; Kile, Benjamin T; Sola-Visner, Martha; Ferrer-Marin, Francisca

    2017-12-01

    Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numbers. To investigate this, we characterized MKs and platelets in newborn c-MPL –/– mice. Liver MKs in c-MPL –/– neonates were reduced in number and size compared with wild-type (WT) age-matched MKs, and exhibited ultrastructural abnormalities not found in adult c-MPL –/– MKs. Platelet counts were lower in c-MPL –/– compared with WT mice at birth and did not increase over the first 2 weeks of life. In vivo biotinylation revealed a significant reduction in the platelet half-life of c-MPL –/– newborn mice (P2) compared with age-matched WT pups, which was not associated with ultrastructural abnormalities. Genetic deletion of the pro-apoptotic Bak did not rescue the severely reduced platelet half-life of c-MPL –/– newborn mice, suggesting that it was due to factors other than platelets entering apoptosis early. Indeed, adult GFP+ (green fluorescent protein transgenic) platelets transfused into thrombocytopenic c-MPL –/– P2 pups also had a shortened lifespan, indicating the importance of cell-extrinsic factors. In addition, neonatal platelets from WT and c-MPL –/– mice exhibited reduced P-selectin surface expression following stimulation compared with adult platelets of either genotype, and platelets from c-MPL –/– neonates exhibited reduced glycoprotein IIb/IIIa (GPIIb/IIIa) activation in response to thrombin compared with age-matched WT platelets. Taken together, our findings indicate that c-MPL deficiency is associated with abnormal maturation of neonatal MKs and developmental stage-specific defects in platelet function.

  7. Physical activity and quality of life in long-term hospitalized patients with severe mental illness: a cross-sectional study.

    PubMed

    Deenik, Jeroen; Kruisdijk, Frank; Tenback, Diederik; Braakman-Jansen, Annemarie; Taal, Erik; Hopman-Rock, Marijke; Beekman, Aartjan; Tak, Erwin; Hendriksen, Ingrid; van Harten, Peter

    2017-08-18

    Increasing physical activity in patients with severe mental illness is believed to have positive effects on physical health, psychiatric symptoms and as well quality of life. Till now, little is known about the relationship between physical activity and quality of life in long-term hospitalized patients with severe mental illness and knowledge of the determinants of behavioural change is lacking. The purpose of this study was to elucidate the relationship between objectively measured physical activity and quality of life, and explore modifiable psychological determinants of change in physical activity in long-term hospitalized patients with severe mental illness. In 184 inpatients, physical activity was measured using an accelerometer (ActiGraph GTX+). Quality of life was assessed by EuroQol-5D and WHOQol-Bref. Attitude and perceived self-efficacy towards physical activity were collected using the Physical Activity Enjoyment Scale and the Multidimensional Self Efficacy Questionnaire, respectively. Patient and disease characteristics were derived retrospectively from electronic patient records. Associations and potential predictors were analysed using hierarchical regression. Physical activity was positively related with and a predictor of all quality of life outcomes except on the environmental domain, independent of patient and disease characteristics. However, non-linear relationships showed that most improvement in quality of life lies in the change from sedentary to light activity. Attitude and self-efficacy were not related to physical activity. Physical activity is positively associated with quality of life, especially for patients in the lower spectrum of physical activity. An association between attitude and self-efficacy and physical activity was absent. Therefore, results suggest the need of alternative, more integrated and (peer-)supported interventions to structurally improve physical activity in this inpatient population. Slight changes from sedentary

  8. Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes.

    PubMed

    Shukunami, Chisa; Takimoto, Aki; Nishizaki, Yuriko; Yoshimoto, Yuki; Tanaka, Seima; Miura, Shigenori; Watanabe, Hitomi; Sakuma, Tetsushi; Yamamoto, Takashi; Kondoh, Gen; Hiraki, Yuji

    2018-02-16

    Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption. Tnmd mRNA levels were dramatically decreased during serial passages of rat tenocytes. Scx silencing by small interfering RNA significantly suppressed endogenous Tnmd mRNA levels in tenocytes. Mouse Tnmd contains five E-box sites in the ~1-kb 5'-flanking region. A 174-base pair genomic fragment containing a TATA box drives transcription in tenocytes. Enhancer activity was increased in the upstream region (-1030 to -295) of Tnmd in tenocytes, but not in NIH3T3 and C3H10T1/2 cells. Preferential binding of both Scx and Twist1 as a heterodimer with E12 or E47 to CAGATG or CATCTG and transactivation of the 5'-flanking region were confirmed by electrophoresis mobility shift and dual luciferase assays, respectively. Scx directly transactivates Tnmd via these E-boxes to positively regulate tenocyte differentiation and maturation.

  9. Dynamics of passive and active particles in the cell nucleus.

    PubMed

    Hameed, Feroz M; Rao, Madan; Shivashankar, G V

    2012-01-01

    Inspite of being embedded in a dense meshwork of nuclear chromatin, gene loci and large nuclear components are highly dynamic at 37°C. To understand this apparent unfettered movement in an overdense environment, we study the dynamics of a passive micron size bead in live cell nuclei at two different temperatures (25 and 37°C) with and without external force. In the absence of a force, the beads are caged over large time scales. On application of a threshold uniaxial force (about 10(2) pN), the passive beads appear to hop between cages; this large scale movement is absent upon ATP-depletion, inhibition of chromatin remodeling enzymes and RNAi of lamin B1 proteins. Our results suggest that the nucleus behaves like an active solid with a finite yield stress when probed at a micron scale. Spatial analysis of histone fluorescence anisotropy (a measure of local chromatin compaction, defined as the volume fraction of tightly bound chromatin) shows that the bead movement correlates with regions of low chromatin compaction. This suggests that the physical mechanism of the observed yielding is the active opening of free-volume in the nuclear solid via chromatin remodeling. Enriched transcription sites at 25°C also show caging in the absence of the applied force and directed movement beyond a yield stress, in striking contrast with the large scale movement of transcription loci at 37°C in the absence of a force. This suggests that at physiological temperatures, the loci behave as active particles which remodel the nuclear mesh and reduce the local yield stress.

  10. Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function.

    PubMed

    Concepcion, Axel R; Vaeth, Martin; Wagner, Larry E; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S; Cuk, Mario; Yule, David I; Feske, Stefan

    2016-11-01

    Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice.

  11. Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9

    PubMed Central

    2017-01-01

    The sensitivity of ocular dominance to regulation by monocular deprivation is the canonical model of plasticity confined to a critical period. However, we have previously shown that visual deprivation through dark exposure (DE) reactivates critical period plasticity in adults. Previous work assumed that the elimination of visual input was sufficient to enhance plasticity in the adult mouse visual cortex. In contrast, here we show that light reintroduction (LRx) after DE is responsible for the reactivation of plasticity. LRx triggers degradation of the ECM, which is blocked by pharmacological inhibition or genetic ablation of matrix metalloproteinase-9 (MMP-9). LRx induces an increase in MMP-9 activity that is perisynaptic and enriched at thalamo-cortical synapses. The reactivation of plasticity by LRx is absent in Mmp9−/− mice, and is rescued by hyaluronidase, an enzyme that degrades core ECM components. Thus, the LRx-induced increase in MMP-9 removes constraints on structural and functional plasticity in the mature cortex. PMID:28875930

  12. Automatic seizure detection in SEEG using high frequency activities in wavelet domain.

    PubMed

    Ayoubian, L; Lacoma, H; Gotman, J

    2013-03-01

    Existing automatic detection techniques show high sensitivity and moderate specificity, and detect seizures a relatively long time after onset. High frequency (80-500 Hz) activity has recently been shown to be prominent in the intracranial EEG of epileptic patients but has not been used in seizure detection. The purpose of this study is to investigate if these frequencies can contribute to seizure detection. The system was designed using 30 h of intracranial EEG, including 15 seizures in 15 patients. Wavelet decomposition, feature extraction, adaptive thresholding and artifact removal were employed in training data. An EMG removal algorithm was developed based on two features: Lack of correlation between frequency bands and energy-spread in frequency. Results based on the analysis of testing data (36 h of intracranial EEG, including 18 seizures) show a sensitivity of 72%, a false detection of 0.7/h and a median delay of 5.7 s. Missed seizures originated mainly from seizures with subtle or absent high frequencies or from EMG removal procedures. False detections were mainly due to weak EMG or interictal high frequency activities. The system performed sufficiently well to be considered for clinical use, despite the exclusive use of frequencies not usually considered in clinical interpretation. High frequencies have the potential to contribute significantly to the detection of epileptic seizures. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  13. Automatic seizure detection in SEEG using high frequency activities in wavelet domain

    PubMed Central

    Ayoubian, L.; Lacoma, H.; Gotman, J.

    2015-01-01

    Existing automatic detection techniques show high sensitivity and moderate specificity, and detect seizures a relatively long time after onset. High frequency (80–500 Hz) activity has recently been shown to be prominent in the intracranial EEG of epileptic patients but has not been used in seizure detection. The purpose of this study is to investigate if these frequencies can contribute to seizure detection. The system was designed using 30 h of intracranial EEG, including 15 seizures in 15 patients. Wavelet decomposition, feature extraction, adaptive thresholding and artifact removal were employed in training data. An EMG removal algorithm was developed based on two features: Lack of correlation between frequency bands and energy-spread in frequency. Results based on the analysis of testing data (36 h of intracranial EEG, including 18 seizures) show a sensitivity of 72%, a false detection of 0.7/h and a median delay of 5.7 s. Missed seizures originated mainly from seizures with subtle or absent high frequencies or from EMG removal procedures. False detections were mainly due to weak EMG or interictal high frequency activities. The system performed sufficiently well to be considered for clinical use, despite the exclusive use of frequencies not usually considered in clinical interpretation. High frequencies have the potential to contribute significantly to the detection of epileptic seizures. PMID:22647836

  14. Expression of Vitamin D-Activating Enzyme 1α-Hydroxylase (CYP27B1) Decreases during Melanoma Progression**

    PubMed Central

    Brożyna, Anna A.; Jóźwicki, Wojciech; Janjetovic, Zorica; Slominski, Andrzej T.

    2012-01-01

    Summary 1α-Hydroxylase (CYP27B1), the enzyme responsible for the synthesis of the biologically active form of vitamin D (1,25(OH)2D3), is expressed in the skin. To assess the correlation between progression of melanocytic tumors and CYP27B1, we analyzed its expression in 29 benign nevi, 75 primary cutaneous melanomas, 40 metastases, and 4 re-excision and 6 normal skin biopsies. Immunoreactivity for CYP27B1 was significantly lower in the vertical growth phase (VGP) and metastatic melanomas (0.6 and 0.5 arbitrary units [AU], respectively) in comparison with nevi and radial growth phase (RGP) tumors (1.2 and 1.1 AU, respectively); and expression was reduced in more advanced lesions (Clark levels III–V, Breslow thickness ≥2.1 mm; 0.8 and 0.7 AU, respectively). There was an inverse correlation between CYP27B1 and Ki-67 expression. Furthermore, CYP27B1 expression was reduced in primary melanomas that created metastases in comparison with non-metastasizing melanomas. Reduced CYP27B1 expression in RGP was related to shorter overall survival (810 vs 982 vs 1151 days in melanomas with absent, low, and high CYP27B1 immunoreactivity), and low CYP27B1 expression in RGP and VGP was related to shorter disease-free survival (114 vs 339 vs 737 days and 129 vs 307 vs 737 days, respectively, in melanomas with absent, low, and high CYP27B1). Also, CYP27B1 expression was inversely related to melanin in melanoma cells in vivo and melanoma cells cultured in vitro. Thus, reduction of CYP27B1 correlates with melanoma phenotype and behavior, and its lack affects the survival of melanoma patients, indicating a role in the pathogenesis and progression of this cancer. PMID:22995334

  15. The Major Apoptotic Pathway Activated and Suppressed by Poliovirus

    PubMed Central

    Belov, George A.; Romanova, Lyudmila I.; Tolskaya, Elena A.; Kolesnikova, Marina S.; Lazebnik, Yuri A.; Agol, Vadim I.

    2003-01-01

    Cells respond to poliovirus infection by switching on the apoptotic program, implementation of which is usually suppressed by viral antiapoptotic functions. We show here that poliovirus infection of HeLa cells or derivatives of MCF-7 cells was accompanied by the efflux of cytochrome c from mitochondria. This efflux occurred during both abortive infection (e.g., interrupted by guanidine-HCl and ending with apoptosis) and productive infection (leading to cytopathic effect). The former type of infection, but not the latter, was accompanied by truncation of the proapoptotic protein Bid. The virus-triggered cytochrome c efflux was suppressed by overexpression of Bcl-2. Both abortive and productive infections also resulted in a decreased level of procaspase-9, as revealed by Western blotting. In the former case, this decrease was accompanied by the accumulation of a protein with the electrophoretic mobility of active caspase-9. In contrast, in the productively infected cells, the latter protein was absent but caspase-9-related polypeptides with altered mobility could be detected. Both caspase-9 and caspase-3 were shown to be essential for the development of such hallmarks of virus-induced apoptosis as chromatin condensation, DNA degradation, and nuclear fragmentation. These and some other results suggest the following scenario. Poliovirus infection activates the apoptotic pathway, involving mitochondrial damage, cytochrome c efflux, and consecutive activation of caspase-9 and caspase-3. The apoptotic signal appears to be amplified by a loop which includes secondary processing of Bid. The implementation of the apoptotic program in productively infected cells may be suppressed, however, by the viral antiapoptotic functions, which act at a step(s) downstream of the cytochrome c efflux. The suppression appears to be caused, at least in part, by aberrant processing and degradation of procaspase-9. PMID:12477809

  16. Structural variation of the oceanic Moho in the Pacific plate revealed by active-source seismic data

    NASA Astrophysics Data System (ADS)

    Ohira, Akane; Kodaira, Shuichi; Nakamura, Yasuyuki; Fujie, Gou; Arai, Ryuta; Miura, Seiichi

    2017-10-01

    The characteristics of the oceanic Moho are known to depend on various factors, such as seafloor spreading rate, crustal age, and accretionary processes at a ridge. However, the effect of local magmatic activities on the seismic signature of the Moho is poorly understood. Here an active-source reflection and refraction survey is used to investigate crustal structure and Moho characteristics along a >1000-km-long profile southeast of the Shatsky Rise in a Pacific Ocean basin formed from the Late Jurassic to Early Cretaceous and spanning the onset of Shatsky Rise volcanism. Although the seismic velocity structure estimated from the refraction data showed typical characteristics of the oceanic crust of the old Pacific plate, the appearance of the Moho reflections was spatially variable. We observed clear Moho reflections such as those to be expected where the spreading rate is fast to intermediate only at the southwestern end of the profile, whereas Moho reflections were diffuse, weak, or absent along other parts of the profile. The poor Moho reflections can be explained by the presence of a thick crust-mantle transition layer, which is temporally coincident with the formation of the Shatsky Rise. We inferred that the crust-mantle transition layer was formed by changes in on-axis accretion process or modification of the primary Moho by off-axis magmatism, induced by magmatic activity of the Shatsky Rise.

  17. Antagonistic actions of renal dopamine and 5-hydroxytryptamine: increase in Na+, K(+)-ATPase activity in renal proximal tubules via activation of 5-HT1A receptors.

    PubMed Central

    Soares-da-Silva, P.; Pinto-do-O, P. C.; Bertorello, A. M.

    1996-01-01

    1. 5-Hydroxytryptamine (5-HT) is antinatriuretic. Since this effect of 5-HT is not accomplished by changes in glomerular haemodynamics, we have examined in this study whether 5-HT may influence sodium excretion by affecting the Na+, K(+)-ATPase activity in renal cortical tubules. 2. Na+, K(+)-ATPase activity was determined as the rate of [32P]-ATP hydrolysis in renal cortical tubules in suspension. Basal Na+, K(+)-ATPase activity in renal tubules was 4.8 +/- 0.4 mumol Pi mg-1 protein h-1 (n = 8). The 5-HT1A receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) (10 to 3000 nM) induced a concentration-dependent increase (P < 0.05) in Na+, K(+)-ATPase activity with an EC50 value of 355 nM (95% confidence limits: 178, 708). Maximal stimulation elicited by 3000 nM of 8-OH-DPAT was antagonized by the selective 5-HT1A receptor antagonist, (+)-WAY 100135 10 to 1000 nM) with an IC50 value of 20 nM (14, 29); 0.3 microM (+)-WAY 100135 completely abolished (P < 0.01) the stimulatory effect of 8-OH-DPAT. The stimulatory effect of 8-OH-DPAT was found to be time-dependent (15 +/- 2% and 66 +/- 7% increase at 2.5 and 5.0 min, respectively). The 5-HT2 receptor agonist alpha-methyl-5-HT (100 to 3000 nM) did not induce any significant changes in Na+, K(+)-ATPase activity (5.0 +/- 1.5 mumol Pi mg-1 protein h-1; n = 4). 3. The stimulatory effect 8-OH-DPAT was absent when homogenates were used. Stimulation occurred at a Vmax concentration (70 mM) of sodium supporting the notion that stimulation occurs independently of increasing sodium permeability. 4. The inhibitory effect of dopamine (P < 0.05) on Na+, K(+)-ATPase activity was blunted by co-incubation with 8-OH-DPAT (0.5 microM). 5. It is concluded that activation of 5-HT1A receptors increases Na+, K(+)-ATPase activity in renal cortical tubules; this effect may represent an important cellular mechanism, at the tubule level, responsible for the antinatriuretic effect of 5-HT. Images Figure 4 PMID:8882616

  18. Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

    PubMed

    Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H

    2004-07-01

    This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.

  19. Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers

    PubMed Central

    Gu, Xiaosi; Lohrenz, Terry; Salas, Ramiro; Baldwin, Philip R.; Soltani, Alireza; Kirk, Ulrich; Cinciripini, Paul M.; Montague, P. Read

    2016-01-01

    Little is known about the specific neural mechanisms through which cognitive factors influence craving and associated brain responses, despite the initial success of cognitive therapies in treating drug addiction. In this study, we investigated how cognitive factors such as beliefs influence subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told “nicotine” vs. told “no nicotine”) with the nicotine content in a cigarette (nicotine vs. placebo) which participants smoked immediately before performing a fMRI task involving reward learning. Subjects’ reported craving was measured both before smoking and after the fMRI session. We found that first, in the presence of nicotine, smokers demonstrated significantly reduced craving after smoking when told “nicotine in cigarette” but showed no change in craving when told “no nicotine.” Second, neural activity in the insular cortex related to craving was only significant when smokers were told “nicotine” but not when told “no nicotine.” Both effects were absent in the placebo condition. Third, insula activation related to computational learning signals was modulated by belief about nicotine regardless of nicotine’s presence. These results suggest that belief about nicotine has a strong impact on subjective craving and insula responses related to both craving and learning in deprived smokers, providing insights into the complex nature of belief–drug interactions. PMID:27468271

  20. Osmolality and respiratory regulation in humans: respiratory compensation for hyperchloremic metabolic acidosis is absent after infusion of hypertonic saline in healthy volunteers.

    PubMed

    Moen, Vibeke; Brudin, Lars; Rundgren, Mats; Irestedt, Lars

    2014-10-01

    results indicate that osmolality has an influence on ventilation. Respiratory compensation for hyperchloremic metabolic acidosis was suppressed during hyperosmolality. Water loading caused a decrease in plasma osmolality and metabolic acidosis, and although the decrease in SID was smaller compared with salt loading, the expected respiratory compensation was observed. Ventilation was also stimulated in men, therefore independently of progesterone levels. We propose that the influence of osmolality on ventilation consists mainly as depression in conditions of hyperosmolality and that this depression is absent during hypoosmolality.

  1. Evidence for vestibular dysfunction in orthostatic hypotension.

    PubMed

    Aoki, Mitsuhiro; Sakaida, Yuzuru; Tanaka, Kunihiko; Mizuta, Keisuke; Ito, Yatsuji

    2012-03-01

    There is little definitive evidence of the clinical significance of the vestibular-cardiovascular reflex in humans, despite the fact that the vestibular system is known to contribute to cardiovascular control in animals. The present study involved 248 dizzy patients (127 male patients and 121 female patients) aged 65 years and younger. We classified all participants into three groups based on their vestibular evoked myogenic potential (VEMP) responses; absent VEMP, asymmetry VEMP and normal VEMP. To investigate the effect of the otolith disorder, which was estimated by the VEMP, on the orthostatic blood pressure responses, the subjects' systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were monitored during the orthostatic test after they actively stood up. The male patients in the absent VEMP group had a significant drop in their DBP at 1 min after active standing up (P < 0.05) without any change in their SBP. Conversely, male patients in the asymmetry VEMP and normal VEMP groups showed a significant increase in the SBP at 1 min after active standing up (P < 0.05). Female patients in the absent VEMP group did not show any significant drop in their blood pressure after standing up (P > 0.05). In the entire group of participants, a total of 19.6% of the patients in the absent VEMP group fulfilled the criteria for orthostatic hypotension (OH), which was significantly > the 8.6% of patients in the normal VEMP group and the 7.2% in the asymmetry VEMP group (P < 0.05). Our results suggest that vestibular disorders due to the dysfunction of otolith organs provoke OH.

  2. Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach

    PubMed Central

    Shaylor, Lara A.; Hwang, Sung Jin; Sanders, Kenton M.

    2016-01-01

    Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase (Nos1−/−) and P2Y1 receptors (P2ry1−/−) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1−/− mice IJPs and relaxations persisted whereas in P2ry1−/− mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species. PMID:27634009

  3. Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach.

    PubMed

    Shaylor, Lara A; Hwang, Sung Jin; Sanders, Kenton M; Ward, Sean M

    2016-11-01

    Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase (Nos1 -/- ) and P2Y1 receptors (P2ry1 -/- ) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1 -/- mice IJPs and relaxations persisted whereas in P2ry1 -/- mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species. Copyright © 2016 the American Physiological Society.

  4. Critical Community Building: Beyond Belonging

    ERIC Educational Resources Information Center

    Bettez, Silvia Cristina

    2011-01-01

    In this paper, the author talks about community building and the power of active listening. Active listening is a particular kind of listening that requires conscious effort; it is a type of listening that some rarely practice and sometimes is virtually absent from classroom interactions. Thus active listening itself may be deceptively simple…

  5. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study

    PubMed Central

    Di Lorenzo, Chiara; Sangiovanni, Enrico; Fumagalli, Marco; Colombo, Elisa; Frigerio, Gianfranco; Colombo, Francesca; Peres de Sousa, Luis; Altindişli, Ahmet; Restani, Patrizia; Dell’Agli, Mario

    2016-01-01

    Raisins (Vitis vinifera L.) are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL)-8 and Nuclear Factor (NF)-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis and screened for their ability to inhibit Tumor necrosis factor (TNF)α-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases. PMID:27447609

  6. Antagonism of the STING Pathway via Activation of the AIM2 Inflammasome by Intracellular DNA.

    PubMed

    Corrales, Leticia; Woo, Seng-Ryong; Williams, Jason B; McWhirter, Sarah M; Dubensky, Thomas W; Gajewski, Thomas F

    2016-04-01

    Recent evidence has indicated that innate immune sensing of cytosolic DNA in dendritic cells via the host STING pathway is a major mechanism leading to spontaneous T cell responses against tumors. However, the impact of the other major pathway triggered by intracellular DNA, the absent in melanoma 2 (AIM2) inflammasome, on the functional output from the stimulator of IFN genes (STING) pathway is poorly understood. We found that dendritic cells and macrophages deficient in AIM2, apoptosis-associated specklike protein, or caspase-1 produced markedly higher IFN-β in response to DNA. Biochemical analyses showed enhanced generation of cyclic GMP-AMP, STING aggregation, and TANK-binding kinase 1 and IFN regulatory factor 3 phosphorylation in inflammasome-deficient cells. Induction of pyroptosis by the AIM2 inflammasome was a major component of this effect, and inhibition of caspase-1 reduced cell death, augmenting phosphorylation of TANK-binding kinase 1/IFN regulatory factor 3 and production of IFN-β. Our data suggest that in vitro activation of the AIM2 inflammasome in murine macrophages and dendritic cells leads to reduced activation of the STING pathway, in part through promoting caspase-1-dependent cell death. Copyright © 2016 by The American Association of Immunologists, Inc.

  7. Phase retrieval in digital speckle pattern interferometry by application of two-dimensional active contours called snakes.

    PubMed

    Federico, Alejandro; Kaufmann, Guillermo H

    2006-03-20

    We propose a novel approach to retrieving the phase map coded by a single closed-fringe pattern in digital speckle pattern interferometry, which is based on the estimation of the local sign of the quadrature component. We obtain the estimate by calculating the local orientation of the fringes that have previously been denoised by a weighted smoothing spline method. We carry out the procedure of sign estimation by determining the local abrupt jumps of size pi in the orientation field of the fringes and by segmenting the regions defined by these jumps. The segmentation method is based on the application of two-dimensional active contours (snakes), with which one can also estimate absent jumps, i.e., those that cannot be detected from the local orientation of the fringes. The performance of the proposed phase-retrieval technique is evaluated for synthetic and experimental fringes and compared with the results obtained with the spiral-phase- and Fourier-transform methods.

  8. Varying and unchanging whiteness on the wings of dusk-active and shade-inhabiting Carystoides escalantei butterflies.

    PubMed

    Ge, Dengteng; Wu, Gaoxiang; Yang, Lili; Kim, Hye-Na; Hallwachs, Winnie; Burns, John M; Janzen, Daniel H; Yang, Shu

    2017-07-11

    Whiteness, although frequently apparent on the wings, legs, antennae, or bodies of many species of moths and butterflies, along with other colors and shades, has often escaped our attention. Here, we investigate the nanostructure and microstructure of white spots on the wings of Carystoides escalantei , a dusk-active and shade-inhabiting Costa Rican rain forest butterfly (Hesperiidae). On both males and females, two types of whiteness occur: angle dependent (dull or bright) and angle independent, which differ in the microstructure, orientation, and associated properties of their scales. Some spots on the male wings are absent from the female wings. Whether the angle-dependent whiteness is bright or dull depends on the observation directions. The angle-dependent scales also show enhanced retro-reflection. We speculate that the biological functions and evolution of Carystoides spot patterns, scale structures, and their varying whiteness are adaptations to butterfly's low light habitat and to airflow experienced on the wing base vs. wing tip.

  9. Prospective evaluation of femoral head viability following femoral neck fracture

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

    Binkert, B.; Kroop, S.A.; Nepola, I.V.

    1984-01-01

    The bone scans of 33 patients (pts) with recent subcapital fractures (fx) of the femur were evaluated prospectively to determine their value in predicting femoral head visability. Each of the 33 pts (ll men, 22 women, age range 30-92) had a pre-operative bone scan within 72 hrs of the fx (23 pts within 24 hrs). Anterior and posterior planar views of both hips and pinhole views (50% of pts) were obtained 2 hrs after administration of Tc-99m HDP. The femoral head was classified as perfused if it showed the same activity as the opposite normal side or if it showedmore » only slightly decreased activity. Femoral heads showing absent activity were classified as nonperfused. Overall, 20 of the 33 pts showed a photopenic femoral head on the side of the fx. Only 2 pts showed increased activity at hte site of the fx. Internal fixation of the fx was performed in 23 pts, 12 of whom had one or more follow-up scans. Five of these 12 pts showed absent femoral head activity on their initial scan, but 2 showed later reperfusion. The other 7 pts showed good perfusion initially, with only 1 later showing decreased femoral head activity. The other 10 pts (7 of whom had absent femoral head activity) had immediate resection of the femoral head and insertion of a Cathcart prosthesis. The results suggest that femoral head activity seen on a bone scan in the immediate post-fx period is not always a reliable indicator of femoral head viability. Decreased femoral head activity may reflect, in part, compromised perfusion secondary to post-traumatic edema, with or without anatomic disruption of the blood supply.« less

  10. Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice

    NASA Astrophysics Data System (ADS)

    de Souza, Ludmilla Regina; Alexandre Muehlmann, Luis; Carneiro Matos, Lívia; Simón-Vázquez, Rosana; Guerreiro Marques Lacava, Zulmira; Maurício Batista De-Paula, Alfredo; Mosiniewicz-Szablewska, Ewa; Suchocki, Piotr; César Morais, Paulo; González-Fernández, África; Nair Báo, Sônia; Bentes Azevedo, Ricardo

    2015-12-01

    Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.

  11. Subclinical nonautoimmune hyperthyroidism in a family segregates with a thyrotropin receptor mutation with weakly increased constitutive activity.

    PubMed

    Nishihara, Eijun; Chen, Chun-Rong; Higashiyama, Takuya; Mizutori-Sasai, Yumiko; Ito, Mitsuru; Kubota, Sumihisa; Amino, Nobuyuki; Miyauchi, Akira; Rapoport, Basil

    2010-11-01

    Subclinical hyperthyroidism is usually associated with Graves' disease or toxic nodular goiter. Here we report a family with hereditary subclinical hyperthyroidism caused by a constitutively activating germline mutation of the thyrotropin receptor (TSHR) gene. The proband was a 64-year-old Japanese woman who presented with a thyroid nodule and was found to be euthyroid with a suppressed serum TSH. The nodule was not hot. Although antibodies to thyroid peroxidase and thyroglobulin antibodies were present, TSHR antibodies were not detected by TSH-binding inhibition or by bioassay. Two of her middle-aged sons, but not her daughter, also had subclinical hyperthyroidism without TSHR antibodies. Without therapy, the clinical condition of the affected individuals remained unchanged over 3 years without development of overt hyperthyroidism. A novel heterozygous TSHR point mutation causing a glutamic acid to lysine substitution at codon 575 (E575K) in the second extracellular loop was detected in the three family members with subclinical hyperthyroidism, but was absent in her one daughter with normal thyroid function. In vitro functional studies of the E575K TSHR mutation demonstrated a weak, but significant, increase in constitutive activation of the cAMP pathway. Although hereditary nonautoimmune overt hyperthyroidism is very rare, TSHR activating mutations as a cause of subclinical hyperthyroidism may be more common and should be considered in the differential diagnosis, especially if familial.

  12. Subclinical Nonautoimmune Hyperthyroidism in a Family Segregates with a Thyrotropin Receptor Mutation with Weakly Increased Constitutive Activity

    PubMed Central

    Chen, Chun-Rong; Higashiyama, Takuya; Mizutori-Sasai, Yumiko; Ito, Mitsuru; Kubota, Sumihisa; Amino, Nobuyuki; Miyauchi, Akira; Rapoport, Basil

    2010-01-01

    Background Subclinical hyperthyroidism is usually associated with Graves' disease or toxic nodular goiter. Here we report a family with hereditary subclinical hyperthyroidism caused by a constitutively activating germline mutation of the thyrotropin receptor (TSHR) gene. Methods The proband was a 64-year-old Japanese woman who presented with a thyroid nodule and was found to be euthyroid with a suppressed serum TSH. The nodule was not hot. Although antibodies to thyroid peroxidase and thyroglobulin antibodies were present, TSHR antibodies were not detected by TSH-binding inhibition or by bioassay. Two of her middle-aged sons, but not her daughter, also had subclinical hyperthyroidism without TSHR antibodies. Without therapy, the clinical condition of the affected individuals remained unchanged over 3 years without development of overt hyperthyroidism. Results A novel heterozygous TSHR point mutation causing a glutamic acid to lysine substitution at codon 575 (E575K) in the second extracellular loop was detected in the three family members with subclinical hyperthyroidism, but was absent in her one daughter with normal thyroid function. In vitro functional studies of the E575K TSHR mutation demonstrated a weak, but significant, increase in constitutive activation of the cAMP pathway. Conclusion Although hereditary nonautoimmune overt hyperthyroidism is very rare, TSHR activating mutations as a cause of subclinical hyperthyroidism may be more common and should be considered in the differential diagnosis, especially if familial. PMID:20929407

  13. Differential Regulatory Role of Pituitary Adenylate Cyclase–Activating Polypeptide in the Serum-Transfer Arthritis Model

    PubMed Central

    Botz, Bálint; Bölcskei, Kata; Kereskai, László; Kovács, Miklós; Németh, Tamás; Szigeti, Krisztián; Horváth, Ildikó; Máthé, Domokos; Kovács, Noémi; Hashimoto, Hitoshi; Reglődi, Dóra; Szolcsányi, János; Pintér, Erika; Mócsai, Attila; Helyes, Zsuzsanna

    2014-01-01

    Objective Pituitary adenylate cyclase–activating polypeptide (PACAP) expressed in capsaicin-sensitive sensory neurons and immune cells has divergent functions in inflammatory and pain processes. This study was undertaken to investigate the involvement of PACAP in a mouse model of rheumatoid arthritis. Methods Arthritis was induced in PACAP−/− and wild-type (PACAP+/+) mice by K/BxN serum transfer. General features of the disease were investigated by semiquantitative scoring, plethysmometry, and histopathologic analysis. Mechano- and thermonociceptive thresholds and motor functions were also evaluated. Metabolic activity was assessed by positron emission tomography. Bone morphology was measured by in vivo micro–computed tomography, myeloperoxidase activity and superoxide production by bioluminescence imaging with luminol and lucigenin, respectively, and vascular permeability by fluorescent indocyanine green dye study. Results PACAP+/+ mice developed notable joint swelling, reduced grasping ability, and mechanical (but not thermal) hyperalgesia after K/BxN serum transfer. In PACAP−/− mice clinical scores and edema were significantly reduced, and mechanical hyperalgesia and motor impairment were absent, throughout the 2-week period of observation. Metabolic activity and superoxide production increased in the tibiotarsal joints of wild-type mice but were significantly lower in PACAP−/− animals. Myeloperoxidase activity in the ankle joints of PACAP−/− mice was significantly reduced in the early phase of arthritis, but increased in the late phase. Synovial hyperplasia was also significantly increased, and progressive bone spur formation was observed in PACAP-deficient mice only. Conclusion In PACAP-deficient mice with serum-transfer arthritis, joint swelling, vascular leakage, hyperalgesia, and early inflammatory cell accumulation are reduced; in the later phase of the disease, immune cell function and bone neoformation are increased. Elucidation of

  14. Portal inflammation during NAFLD is frequent and associated with the early phases of putative hepatic progenitor cell activation.

    PubMed

    Carotti, Simone; Vespasiani-Gentilucci, Umberto; Perrone, Giuseppe; Picardi, Antonio; Morini, Sergio

    2015-11-01

    We investigated whether portal tract inflammation observed in non-alcoholic fatty liver disease (NAFLD) is associated with hepatic progenitor cell compartment activation, as thoroughly evaluated with different markers of the staminal lineage. Fifty-two patients with NAFLD were studied. NAFLD activity score, fibrosis and portal inflammation were histologically evaluated. Putative hepatic progenitor cells, intermediate hepatobiliary cells and bile ductules/interlobular bile ducts were evaluated by immunohistochemistry for cytokeratin (CK)-7, CK-19 and epithelial cell adhesion molecule (EpCAM), and a hepatic progenitor cell compartment score was derived. Hepatic stellate cell and myofibroblast activity was determined by immunohistochemistry for α-smooth muscle actin. Portal inflammation was absent in a minority of patients, mild in 40% of cases and more than mild in about half of patients, showing a strong correlation with fibrosis (r=0.76, p<0.001). Portal inflammation correlated with CK-7-counted putative hepatic progenitor cells (r=0.48, p<0.001), intermediate hepatobiliary cells (r=0.6, p<0.001) and bile ductules/interlobular bile ducts (r=0.6, p<0.001), and with the activity of myofibroblasts (r=0.5, p<0.001). Correlations were confirmed when elements were counted by immunostaining for CK-19 and EpCAM. Lobular inflammation, ballooning, myofibroblast activity and hepatic progenitor cell compartment activation were associated with portal inflammation by univariate analysis. In the multivariate model, the only variable independently associated with portal inflammation was hepatic progenitor cell compartment activation (OR 3.7, 95% CI 1.1 to 12.6). Portal inflammation is frequent during NAFLD and strongly associated with activation of putative hepatic progenitor cells since the first steps of their differentiation, portal myofibroblast activity and fibrosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  15. Loosenin, a novel protein with cellulose-disrupting activity from Bjerkandera adusta

    PubMed Central

    2011-01-01

    Background Expansins and expansin-like proteins loosen cellulose microfibrils, possibly through the rupture of intramolecular hydrogen bonds. Together with the use of lignocellulolytic enzymes, these proteins are potential molecular tools to treat plant biomass to improve saccharification yields. Results Here we describe a new type of expansin-related fungal protein that we have called loosenin. Its corresponding gene, loos1, from the basidiomycete Bjerkandera adusta, was cloned and heterologously expressed in Saccharomyces cerevisiae. LOOS1 is distantly related to plant expansins through the shared presence of a DPBB domain, however domain II found in plant expansins is absent. LOOS1 binds tightly to cellulose and chitin, and we demonstrate that cotton fibers become susceptible to the action of a commercial cellulase following treatment with LOOS1. Natural fibers of Agave tequilana also become susceptible to hydrolysis by cellulases after loosenin treatment. Conclusions LOOS1 is a new type of protein with disrupting activity on cellulose. LOOS1 binds polysaccharides, and given its enhancing properties on the action of hydrolytic enzymes, LOOS1 represents a potential additive in the production of fermentable sugars from lignocellulose. PMID:21314954

  16. Cerveau isolé and pretrigeminal rat preparations.

    PubMed

    Zernicki, B; Gandolfo, G; Glin, L; Gottesmann, C

    1985-01-01

    Cortical and hippocampal EEG activity was analysed in cerveau isolé and and pretrigeminal rats. In the acute stage, waking EEG patterns were absent in the cerveau isolé, whereas sleep EGG patterns were absent in the preparations. However, already on the second day the EEG waking sleep cycle recovered in the majority of rats. Paradoxically, stimuli directed to the caudal part of the preparations evoked stronger cortical and hippocampal EEG arousal than olfactory and visual stimuli. The rats exhibited some locomotor and grooming behaviour and could be fed orally. It is concluded that the activity of the isolated cerebrum of the rat is similar to that of cat preparations, but that functions of the caudal neuraxis are superior in rats.

  17. Evaluation of antifungal activity in essential oil of the Syzygium aromaticum (L.) by extraction, purification and analysis of its main component eugenol.

    PubMed

    Rana, Inder Singh; Rana, Aarti Singh; Rajak, Ram Charan

    2011-10-01

    Antifungal properties of some essential oils have been well documented. Clove oil is reported to have strong antifungal activity against many fungal species. In this study we have evaluated antifungal potential of essential oil of Syzygium aromaticum (L.) against some common fungal pathogens of plants and animals namely, Fusarium moniliforme NCIM 1100, Fusarium oxysporum MTCC 284, Aspergillus sp., Mucor sp., Trichophyton rubrum and Microsporum gypseum. All fungal species were found to be inhibited by the oil when tested through agar well diffusion method. Minimum inhibitory concentration (MIC) was determined for all the species. Column chromatography was performed to separate the eugenol rich fraction from clove oil. Out of seven fractions maximum activity was obtained in column fraction II. TLC and HPLC data confirmed presence of considerable Eugenol in fraction II and clove oil. Microscopic study on effect of clove oil and column fraction II on spores of Mucor sp. and M. gypseum showed distortion and shrinkage while it was absent in other column fractions. So it can be concluded that the antifungal action of clove oil is due to its high eugenol content.

  18. Sperm dynamics in spiders (Araneae): ultrastructural analysis of the sperm activation process in the garden spider Argiope bruennichi (Scopoli, 1772).

    PubMed

    Vöcking, Oliver; Uhl, Gabriele; Michalik, Peter

    2013-01-01

    Storage of sperm inside the female genital tract is an integral phase of reproduction in many animal species. The sperm storage site constitutes the arena for sperm activation, sperm competition and female sperm choice. Consequently, to understand animal mating systems information on the processes that occur from sperm transfer to fertilization is required. Here, we focus on sperm activation in spiders. Male spiders produce sperm whose cell components are coiled within the sperm cell and that are surrounded by a proteinaceous sheath. These inactive and encapsulated sperm are transferred to the female spermathecae where they are stored for later fertilization. We analyzed the ultrastructural changes of sperm cells during residency time in the female genital system of the orb-web spider Argiope bruennichi. We found three clearly distinguishable sperm conditions: encapsulated sperm (secretion sheath present), decapsulated (secretion sheath absent) and uncoiled sperm (cell components uncoiled, presumably activated). After insemination, sperm remain in the encapsulated condition for several days and become decapsulated after variable periods of time. A variable portion of the decapsulated sperm transforms rapidly to the uncoiled condition resulting in a simultaneous occurrence of decapsulated and uncoiled sperm. After oviposition, only decapsulated and uncoiled sperm are left in the spermathecae, strongly suggesting that the activation process is not reversible. Furthermore, we found four different types of secretion in the spermathecae which might play a role in the decapsulation and activation process.

  19. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

    PubMed Central

    Datta, Subimal; O'Malley, Matthew W .

    2013-01-01

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

  20. Anxiety is correlated with running in adolescent female mice undergoing activity-based anorexia

    PubMed Central

    Wable, Gauri S.; Min, Jung-Yun; Chen, Yi-Wen; Aoki, Chiye

    2015-01-01

    Activity-based anorexia (ABA) is a widely used animal model for identifying the biological basis of excessive exercise and starvation, two hallmarks of anorexia nervosa (AN). Anxiety is correlated with exercise in AN. Yet the anxiety level of animals in ABA has not been reported. We asked: Does food restriction as part of ABA induction change the anxiety level of animals? If so, is the degree of anxiety correlated with degree of hyperactivity? We used the open field test before food restriction and the elevated plus maze test (EPM) during food restriction to quantify anxiety among singly housed adolescent female mice and determined whether food restriction alone or combined with exercise (i.e., ABA induction) abates or increases anxiety. We show that food restriction, with or without exercise, reduced anxiety significantly, as measured by the proportion of entries into the open arms of EPM (35.73 %, p= .04). Moreover, ABA-induced individuals varied in their open arm time measure of anxiety and this value was highly and negatively correlated to the individual’s food restriction-evoked wheel activity during the 24 hours following the anxiety test (R = − .75, p= .004, N = 12). This correlation was absent among the exercise-only controls. Additionally, mice with higher increase in anxiety ran more following food restriction. Our data suggest that food restriction-evoked wheel running hyperactivity can be used as a reliable and continuous measure of anxiety in ABA. The parallel relationship between anxiety level and activity in AN and ABA-induced female mice strengthens the animal model. PMID:25730124

  1. Defining boundaries for the distribution of microbial communities beneath the sediment-buried, hydrothermally active seafloor

    PubMed Central

    Yanagawa, Katsunori; Ijiri, Akira; Breuker, Anja; Sakai, Sanae; Miyoshi, Youko; Kawagucci, Shinsuke; Noguchi, Takuroh; Hirai, Miho; Schippers, Axel; Ishibashi, Jun-ichiro; Takaki, Yoshihiro; Sunamura, Michinari; Urabe, Tetsuro; Nunoura, Takuro; Takai, Ken

    2017-01-01

    Subseafloor microbes beneath active hydrothermal vents are thought to live near the upper temperature limit for life on Earth. We drilled and cored the Iheya North hydrothermal field in the Mid-Okinawa Trough, and examined the phylogenetic compositions and the products of metabolic functions of sub-vent microbial communities. We detected microbial cells, metabolic activities and molecular signatures only in the shallow sediments down to 15.8 m below the seafloor at a moderately distant drilling site from the active hydrothermal vents (450 m). At the drilling site, the profiles of methane and sulfate concentrations and the δ13C and δD isotopic compositions of methane suggested the laterally flowing hydrothermal fluids and the in situ microbial anaerobic methane oxidation. In situ measurements during the drilling constrain the current bottom temperature of the microbially habitable zone to ~45 °C. However, in the past, higher temperatures of 106–198 °C were possible at the depth, as estimated from geochemical thermometry on hydrothermally altered clay minerals. The 16S rRNA gene phylotypes found in the deepest habitable zone are related to those of thermophiles, although sequences typical of known hyperthermophilic microbes were absent from the entire core. Overall our results shed new light on the distribution and composition of the boundary microbial community close to the high-temperature limit for habitability in the subseafloor environment of a hydrothermal field. PMID:27754478

  2. Defining boundaries for the distribution of microbial communities beneath the sediment-buried, hydrothermally active seafloor.

    PubMed

    Yanagawa, Katsunori; Ijiri, Akira; Breuker, Anja; Sakai, Sanae; Miyoshi, Youko; Kawagucci, Shinsuke; Noguchi, Takuroh; Hirai, Miho; Schippers, Axel; Ishibashi, Jun-Ichiro; Takaki, Yoshihiro; Sunamura, Michinari; Urabe, Tetsuro; Nunoura, Takuro; Takai, Ken

    2017-02-01

    Subseafloor microbes beneath active hydrothermal vents are thought to live near the upper temperature limit for life on Earth. We drilled and cored the Iheya North hydrothermal field in the Mid-Okinawa Trough, and examined the phylogenetic compositions and the products of metabolic functions of sub-vent microbial communities. We detected microbial cells, metabolic activities and molecular signatures only in the shallow sediments down to 15.8 m below the seafloor at a moderately distant drilling site from the active hydrothermal vents (450 m). At the drilling site, the profiles of methane and sulfate concentrations and the δ 13 C and δD isotopic compositions of methane suggested the laterally flowing hydrothermal fluids and the in situ microbial anaerobic methane oxidation. In situ measurements during the drilling constrain the current bottom temperature of the microbially habitable zone to ~45 °C. However, in the past, higher temperatures of 106-198 °C were possible at the depth, as estimated from geochemical thermometry on hydrothermally altered clay minerals. The 16S rRNA gene phylotypes found in the deepest habitable zone are related to those of thermophiles, although sequences typical of known hyperthermophilic microbes were absent from the entire core. Overall our results shed new light on the distribution and composition of the boundary microbial community close to the high-temperature limit for habitability in the subseafloor environment of a hydrothermal field.

  3. NN′-Diacetylchitobiase activity in Tay–Sachs disease and Sandhoff's disease (Short Communication)

    PubMed Central

    Stirling, John L.

    1974-01-01

    In Tay–Sachs disease and Sandhoff's disease respectively, one of the N-acetyl-β-hexosaminidases (form A) or both (forms A and B) are absent, but glycosaminoglycans containing N-acetylhexosamines are not accumulated. The presence of NN′-diacetylchitobiase in livers from patients with these diseases raises the possibility that this new enzyme is involved in the metabolism of glycosaminoglycans rather than the enzymes previously described. PMID:4455225

  4. Nanospan, an alternatively spliced isoform of sarcospan, localizes to the sarcoplasmic reticulum in skeletal muscle and is absent in limb girdle muscular dystrophy 2F.

    PubMed

    Peter, Angela K; Miller, Gaynor; Capote, Joana; DiFranco, Marino; Solares-Pérez, Alhondra; Wang, Emily L; Heighway, Jim; Coral-Vázquez, Ramón M; Vergara, Julio; Crosbie-Watson, Rachelle H

    2017-06-06

    Sarcospan (SSPN) is a transmembrane protein that interacts with the sarcoglycans (SGs) to form a tight subcomplex within the dystrophin-glycoprotein complex that spans the sarcolemma and interacts with laminin in the extracellular matrix. Overexpression of SSPN ameliorates Duchenne muscular dystrophy in murine models. Standard cloning approaches were used to identify nanospan, and nanospan-specific polyclonal antibodies were generated and validated. Biochemical isolation of skeletal muscle membranes and two-photon laser scanning microscopy were used to analyze nanospan localization in muscle from multiple murine models. Duchenne muscular dystrophy biopsies were analyzed by immunoblot analysis of protein lysates as well as indirect immunofluorescence analysis of muscle cryosections. Nanospan is an alternatively spliced isoform of sarcospan. While SSPN has four transmembrane domains and is a core component of the sarcolemmal dystrophin-glycoprotein complex, nanospan is a type II transmembrane protein that does not associate with the dystrophin-glycoprotein complex. We demonstrate that nanospan is enriched in the sarcoplasmic reticulum (SR) fractions and is not present in the T-tubules. SR fractions contain membranes from three distinct structural regions: a region flanking the T-tubules (triadic SR), a SR region across the Z-line (ZSR), and a longitudinal SR region across the M-line (LSR). Analysis of isolated murine muscles reveals that nanospan is mostly associated with the ZSR and triadic SR, and only minimally with the LSR. Furthermore, nanospan is absent from the SR of δ-SG-null (Sgcd -/- ) skeletal muscle, a murine model for limb girdle muscular dystrophy 2F. Analysis of skeletal muscle biopsies from Duchenne muscular dystrophy patients reveals that nanospan is preferentially expressed in type I (slow) fibers in both control and Duchenne samples. Furthermore, nanospan is significantly reduced in Duchenne biopsies. Alternative splicing of proteins from the SG

  5. High prevalence of cardiac hypertophy without detectable signs of fibrosis in patients with untreated active acromegaly: an in vivo study using magnetic resonance imaging.

    PubMed

    Bogazzi, Fausto; Lombardi, Massimo; Strata, Elisabetta; Aquaro, Giovanni; Di Bello, Vitantonio; Cosci, Chiara; Sardella, Chiara; Talini, Enrica; Martino, Enio

    2008-03-01

    Left ventricular (LV) hypertrophy and myocardial fibrosis are considered the main pathological features of acromegalic cardiomyopathy. The aim of the study was to evaluate the proportion of LV hypertrophy and the presence of fibrosis in acromegalic cardiomyopathy in vivo using cardiac magnetic resonance (CMR). Fourteen consecutive patients (eight women, mean age 46 +/- 10 years) with untreated active acromegaly were submitted to two-dimensional (2D) colour Doppler and integrated backscatter (IBS) echocardiography and CMR. LV volume, mass and wall thickness and myocardial tissue characterization (IBS and CMR). On echocardiography: mean LV mass (LVM) and LVM index (LVMi) were 209 +/- 48 g and 110 +/- 24 g/m(2), respectively; hypertrophy was revealed in five patients (36%); abnormal diastolic function [evaluated by isovolumic relaxation time (IVRT) or early (E) to late or atrial (A) peak velocities (E/A ratio)] was found in four patients (29%). Systolic function evaluated by measuring LV ejection fraction (LVEF) was normal (mean 72 +/- 12%) in all patients. Six patients (43%) had increased IBS (mean 57.4 +/- 6.2%). On CMR: mean LVM and LVMi were 151 +/- 17 g and 76 +/- 9 g/m(2), respectively; 10 patients (72%) had LV hypertrophy. Contrastographic delayed hyperenhancement was absent in all patients; on the contrary, mild enhancement was revealed in one patient. Systolic function was normal in all patients (LVEF 67 +/- 11%). LVMi was not related to serum IGF-1 concentrations or the estimated duration of disease. CMR is considered to be the gold standard for evaluating cardiac hypertrophy, fibrosis and systolic function. Using CMR, 72% patients with untreated active acromegaly had LV hypertrophy, which was only detected in 36% patients by echocardiography. However, cardiac fibrosis was absent in all patients irrespective of the estimated duration of disease. Although a very small increase in collagen content (as suggested by increased cardiac reflectivity at IBS), not

  6. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site.

    PubMed

    Kassotis, Christopher D; Iwanowicz, Luke R; Akob, Denise M; Cozzarelli, Isabelle M; Mumford, Adam C; Orem, William H; Nagel, Susan C

    2016-07-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site

    USGS Publications Warehouse

    Kassotis, Christopher D.; Iwanowicz, Luke R.; Akob, Denise M.; Cozzarelli, Isabelle M.; Mumford, Adam; Orem, William H.; Nagel, Susan C.

    2016-01-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby.

  8. Self-enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia

    PubMed Central

    Geng, Huimin; Hurtz, Christian; Lenz, Kyle B.; Chen, Zhengshan; Baumjohann, Dirk; Thompson, Sarah; Goloviznina, Natalya; Chen, Wei-Yi; Huan, Jianya; LaTocha, Dorian; Ballabio, Erica; Xiao, Gang; Lee, Jae-Woong; Deucher, Anne; Qi, Zhongxia; Park, Eugene; Huang, Chuanxin; Nahar, Rahul; Kweon, Soo-Mi; Shojaee, Seyedmehdi; Chan, Lai N.; Yu, Jingwei; Kornblau, Steven M.; Bijl, Janetta J.; Ye, B. Hilda; Ansel, Mark; Paietta, Elisabeth; Melnick, Ari; Hunger, Stephen P.; Kurre, Peter; Tyner, Jeffrey W.; Loh, Mignon L.; Roeder, Robert G.; Druker, Brian J.; Burger, Jan. A.; Milne, Thomas A.; Chang, Bill H.; Müschen, Markus

    2015-01-01

    SUMMARY Studying 830 pre-B ALL cases from four clinical trials, we found that human ALL can be divided into two fundamentally distinct subtypes based on pre-BCR function. While absent in the majority of ALL cases, tonic pre-BCR signaling was found in 112 cases (13.5%). In these cases, tonic pre-BCR signaling induced activation of BCL6, which in turn increased pre-BCR signaling output at the transcriptional level. Interestingly, inhibition of pre-BCR-related tyrosine kinases reduced constitutive BCL6 expression and selectively killed patient-derived pre-BCR+ ALL cells. These findings identify a genetically and phenotypically distinct subset of human ALL that critically depends on tonic pre-BCR signaling. In vivo treatment studies suggested that pre-BCR tyrosine kinase inhibitors are useful for the treatment of patients with pre-BCR+ ALL. PMID:25759025

  9. MicroRNA signatures characterizing caste-independent ovarian activity in queen and worker honeybees (Apis mellifera L.).

    PubMed

    Macedo, L M F; Nunes, F M F; Freitas, F C P; Pires, C V; Tanaka, E D; Martins, J R; Piulachs, M-D; Cristino, A S; Pinheiro, D G; Simões, Z L P

    2016-06-01

    Queen and worker honeybees differ profoundly in reproductive capacity. The queen of this complex society, with 200 highly active ovarioles in each ovary, is the fertile caste, whereas the workers have approximately 20 ovarioles as a result of receiving a different diet during larval development. In a regular queenright colony, the workers have inactive ovaries and do not reproduce. However, if the queen is sensed to be absent, some of the workers activate their ovaries, producing viable haploid eggs that develop into males. Here, a deep-sequenced ovary transcriptome library of reproductive workers was used as supporting data to assess the dynamic expression of the regulatory molecules and microRNAs (miRNAs) of reproductive and nonreproductive honeybee females. In this library, most of the differentially expressed miRNAs are related to ovary physiology or oogenesis. When we quantified the dynamic expression of 19 miRNAs in the active and inactive worker ovaries and compared their expression in the ovaries of virgin and mated queens, we noted that some miRNAs (miR-1, miR-31a, miR-13b, miR-125, let-7 RNA, miR-100, miR-276, miR-12, miR-263a, miR-306, miR-317, miR-92a and miR-9a) could be used to identify reproductive and nonreproductive statuses independent of caste. Furthermore, integrative gene networks suggested that some candidate miRNAs function in the process of ovary activation in worker bees. © 2016 The Royal Entomological Society.

  10. Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function

    PubMed Central

    Concepcion, Axel R.; Vaeth, Martin; Wagner, Larry E.; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P.; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E.; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S.; Cuk, Mario; Yule, David I.

    2016-01-01

    Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release–activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel–deficient patients and mice with ectodermal tissue–specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice. PMID:27721237

  11. Primary motor cortex of the parkinsonian monkey: altered encoding of active movement

    PubMed Central

    Pasquereau, Benjamin; DeLong, Mahlon R.

    2016-01-01

    Abnormalities in the movement-related activation of the primary motor cortex (M1) are thought to be a major contributor to the motor signs of Parkinson’s disease. The existing evidence, however, variably indicates that M1 is under-activated with movement, overactivated (due to a loss of functional specificity) or activated with abnormal timing. In addition, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those gaps in knowledge were addressed by studying the extracellular activity of antidromically-identified lamina 5b pyramidal-tract type neurons (n = 153) and intratelencephalic-type corticostriatal neurons (n = 126) in the M1 of two monkeys as they performed a step-tracking arm movement task. We compared movement-related discharge before and after the induction of parkinsonism by administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and quantified the spike rate encoding of specific kinematic parameters of movement using a generalized linear model. The fraction of M1 neurons with movement-related activity declined following MPTP but only marginally. The strength of neuronal encoding of parameters of movement was reduced markedly (mean 29% reduction in the coefficients from the generalized linear model). This relative decoupling of M1 activity from kinematics was attributable to reductions in the coefficients that estimated the spike rate encoding of movement direction (−22%), speed (−40%), acceleration (−49%) and hand position (−33%). After controlling for MPTP-induced changes in motor performance, M1 activity related to movement itself was reduced markedly (mean 36% hypoactivation). This reduced activation was strong in pyramidal tract-type neurons (−50%) but essentially absent in corticostriatal neurons. The timing of M1 activation was also abnormal, with earlier onset times, prolonged response durations, and a 43% reduction in the prevalence of movement-related changes

  12. Histomorphology and proteolytic activity in the gastric apparatus of frugivorous, carnivorous and omnivorous species of birds.

    PubMed

    Jain, D K

    1976-01-01

    The histomorphology of the gastric apparatus, the pepsin level and the optimum pH for pepsin were investigated in Psittacula krameri (frugivore), Lanius schach (carnivore) and Acridotheres tristis (omnivore) species of birds. The proventricular glands were found to be made up of oxynticopeptic cells. The lobules of the oxynticopeptic cells are polyhedral; they are the largest in P. krameri, and the smallest in A. tristis. However, their greater number in A. tristis enables a higher secretion of hydrochloric acid and pepsin. The villi are more developed in A. tristis than in L. schach and P. krameri. The gizzard is larger in A. tristis than in P. krameri and A. tritis than in the carnivore L. schach. Koilin lining is beset with horny cones, which were well developed in A. tristis, moderately developed in P. krameri and absent in L. schach. The pepsin activity is higher in the proventriculus of the carnivorous L. schach and the omnivorous A. tristis than in the frugivorous P. krameri. Slight pepsin activity was also observed in gizzard tissue extracts in all the three species. The optimum pH for pepsin was found to be 1.5 for P. krameri and 1.8 for both L. schach and A. tristis.

  13. Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA domain Ubiquitination

    PubMed Central

    Lee, YouJin; Chou, Tsui-Fen; Pittman, Sara K.; Keith, Amy L.; Razani, Babak; Weihl, Conrad C.

    2017-01-01

    Summary p62/SQSTM1 (p62) is a scaffolding protein that facilitates the formation and degradation of ubiquitinated aggregates via its self-interaction and ubiquitin binding domains. The regulation of this process is unclear but may relate to the post-translational modification of p62. In the present study, we find that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain. Substitution of lysine 420 with an arginine diminishes p62 sequestration and degradation activity similar to that seen when the UBA domain is deleted. Overexpression of Keap1/Cullin3 in p62-WT expressing cells increases ubiquitinated inclusion formation, p62’s association with LC3 and rescues proteotoxicity. This effect is not seen in cells expressing a mutant p62 that fails to interact with Keap1. Interestingly, p62 disease mutants have diminished or absent UBA domain ubiquitination. These data suggest that the ubiquitination of p62’s UBA domain at lysine 420 may regulate p62’s function and be disrupted in p62 associated disease. PMID:28380357

  14. Niemann-Pick disease, Type C: evidence for the deficiency of an activating factor stimulating sphingomyelin and glucocerebroside degradation.

    PubMed

    Christomanou, H

    1980-10-01

    1) Qualitative lipid analyses by thin-layer chromatography of 4 Niemann-Pick type C spleens confirmed sphingomyelin accumulation together with increase in the amount of glucocerebroside. 2) In the presence of crude sodium taurocholate as detergent, sphingomyelin degradation rates of normal and Niemann-Pick type C-cultured fibroblasts were fairly close under standard conditions at pH 5.0. In the absence of sodium taurocholate, sphingomyelinase activity was optimal at pH 4.0. Sphingomyelinase activities of fibroblasts from two patients with Niemann-Pick disease type C measured without detergent, were about 30% of that of controls. 3) Extracts from Gaucher spleen heated to 90 degrees C and devoid of sphingomyelinase activity stimulated at the optimal pH of 4.0 sphingomyelin degradation by cultured normal fibroblasts (2--4-fold, Niemann-Pick type C fibroblasts (5--9-fold), whereas similarly treated extracts from Niemann-Pick type C spleen showed no stimulation of sphingomyelin catabolism. Heated extracts from normal human spleen exhibited a smaller stimulation than that shown by Gaucher spleen. This stimulating effect could not be observed in fibroblasts from patients suffering from Niemann-Pick type B (sphingomyelinase defect). 4) Heat-treated extracts of Gaucher spleen were fractionated by ion exchange chromatography, isoelectric focusing and gel filtration. The active fractions obtained by these procedures stimulated sphingomyelin as well as glucocerebroside degradation and were absent from the corresponding Niemann-Pick type C preparations. Enriched activator preparations of Gaucher spleen stimulated sphingomyelinase activity of Niemann-Pick type C fibroblasts 25--38-fold and that of normal cells 3-fold. 5) The activating factor had an isoelectric point of 4.0 and an apparent molecular weight, as estimated by gel filtration, of 25000. Treatment with pronase E abolished its activity.

  15. Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa

    PubMed Central

    Büttner, Dietrich W; Wanji, Samuel; Bazzocchi, Chiara; Bain, Odile; Fischer, Peter

    2003-01-01

    Background Many filarial nematodes harbour Wolbachia endobacteria. These endobacteria are transmitted vertically from one generation to the next. In several filarial species that have been studied to date they are obligatory symbionts of their hosts. Elimination of the endobacteria by antibiotics interrupts the embryogenesis and hence the production of microfilariae. The medical implication of this being that the use of doxycycline for the treatment of human onchocerciasis and bancroftian filariasis leads to elimination of the Wolbachia and hence sterilisation of the female worms. Wolbachia play a role in the immunopathology of patients and may contribute to side effects seen after antifilarial chemotherapy. In several studies Wolbachia were not observed in Loa loa. Since these results have been doubted, and because of the medical significance, several independent methods were applied to search for Wolbachia in L. loa. Methods Loa loa and Onchocerca volvulus were studied by electron microscopy, histology with silver staining, and immunohistology using antibodies against WSP, Wolbachia aspartate aminotransferase, and heat shock protein 60. The results achieved with L. loa and O. volvulus were compared. Searching for Wolbachia, genes were amplified by PCR coding for the bacterial 16S rDNA, the FTSZ cell division protein, and WSP. Results No Wolbachia endobacteria were discovered by immunohistology in 13 male and 14 female L. loa worms and in numerous L. loa microfilariae. In contrast, endobacteria were found in large numbers in O. volvulus and 14 other filaria species. No intracellular bacteria were seen in electron micrographs of oocytes and young morulae of L. loa in contrast to O. volvulus. In agreement with these results, Wolbachia DNA was not detected by PCR in three male and six female L. loa worms and in two microfilariae samples of L. loa. Conclusions Loa loa do not harbour obligatory symbiotic Wolbachia endobacteria in essential numbers to enable their efficient vertical transmission or to play a role in production of microfilariae. Exclusively, the filariae cause the immunopathology of loiasis is patients and the adverse side effects after antifilarial chemotherapy. Doxycycline cannot be used to cure loiais but it probably does not represent a risk for L. loa patients when administered to patients with co-infections of onchocerciasis. PMID:12801420

  16. Minding the Absent: Arguments for the Full Competence Hypothesis.

    ERIC Educational Resources Information Center

    Borer, Hagit; Rohrbacher, Bernhard

    2002-01-01

    Suggests that the systematic omission of functional material by young children, contrary to current beliefs, argues for the presence of functional structure,because in the absence of such structure what is expected is not a systematic omission of functional material but rather its random use. (Author/VWL)

  17. Absent Audiences: Youth Identity Formation in Preparations for Performance

    ERIC Educational Resources Information Center

    Thompson, Carol C.

    2011-01-01

    This article explores the use of audiences in preparation for public presentation by an urban youth organization in Camden, New Jersey (U.S.). Camden is an impoverished city with few opportunities for youth. The organization, a hybrid of youth development, technology, business, and college preparation, prepared youth for good jobs or college.…

  18. Absent from the Majority: Working Class Women in America.

    ERIC Educational Resources Information Center

    Seifer, Nancy

    This report is an attempt to draw together the few existing studies and surveys of working class women, as well as the firsthand experiences of community leaders, organizers, and observers around the country, to provide an impressionistic overview of the ways in which working class women's lives are beginning to depart from many long-standing…

  19. Heavy-light, absent-present: rethinking the 'weight' of imprisonment.

    PubMed

    Crewe, Ben; Liebling, Alison; Hulley, Susie

    2014-09-01

    Since King and McDermott (1995), following Downes (1988), defined the psychological oppressiveness of incarceration in terms of 'weight', little has been written about the 'weight of imprisonment'. None the less, it is generally assumed that prisons that are 'light' are preferable to those that are 'heavy' - in part because of an assumption among many penologists that power, and its application, is dangerous and antagonistic. This article does not dispute that 'heavy' prisons are undesirable. Its argument is that there can also be dangers if prisons are excessively light. Many of these dangers are linked to the under-use of power. The tone and quality of prison life depends on the combined effects of institutional weight with the 'absence' or 'presence' of staff power. Drawing on prisoners' descriptions of their experiences in public and private sector prisons, and their assessments of important aspects of their quality of life, the article outlines what these concepts mean in practice. The authors develop a four-quadrant framework for conceptualizeng penal legitimacy and the experience of penal authority. © London School of Economics and Political Science 2014.

  20. The Economic Consequences of Absent Parents. JCPR Working Paper.

    ERIC Educational Resources Information Center

    Page, Marianne E.; Stevens, Ann Huff

    In recent years, the belief that marriage bestows large economic gains has generated enthusiasm for policy proposals that encourage the formation and continuation of two-parent families. This study examined the effects of family structure on economic resources, controlling for unobservable family background characteristics. Data were drawn from…

  1. Impacts of dissolved organic matter on aqueous behavior of nano/micron-titanium nitride and their induced enzymatic/non-enzymatic antioxidant activities in Scenedesmus obliquus.

    PubMed

    Zhang, Xin; Wang, Zhuang; Wang, Se; Fang, Hao; Zhang, Fan; Wang, De-Gao

    2017-01-02

    Freshwater dispersion stability and ecotoxicological effects of titanium nitride (TiN) with particle size of 20 nm, 50 nm, and 2-10 μm in the presence of dissolved organic matter (DOM) at various concentrations were studied. The TiN particles that had a more negative zeta potential and smaller hydrodynamic size showed more stable dispersion in an aqueous medium when DOM was present than when DOM was absent. Biochemical assays indicated that relative to the control, the TiN particles in the presence of DOM alleviated to some extent the antioxidative stress enzyme activity in Scenedesmus obliquus. In addition, it was found that the TiN with a primary size of 50 nm at a high concentration presented a significant impact on non-enzymatic antioxidant defense in algal cells.

  2. Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: evidence for the pathophysiological role of PHEX in X-linked hypophosphatemia.

    PubMed

    Nesbitt, T; Fujiwara, I; Thomas, R; Xiao, Z S; Quarles, L D; Drezner, M K

    1999-12-01

    The mechanism by which inactivating mutations of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) cause X-linked hypophosphatemia remains unknown. However, recent reports suggest errant PHEX activity in osteoblasts may fail to inactivate a phosphaturic factor produced by these cells. To test this possibility, we examined coordinated maturational expression of PHEX and production of phosphate transport inhibitory activity in osteoblasts from normal and hyp-mice. We assessed the inhibitory activity in conditioned medium by examining the effects on opossum kidney cell phosphate transport and osteoblast PHEX expression by reverse transcriptase-polymerase chain reaction during a 17-day maturational period. Inhibitory activity increased as a function of osteoblast maturational stage, with no activity after 3 days and persistent activity by 6 days of culture. More significantly, equal phosphate transport inhibitory activity in conditioned medium from normal and hyp-mouse osteoblasts (control 1.90 +/- 0.12, normal 1.48 +/- 0.10, hyp 1.45 +/- 0.04 nmol/mg of protein/minute) was observed at 6 days. However, by 10 days hyp-mouse osteoblasts exhibited greater inhibitory activity than controls, and by 17 days the difference in phosphate transport inhibition maximized (control 2.08 +/- 0.09, normal 1.88 +/- 0.06, hyp 1.58 +/- 0.06 nmol/mg of protein/minute). Concurrently, we observed absent PHEX expression in normal osteoblasts after 3 days, limited production at 6 days, and significant production by day 10 of culture, while hyp-mouse osteoblasts exhibited limited PHEX activity secondary to an inactivating mutation. The data suggest that the presence of inactivating PHEX mutations results in the enhanced renal phosphate transport inhibitory activity exhibited by hyp-mouse osteoblasts.

  3. On dependence of seismic activity on 11 year variations in solar activity and/or cosmic rays

    NASA Astrophysics Data System (ADS)

    Zhantayev, Zhumabek; Khachikyan, Galina; Breusov, Nikolay

    2014-05-01

    It is found in the last decades that seismic activity of the Earth has a tendency to increase with decreasing solar activity (increasing cosmic rays). A good example of this effect may be the growing number of catastrophic earthquakes in the recent rather long solar minimum. Such results support idea on existence a solar-lithosphere relationship which, no doubts, is a part of total pattern of solar-terrestrial relationships. The physical mechanism of solar-terrestrial relationships is not developed yet. It is believed at present that one of the main contenders for such mechanism may be the global electric circuit (GEC) - vertical current loops, piercing and electrodynamically coupling all geospheres. It is also believed, that the upper boundary of the GEC is located at the magnetopause, where magnetic field of the solar wind reconnects with the geomagnetic field, that results in penetrating solar wind energy into the earth's environment. The effectiveness of the GEC operation depends on intensity of cosmic rays (CR), which ionize the air in the middle atmosphere and provide its conductivity. In connection with the foregoing, it can be expected: i) quantitatively, an increasing seismic activity from solar maximum to solar minimum may be in the same range as increasing CR flux; and ii) in those regions of the globe, where the crust is shipped by the magnetic field lines with number L= ~ 2.0, which are populated by anomalous cosmic rays (ACR), the relationship of seismic activity with variations in solar activity will be manifested most clearly, since there is a pronounced dependence of ACR on solar activity variations. Checking an assumption (i) with data of the global seismological catalog of the NEIC, USGS for 1973-2010, it was found that yearly number of earthquake with magnitude M≥4.5 varies into the 11 year solar cycle in a quantitative range of about 7-8% increasing to solar minimum, that qualitatively and quantitatively as well is in agreement with the

  4. Oncogenically active MYD88 mutations in human lymphoma.

    PubMed

    Ngo, Vu N; Young, Ryan M; Schmitz, Roland; Jhavar, Sameer; Xiao, Wenming; Lim, Kian-Huat; Kohlhammer, Holger; Xu, Weihong; Yang, Yandan; Zhao, Hong; Shaffer, Arthur L; Romesser, Paul; Wright, George; Powell, John; Rosenwald, Andreas; Muller-Hermelink, Hans Konrad; Ott, German; Gascoyne, Randy D; Connors, Joseph M; Rimsza, Lisa M; Campo, Elias; Jaffe, Elaine S; Delabie, Jan; Smeland, Erlend B; Fisher, Richard I; Braziel, Rita M; Tubbs, Raymond R; Cook, J R; Weisenburger, Denny D; Chan, Wing C; Staudt, Louis M

    2011-02-03

    The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.

  5. Aggregatibacter actinomycetemcomitans-Induced AIM2 Inflammasome Activation Is Suppressed by Xylitol in Differentiated THP-1 Macrophages.

    PubMed

    Kim, Seyeon; Park, Mi Hee; Song, Yu Ri; Na, Hee Sam; Chung, Jin

    2016-06-01

    Aggressive periodontitis is characterized by rapid destruction of periodontal tissue caused by Aggregatibacter actinomycetemcomitans. Interleukin (IL)-1β is a proinflammatory cytokine, and its production is tightly regulated by inflammasome activation. Xylitol, an anticaries agent, is anti-inflammatory, but its effect on inflammasome activation has not been researched. This study investigates the effect of xylitol on inflammasome activation induced by A. actinomycetemcomitans. The differentiated THP-1 macrophages were stimulated by A. actinomycetemcomitans with or without xylitol and the expressions of IL-1β and inflammasome components were detected by real time PCR, ELISA, confocal microscopy and Immunoblot analysis. The effects of xylitol on the adhesion and invasion of A. actinomycetemcomitans to cells were measured by viable cell count. A. actinomycetemcomitans increased pro IL-1β synthesis and IL-1β secretion in a multiplicity of infection- and time-dependent manner. A. actinomycetemcomitans also stimulated caspase-1 activation. Among inflammasome components, apoptosis-associated speck-like protein containing a CARD (ASC) and absent in melanoma 2 (AIM2) proteins were upregulated by A. actinomycetemcomitans infection. When cells were pretreated with xylitol, proIL-1β and IL-1β production by A. actinomycetemcomitans infection was significantly decreased. Xylitol also inhibited ASC and AIM2 proteins and formation of ASC puncta. Furthermore, xylitol suppressed internalization of A. actinomycetemcomitans into differentiated THP-1 macrophages without affecting viability of A. actinomycetemcomitans within cells. A. actinomycetemcomitans induced IL-1β production and AIM2 inflammasome activation. Xylitol inhibited these effects, possibly by suppressing internalization of A. actinomycetemcomitans into cells. Thus, this study proposes a mechanism for IL-1β production via inflammasome activation and discusses a possible use for xylitol in periodontal inflammation

  6. Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities

    PubMed Central

    Dick, Thomas E.; Hsieh, Yee-Hsee; Dhingra, Rishi R.; Baekey, David M.; Galán, Roberto F.; Wehrwein, Erica; Morris, Kendall F.

    2014-01-01

    Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic

  7. Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia.

    PubMed

    Gozal, Evelyne; Shah, Zahoor A; Pequignot, Jean-Marc; Pequignot, Jacqueline; Sachleben, Leroy R; Czyzyk-Krzeska, Maria F; Li, Richard C; Guo, Shang-Z; Gozal, David

    2005-08-01

    Tyrosine hydroxylase, a hypoxia-regulated gene, may be involved in tissue adaptation to hypoxia. Intermittent hypoxia, a characteristic feature of sleep apnea, leads to significant memory deficits, as well as to cortex and hippocampal apoptosis that are absent after sustained hypoxia. To examine the hypothesis that sustained and intermittent hypoxia induce different catecholaminergic responses, changes in tyrosine hydroxylase mRNA, protein expression, and activity were compared in various brain regions of male rats exposed for 6 h, 1 day, 3 days, and 7 days to sustained hypoxia (10% O(2)), intermittent hypoxia (alternating room air and 10% O(2)), or normoxia. Tyrosine hydroxylase activity, measured at 7 days, increased in the cortex as follows: sustained > intermittent > normoxia. Furthermore, activity decreased in the brain stem and was unchanged in other brain regions of sustained hypoxia-exposed rats, as well as in all regions from animals exposed to intermittent hypoxia, suggesting stimulus-specific and heterotopic catecholamine regulation. In the cortex, tyrosine hydroxylase mRNA expression was increased, whereas protein expression remained unchanged. In addition, significant differences in the time course of cortical Ser(40) tyrosine hydroxylase phosphorylation were present in the cortex, suggesting that intermittent and sustained hypoxia-induced enzymatic activity differences are related to different phosphorylation patterns. We conclude that long-term hypoxia induces site-specific changes in tyrosine hydroxylase activity and that intermittent hypoxia elicits reduced tyrosine hydroxylase recruitment and phosphorylation compared with sustained hypoxia. Such changes may not only account for differences in enzyme activity but also suggest that, with differential regional brain susceptibility to hypoxia, recruitment of different mechanisms in response to hypoxia will elicit region-specific modulation of catecholamine response.

  8. Transcranial direct-current stimulation modulates offline visual oscillatory activity: A magnetoencephalography study

    PubMed Central

    Heinrichs-Graham, Elizabeth; McDermott, Timothy J.; Mills, Mackenzie S.; Coolidge, Nathan M.; Wilson, Tony W.

    2017-01-01

    Transcranial direct-current stimulation (tDCS) is a noninvasive neuromodulatory method that involves delivering low amplitude, direct current to specific regions of the brain. While a wealth of literature shows changes in behavior and cognition following tDCS administration, the underlying neuronal mechanisms remain largely unknown. Neuroimaging studies have generally used fMRI and shown only limited consensus to date, while the few electrophysiological studies have reported mostly null or counterintuitive findings. The goal of the current investigation was to quantify tDCS-induced alterations in the oscillatory dynamics of visual processing. To this end, we performed either active or sham tDCS using an occipital-frontal electrode configuration, and then recorded magnetoencephalography (MEG) offline during a visual entrainment task. Significant oscillatory responses were imaged in the time-frequency domain using beamforming, and the effects of tDCS on absolute and relative power were assessed. The results indicated significantly increased basal alpha levels in the occipital cortex following anodal tDCS, as well as reduced occipital synchronization at the second harmonic of the stimulus-flicker frequency relative to sham stimulation. In addition, we found reduced power in brain regions near the cathode (e.g., right inferior frontal gyrus) following active tDCS, which was absent in the sham group. Taken together, these results suggest that anodal tDCS of the occipital cortices differentially modulates spontaneous and induced activity, and may interfere with the entrainment of neuronal populations by a visual-flicker stimulus. These findings also demonstrate the importance of electrode configuration on whole-brain dynamics, and highlight the deceptively complicated nature of tDCS in the context of neurophysiology. PMID:28042984

  9. Drosophila Hox and Sex-Determination Genes Control Segment Elimination through EGFR and extramacrochetae Activity

    PubMed Central

    Foronda, David; Martín, Paloma; Sánchez-Herrero, Ernesto

    2012-01-01

    The formation or suppression of particular structures is a major change occurring in development and evolution. One example of such change is the absence of the seventh abdominal segment (A7) in Drosophila males. We show here that there is a down-regulation of EGFR activity and fewer histoblasts in the male A7 in early pupae. If this activity is elevated, cell number increases and a small segment develops in the adult. At later pupal stages, the remaining precursors of the A7 are extruded under the epithelium. This extrusion requires the up-regulation of the HLH protein Extramacrochetae and correlates with high levels of spaghetti-squash, the gene encoding the regulatory light chain of the non-muscle myosin II. The Hox gene Abdominal-B controls both the down-regulation of spitz, a ligand of the EGFR pathway, and the up-regulation of extramacrochetae, and also regulates the transcription of the sex-determining gene doublesex. The male Doublesex protein, in turn, controls extramacrochetae and spaghetti-squash expression. In females, the EGFR pathway is also down-regulated in the A7 but extramacrochetae and spaghetti-squash are not up-regulated and extrusion of precursor cells is almost absent. Our results show the complex orchestration of cellular and genetic events that lead to this important sexually dimorphic character change. PMID:22912593

  10. Concerted vs. Sequential. Two Activation Patterns of Vast Arrays of Intracellular Ca2+ Channels in Muscle

    PubMed Central

    Zhou, Jinsong; Brum, Gustavo; González, Adom; Launikonis, Bradley S.; Stern, Michael D.; Ríos, Eduardo

    2005-01-01

    To signal cell responses, Ca2+ is released from storage through intracellular Ca2+ channels. Unlike most plasmalemmal channels, these are clustered in quasi-crystalline arrays, which should endow them with unique properties. Two distinct patterns of local activation of Ca2+ release were revealed in images of Ca2+ sparks in permeabilized cells of amphibian muscle. In the presence of sulfate, an anion that enters the SR and precipitates Ca2+, sparks became wider than in the conventional, glutamate-based solution. Some of these were “protoplatykurtic” (had a flat top from early on), suggesting an extensive array of channels that activate simultaneously. Under these conditions the rate of production of signal mass was roughly constant during the rise time of the spark and could be as high as 5 μm3 ms−1, consistent with a release current >50 pA since the beginning of the event. This pattern, called “concerted activation,” was observed also in rat muscle fibers. When sulfate was combined with a reduced cytosolic [Ca2+] (50 nM) these sparks coexisted (and interfered) with a sequential progression of channel opening, probably mediated by Ca2+-induced Ca2+ release (CICR). Sequential propagation, observed only in frogs, may require parajunctional channels, of RyR isoform β, which are absent in the rat. Concerted opening instead appears to be a property of RyR α in the amphibian and the homologous isoform 1 in the mammal. PMID:16186560

  11. Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa.

    PubMed

    Holsen, Laura M; Lawson, Elizabeth A; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M

    2014-08-30

    Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa

    PubMed Central

    Holsen, Laura M.; Lawson, Elizabeth A.; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M.

    2014-01-01

    Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. PMID:24862390

  13. Alkaline Phosphatase Activity : an overlooked player on the phosphate behavior in macrotidal estuaries

    NASA Astrophysics Data System (ADS)

    Delmas, Daniel; Labry, Claire; Youenou, Agnes; Quere, Julien; Auguet, Jean Christophe; Montanie, Helene

    2014-05-01

    The non-conservative behavior of phosphate within the estuarine salinity gradient is essentially assigned to physico-chemical processes, such as desorption at low salinity and to benthic exchanges. Microbial phosphatase activity (APA), generally related to phosphate deficiency, is seldom studied in phosphate rich estuarine waters. In order to address the impact of microbial activity (bacterial abundance, production BSP, APA) on phosphate behavior, we studied these activities on a seasonal basis within the salinity gradient of two macrotidal estuaries presenting different levels of suspended solids. Whatever the season the Charente estuary is characterized by high levels of Suspended Particulate Matter (SPM > 1g.L-1), particularly in the Maximum Turbidity Zone (MTZ) located at the 5-10 psu. In this area characterized by high BSP and APA there is a significant increase of PO4 levels especially during summer. In the Aulne estuary the particle load is significantly lower (1/10) but high BSP and APA are equally recorded. In the highly turbid waters of the Charente estuary, active phytoplankton is virtually absent as pheopigments constitute up to 80% of the total pigments, particularly in the MTZ, therefore APA may essentially have a bacterial origin. In the Aulne estuary attached bacteria are dominant, both in numbers and production, and their distribution along the haline gradient perfectly follows those of APA and phosphate levels. These observations, associated with the very close relationships observed between APA, SPM and BSP, suggest that APA derive mainly from bacterial (attached) origin and operate at the expense of particulate phosphorus and hence contribute to PO4 regeneration, especially in spring and summer. Finally, as APA increased as PO4, whereas the reverse is observed in both fresh and marine waters, an original scheme for APA regulation, related to the large dominance of attached bacteria can be described for the estuarine waters.

  14. Physical Activity and Exercise Interventions in the Workplace Impacting Work Outcomes: A Stakeholder-Centered Best Evidence Synthesis of Systematic Reviews.

    PubMed

    White, M I; Dionne, C E; Wärje, O; Koehoorn, M; Wagner, S L; Schultz, I Z; Koehn, C; Williams-Whitt, K; Harder, H G; Pasca, R; Hsu, V; McGuire, L; Schulz, W; Kube, D; Wright, M D

    2016-04-01

    The prevention of work disability is beneficial to employees and employers, and mitigates unnecessary societal costs associated with social welfare. Many service providers and employers have initiated workplace interventions designed to reduce unnecessary work disability. To conduct a best-evidence synthesis of systematic reviews on workplace interventions that address physical activities or exercise and their impact on workplace absence, work productivity or financial outcomes. Using a participatory research approach, academics and stakeholders identified inclusion and exclusion criteria, built an abstraction table, evaluated systematic review quality and relevance, and interpreted the combined findings. A minimum of two scientists participated in a methodological review of the literature followed by a consensus process. Stakeholders and researchers participated as a collaborative team. 3363 unique records were identified, 115 full text articles and 46 systematic reviews were included, 18 assessed the impact of physical fitness or exercise interventions. 11 focused on general workers rather than workers who were absent from work at baseline; 16 of the reviews assessed work absence, 4 assessed productivity and 6 assessed financial impacts. The strongest evidence supports the use of short, simple exercise or fitness programs for both workers at work and those absent from work at baseline. For workers at work, simple exercise programs (1-2 modal components) appear to provide similar benefits to those using more complex multimodal interventions. For workers off-work with subacute low back pain, there is evidence that some complex exercise programs may be more effective than simple exercise interventions, especially if they involve workplace stakeholder engagement, communication and coordination with employers and other stakeholders. The development and utilization of standardized definitions, methods and measures and blinded evaluation would improve research quality

  15. Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells.

    PubMed

    Montoya, Carlos J; Jie, Hyun-Bae; Al-Harthi, Lena; Mulder, Candice; Patiño, Pablo J; Rugeles, María T; Krieg, Arthur M; Landay, Alan L; Wilson, S Brian

    2006-07-15

    CD1d-restricted invariant NK T (iNKT) cells and dendritic cells (DCs) have been shown to play crucial roles in various types of immune responses, including TLR9-dependent antiviral responses initiated by plasmacytoid DCs (pDCs). However, the mechanism by which this occurs is enigmatic because TLRs are absent in iNKT cells and human pDCs do not express CD1d. To explore this process, pDCs were activated with CpG oligodeoxyribonucleotides, which stimulated the secretion of several cytokines such as type I and TNF-alpha. These cytokines and other soluble factors potently induced the expression of activation markers on iNKT cells, selectively enhanced double-negative iNKT cell survival, but did not induce their expansion or production of cytokines. Notably, pDC-derived factors licensed iNKT cells to respond to myeloid DCs: an important downstream cellular target of iNKT cell effector function and a critical contributor to the initiation of adaptive immune responses. This interaction supports the notion that iNKT cells can mediate cross-talk between DC subsets known to express mutually exclusive TLR and cytokine profiles.

  16. Assessment of Myeloperoxidase Activity by the Conversion of Hydroethidine to 2-Chloroethidium*

    PubMed Central

    Maghzal, Ghassan J.; Cergol, Katie M.; Shengule, Sudhir R.; Suarna, Cacang; Newington, Darren; Kettle, Anthony J.; Payne, Richard J.; Stocker, Roland

    2014-01-01

    Oxidants derived from myeloperoxidase (MPO) contribute to inflammatory diseases. In vivo MPO activity is commonly assessed by the accumulation of 3-chlorotyrosine (3-Cl-Tyr), although 3-Cl-Tyr is formed at low yield and is subject to metabolism. Here we show that MPO activity can be assessed using hydroethidine (HE), a probe commonly employed for the detection of superoxide. Using LC/MS/MS, 1H NMR, and two-dimensional NOESY, we identified 2-chloroethidium (2-Cl-E+) as a specific product when HE was exposed to hypochlorous acid (HOCl), chloramines, MPO/H2O2/chloride, and activated human neutrophils. The rate constant for HOCl-mediated conversion of HE to 2-Cl-E+ was estimated to be 1.5 × 105 m−1s−1. To investigate the utility of 2-Cl-E+ to assess MPO activity in vivo, HE was injected into wild-type and MPO-deficient (Mpo−/−) mice with established peritonitis or localized arterial inflammation, and tissue levels of 2-Cl-E+ and 3-Cl-Tyr were then determined by LC/MS/MS. In wild-type mice, 2-Cl-E+ and 3-Cl-Tyr were detected readily in the peritonitis model, whereas in the arterial inflammation model 2-Cl-E+ was present at comparatively lower concentrations (17 versus 0.3 pmol/mg of protein), and 3-Cl-Tyr could not be detected. Similar to the situation with 3-Cl-Tyr, tissue levels of 2-Cl-E+ were decreased substantially in Mpo−/− mice, indicative of the specificity of the assay. In the arterial inflammation model, 2-Cl-E+ was absent from non-inflamed arteries and blood, suggesting that HE oxidation occurred locally in the inflamed artery. Our data suggest that the conversion of exogenous HE to 2-Cl-E+ may be a useful selective and sensitive marker for MPO activity in addition to 3-Cl-Tyr. PMID:24436331

  17. Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report.

    PubMed

    Wang, Dong; Tian, Min; Cui, Guanglin; Wang, Dao Wen

    2018-06-01

    Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in SERPINC1 and PROC lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of PROC and SERPINC1 were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in SERPINC1 and a short deletion variant c.572_574delAGA in PROC. This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the SERPINC1 and PROC gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.

  18. Biologically Inspired Visual Model With Preliminary Cognition and Active Attention Adjustment.

    PubMed

    Qiao, Hong; Xi, Xuanyang; Li, Yinlin; Wu, Wei; Li, Fengfu

    2015-11-01

    Recently, many computational models have been proposed to simulate visual cognition process. For example, the hierarchical Max-Pooling (HMAX) model was proposed according to the hierarchical and bottom-up structure of V1 to V4 in the ventral pathway of primate visual cortex, which could achieve position- and scale-tolerant recognition. In our previous work, we have introduced memory and association into the HMAX model to simulate visual cognition process. In this paper, we improve our theoretical framework by mimicking a more elaborate structure and function of the primate visual cortex. We will mainly focus on the new formation of memory and association in visual processing under different circumstances as well as preliminary cognition and active adjustment in the inferior temporal cortex, which are absent in the HMAX model. The main contributions of this paper are: 1) in the memory and association part, we apply deep convolutional neural networks to extract various episodic features of the objects since people use different features for object recognition. Moreover, to achieve a fast and robust recognition in the retrieval and association process, different types of features are stored in separated clusters and the feature binding of the same object is stimulated in a loop discharge manner and 2) in the preliminary cognition and active adjustment part, we introduce preliminary cognition to classify different types of objects since distinct neural circuits in a human brain are used for identification of various types of objects. Furthermore, active cognition adjustment of occlusion and orientation is implemented to the model to mimic the top-down effect in human cognition process. Finally, our model is evaluated on two face databases CAS-PEAL-R1 and AR. The results demonstrate that our model exhibits its efficiency on visual recognition process with much lower memory storage requirement and a better performance compared with the traditional purely computational

  19. Characterization of hsp27 kinases activated by elevated aortic pressure in heart

    PubMed Central

    Boivin, Benoit; Khairallah, Maya; Cartier, Raymond; Allen, Bruce G.

    2013-01-01

    Chronic hemodynamic overload results in left ventricular hypertrophy, fibroblast proliferation, and interstitial fibrosis. The small heat shock protein hsp27 has been shown to be cardioprotective and this requires a phosphorylatable form of this protein. To further understand the regulation of hsp27 in heart in response to stress, we investigated the ability of elevated aortic pressure to activate hsp27-kinase activities. Isolated hearts were subjected to retrograde perfusion and then snap-frozen. Hsp27-kinase activity was measured in vitro as hsp27 phosphorylation. Immune complex assays revealed that MK2 activity was low in non-perfused hearts and increased following crystalline perfusion at 60 or 120 mmHg. Hsp27-kinase activities were further studied following ion-exchange chromatography. Anion exchange chromatography on Mono Q revealed 2 peaks (‘b’ and ‘c’) of hsp27-kinase activity. A third peak ‘a’ was detected upon chromatography of the Mono Q flow-through fractions on the cation exchange resin, Mono S. The hsp27-kinase activity underlying peaks ‘a’ and ‘c’ increased as perfusion pressure was increased from 40 to 120 mmHg. In contrast, peak ‘b’ increased over pressures 60–100 mmHg but was decreased at 120 mmHg. Peaks ‘a’, ‘b’, and ‘c’ contained MK2 immunoreactivity, whereas MK3 and MK5 immunoreactivity was detected in peak ‘a’. p38 MAPK and phospho-p38 MAPK were also detected in peaks ‘b’ and ‘c’ but absent from peak ‘a’. Hsp27-kinase activity in peaks ‘b’ and ‘c’ (120 mmHg) eluted from a Superose 12 gel filtration column with an apparent molecular mass of 50-kDa. Hence, peaks ‘b’ and ‘c’ were not a result of MK2 forming complexes. In-gel hsp27-kinase assays revealed a single 49-kDa renaturable hsp27-kinase activity in peaks ‘b’ and ‘c’ at 60 mmHg, whereas several hsp27-kinases (p43, p49, p54, p66) were detected in peaks ‘b’ and ‘c’ from hearts perfused at 120 mmHg. Thus

  20. Sympathetic activation in exercise is not dependent on muscle acidosis. Direct evidence from studies in metabolic myopathies

    NASA Technical Reports Server (NTRS)

    Vissing, J.; Vissing, S. F.; MacLean, D. A.; Saltin, B.; Quistorff, B.; Haller, R. G.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    Muscle acidosis has been implicated as a major determinant of reflex sympathetic activation during exercise. To test this hypothesis we studied sympathetic exercise responses in metabolic myopathies in which muscle acidosis is impaired or augmented during exercise. As an index of reflex sympathetic activation to muscle, microneurographic measurements of muscle sympathetic nerve activity (MSNA) were obtained from the peroneal nerve. MSNA was measured during static handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in patients in whom exercise-induced muscle acidosis is absent (seven myophosphorylase deficient patients; MD [McArdle's disease], and one patient with muscle phosphofructokinase deficiency [PFKD]), augmented (one patient with mitochondrial myopathy [MM]), or normal (five healthy controls). Muscle pH was monitored by 31P-magnetic resonance spectroscopy during handgrip exercise in the five control subjects, four MD patients, and the MM and PFKD patients. With handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute [bpm] and total activity [%]) was not impaired in patients with MD (17+/-2 bpm, 124+/-42%) or PFKD (65 bpm, 307%), and was not enhanced in the MM patient (24 bpm, 131%) compared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia studied in one McArdle patient, caused sustained elevation of MSNA above basal suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an enhanced drop in muscle pH of 0.51 U in the MM patient compared with the decrease in controls of 0.13+/-0.02 U. In contrast, muscle pH increased with exercise in MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with glycogenolytic, glycolytic, and oxidative phosphorylation defects show normal muscle sympathetic nerve responses to static exercise. These findings indicate that muscle acidosis is not a prerequisite for sympathetic activation in exercise.

  1. Meeting the Challenge: Creating Engaging and Powerful Contexts for Literacy Learning

    ERIC Educational Resources Information Center

    Wilhelm, Jeffrey D.

    2007-01-01

    This article explores the conditions of "flow" experience from two studies into the literate lives of young men (Smith and Wilhelm 2002; 2006) that were explanatory, when present, of motivation and engagement in various activities including literacy, and when absent, of a lack of motivation and engagement in various activities including literacy.…

  2. The Relationship between Student Self-Regulation Strategies and Increased Student Achievement: A Study on How the Explicit Integration of Self-Regulation Strategies Impacts Student Reading Achievement in the Elementary Classroom

    ERIC Educational Resources Information Center

    Egan, Patti A.

    2017-01-01

    Student ownership in learning is a topic that has become quite prevalent in recent years. While emphasis has grown on the importance of active student involvement in learning, integration of student self-regulation strategies is often absent in elementary classrooms. A paradigm shift that encourages active involvement of students in the learning…

  3. Immunogenic Activity of a Ribosomal Fraction Obtained from Mycobacterium tuberculosis

    PubMed Central

    Youmans, Anne S.; Youmans, Guy P.

    1965-01-01

    Youmans, Anne S. (Northwestern University Medical School, Chicago, Ill.), and Guy P. Youmans. Immunogenic activity of a ribosomal fraction obtained from Mycobacterium tuberculosis. J. Bacteriol. 89:1291–1298. 1965.—The highly immunogenic particulate fraction obtained from mechanically ruptured cells of the H37Ra strain of Mycobacterium tuberculosis was suspended and centrifuged at 20,360 × g. The supernatant liquid from this centrifugation was centrifuged at 56,550 × g to remove the larger particles, and the supernatant liquid from this was centrifuged at 144,000 × g to obtain a ribosomal fraction. The sediments from the first two centrifugations were highly immunogenic, but the ribosomal fraction showed only slight capacity to immunize mice. However, when the ribosomal fraction was mixed with Freund's incomplete adjuvant, the immunogenic activity was equivalent to the particulate fraction from which it was prepared. To test the hypothesis that some membranous substance in the particulate fraction was acting as an adjuvant for the smaller particles in the ribosomal fraction, portions of the particulate fraction were treated separately with each of the membrane-disrupting agents, sodium deoxycholate, sodium lauryl sulfate, and 1 m sodium chloride. The treated materials were then centrifuged at 144,000 × g, and the sediments were tested for immunogenicity both with and without the addition of Freund's incomplete adjuvant. Without the adjuvant, the immunizing activities were very weak or absent; with the adjuvant, they were equivalent to that of the particulate fraction from which they were prepared. Other factors which have been found to damage or destroy membranes, such as freezing and thawing, and heat, also significantly decreased the immunogenic activity of the particulate fraction unless it was incorporated into Freund's incomplete adjuvant. The larger particles which sedimented at 56,550 × g were also treated with sodium lauryl sulfate and sodium

  4. Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands

    PubMed Central

    Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon

    2015-01-01

    Background Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. Objective To evaluate the basic physiological role of PAR-2 in skin. Methods We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Results Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Conclusion Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands. PMID:26273149

  5. Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands.

    PubMed

    Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon; Lee, Young Ho

    2015-08-01

    Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. To evaluate the basic physiological role of PAR-2 in skin. We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.

  6. QM/MM simulations identify the determinants of catalytic activity differences between type II dehydroquinase enzymes.

    PubMed

    Lence, Emilio; van der Kamp, Marc W; González-Bello, Concepción; Mulholland, Adrian J

    2018-05-16

    Type II dehydroquinase enzymes (DHQ2), recognized targets for antibiotic drug discovery, show significantly different activities dependent on the species: DHQ2 from Mycobacterium tuberculosis (MtDHQ2) and Helicobacter pylori (HpDHQ2) show a 50-fold difference in catalytic efficiency. Revealing the determinants of this activity difference is important for our understanding of biological catalysis and further offers the potential to contribute to tailoring specificity in drug design. Molecular dynamics simulations using a quantum mechanics/molecular mechanics potential, with correlated ab initio single point corrections, identify and quantify the subtle determinants of the experimentally observed difference in efficiency. The rate-determining step involves the formation of an enolate intermediate: more efficient stabilization of the enolate and transition state of the key step in MtDHQ2, mainly by the essential residues Tyr24 and Arg19, makes it more efficient than HpDHQ2. Further, a water molecule, which is absent in MtDHQ2 but involved in generation of the catalytic Tyr22 tyrosinate in HpDHQ2, was found to destabilize both the transition state and the enolate intermediate. The quantification of the contribution of key residues and water molecules in the rate-determining step of the mechanism also leads to improved understanding of higher potencies and specificity of known inhibitors, which should aid ongoing inhibitor design.

  7. Active eye fixation performance in 940 young men: effects of IQ, schizotypy, anxiety and depression.

    PubMed

    Smyrnis, N; Kattoulas, E; Evdokimidis, I; Stefanis, N C; Avramopoulos, D; Pantes, G; Theleritis, C; Stefanis, C N

    2004-05-01

    A total of 940 young men performed a task in which they actively maintained fixation for 50 s in three conditions: a). on a visual target, b). on a visual target while distracting targets appeared briefly on the periphery and c). with no visual target present. The same individuals completed psychometric evaluation tests measuring IQ, schizotypy and current state-dependent psychopathology. The proportion of fixation time decreased and saccade frequency increased in condition b compared wih condition a, and sequentially in condition c compared with condition b. A trend towards a decrease in proportion of fixation time and increase in saccade frequency was found as the subjects maintained fixation during the task and this time-dependent deterioration of performance was again most pronounced in condition c, less so in condition b and absent in condition a. Psychometric test scores were significantly correlated with fixation performance in the population. Worse performance in all three fixation conditions was observed for individuals with lower IQ scores. A deterioration of fixation performance with time in condition b was correlated with disorganization characteristics of schizotypy, suggesting that these individuals had difficulty maintaining active fixation in the presence of increased inhibitory load. A connection of such a difficulty with the frontal lobes and their role in the control of voluntary inhibitory functions is discussed.

  8. Lineage-specific SoxR-mediated Regulation of an Endoribonuclease Protects Non-enteric Bacteria from Redox-active Compounds*

    PubMed Central

    Kim, Jisun; Park, Chulwoo; Imlay, James A.; Park, Woojun

    2017-01-01

    Bacteria use redox-sensitive transcription factors to coordinate responses to redox stress. The [2Fe-2S] cluster-containing transcription factor SoxR is particularly tuned to protect cells against redox-active compounds (RACs). In enteric bacteria, SoxR is paired with a second transcription factor, SoxS, that activates downstream effectors. However, SoxS is absent in non-enteric bacteria, raising questions as to how SoxR functions. Here, we first show that SoxR of Acinetobacter oleivorans displayed similar activation profiles in response to RACs as did its homolog from Escherichia coli but controlled a different set of target genes, including sinE, which encodes an endoribonuclease. Expression, gel mobility shift, and mutational analyses indicated that sinE is a direct target of SoxR. Redox potentials and permeability of RACs determined optimal sinE induction. Bioinformatics suggested that only a few γ- and β-proteobacteria might have SoxR-regulated sinE. Purified SinE, in the presence of Mg2+ ions, degrades rRNAs, thus inhibiting protein synthesis. Similarly, pretreatment of cells with RACs demonstrated a role for SinE in promoting persistence in the presence of antibiotics that inhibit protein synthesis. Our data improve our understanding of the physiology of soil microorganisms by suggesting that both non-enteric SoxR and its target SinE play protective roles in the presence of RACs and antibiotics. PMID:27895125

  9. Envelope statistics of self-motion signals experienced by human subjects during everyday activities: Implications for vestibular processing.

    PubMed

    Carriot, Jérome; Jamali, Mohsen; Cullen, Kathleen E; Chacron, Maurice J

    2017-01-01

    There is accumulating evidence that the brain's neural coding strategies are constrained by natural stimulus statistics. Here we investigated the statistics of the time varying envelope (i.e. a second-order stimulus attribute that is related to variance) of rotational and translational self-motion signals experienced by human subjects during everyday activities. We found that envelopes can reach large values across all six motion dimensions (~450 deg/s for rotations and ~4 G for translations). Unlike results obtained in other sensory modalities, the spectral power of envelope signals decreased slowly for low (< 2 Hz) and more sharply for high (>2 Hz) temporal frequencies and thus was not well-fit by a power law. We next compared the spectral properties of envelope signals resulting from active and passive self-motion, as well as those resulting from signals obtained when the subject is absent (i.e. external stimuli). Our data suggest that different mechanisms underlie deviation from scale invariance in rotational and translational self-motion envelopes. Specifically, active self-motion and filtering by the human body cause deviation from scale invariance primarily for translational and rotational envelope signals, respectively. Finally, we used well-established models in order to predict the responses of peripheral vestibular afferents to natural envelope stimuli. We found that irregular afferents responded more strongly to envelopes than their regular counterparts. Our findings have important consequences for understanding the coding strategies used by the vestibular system to process natural second-order self-motion signals.

  10. Envelope statistics of self-motion signals experienced by human subjects during everyday activities: Implications for vestibular processing

    PubMed Central

    Carriot, Jérome; Jamali, Mohsen; Cullen, Kathleen E.

    2017-01-01

    There is accumulating evidence that the brain’s neural coding strategies are constrained by natural stimulus statistics. Here we investigated the statistics of the time varying envelope (i.e. a second-order stimulus attribute that is related to variance) of rotational and translational self-motion signals experienced by human subjects during everyday activities. We found that envelopes can reach large values across all six motion dimensions (~450 deg/s for rotations and ~4 G for translations). Unlike results obtained in other sensory modalities, the spectral power of envelope signals decreased slowly for low (< 2 Hz) and more sharply for high (>2 Hz) temporal frequencies and thus was not well-fit by a power law. We next compared the spectral properties of envelope signals resulting from active and passive self-motion, as well as those resulting from signals obtained when the subject is absent (i.e. external stimuli). Our data suggest that different mechanisms underlie deviation from scale invariance in rotational and translational self-motion envelopes. Specifically, active self-motion and filtering by the human body cause deviation from scale invariance primarily for translational and rotational envelope signals, respectively. Finally, we used well-established models in order to predict the responses of peripheral vestibular afferents to natural envelope stimuli. We found that irregular afferents responded more strongly to envelopes than their regular counterparts. Our findings have important consequences for understanding the coding strategies used by the vestibular system to process natural second-order self-motion signals. PMID:28575032

  11. Online social networks that connect users to physical activity partners: a review and descriptive analysis.

    PubMed

    Nakhasi, Atul; Shen, Album Xiaotian; Passarella, Ralph Joseph; Appel, Lawrence J; Anderson, Cheryl Am

    2014-06-16

    absent were more sophisticated features that would enable greater usability, such as interactive engagement prompts (3/13, 23%) and system-created best fit activities (3/13, 23%). Several major online social networks that connect users to physical activity partners currently exist and use standardized features to achieve their goals. Future research is needed to better understand how users utilize these features and how helpful they truly are.

  12. Structural and dynamic determinants of ligand binding and regulation of cyclin-dependent kinase 5 by pathological activator p25 and inhibitory peptide CIP.

    PubMed

    Cardone, A; Hassan, S A; Albers, R W; Sriram, R D; Pant, H C

    2010-08-20

    The crystal structure of the cdk5/p25 complex has provided information on possible molecular mechanisms of the ligand binding, specificity, and regulation of the kinase. Comparative molecular dynamics simulations are reported here for physiological conditions. This study provides new insight on the mechanisms that modulate such processes, which may be exploited to control pathological activation by p25. The structural changes observed in the kinase are stabilized by a network of interactions involving highly conserved residues within the cyclin-dependent kinase (cdk) family. Collective motions of the proteins (cdk5, p25, and CIP) and their complexes are identified by principal component analysis, revealing two conformational states of the activation loop upon p25 complexation, which are absent in the uncomplexed kinase and not apparent from the crystal. Simulations of the uncomplexed inhibitor CIP show structural rearrangements and increased flexibility of the interfacial loop containing the critical residue E240, which becomes fully hydrated and available for interactions with one of several positively charged residues in the kinase. These changes provide a rationale for the observed high affinity and enhanced inhibitory action of CIP when compared to either p25 or the physiological activators of cdk5. Published by Elsevier Ltd.

  13. O6-methylguanine-DNA methyltransferase activity is associated with response to alkylating agent therapy and with MGMT promoter methylation in glioblastoma and anaplastic glioma

    PubMed Central

    Bobola, Michael S.; Alnoor, Mohammad; Chen, John Y.-S.; Kolstoe, Douglas D.; Silbergeld, Daniel L.; Rostomily, Robert C.; Blank, A.; Chamberlain, Marc C.; Silber, John R.

    2014-01-01

    Background CpG methylation in the O6-methylguanine-DNA methyltransferase (MGMT) promoter is associated with better outcome following alkylating agent chemotherapy in glioblastoma (GBM) and anaplastic glioma (AG). To what extent improved response reflects low or absent MGMT activity in glioma tissue has not been unequivocally assessed. This information is central to developing anti-resistance therapies. Methods We examined the relationship of MGMT activity in 91 GBMs and 84 AGs with progression-free survival (PFS) following alkylator therapy and with promoter methylation status determined by methylation-specific PCR (MSP). Results Cox regression analysis revealed that GBMs with high activity had a significantly greater risk for progression in dichotomous (P ≤ 0.001) and continuous (P ≤ 0.003) models, an association observed for different alkylator regimens, including concurrent chemo-radiation with temozolomide. Analysis of MGMT promoter methylation status in 47 of the GBMs revealed that methylated tumors had significantly lower activity (P ≤ 0.005) and longer PFS (P ≤ 0.036) compared to unmethylated tumors, despite overlapping activities. PFS was also significantly greater in methylated vs. unmethylated GBMs with comparable activity (P ≤ 0.005), and among unmethylated tumors with less than median activity (P ≤ 0.026), suggesting that mechanisms in addition to MGMT promote alkylator resistance. Similar associations of MGMT activity with PFS and promoter methylation status were observed for AGs. Conclusions Our results provide strong support for the hypotheses that MGMT activity promotes alkylator resistance and reflects promoter methylation status in malignant gliomas. General significance MGMT activity is an attractive target for anti-resistance therapy regardless of methylation status. PMID:25558448

  14. Maintenance of neuronal size gradient in MNTB requires sound-evoked activity.

    PubMed

    Weatherstone, Jessica H; Kopp-Scheinpflug, Conny; Pilati, Nadia; Wang, Yuan; Forsythe, Ian D; Rubel, Edwin W; Tempel, Bruce L

    2017-02-01

    The medial nucleus of the trapezoid body (MNTB) is an important source of inhibition during the computation of sound location. It transmits fast and precisely timed action potentials at high frequencies; this requires an efficient calcium clearance mechanism, in which plasma membrane calcium ATPase 2 (PMCA2) is a key component. Deafwaddler ( dfw 2J ) mutant mice have a null mutation in PMCA2 causing deafness in homozygotes ( dfw 2J / dfw 2J ) and high-frequency hearing loss in heterozygotes (+/ dfw 2J ). Despite the deafness phenotype, no significant differences in MNTB volume or cell number were observed in dfw 2J homozygous mutants, suggesting that PMCA2 is not required for MNTB neuron survival. The MNTB tonotopic axis encodes high to low sound frequencies across the medial to lateral dimension. We discovered a cell size gradient along this axis: lateral neuronal somata are significantly larger than medially located somata. This size gradient is decreased in +/ dfw 2J and absent in dfw 2J / dfw 2J The lack of acoustically driven input suggests that sound-evoked activity is required for maintenance of the cell size gradient. This hypothesis was corroborated by selective elimination of auditory hair cell activity with either hair cell elimination in Pou4f3 DTR mice or inner ear tetrodotoxin (TTX) treatment. The change in soma size was reversible and recovered within 7 days of TTX treatment, suggesting that regulation of the gradient is dependent on synaptic activity and that these changes are plastic rather than permanent. NEW & NOTEWORTHY Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The MNTB is topographically organized, with low sound frequencies encoded laterally and high frequencies medially. We discovered a cell size gradient along this axis: lateral neurons are larger than medial neurons. The absence of this gradient in deaf mice lacking plasma membrane calcium ATPase 2

  15. Measuring everyday functional competence using the Rasch assessment of everyday activity limitations (REAL) item bank.

    PubMed

    Oude Voshaar, Martijn A H; Ten Klooster, Peter M; Vonkeman, Harald E; van de Laar, Mart A F J

    2017-11-01

    Traditional patient-reported physical function instruments often poorly differentiate patients with mild-to-moderate disability. We describe the development and psychometric evaluation of a generic item bank for measuring everyday activity limitations in outpatient populations. Seventy-two items generated from patient interviews and mapped to the International Classification of Functioning, Disability and Health (ICF) domestic life chapter were administered to 1128 adults representative of the Dutch population. The partial credit model was fitted to the item responses and evaluated with respect to its assumptions, model fit, and differential item functioning (DIF). Measurement performance of a computerized adaptive testing (CAT) algorithm was compared with the SF-36 physical functioning scale (PF-10). A final bank of 41 items was developed. All items demonstrated acceptable fit to the partial credit model and measurement invariance across age, sex, and educational level. Five- and ten-item CAT simulations were shown to have high measurement precision, which exceeded that of SF-36 physical functioning scale across the physical function continuum. Floor effects were absent for a 10-item empirical CAT simulation, and ceiling effects were low (13.5%) compared with SF-36 physical functioning (38.1%). CAT also discriminated better than SF-36 physical functioning between age groups, number of chronic conditions, and respondents with or without rheumatic conditions. The Rasch assessment of everyday activity limitations (REAL) item bank will hopefully prove a useful instrument for assessing everyday activity limitations. T-scores obtained using derived measures can be used to benchmark physical function outcomes against the general Dutch adult population.

  16. Antioxidative capacity and enzyme activity in Haematococcus pluvialis cells exposed to superoxide free radicals

    NASA Astrophysics Data System (ADS)

    Liu, Jianguo; Zhang, Xiaoli; Sun, Yanhong; Lin, Wei

    2010-01-01

    The antioxidative capacity of astaxanthin and enzyme activity of reactive oxygen eliminating enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) were studied in three cell types of Haematococcus pluvialis exposed to high concentrations of a superoxide anion radical (O{2/-}). The results show that defensive enzymes and astaxanthin-related mechanisms were both active in H. pluvialis during exposure to reactive oxygen species (ROS) such as O{2/-}. Astaxanthin reacted with ROS much faster than did the protective enzymes, and had the strongest antioxidative capacity to protect against lipid peroxidation. The defensive mechanisms varied significantly between the three cell types and were related to the level of astaxanthin that had accumulated in those cells. Astaxanthin-enriched red cells had the strongest antioxidative capacity, followed by brown cells, and astaxanthin-deficient green cells. Although there was no significant increase in expression of protective enzymes, the malondialdehyde (MDA) content in red cells was sustained at a low level because of the antioxidative effect of astaxanthin, which quenched O{2/-} before the protective enzymes could act. In green cells, astaxanthin is very low or absent; therefore, scavenging of ROS is inevitably reliant on antioxidative enzymes. Accordingly, in green cells, these enzymes play the leading role in scavenging ROS, and the expression of these enzymes is rapidly increased to reduce excessive ROS. However, because ROS were constantly increased in this study, the enhance enzyme activity in the green cells was not able to repair the ROS damage, leading to elevated MDA content. Of the four defensive enzymes measured in astaxanthin-deficient green cells, SOD eliminates O{2/-}, POD eliminates H2O2, which is a by-product of SOD activity, and APX and CAT are then initiated to scavenge excessive ROS.

  17. Transcription of fgf8 is regulated by activating and repressive cis-elements at the midbrain-hindbrain boundary in zebrafish embryos.

    PubMed

    Inoue, Fumitaka; Parvin, Mst Shahnaj; Yamasu, Kyo

    2008-04-15

    Fgf8 is expressed in the isthmic region of the developing brain, serving an organizing function in vertebrate embryos. We previously identified S4.2 downstream to the zebrafish fgf8 gene as a regulatory region that drives transcription in the anterior hindbrain. Here, we investigated the mechanism of fgf8 regulation by the S4.2 region during development. Reporter analyses in embryos revealed that S4.2 closely recapitulates fgf8 expression in the anteriormost hindbrain during somitogenesis. This region contains a sequence highly conserved in fgf8 of diverse vertebrates. Further analyses of S4.2 revealed a 342-bp core region composed of three subregions (#2, #3, and #4). Regions #3 and #4 drove expression broadly in the brain from the midbrain to r5 of the hindbrain, whereas a 28-bp sequence in #2 repressed ectopic expression in the midbrain and in r2 to r5. The enhancer function of S4.2 was absent in pax2a mutant embryos, while it was activated ectopically by pax2a misexpression in the hindbrain. We identified two sites in the core region that are bound by Pax2a in vitro and in vivo, the disruption of which abrogated the S4.2 activity. Thus, fgf8 expression in the anteriormost hindbrain involves activation and repression, with Pax2a as a pivotal regulator.

  18. Functional significance of the intermediate conductance Ca2+-activated K+ channel for the short-term survival of injured erythrocytes.

    PubMed

    Föller, Michael; Bobbala, Diwakar; Koka, Saisudha; Boini, Krishna M; Mahmud, Hasan; Kasinathan, Ravi S; Shumilina, Ekaterina; Amann, Kerstin; Beranek, Golo; Sausbier, Ulrike; Ruth, Peter; Sausbier, Matthias; Lang, Florian; Huber, Stephan M

    2010-11-01

    Increased cytosolic Ca(2+) concentrations activate Gardos K(+) channels in human erythrocytes with membrane hyperpolarization, efflux of K(+), Cl⁻, and osmotically obliged H₂O resulting in cell shrinkage, a phenomenon referred to as Gardos effect. We tested whether the Gardos effect delays colloid osmotic hemolysis of injured erythrocytes from mice lacking the Ca(2+)-activated K(+) channel K(Ca)3.1. To this end, we applied patch clamp and flow cytometry and determined in vitro as well as in vivo hemolysis. As a result, erythrocytes from K(Ca)3.1-deficient (K(Ca)3.1(-/-)) mice lacked Gardos channel activity and the Gardos effect. Blood parameters, reticulocyte count, or osmotic erythrocyte resistance, however, did not differ between K(Ca)3.1(-/-) mice and their wild-type littermates, suggesting low or absent Gardos channel activity in unstressed erythrocytes. Oxidative stress-induced Ca(2+) entry and phospholipid scrambling were significantly less pronounced in K(Ca)3.1(-/-) than in wild-type erythrocytes. Moreover, in vitro treatment with α-toxin from Staphylococcus aureus, which forms pores in the cellular membrane, resulted in significantly stronger hemolysis of K(Ca)3.1(-/-) than of wild-type erythrocytes. Intravenous injection of α-toxin induced more profound hemolysis in K(Ca)3.1(-/-) than in wild-type mice. Similarly, intra-peritoneal application of the redox-active substance phenylhydrazine, an agent for the induction of hemolytic anemia, was followed by a significantly stronger decrease of hematocrit in K(Ca)3.1(-/-) than in wild-type mice. Finally, malaria infection triggered the activation of K(Ca)3.1 and transient shrinkage of the infected erythrocytes. In conclusion, K(Ca)3.1 channel activity and Gardos effect counteract hemolysis of injured erythrocytes, thus decreasing hemoglobin release into circulating blood.

  19. Isozvme specificity during germination and early growth of knobcone pine

    Treesearch

    M. Thompson Conkle

    1971-01-01

    Five enzyme classes from 11 developmental stages of germinating embryos were separated by starch gel electrophoresis. Alcohol dehydrogenase isozymes found in embryos of dry seed were most active at the time of radicle emergence; activity decreased thereafter, fading below the level of detection when seed coats were shed. Peroxidase isozymes were absent and esterase...

  20. Achilles tendon shape and echogenicity on ultrasound among active badminton players.

    PubMed

    Malliaras, P; Voss, C; Garau, G; Richards, P; Maffulli, N

    2012-04-01

    The relationship between Achilles tendon ultrasound abnormalities, including a spindle shape and heterogeneous echogenicity, is unclear. This study investigated the relationship between these abnormalities, tendon thickness, Doppler flow and pain. Sixty-one badminton players (122 tendons, 36 men, and 25 women) were recruited. Achilles tendon thickness, shape (spindle, parallel), echogenicity (heterogeneous, homogeneous) and Doppler flow (present or absent) were measured bilaterally with ultrasound. Achilles tendon pain (during or after activity over the last week) and pain and function [Victorian Institute of Sport Achilles Assessment (VISA-A)] were measured. Sixty-eight (56%) tendons were parallel with homogeneous echogenicity (normal), 22 (18%) were spindle shaped with homogeneous echogenicity, 16 (13%) were parallel with heterogeneous echogenicity and 16 (13%) were spindle shaped with heterogeneous echogenicity. Spindle shape was associated with self-reported pain (P<0.05). Heterogeneous echogenicity was associated with lower VISA-A scores than normal tendon (P<0.05). There was an ordinal relationship between normal tendon, parallel and heterogeneous and spindle shaped and heterogeneous tendons with regard to increasing thickness and likelihood of Doppler flow. Heterogeneous echogenicity with a parallel shape may be a physiological phase and may develop into heterogeneous echogenicity with a spindle shape that is more likely to be pathological. © 2010 John Wiley & Sons A/S.

  1. THE UBIQUITOUS PRESENCE OF LOOPLIKE FINE STRUCTURE INSIDE SOLAR ACTIVE REGIONS

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

    Wang, Y.-M., E-mail: yi.wang@nrl.navy.mil

    Although most of the solar surface outside active regions (ARs) is pervaded by small-scale fields of mixed polarity, this magnetic “carpet” or “junkyard” is thought to be largely absent inside AR plages and strong network. However, using extreme-ultraviolet images and line-of-sight magnetograms from the Solar Dynamics Observatory, we find that unipolar flux concentrations, both inside and outside ARs, often have small, loop-shaped Fe ix 17.1 and Fe xii 19.3 nm features embedded within them, even though no minority-polarity flux is visible in the corresponding magnetograms. Such looplike structures, characterized by horizontal sizes of ∼3–5 Mm and varying on timescales ofmore » minutes or less, are seen inside bright 17.1 nm moss, as well as in fainter moss-like regions associated with weaker network outside ARs. We also note a tendency for bright coronal loops to show compact, looplike features at their footpoints. Based on these observations, we suggest that present-day magnetograms may be substantially underrepresenting the amount of minority-polarity flux inside plages and strong network, and that reconnection between small bipoles and the overlying large-scale field could be a major source of coronal heating both in ARs and in the quiet Sun.« less

  2. GPS Based Daily Activity Patterns in European Red Deer and North American Elk (Cervus elaphus): Indication for a Weak Circadian Clock in Ungulates

    PubMed Central

    Ensing, Erik P.; Ciuti, Simone; de Wijs, Freek A. L. M.; Lentferink, Dennis H.; ten Hoedt, André; Boyce, Mark S.; Hut, Roelof A.

    2014-01-01

    Long-term tracking using global positioning systems (GPS) is widely used to study vertebrate movement ecology, including fine-scale habitat selection as well as large-scale migrations. These data have the potential to provide much more information about the behavior and ecology of wild vertebrates: here we explore the potential of using GPS datasets to assess timing of activity in a chronobiological context. We compared two different populations of deer (Cervus elaphus), one in the Netherlands (red deer), the other in Canada (elk). GPS tracking data were used to calculate the speed of the animals as a measure for activity to deduce unbiased daily activity rhythms over prolonged periods of time. Speed proved a valid measure for activity, this being validated by comparing GPS based activity data with head movements recorded by activity sensors, and the use of GPS locations was effective for generating long term chronobiological data. Deer showed crepuscular activity rhythms with activity peaks at sunrise (the Netherlands) or after sunrise (Canada) and at the end of civil twilight at dusk. The deer in Canada were mostly diurnal while the deer in the Netherlands were mostly nocturnal. On an annual scale, Canadian deer were more active during the summer months while deer in the Netherlands were more active during winter. We suggest that these differences were mainly driven by human disturbance (on a daily scale) and local weather (on an annual scale). In both populations, the crepuscular activity peaks in the morning and evening showed a stable timing relative to dawn and dusk twilight throughout the year, but marked periods of daily a-rhythmicity occurred in the individual records. We suggest that this might indicate that (changes in) light levels around twilight elicit a direct behavioral response while the contribution of an internal circadian timing mechanism might be weak or even absent. PMID:25208246

  3. GPS based daily activity patterns in European red deer and North American elk (Cervus elaphus): indication for a weak circadian clock in ungulates.

    PubMed

    Ensing, Erik P; Ciuti, Simone; de Wijs, Freek A L M; Lentferink, Dennis H; Ten Hoedt, André; Boyce, Mark S; Hut, Roelof A

    2014-01-01

    Long-term tracking using global positioning systems (GPS) is widely used to study vertebrate movement ecology, including fine-scale habitat selection as well as large-scale migrations. These data have the potential to provide much more information about the behavior and ecology of wild vertebrates: here we explore the potential of using GPS datasets to assess timing of activity in a chronobiological context. We compared two different populations of deer (Cervus elaphus), one in the Netherlands (red deer), the other in Canada (elk). GPS tracking data were used to calculate the speed of the animals as a measure for activity to deduce unbiased daily activity rhythms over prolonged periods of time. Speed proved a valid measure for activity, this being validated by comparing GPS based activity data with head movements recorded by activity sensors, and the use of GPS locations was effective for generating long term chronobiological data. Deer showed crepuscular activity rhythms with activity peaks at sunrise (the Netherlands) or after sunrise (Canada) and at the end of civil twilight at dusk. The deer in Canada were mostly diurnal while the deer in the Netherlands were mostly nocturnal. On an annual scale, Canadian deer were more active during the summer months while deer in the Netherlands were more active during winter. We suggest that these differences were mainly driven by human disturbance (on a daily scale) and local weather (on an annual scale). In both populations, the crepuscular activity peaks in the morning and evening showed a stable timing relative to dawn and dusk twilight throughout the year, but marked periods of daily a-rhythmicity occurred in the individual records. We suggest that this might indicate that (changes in) light levels around twilight elicit a direct behavioral response while the contribution of an internal circadian timing mechanism might be weak or even absent.

  4. 2011 Final Report - Nano-Oxide Photocatalysis for Solar Energy Conversion

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

    Eckstein, James N.; Suslick, Kenneth S.

    2011-10-19

    We have very recently discovered a new hydrogen-producing photocatalyst is BiNbO4. BiNbO4 powders prepared by solid state reaction were tested for photocatalytic activity in methanol solutions under UV irradiation. When the material is tested without the presence of a Pt co-catalyst, photocatalytic activity for H2 evolution is superior to that of TiO2. It was also found that BiNbO4 photodegrades into metallic Bi and reduced Nb oxides after use; materials were characterized by SEM, XRD, and XPS. Adding Pt to the surface of the photocatalyst increases photocatalytic activity and importantly, helps to prevent photodegradation of the oxide material. With 1 wt.more » % Pt loading, photodegradation is essentially absent. BiNbO4 photodegrades into metallic Bi and reduced Nb oxides after use; materials were characterized by SEM, XRD, and XPS. Adding Pt to the surface of the photocatalyst increases photocatalytic activity and importantly, helps to prevent photodegradation of the oxide material. With 1 wt. % Pt loading, photodegradation is essentially absent.« less

  5. Cataplexy and monoamine oxidase deficiency in Norrie disease.

    PubMed

    Vossler, D G; Wyler, A R; Wilkus, R J; Gardner-Walker, G; Vlcek, B W

    1996-05-01

    Norrie disease (ND) is an X-linked recessive disorder causing ocular atrophy, mental retardation, deafness, and dysmorphic features. Virtually absent monoamine oxidase (MAO) type-A and -B activity has been found in some boys with chromosome deletions. We report the coexistence of cataplexy and abnormal REM sleep organization with ND. Three related boys, referred for treatment of medically refractory atonic spells and apneas, underwent extended EEG-video-polysomnographic monitoring. They demonstrated attacks of cataplexy and inappropriate periods of REM sleep during which they were unarousable. One boy also had generalized tonic-clonic seizures. Previous testing revealed that all three have complete ND gene deletions. In all subjects, platelet MAO-B activity was absent, serum serotonin levels were markedly increased, and plasma catecholamine levels were normal. Data from the canine narcolepsy syndrome model implicate abnormal catecholaminergic and cholinergic activities in the pathogenesis of cataplexy. Our findings suggest that abnormal MAO activity or an imbalance between serotonin and other neurotransmitter levels may be involved in the pathogenesis of human cataplexy.

  6. Interleukin-1 Receptor Activation by Systemic Lipopolysaccharide Induces Behavioral Despair Linked to MAPK Regulation of CNS Serotonin Transporters

    PubMed Central

    Zhu, Chong-Bin; Lindler, Kathryn M; Owens, Anthony W; Daws, Lynette C; Blakely, Randy D; Hewlett, William A

    2010-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) has long been implicated in regulation of mood. Medications that block the neuronal 5-HT transporter (SERT) are used as major pharmacological treatment for mood disorders. Conversely, stimuli that enhance SERT activity might be predicted to diminish synaptic 5-HT availability and increase the risk for 5-HT-related CNS disorders. We have shown that the inflammatory cytokines enhance brain SERT activity in cultured serotonergic cells and nerve terminal preparations in vitro. In this study, we establish that intraperitoneal injection of the cytokine-inducer lipopolysaccharide (LPS) stimulates brain SERT activity, acting at doses below those required to induce overt motor suppression. SERT stimulation by LPS is paralleled by increased immobility in both the tail suspension test (TST) and the forced swim test (FST); antidepressant-sensitive alterations are thought to model aspects of behavioral despair. Both the stimulation of SERT activity and induced immobility are absent when LPS is administered to interleukin-1 receptor (IL-1R)-deficient mice and in the presence of SB203580, an inhibitor of IL-1R-stimulated p38 MAPK. Moreover, the ability of LPS to enhance immobility in TST is lost in SERT knockout mice. These findings reveal an ability of peripheral inflammatory stimuli to enhance brain SERT activity through IL-1R and p38 MAPK pathways in vivo and identify a requirement for SERT expression in immune-system-modulated despair behaviors. Our studies identify IL-1R- and p38 MAPK-dependent regulation of SERT as one of the mechanisms by which environmentally driven immune system activation can trigger despair-like behavior in an animal model, encouraging future analysis of the pathway for risk factors in neuropsychiatric disorders. PMID:20827273

  7. Inactivation of vimF, a Putative Glycosyltransferase Gene Downstream of vimE, Alters Glycosylation and Activation of the Gingipains in Porphyromonas gingivalis W83

    PubMed Central

    Vanterpool, Elaine; Roy, Francis; Fletcher, Hansel M.

    2005-01-01

    Regulation/activation of the Porphyromonas gingivalis gingipains is poorly understood. A 1.2-kb open reading frame, a putative glycosyltransferase, downstream of vimE, was cloned, insertionally inactivated using the ermF-ermAM antibiotic resistance cassette, and used to create a defective mutant by allelic exchange. In contrast to the wild-type W83 strain, this mutant, designated P. gingivalis FLL95, was nonpigmented and nonhemolytic when plated on Brucella blood agar. Arginine- and lysine-specific gingipain activities were reduced by approximately 97% and 96%, respectively, relative to that of the parent strain. These activities were unaffected by the growth phase, in contrast to the vimA-defective mutant P. gingivalis FLL92. Expression of the rgpA, rgpB, and kgp gingipain genes was unaffected in P. gingivalis FLL95 in comparison to the wild-type strain. In nonactive gingipain extracellular protein fractions, multiple high-molecular-weight proteins immunoreacted with gingipain-specific antibodies. The specific gingipain-associated sugar moiety recognized by monoclonal antibody 1B5 was absent in FLL95. Taken together, these results suggest that the vimE downstream gene, designated vimF (virulence modulating gene F), which is a putative glycosyltransferase group 1, is involved in the regulation of the major virulence factors of P. gingivalis. PMID:15972484

  8. Biological and Computational Modeling of Mammographic Density and Stromal Patterning

    DTIC Science & Technology

    2010-07-01

    clumping Score Monolayer Absent Many Absent Absent Absent 1 Nucl. overlap Mild Moderate Mild Micro- nucleoli Rare 2 Clustering Moderate...Few Moderate Micro- nucleoli Occasional 3 Loss cohesion Conspicuous Absent Frequent Macro- nucleoli Frequent 4 We performed serial RPFNA

  9. Downregulation of telomerase activity by diclofenac and curcumin is associated with cell cycle arrest and induction of apoptosis in colon cancer.

    PubMed

    Rana, Chandan; Piplani, Honit; Vaish, Vivek; Nehru, Bimla; Sanyal, S N

    2015-08-01

    Uncontrolled cell proliferation is the hallmark of cancer, and cancer cells have typically acquired damage to genes that directly regulate their cell cycles. The synthesis of DNA onto the end of chromosome during the replicative phase of cell cycle by telomerase may be necessary for unlimited proliferation of cells. Telomerase, a ribonucleoprotein enzyme is considered as a universal therapeutic target of cancer because of its preferential expression in cancer cells and its presence in 90 % of tumors. We studied the regulation of telomerase and telomerase reverse transcriptase catalytic subunit (TERT) by diclofenac and curcumin, alone and also in combination, in 1, 2-dimethylhydrazine dihydrochloride-induced colorectal cancer in rats. The relationship of telomerase activity with tumors suppressor proteins (p51, Rb, p21), cell cycle machinery, and apoptosis was also studied. Telomerase is highly expressed in DMH group and its high activity is associated with increased TERT expression. However, telomerase is absent or is present at lower levels in normal tissue. CDK4, CDK2, cyclin D1, and cyclin E are highly expressed in DMH as assessed by RT-PCR, qRT-PCR, Western blot, and immunofluorescence analysis. Diclofenac and curcumin overcome these carcinogenic effects by downregulating telomerase activity, diminishing the expression of TERT, CDK4, CDK2, cyclin D1, and cyclin E. The anticarcinogenic effects shown after the inhibition of telomerase activity by diclofenac and curcumin may be associated with upregulation of tumor suppressor proteins p51, Rb, and p21, whose activation induces the cells cycle arrest and apoptosis.

  10. Evaluation of antifungal activity in essential oil of the Syzygium aromaticum (L.) by extraction, purification and analysis of its main component eugenol

    PubMed Central

    Rana, Inder Singh; Rana, Aarti Singh; Rajak, Ram Charan

    2011-01-01

    Antifungal properties of some essential oils have been well documented. Clove oil is reported to have strong antifungal activity against many fungal species. In this study we have evaluated antifungal potential of essential oil of Syzygium aromaticum (L.) against some common fungal pathogens of plants and animals namely, Fusarium moniliforme NCIM 1100, Fusarium oxysporum MTCC 284, Aspergillus sp., Mucor sp., Trichophyton rubrum and Microsporum gypseum. All fungal species were found to be inhibited by the oil when tested through agar well diffusion method. Minimum inhibitory concentration (MIC) was determined for all the species. Column chromatography was performed to separate the eugenol rich fraction from clove oil. Out of seven fractions maximum activity was obtained in column fraction II. TLC and HPLC data confirmed presence of considerable Eugenol in fraction II and clove oil. Microscopic study on effect of clove oil and column fraction II on spores of Mucor sp. and M. gypseum showed distortion and shrinkage while it was absent in other column fractions. So it can be concluded that the antifungal action of clove oil is due to its high eugenol content. PMID:24031751

  11. Interferon-γ regulates the function of mesenchymal stem cells from oral lichen planus via indoleamine 2,3-dioxygenase activity.

    PubMed

    Zhang, Zhihui; Han, Ying; Song, Jiangyuan; Luo, Ruxi; Jin, Xin; Mu, Dongdong; Su, Sha; Ji, Xiaoli; Ren, Yan-Fang; Liu, Hongwei

    2015-01-01

    Little is known about mesenchymal stem cells (MSCs) in normal or inflammatory oral mucosal tissues, such as in oral lichen planus (OLP). Our objectives were to identify, isolate, and characterize MSCs from normal human oral mucosa and OLP lesions, and to evaluate indoleamine 2,3 dioxygenase (IDO) activity in mediating immunomodulation of MSCs from these tissues. Expressions of MSCs-related markers were examined in isolated cells by flow cytometry. Self-renewal and multilineage differentiations were studied to characterize these MSCs. Interferon-γ (IFN-γ), IDO, and STRO-1 were assessed by immunofluorescence. MSCs from oral mucosa and OLP or IFN-γ-pretreated MSCs were co-cultured with allogeneic mixed lymphocyte reaction assays (MLR). Proliferation and apoptosis of MLR or MSCs were detected by CCK8 and the annexin V-FITC apoptosis detection kit, respectively. IDO expression and activity were measured by real-time PCR, Western blotting, and high-performance liquid chromatography. Isolated cells from oral mucosa and OLP expressed MSC-related markers STRO-1, CD105, and CD90 but were absent for hematopoietic stem cell markers CD34. Besides, they all showed self-renewal and multilineage differentiation capacities. MSCs in OLP presented STRO-1/IDO+ phenotype by immunofluorescence. MSCs and IFN-γ-pretreated MSCs could inhibit lymphocyte proliferation via IDO activity, but not via cell apoptosis. Long-term IFN-γ could also inhibit MSC proliferation via IDO activity. Mesenchymal stem cells can be isolated from human oral mucosa and OLP tissues. Besides self-renewal and multilineage differentiation properties, these cells may participate in immunomodulation mediated by IFN-γ via IDO activity in human OLP. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Bacillus subtilis from Soybean Food Shows Antimicrobial Activity for Multidrug-Resistant Acinetobacter baumannii by Affecting the adeS Gene.

    PubMed

    Wang, Tieshan; Su, Jianrong

    2016-12-28

    Exploring novel antibiotics is necessary for multidrug-resistant pathogenic bacteria. Because the probiotics in soybean food have antimicrobial activities, we investigated their effects on multidrug-resistant Acinetobacter baumannii . Nineteen multidrug-resistant A. baumannii strains were clinifcally isolated as an experimental group and 11 multidrug-sensitive strains as controls. The growth rates of all bacteria were determined by using the analysis for xCELLigence Real-Time Cell. The combination of antibiotics showed synergistic effects on the strains in the control group but no effect on the strains in the experimental group. Efflux pump gene adeS was absent in all the strains from the control group, whereas it exists in all the strains from the experimental group. Furthermore, all the strains lost multidrug resistance when an adeS inhibitor was used. One strain of probiotics isolated from soybean food showed high antimicrobial activity for multidrug-resistant A. baumannii . The isolated strain belongs to Bacillus subtilis according to 16S RNA analysis. Furthermore, E. coli showed multidrug resistance when it was transformed with the adeS gene from A. baumannii whereas the resistant bacteria could be inhibited completely by isolated Bacillus subtilis . Thus, probiotics from soybean food provide potential antibiotics against multidrug-resistant pathogenic bacteria.

  13. Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway

    PubMed Central

    Feng, Xiaoli; Luo, Zhidan; Ma, Liqun; Ma, Shuangtao; Yang, Dachun; Zhao, Zhigang; Yan, Zhencheng; He, Hongbo; Cao, Tingbing; Liu, Daoyan; Zhu, Zhiming

    2011-01-01

    Abstract Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor γ (PPAR-δ) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-δ-deficient mice. Administration of telmisartan up-regulated levels of PPAR-δ and phospho-AMPKα in cultured myotubes. However, PPAR-δ gene deficiency completely abolished the telmisartan effect on phospho-AMPKαin vitro. Chronic administration of telmisartan remarkably prevented weight gain, enhanced running endurance and post-exercise oxygen consumption, and increased slow-twitch skeletal muscle fibres in wild-type mice, but these effects were absent in PPAR-δ-deficient mice. The mechanism is involved in PPAR-δ-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPKα level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPKα expression in skeletal muscle was unchanged in PPAR-δ-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-δ as a potential therapeutic target for the prevention of type 2 diabetes. PMID:20477906

  14. Platelet-Activating Factor (PAF) Receptor Antagonism Modulates Inflammatory Signaling in Experimental Uveitis.

    PubMed

    Elison, Jasmine R; Weinstein, Jessica E; Sheets, Kristopher G; Regan, Cornelius E; Lentz, Jennifer J; Reinoso, Maria; Gordon, William C; Bazan, Nicolas G

    2018-04-11

    The phospholipid mediator platelet-activating factor (PAF) activates an inflammatory response that includes arachidonic acid release and prostaglandin production in the eye, increasing vascular permeability and inflammation. The purpose of this study is to investigate the action of LAU-0901, a novel PAF receptor antagonist, on experimental uveitis. Uveitis was induced in Lewis rats by lipopolysaccharide treatment. LAU-0901 was then delivered systemically in different concentrations at plus 4 and 16 hours, or vehicle injected as controls. Additional animals were used for histological analyses of untreated, uveitis, and uveitis-plus-LAU-0901 retinas. Conventional histological and immunohistochemical methods were employed. A slit lamp and Spectral Domain-Ocular Coherence Tomography (SD-OCT) retinal imager was used for anterior segment photography and posterior pole OCT. Rats were euthanized 4 hours after the second LAU-0901 injection in this 24-hour model. Aqueous humor was collected and quantified, and also analyzed for tumor necrosis factor alpha (TNF-α). Uveitic eyes demonstrated hypopyon formation, leukocyte infiltration, and an increase in aqueous protein and TNF-α levels. LAU-0901 treatment resulted in a dose-dependent reduction in inflammation, reflected by reduced total protein levels (up to a 64% reduction). Moreover, hypopyon was prevented, leukocytes were absent in vitreous and aqueous humor, and TNF-α levels were reduced by 91%. The PAF receptor antagonist LAU-0901 decreases ocular inflammation in a rat model of anterior uveitis in a dose-dependent manner, suggesting that use of this molecule may provide a means to attenuate inflammation onset and offer a future alternative or adjunctive treatment for ocular inflammation.

  15. A comparative study of skin cell activities in collagen and fibrin constructs.

    PubMed

    Law, Jia Xian; Musa, Faiza; Ruszymah, Bt Hj Idrus; El Haj, Alicia J; Yang, Ying

    2016-09-01

    Collagen and fibrin are widely used in tissue engineering due to their excellent biocompatibility and bioactivities that support in vivo tissue formation. These two hydrogels naturally present in different wound healing stages with different regulatory effects on cells, and both of them are mechanically weak in the reconstructed hydrogels. We conducted a comparative study by the growth of rat dermal fibroblasts or dermal fibroblasts and epidermal keratinocytes together in collagen and fibrin constructs respectively with and without the reinforcement of electrospun poly(lactic acid) nanofiber mesh. Cell proliferation, gel contraction and elastic modulus of the constructs were measured on the same gels at multiple time points during the 22 day culturing period using multiple non-destructive techniques. The results demonstrated considerably different cellular activities within the two types of constructs. Co-culturing keratinocytes with fibroblasts in the collagen constructs reduced the fibroblast proliferation, collagen contraction and mechanical strength at late culture point regardless of the presence of nanofibers. Co-culturing keratinocytes with fibroblasts in the fibrin constructs promoted fibroblast proliferation but exerted no influence on fibrin contraction and mechanical strength. The presence of nanofibers in the collagen and fibrin constructs played a favorable role on the fibroblast proliferation when keratinocytes were absent. Thus, this study exhibited new evidence of the strong cross-talk between keratinocytes and fibroblasts, which can be used to control fibroblast proliferation and construct contraction. This cross-talk activity is extracellular matrix-dependent in terms of the fibrous network morphology, density and strength. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  16. Asymmetric pallidal neuronal activity in patients with cervical dystonia

    PubMed Central

    Moll, Christian K. E.; Galindo-Leon, Edgar; Sharott, Andrew; Gulberti, Alessandro; Buhmann, Carsten; Koeppen, Johannes A.; Biermann, Maxine; Bäumer, Tobias; Zittel, Simone; Westphal, Manfred; Gerloff, Christian; Hamel, Wolfgang; Münchau, Alexander; Engel, Andreas K.

    2014-01-01

    The origin of asymmetric clinical manifestation of symptoms in patients suffering from cervical dystonia (CD) is hitherto poorly understood. Dysregulated neuronal activity in the basal ganglia has been suggested to have a role in the pathophysiology of CD. Here, we re-assessed the question to what extent relative changes occur in the direct vs. indirect basal ganglia pathway in CD, whether these circuit changes are lateralized, and how these alterations relate to CD symptoms. To this end, we recorded ongoing single cell and local field potential (LFP) activity from the external (GPe) and internal pallidal segment (GPi) of 13 CD patients undergoing microelectrode-guided stereotactic surgery for deep brain stimulation in the GPi. We compared pallidal recordings from CD patients operated under local anaesthesia (LA) with those obtained in CD patients operated under general anaesthesia (GA). In awake patients, mean GPe discharge rate (52 Hz) was lower than that of GPi (72 Hz). Mean GPi discharge ipsilateral to the side of head turning was higher than contralateral and correlated with torticollis symptom severity. Lateralized differences were absent at the level of the GPe and in recordings from patients operated under GA. Furthermore, in the GPi of CD patients there was a subpopulation of theta-oscillatory cells with unique bursting characteristics. Power and coherence of GPe– and GPi–LFPs were dominated by a theta peak and also exhibited band-specific interhemispheric differences. Strong cross-frequency coupling of low-gamma amplitude to theta phase was a feature of pallidal LFPs recorded under LA, but not GA. These results indicate that CD is associated with an asymmetric pallidal outflow. Based on the finding of symmetric neuronal discharges in the GPe, we propose that an imbalanced interhemispheric direct pathway gain may be involved in CD pathophysiology. PMID:24574981

  17. SVEP1 is a novel marker of activated pre-determined skeletal muscle satellite cells.

    PubMed

    Shefer, Gabi; Benayahu, Dafna

    2010-03-01

    In this study we explored the expression pattern of SVEP1, a novel cell adhesion molecule (CAM), in bona fide satellite cells and their immediate progeny. We show that SVEP1 is expressed in activated satellite cells prior to their determination to the myogenic lineage. SVEP1 was also expressed during early phases of myogenic differentiation through the initial stage of myoblast fusion and myotube formation. The expression of SVEP1 was shown by immunostaining two cell culture systems: freshly isolated myofibers and primary myoblasts. Pax7 was used to pinpoint satellite cells situated in their niche on myofibers, and activated satellite cells were determined based on BrdU incorporation (Pax7(+)/BrdU(+)cells). MyoD marked satellite cells fated to undergo myogenesis as well as proliferating and differentiating myoblasts. Differentiating myoblasts and myotubes were identified based on their sarcomeric myosin expression. We showed that SVEP1 was specifically expressed in pre-determined activated satellite cells (Pax7(+)/ BrdU(+) /MyoD(-)) accounting for about 24% of total satellite cells. On the other hand, SVEP1 expression was absent in quiescent satellite cells (Pax7(+)/BrdU(-)/MyoD(-)). Moreover, based on MyoD/sarcomeric myosin co-expression SVEP1 was shown to be expressed throughout the early phases of myogenesis up until myoblast fusion and myotube formation. A decline in SVEP1 expression occurred upon myotube maturation. We suggest SVEP1 as a potential biomarker for pre-fated satellite cells. The impact of this finding is that it may allow scrutinizing signals that affect differentiation commitment. Thus, holds a therapeutic potential for maladies that involve deregulated stem cell fate-decision.

  18. Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

    PubMed

    Murphy, D L; Sims, K B; Karoum, F; Garrick, N A; de la Chapelle, A; Sankila, E M; Norio, R; Breakefield, X O

    1991-01-01

    Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.

  19. Sequence Analysis and Characterization of Active Human Alu Subfamilies Based on the 1000 Genomes Pilot Project.

    PubMed

    Konkel, Miriam K; Walker, Jerilyn A; Hotard, Ashley B; Ranck, Megan C; Fontenot, Catherine C; Storer, Jessica; Stewart, Chip; Marth, Gabor T; Batzer, Mark A

    2015-08-29

    The goal of the 1000 Genomes Consortium is to characterize human genome structural variation (SV), including forms of copy number variations such as deletions, duplications, and insertions. Mobile element insertions, particularly Alu elements, are major contributors to genomic SV among humans. During the pilot phase of the project we experimentally validated 645 (611 intergenic and 34 exon targeted) polymorphic "young" Alu insertion events, absent from the human reference genome. Here, we report high resolution sequencing of 343 (322 unique) recent Alu insertion events, along with their respective target site duplications, precise genomic breakpoint coordinates, subfamily assignment, percent divergence, and estimated A-rich tail lengths. All the sequenced Alu loci were derived from the AluY lineage with no evidence of retrotransposition activity involving older Alu families (e.g., AluJ and AluS). AluYa5 is currently the most active Alu subfamily in the human lineage, followed by AluYb8, and many others including three newly identified subfamilies we have termed AluYb7a3, AluYb8b1, and AluYa4a1. This report provides the structural details of 322 unique Alu variants from individual human genomes collectively adding about 100 kb of genomic variation. Many Alu subfamilies are currently active in human populations, including a surprising level of AluY retrotransposition. Human Alu subfamilies exhibit continuous evolution with potential drivers sprouting new Alu lineages. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  20. Molecular signatures distinguishing active from latent tuberculosis in peripheral blood mononuclear cells, after in vitro antigenic stimulation with purified protein derivative of tuberculin (PPD) or Candida: a preliminary report.

    PubMed

    Stern, Joel N H; Keskin, Derin B; Romero, Viviana; Zuniga, Joaquin; Encinales, Liliana; Li, Changlin; Awad, Carlos; Yunis, Edmond J

    2009-01-01

    Purified protein derivative (PPD) or tuberculin skin testing is used to identify infected individuals with Mycobacterium tuberculosis (Mtb) and to assess cell-mediated immunity to Mtb. In the present study, we compared PBMC cultures in the presence of tuberculin or Candida antigens using cytokine bead arrays and RNA microarrays. Measurements of different cytokines and chemokines in supernatants of PMBC cultures in the presence of PPD showed increased levels of interferon (IFN)-gamma in active tuberculosis infection (ATBI) and latent TB infected (LTBI) compared to controls, and increased levels of TNF-alpha in ATBI compared with LTBI. Also, we found increase of IL-6 in cultures of PPD positive and controls but not in the cultures with Candida. We also report the molecular signature of tuberculosis infection, in ATBI patients, the following genes were found to be up-regulated and absent in LTBI individuals: two kinases (JAK3 and p38MAPK), four interleukins (IL-7, IL-2, IL-6, and IFNbeta1), a chemokine (HCC-4) a chemokine receptor (CxCR5), two interleukin receptors (IL-1R2 and IL-18R1), and three additional ones (TRAF5, Smad2, CIITA, and NOS2A). By contrast, IL-17 and IGFBP3 were significantly up-regulated in LTBI. And, STAT4, GATA3, Fra-1, and ICOS were down-regulated in ATBI but absent in LTBI. Conversely, TLR-10, IL-15, DORA, and IKK-beta were down-regulated in LTBI but not in ATBI. Interestingly, the majority of the up-regulated genes found in ATBI were found in cultures stimulated with tuberculin (PPD) or Candida antigens, suggesting that these pathogens stimulate similar immunological pathways. We believe that the molecular signature distinguishing active from latent tuberculosis infection may require using cytokine bead arrays along with RNA microarrays testing cell cultures at different times following in vitro proliferation assays using several bacterial antigens and PPD.

  1. Leishmanicidal activity of an alkenylphenol from Piper malacophyllum is related to plasma membrane disruption.

    PubMed

    de Oliveira, Alberto; Mesquita, Juliana T; Tempone, André G; Lago, João Henrique G; Guimarães, Elsie F; Kato, Massuo J

    2012-11-01

    Leishmaniasis and Chagas disease are parasitic protozoan infections that affect the poorest population in the world, causing high mortality and morbidity. As a result of highly toxic and long-duration treatments, novel, safe and more efficacious drugs are essential. In this work, the methanol (MeOH) extract from the leaves of Piper malacophyllum (Piperaceae) was fractioned to afford one alkenylphenol, which was characterized as 4-[(3'E)-decenyl]phenol (gibbilimbol B) by spectroscopic methods. Anti-protozoan in vitro assays demonstrated for the first time that Leishmania (L.) infantum chagasi was susceptible to gibbilimbol B, with an in vitro EC(50) of 23 μg/mL against axenic promastigotes and an EC(50) of 22 μg/mL against intracellular amastigotes. Gibbilimbol B was also tested for anti-trypanosomal activity (Trypanosoma cruzi) and showed an EC(50) value of 17 μg/mL against trypomastigotes. To evaluate the cytotoxic parameters, this alkenylphenol was tested in vitro against NCTC cells, showing a CC(50) of 59 μg/mL and absent hemolytic activity at the highest concentration of 75 μg/mL. Using the fluorescent probe SYTOX Green suggested that the alkenylphenol disrupted the Leishmania plasma membrane upon initial incubation. Further drug design studies aiming at derivatives could be a promising tool for the development of new therapeutic agents for leishmaniasis and Chagas disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Impairments in Activities of Daily Living in Older Japanese Men in Hawaii and Japan

    PubMed Central

    Abbott, Robert D.; Kadota, Aya; Miura, Katsuyuki; Hayakawa, Takehito; Kadowaki, Takashi; Okamura, Tomonori; Okayama, Akira; Masaki, Kamal H.; Ueshima, Hirotsugu

    2011-01-01

    Introduction. Hypertension and cigarette smoking are dominant risk factors for cardiovascular disease in Japan while in westernized countries, broader effects encompass obesity, diabetes, and hypercholesterolemia. This paper examines whether different associations also appear important in the manifestation of activities of daily living (ADL) in older Japanese men in Hawaii and Japan. Methods. Measures of ADL (feeding, toileting, dressing, bathing, and walking around the house) were assessed from 1995 to 1999 in 1,893 men in Hawaii and 543 men in Japan. Concomitant risk factors were measured from 1990 to 1993. Results. In Hawaii, diabetes increased the odds of ≥1 ADL impairment nearly 1.5-fold (P = .020). A similar association was absent in Japan. In contrast, the odds of an ADL impairment in Japan was increased more than 5-fold in the presence of stroke (P < .001). The association in Hawaii was significantly weaker (P = .007). In both cohorts, past alcohol use was associated with a greater likelihood of ADL impairment. Conclusion. In this comparison of genetically similar samples, findings suggest that different strengths in risk factor associations with cardiovascular disease in Japan and westernized countries may also include different strengths in associations with impaired ADL. PMID:21766031

  3. Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA Domain Ubiquitination.

    PubMed

    Lee, YouJin; Chou, Tsui-Fen; Pittman, Sara K; Keith, Amy L; Razani, Babak; Weihl, Conrad C

    2017-04-04

    p62/SQSTM1 (p62) is a scaffolding protein that facilitates the formation and degradation of ubiquitinated aggregates via its self-interaction and ubiquitin binding domains. The regulation of this process is unclear but may relate to the post-translational modification of p62. In the present study, we find that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain. Substitution of lysine 420 with an arginine diminishes p62 sequestration and degradation activity similar what is seen when the UBA domain is deleted. Overexpression of Keap1/Cullin3 in p62-WT-expressing cells increases ubiquitinated inclusion formation and p62's association with LC3 and rescues proteotoxicity. This effect is not seen in cells expressing a mutant p62 that fails to interact with Keap1. Interestingly, p62 disease mutants have diminished or absent UBA domain ubiquitination. These data suggest that the ubiquitination of p62's UBA domain at lysine 420 may regulate p62's function and be disrupted in p62-associated disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Neurotensin receptor 1 gene activation by the Tcf/beta-catenin pathway is an early event in human colonic adenomas.

    PubMed

    Souazé, Frédérique; Viardot-Foucault, Véronique; Roullet, Nicolas; Toy-Miou-Leong, Mireille; Gompel, Anne; Bruyneel, Erik; Comperat, Eva; Faux, Maree C; Mareel, Marc; Rostène, William; Fléjou, Jean-François; Gespach, Christian; Forgez, Patricia

    2006-04-01

    Alterations in the Wnt/APC (adenomatous polyposis coli) signalling pathway, resulting in beta-catenin/T cell factor (Tcf)-dependent transcriptional gene activation, are frequently detected in familial and sporadic colon cancers. The neuropeptide neurotensin (NT) is widely distributed in the gastrointestinal tract. Its proliferative and survival effects are mediated by a G-protein coupled receptor, the NT1 receptor. NT1 receptor is not expressed in normal colon epithelial cells, but is over expressed in a number of cancer cells and tissues suggesting a link to the outgrowth of human colon cancer. Our results demonstrate that the upregulation of NT1 receptor occurring in colon cancer is the result of Wnt/APC signalling pathway activation. We first established the functionality of the Tcf response element within the NT1 receptor promoter. Consequently, we observed the activation of NT1 receptor gene by agents causing beta-catenin cytosolic accumulation, as well as a strong decline of endogenous receptor when wt-APC was restored. At the cellular level, the re-establishment of wt-APC phenotype resulted in the impaired functionality of NT1 receptor, like the breakdown in NT-induced intracellular calcium mobilization and the loss of NT pro-invasive effect. We corroborated the Wnt/APC signalling pathway on the NT1 receptor promoter activation with human colon carcinogenesis, and showed that NT1 receptor gene activation was perfectly correlated with nuclear or cytoplasmic beta-catenin localization while NT1 receptor was absent when beta-catenin was localized at the cell-cell junction in early adenomas of patients with familial adenomatous polyposis, hereditary non-polyposis colorectal cancer and loss of heterozygosity tumours. In this report we establish a novel link in vitro between the Tcf/beta-catenin pathway and NT1 receptor promoter activation.

  5. Age-Specific Effects of Mirror-Muscle Activity on Cross-Limb Adaptations Under Mirror and Non-Mirror Visual Feedback Conditions.

    PubMed

    Reissig, Paola; Stöckel, Tino; Garry, Michael I; Summers, Jeffery J; Hinder, Mark R

    2015-01-01

    Cross-limb transfer (CLT) describes the observation of bilateral performance gains due to unilateral motor practice. Previous research has suggested that CLT may be reduced, or absent, in older adults, possibly due to age-related structural and functional brain changes. Based on research showing increases in CLT due to the provision of mirror visual feedback (MVF) during task execution in young adults, our study aimed to investigate whether MVF can facilitate CLT in older adults, who are known to be more reliant on visual feedback for accurate motor performance. Participants (N = 53) engaged in a short-term training regime (300 movements) involving a ballistic finger task using their dominant hand, while being provided with either visual feedback of their active limb, or a mirror reflection of their active limb (superimposed over the quiescent limb). Performance in both limbs was examined before, during and following the unilateral training. Furthermore, we measured corticospinal excitability (using TMS) at these time points, and assessed muscle activity bilaterally during the task via EMG; these parameters were used to investigate the mechanisms mediating and predicting CLT. Training resulted in significant bilateral performance gains that did not differ as a result of age or visual feedback (both p > 0.1). Training also elicited bilateral increases in corticospinal excitability (p < 0.05). For younger adults, CLT was significantly predicted by performance gains in the trained hand (β = 0.47), whereas for older adults it was significantly predicted by mirror activity in the untrained hand during training (β = 0.60). The present study suggests that older adults are capable of exhibiting CLT to a similar degree to younger adults. The prominent role of mirror activity in the untrained hand for CLT in older adults indicates that bilateral cortical activity during unilateral motor tasks is a compensatory mechanism. In this particular task, MVF did not facilitate the

  6. [Eight new species of coccidia (Sporozoa, Coccidia) in fishes from the continental waters of Russia].

    PubMed

    Belova, L M; Krylov, M V

    2001-01-01

    Description of coccidian species infecting freshwater fishes is given. Localities: Neman river, Goussia peleci sp. n.--oocyst 37.5-45 x 35-42.5 microns, oocyst residuum (OR) absent, sporocysts 20-22.5 x 15-17.5 microns, Stieda body (SB) absent, sporocyst residuum (SR) present, host (h)--Pelecus cultratus; G. cultrati sp. n.--oocyst 22.5-30 microns, OR absent, sporocysts 12.5 x 15 microns, SR, SB absent, wall 2-2.5 microns, h--P. cultratus; G. arinae sp. n.--oocyst 12.5 x 17.5 microns, OR present, sporocysts 5-7.5 microns, SR, SB absent, h--P. cultratus; G. vimbae sp. n.--oocyst 15-22.5 microns, OR absent, wall 2.5 microns, sporocysts 5-7.5 microns, SR, SB absent, h--Vimba vimba vimba; G. gymnocephali sp. n.--oocyst 25 x 25 microns, OR absent, sporocysts 10 x 12.5 microns, SR, SB absent, h--Gymnocephalus cernuus; G. cernui sp. n.--oocyst 15-22.5 microns, OR present, sporocysts 5-12.5 microns, SR, SB absent, h--Gym. cernuus; G. luciopercae sp. n.--oocyst 30-35 x 30 microns, OR absent, sporocysts 12.5-15 x 10-12.5 microns, SB absent, SR present, h--Stizostedion lucioperca; Eimeria fluviatili sp. n.--oocyst 20-22.5 microns, OR present, sporocysts 7.5 x 12.5 microns, SB present, SR absent, h--Perca fluviatilis.

  7. 13C-breath tests for sucrose digestion in congenital sucrase isomaltase-deficient and sacrosidase-supplemented patients

    USDA-ARS?s Scientific Manuscript database

    Congenital sucrase-isomaltase deficiency (CSID) is characterized by absence or deficiency of the mucosal sucrase-isomaltase enzyme. Specific diagnosis requires upper gastrointestinal biopsy with evidence of low to absent sucrase enzyme activity and normal histology. The hydrogen breath test (BT) is ...

  8. Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis.

    PubMed

    Piqueras, Laura; Reynolds, Andrew R; Hodivala-Dilke, Kairbaan M; Alfranca, Arántzazu; Redondo, Juan M; Hatae, Toshihisa; Tanabe, Tadashi; Warner, Timothy D; Bishop-Bailey, David

    2007-01-01

    The role of the nuclear receptor peroxisome-proliferator activated receptor (PPAR)-beta/delta in endothelial cells remains unclear. Interestingly, the selective PPARbeta/delta ligand GW501516 is in phase II clinical trials for dyslipidemia. Here, using GW501516, we have assessed the involvement of PPARbeta/delta in endothelial cell proliferation and angiogenesis. Western blot analysis indicated PPARbeta/delta was expressed in primary human umbilical and aortic endothelial cells, and in the endothelial cell line, EAHy926. Treatment with GW501516 increased human endothelial cell proliferation and morphogenesis in cultures in vitro, endothelial cell outgrowth from murine aortic vessels in vitro, and angiogenesis in a murine matrigel plug assay in vivo. GW501516 induced vascular endothelial cell growth factor mRNA and peptide release, as well as adipose differentiation-related protein (ADRP), a PPARbeta/delta target gene. GW501516-induced proliferation, morphogenesis, vascular endothelial growth factor (VEGF), and ADRP were absent in endothelial cells transfected with dominant-negative PPARbeta/delta. Furthermore, treatment of cells with cyclo-VEGFI, a VEGF receptor1/2 antagonist, abolished GW501516-induced endothelial cell proliferation and tube formation. PPARbeta/delta is a novel regulator of endothelial cell proliferation and angiogenesis through VEGF. The use of GW501516 to treat dyslipidemia may need to be carefully monitored in patients susceptible to angiogenic disorders.

  9. Probing Metabolic Activity of Deep Subseafloor Life with NanoSIMS

    NASA Astrophysics Data System (ADS)

    Morono, Y.; Terada, T.; Itoh, M.; Inagaki, F.

    2014-12-01

    There are very few natural environments where life is absent in the Earth's surface biosphere. However, uninhabitable region is expected to be exist in the deep subsurface biosphere, of which extent and constraining factor(s) have still remained largly unknown. Scientific ocean drilling have revealed that microbial communities in sediments are generally phylogenetically distinct from known spieces isolated from the Earth's surface biosphere, and hence metabolic functions of the deep subseafloor life remain unknown. In addition, activity of subseafloor microbial cells are thought to be extraordinally slow, as indicated by limited supply of neutrient and energy substrates. To understand the limits of the Earth's subseafloor biosphere and metabolic functions of microbial populations, detection and quantification of the deeply buried microbial cells in geological habitats are fundamentary important. Using newly developed cell separation techniques as well as an discriminative cell detection system, the current quantification limit of sedimentary microbial cells approaches to 102 cells/cm3. These techniques allow not only to assess very small microbial population close to the subsurface biotic fringe, but also to separate and sort the target cells using flow cytometric cell sorter. Once the deep subseafloor microbial cells are detached from mineral grains and sorted, it opens new windows to subsequent molecular ecological and element/isotopic analyses. With a combined use of nano-scale secondary ion masspectrometry (NanoSIMS) and stable isotope-probing techniques, it is possible to detect and measure activity of substrate incorporation into biomass, even for extremely slow metabolic processes such as uncharacteriszed deep subseafloor life. For example, it was evidenced by NanoSIMS that at least over 80% of microbial cells at ~200 meters-deep, 460,000-year-old sedimentary habitat are indeed live, which substrate incooporation was found to be low (10-15 gC/cell/day) even

  10. HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.

    PubMed

    Abdulhaqq, S A; Zorrilla, C; Kang, G; Yin, X; Tamayo, V; Seaton, K E; Joseph, J; Garced, S; Tomaras, G D; Linn, K A; Foulkes, A S; Azzoni, L; VerMilyea, M; Coutifaris, C; Kossenkov, A V; Showe, L; Kraiselburd, E N; Li, Q; Montaner, L J

    2016-07-01

    Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: P<0.001) together with lower cervical gene expression of genes associated with leukocyte homing and chemotaxis. FSWs also had increased levels of interferon-ɛ (IFNɛ) gene and protein expression in the cervical epithelium together with reduced expression of genes associated with HIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses.

  11. Active flow control insight gained from a modified integral boundary layer equation

    NASA Astrophysics Data System (ADS)

    Seifert, Avraham

    2016-11-01

    Active Flow Control (AFC) can alter the development of boundary layers with applications (e.g., reducing drag by separation delay or separating the boundary layers and enhancing vortex shedding to increase drag). Historically, significant effects of steady AFC methods were observed. Unsteady actuation is significantly more efficient than steady. Full-scale AFC tests were conducted with varying levels of success. While clearly relevant to industry, AFC implementation relies on expert knowledge with proven intuition and or costly and lengthy computational efforts. This situation hinders the use of AFC while simple, quick and reliable design method is absent. An updated form of the unsteady integral boundary layer (UIBL) equations, that include AFC terms (unsteady wall transpiration and body forces) can be used to assist in AFC analysis and design. With these equations and given a family of suitable velocity profiles, the momentum thickness can be calculated and matched with an outer, potential flow solution in 2D and 3D manner to create an AFC design tool, parallel to proven tools for airfoil design. Limiting cases of the UIBL equation can be used to analyze candidate AFC concepts in terms of their capability to modify the boundary layers development and system performance.

  12. Transcription, Signaling Receptor Activity, Oxidative Phosphorylation, and Fatty Acid Metabolism Mediate the Presence of Closely Related Species in Distinct Intertidal and Cold-Seep Habitats.

    PubMed

    Van Campenhout, Jelle; Vanreusel, Ann; Van Belleghem, Steven; Derycke, Sofie

    2015-12-03

    Bathyal cold seeps are isolated extreme deep-sea environments characterized by low species diversity while biomass can be high. The Håkon Mosby mud volcano (Barents Sea, 1,280 m) is a rather stable chemosynthetic driven habitat characterized by prominent surface bacterial mats with high sulfide concentrations and low oxygen levels. Here, the nematode Halomonhystera hermesi thrives in high abundances (11,000 individuals 10 cm(-2)). Halomonhystera hermesi is a member of the intertidal Halomonhystera disjuncta species complex that includes five cryptic species (GD1-5). GD1-5's common habitat is characterized by strong environmental fluctuations. Here, we compared the transcriptomes of H. hermesi and GD1, H. hermesi's closest relative. Genes encoding proteins involved in oxidative phosphorylation are more strongly expressed in H. hermesi than in GD1, and many genes were only observed in H. hermesi while being completely absent in GD1. Both observations could in part be attributed to high sulfide concentrations and low oxygen levels. Additionally, fatty acid elongation was also prominent in H. hermesi confirming the importance of highly unsaturated fatty acids in this species. Significant higher amounts of transcription factors and genes involved in signaling receptor activity were observed in GD1 (many of which were completely absent in H. hermesi), allowing fast signaling and transcriptional reprogramming which can mediate survival in dynamic intertidal environments. GC content was approximately 8% higher in H. hermesi coding unigenes resulting in differential codon usage between both species and a higher proportion of amino acids with GC-rich codons in H. hermesi. In general our results showed that most pathways were active in both environments and that only three genes are under natural selection. This indicates that also plasticity should be taken in consideration in the evolutionary history of Halomonhystera species. Such plasticity, as well as possible

  13. A gene encoding the plant-like alternative oxidase is present in Phytomonas but absent in Leishmania spp.

    PubMed

    Van Hellemond, J J; Simons, B; Millenaar, F F; Tielens, A G

    1998-01-01

    The constituents of the respiratory chain are believed to differ among the trypanosomatids; bloodstream stages of African trypanosomes and Phytomonas promastigotes oxidize ubiquinol by a ubiquinol:oxygen oxidoreductase, also known as alternative oxidase, whereas Leishmania spp. oxidize ubiquinol via a classic cytochrome-containing respiratory chain. The molecular basis for this elementary difference in ubiquinol oxidation by the mitochondrial electron-transport chain in distinct trypanosomatids was investigated. The presence of a gene encoding the plant-like alternative oxidase could be demonstrated in Phytomonas and Trypanosoma brucei, trypanosomatids that are known to contain alternative oxidase activity. Our results further demonstrated that Leishmania spp. lack a gene encoding the plant-like alternative oxidase, and therefore, all stages of Leishmania spp. will lack the alternative oxidase protein. The observed fundamental differences between the respiratory chains of distinct members of the trypanosomatid family are thus caused by the presence or absence of a gene encoding the plant-like alternative oxidase.

  14. The Effect of Involuntary Motor Activity on Myoelectric Pattern Recognition: A Case Study with Chronic Stroke Patients

    PubMed Central

    Zhang, Xu; Li, Yun; Chen, Xiang; Li, Guanglin; Rymer, William Zev; Zhou, Ping

    2013-01-01

    This study investigates the effect of involuntary motor activity of paretic-spastic muscles on classification of surface electromyography (EMG) signals. Two data collection sessions were designed for 8 stroke subjects to voluntarily perform 11 functional movements using their affected forearm and hand at a relatively slow and fast speed. For each stroke subject, the degree of involuntary motor activity present in voluntary surface EMG recordings was qualitatively described from such slow and fast experimental protocols. Myoelectric pattern recognition analysis was performed using different combinations of voluntary surface EMG data recorded from slow and fast sessions. Across all tested stroke subjects, our results revealed that when involuntary surface EMG was absent or present in both training and testing datasets, high accuracies (> 96%, > 98%, respectively, averaged over all the subjects) can be achieved in classification of different movements using surface EMG signals from paretic muscles. When involuntary surface EMG was solely involved in either training or testing datasets, the classification accuracies were dramatically reduced (< 89%, < 85%, respectively). However, if both training and testing datasets contained EMG signals with presence and absence of involuntary EMG interference, high accuracies were still achieved (> 97%). The findings of this study can be used to guide appropriate design and implementation of myoelectric pattern recognition based systems or devices toward promoting robot-aided therapy for stroke rehabilitation. PMID:23860192

  15. Stress-specific p38 MAPK activation is sufficient to drive EGFR endocytosis but not its nuclear translocation.

    PubMed

    Tomas, Alejandra; Jones, Sylwia; Vaughan, Simon O; Hochhauser, Daniel; Futter, Clare E

    2017-08-01

    EGF receptor (EGFR) endocytosis is induced by stress in a manner dependent on the p38 MAPK family. Ligand and stresses such as X-rays, reportedly promote nuclear trafficking of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression, and so did not represent nuclear EGFR. UVB and UVC, but not X-ray or UVA, treatment induced p38 activation and EGFR endocytosis, although all of these stresses induced DNA damage, indicating that DNA damage alone is not sufficient to induce EGFR endocytosis. Increased reactive oxygen species (ROS) levels following UVB treatment, compared to that seen with X-rays, do not alone explain differences in p38 activation. UVB, like UVC, induced EGFR accumulation predominantly in perinuclear endosomes, rather than in the nucleus. Our morphological techniques identifying major changes in receptor distribution do not exclude the possibility that small but biologically relevant amounts of EGFR enter the nucleus. This study highlights the importance and limitations of morphological analyses of receptor distribution in understanding signaling outcome. © 2017. Published by The Company of Biologists Ltd.

  16. Activation of the Saccharomyces cerevisiae filamentation/invasion pathway by osmotic stress in high-osmolarity glycogen pathway mutants

    NASA Technical Reports Server (NTRS)

    Davenport, K. D.; Williams, K. E.; Ullmann, B. D.; Gustin, M. C.; McIntire, L. V. (Principal Investigator)

    1999-01-01

    Mitogen-activated protein kinase (MAPK) cascades are frequently used signal transduction mechanisms in eukaryotes. Of the five MAPK cascades in Saccharomyces cerevisiae, the high-osmolarity glycerol response (HOG) pathway functions to sense and respond to hypertonic stress. We utilized a partial loss-of-function mutant in the HOG pathway, pbs2-3, in a high-copy suppressor screen to identify proteins that modulate growth on high-osmolarity media. Three high-copy suppressors of pbs2-3 osmosensitivity were identified: MSG5, CAK1, and TRX1. Msg5p is a dual-specificity phosphatase that was previously demonstrated to dephosphorylate MAPKs in yeast. Deletions of the putative MAPK targets of Msg5p revealed that kss1delta could suppress the osmosensitivity of pbs2-3. Kss1p is phosphorylated in response to hyperosmotic shock in a pbs2-3 strain, but not in a wild-type strain nor in a pbs2-3 strain overexpressing MSG5. Both TEC1 and FRE::lacZ expressions are activated in strains lacking a functional HOG pathway during osmotic stress in a filamentation/invasion-pathway-dependent manner. Additionally, the cellular projections formed by a pbs2-3 mutant on high osmolarity are absent in strains lacking KSS1 or STE7. These data suggest that the loss of filamentation/invasion pathway repression contributes to the HOG mutant phenotype.

  17. Activation of the Saccharomyces cerevisiae filamentation/invasion pathway by osmotic stress in high-osmolarity glycogen pathway mutants.

    PubMed Central

    Davenport, K D; Williams, K E; Ullmann, B D; Gustin, M C

    1999-01-01

    Mitogen-activated protein kinase (MAPK) cascades are frequently used signal transduction mechanisms in eukaryotes. Of the five MAPK cascades in Saccharomyces cerevisiae, the high-osmolarity glycerol response (HOG) pathway functions to sense and respond to hypertonic stress. We utilized a partial loss-of-function mutant in the HOG pathway, pbs2-3, in a high-copy suppressor screen to identify proteins that modulate growth on high-osmolarity media. Three high-copy suppressors of pbs2-3 osmosensitivity were identified: MSG5, CAK1, and TRX1. Msg5p is a dual-specificity phosphatase that was previously demonstrated to dephosphorylate MAPKs in yeast. Deletions of the putative MAPK targets of Msg5p revealed that kss1delta could suppress the osmosensitivity of pbs2-3. Kss1p is phosphorylated in response to hyperosmotic shock in a pbs2-3 strain, but not in a wild-type strain nor in a pbs2-3 strain overexpressing MSG5. Both TEC1 and FRE::lacZ expressions are activated in strains lacking a functional HOG pathway during osmotic stress in a filamentation/invasion-pathway-dependent manner. Additionally, the cellular projections formed by a pbs2-3 mutant on high osmolarity are absent in strains lacking KSS1 or STE7. These data suggest that the loss of filamentation/invasion pathway repression contributes to the HOG mutant phenotype. PMID:10545444

  18. The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis.

    PubMed

    Algaba-Chueca, Francisco; de-Madaria, Enrique; Lozano-Ruiz, Beatriz; Martínez-Cardona, Claudia; Quesada-Vázquez, Noé; Bachiller, Victoria; Tarín, Fabián; Such, José; Francés, Rubén; Zapater, Pedro; González-Navajas, José M

    Acute pancreatitis is an inflammatory disorder of the pancreas that is responsible for significant morbidity and mortality. The inflammasome pathway has acquired significant relevance in the pathogenesis of many inflammatory disorders, but its role in patients with acute pancreatitis still awaits clarification. We performed a prospective study in which 27 patients with acute pancreatitis and 16 healthy controls were included. We isolated peripheral blood mononuclear cells (PBMCs) and we assessed the expression and activation of different inflammasomes as well as their association with the clinical course of the disease. Our results show that PBMCs from patients with acute pancreatitis have elevated expression of several components of the inflammasome complex, including the inflammasome-forming receptor absent in melanoma 2 (AIM2), early during the onset of the disease. Activation of the AIM2 or NLRP3 inflammasomes in PBMCs from patients with acute pancreatitis results in exacerbated IL-1β and IL-18 production compared with PBMCs from healthy controls. Furthermore, both AIM2 mRNA expression and AIM2-mediated production of IL-1β by PBMCs correlated with increased systemic inflammation in these patients. Last, AIM2 expression was further increased in those patients that developed transient or persistent organ failure (moderate or severe acute pancreatitis). Our data demonstrates that AIM2 inflammasome expression and activation is increased early during the course of acute pancreatitis, and suggests that AIM2 activation may affect systemic inflammation and organ failure in these patients. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  19. Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate.

    PubMed

    Lange, Sofie C; Winkler, Ulrike; Andresen, Lars; Byhrø, Mathilde; Waagepetersen, Helle S; Hirrlinger, Johannes; Bak, Lasse K

    2015-12-01

    We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.

  20. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

    PubMed

    Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

    2016-02-01

    Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.