The Changing Life Space of Early Adolescence.

ERIC Educational Resources Information Center

Larson, Reed, Ed.; Richards, Maryse, H., Ed.

1989-01-01

Eight papers are presented that describe the daily experience of White American children in grades 5 through 9. Each paper examines a segment of daily activity (e.g., schoolwork, talking, sports) and the associated affective states for 401 participants to provide a picture of the life space of early adolescence. (SLD)

Face-elicited ERPs and affective attitude: brain electric microstate and tomography analyses.

PubMed

Pizzagalli, D; Lehmann, D; Koenig, T; Regard, M; Pascual-Marqui, R D

2000-03-01

Although behavioral studies have demonstrated that normative affective traits modulate the processing of facial and emotionally charged stimuli, direct electrophysiological evidence for this modulation is still lacking. Event-related potential (ERP) data associated with personal, traitlike approach- or withdrawal-related attitude (assessed post-recording and 14 months later) were investigated in 18 subjects during task-free (i.e. unrequested, spontaneous) emotional evaluation of faces. Temporal and spatial aspects of 27 channel ERP were analyzed with microstate analysis and low resolution electromagnetic tomography (LORETA), a new method to compute 3 dimensional cortical current density implemented in the Talairach brain atlas. Microstate analysis showed group differences 132-196 and 196-272 ms poststimulus, with right-shifted electric gravity centers for subjects with negative affective attitude. During these (over subjects reliably identifiable) personality-modulated, face-elicited microstates, LORETA revealed activation of bilateral occipito-temporal regions, reportedly associated with facial configuration extraction processes. Negative compared to positive affective attitude showed higher activity right temporal; positive compared to negative attitude showed higher activity left temporo-parieto-occipital. These temporal and spatial aspects suggest that the subject groups differed in brain activity at early, automatic, stimulus-related face processing steps when structural face encoding (configuration extraction) occurs. In sum, the brain functional microstates associated with affect-related personality features modulate brain mechanisms during face processing already at early information processing stages.

Perceived Barriers to Teaching Movement and Physical Activity to Kindergarteners in Ghana

ERIC Educational Resources Information Center

Sofo, Seidu; Asola, Eugene F.

2015-01-01

Regular participation in physical activity can improve students' health and academic achievement. It is important to develop a positive attitude toward participation in regular physical activity early in life. Thus, an understanding of factors that affect the activity levels of young children is essential. Therefore, the purpose of the study was…

Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.

PubMed

Wagner, Isabella C; van Buuren, Mariët; Bovy, Leonore; Morris, Richard G; Fernández, Guillén

2017-02-01

Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans. Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity. Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later. Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity. Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.

Study on the apoptosis mediated by cytochrome c and factors that affect the activation of bovine longissimus muscle during postmortem aging.

PubMed

Zhang, Jiaying; Yu, Qunli; Han, Ling; Chen, Cheng; Li, Hang; Han, Guangxing

2017-06-01

This study investigates whether bovine longissimus muscle cell apoptosis occurs during postmortem aging and whether apoptosis is dependent on the mitochondria pathway. This study also determines the apoptosis process mediated by cytochrome c after its release from mitochondria and the factors that affect the activation processes. Results indicate that apoptotic nuclei were detected at 12 h postmortem. Cytochrome c release from the mitochondria to the cytoplasm activated the caspase-9 and caspase-3 at early postmortem aging and the activation of caspase-9 occurs before the activation of caspase-3. The pH level decreased during the first 48 h postmortem, whereas the mitochondria membrane permeability increased from 6 to 12 h. Results demonstrate that an apoptosis process of bovine muscle occurred during postmortem aging. Apoptosis was dependent on the mitochondria pathway and occurred at early postmortem aging. Increased mitochondria membrane permeability and low pH are necessary conditions for the release of cytochrome c during postmortem aging.

Autism as a developmental disorder in intentional movement and affective engagement

PubMed Central

Trevarthen, Colwyn; Delafield-Butt, Jonathan T.

2013-01-01

We review evidence that autistic spectrum disorders have their origin in early prenatal failure of development in systems that program timing, serial coordination and prospective control of movements, and that regulate affective evaluations of experiences. There are effects in early infancy, before medical diagnosis, especially in motor sequencing, selective or exploratory attention, affective expression and intersubjective engagement with parents. These are followed by retardation of cognitive development and language learning in the second or third year, which lead to a diagnosis of ASD. The early signs relate to abnormalities that have been found in brain stem systems and cerebellum in the embryo or early fetal stage, before the cerebral neocortex is functional, and they have clear consequences in infancy when neocortical systems are intensively elaborated. We propose, with evidence of the disturbances of posture, locomotion and prospective motor control in children with autism, as well as of their facial expression of interest and affect, and attention to other persons' expressions, that examination of the psychobiology of motor affective disorders, rather than later developing cognitive or linguistic ones, may facilitate early diagnosis. Research in this area may also explain how intense interaction, imitation or “expressive art” therapies, which respond intimately with motor activities, are effective at later stages. Exceptional talents of some autistic people may be acquired compensations for basic problems with expectant self-regulations of movement, attention and emotion. PMID:23882192

Macroscopic brain dynamics during verbal and pictorial processing of affective stimuli.

PubMed

Keil, Andreas

2006-01-01

Emotions can be viewed as action dispositions, preparing an individual to act efficiently and successfully in situations of behavioral relevance. To initiate optimized behavior, it is essential to accurately process the perceptual elements indicative of emotional relevance. The present chapter discusses effects of affective content on neural and behavioral parameters of perception, across different information channels. Electrocortical data are presented from studies examining affective perception with pictures and words in different task contexts. As a main result, these data suggest that sensory facilitation has an important role in affective processing. Affective pictures appear to facilitate perception as a function of emotional arousal at multiple levels of visual analysis. If the discrimination between affectively arousing vs. nonarousing content relies on fine-grained differences, amplification of the cortical representation may occur as early as 60-90 ms after stimulus onset. Affectively arousing information as conveyed via visual verbal channels was not subject to such very early enhancement. However, electrocortical indices of lexical access and/or activation of semantic networks showed that affectively arousing content may enhance the formation of semantic representations during word encoding. It can be concluded that affective arousal is associated with activation of widespread networks, which act to optimize sensory processing. On the basis of prioritized sensory analysis for affectively relevant stimuli, subsequent steps such as working memory, motor preparation, and action may be adjusted to meet the adaptive requirements of the situation perceived.

Les marqueurs structuraux et magmatiques de l'extension crustale au Protérozoïque terminal-Cambrien basal autour du massif de Kerdous (Anti-Atlas occidental, Maroc)

NASA Astrophysics Data System (ADS)

Soulaimani, Abderrahmane; Essaifi, Abderrahim; Youbi, Nassrddine; Hafid, Ahmid

2004-12-01

During the Late Precambrian-Early Cambrian times, the borders of the Kerdous inlier were affected by normal faults where thick conglomerates (Ouarzazate Group: PIII), grading progressively upwards into Cambrian marine sediments, were accumulated along their hanging walls. This tectonic activity persisted during the Early Cambrian and was accompanied by a magmatic activity resulting mainly in the emplacement of continental tholeiitic basalts. These tectono-sedimentary and magmatic events are related to the crustal extensional episode that affected the northwestern Gondwana margin during the opening of the Iapetus Ocean during Late Proterozoic times. To cite this article: A. Soulaimani et al., C. R. Geoscience 336 (2004).

Augmenting Caregiver Responsiveness: An Intervention Proposal for Youngsters with Autism in Brazil

ERIC Educational Resources Information Center

Nunes, Débora R. P.; Araújo, Eliana R.; Walter, Elizabeth; Soares, Rute; Mendonça, Camila

2016-01-01

Language disorders that affect children with autism spectrum disorder can bring significant damage to their overall development. Research shows that the best treatment practices for this population are those that start early, have active parental collaboration and are held in natural milieu. In Brazil, early intervention programs are typically…

Decadal variability in the Northern Hemisphere winter circulation: Role of internal and external drivers

NASA Astrophysics Data System (ADS)

Maliniemi, V.; Asikainen, T.; Mursula, K.

2017-12-01

Northern Hemisphere winter circulation is known to be affected by both internal and external (solar-related) forcings. Earlier studies have shown ENSO and volcanic activity to produce negative and positive North Atlantic Oscillation (NAO) type responses, respectively. In addition, recent studies have shown a positive NAO response related to both geomagnetic activity (proxy for solar wind driven particle precipitation) and sunspot activity (proxy for solar irradiance). These solar-related signals have been suggested to be due to the changes in the polar vortex. Here the relative role of these four internal and external drivers on wintertime circulation in the Northern Hemisphere is studied. The phase of the quasi-biennial oscillation (QBO) is used to study the driver responses for different stratospheric conditions. Moreover, the effects are separated for early (Dec/Jan) and late (Feb/Mar) winter. The global pattern of ENSO is very similar (negative NAO) otherwise, but in early winter and westerly QBO the pattern is changed in the Atlantic sector to a weakly positive NAO. The positive NAO pattern due to volcanic activity is more pronounced for westerly QBO in both early and late winter. The positive NAO pattern produced by geomagnetic activity is obtained during easterly QBO phase in both early and late winter. Sunspot related NAO response in late winter is also strongly modulated by the QBO phase. These results imply that the stratospheric conditions expressed by QBO significantly modulate the way the internal and external drivers affect the Northern Hemisphere winter climate.

Two critical periods in early visual cortex during figure-ground segregation.

PubMed

Wokke, Martijn E; Sligte, Ilja G; Steven Scholte, H; Lamme, Victor A F

2012-11-01

The ability to distinguish a figure from its background is crucial for visual perception. To date, it remains unresolved where and how in the visual system different stages of figure-ground segregation emerge. Neural correlates of figure border detection have consistently been found in early visual cortex (V1/V2). However, areas V1/V2 have also been frequently associated with later stages of figure-ground segregation (such as border ownership or surface segregation). To causally link activity in early visual cortex to different stages of figure-ground segregation, we briefly disrupted activity in areas V1/V2 at various moments in time using transcranial magnetic stimulation (TMS). Prior to stimulation we presented stimuli that made it possible to differentiate between figure border detection and surface segregation. We concurrently recorded electroencephalographic (EEG) signals to examine how neural correlates of figure-ground segregation were affected by TMS. Results show that disruption of V1/V2 in an early time window (96-119 msec) affected detection of figure stimuli and affected neural correlates of figure border detection, border ownership, and surface segregation. TMS applied in a relatively late time window (236-259 msec) selectively deteriorated performance associated with surface segregation. We conclude that areas V1/V2 are not only essential in an early stage of figure-ground segregation when figure borders are detected, but subsequently causally contribute to more sophisticated stages of figure-ground segregation such as surface segregation.

Two critical periods in early visual cortex during figure–ground segregation

PubMed Central

Wokke, Martijn E; Sligte, Ilja G; Steven Scholte, H; Lamme, Victor A F

2012-01-01

The ability to distinguish a figure from its background is crucial for visual perception. To date, it remains unresolved where and how in the visual system different stages of figure–ground segregation emerge. Neural correlates of figure border detection have consistently been found in early visual cortex (V1/V2). However, areas V1/V2 have also been frequently associated with later stages of figure–ground segregation (such as border ownership or surface segregation). To causally link activity in early visual cortex to different stages of figure–ground segregation, we briefly disrupted activity in areas V1/V2 at various moments in time using transcranial magnetic stimulation (TMS). Prior to stimulation we presented stimuli that made it possible to differentiate between figure border detection and surface segregation. We concurrently recorded electroencephalographic (EEG) signals to examine how neural correlates of figure–ground segregation were affected by TMS. Results show that disruption of V1/V2 in an early time window (96–119 msec) affected detection of figure stimuli and affected neural correlates of figure border detection, border ownership, and surface segregation. TMS applied in a relatively late time window (236–259 msec) selectively deteriorated performance associated with surface segregation. We conclude that areas V1/V2 are not only essential in an early stage of figure–ground segregation when figure borders are detected, but subsequently causally contribute to more sophisticated stages of figure–ground segregation such as surface segregation. PMID:23170239

Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

PubMed

Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

2017-09-01

The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of the adenosine A2A receptor antagonist MSX-3 on motivational disruptions of maternal behavior induced by dopamine antagonism in the early postpartum rat.

PubMed

Pereira, Mariana; Farrar, Andrew M; Hockemeyer, Jörg; Müller, Christa E; Salamone, John D; Morrell, Joan I

2011-01-01

Mesolimbic dopamine (DA), particularly in the nucleus accumbens, importantly regulates activational aspects of maternal responsiveness. DA antagonism and accumbens DA depletions interfere with early postpartum maternal motivation by selectively affecting most forms of active maternal behaviors, while leaving nursing behavior relatively intact. Considerable evidence indicates that there is a functional interaction between DA D2 and adenosine A(2A) receptors in striatal areas, including the nucleus accumbens. This study was conducted to determine if adenosine A(2A) receptor antagonism could reverse the effects of DA receptor antagonism on early postpartum maternal behavior. The adenosine A(2A) receptor antagonist MSX-3 (0.25-2.0 mg/kg, IP) was investigated for its ability to reverse the effects of the DA D2 receptor antagonist haloperidol (0.1 mg/kg, IP) on the maternal behavior of early postpartum female rats. Haloperidol severely impaired the expression of active maternal components, including retrieval and grouping the pups at the nest site, pup licking, and nest building. Co-administration of MSX-3 (0.25-2.0 mg/kg, IP) with haloperidol produced a dose-related attenuation of the haloperidol-induced behavioral deficits in early postpartum females. Doses of MSX-3 that effectively reversed the effects of haloperidol (0.5, 1.0 mg/kg), when administered in the absence of haloperidol, did not affect maternal responding or locomotor activity. Adenosine and DA systems interact to regulate early postpartum maternal responsiveness. This research may potentially contribute to the development of strategies for treatments of psychiatric disorders during the postpartum period, with particular emphasis in maintaining or restoring the mother-infant relationship.

Effect of the adenosine A2A receptor antagonist MSX-3 on motivational disruptions of maternal behavior induced by dopamine antagonism in the early postpartum rat

PubMed Central

Farrar, Andrew M.; Hockemeyer, Jörg; Müller, Christa E.; Salamone, John D.; Morrell, Joan I.

2011-01-01

Rationale Mesolimbic dopamine (DA), particularly in the nucleus accumbens, importantly regulates activational aspects of maternal responsiveness. DA antagonism and accumbens DA depletions interfere with early postpartum maternal motivation by selectively affecting most forms of active maternal behaviors, while leaving nursing behavior relatively intact. Considerable evidence indicates that there is a functional interaction between DA D2 and adenosine A2A receptors in striatal areas, including the nucleus accumbens. Objective This study was conducted to determine if adenosine A2A receptor antagonism could reverse the effects of DA receptor antagonism on early postpartum maternal behavior. Methods The adenosine A2A receptor antagonist MSX-3 (0.25–2.0 mg/kg, IP) was investigated for its ability to reverse the effects of the DA D2 receptor antagonist haloperidol (0.1 mg/kg, IP) on the maternal behavior of early postpartum female rats. Results Haloperidol severely impaired the expression of active maternal components, including retrieval and grouping the pups at the nest site, pup licking, and nest building. Co-administration of MSX-3 (0.25–2.0 mg/kg, IP) with haloperidol produced a dose-related attenuation of the haloperidol-induced behavioral deficits in early postpartum females. Doses of MSX-3 that effectively reversed the effects of haloperidol (0.5, 1.0 mg/kg), when administered in the absence of haloperidol, did not affect maternal responding or locomotor activity. Conclusions Adenosine and DA systems interact to regulate early postpartum maternal responsiveness. This research may potentially contribute to the development of strategies for treatments of psychiatric disorders during the postpartum period, with particular emphasis in maintaining or restoring the mother–infant relationship. PMID:20848086

Optical Topography of Evoked Brain Activity during Mental Tasks Involving Whole Number Operations

ERIC Educational Resources Information Center

Ortiz, Enrique

2014-01-01

Students start to memorize arithmetic facts from early elementary school mathematics activities. Their fluency or lack of fluency with these facts could affect their efforts as they carry out mental calculations as adults. This study investigated participants' levels of brain activation and possible reasons for these levels as they solved…

The Policies and Practice of Preschoolers' Outdoor Play: A Chinese Perspective on Greeting the Millennium

ERIC Educational Resources Information Center

Hu, Bi Ying; Kong, Zhaowei; Roberts, Sherron Killingsworth

2014-01-01

Early childhood education and care (ECEC) scholars and health professionals worldwide share a common concern about the decline in children's physical development and activity due to lack of access to good quality outdoor environments. Early childhood education and care facilities across the world have been affected by trends that are limiting…

Early Sensory Over-Responsivity in Toddlers with Autism Spectrum Disorders as a Predictor of Family Impairment and Parenting Stress

ERIC Educational Resources Information Center

Ben-Sasson, A.; Soto, T. W.; Martinez-Pedraza, F.; Carter, A. S.

2013-01-01

Background: Sensory over-responsivity (SOR) affects many individuals with autism spectrum disorders (ASD), often leading to stressful encounters during daily routines. Methods: This study describes the associations between early SOR symptoms and the longitudinal course of restrictions in family life activities and parenting stress across three…

Age of Supergene oxidation and enrichment in the chilean porphyry copper province

USGS Publications Warehouse

Sillitoe, R.H.; McKee, E.H.

1996-01-01

Twenty-five samples of supergene alunite collected from deeply developed supergene profiles in porphyry copper deposits and prospects between latitudes 20?? and 27?? S in northern Chile yield K/Ar ages ranging from about 34 to 14 Ma. Therefore supergene oxidation and enrichment processes were active from the early Oligocene to the middle Miocene, a minimum of 20 m.y. Supergene activity at individual deposits lasted for at least 0.4 to 6.2 m.y. The early Oligocene supergene activity affected deposits in the Paleocene porphyry copper belt, whereas early and middle Miocene supergene processes are documented in the Early Cretaceous, Paleocene, and late Eocene to early Oligocene porphyry copper belts. Middle Miocene oxidation also affected the oldest epithermal gold-silver deposits in the Maricunga belt farther east. Supergene activity commenced no less than 11 m.y. after generation of each porphyry copper deposit because of the time required to unroof the copper-bearing parts of the system. Supergene activity throughout northern Chile ceased at -14 Ma. The geologic features of deposits and prospects and their morphotectonic positions, present latitudes, and present elevations display no obvious correlations with the supergene chronology. Exploration for major cumulative enrichment blankets should not be carried out either beneath thick sequences of piedmont gravels (?? ignimbrites) of Oligocene through middle Miocene age unless their accumulation is demonstrably late in the documented history of supergene activity, or in porphyry copper provinces, such as those of central Chile and northwestern Argentina, which formed after ??? 14 Ma. The uplift responsible for efficient cumulative copper enrichment is difficult to correlate convincingly with the brief pulses of compressive tectonism postulated for northern Chile and contiguous areas unless their effects were much more prolonged. Intensifying aridity is confirmed as the likely reason for the cessation of supergene activity in northern Chile, and tectonic uplift was its most probable cause. However, more fundamental global controls producing a period of chemical weathering followed by worldwide dessication also may have played a role.

Active Music Classes in Infancy Enhance Musical, Communicative and Social Development

ERIC Educational Resources Information Center

Gerry, David; Unrau, Andrea; Trainor, Laurel J.

2012-01-01

Previous studies suggest that musical training in children can positively affect various aspects of development. However, it remains unknown as to how early in development musical experience can have an effect, the nature of any such effects, and whether different types of music experience affect development differently. We found that random…

Anticipated affective consequences of physical activity adoption and maintenance.

PubMed

Dunton, Genevieve Fridlund; Vaughan, Elaine

2008-11-01

The expected emotional consequences of future actions are thought to play an important role in health behavior change. This research examined whether anticipated affective consequences of success and failure vary across stages of physical activity change and differentially predict physical activity adoption as compared to maintenance. Using a prospective design over a 3-month period, a community sample of 329 healthy, middle-aged adults were assessed at 2 time points. Anticipated positive and negative emotions, stage of behavior change (precontemplation [PC], contemplation [C], preparation [P], action [A], maintenance [M]), and level of physical activity. At baseline, anticipated positive emotions were greater in C versus PC, whereas anticipated negative emotions were greater in M versus A and in M versus P. Higher anticipated positive but not negative emotions predicted physical activity adoption and maintenance after 3 months. Although the expected affective consequences of future success and failure differentiated among individuals in the early and later stages of physical activity change, respectively; only the anticipated affective consequences of success predicted future behavior.

Learning what feelings to desire: socialization of ideal affect through children's storybooks.

PubMed

Tsai, Jeanne L; Louie, Jennifer Y; Chen, Eva E; Uchida, Yukiko

2007-01-01

Previous findings suggest that cultural factors influence ideal affect (i.e., the affective states that people ideally want to feel). Three studies tested the hypothesis that cultural differences in ideal affect emerge early in life and are acquired through exposure to storybooks. In Study 1, the authors established that consistent with previous findings, European American preschoolers preferred excited (vs. calm) states more (indexed by activity and smile preferences) and perceived excited (vs. calm) states as happier than Taiwanese Chinese preschoolers. In Study 2, it was observed that similar differences were reflected in the pictures (activities, expressions, and smiles) of best-selling storybooks in the United States and Taiwan. Study 3 found that across cultures, exposure to exciting (vs. calm) storybooks altered children's preferences for excited (vs. calm) activities and their perceptions of happiness. These findings suggest that cultural differences in ideal affect may be due partly to differential exposure to calm and exciting storybooks.

Relational Schemas and the Developing Self: Perceptions of Mother and of Self as Joint Predictors of Early Adolescents' Self-Esteem

ERIC Educational Resources Information Center

Ojanen, Tiina; Perry, David G.

2007-01-01

This 1-year longitudinal study examined early adolescents' (N=278, age 11-13 years) perceptions of their mother's behavior (affection, knowledge of child's activities, and psychological control) and of how they react to their mother (trust in mother, defiance, and debilitation) as predictors of self-esteem among peers. Perceived maternal affection…

Early warning signals of regime shifts from cross-scale connectivity of land-cover patterns

Treesearch

Giovanni Zurlini; Kenneth Bruce Jones; Kurt Hans Riitters; Bai-Lian Li; Irene Petrosillo

2014-01-01

Increasing external pressures from human activities and climate change can lead to desertification, affecting the livelihood of more than 25% of the world’s population. Thus, determining proximity to transition to desertification is particularly central for arid regions before they may convert into deserts, and recent research has focused on devising early warning...

Probiotic legacy effects on gut microbial assembly in tilapia larvae

PubMed Central

Giatsis, Christos; Sipkema, Detmer; Ramiro-Garcia, Javier; Bacanu, Gianina M.; Abernathy, Jason; Verreth, Johan; Smidt, Hauke; Verdegem, Marc

2016-01-01

The exposure of fish to environmental free-living microbes and its effect on early colonization in the gut have been studied in recent years. However, little is known regarding how the host and environment interact to shape gut communities during early life. Here, we tested whether the early microbial exposure of tilapia larvae affects the gut microbiota at later life stages. The experimental period was divided into three stages: axenic, probiotic and active suspension. Axenic tilapia larvae were reared either under conventional conditions (active suspension systems) or exposed to a single strain probiotic (Bacillus subtilis) added to the water. Microbial characterization by Illumina HiSeq sequencing of 16S rRNA gene amplicons showed the presence of B. subtilis in the gut during the seven days of probiotic application. Although B. subtilis was no longer detected in the guts of fish exposed to the probiotic after day 7, gut microbiota of the exposed tilapia larvae remained significantly different from that of the control treatment. Compared with the control, fish gut microbiota under probiotic treatment was less affected by spatial differences resulting from tank replication, suggesting that the early probiotic contact contributed to the subsequent observation of low inter-individual variation. PMID:27670882

Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of ST-Segment-Elevation Myocardial Infarction.

PubMed

Nishiguchi, Tsuyoshi; Tanaka, Atsushi; Taruya, Akira; Emori, Hiroki; Ozaki, Yuichi; Orii, Makoto; Shiono, Yasutsugu; Shimamura, Kunihiro; Kameyama, Takeyoshi; Yamano, Takashi; Yamaguchi, Tomoyuki; Matsuo, Yoshiki; Ino, Yasushi; Kubo, Takashi; Hozumi, Takeshi; Hayashi, Yasushi; Akasaka, Takashi

2016-12-01

Early clinical presentation of ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction affects patient management. Although local inflammatory activities are involved in the onset of MI, little is known about their impact on early clinical presentation. This study aimed to investigate whether local inflammatory activities affect early clinical presentation. This study comprised 94 and 17 patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris, respectively. We simultaneously investigated the culprit lesion morphologies using optical coherence tomography and inflammatory activities assessed by shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary circulation before and after stenting. Prevalence of plaque rupture, thin-cap fibroatheroma, and lipid arc or macrophage count was higher in patients with STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was frequently observed in STEMI compared with others. Local MMP-9 levels were significantly higher than systemic levels (systemic, 42.0 [27.9-73.2] ng/mL versus prestent local, 69.1 [32.2-152.3] ng/mL versus poststent local, 68.0 [35.6-133.3] ng/mL; P<0.01). Poststent local MMP-9 level was significantly elevated in patients with STEMI (STEMI, 109.9 [54.5-197.8] ng/mL versus non-STEMI: 52.9 [33.0-79.5] ng/mL; stable angina pectoris, 28.3 [14.2-40.0] ng/mL; P<0.01), whereas no difference was observed in the myeloperoxidase level. Poststent local MMP-9 and the presence of red thrombus are the independent determinants for STEMI in multivariate analysis. Local MMP-9 level could determine the early clinical presentation in patients with MI. Local inflammatory activity for atherosclerosis needs increased attention. © 2016 American Heart Association, Inc.

Passion in breast cancer survivors: examining links to emotional well-being.

PubMed

Burke, Shaunna M; Sabiston, Catherine M; Vallerand, Robert J

2012-11-01

This study (1) identified the activities that breast cancer survivors report as passionate; (2) examined whether levels of passion differed based on the types of passionate activities reported and; (3) examined the association between harmonious and obsessive passion and emotional well-being. Early post-treatment breast cancer survivors (N = 177) reported passionate physical activities as most prevalent, and reported higher harmonious passion scores compared to women reporting relaxing and social leisure activities. Harmonious passion was associated with higher positive affect and lower cancer worry. Obsessive passion was linked to higher negative affect, cancer worry, and posttraumatic growth. Passion is important for enhanced well-being.

Can you un-ring the bell? A qualitative study of how affect influences cancer screening decisions.

PubMed

Driedger, S Michelle; Annable, Gary; Brouwers, Melissa; Turner, Donna; Maier, Ryan

2017-09-13

The belief that early detection is the best protection against cancer underlies cancer screening. Emerging research now suggests harms associated with early detection may sometimes outweigh the benefits. Governments, cancer agencies, and organizations that publish screening guidelines have found it is difficult to "un-ring the bell" on the message that "early detection is your best protection" because of its widespread communication and enduring resonance. This study explores affective factors-and their interplay with relevant analytical factors-in public/laypersons' decision making about cancer screening. A total of 93 people (47 men, 46 women) attended focus groups about, respectively, prostate cancer screening and breast cancer screening in two Canadian cities. Affective factors were a major influence on many focus group participants' decision making about cancer screening, including fear of cancer and a generalized enthusiasm for prevention/screening, and they were often inspired by anecdotes about the cancer experiences of family and friends. Affect also existed alongside more analytical factors including assessments of reduced risk in the management of any cancer diagnosis if caught early, and, for men, the belief that an unreliable test is "better than nothing," and that men deserve prostate cancer screening because women have breast and cervical cancer screening. Affective factors were particularly noticeable in the sub-groups most supportive of screening and the "early detection" message: older women who felt that mammogram screening should begin at age 40 rather than 50, and older men who felt that prostate cancer screening should be expanded beyond its current unorganized, opportunistic usage. In contrast, younger participants displayed less affective attachments to "early detection" messages and had greater concerns about harms of screening and were more receptive to nuanced messages informed by evidence. Policymakers attempting to communicate more nuanced versions of the "early detection" message need to understand the role of affect alongside other judgments brought into laypersons' decision making processes and anticipate how affective responses to their messages will be shaped, transformed, and potentially subverted by external forces beyond their control. Particularly overt external factors are campaigns by cancer advocacy organizations actively promoting breast and prostate cancer awareness and screening to younger women and men using affectively-charged messages.

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

PubMed Central

Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M.; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2017-01-01

Abstract Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. PMID:27694318

Differences In Early T-Cell Signaling In Cultures Grown In a Rotating Clinostat vs. Static Controls

NASA Technical Reports Server (NTRS)

Alexamder. M.; Nelman-Gonzales, M.; Penkala, J.; Sams, C.

1999-01-01

Altered gravity has previously been demonstrated to be a stress that can influence components of the immune system. Specifically, T-cell activation has been shown to be affected by changes in gravity, exhibiting a decrease in proliferative response to in vitro stimulation in microgravity. Subsequent ground based studies utilizing a rotating clinostat to model some of the effects of microgravity have been consistent with earlier flight based experiments. These ground and flight experiments have examined T-cell activation by measuring various responses including production of cytokines, DNA synthesis and the production of various cell surface activation markers. These indicators of T-cell activation were measured anywhere from 4 to 72 hours after stimulation. Prior to the work described here, the initial signaling events in T-cell activation had not been directly examined. The goal of this project was to determine how the process of early signal transduction was affected by growth in a rotating clinostat. Here we directly show a defect in signaling from TCR to MAPK in purified peripheral T-cells activated in the clinostat by OKT3/antiCD28 coated microbeads as compared to static controls.

Temporal orienting precedes intersensory attention and has opposing effects on early evoked brain activity.

PubMed

Keil, Julian; Pomper, Ulrich; Feuerbach, Nele; Senkowski, Daniel

2017-03-01

Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm. IA was manipulated by presenting auditory cues to indicate whether participants should detect visual or tactile targets in visuo-tactile stimuli. TO was manipulated by presenting stimuli block-wise at fixed or variable inter-stimulus intervals. We observed that TO affects evoked activity to visuo-tactile stimuli prior to IA. Moreover, we found that TO reduces the amplitude of early evoked brain activity, whereas IA enhances it. Using beamformer source-localization, we observed that IA increases neural responses in sensory areas of the attended modality whereas TO reduces brain activity in widespread cortical areas. Based on these findings we derive an updated working model for the effects of temporal and intersensory attention on early evoked brain activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Deep vein thrombosis in hospitalized patients: a review of evidence-based guidelines for prevention.

PubMed

Kehl-Pruett, Wendy

2006-01-01

Deep vein thrombosis affects many hospitalized patients because of decreased activity and therapeutic equipment. This article reviews known risk factors for developing deep vein thrombosis, current prevention methods, and current evidence-based guidelines in order to raise nurses' awareness of early prevention methods in all hospitalized patients. Early prophylaxis can reduce patient risk of deep vein thrombosis and its complications.

Early Fishing Peoples of Puget Sound. Ocean Related Curriculum Activities. Revised Edition.

ERIC Educational Resources Information Center

McNutt, Nan

The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in Type 2 diabetes.

PubMed

Kong, C; Nimmo, L; Elatrozy, T; Anyaoku, V; Hughes, C; Robinson, S; Richmond, W; Elkeles, R S

2001-06-01

We have studied the relationships between hepatic lipase activity, smoking, dyslipidaemia insulin resistance, and early atherosclerosis in 67 Type 2 diabetic subjects, 47 non-smokers and 20 smokers. Insulin resistance was measured using an insulin modified frequently sampled intravenous glucose tolerance test. Early atherosclerosis was assessed using high-resolution ultrasound to measure carotid intima media thickness (IMT) and an arterial ultrasonic score (AUS). Smokers had higher serum cholesterol and triglyceride, lower HDL and HDL2 cholesterol as well as increased hepatic lipase activity. They were also more insulin resistant than non-smokers. Smokers also had higher patient AUS scores. On multiple regression analysis, hepatic lipase activity emerged as the most significant variable affecting patient AUS. We suggest that smoking accentuates the dyslipidaemia of Type 2 diabetic subjects and this is associated with increased hepatic lipase activity. This may be one mechanism whereby smoking further increases the risk of cardiovascular disease in Type 2 diabetes.

Taking the brakes off the learning curve.

PubMed

Gheysen, Freja; Lasne, Gabriel; Pélégrini-Issac, Mélanie; Albouy, Genevieve; Meunier, Sabine; Benali, Habib; Doyon, Julien; Popa, Traian

2017-03-01

Motor learning is characterized by patterns of cerebello-striato-cortical activations shifting in time, yet the early dynamic and function of these activations remains unclear. Five groups of subjects underwent either continuous or intermittent theta-burst stimulation of one cerebellar hemisphere, or no stimulation just before learning a new motor sequence during fMRI scanning. We identified three phases during initial learning: one rapid, one slow, and one quasi-asymptotic performance phase. These phases were not changed by left cerebellar stimulation. Right cerebellar inhibition, however, accelerated learning and enhanced brain activation in critical motor learning-related areas during the first phase, continuing with reduced brain activation but high-performance in late phase. Right cerebellar excitation did not affect the early learning process, but slowed learning significantly in late phase, along with increased brain activation. We conclude that the right cerebellum is a key factor coordinating other neuronal loops in the early acquisition of an explicit motor sequential skill. Hum Brain Mapp 38:1676-1691, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model

PubMed Central

Fu, Zhong-Hua; Guo, Guang-Hua; Xiong, Zhen-Fang; Liao, Xincheng; Liu, Ming-Zhuo; Luo, Jinhua

2017-01-01

The aim of the present study was to determine the effects of early anticoagulation treatment on severe burns complicated by inhalation injury in a rabbit model. Under anesthetization, an electrical burns instrument (100°C) was used to scald the backs of rabbits for 15 sec, which established a 30% III severe burns model. Treatment of the rabbits with early anticoagulation effectively improved the severe burns complicated by inhalation injury-induced lung injury, reduced PaO2, PaCO2 and SPO2 levels, suppressed the expression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and increased the activity of IL-10. In addition, it was found that early anticoagulation treatment effectively suppressed the activities of caspase-3 and caspase-9, upregulated the protein expression of vascular endothelial growth factor (VEGF) and decreased the protein expression of protease-activated receptor 1 (PAR1) in the severe burns model. It was concluded that early anticoagulation treatment affected the severe burns complicated by inhalation injury in a rabbit model through the upregulation of VEGF and downregulation of PAR1 signaling pathways. Thus, early anticoagulation is a potential therapeutic option for severe burns complicated by inhalation injury. PMID:28944866

Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus macaques (Macaca mulatta).

PubMed

Barr, C S; Newman, T K; Lindell, S; Becker, M L; Shannon, C; Champoux, M; Suomi, S J; Higley, J D

2004-07-01

Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

The relationship between early ego strength and adolescent responses to the threat of nuclear war

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

Andrekus, N.J.

Ego resiliency and ego control, measured when subjects were 3 or 4 years old, were related to expectation of war, concern for the future, and activism in response to the threat of nuclear war, measured when subjects were 18 years old. Data from 92 participants in a longitudinal study of ego and cognitive development conducted by Jeanne and Jack Block at the University of California, Berkeley were used to test hypotheses. Assessments with the California Child Q-set, composited across multiple independent observers, provide measures of ego resiliency and ego control. Adolescent interviews regarding the perception of likelihood of nuclear war,more » how this affects their future, and their antinuclear and general political activism were scaled and rated. Early ego resiliency and ego under control were hypothesized to account for the variance in adolescent nuclear responses and activism. The only significant longitudinal relationships were in the female sample, where ego under control was found to be a significant predictor of both general political activism (p<.01) and ideas of the future being affected by the nuclear threat (p<.05). Among males, the relationship between early ego resiliency and adolescent antinuclear activism approached significance (p<.10). Adolescent personality was significantly related to several measures of nuclear response. In girls, adolescent ego under control related to perception of likelihood of nuclear war (p<.05) and antinuclear activism (p<.05), and the interaction of ego resiliency and ego under control predicted general political activism (p<.0005). In boys, adolescent ego resiliency correlated with antinuclear activism (p<.05). These findings were discussed in terms of antecedent parenting styles, and conceptual links were drawn between children's ego resiliency and security of attachment, perspective taking, and moral development.« less

Increasing Adolescents' Subjective Well-Being: Effects of a Positive Psychology Intervention in Comparison to the Effects of Therapeutic Alliance, Youth Factors, and Expectancy for Change

ERIC Educational Resources Information Center

Savage, Jessica Ann

2011-01-01

This study investigated the variance in subjective well-being (SWB) of early adolescents ( n = 54) exposed to a positive psychology intervention aimed at increasing positive affect and life satisfaction as well as decreasing negative affect through intentional activities (e.g., gratitude journals, acts of kindness, use of character strengths,…

Early and Later Life Stress Alter Brain Activity and Sleep in Rats

PubMed Central

Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

2013-01-01

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

Beyond pleasure and arousal: appetitive erotic stimuli modulate electrophysiological brain correlates of early attentional processing.

PubMed

Kuhr, Benjamin; Schomberg, Jessica; Gruber, Thomas; Quirin, Markus

2013-03-27

Previous studies investigating affective reactions to pictures that elicit a specific effect have mainly focused on the dimensions valence and arousal. Using an event-related picture-viewing paradigm in electroencephalography, we investigated whether erotica - that is appetitive, evolutionarily relevant stimuli - have effects on early stages of attentional processing that are distinct from those of other positive and arousing stimuli. Seventeen male students viewed arousing photos of erotic, nude women or pictures of extreme sport scenes, as well as control pictures of attractive, dressed women or daily activities. Erotic pictures differed from extreme sport pictures not only in late but also in early attentional processes, as indicated by event-related potentials appearing from 130 ms after stimulus onset (P1). The findings suggest (a) that the dimension of appetence should be considered in addition to valence and arousal when investigating psychophysiological reactions to affective-motivational stimuli and (b) that early attentional processing as mirrored by the P1 can be influenced by motivational systems.

The role of asymmetric frontal cortical activity in emotion-related phenomena: a review and update.

PubMed

Harmon-Jones, Eddie; Gable, Philip A; Peterson, Carly K

2010-07-01

Conceptual and empirical approaches to the study of the role of asymmetric frontal cortical activity in emotional processes are reviewed. Although early research suggested that greater left than right frontal cortical activity was associated with positive affect, more recent research, primarily on anger, suggests that greater left than right frontal cortical activity is associated with approach motivation, which can be positive (e.g., enthusiasm) or negative in valence (e.g., anger). In addition to reviewing this research on anger, research on guilt, bipolar disorder, and various types of positive affect is reviewed with relation to their association with asymmetric frontal cortical activity. The reviewed research not only contributes to a more complete understanding of the emotive functions of asymmetric frontal cortical activity, but it also points to the importance of considering motivational direction as separate from affective valence in psychological models of emotional space. Copyright © 2009 Elsevier B.V. All rights reserved.

Affective Imagination in Science Education: Determining the Emotional Nature of Scientific and Technological Learning of Young Children

NASA Astrophysics Data System (ADS)

Fleer, Marilyn

2013-10-01

Vygotsky (1986) draws attention to the interrelationship between thought and language and other aspects of mind. Although not widely acknowledged, Vygotsky (1999) also drew attention to the search for the relations between cognition and emotions. This paper discusses the findings of a study which examined imaginary scientific situations within the early years. The central research questions examined: What is the emotional nature of scientific learning? and How does affective imagination support early childhood science learning? Video observations were made of the teaching of science from one site in a south-eastern community in Australia (232 h of video observations). The teachers used fairy tales and Slowmation as cultural devices to support the concept formation of 3- and 4-year-old children (n = 53; range of 3.3 to 4.4; mean of 3.8 years). The findings of this under-researched area (e.g. Roth, Mind, Culture, and Activity 15:2-7, 2008) make a contribution to understanding how affective imagination can work in science education in the early years.

Diet and gender are important factors modulating low frequency EEG activity during processing of language sounds in 3 month old infants

USDA-ARS?s Scientific Manuscript database

Little is known about how early postnatal diet affects brain processes related to cognitive function in healthy infants. To address this question we examined EEG activity recorded from 3 month old infants [breastfed (BF: n = 104, 55 males), milk-based formula fed (MF: n = 114, 57 males) or soy for...

A Time of Quiet Activism: Research, Practice, and Policy in American Women's Higher Education, 1945-1965

ERIC Educational Resources Information Center

Eisenmann, Linda

2005-01-01

This article reflects on three narratives that affected American women's participation in higher education during the first twenty years after World War II. In hindsight, the educators of the 1950s and early 1960s may seem gratuitously meek and self-effacing. In comparison to later efforts, their activism can appear unnecessarily limited and too…

Magnetoencephalographic responses to illusory figures: early evoked gamma is affected by processing of stimulus features.

PubMed

Herrmann, C S; Mecklinger, A

2000-12-01

We examined evoked and induced responses in event-related fields and gamma activity in the magnetoencephalogram (MEG) during a visual classification task. The objective was to investigate the effects of target classification and the different levels of discrimination between certain stimulus features. We performed two experiments, which differed only in the subjects' task while the stimuli were identical. In Experiment 1, subjects responded by a button-press to rare Kanizsa squares (targets) among Kanizsa triangles and non-Kanizsa figures (standards). This task requires the processing of both stimulus features (colinearity and number of inducer disks). In Experiment 2, the four stimuli of Experiment 1 were used as standards and the occurrence of an additional stimulus without any feature overlap with the Kanizsa stimuli (a rare and highly salient red fixation cross) had to be detected. Discrimination of colinearity and number of inducer disks was not necessarily required for task performance. We applied a wavelet-based time-frequency analysis to the data and calculated topographical maps of the 40 Hz activity. The early evoked gamma activity (100-200 ms) in Experiment 1 was higher for targets as compared to standards. In Experiment 2, no significant differences were found in the gamma responses to the Kanizsa figures and non-Kanizsa figures. This pattern of results suggests that early evoked gamma activity in response to visual stimuli is affected by the targetness of a stimulus and the need to discriminate between the features of a stimulus.

Alkaline phosphatase activity in human colostrum as a valuable predictive biomarker for lactational mastitis in nursing mothers.

PubMed

Bjelakovic, Ljiljana; Kocic, Gordana; Bjelakovic, Bojko; Zivkovic, Nikola; Stojanović, Dusica; Sokolovic, Danka; Mladenovic-Ciric, Ivana; Sokolovic, Dusan

2012-08-01

Biochemical investigations have shown that an indigenous milk enzyme - alkaline phosphatase (ALP) - which is detectable in the lactocytes, plays a very important diagnostic role in clinical medicine, since its activity varies in different tissues and serves as a specific indicator of disease states. The purpose of this study was to evaluate ALP activity in human colostrum as a possible early predictive biomarker for lactational mastitis in nursing mothers. During a period from May to July 2010, a total of 60 healthy nursing mothers were recruited for this study. The mean level of colostrum ALP activity from the affected breasts was significantly higher when compared with ALP activity from the contralateral asymptomatic as well as 'healthy' breasts (p < 0.01). Determining ALP activity in colostrum could be a valuable biochemical marker for an early prediction of mastitis in nursing mothers.

Early prediction of student goals and affect in narrative-centered learning environments

NASA Astrophysics Data System (ADS)

Lee, Sunyoung

Recent years have seen a growing recognition of the role of goal and affect recognition in intelligent tutoring systems. Goal recognition is the task of inferring users' goals from a sequence of observations of their actions. Because of the uncertainty inherent in every facet of human computer interaction, goal recognition is challenging, particularly in contexts in which users can perform many actions in any order, as is the case with intelligent tutoring systems. Affect recognition is the task of identifying the emotional state of a user from a variety of physical cues, which are produced in response to affective changes in the individual. Accurately recognizing student goals and affect states could contribute to more effective and motivating interactions in intelligent tutoring systems. By exploiting knowledge of student goals and affect states, intelligent tutoring systems can dynamically modify their behavior to better support individual students. To create effective interactions in intelligent tutoring systems, goal and affect recognition models should satisfy two key requirements. First, because incorrectly predicted goals and affect states could significantly diminish the effectiveness of interactive systems, goal and affect recognition models should provide accurate predictions of user goals and affect states. When observations of users' activities become available, recognizers should make accurate early" predictions. Second, goal and affect recognition models should be highly efficient so they can operate in real time. To address key issues, we present an inductive approach to recognizing student goals and affect states in intelligent tutoring systems by learning goals and affect recognition models. Our work focuses on goal and affect recognition in an important new class of intelligent tutoring systems, narrative-centered learning environments. We report the results of empirical studies of induced recognition models from observations of students' interactions in narrative-centered learning environments. Experimental results suggest that induced models can make accurate early predictions of student goals and affect states, and they are sufficiently efficient to meet the real-time performance requirements of interactive learning environments.

Effect of fast pH decline during the early postmortem period on calpain activity and cytoskeletal protein degradation of broiler M. pectoralis major.

PubMed

Huang, J C; Yang, J; Huang, F; Huang, M; Chen, K J; Xu, X L; Zhou, G H

2016-10-01

The objective of this study was to determine the effects of fast pH decline during the early postmortem period on calpain activity and the degradation of cytoskeletal proteins in broilers. Eighty broilers were randomly categorized into two groups: physical restraint (PR) and free struggle (FS). M. pectoralis major (PM) was used for determination of calpain activity, shear value, ultrastructure of myofibrils, and the degradation of desmin, titin, nebulin, and troponin-T. The pH (6.05) of FS group is significantly low than PR group (6.38) at 0.3 h postmortem. Fast pH decline during the early postmortem period led to a decrease of μ/m-calpain activities at 0.3 and 3 h postmortem (P < 0.05), but did not affect the ultimate μ/m-calpain activity. An initial fast decrease in pH increased the degradation of desmin, titin, nebulin, and increased the 30 kDa degradation fragments of troponin-T. Therefore, the fast pH decline during the early postmortem period decreased the μ/m-calpain activity and increased the degradation of cytoskeletal proteins in broiler muscle. It is possible that the fast pH decline experienced an earlier activation of calpains that resulted in earlier protein degradation and ultimately lower shear force. © 2016 Poultry Science Association Inc.

Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors

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

Maroni, Paola; Brini, Anna Teresa; Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Universita degli Studi di Milano, Milano

2012-11-16

Highlights: Black-Right-Pointing-Pointer Acetylation affected hASCs osteodifferentiation through Runx2-PPAR{gamma}. Black-Right-Pointing-Pointer HDACs knocking-down favoured the commitment effect of osteogenic medium. Black-Right-Pointing-Pointer HDACs silencing early activated Runx2 and ALP. Black-Right-Pointing-Pointer PPAR{gamma} reduction and calcium/collagen deposition occurred later. Black-Right-Pointing-Pointer Runx2/PPAR{gamma} target genes were modulated in line with HDACs role in osteo-commitment. -- Abstract: The human adipose-tissue derived stem/stromal cells (hASCs) are an interesting source for bone-tissue engineering applications. Our aim was to clarify in hASCs the role of acetylation in the control of Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator activated receptor (PPAR) {gamma}. These key osteogenic and adipogenic transcription factors are oppositelymore » involved in osteo-differentiation. The hASCs, committed or not towards bone lineage with osteoinductive medium, were exposed to HDACs chemical blockade with Trichostatin A (TSA) or were genetically silenced for HDACs. Alkaline phosphatase (ALP) and collagen/calcium deposition, considered as early and late osteogenic markers, were evaluated concomitantly as index of osteo-differentiation. TSA pretreatment, useful experimental protocol to analyse pan-HDAC-chemical inhibition, and switch to osteogenic medium induced early-osteoblast maturation gene Runx2, while transiently decreased PPAR{gamma} and scarcely affected late-differentiation markers. Time-dependent effects were observed after knocking-down of HDAC1 and 3: Runx2 and ALP underwent early activation, followed by late-osteogenic markers increase and by PPAR{gamma}/ALP activity diminutions mostly after HDAC3 silencing. HDAC1 and 3 genetic blockade increased and decreased Runx2 and PPAR{gamma} target genes, respectively. Noteworthy, HDACs knocking-down favoured the commitment effect of osteogenic medium. Our results reveal a role for HDACs in orchestrating osteo-differentiation of hASCs at transcriptional level, and might provide new insights into the modulation of hASCs-based regenerative therapy.« less

Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors

PubMed Central

Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dubé, Céline; Maras, Pamela M.; Grigoriadis, Dimitri E.; Gall, Christine M.; Lynch, Gary; Baram, Tallie Z.

2010-01-01

Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly understood. Stress promotes secretion of the neuropeptide corticotropin-releasing hormone (CRH) from hippocampal interneurons, activating receptors (CRF1) located on pyramidal cell dendrites. Additionally, chronic CRF1 occupancy negatively affects dendritic arborization in mouse organotypic slice cultures, similar to the pattern observed in middle-aged, early-stressed (CES) rats. Here we found that CRH-expression is augmented in hippocampus of middle-aged CES rats, and then tested if the morphological defects and poor memory performance in these animals involve excessive activation of CRF1 receptors. Central or peripheral administration of a CRF1 blocker following the stress period improved memory performance of CES rats in novel object recognition tests and in the Morris water maze. Consonant with these effects, the antagonist also prevented dendritic atrophy and LTP attenuation in CA1 Schaffer collateral synapses. Together, these data suggest that persistently elevated hippocampal CRH-CRF1 interaction contributes importantly to the structural and cognitive impairments associated with early-life stress. Reducing CRF1 occupancy post-hoc normalized hippocampal function during middle-age, thus offering potential mechanism-based therapeutic interventions for children affected by chronic stress. PMID:20881118

The effect of hand movements on numerical bisection judgments in early blind and sighted individuals.

PubMed

Rinaldi, Luca; Vecchi, Tomaso; Fantino, Micaela; Merabet, Lotfi B; Cattaneo, Zaira

2015-10-01

Recent evidence suggests that in representing numbers blind individuals might be affected differently by proprioceptive cues (e.g., hand positions, head turns) than are sighted individuals. In this study, we asked a group of early blind and sighted individuals to perform a numerical bisection task while executing hand movements in left or right peripersonal space and with either hand. We found that in bisecting ascending numerical intervals, the hemi-space in which the hand was moved (but not the moved hand itself) influenced the bisection bias similarly in both early blind and sighted participants. However, when numerical intervals were presented in descending order, the moved hand (and not the hemi-space in which it was moved) affected the bisection bias in all participants. Overall, our data show that the operation to be performed on the mental number line affects the activated spatial reference frame, regardless of participants' previous visual experience. In particular, both sighted and early blind individuals' representation of numerical magnitude is mainly rooted in world-centered coordinates when numerical information is given in canonical orientation (i.e., from small to large), whereas hand-centered coordinates become more relevant when the scanning of the mental number line proceeds in non-canonical direction. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of hand movements on numerical bisection judgments in early blind and sighted individuals

PubMed Central

Rinaldi, Luca; Vecchi, Tomaso; Fantino, Micaela; Merabet, Lotfi B.; Cattaneo, Zaira

2017-01-01

Recent evidence suggests that in representing numbers blind individuals might be affected differently by proprioceptive cues (e.g., hand positions, head turns) than are sighted individuals. In this study, we asked a group of early blind and sighted individuals to perform a numerical bisection task while executing hand movements in left or right peripersonal space and with either hand. We found that in bisecting ascending numerical intervals, the hemi-space in which the hand was moved (but not the moved hand itself) influenced the bisection bias similarly in both early blind and sighted participants. However, when numerical intervals were presented in descending order, the moved hand (and not the hemi-space in which it was moved) affected the bisection bias in all participants. Overall, our data show that the operation to be performed on the mental number line affects the activated spatial reference frame, regardless of participants’ previous visual experience. In particular, both sighted and early blind individuals’ representation of numerical magnitude is mainly rooted in world-centered coordinates when numerical information is given in canonical orientation (i.e. from small to large), whereas hand-centered coordinates become more relevant when the scanning of the mental number line proceeds in non-canonical direction. PMID:26184675

Emotional facilitation of sensory processing in the visual cortex.

PubMed

Schupp, Harald T; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

2003-01-01

A key function of emotion is the preparation for action. However, organization of successful behavioral strategies depends on efficient stimulus encoding. The present study tested the hypothesis that perceptual encoding in the visual cortex is modulated by the emotional significance of visual stimuli. Event-related brain potentials were measured while subjects viewed pleasant, neutral, and unpleasant pictures. Early selective encoding of pleasant and unpleasant images was associated with a posterior negativity, indicating primary sources of activation in the visual cortex. The study also replicated previous findings in that affective cues also elicited enlarged late positive potentials, indexing increased stimulus relevance at higher-order stages of stimulus processing. These results support the hypothesis that sensory encoding of affective stimuli is facilitated implicitly by natural selective attention. Thus, the affect system not only modulates motor output (i.e., favoring approach or avoidance dispositions), but already operates at an early level of sensory encoding.

Resident-Assisted Montessori Programming (RAMP): use of a small group reading activity run by persons with dementia in adult day health care and long-term care settings.

PubMed

Skrajner, Michael J; Camp, Cameron J

2007-01-01

Six persons in the early to middle stages of dementia ("leaders") were trained in Resident-Assisted Montessori Programming (RAMP) to lead a reading activity for 22 persons with more advanced dementia ("participants") in an adult day health center (ADHC) and a special care unit (SCU) in a skilled nursing facility. Researchers assessed the leaders' abilities to learn and follow the procedures of leading a group, as well as their satisfaction with their roles. In addition, participants' engagement and affect were measured, both during standard activities programming and during client-led activities. Results of this study suggest that persons with dementia can indeed successfully lead small group activities, if several important prerequisites are met. Furthermore, the engagement and affect of participants was more positive in client-led activities than in standard activities programming.

Effects of touch on emotional face processing: A study of event-related potentials, facial EMG and cardiac activity.

PubMed

Spapé, M M; Harjunen, Ville; Ravaja, N

2017-03-01

Being touched is known to affect emotion, and even a casual touch can elicit positive feelings and affinity. Psychophysiological studies have recently shown that tactile primes affect visual evoked potentials to emotional stimuli, suggesting altered affective stimulus processing. As, however, these studies approached emotion from a purely unidimensional perspective, it remains unclear whether touch biases emotional evaluation or a more general feature such as salience. Here, we investigated how simple tactile primes modulate event related potentials (ERPs), facial EMG and cardiac response to pictures of facial expressions of emotion. All measures replicated known effects of emotional face processing: Disgust and fear modulated early ERPs, anger increased the cardiac orienting response, and expressions elicited emotion-congruent facial EMG activity. Tactile primes also affected these measures, but priming never interacted with the type of emotional expression. Thus, touch may additively affect general stimulus processing, but it does not bias or modulate immediate affective evaluation. Copyright © 2017. Published by Elsevier B.V.

Microparticles (CD146) and Arterial Stiffness Versus Carotid Intima Media Thickness as an Early Predictors of Vascular Affection in Systemic Lupus Patients.

PubMed

Nassef, Sahar; El Guindey, Hala; Fawzy, Mary; Nasser, Amal; Reffai, Rasha; Shemiy, Doa

2016-03-01

This study aims to evaluate cluster of differentiation 146 (CD146) and pulse wave velocity (PWV) as non-invasive methods for prediction of early vascular affection in systemic lupus erythematosus (SLE) patients without symptoms of vascular disease, to detect the outcome and reproducibility of these methods, and to correlate CD146 and PWV with lipid profile, intima media thickness (IMT), and ankle brachial index. Thirty female SLE patients (mean age 26.6±6.6 years; range 15 to 35 years) fulfilling the American College of Rheumatology 1997 revised criteria for SLE classification, and 15 age and sex matched healthy controls were included. All participants were performed full clinical assessments including measurement of Systemic Lupus Erythematosus Disease Activity Index, lipid profile, CD146, carotid IMT, PWV, and rise time as an indication of how fast the waveform rises. Cluster of differentiation 146 levels were elevated in patients with SLE compared to controls (p<0.001). There was a statistically significant difference between patients and controls in the femoral, lower thigh, and ankle rise time. There was a statistically significant correlation between IMT and ages of patients, Systemic Lupus Erythematosus Disease Activity Index, and brachial-below knee PWV, while there was no correlation between IMT and disease duration, lipid profile, brachial-femoral PWV, and brachial-ankle PWV. There was statistically significant correlations between brachial-femoral PWV and serum cholesterol level, and between brachial-ankle PWV and low density lipoprotein cholesterol. Our results showed that SLE vascular affection is more pronounced in small arteries. Also, elevated CD146 and brachial-femoral PWV are useful early markers of vascular affection in SLE as well as rise time may be a marker for arterial stiffness.

Computing the proton aurora at early Mars

NASA Astrophysics Data System (ADS)

Lovato, K.; Gronoff, G.; Curry, S.; Simon Wedlund, C.; Moore, W. B.

2017-12-01

In the early Solar System, ( 4 Gyr ago) our Sun was 70% less luminous than what is seen today but much more active. Indeed, for young stars, solar flares occurs more frequently and therefore so do coronal mass ejections and solar energetic particle events. With an increase in solar events, the flux of protons becomes extremely high, and affects planetary atmosphere in a more extreme way as today. Proton precipitation on planets has an impact on the energy balance of their upper atmospheres, can affect the photochemistry and create auroral emissions. Understanding the protons precipitation at the early Mars can help in understanding occurring chemical process as well as atmospheric evolution and escape. We concentrated our effort on the proton up to a MeV since they have the most important influence on the upper atmosphere. Using scaling laws, we estimated the proton flux for the Early Mars up to a MeV. A kinetic 1D code, validated for the current Mars, was used to compute the effects of the low energy protons precipitation on the Early Mars. This model solves the coupled H+/H multi-stream dissipative transport equation as well as the transport of the secondary electron. For the Early Mars, it allowed to compute the magnitude of the proton Aurora, as well as the corresponding upwards H flux.

Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

PubMed Central

2017-01-01

Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

Early expression of triggering receptors and regulatory role of 2B4 in human natural killer cell precursors undergoing in vitro differentiation

PubMed Central

Sivori, Simona; Falco, Michela; Marcenaro, Emanuela; Parolini, Silvia; Biassoni, Roberto; Bottino, Cristina; Moretta, Lorenzo; Moretta, Alessandro

2002-01-01

In this study we analyzed the progression of cell surface receptor expression during the in vitro-induced human natural killer (NK) cell maturation from CD34+ Lin− cell precursors. NKp46 and NKp30, two major triggering receptors that play a central role in natural cytotoxicity, were expressed before the HLA class I-specific inhibitory receptors. Moreover, their appearance at the cell surface correlated with the acquisition of cytolytic activity by developing NK cells. Although the early expression of triggering receptors may provide activating signals required for inducing further cell differentiation, it may also affect the self-tolerance of developing NK cells. Our data show that a fail-safe mechanism preventing killing of normal autologous cells may be provided by the 2B4 surface molecule, which, at early stages of NK cell differentiation, functions as an inhibitory rather than as an activating receptor. PMID:11917118

Inhibition of the early stage of Salmonella enterica serovar Enteritidis biofilm development on stainless steel by cell-free supernatant of a Hafnia alvei culture.

PubMed

Chorianopoulos, Nikos G; Giaouris, Efstathios D; Kourkoutas, Yiannis; Nychas, George-John E

2010-03-01

Compounds present in Hafnia alvei cell-free culture supernatant cumulatively negatively influence the early stage of biofilm development by Salmonella enterica serovar Enteritidis on stainless steel while they also reduce the overall metabolic activity of S. Enteritidis planktonic cells. Although acylhomoserine lactones (AHLs) were detected among these compounds, the use of several synthetic AHLs was not able to affect the initial stage of biofilm formation by this pathogen.

Increasing Early Detection of Prostate Cancer in African American Men through a Culturally Targeted Print Intervention

DTIC Science & Technology

2008-06-01

and brittle bones . 8 INFORM YOUR DOCTOR Certain activities, conditions, and substances can also affect PSA levels, including: • medicines (such as...Growth rates for this type of cancer can vary. Studies have shown that prostate tumors grow at different rates in different people . While some...This is one reason why early detection may be important. • When the cancer spreads beyond the prostate, it becomes more difficult to manage and the

Daily Physical Activity Patterns During the Early Stage of Alzheimer's Disease.

PubMed

Varma, Vijay R; Watts, Amber

2017-01-01

Alzheimer's disease (AD) is a neurodegenerative disease that results in severe disability. Very few studies have explored changes in daily physical activity patterns during early stages of AD when components of physical function and mobility may be preserved. Our study explored differences in daily physical activity profiles, independent of the effects of non-cognitive factors including physical function and age, among individuals with mild AD compared to controls. Patients with mild AD and controls (n = 92) recruited from the University of Kansas Alzheimer's Disease Center Registry, wore the Actigraph GT3X+ for seven days, and provided objective physical function (VO2 max) and mobility data. Using multivariate linear regression, we explored whether individuals with mild AD had different daily average and diurnal physical activity patterns compared to controls independent of non-cognitive factors that may affect physical activity, including physical function and mobility. We found that mild AD was associated with less moderate-intensity physical activity (p < 0.05), lower peak activity (p < 0.01), and lower physical activity complexity (p < 0.05) particularly during the morning. Mild AD was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for non-cognitive covariates. These findings suggest that factors independent of physical capacity and mobility may drive declines in moderate-intensity physical activity, and not lower-intensity or sedentary activity, during the early stage of AD. This underscores the importance of a better mechanistic understanding of how cognitive decline and AD pathology impact physical activity. Findings emphasize the potential value of designing and testing time-of-day specific physical activity interventions targeting individuals in the early stages of AD, prior to significant declines in mobility and physical function.

Adrenocortical responses of the Apollo 17 crew members

NASA Technical Reports Server (NTRS)

Leach, C. S.; Rambaut, P. C.; Johnson, P. C.

1974-01-01

Changes in adrenal activity of the three Apollo 17 crew members were studied during the 12.55-day mission and during selected post-recovery days. Aldosterone excretion was normal early and elevated later in the mission, probably causing a loss in total body exchangeable potassium. There was decreased 17-hydroxycorticosteroid excretion only during the early mission days for the two moon landers and throughout the mission for the other astronaut. Cortisol excretion was elevated on physically stressful mission days. At recovery, plasma ACTH was elevated without a similar increase in plasma cortisol. Angiotensin I activity was elevated at recovery in only one crewman. This crewman was the only one with a decreased extracellular fluid volume. These results indicate that the mission and its activities affect adrenal function of the crewmen.

Late cretaceous extensional tectonics and associated igneous activity on the northern margin of the Gulf of Mexico Basin

NASA Technical Reports Server (NTRS)

Bowen, R. L.; Sundeen, D. A.

1985-01-01

Major, dominantly compressional, orogenic episodes (Taconic, Acadian, Alleghenian) affected eastern North America during the Paleozoic. During the Mesozoic, in contrast, this same region was principally affected by epeirogenic and extensional tectonism; one episode of comparatively more intense tectonic activity involving extensive faulting, uplift, sedimentation, intrusion and effusion produced the Newark Series of eposits and fault block phenomena. This event, termed the Palisades Disturbance, took place during the Late Triassic - Earliest Jurassic. The authors document a comparable extensional tectonic-igneous event occurring during the Late Cretaceous (Early Gulfian; Cenomanian-Santonian) along the southern margin of the cratonic platform from Arkansas to Georgia.

Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone.

PubMed

Krivic, A; Majerovic, M; Jelic, I; Seiwerth, S; Sikiric, P

2008-05-01

In the presented study we compared the effect of stable peptide BPC 157 and methylprednisolone on early functional recovery after Achilles tendon to bone transection in a rat model before collagen healing started. Surgical transection of the right Achilles tendon to bone area was performed in seventy two Wistar Albino male rats. Healing Achilles tendon edges were harvested at days 1-4 following the transection. Using Achilles functional index (AFI), myeloperoxidase activity, histological inflammatory cell influx and vascular index early functional recovery was evaluated. Agents (stable peptide BPC 157 10 microg methylprednisolone 5 mg, normal saline 5 ml) were given alone (/kg b.w., intraperitoneally, once daily, first 30 min after surgery, last 24 h before analysis). Control group received normal saline 5 ml/kg. BPC 157 improved functional recovery (AFI values increased at all time points, p <0.05) by anti-inflammatory (decreased myeloperoxidase (MPO) activity and histological inflammatory cell influx, p <0.05) and increased new blood vessel formation (increased vascular index, p <0.05). Methyprednisolone decreased MPO activity and histological inflammatory cell influx, (p <0.05) but also decreased new blood vessel formation and did not affect early functional recovery. Stable peptide BPC 157 with combined anti-inflammatory action and induction of early new blood vessel formation facilitates early functional recovery in Achilles tendon to bone healing.

Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer's disease pathology.

PubMed

Alonso-Andrés, Patricia; Albasanz, José Luis; Ferrer, Isidro; Martín, Mairena

2018-01-24

Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β-amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines. © 2018 International Society of Neuropathology.

Survival Analysis Of The Modernized Retirement System For The United States Marine Corps

DTIC Science & Technology

2016-03-01

November 2015 to begin as early as 2018. This online survey will assist the Marine Corps in determining the retention impacts of the new retirement...thesis determines if the Modernized Retirement System is likely to affect manpower levels. A survey was conducted within the active component of the U.S...2016. Specifically, this thesis determines if the Modernized Retirement System is likely to affect manpower levels. A survey was conducted within

Visual disability and quality of life in glaucoma patients.

PubMed

Cesareo, Massimo; Ciuffoletti, Elena; Ricci, Federico; Missiroli, Filippo; Giuliano, Mario Alberto; Mancino, Raffaele; Nucci, Carlo

2015-01-01

Glaucoma is an optic neuropathy that can result in progressive and irreversible vision loss, thereby affecting quality of life (QoL) of patients. Several studies have shown a strong correlation between visual field damage and visual disability in patients with glaucoma, even in the early stages of the disease. Visual impairment due to glaucoma affects normal daily activities required for independent living, such as driving, walking, and reading. There is no generally accepted instrument for assessing quality of life in glaucoma patients; different factors involved in visual disability from the disease are difficult to quantify and not easily standardized. This chapter summarizes recent works from clinical and epidemiological studies, which describe how glaucoma affects the performance of important vision-related activities and QoL. © 2015 Elsevier B.V. All rights reserved.

Cognitive functioning in healthy aging: the role of reserve and lifestyle factors early in life.

PubMed

Fritsch, Thomas; McClendon, McKee J; Smyth, Kathleen A; Lerner, Alan J; Friedland, Robert P; Larsen, Janet D

2007-06-01

According to the reserve perspective on cognitive aging, individuals are born with or can develop resources that help them resist normal and disease-related cognitive changes that occur in aging. The reserve perspective is becoming more sophisticated, but gaps in knowledge persist. In the present research, we considered three understudied questions about reserve: Is reserve primarily static (unchangeable) throughout the life course or dynamic (changeable, in terms of increases or decreases)? Can reserve be increased at any point in life, or are there optimal time periods--such as early life, midlife, or late life--to increase it? Does participation in different types of leisure and occupational activities in early life and midlife have different effects depending on specific domains of late-life cognitive functioning? Here we link early cognitive and activity data--gathered from archival sources--with cognitive data from older adults to examine these issues. 349 participants, all mid-1940s graduates of the same high school, underwent telephone cognitive screening. All participants provided access to adolescent IQ scores; we determined activity levels from yearbooks. We used path analysis to evaluate the complex relationships between early life, midlife, and late-life variables. Adolescent IQ had strong direct effects on global cognitive functioning, episodic memory, verbal fluency, and processing speed. Participants' high school mental activities had direct effects on verbal fluency, but physical and social activities did not predict any cognitive measure. Education had direct effects on global cognitive functioning, episodic memory, and, most strongly, processing speed, but other midlife factors (notably, occupational demands) were not significant predictors of late-life cognition. There were weak indirect effects of adolescent IQ on global cognitive functioning, episodic memory, and processing speed, working through high school mental activities and education. Verbal fluency, in contrast, was affected by adolescent IQ through links with high school mental activities, but not education. Our study suggests that reserve is dynamic, but it is most amenable to change in early life. We conclude that an active, engaged lifestyle, emphasizing mental activity and educational pursuits in early life, can have a positive impact on cognitive functioning in late life.

The secret life of ground squirrels: accelerometry reveals sex-dependent plasticity in above-ground activity

PubMed Central

Wilsterman, Kathryn; Zhang, Victor; Moore, Jeanette; Barnes, Brian M.; Buck, C. Loren

2016-01-01

The sexes differ in how and when they allocate energy towards reproduction, but how this influences phenotypic plasticity in daily activity patterns is unclear. Here, we use collar-mounted light loggers and triaxial accelerometers to examine factors that affect time spent above ground and overall dynamic body acceleration (ODBA), an index of activity-specific energy expenditure, across the active season of free-living, semi-fossorial arctic ground squirrels (Urocitellus parryii). We found high day-to-day variability in time spent above ground and ODBA with most of the variance explained by environmental conditions known to affect thermal exchange. In both years, females spent more time below ground compared with males during parturition and early lactation; however, this difference was fourfold larger in the second year, possibly, because females were in better body condition. Daily ODBA positively correlated with time spent above ground in both sexes, but females were more active per unit time above ground. Consequently, daily ODBA did not differ between the sexes when females were early in lactation, even though females were above ground three to six fewer hours each day. Further, on top of having the additional burden of milk production, ODBA data indicate females also had fragmented rest patterns and were more active during late lactation. Our results indicate that sex differences in reproductive requirements can have a substantial influence on activity patterns, but the size of this effect may be dependent on capital resources accrued during gestation. PMID:27703706

CRITICAL OVERVIEW OF EARLY CHILDHOOD EDUCATION PROGRAMS.

ERIC Educational Resources Information Center

LAVATELLI, C.B.

PRESENT PRESCHOOL PROGRAMS FOR DISADVANTAGED CHILDREN ARE OF 3 KINDS--(1) AN INVENTORY TYPE WHICH ATTEMPTS TO IDENTIFY DEFICITS WHICH WILL AFFECT SCHOOL LEARNING AND TO OVERCOME THESE THROUGH EDUCATIONAL ACTIVITIES, (2) A PLAN BASED ON A RECAPITULATION THEORY WHICH ATTEMPTS TO DESCRIBE DEVELOPMENTAL STAGES AND TO COMPENSATE FOR THOSE WHICH A…

Future Cities Engineering: Early Engineering Interventions in the Middle Grades

ERIC Educational Resources Information Center

McCue, Camille; James, David

2008-01-01

This paper describes qualitative and quantitative research conducted with middle school students participating in a Future Cities Engineering course. Insights were sought regarding both affective and cognitive changes which transpired during the one-semester schedule of activities focused on modeling the infrastructure of a city built 150 years in…

How Emotions Affect Learning.

ERIC Educational Resources Information Center

Sylwester, Robert

1994-01-01

Studies show our emotional system is a complex, widely distributed, and error-prone system that defines our basic personality early in life and is quite resistant to change. This article describes our emotional system's major parts (the peptides that carry emotional information and the body and brain structures that activate and regulate emotions)…

Contribution of Egr1/zif268 to Activity-Dependent Arc/Arg3.1 Transcription in the Dentate Gyrus and Area CA1 of the Hippocampus

PubMed Central

Penke, Zsuzsa; Chagneau, Carine; Laroche, Serge

2011-01-01

Egr1, a member of the Egr family of transcription factors, and Arc are immediate early genes known to play major roles in synaptic plasticity and memory. Despite evidence that Egr family members can control Arc transcriptional regulation, demonstration of a selective role of Egr1 alone is lacking. We investigated the extent to which activity-dependent Arc expression is dependent on Egr1 by analyzing Arc mRNA expression using fluorescence in situ hybridization in the dorsal dentate gyrus and CA1 of wild-type (WT) and Egr1 knockout mice. Following electroconvulsive shock, we found biphasic expression of Arc in area CA1 in mice, consisting in a rapid (30 min) and transient wave followed by a second late-phase of expression (8 h), and a single but prolonged wave of expression in the dentate gyrus. Egr1 deficiency abolished the latest, but not the early wave of Arc expression in CA1, and curtailed that of the dentate gyrus. Since the early wave of Arc expression was not affected in Egr1 mutant mice, we next analyzed behaviorally induced Arc expression patterns as an index of neural ensemble activation in the dentate gyrus and area CA1 of WT and Egr1 mutant mice. Spatial exploration of novel or familiar environments induced in mice a single early and transient wave of Arc expression in the dentate gyrus and area CA1, which were not affected in Egr1 mutant mice. Analyses of Arc-expressing cells revealed that exploration recruits similar size dentate gyrus and CA1 neural ensembles in WT and Egr1 knockout mice. These findings suggest that hippocampal neural ensembles are normally activated immediately following spatial exploration in Egr1 knockout mice, indicating normal hippocampal encoding of information. They also provide evidence that in condition of strong activation Egr1 alone can control late-phases of activity-dependent Arc transcription in the dentate gyrus and area CA1 of the hippocampus. PMID:21887136

Early physiological abnormalities after simian immunodeficiency virus infection.

PubMed

Horn, T F; Huitron-Resendiz, S; Weed, M R; Henriksen, S J; Fox, H S

1998-12-08

Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.

Early physiological abnormalities after simian immunodeficiency virus infection

PubMed Central

Horn, Thomas F. W.; Huitron-Resendiz, Salvador; Weed, Michael R.; Henriksen, Steven J.; Fox, Howard S.

1998-01-01

Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction. PMID:9844017

The first national clinical audit for rheumatoid arthritis.

PubMed

Firth, J; Snowden, N; Ledingham, J; Rivett, A; Galloway, J; Dennison, E M; MacPhie, E; Ide, Z; Rowe, I; Kandala, N; Jameson, K

The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first 3 months of follow-up activity from first presentation to a rheumatology service. Access to care, management of early rheumatoid arthritis and support for self care were measured against National Institute for Health and Care Excellence quality standards; impact of early arthritis and experience of care were measured using patient-reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient-reported outcomes within 3 months and high levels of overall satisfaction were reported but these results were affected by low response rates. This article presents a summary of the national data from the audit and discusses the implications for nursing practice.

Cell phone radiations affect early growth of Vigna radiata (mung bean) through biochemical alterations.

PubMed

Sharma, Ved Parkash; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

2010-01-01

The indiscriminate use of wireless technologies, particularly of cell phones, has increased the health risks among living organisms including plants. We investigated the impact of cell phone electromagentic field (EMF) radiations (power density, 8.55 microW cm(-2)) on germination, early growth, proteins and carbohydrate contents, and activities of some enzymes in Vigna radiata. Cell phone EMF radiations significantly reduced the seedling length and dry weight of V radiata after exposure for 0.5, 1, 2, and 4 h. Furthermore, the contents of proteins and carbohydrates were reduced in EMF-exposed plants. However, the activities of proteases, alpha-amylases, beta-amylases, polyphenol oxidases, and peroxidases were enhanced in EMF-exposed radicles indicating their role in providing protection against EMF-induced stress. The study concludes that cell phone EMFs impair early growth of V radiata seedlings by inducing biochemical changes.

Cofilin 1-Mediated Biphasic F-Actin Dynamics of Neuronal Cells Affect Herpes Simplex Virus 1 Infection and Replication

PubMed Central

Xiang, Yangfei; Zheng, Kai; Ju, Huaiqiang; Wang, Shaoxiang; Pei, Ying; Ding, Weichao; Chen, Zhenping; Wang, Qiaoli; Qiu, Xianxiu; Zhong, Meigong; Zeng, Fanli; Ren, Zhe; Qian, Chuiwen; Liu, Ge

2012-01-01

Herpes simplex virus 1 (HSV-1) invades the nervous system and causes pathological changes. In this study, we defined the remodeling of F-actin and its possible mechanisms during HSV-1 infection of neuronal cells. HSV-1 infection enhanced the formation of F-actin-based structures in the early stage of infection, which was followed by a continuous decrease in F-actin during the later stages of infection. The disruption of F-actin dynamics by chemical inhibitors significantly reduced the efficiency of viral infection and intracellular HSV-1 replication. The active form of the actin-depolymerizing factor cofilin 1 was found to increase at an early stage of infection and then to continuously decrease in a manner that corresponded to the remodeling pattern of F-actin, suggesting that cofilin 1 may be involved in the biphasic F-actin dynamics induced by HSV-1 infection. Knockdown of cofilin 1 impaired HSV-1-induced F-actin assembly during early infection and inhibited viral entry; however, overexpression of cofilin 1 did not affect F-actin assembly or viral entry during early infection but decreased intracellular viral reproduction efficiently. Our results, for the first time, demonstrated the biphasic F-actin dynamics in HSV-1 neuronal infection and confirmed the association of F-actin with the changes in the expression and activity of cofilin 1. These results may provide insight into the mechanism by which HSV-1 productively infects neuronal cells and causes pathogenesis. PMID:22623803

Reward and motivation systems: a brain mapping study of early-stage intense romantic love in Chinese participants.

PubMed

Xu, Xiaomeng; Aron, Arthur; Brown, Lucy; Cao, Guikang; Feng, Tingyong; Weng, Xuchu

2011-02-01

Early-stage romantic love has been studied previously in the United States and United Kingdom (Aron et al. [2005]: J Neurophysiol 94:327–337; Bartels and Zeki [2000]: Neuroreport 11:3829–3834; Ortigue et al. [2007]: J Cogn Neurosci 19:1218–1230), revealing activation in the reward and motivation systems of the brain. In this study, we asked what systems are activated for early-stage romantic love in Easterners, specifically Chinese participants? Are these activations affected by individual differences within a cultural context of Traditionality and Modernity? Also, are these brain activations correlated with later satisfaction in the relationship? In Beijing, we used the same procedure used by Aron et al. (Aron et al. [2005]: J Neurophysiol 94:327–337). The stimuli for 18 Chinese participants were a picture of the face of their beloved, the face of a familiar acquaintance, and a countback task. We found significant activations specific to the beloved in the reward and motivation systems, particularly, the ventral tegmental area and the caudate. The mid-orbitofrontal cortex and cerebellum were also activated, whereas amygdala, medial orbitofrontal, and medial accumbens activity were decreased relative to the familiar acquaintance. Self-reported Traditionality and Modernity scores were each positively correlated with activity in the nucleus accumbens, although in different regions and sides of the brain. Activity in the subgenual area and the superior frontal gyrus was associated with higher relationship happiness at 18-month follow-up. Our results show that midbrain dopamine-rich reward/motivation systems were activated by early-stage romantic love in Chinese participants, as found by other studies. Neural activity was associated with Traditionality and Modernity attitudes as well as with later relationship happiness for Chinese participants.

Judging arrival times of incoming traffic vehicles is not a prerequisite for safely crossing an intersection: Differential effects of vehicle size and type in passive judgment and active driving tasks.

PubMed

Mathieu, Julie; Bootsma, Reinoud J; Berthelon, Catherine; Montagne, Gilles

2017-02-01

Using a fixed-base driving simulator we compared the effects of the size and type of traffic vehicles (i.e., normal-sized or double-sized cars or motorcycles) approaching an intersection in two different tasks. In the perceptual judgment task, passively moving participants estimated when a traffic vehicle would reach the intersection for actual arrival times (ATs) of 1, 2, or 3s. In line with earlier findings, ATs were generally underestimated, the more so the longer the actual AT. Results revealed that vehicle size affected judgments in particular for the larger actual ATs (2 and 3s), with double-sized vehicles then being judged as arriving earlier than normal-sized vehicles. Vehicle type, on the other hand, affected judgments at the smaller actual ATs (1 and 2s), with cars then being judged as arriving earlier than motorcycles. In the behavioral task participants actively drove the simulator to cross the intersection by passing through a gap in a train of traffic. Analyses of the speed variations observed during the active intersection-crossing task revealed that the size and type of vehicles in the traffic train did not affect driving behavior in the same way as in the AT judgment task. First, effects were considerably smaller, affecting driving behavior only marginally. Second, effects were opposite to expectations based on AT judgments: driver approach speeds were smaller (rather than larger) when confronted with double-sized vehicles as compared to their normal-sized counterparts and when confronted with cars as compared to motorcycles. Finally, the temporality of the effects was different on the two tasks: vehicle size affected driver approach speed in the final stages of approach rather than early on, while vehicle type affected driver approach speed early on rather than later. Overall, we conclude that the active control of approach to the intersection is not based on successive judgments of traffic vehicle arrival times. These results thereby question the general belief that arrival time estimates are crucial for safe interaction with traffic. Copyright © 2016 Elsevier B.V. All rights reserved.

Changes in the antioxidant metabolism in the embryonic development of the common South American toad Bufo arenarum: differential responses to pesticide in early embryos and autonomous-feeding larvae.

PubMed

Ferrari, Ana; Anguiano, Liliana; Lascano, Cecilia; Sotomayor, Verónica; Rosenbaum, Enrique; Venturino, Andrés

2008-01-01

Amphibians may be critically challenged by aquatic contaminants during their embryonic development. Many classes of compounds, including organophosphorus pesticides, are able to cause oxidative stress that affects the delicate cellular redox balance regulating tissue modeling. We determined the progression of antioxidant defenses during the embryonic development of the South American common toad, Bufo arenarum. Superoxide dismutase (SOD) and catalase (CAT) activities were high in the unfertilized eggs, and remained constant during the first stages of development. SOD showed a significant increase when the gills were completely active and opercular folds began to form. Reductase (GR) activity was low in the oocytes and increased significantly when gills and mouth were entirely developed and the embryos presented a higher exposure to pro-oxidant conditions suggesting an environmental control. Reduced glutathione (GSH) content was also initially low, and rose continuously pointing out an increasing participation of GSH-related enzymes in the control of oxidative stress. GSH peroxidases and GSH-S-transferases showed relatively high and constant activities, probably related to lipid peroxide control. B. arenarum embryos have plenty of yolk platelets containing lipids, which provide the energy and are actively transferred to the newly synthesized membranes during the early embryonic development. Exposure to the pro-oxidant pesticide malathion during 48 h did not significantly affect the activity of antioxidant enzymes in early embryos, but decreased the activities of CAT, GR, and the pool of GSH in larvae. Previous work indicated that lipid peroxide levels were kept low in malathion-exposed larvae, thus we conclude that oxidative stress is overcome by the antioxidant defenses. The increase in the antioxidant metabolism observed in the posthatching phase of development of B. arenarum embryo, thus constitutes a defense against natural and human-generated pro-oxidants present in the aquatic environment.

Positive and negative symptom scores are correlated with activation in different brain regions during facial emotion perception in schizophrenia patients: a voxel-based sLORETA source activity study.

PubMed

Kim, Do-Won; Kim, Han-Sung; Lee, Seung-Hwan; Im, Chang-Hwan

2013-12-01

Schizophrenia is one of the most devastating of all mental illnesses, and has dimensional characteristics that include both positive and negative symptoms. One problem reported in schizophrenia patients is that they tend to show deficits in face emotion processing, on which negative symptoms are thought to have stronger influence. In this study, four event-related potential (ERP) components (P100, N170, N250, and P300) and their source activities were analyzed using EEG data acquired from 23 schizophrenia patients while they were presented with facial emotion picture stimuli. Correlations between positive and negative syndrome scale (PANSS) scores and source activations during facial emotion processing were calculated to identify the brain areas affected by symptom scores. Our analysis demonstrates that PANSS positive scores are negatively correlated with major areas of the left temporal lobule for early ERP components (P100, N170) and with the right middle frontal lobule for a later component (N250), which indicates that positive symptoms affect both early face processing and facial emotion processing. On the other hand, PANSS negative scores are negatively correlated with several clustered regions, including the left fusiform gyrus (at P100), most of which are not overlapped with regions showing correlations with PANSS positive scores. Our results suggest that positive and negative symptoms affect independent brain regions during facial emotion processing, which may help to explain the heterogeneous characteristics of schizophrenia. © 2013 Elsevier B.V. All rights reserved.

Influence of hepatic load from far-off dry period to early postpartum period on the first postpartum ovulation and accompanying subsequent fertility in dairy cows.

PubMed

Kawashima, Chiho; Ito, Nozomi; Nagashima, Shuntarou; Matsui, Motozumi; Sawada, Kumiko; Schweigert, Florian J; Miyamoto, Akio; Kida, Katsuya

2016-06-17

The aim of the present study was to investigate nutritional and metabolic parameters during the dry and early postpartum periods of ovulatory and anovulatory cows, as well as their postpartum reproductive performance. Blood samples from 20 multiparous Holstein cows were collected once a week from the far-off dry period to 3 weeks postpartum. Early postpartum (0-3 weeks) ovulation was confirmed using plasma progesterone concentration profiles, and cows were considered ovulatory if they had resumed luteal activity by this point (n = 9), whereas cows that had not were considered anovulatory (n = 11). Data from the ovulatory and anovulatory cows were analyzed separately for the far-off dry period (7-4 weeks prepartum), the close-up dry period (3-1 weeks prepartum), and the early postpartum period (0-3 weeks). Serum gamma-glutamyl transpeptidase activity (far-off, P = 0.065; close-up, P = 0.051; and early postpartum, P = 0.030) and aspartate aminotransferase (close-up, P = 0.050 and early postpartum, P = 0.087) activities were higher in anovulatory than in ovulatory cows. The days open period was longer (P = 0.019) in anovulatory than in ovulatory cows, and the number of artificial inseminations per conception (P = 0.025) was greater. In conclusion, we found that continuously high gamma-glutamyl transpeptidase activities in serum, which may be induced by liver disorders, prevent subsequent ovulation and affect subsequent fertility, even if cows obtain sufficient ovulation-related energy and β-carotene.

The role of pregnancy awareness on female sexual function in early gestation.

PubMed

Corbacioglu, Aytul; Bakir, Vuslat Lale; Akbayir, Ozgur; Cilesiz Goksedef, Behiye Pinar; Akca, Aysu

2012-07-01

Female sexual function is negatively influenced by pregnancy due to the physical and emotional changes. Although the most significant effect is seen in the third trimester of pregnancy, a considerable decrease in the frequency of intercourse and sexual desire in the first trimester has also been shown. To investigate the factors that affect sexuality in early pregnancy and the impact of awareness of pregnancy on female sexual function in the first trimester of pregnancy using two self-reported questionnaires. In this cross-sectional study, 130 healthy, married pregnant women who were admitted to the gynecology clinic between the 4th and 10th week of gestation were asked to complete a self-administered questionnaire and the female sexual function index (FSFI). The factors associated with FSFI score and monthly sexual activity frequency in the first trimester, as well as the differences in sexual activity frequency and FSFI scores between the women who were previously aware of their pregnancy and those who were yet unaware of their pregnancy. Women who were unaware of their pregnancy had significantly higher coitus frequency in comparison with the aware group (P = 0.002). Total FSFI score was 21.99 ± 8.13 in the aware group and 24.66 ± 3.76 in the unaware group (P = 0.02). None of the obstetric and sociodemographic variables had an influence on desire and pain scores. Arousal, lubrication, and satisfaction scores were adversely affected by awareness of pregnancy. Orgasm scores were influenced negatively by awareness and positively by love marriage; however, in multivariate linear regression analysis none of these were defined as independent factor for orgasm scores. Overall FSFI scores and monthly frequency of sexual activity were only affected by awareness. The results of this study suggest that in early gestation, awareness of pregnancy is associated with lower female sexual function. Furthermore, obstetric and sociodemographic factors seem to be ineffective on sexual function in early pregnancy. © 2012 International Society for Sexual Medicine.

Early-Life Stress Affects Stress-Related Prefrontal Dopamine Activity in Healthy Adults, but Not in Individuals with Psychotic Disorder

PubMed Central

Kasanova, Zuzana; Hernaus, Dennis; Vaessen, Thomas; van Amelsvoort, Thérèse; Winz, Oliver; Heinzel, Alexander; Pruessner, Jens; Mottaghy, Felix M.

2016-01-01

Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual’s fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0–11 years) and late (12–18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23) = -3.35, p = .004) and late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11) = 3.06, p = .016) as well as late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11) = -2, p = .07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11) = .01, p = .99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis. PMID:27007554

Early exposure to caffeine affects gene expression of adenosine receptors, DARPP-32 and BDNF without affecting sensibility and morphology of developing zebrafish (Danio rerio).

PubMed

Capiotti, Katiucia Marques; Menezes, Fabiano Peres; Nazario, Luiza Reali; Pohlmann, Julhana Bianchini; de Oliveira, Giovanna M T; Fazenda, Lidiane; Bogo, Maurício Reis; Bonan, Carla Denise; Da Silva, Rosane Souza

2011-01-01

Adenosine receptors are the most important biochemical targets of caffeine, a common trimethylxanthine found in food and beverages. Adenosine plays modulatory action during the development through adenosine receptors and their intracellular pathways activation. In this study, we aimed to evaluate if caffeine gave to zebrafish in the very first steps of development is able to affect its direct targets, through the adenosine receptors mRNA expression evaluation, and latter indirect targets, through evaluation of the pattern of dopamine and cAMP-regulated phosphoprotein and brain-derived neurotrophic factor (BDNF) mRNA expression. Here, we demonstrate that zebrafish express adenosine receptor subtypes (A1, A2A1, A2A2 and A2B) since 24h post-fertilization (hpf) and that caffeine exposure is able to affect the expression of these receptors. Caffeine exposure from 1 hpf is able to increase A1 expression at 72-96 hpf and A2A1 expression at 72 hpf. No alterations occurred in A2A2 and A2B expression after caffeine treatment. DARPP-32, a phosphoprotein involved in adenosine intracellular pathway is also expressed since 24 hpf and early exposure to caffeine increased DARPP-32 expression at 168 hpf. We also evaluate the expression of BDNF as one of the targets of adenosine intracellular pathway activation. BDNF was also expressed since 24 hpf and caffeine treatment increased its expression at 48 and 72 hpf. No morphological alterations induced by caffeine treatment were registered by the check of general body features and total body length. Assessment of tactile sensibility also demonstrated no alterations by caffeine treatment. Altogether, these results suggest that caffeine is able to affect expression of its cellular targets since early phases of development in zebrafish without affect visible features. The up-regulation of direct and indirect targets of caffeine presents as a compensatory mechanism of maintenance of adenosinergic modulation during the developmental phase. Copyright © 2011 Elsevier Inc. All rights reserved.

Autonomous motivation is associated with the maintenance stage of behaviour change in people with affective disorders.

PubMed

Vancampfort, Davy; Moens, Herman; Madou, Tomas; De Backer, Tanja; Vallons, Veerle; Bruyninx, Peter; Vanheuverzwijn, Sarah; Mota, Cindy Teixeira; Soundy, Andy; Probst, Michel

2016-06-30

The present study examined whether in people with affective disorders motives for adopting and maintaining physical activity recommendations (as formulated by the self-determination theory) differed across the stages of behaviour change (identified by the transtheoretical model). A total of 165 (105♀) persons (45.6±14.2years) with affective disorders [major depressive disorder (n=96) or bipolar disorder (n=69)] completed the Behavioural Regulation in Exercise Questionnaire-2 and the Patient-centred Assessment and Counselling for Exercise questionnaire. Discriminant and multivariate analyses demonstrated that persons with affective disorders at the early stages of change have less autonomous and more controlled physical activity motives than those at the later stages. Our results suggest that autonomous motivation may have an important role to play in the maintenance of health recommendations in persons with affective disorders. Longitudinal and intervention studies should be designed in people with affective disorders to identify the causal pathways between motives for maintaining health recommendations, effective changes in health behaviour and physical and mental health outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Early interleukin-6 enhances hepatic ketogenesis in APPSWE/PSEN1dE9 mice via 3-hydroxy-3-methylglutary-CoA synthase 2 signaling activation by p38/nuclear factor κB p65.

PubMed

Shi, Le; Zhao, Daina; Hou, Chen; Peng, Yunhua; Liu, Jing; Zhang, Shuangxi; Liu, Jiankang; Long, Jiangang

2017-08-01

Alzheimer's disease (AD) is considered a multifactorial disease that affects the central nervous system and periphery. A decline in brain glucose metabolism is an early feature of AD and is accompanied by a phenotypic shift from aerobic glycolysis to ketogenesis. The liver is responsible for the generation of the ketone body. However, the mechanism that underlies hepatic ketogenesis in AD remains unclear. Here, we investigated hepatic ketogenesis during the early stage of AD pathogenesis in amyloid precursor protein (APP SWE ) and presenilin (PSEN1dE9) (APP/PS1) mice. We observed that β-hydroxybutyric acid was increased in the brain of the postmortem mild cognitive impairment and AD subjects and in 3-month-old APP/PS1 AD mice. A rise in 3-hydroxy-3-methylglutary-CoA synthase 2 (HMGCS2), a key enzyme for catalyzing β-hydroxybutyric acid production, was observed in early AD mice. We further showed that proinflammatory cytokines were activated in the liver prior to their activation in the brain of 3-month-old APP/PS1 mice. Among the cytokines, interleukin-6 significantly activated HMGCS2 through the binding of nuclear factor κB (NF-κB) p65 to the HMGCS2 promoter. Additionally, interleukin-6 stimulated phosphorylation of p38 mitogen activated protein kinases, an upstream molecule for NF-κB p65 signaling. We have demonstrated that a hepatic inflammatory factor enhances ketogenesis through HMGCS2 signaling activation by p38/NF-κB p65. These results provide a novel peripheral metabolic mechanism for enhanced ketone production and suggest a plausible early AD phenotype to diagnose AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Interleukin-4 Ameliorates the Functional Recovery of Intracerebral Hemorrhage Through the Alternative Activation of Microglia/Macrophage.

PubMed

Yang, Jianjing; Ding, Saidan; Huang, Weilong; Hu, Jiangnan; Huang, Shengwei; Zhang, Yu; Zhuge, Qichuan

2016-01-01

Neuro-inflammation plays an important role in the recovery of brain injury after stroke. Microglia/macrophage is the major executor in the neuro-inflammation, which can be polarized into two distinct phenotypes: injurious/toxic classical activation (M1 phenotype) and protective alternative activation (M2 phenotype). Here, we investigated whether intracerebral administration of interleukin-4 (IL-4) at an early stage could affect the activation of microglia/macrophage and the corresponding outcome after intracerebral hemorrhage (ICH). The neuro-behavior was recorded between different groups in the rat ICH model. The M1 and M2 markers were then determined by qRT-PCR, western blotting, ELISA, and immunofluorescence, respectively. We observed aberrant activation of microglia/macrophage after ICH. After intracerebral injection of IL-4, M1 activation was greatly inhibited while M2 activation was enhanced, along with improving neurobehavioral recovery from deficits after ICH. Our study showed that early intracerebral injection of IL-4 potentially promotes neuro-functional recovery, probably through enhancing the alternative activation of microglia/macrophage.

Impacts of trapping and banding activities on productivity of Roseate Terns (Sterna Dougallii)

USGS Publications Warehouse

Zingo, James M.

1998-01-01

Although Roseate Terns (Sterna dougallii) habituate to many research activities, trapping and handling breeding adults, or repeatedly handling chicks, may affect reproductive success or chick growth. Protocols for trapping adult Roseate Terns that reduce the chances of nest desertion, neglect of chicks, and injury to adults were developed in the early 1980s, but neither short-term nor long-term effects of research activities on this endangered species have been fully investigated. Therefore, this study had the following main objectives: 1) examine long-term data (1978-1996) to determine if trapping activities have had a major effect on annual reproductive success of a Roseate Tern colony, 2) evaluate the effects of trapping adult terns on reproductive success and chick growth, and 3) evaluate the effects of handling chicks on their growth and survival. There were no significant correlations between measures of trapping disturbance and annual reproductive success in 1978-1996 for the Falkner Island (Stewart B. McKinney National Wildlife Refuge, Connecticut) colony, suggesting that trapping from late incubation through chick rearing using the field protocols described herein does not have a major effect on nesting success of Roseate Terns. In 1987-1996, adult trapping did not reduce prefledging survival of first-hatched chicks, and reduced survival of second-hatched chicks only in 1994 and 1995. Results of more detailed research in 1994-1996 suggest that Roseate Terns may be susceptible to trapping effects only when also faced with extreme conditions such as low food availability and/or high predation pressure. Trapping effects did not occur in most years under apparently average or typical conditions, and otherwise seem to be much less important than other factors affecting nesting success (e.g., predation and food availability). Analyses of chick growth data from 1987-1996 showed that while trapping significantly reduced early growth compared to untrapped controls, most of these effects disappeared after controlling for variation due to laying variables and other indices of parental age and quality. Trapping had little or no effect on later growth (indices of fledgling quality) and thus is unlikely to affect postfledging survival and fitness. For chicks whose parents were trapped, the sex of the adult(s), timing of trapping during the nesting stage, and interval between trapping events (if both parents were trapped) had little or no effect on growth. Daily or near-daily handling of chicks did not significantly affect their growth, prefledging survival, or postfledging survival. These results suggest that while trapping adult Roseate Terns can sometimes affect reproductive success and early chick growth and should be taken into account during research, trapping effects tend to be minor, short-lived, and unlikely to affect overall population health. While the full implications for population health and individual fitness are not entirely clear, there appears to be little cause for concern that trapping and banding activities are a significant problem for Roseate Terns. However, this qualitative assessment of the biological significance of trapping effects needs empirical testing. There remains a practical need to explore the ramifications of trapping effects and to consider local conditions when planning trapping activities. We also need to consider how investigator-induced effects might affect research results, and to balance potential effects of research activities against the value of the information gained.

Evolving Complexity in Hemophilia Management.

PubMed

Croteau, Stacy E

2018-06-01

Rapid expansion of therapeutic options have increased the complexity of hemophilia care. Previously, on-demand therapy aimed to reduce morbidity and early mortality; however, now aggressive prophylaxis, particularly in children, encourages an active lifestyle. Accurate diagnosis, recognition of early threats to musculoskeletal health, and optimization of therapy are critical for both males and females affected by hemophilia. The diversity of emerging hemophilia therapies, from modified factor protein concentrates, to gene therapy, to nonfactor hemostatic strategies, provide an exciting opportunity to target unmet needs in the bleeding disorder community. Copyright © 2018 Elsevier Inc. All rights reserved.

Climate change implications and use of early warning systems for global dust storms

USGS Publications Warehouse

Harriman, Lindsey M.

2014-01-01

With increased changes in land cover and global climate, early detection and warning of dust storms in conjunction with effective and widespread information broadcasts will be essential to the prevention and mitigation of future risks and impacts. Human activities, seasonal variations and long-term climatic patterns influence dust storms. More research is needed to analyse these factors of dust mobilisation to create more certainty for the fate of vulnerable populations and ecosystems in the future. Early warning and communication systems, when in place and effectively implemented, can offer some relief to these vulnerable areas. As an issue that affects many regions of the world, there is a profound need to understand the potential changes and ultimately create better early warning systems for dust storms.

Rehabilitation Strategies for the Athletic Individual with Early Knee Osteoarthritis.

PubMed

Jayabalan, Prakash; Ihm, Joseph

2016-01-01

Knee osteoarthritis (OA) is a major cause of disability in the United States. The condition has most commonly been associated with elderly sedentary individuals; however, it also can affect those who participate in regular athletic activities. The diagnosis and management of these individuals can be challenging because of both their higher level of physical activity and their overall athletic goals. Treatment requires an appropriate exercise regimen, rehabilitation program, and education of both the athlete and the coach. The focus of our article is to provide an up-to-date overview of the evaluation and management of the athletic individual who presents with symptomatic early knee OA, in particular, the nonsurgical rehabilitation treatment options available to the practitioner and the evidence to support these recommendations.

Effects of therapeutic interventions for foster children on behavioral problems, caregiver attachment, and stress regulatory neural systems.

PubMed

Fisher, Philip A; Gunnar, Megan R; Dozier, Mary; Bruce, Jacqueline; Pears, Katherine C

2006-12-01

Young children in foster care are exposed to high levels of stress. These experiences place foster children at risk for poor social, academic, and mental heath outcomes. The role of adverse events in stimulating neurobiological stress responses presumably plays a role in shaping neural systems that contribute to these problems. Systematic and developmentally well-timed interventions might have the potential to change developmental trajectories and promote resilience. Moreover, understanding how specific dimensions of early adversity affect underlying stress response systems and how alterations in these systems are related to later psychosocial outcomes might facilitate more precise and targeted interventions. Data are drawn from two ongoing randomized trials involving foster infants/toddlers and preschoolers. Consistent with prior animal models of early adversity, these studies have shown that early adversity-particularly neglect, younger age at first foster placement, and higher number of placements-is associated with altered hypothalamic-pituitary-adrenal (HPA) axis function. The interventions under investigation have produced evidence that it is possible to impact many areas that have been negatively affected by early stress, including HPA axis activity, behavior, and attachment to caregivers.

Effortful Control and Parenting: Associations with HPA Axis Reactivity in Early Childhood

ERIC Educational Resources Information Center

Kryski, Katie R.; Dougherty, Lea R.; Dyson, Margaret W.; Olino, Thomas M.; Laptook, Rebecca S.; Klein, Daniel N.; Hayden, Elizabeth P.

2013-01-01

While activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent-child interactions, may play an important role in shaping the developing HPA system; however,…

Design and Development of "The Reading Biographer": An Application of Function Specific Assessment.

ERIC Educational Resources Information Center

Hanson, Ralph A.; Siegel, Donna Farrell

The general features of function-specific assessment are described and illustrated via a discussion of the design and development of "The Reading Biographer," an instrument for assessing experiences and activities of students (from early childhood through high school) that affect their reading achievement as high school seniors. The…

Do Preschool Programs Affect Social Disadvantage? What Social Workers Should Know

ERIC Educational Resources Information Center

Herman-Smith, Robert

2013-01-01

The majority of children from lower income families enter elementary school well behind their peers in reading, math, and general knowledge. Poor academic achievement in the early grades is associated with a range of social problems such as failure to complete high school, increased risk of unintended pregnancy, increased criminal activity, and…

Parent Engagement: Strategies for Involving Parents in School Health

ERIC Educational Resources Information Center

Centers for Disease Control and Prevention, 2012

2012-01-01

Children and adolescents are establishing patterns of behavior that affect both their current and future health. Young people are at risk for engaging in tobacco, alcohol, or other drug use, participating in violence or gang activities, and initiating sex at an early age. However, a growing body of research demonstrates that enhancing protective…

THE MENTALLY RETARDED CHILD AT HOME, A MANUAL FOR PARENTS.

ERIC Educational Resources Information Center

DITTMANN, LAURA L.

THIS MANUAL IS DEVOTED CHIEFLY TO THE MANAGEMENT OF YOUNG RETARDED CHILDREN AND CONCENTRATES ON DAY-TO-DAY ACTIVITIES--PHYSICAL HEALTH, MENTAL HEALTH, NEED FOR LOVE AND AFFECTION, SIBLING UNDERSTANDING, AND TRAINING IN SELF HELP AND OTHER SKILLS. EARLY CHARACTERISTICS AND NEEDS ARE DISCUSSED. THE FOLLOWING SKILLS ARE TREATED--FEEDING, DRINKING,…

The Play of Risk, Affect, and the Enterprising Self in a Fourth-Grade Classroom

ERIC Educational Resources Information Center

Bialostok, Steven; Kamberelis, George

2012-01-01

As a predominant discourse of the early twenty-first century, the new capitalism (and its companion cultural system, neoliberalism) privilege flexibility, risk, emotional intelligence, and the enterprising self. New capitalist discourses exert powerful and pervasive effects across all dimensions of human experience and activity from personal…

Awakening Young Children to Foreign Languages: Openness to Diversity Highlighted

ERIC Educational Resources Information Center

Ben Maad, Mohamed Ridha

2016-01-01

The study of how foreign languages affect the personality-building process has received considerable attention in early childhood research. A number of related projects implemented across Europe have been conducted to establish how such influence may contribute to active citizenship education. However, no echoes of this research line have reached…

A History of Study Skills: Not Hot, but Not Forgotten

ERIC Educational Resources Information Center

Richardson, Judy S.; Robnolt, Valerie J.; Rhodes, Joan A.

2010-01-01

Study skills were an early and important topic in reading; however, since the 1970s, they have received relatively little research attention. The authors systematically analyzed the research conducted on study skills from 1900 to the present. Several themes emerged including: (a) motivation and affect; (b) activities described; (c) metacognition;…

"The effects of diffuse and distinct affect": retraction of Stapel, Koomen, and Ruys (2002).

PubMed

2013-02-01

Reports the retraction of "The effects of diffuse and distinct affect. " by Diederik A. Stapel, Willem Koomen and Kirsten I. Ruys (Journal of Personality and Social Psychology, 2002[Jul], Vol 83[1], 60-74). This retraction follows the results of an investigation into the work of Diederik A. Stapel. The Noort Committee has found evidence of fraud, leading to the conclusion that fraud is most likely in the data supplied by Diederik A. Stapel. His co-authors were unaware of his actions and were not involved in the collection of the likely fraudulent data. (The following abstract of the original article appeared in record 2002-01515-004.) In a series of suboptimal priming studies, it was shown that both affective and nonaffective reactions to a stimulus may occur without awareness. Moreover, it was demonstrated that affective information is detected earlier than nonaffective information. Therefore, early reactions to an affect-laden stimulus (e.g., a smiling man) are cognitively unappraised and thus diffuse (e.g., "positive"), whereas later affective reactions can be more specific and distinct (e.g., "a smiling man"). Through variations of prime exposure (extremely short, moderately short) the impact of early diffuse and late distinct affect on judgment was investigated. Findings show that distinctness (and prime-target similarity) is an essential determinant of whether the effect of affect is null, assimilation, or contrast. Furthermore, whether affect priming activates diffuse or distinct reactions is a matter of a fraction of seconds. (c) 2013 APA, all rights reserved.

Early-developmental stress, repeatability, and canalization in a suite of physiological and behavioral traits in female zebra finches.

PubMed

Careau, Vincent; Buttemer, William A; Buchanan, Katherine L

2014-10-01

Adaptive developmental plasticity allows individuals experiencing poor environmental conditions in early life to adjust their life-history strategy in order to prioritize short-term fitness benefits and maximize reproductive output in challenging environments. Much research has been conducted to test whether such adoption of a "faster" life-history strategy is accompanied by concordant changes in behavior and physiology, with mixed results. As research in this field has focused on comparison of mean-level responses of treatment groups, few studies include repeated measures of response variables and the effect that developmental stress may have on repeatability per se. We investigated how early-developmental stress affects the mean expression of (and repeatability in) a variety of behavioral and physiological traits in female zebra finches. We predicted that: (1) individuals subjected to nutritional restriction in the nestling phase would have higher feeding and activity rates, with associated increases in hematocrit and basal metabolic rates (BMRs), (2) nutritional restriction in early life would alter adults' stress-induced corticosterone level, and (3) developmental stress would, respectively, influence the amount of among-individual and within-individual variation in behavioral and physiological traits, hence affecting the repeatability of these traits. In comparison to control females, stressed females did not differ in activity rate or stress-induced corticosterone level, but they did have higher levels of feeding, hematocrit, and BMR. Among-individual variance and repeatability were generally higher in stressed females than in controls. Finally, we found that developmental dietary restriction significantly reduced the amount of within-individual variance both in activity rate in the novel environment and in stress-induced corticosterone level. Our results not only confirm previous findings on the effect of early-developmental stress on BMR, but also extend its effect to feeding rate and hematocrit, suggesting that developmental plasticity in these traits is ontogenetically linked. Early-developmental stress may disable particular genetic canalizing processes, which would release cryptic genetic variation and explain why repeatability and among-individual variance were generally higher in the stressed groups than in controls. For activity rate in the novel environment and with stress-induced corticosterone level, however, early-developmental stress significantly reduced within-individual variance, which may be a consequence of increased canalization of these traits at the micro-environmental level. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Identification of functional domains of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication

PubMed Central

Kim, Seong K.; Kim, Seongman; Dai, Gan; Zhang, Yunfei; Ahn, Byung C.; O'Callaghan, Dennis J.

2012-01-01

The equine herpesvirus 1 (EHV-1) negative regulatory IR2 protein (IR2P), an early 1,165-amino acid (aa) truncated form of the 1,487-aa immediate-early protein (IEP), lacks the trans-activation domain essential for IEP activation functions but retains domains for binding DNA, TFIIB, and TBP and the nuclear localization signal. IR2P mutants of the N-terminal region which lack either DNA-binding activity or TFIIB-binding activity were unable to down-regulate EHV-1 promoters. In EHV-1-infected cells expressing full-length IR2P, transcription and protein expression of viral regulatory IE, early EICP0, IR4, and UL5, and late ETIF genes were dramatically inhibited. Viral DNA levels were reduced to 2.1% of control infected cells, but were vey weakly affected in cells that express the N-terminal 706 residues of IR2P. These results suggest that IR2P function requires the two N-terminal domains for binding DNA and TFIIB as well as the C-terminal residues 707 to 1116 containing the TBP-binding domain. PMID:21794889

Scanning laser Doppler imaging may predict disease progression of localized scleroderma in children and young adults.

PubMed

Shaw, L J; Shipley, J; Newell, E L; Harris, N; Clinch, J G; Lovell, C R

2013-07-01

Localized scleroderma is a rare but potentially disfiguring and disabling condition. Systemic treatment should be started early in those with active disease in key functional and cosmetic sites, but disease activity is difficult to determine clinically. Superficial blood flow has been shown to correlate with disease activity in localized scleroderma. To examine whether superficial blood flow measured by laser Doppler imaging (LDI) has the potential to predict disease progression and therefore select patients for early systemic treatment. A group of 20 individuals had clinical assessment and scanning LDI blood-flow measurements of 32 affected body sites. After a mean follow-up of 8.7 months their clinical outcome was compared with the results of the initial LDI assessment. Eleven out of 15 patients with an assessment of active LDI had progressed clinically, and 16 out of the 17 scans with inactive LDI assessment had not progressed, giving a positive predictive value of 73% and a negative predictive value of 94%. We believe that LDI can be a useful tool in predicting disease progression in localized scleroderma, and it may help clinicians to decide which patients to treat early. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Recognition Alters the Spatial Pattern of fMRI Activation in Early Retinotopic Cortex

PubMed Central

Vul, E.; Kanwisher, N.

2010-01-01

Early retinotopic cortex has traditionally been viewed as containing a veridical representation of the low-level properties of the image, not imbued by high-level interpretation and meaning. Yet several recent results indicate that neural representations in early retinotopic cortex reflect not just the sensory properties of the image, but also the perceived size and brightness of image regions. Here we used functional magnetic resonance imaging pattern analyses to ask whether the representation of an object in early retinotopic cortex changes when the object is recognized compared with when the same stimulus is presented but not recognized. Our data confirmed this hypothesis: the pattern of response in early retinotopic visual cortex to a two-tone “Mooney” image of an object was more similar to the response to the full grayscale photo version of the same image when observers knew what the two-tone image represented than when they did not. Further, in a second experiment, high-level interpretations actually overrode bottom-up stimulus information, such that the pattern of response in early retinotopic cortex to an identified two-tone image was more similar to the response to the photographic version of that stimulus than it was to the response to the identical two-tone image when it was not identified. Our findings are consistent with prior results indicating that perceived size and brightness affect representations in early retinotopic visual cortex and, further, show that even higher-level information—knowledge of object identity—also affects the representation of an object in early retinotopic cortex. PMID:20071627

Gender differences in response to a school-based mindfulness training intervention for early adolescents.

PubMed

Kang, Yoona; Rahrig, Hadley; Eichel, Kristina; Niles, Halsey F; Rocha, Tomas; Lepp, Nathaniel E; Gold, Jonathan; Britton, Willoughby B

2018-06-01

Mindfulness training has been used to improve emotional wellbeing in early adolescents. However, little is known about treatment outcome moderators, or individual differences that may differentially impact responses to treatment. The current study focused on gender as a potential moderator for affective outcomes in response to school-based mindfulness training. Sixth grade students (N = 100) were randomly assigned to either the six weeks of mindfulness meditation or the active control group as part of a history class curriculum. Participants in the mindfulness meditation group completed short mindfulness meditation sessions four to five times per week, in addition to didactic instruction (Asian history). The control group received matched experiential activity in addition to didactic instruction (African history) from the same teacher with no meditation component. Self-reported measures of emotional wellbeing/affect, mindfulness, and self-compassion were obtained at pre and post intervention. Meditators reported greater improvement in emotional wellbeing compared to those in the control group. Importantly, gender differences were detected, such that female meditators reported greater increases in positive affect compared to females in the control group, whereas male meditators and control males displayed equivalent gains. Uniquely among females but not males, increases in self-reported self-compassion were associated with improvements in affect. These findings support the efficacy of school-based mindfulness interventions, and interventions tailored to accommodate distinct developmental needs of female and male adolescents. Copyright © 2018 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Differences in Muscle Activity between Natural Forefoot and Rearfoot Strikers during Running

PubMed Central

Yong, Jennifer R.; Silder, Amy; Delp, Scott L.

2014-01-01

Running research has focused on reducing injuries by changing running technique. One proposed method is to change from rearfoot striking (RFS) to forefoot striking (FFS) because FFS is thought to be a more natural running pattern that may reduce loading and injury risk. Muscle activity affects loading and influences running patterns; however, the differences in muscle activity between natural FFS runners and natural RFS runners are unknown. The purpose of this study was to measure muscle activity in natural FFS runners and natural RFS runners. We tested the hypotheses that tibialis anterior activity would be significantly lower while activity of the plantarflexors would be significantly greater in FFS runners, compared to RFS runners, during late swing phase and early stance phase. Gait kinematics, ground reaction forces and electromyographic patterns of ten muscles were collected from twelve natural RFS runners and ten natural FFS runners. The root mean square (RMS) of each muscle’s activity was calculated during terminal swing phase and early stance phase. We found significantly lower RMS activity in the tibialis anterior in FFS runners during terminal swing phase, compared to RFS runners. In contrast, the medial and lateral gastrocnemius showed significantly greater RMS activity in terminal swing phase in FFS runners. No significant differences were found during early stance phase for the tibialis anterior or the plantarflexors. Recognizing the differences in muscle activity between FFS and RFS runners is an important step toward understanding how foot strike patterns may contribute to different types of injury. PMID:25458201

A comparison of functional magnetic resonance imaging findings in children with and without a history of early exposure to general anesthesia.

PubMed

Taghon, Thomas A; Masunga, Abigail N; Small, Robert H; Kashou, Nasser H

2015-03-01

Functional magnetic resonance imaging (fMRI) has been used to evaluate the long-term consequences of early exposure to neurotoxic agents. fMRI shows that different patterns of brain activation occur in ethanol-exposed subjects performing a go/no-go response inhibition task. Pharmacologically, ethanol and general anesthetics have similar receptor-level activity in the brain. This study utilizes fMRI to examine brain activation patterns in children exposed to general anesthesia and surgery during early brain development. After obtaining Nationwide Children's Hospital IRB approval, a surgical database was utilized to identify children aged 10-17 years with a history of at least 1 h of exposure to general anesthetics and surgery when they were between 0 and 24 months of age. Age- and gender-matched children without anesthesia exposure were recruited as a control group. All subjects were scanned while being presented with a go/no-go response inhibition task. Reaction time and accuracy data were acquired, and the blood-oxygen-level-dependent (BOLD) fMRI signal was measured as a biomarker for regional neuronal activity. There were no differences in terms of performance accuracy and response time. The analysis did not reveal any significant activation differences in the primary region of interest (prefrontal cortex and caudate nucleus); however, activation differences were seen in other structures, including the cerebellum, cingulate gyrus, and paracentral lobule. Early anesthetic exposure and surgery did not affect accuracy, response time, or activation patterns in the primary region of interest during performance of the task. Intergroup differences in activation patterns in other areas of the brain were observed, and the significance of these findings is unknown. fMRI appears to be a useful tool in evaluating the long-term effects of early exposure to general anesthesia. © 2015 John Wiley & Sons Ltd.

Digestive evaluation of soy isolate protein as affected by heat treatment and soy oil inclusion in broilers at an early age.

PubMed

Zhang, Xianglun; Lu, Peng; Xue, Wenyue; Wu, Dawei; Wen, Chao; Zhou, Yanmin

2016-10-01

Soy protein isolate (SPI) mixed with soybean oil (SPIO) incubated at 100°C for 8 h was used to evaluate changes of solubility and digestibility of SPI in vitro and digestive function in broilers at an early age. Arbor Acres broilers were allocated to three groups with six replicates of 12 birds, receiving basal diet (CON), 8 h heat-oxidized SPI diet (HSPI) and 8 h heat-oxidized mixture of SPI and 2% soybean oil diet (HSPIO) for 21 days, respectively. Nitrogen solubility index (NSI) declined and soybean oil accelerated the decline of NSI during incubation (P < 0.05). Decreased in vitro digestibility of dry matter (DM) and crude protein (CP) were observed in SPIO (P < 0.05). HSPI and HSPIO decreased body weight gain, relative jejunum weight and pancreatic trypsin activity at day 21 (P < 0.05). HSPIO decreased anterior intestinal trypsin activity at day 14 and amylase and trypsin activity at day 21, pancreatic amylase activity at day 21 and apparent digestibility of DM, organic matter and CP of broilers from days 18 to 20 (P < 0.05). Heat treatment and soybean oil could induce oxidative modification of SPI, and oxidized SPI negatively affected growth and digestion of broilers. © 2016 Japanese Society of Animal Science. © 2016 Japanese Society of Animal Science.

Suitability of Open-Ocean Instrumentation for Use in Near-Field Tsunami Early Warning Along Seismically Active Subduction Zones

NASA Astrophysics Data System (ADS)

Williamson, Amy L.; Newman, Andrew V.

2018-05-01

Over the past decade, the number of open-ocean gauges capable of parsing information about a passing tsunami has steadily increased, particularly through national cable networks and international buoyed efforts such as the Deep-ocean Assessment and Reporting of Tsunami (DART). This information is analyzed to disseminate tsunami warnings to affected regions. However, most current warnings that incorporate tsunami are directed at mid- and far-field localities. In this study, we analyze the region surrounding four seismically active subduction zones, Cascadia, Japan, Chile, and Java, for their potential to facilitate local tsunami early warning using such systems. We assess which locations currently have instrumentation in the right locations for direct tsunami observations with enough time to provide useful warning to the nearest affected coastline—and which are poorly suited for such systems. Our primary findings are that while some regions are ill-suited for this type of early warning, such as the coastlines of Chile, other localities, like Java, Indonesia, could incorporate direct tsunami observations into their hazard forecasts with enough lead time to be effective for coastal community emergency response. We take into account the effect of tsunami propagation with regard to shallow bathymetry on the fore-arc as well as the effect of earthquake source placement. While it is impossible to account for every type of off-shore tsunamigenic event in these locales, this study aims to characterize a typical large tsunamigenic event occurring in the shallow part of the megathrust as a guide in what is feasible with early tsunami warning.

Maternal sensitivity and infant autonomic and endocrine stress responses.

PubMed

Bosquet Enlow, Michelle; King, Lucy; Schreier, Hannah Mc; Howard, Jamie M; Rosenfield, David; Ritz, Thomas; Wright, Rosalind J

2014-07-01

Early environmental exposures may help shape the development of the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis, influencing vulnerability for health problems across the lifespan. Little is known about the role of maternal sensitivity in influencing the development of the ANS in early life. To examine associations among maternal sensitivity and infant behavioral distress and ANS and HPA axis reactivity to the Repeated Still-Face Paradigm (SFP-R), a dyadic stress task. Observational repeated measures study. Thirty-five urban, sociodemographically diverse mothers and their 6-month-old infants. Changes in infant affective distress, heart rate, respiratory sinus arrhythmia (RSA), and T-wave amplitude (TWA) across episodes of the SFP-R were assessed. A measure of cortisol output (area under the curve) in the hour following cessation of the SFP-R was also obtained. Greater maternal insensitivity was associated with greater infant sympathetic activation (TWA) during periods of stress and tended to be associated with greater cortisol output following the SFP-R. There was also evidence for greater affective distress and less parasympathetic activation (RSA) during the SFP-R among infants of predominantly insensitive mothers. Caregiving quality in early life may influence the responsiveness of the sympathetic and parasympathetic branches of the ANS as well as the HPA axis. Consideration of the ANS and HPA axis systems together provides a fuller representation of adaptive versus maladaptive stress responses. The findings highlight the importance of supporting high quality caregiving in the early years of life, which is likely to promote later health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Translatome analysis at the egg-to-embryo transition in sea urchin

PubMed Central

Chassé, Héloïse; Aubert, Julie; Boulben, Sandrine; Le Corguillé, Gildas; Corre, Erwan; Cormier, Patrick

2018-01-01

Abstract Early embryogenesis relies on the translational regulation of maternally stored mRNAs. In sea urchin, fertilization triggers a dramatic rise in translation activity, necessary for the onset of cell division. Here, the full spectrum of the mRNAs translated upon fertilization was investigated by polysome profiling and sequencing. The translatome of the early sea urchin embryo gave a complete picture of the polysomal recruitment dynamics following fertilization. Our results indicate that only a subset of maternal mRNAs were selectively recruited onto polysomes, with over-represented functional categories in the translated set. The increase in translation upon fertilization depends on the formation of translation initiation complexes following mTOR pathway activation. Surprisingly, mTOR pathway inhibition differentially affected polysomal recruitment of the newly translated mRNAs, which thus appeared either mTOR-dependent or mTOR-independent. Therefore, our data argue for an alternative to the classical cap-dependent model of translation in early development. The identification of the mRNAs translated following fertilization helped assign translational activation events to specific mRNAs. This translatome is the first step to a comprehensive analysis of the molecular mechanisms governing translation upon fertilization and the translational regulatory networks that control the egg-to-embryo transition as well as the early steps of embryogenesis. PMID:29660001

Post-conditioning preserves glycolytic ATP during early reperfusion: a survival mechanism for the reperfused heart.

PubMed

Correa, Francisco; García, Noemí; Gallardo-Pérez, Juan; Carreno-Fuentes, Liliana; Rodríguez-Enríquez, Sara; Marín-Hernández, Alvaro; Zazueta, Cecilia

2008-01-01

Glycolytic activity during the transition period from anaerobic to aerobic metabolism has been demonstrated to be critical for heart recovery in isolated reperfused hearts. The purpose of this work was to investigate the relevance of the glycolytic pathway in preserving the cardiac function of post-conditioned hearts. The activation of the glycolytic pathway in post-conditioned hearts was evaluated by measuring GLUT-4 insertion, glucose consumption and lactate production. Iodoacetic acid and 2-deoxy-D-glucose were administrated to the working hearts to evaluate the effect of glycolytic inhibition in the post-conditioning protective effect. Post-conditioning maneuvers applied to isolated rat hearts, after prolonged ischemia and before reperfusion, promoted recovery of cardiac mechanical function with sustained increase of GLUT-4 translocation and activation of the glycolytic pathway during ischemia and early reperfusion. Iodoacetate inhibited the protective effect of post-conditioning, without affecting the mitochondrial oxidative capacity. Glycolysis contribution to maintain mechanical function at early reperfusion was observed in post-conditioned hearts perfused with 2-deoxy-D-glucose and in hearts in which iodoacetate was administered only during reperfusion. It is concluded that in the post-conditioned heart, a functional compartmentation of anaerobic energy metabolism, at early reperfusion, plays a significant role in cardiac protection against reperfusion damage. Copyright 2008 S. Karger AG, Basel.

Translatome analysis at the egg-to-embryo transition in sea urchin.

PubMed

Chassé, Héloïse; Aubert, Julie; Boulben, Sandrine; Le Corguillé, Gildas; Corre, Erwan; Cormier, Patrick; Morales, Julia

2018-05-18

Early embryogenesis relies on the translational regulation of maternally stored mRNAs. In sea urchin, fertilization triggers a dramatic rise in translation activity, necessary for the onset of cell division. Here, the full spectrum of the mRNAs translated upon fertilization was investigated by polysome profiling and sequencing. The translatome of the early sea urchin embryo gave a complete picture of the polysomal recruitment dynamics following fertilization. Our results indicate that only a subset of maternal mRNAs were selectively recruited onto polysomes, with over-represented functional categories in the translated set. The increase in translation upon fertilization depends on the formation of translation initiation complexes following mTOR pathway activation. Surprisingly, mTOR pathway inhibition differentially affected polysomal recruitment of the newly translated mRNAs, which thus appeared either mTOR-dependent or mTOR-independent. Therefore, our data argue for an alternative to the classical cap-dependent model of translation in early development. The identification of the mRNAs translated following fertilization helped assign translational activation events to specific mRNAs. This translatome is the first step to a comprehensive analysis of the molecular mechanisms governing translation upon fertilization and the translational regulatory networks that control the egg-to-embryo transition as well as the early steps of embryogenesis.

Participant recruitment and retention in a pilot program to prevent weight gain in low-income overweight and obese mothers.

PubMed

Chang, Mei-Wei; Brown, Roger; Nitzke, Susan

2009-11-21

Recruitment and retention are key functions for programs promoting nutrition and other lifestyle behavioral changes in low-income populations. This paper describes strategies for recruitment and retention and presents predictors of early (two-month post intervention) and late (eight-month post intervention) dropout (non retention) and overall retention among young, low-income overweight and obese mothers participating in a community-based randomized pilot trial called Mothers In Motion. Low-income overweight and obese African American and white mothers ages 18 to 34 were recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children in southern Michigan. Participants (n = 129) were randomly assigned to an intervention (n = 64) or control (n = 65) group according to a stratification procedure to equalize representation in two racial groups (African American and white) and three body mass index categories (25.0-29.9 kg/m(2), 30.0-34.9 kg/m(2), and 35.0-39.9 kg/m(2)). The 10-week theory-based culturally sensitive intervention focused on healthy eating, physical activity, and stress management messages that were delivered via an interactive DVD and reinforced by five peer-support group teleconferences. Forward stepwise multiple logistic regression was performed to examine whether dietary fat, fruit and vegetable intake behaviors, physical activity, perceived stress, positive and negative affect, depression, and race predicted dropout as data were collected two-month and eight-month after the active intervention phase. Trained personnel were successful in recruiting subjects. Increased level of depression was a predictor of early dropout (odds ratio = 1.04; 95% CI = 1.00, 1.08; p = 0.03). Greater stress predicted late dropout (odds ratio = 0.20; 95% CI = 0.00, 0.37; p = 0.01). Dietary fat, fruit, and vegetable intake behaviors, physical activity, positive and negative affect, and race were not associated with either early or late dropout. Less negative affect was a marginal predictor of participant retention (odds ratio = 0.57; 95% CI = 0.31, 1.03; p = 0.06). Dropout rates in this study were higher for participants who reported higher levels of depression and stress. Current Controlled Trials NCT00944060.

A dominant bursting electromyograph pattern in dystonic conditions predicts an early response to pallidal stimulation.

PubMed

Yianni, John; Wang, Shou Yan; Liu, Xuguang; Bain, Peter G; Nandi, Dipankar; Gregory, Ralph; Joint, Carole; Stein, John F; Aziz, Tipu Z

2006-08-01

Although chronic pallidal deep brain stimulation (DBS) is effective in the treatment of medically intractable dystonia, there is no way of predicting the variations in clinical outcome, partly due to our limited understanding of the pathophysiological mechanisms underlying this condition. We recorded electromyographic (EMG) activity from the most severely affected muscle groups in seven dystonia patients before and after pallidal DBS. Patient EMG recordings could be classified into two groups: one consisting of patients who at rest demonstrated a dominant low frequency component of activity on power spectral analysis (ranging from 2 to 5 Hz), and one group in which this dominant pattern was absent. Early postoperative improvements (within 2-3 days) were observed in the former group, whereas the latter group benefited more gradually (over several months). Analysis of EMG activity may provide a sensitive means of identifying dystonic patients who are likely to be most responsive to functional neurosurgical intervention.

An 'Early Warning System' for the prevention of dredging potential impacts on sensitive areas

NASA Astrophysics Data System (ADS)

Piermattei, Viviana; Martellucci, Riccardo; Pierattini, Alberto; Bonamano, Simone; Paladini de Mendoza, Francesco; Albani, Marta; Stefanì, Chiara; Madonia, Alice; Fersini, Giorgio; Marcelli, Marco

2016-04-01

Coastal marine ecosystems are increasingly subject to multiple pressures and stressors produced by the effects of human activities. Intense and frequent disturbances which affect marine environment can derive from dredging activity, which is a fundamental management for most ports and harbours. The potential environmental effects of dredging procedures are generally due to the excavation of material from the sea bottom and the relocation elsewhere for disposal, overflow from the dredger and loss of material from pipelines during transport. Depending on the location and the intensity of these activities the marine environment, particularly sensitive areas, may be affected by dredging. The main environmental effects can be associated with suspended sediments and increases in turbidity into the water column, which can have adverse effects on marine animals and plants by reducing light penetration and by physical disturbance. For this reason it is fundamental to implement a real time monitoring system to control and prevent negative effects, enabling a rapid response to adverse water quality conditions and a fast activation of mitigation procedures, in agreement with all the reference authorities. In this work we present the development of an innovative 'Early Warning System' based on fixed stations, ad hoc in situ surveys and forecasting models, which was applied to a dredging activity carried out in the Gulf of Gaeta (Latium, Italy). It represents an extension of the C-CEMS (Civitavecchia Coastal Environmental Monitoring System) network, which is operative in the Tyrrhenian sea since 2005.

Why are maternally separated females inflexible? Brain activity pattern of COx and c-Fos.

PubMed

Banqueri, María; Méndez, Marta; Arias, Jorge L

2018-06-15

Subjects' early life events will affect them later in life. When these events are stressful, such as child abuse in humans or repeated maternal separation in rodents, subjects can show some behavioral and brain alterations. This study used young adult female Wistar rats that were maternally raised (AFR), maternally separated from post-natal day (PND) 1 to PND10 (MS10), or maternally separated from PND1 to PND21 (MS21), in order to assess the effects of maternal separation (MS) on spatial learning and memory, as well as cognitive flexibility, using the Morris Water Maze (MWM). We performed quantitative cytochrome oxidase (COx) histochemistry on selected brain areas in order to identify whether maternal separation affects brain energy metabolism. We also performed c-Fos immunohistochemistry on the medial prefrontal cortex (mPFC), thalamus, and hippocampus to explore whether this immediate early gene activity was altered in stressed subjects. We obtained a similar spatial learning pattern in maternally raised and maternally separated subjects on the reference memory task, but only the controls were flexible enough to solve the reversal learning successfully. Separated groups showed less c-Fos activity in the mPFC and less complex neural networks on COx. Copyright © 2018 Elsevier Inc. All rights reserved.

Affective picture modulation: valence, arousal, attention allocation and motivational significance.

PubMed

Leite, Jorge; Carvalho, Sandra; Galdo-Alvarez, Santiago; Alves, Jorge; Sampaio, Adriana; Gonçalves, Oscar F

2012-03-01

The present study analyses the modulatory effects of affective pictures in the early posterior negativity (EPN), the late positive potential (LPP) and the human startle response on both the peripheral (eye blink EMG) and central neurophysiological levels (Probe P3), during passive affective pictures viewing. The affective pictures categories were balanced in terms of valence (pleasant; unpleasant) and arousal (high; low). The data shows that EPN may be sensitive to specific stimulus characteristics (affective relevant pictures versus neutral pictures) associated with early stages of attentional processing. In later stages, the heightened attentional resource allocation as well as the motivated significance of the affective stimuli was found to elicit enhanced amplitudes of slow wave processes thought to be related to enhanced encoding, namely LPP,. Although pleasant low arousing pictures were effective in engaging the resources involved in the slow wave processes, the highly arousing affective stimuli (pleasant and unpleasant) were found to produce the largest enhancement of the LPP, suggesting that high arousing stimuli may are associated with increased motivational significance. Additionally the response to high arousing stimuli may be suggestive of increased motivational attention, given the heightened attentional allocation, as expressed in the P3 probe, especially for the pleasant pictures. The hedonic valence may then serve as a mediator of the attentional inhibition to the affective priming, potentiating or inhibiting a shift towards defensive activation, as measured by the startle reflex. Copyright © 2011 Elsevier B.V. All rights reserved.

New insights into Clostridium perfringens epsilon toxin activation and action on the brain during enterotoxemia.

PubMed

Freedman, John C; McClane, Bruce A; Uzal, Francisco A

2016-10-01

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, is responsible for diseases that occur mostly in ruminants. ETX is produced in the form of an inactive prototoxin that becomes proteolytically-activated by several proteases. A recent ex vivo study using caprine intestinal contents demonstrated that ETX prototoxin is processed in a step-wise fashion into a stable, active ∼27 kDa band on SDS-PAGE. When characterized further by mass spectrometry, the stable ∼27 kDa band was shown to contain three ETX species with varying C-terminal residues; each of these ETX species is cytotoxic. This study also demonstrated that, in addition to trypsin and chymotrypsin, proteases such as carboxypeptidases are involved in processing ETX prototoxin. Once absorbed, activated ETX species travel to several internal organs, including the brain, where this toxin acts on the vasculature to cross the blood-brain barrier, produces perivascular edema and affects several types of brain cells including neurons, astrocytes, and oligodendrocytes. In addition to perivascular edema, affected animals show edema within the vascular walls. This edema separates the astrocytic end-feet from affected blood vessels, causing hypoxia of nervous system tissue. Astrocytes of rats and sheep affected by ETX show overexpression of aquaporin-4, a membrane channel protein that is believed to help remove water from affected perivascular spaces in an attempt to resolve the perivascular edema. Amyloid precursor protein, an early astrocyte damage indicator, is also observed in the brains of affected sheep. These results show that ETX activation in vivo seems to be more complex than previously thought and this toxin acts on the brain, affecting vascular permeability, but also damaging neurons and other cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Light Regimes on the Growth of Cherrybark Oak Seedlings

Treesearch

Yanfei Guo; Michael G. Shelton; Brian R. Lockhart

2001-01-01

Light regimes vary significantly within small forest openings, ranging from full sunlight to total shade, and they may affect the establishment and early growth of oak seedlings. We designed modified shadehouses to simulate the complex light conditions within forest openings and tested the effects of daily photosynthetically active radiation (PAR), time of direct light...

Effects of Light Regimes on 1-Year-Old Sweetgum and Water Oak Seedlings

Treesearch

Yanfei Guo; Michael G. Shelton; Hui Zhang

2002-01-01

Light regimes vary significantly within small forest openings, ranging from full sunlight to total shade. This may affect establishment, early growth, and competitive status of hardwood seedlings. We used modified shadehouses to simulate light conditions within forest openings and to test the effects of daily photosynthetically active radiation and time of direct light...

The Example of Eastern Africa: the dynamic of Rift Valley fever and tools for monitoring virus activity

USDA-ARS?s Scientific Manuscript database

Rift Valley fever is a mosquito-borne viral zoonosis that primarily affects animals but also has the capacity to infect humans. Outbreaks of this disease in eastern Africa are closely associated with periods of heavy rainfall and forecasting models and early warning systems have been developed to en...

Resident-Assisted Montessori Programming (RAMP): training persons with dementia to serve as group activity leaders.

PubMed

Camp, Cameron J; Skrajner, Michael J

2004-06-01

The purpose of this study was to determine the effects of an activity implemented by means of Resident-Assisted Montessori Programming (RAMP). Four persons with early-stage dementia were trained to serve as leaders for a small-group activity played by nine persons with more advanced dementia. Assessments of leaders' ability to learn the procedures of leading a group, as well as their satisfaction with this role, were taken, as were measures of players' engagement and affect during standard activities programming and RAMP activities. Leaders demonstrated the potential to fill the role of group activity leader effectively, and they expressed a high level of satisfaction with this role. Players' levels of positive engagement and pleasure during the RAMP activity were higher than during standard group activities. This study suggests that to the extent that procedural learning is available to persons with early-stage dementia, especially when they are assisted with external cueing, these individuals can successfully fill the role of volunteers when working with persons with more advanced dementia. This can provide a meaningful social role for leaders and increase access to high quality activities programming for large numbers of persons with dementia. Copyright 2004 The Gerontological Society of America

Building a Beneficial Microbiome from Birth12

PubMed Central

Castanys-Muñoz, Esther; Martin, Maria J; Vazquez, Enrique

2016-01-01

The microbiota has recently been recognized as a driver of health that affects the immune, nervous, and metabolic systems. This influence is partially exerted through the metabolites produced, which may be relevant for optimal infant development and health. The gut microbiota begins developing early in life, and this initial colonization is remarkably important because it may influence long-term microbiota composition and activity. Considering that the microbiome may play a key role in health and disease, maintaining a protective microbiota could be critical in preventing dysbiosis-related diseases such as allergies, autoimmunity disorders, and metabolic syndrome. Breast milk and milk glycans in particular are thought to play a major role in shaping the early-life microbiota and promoting its development, thus affecting health. This review describes some of the effects the microbiota has on the host and discusses the role microbial metabolites play in shaping newborn health and development. We describe the gut microbiota structure and function during early life and the factors that determine its composition and hypothesize about the effects of human milk oligosaccharides and other prebiotic fibers on the neonatal microbiota. PMID:26980815

Building a Beneficial Microbiome from Birth.

PubMed

Castanys-Muñoz, Esther; Martin, Maria J; Vazquez, Enrique

2016-03-01

The microbiota has recently been recognized as a driver of health that affects the immune, nervous, and metabolic systems. This influence is partially exerted through the metabolites produced, which may be relevant for optimal infant development and health. The gut microbiota begins developing early in life, and this initial colonization is remarkably important because it may influence long-term microbiota composition and activity. Considering that the microbiome may play a key role in health and disease, maintaining a protective microbiota could be critical in preventing dysbiosis-related diseases such as allergies, autoimmunity disorders, and metabolic syndrome. Breast milk and milk glycans in particular are thought to play a major role in shaping the early-life microbiota and promoting its development, thus affecting health. This review describes some of the effects the microbiota has on the host and discusses the role microbial metabolites play in shaping newborn health and development. We describe the gut microbiota structure and function during early life and the factors that determine its composition and hypothesize about the effects of human milk oligosaccharides and other prebiotic fibers on the neonatal microbiota. © 2016 American Society for Nutrition.

Drinking Over the Lifespan: Focus on Early Adolescents and Youth.

PubMed

Windle, Michael

2016-01-01

Historical trends in alcohol use among U.S. adolescents, as well as data regarding alcohol-related traffic fatalities among youth, indicate decreases in alcohol use. Nevertheless, alcohol use patterns still indicate high rates of binge drinking and drunkenness and the co-occurrence of alcohol use among youth with risky sexual activity, illicit substance use, and poor school performance. This article discusses unique elements of alcohol use among adolescents relative to adults that pose risks for alcohol misuse and alcohol-related problems. These differences range from patterns of drinking to differential sensitivity to alcohol. Developmental differences between adolescents and adults also are discussed with regard to age-normative developmental tasks and distinctions in brain development that may affect differences in drinking patterns. Epidemiologic findings on sexual-minority youth are provided, as are global trends in alcohol use among early adolescents and youth. It is proposed that using information about differences between youth and adults will be helpful in directing future etiologic and intervention research by capitalizing on unique biological, psychological, and social factors that may affect the success of efforts to reduce alcohol use among early adolescents and youth.

Internal Dose from Food and Drink Ingestion in the Early Phase after the Accident

NASA Astrophysics Data System (ADS)

Kawai, Masaki; Yoshizawa, Nobuaki; Hirakawa, Sachiko; Murakami, Kana; Takizawa, Mari; Sato, Osamu; Takagi, Shunji; Miyatake, Hirokazu; Takahashi, Tomoyuki; Suzuki, Gen

2017-09-01

Activity concentrations in food and drink, represented by water and vegetables, have been monitored continuously since the Fukushima Daiichi Nuclear Power Plant accident, with a focus on radioactive cesium. On the other hand, iodine-131 was not measured systematically in the early phase after the accident. The activity concentrations of iodine-131 in food and drink are important to estimate internal exposure due to ingestion pathway. When the internal dose from ingestion in the evacuation areas is estimated, water is considered as the main ingestion pathway. In this study, we estimated the values of activity concentrations in water in the early phase after the accident, using a compartment model as an estimation method. The model uses measurement values of activity concentration and deposition rate of iodine-131 onto the ground, which is calculated from an atmospheric dispersion simulation. The model considers how drinking water would be affected by radionuclides deposited into water. We estimated the activity concentrations of water on Kawamata town and Minamisouma city during March of 2011 and the committed effective doses were 0.08 mSv and 0.06 mSv. We calculated the transfer parameters in the model for estimating the activity concentrations in the areas with a small amount of measurement data. In addition, we estimated the committed effective doses from vegetables using atmospheric dispersion simulation and FARMLAND model in case of eating certain vegetables as option information.

Synaptic Phospholipid Signaling Modulates Axon Outgrowth via Glutamate-dependent Ca2+-mediated Molecular Pathways.

PubMed

Vogt, Johannes; Kirischuk, Sergei; Unichenko, Petr; Schlüter, Leslie; Pelosi, Assunta; Endle, Heiko; Yang, Jenq-Wei; Schmarowski, Nikolai; Cheng, Jin; Thalman, Carine; Strauss, Ulf; Prokudin, Alexey; Bharati, B Suman; Aoki, Junken; Chun, Jerold; Lutz, Beat; Luhmann, Heiko J; Nitsch, Robert

2017-01-01

Altered synaptic bioactive lipid signaling has been recently shown to augment neuronal excitation in the hippocampus of adult animals by activation of presynaptic LPA2-receptors leading to increased presynaptic glutamate release. Here, we show that this results in higher postsynaptic Ca2+ levels and in premature onset of spontaneous neuronal activity in the developing entorhinal cortex. Interestingly, increased synchronized neuronal activity led to reduced axon growth velocity of entorhinal neurons which project via the perforant path to the hippocampus. This was due to Ca2+-dependent molecular signaling to the axon affecting stabilization of the actin cytoskeleton. The spontaneous activity affected the entire entorhinal cortical network and thus led to reduced overall axon fiber numbers in the mature perforant path that is known to be important for specific memory functions. Our data show that precise regulation of early cortical activity by bioactive lipids is of critical importance for proper circuit formation. © The Author 2016. Published by Oxford University Press.

Active music classes in infancy enhance musical, communicative and social development.

PubMed

Gerry, David; Unrau, Andrea; Trainor, Laurel J

2012-05-01

Previous studies suggest that musical training in children can positively affect various aspects of development. However, it remains unknown as to how early in development musical experience can have an effect, the nature of any such effects, and whether different types of music experience affect development differently. We found that random assignment to 6 months of active participatory musical experience beginning at 6 months of age accelerates acquisition of culture-specific knowledge of Western tonality in comparison to a similar amount of passive exposure to music. Furthermore, infants assigned to the active musical experience showed superior development of prelinguistic communicative gestures and social behaviour compared to infants assigned to the passive musical experience. These results indicate that (1) infants can engage in meaningful musical training when appropriate pedagogical approaches are used, (2) active musical participation in infancy enhances culture-specific musical acquisition, and (3) active musical participation in infancy impacts social and communication development. © 2012 Blackwell Publishing Ltd.

Evidence for a Caregiving Instinct: Rapid Differentiation of Infant from Adult Vocalizations Using Magnetoencephalography.

PubMed

Young, Katherine S; Parsons, Christine E; Jegindoe Elmholdt, Else-Marie; Woolrich, Mark W; van Hartevelt, Tim J; Stevner, Angus B A; Stein, Alan; Kringelbach, Morten L

2016-03-01

Crying is the most salient vocal signal of distress. The cries of a newborn infant alert adult listeners and often elicit caregiving behavior. For the parent, rapid responding to an infant in distress is an adaptive behavior, functioning to ensure offspring survival. The ability to react rapidly requires quick recognition and evaluation of stimuli followed by a co-ordinated motor response. Previous neuroimaging research has demonstrated early specialized activity in response to infant faces. Using magnetoencephalography, we found similarly early (100-200 ms) differences in neural responses to infant and adult cry vocalizations in auditory, emotional, and motor cortical brain regions. We propose that this early differential activity may help to rapidly identify infant cries and engage affective and motor neural circuitry to promote adaptive behavioral responding, before conscious awareness. These differences were observed in adults who were not parents, perhaps indicative of a universal brain-based "caregiving instinct." © The Author 2015. Published by Oxford University Press.

Physiological correlates of emotional reactivity and regulation in early adolescents.

PubMed

Latham, Melissa D; Cook, Nina; Simmons, Julian G; Byrne, Michelle L; Kettle, Jonathan W L; Schwartz, Orli; Vijayakumar, Nandita; Whittle, Sarah; Allen, Nicholas B

2017-07-01

Few studies have examined physiological correlates of emotional reactivity and regulation in adolescents, despite the occurrence in this group of significant developmental changes in emotional functioning. The current study employed multiple physiological measures (i.e., startle-elicited eyeblink and ERP, skin conductance, facial EMG) to assess the emotional reactivity and regulation of 113 early adolescents in response to valenced images. Reactivity was measured while participants viewed images, and regulation was measured when they were asked to discontinue or maintain their emotional reactions to the images. Adolescent participants did not exhibit fear-potentiated startle blink. However, they did display affect-consistent zygomatic and corrugator activity during reactivity, as well as inhibition of some of these facial patterns during regulation. Skin conductance demonstrated arousal dependent activity during reactivity, and overall decreases during regulation. These findings suggest that early adolescents display reactivity to valenced pictures, but not to startle probes. Psychophysiological patterns during emotion regulation indicate additional effort and/or attention during the regulation process. Copyright © 2017 Elsevier B.V. All rights reserved.

Evidence for a Caregiving Instinct: Rapid Differentiation of Infant from Adult Vocalizations Using Magnetoencephalography

PubMed Central

Young, Katherine S.; Parsons, Christine E.; Jegindoe Elmholdt, Else-Marie; Woolrich, Mark W.; van Hartevelt, Tim J.; Stevner, Angus B. A.; Stein, Alan; Kringelbach, Morten L.

2016-01-01

Crying is the most salient vocal signal of distress. The cries of a newborn infant alert adult listeners and often elicit caregiving behavior. For the parent, rapid responding to an infant in distress is an adaptive behavior, functioning to ensure offspring survival. The ability to react rapidly requires quick recognition and evaluation of stimuli followed by a co-ordinated motor response. Previous neuroimaging research has demonstrated early specialized activity in response to infant faces. Using magnetoencephalography, we found similarly early (100–200 ms) differences in neural responses to infant and adult cry vocalizations in auditory, emotional, and motor cortical brain regions. We propose that this early differential activity may help to rapidly identify infant cries and engage affective and motor neural circuitry to promote adaptive behavioral responding, before conscious awareness. These differences were observed in adults who were not parents, perhaps indicative of a universal brain-based “caregiving instinct.” PMID:26656998

Emotional facial expressions evoke faster orienting responses, but weaker emotional responses at neural and behavioural levels compared to scenes: A simultaneous EEG and facial EMG study.

PubMed

Mavratzakis, Aimee; Herbert, Cornelia; Walla, Peter

2016-01-01

In the current study, electroencephalography (EEG) was recorded simultaneously with facial electromyography (fEMG) to determine whether emotional faces and emotional scenes are processed differently at the neural level. In addition, it was investigated whether these differences can be observed at the behavioural level via spontaneous facial muscle activity. Emotional content of the stimuli did not affect early P1 activity. Emotional faces elicited enhanced amplitudes of the face-sensitive N170 component, while its counterpart, the scene-related N100, was not sensitive to emotional content of scenes. At 220-280ms, the early posterior negativity (EPN) was enhanced only slightly for fearful as compared to neutral or happy faces. However, its amplitudes were significantly enhanced during processing of scenes with positive content, particularly over the right hemisphere. Scenes of positive content also elicited enhanced spontaneous zygomatic activity from 500-750ms onwards, while happy faces elicited no such changes. Contrastingly, both fearful faces and negative scenes elicited enhanced spontaneous corrugator activity at 500-750ms after stimulus onset. However, relative to baseline EMG changes occurred earlier for faces (250ms) than for scenes (500ms) whereas for scenes activity changes were more pronounced over the whole viewing period. Taking into account all effects, the data suggests that emotional facial expressions evoke faster attentional orienting, but weaker affective neural activity and emotional behavioural responses compared to emotional scenes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Mood and its association with metabolic health in adolescents: a longitudinal study, EarlyBird 65.

PubMed

Jeffery, Alison N; Hyland, Michael E; Hosking, Joanne; Wilkin, Terence J

2014-12-01

Mood comprises two main traits - positive and negative affect, both associated with depression and anxiety. Studies in children have linked depression with obesity, but the association with metabolic health is unclear. To explore the relationship between mood and metabolic health in adolescents. We studied 208 healthy children (115 boys) enrolled in the longitudinal EarlyBird Diabetes Study, and reviewed at 7 and 16 yr. Participants completed the Positive Affect and Negative Affect Schedule - Child Form (PANAS-C) at 16yr to assess positive and negative affect, together representing mood. Measures at 7 and 16 yr: body mass index (BMI), fat (%; dual energy X-ray absorptiometry), physical activity (accelerometer), metabolic risk z-score comprising homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol/high density lipoprotein (HDL) ratio and blood pressure. Pubertal development was determined by age at peak height velocity. Positive affect was higher in boys than girls, (50 vs. 46, p = 0.001), negative affect higher in girls than boys (26 vs. 22, p < 0.001). Those with lower mood were fatter (r = -0.24, p < 0.001), had higher HOMA-IR (r = -0.12, p = 0.05), higher cholesterol:HDL ratio (r = -0.14, p = 0.02), were less active (r = 0.20, p = 0.003) and had earlier pubertal development (r = 0.19, p = 0.004). Inverse associations between mood and metabolic risk z-score and change in metabolic risk z-score 7-16yr (β = -0.26, p = 0.006, and -0.40, p = 0.004, respectively) were independent of adiposity, physical activity and puberty and sex. Low mood in healthy children is associated with poorer metabolic health independently of adiposity. These findings may have implications for the physical and mental health of contemporary youngsters, given their increasing obesity and cardiometabolic risk. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clarifying Parent-Child Reciprocities during Early Childhood: The Early Childhood Coercion Model

ERIC Educational Resources Information Center

Scaramella, Laura V.; Leve, Leslie D.

2004-01-01

Consistent with existing theory, the quality of parent-child interactions during early childhood affects children's social relationships and behavioral adjustment during middle childhood and adolescence. Harsh parenting and a propensity toward emotional overarousal interact very early in life to affect risk for later conduct problems. Less…

Differences in muscle activity between natural forefoot and rearfoot strikers during running.

PubMed

Yong, Jennifer R; Silder, Amy; Delp, Scott L

2014-11-28

Running research has focused on reducing injuries by changing running technique. One proposed method is to change from rearfoot striking (RFS) to forefoot striking (FFS) because FFS is thought to be a more natural running pattern that may reduce loading and injury risk. Muscle activity affects loading and influences running patterns; however, the differences in muscle activity between natural FFS runners and natural RFS runners are unknown. The purpose of this study was to measure muscle activity in natural FFS runners and natural RFS runners. We tested the hypotheses that tibialis anterior activity would be significantly lower while activity of the plantarflexors would be significantly greater in FFS runners, compared to RFS runners, during late swing phase and early stance phase. Gait kinematics, ground reaction forces and electromyographic patterns of ten muscles were collected from twelve natural RFS runners and ten natural FFS runners. The root mean square (RMS) of each muscle׳s activity was calculated during terminal swing phase and early stance phase. We found significantly lower RMS activity in the tibialis anterior in FFS runners during terminal swing phase, compared to RFS runners. In contrast, the medial and lateral gastrocnemius showed significantly greater RMS activity in terminal swing phase in FFS runners. No significant differences were found during early stance phase for the tibialis anterior or the plantarflexors. Recognizing the differences in muscle activity between FFS and RFS runners is an important step toward understanding how foot strike patterns may contribute to different types of injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

Regulation of early gene expression from the bovine papillomavirus genome in transiently transfected C127 cells.

PubMed Central

Szymanski, P; Stenlund, A

1991-01-01

Expression of bovine papillomavirus (BPV) early gene products is required for viral DNA replication and establishment of the transformed phenotype. By the use of a highly efficient electroporation system, we have examined for the first time the transcriptional activity of BPV promoters in their natural genomic context in a replication-permissive cell line. We have determined that a qualitatively distinct stage of transcription is not detectable prior to DNA replication in transiently transfected cells. This suggests that the transcriptional activity of the BPV genome in stably transformed cells represents the early stage of BPV gene expression. Quantitative differences in promoter activity between transiently transfected and stably transformed cells suggest that subtle changes in gene expression may control progression of the viral life cycle. Deletion analysis demonstrated that the E2 transactivator protein stimulates all of the early promoters through sequences located in the upstream regulatory region. This E2-dependent enhancer was found to be highly redundant, and particular E2 binding sites did not display a preference for particular promoters. Despite this dependence on a common cis-acting sequence, the various promoters displayed different sensitivities to the E2 transactivator. The findings that E2 regulates all promoters and, with the exception of the E2 repressors, that no other known viral gene product appears to affect transcription indicate that the E2 system functions as the master regulator of BPV early gene expression. Images PMID:1656065

Saliency affects feedforward more than feedback processing in early visual cortex.

PubMed

Emmanouil, Tatiana Aloi; Avigan, Philip; Persuh, Marjan; Ro, Tony

2013-07-01

Early visual cortex activity is influenced by both bottom-up and top-down factors. To investigate the influences of bottom-up (saliency) and top-down (task) factors on different stages of visual processing, we used transcranial magnetic stimulation (TMS) of areas V1/V2 to induce visual suppression at varying temporal intervals. Subjects were asked to detect and discriminate the color or the orientation of briefly-presented small lines that varied on color saliency based on color contrast with the surround. Regardless of task, color saliency modulated the magnitude of TMS-induced visual suppression, especially at earlier temporal processing intervals that reflect the feedforward stage of visual processing in V1/V2. In a second experiment we found that our color saliency effects were also influenced by an inherent advantage of the color red relative to other hues and that color discrimination difficulty did not affect visual suppression. These results support the notion that early visual processing is stimulus driven and that feedforward and feedback processing encode different types of information about visual scenes. They further suggest that certain hues can be prioritized over others within our visual systems by being more robustly represented during early temporal processing intervals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trace elements and REE geochemistry of Middle Devonian carbonate mounds (Maïder Basin, Eastern Anti-Atlas, Morocco): Implications for early diagenetic processes

NASA Astrophysics Data System (ADS)

Franchi, Fulvio; Turetta, Clara; Cavalazzi, Barbara; Corami, Fabiana; Barbieri, Roberto

2016-08-01

Trace and rare earth elements (REEs) have proven their utility as tools for assessing the genesis and early diagenesis of widespread geological bodies such as carbonate mounds, whose genetic processes are not yet fully understood. Carbonates from the Middle Devonian conical mud mounds of the Maïder Basin (eastern Anti-Atlas, Morocco) have been analysed for their REE and trace element distribution. Collectively, the carbonates from the Maïder Basin mud mounds appear to display coherent REE patterns. Three different geochemical patterns, possibly related with three different diagenetic events, include: i) dyke fills with a normal marine REE pattern probably precipitated in equilibrium with seawater, ii) mound micrite with a particular enrichment of overall REE contents and variable Ce anomaly probably related to variation of pH, increase of alkalinity or dissolution/remineralization of organic matter during early diagenesis, and iii) haematite-rich vein fills precipitated from venting fluids of probable hydrothermal origin. Our results reinforce the hypothesis that these mounds were probably affected by an early diagenesis induced by microbial activity and triggered by abundance of dispersed organic matter, whilst venting may have affected the mounds during a later diagenetic phase.

Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis.

PubMed

Parra, Valentina; Eisner, Veronica; Chiong, Mario; Criollo, Alfredo; Moraga, Francisco; Garcia, Alejandra; Härtel, Steffen; Jaimovich, Enrique; Zorzano, Antonio; Hidalgo, Cecilia; Lavandero, Sergio

2008-01-15

In cells, mitochondria are organized as a network of interconnected organelles that fluctuate between fission and fusion events (mitochondrial dynamics). This process is associated with cell death. We investigated whether activation of apoptosis with ceramides affects mitochondrial dynamics and promotes mitochondrial fission in cardiomyocytes. Neonatal rat cardiomyocytes were incubated with C(2)-ceramide or the inactive analog dihydro-C(2)-ceramide for up to 6 h. Three-dimensional images of cells loaded with mitotracker green were obtained by confocal microscopy. Dynamin-related protein-1 (Drp-1) and mitochondrial fission protein 1 (Fis1) distribution and levels were studied by immunofluorescence and western blot. Mitochondrial membrane potential (DeltaPsi(m)) and cytochrome c (cyt c) distribution were used as indexes of early activation of apoptosis. Cell viability and DNA fragmentation were determined by propidium iodide staining/flow cytometry, whereas cytotoxicity was evaluated by lactic dehydrogenase activity. To decrease the levels of the mitochondrial fusion protein mitofusin 2, we used an antisense adenovirus (AsMfn2). C(2)-ceramide, but not dihydro-C(2)-ceramide, promoted rapid fragmentation of the mitochondrial network in a concentration- and time-dependent manner. C(2)-ceramide also increased mitochondrial Drp-1 and Fis1 content, Drp-1 colocalization with Fis1, and caused early activation of apoptosis. AsMfn2 accentuated the decrease in DeltaPsi(m) and cyt c redistribution induced by C(2)-ceramide. Doxorubicin, which induces cardiomyopathy and apoptosis through ceramide generation, also stimulated mitochondrial fragmentation. Ceramides stimulate mitochondrial fission and this event is associated with early activation of cardiomyocyte apoptosis.

Cumulative Effects of Nutrient Enrichment and Elevated Temperature Compromise the Early Life History Stages of the Coral Acropora tenuis

PubMed Central

Noonan, Sam H. C.; Willis, Bette L.; Fabricius, Katharina E.; Negri, Andrew P.

2016-01-01

Inshore coral reefs are experiencing the combined pressures of excess nutrient availability associated with coastal activities and warming seawater temperatures. Both pressures are known to have detrimental effects on the early life history stages of hard corals, but studies of their combined effects on early demographic stages are lacking. We conducted a series of experiments to test the combined effects of nutrient enrichment (three levels) and elevated seawater temperature (up to five levels) on early life history stages of the inshore coral Acropora tenuis, a common species in the Indo-Pacific and Red Sea. Gamete fertilization, larval survivorship and larval settlement were all significantly reduced as temperature increased, but only fertilization was further affected by simultaneous nutrient enrichment. Combined high temperatures and nutrient enrichment affected fertilization in an additive manner, whereas embryo abnormalities increased synergistically. Higher than normal temperatures (32°C) increased coral juvenile growth rates 1.6-fold, but mortality also increased by 50%. The co-occurrence of nutrient enrichment with high temperatures reduced juvenile mortality to 36%, ameliorating temperature stress (antagonistic interaction). Overall, the types of effect (additive vs synergistic or antagonistic) and their magnitude varied among life stages. Gamete and embryo stages were more affected by temperature stress and, in some cases, also by nutrient enrichment than juveniles. The data suggest that coastal runoff events might exacerbate the impacts of warming temperatures on fertilization if these events co-occur during corals spawning. The cumulative impacts of simultaneous exposure to nutrient enrichment and elevated temperatures over all early life history stages increases the likelihood for failure of larval supply and recruitment for this coral species. Our results suggest that improving the water quality of river discharges into coastal areas might help to enhance the thermal tolerances of early life history stages in this common coral species. PMID:27575699

Witnessing peer rejection during early adolescence: Neural correlates of empathy for experiences of social exclusion

PubMed Central

Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Dapretto, Mirella

2010-01-01

Neuroimaging studies with adults have begun to reveal the neural bases of empathy; however, this research has focused on empathy for physical pain, rather than empathy for negative social experiences. Moreover, this work has not examined adolescents who may frequently witness and empathize with others who experience negative social experiences like peer rejection. Here, we examined neural activity among early adolescents observing social exclusion compared to observing inclusion, and how this activity related to both trait empathy and subsequent prosocial behavior. Participants were scanned while they observed an individual whom they believed was being socially excluded. At least one day prior to the scan they reported their trait empathy, and following the scan they wrote emails to the excluded victim that were rated for prosocial behavior (e.g., helping, comforting). Observing exclusion compared to inclusion activated regions involved in mentalizing (i.e., dorsomedial prefrontal cortex; DMPFC), particularly among highly empathic individuals. Additionally, individuals who displayed more activity in affective, pain-related regions during observed exclusion compared to inclusion subsequently wrote more prosocial emails to excluded victims. Overall findings suggest that when early adolescents witness social exclusion in their daily lives, some may actually ‘feel the pain’ of the victims and act more prosocially toward them as a result. PMID:20602283

Early pregnancy factor activity in serum of patients with surgical abortion.

PubMed

Cheng, S J; Ma, A Y; Qiao, C X; Zheng, Z Q

2000-10-01

The presence of early pregnancy factor (EPF) has been repeatedly confirmed as indispensable to successful pregnancy. However, there is as yet little reported about how surgical abortion would affect the EPF activity, owing to the induced embryo loss. The aim of this study was to pursue this among a large number of patients available in the People's Republic of China. Sera from aborters were collected before surgical abortion and again on the 3rd, 5th and 7th day after treatment. EPF activity was detected by rosette inhibition assay. Before surgical abortion, the mean level of EPF in pregnancy sera was about the same as that of the positive control. After surgical abortion, the EPF level declined rapidly for the first 3 days and then dropped gradually within the negative control range after 5-7 days. Quantitative study of EPF activity along temporal dimensions (duration) due to surgical abortion further promotes the efficiency to take EPF activity and its rate of change as truly index for monitoring embryonic care and development of normal pregnancy.

Effects of slow and accelerated rehabilitation protocols on range of motion after arthroscopic rotator cuff repair.

PubMed

Düzgün, İrem; Baltacı, Gül; Turgut, Elif; Atay, O Ahmet

2014-01-01

The aim of the study was to investigate the effects of the early initiation of passive and active range of motion exercises following arthroscopic rotator cuff repair. The study included 40 patients who underwent arthroscopic rotator cuff repair. Patients were quasi-randomly assigned into accelerated (ACCEL) protocol (n=19) and slow (SLOW) protocol (n=21) groups. Patients in both groups were treated with the same protocol. Active range of motion was begun at the 3rd week in the ACCEL group and the 6th week in the SLOW group. Range of motion was recorded at postoperative weeks 3, 5, 8, 12, and 24. While active range of motion for all measurements improved across weeks, there were no differences between groups, with the exception of active total elevation which was greater at all time point measurements in the ACCEL group (p<0.05). The early initiation of passive and gentle controlled active motion exercise following rotator cuff repairs does not appear to affect range of motion in the first 6 postoperative months.

Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise.

PubMed

Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

2016-01-01

This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90-100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important and requires further investigation.

Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise

PubMed Central

Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

2016-01-01

This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90–100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important and requires further investigation. PMID:27096389

Infant diet sets the tone for parasympathetic regulation of resting heart rate: Development of vagal tone from 3 months to 2 years

USDA-ARS?s Scientific Manuscript database

The parasympathetic nervous system (PS) influences are critical in the autonomic control of the heart. To examine how early postnatal diet affects PS development, we used a measure of tonic PS control of cardiac activity, vagal tone, derived from resting heart rate recordings in 158 breastfed (BF), ...

The Cowden Preautism Observation Inventory: With Effective Intervention Activities for Sensory Motor Stimulation and Joint Attention

ERIC Educational Resources Information Center

Cowden, Jo E.

2011-01-01

Written for parents and professionals who want to positively affect the development of infants, this book provides guidance to families for detecting early signs of preautism in their infant or toddler. The Cowden Preautism Observation Inventory (CPAOI) will help parents to establish a baseline of behaviors and skills, along with the use of…

Spinal microglia are required for long-term maintenance of neuropathic pain.

PubMed

Echeverry, Stefania; Shi, Xiang Qun; Yang, Mu; Huang, Hao; Wu, YiChen; Lorenzo, Louis-Etienne; Perez-Sanchez, Jimena; Bonin, Robert P; De Koninck, Yves; Zhang, Ji

2017-09-01

While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity. By contrast, local spinal administration of Mac1-saporin did not affect nociceptive withdrawal threshold in control animals nor did it affect the strength of afferent-evoked synaptic activity in the spinal dorsal horn in normal conditions. These findings show that the long-term, chronic phase of nerve injury-induced pain hypersensitivity is maintained by microglia-neuron interactions. The findings also effectively separate the central signalling pathways underlying the maintenance phase of the pathology from the early and peripheral inflammatory reactions to injury, pointing to different targets for the treatment of acute vs chronic injury-induced pain.

Changes in Spring Vegetation Activity over Eurasian Boreal Forest Associated with Reduction of Arctic Sea Ice

NASA Astrophysics Data System (ADS)

Koh, Y.; Jeong, J. H.; Kim, B. M.; Park, T. W.; Jeong, S. J.

2017-12-01

Vegetation activities over the high-latitude in the Northern-Hemisphere are known to be very sensitive to climate change, which can, in turn, affect the entire climate system. This is one of the important feedback effects on global climate change. In this study, we have detected a declining trend of vegetation index in the boreal forest (Taiga) region of Eurasia in early spring from the late 1990s, and confirmed that the cause is closely related to the decrease in winter temperature linked to the Arctic sea ice change. The reduction of Arctic sea ice induces weakening of the Polar vortex around the Arctic, which has a chilling effect throughout Eurasia until the early spring (March) by strengthening the Siberian high in the Eurasian continent. The decrease of vegetation growth is caused by the extreme cold phenomenon directly affecting the growth of the boreal trees. To verify this, we used vegetation-climate coupled models to investigate climate-vegetation sensitivity to sea ice reduction. As a result, when the Arctic sea ice decreased in the model simulation, the vegetation index of the boreal forest, especially needleleaf evergreen trees, decreased as similarly detected by observations.

A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini.

PubMed

Thrower, Edwin C; Yuan, Jingzhen; Usmani, Ashar; Liu, Yannan; Jones, Courtney; Minervini, Samantha N; Alexandre, Martine; Pandol, Stephen J; Guha, Sushovan

2011-01-01

Novel protein kinase C isoforms (PKC δ and ε) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Gö6976 (10 μM). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 μM), carbachol (CCh, 1 mM), or bombesin (10 μM) to induce initial events of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-κB activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) ∼3.75-5 μM but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Gö6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-κB activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-κB activation induced by a range of secretagogues in pancreatic acinar cells.

Postnatal proteasome inhibition induces neurodegeneration and cognitive deficiencies in adult mice: a new model of neurodevelopment syndrome.

PubMed

Romero-Granados, Rocío; Fontán-Lozano, Ángela; Aguilar-Montilla, Francisco Javier; Carrión, Ángel Manuel

2011-01-01

Defects in the ubiquitin-proteasome system have been related to aging and the development of neurodegenerative disease, although the effects of deficient proteasome activity during early postnatal development are poorly understood. Accordingly, we have assessed how proteasome dysfunction during early postnatal development, induced by administering proteasome inhibitors daily during the first 10 days of life, affects the behaviour of adult mice. We found that this regime of exposure to the proteasome inhibitors MG132 or lactacystin did not produce significant behavioural or morphological changes in the first 15 days of life. However, towards the end of the treatment with proteasome inhibitors, there was a loss of mitochondrial markers and activity, and an increase in DNA oxidation. On reaching adulthood, the memory of mice that were injected with proteasome inhibitors postnatally was impaired in hippocampal and amygdala-dependent tasks, and they suffered motor dysfunction and imbalance. These behavioural deficiencies were correlated with neuronal loss in the hippocampus, amygdala and brainstem, and with diminished adult neurogenesis. Accordingly, impairing proteasome activity at early postnatal ages appears to cause morphological and behavioural alterations in adult mice that resemble those associated with certain neurodegenerative diseases and/or syndromes of mental retardation.

[Long-term effect of a cognitive intervention on learning and participation in a significant leisure activity in early dementia of Alzheimer type: a case study].

PubMed

Provencher, Véronique; Bier, Nathalie; Audet, Thérèse; Gagnon, Lise

2009-06-01

Decreased ability to accomplish significant leisure activities often occurs in early stages of dementia of Alzheimer type (DAT). As a long term effect, it may eventually affect the quality of life of the patient as well as that of the caregiver's. In a previous study, a woman with early DAT (77 years old, MMSE: 24/30) improved her participation in 2 leisure activities (listening to music and praying in a group) following the learning of a few tasks (e.g. using a radio cassette, remembering the significance of an pre-programmed ring) as a result of a cognitive intervention. The present study presents the long term effect of this intervention on the retention of the learned tasks and on spontaneous participation in both leisure activities of her daily living. Measures of tasks' learning and spontaneous participation in activities have been obtained through direct observation (ex: ability to use the tasks learned without assistance) and telephone conversations with the caregiver. The measures were taken 9 to 15 months post-intervention. Nine months after the end of the intervention, the participant could no longer use the radio cassette, but was able to remember the significance of the pre-programmed ring. Similarly, she stopped listening to music, but still attended her prayer group. The intervention appears to maintain participation in a leisure activity for several months in a patient with early DAT, in spite of expected functional decline. This functional impact can be achieved through retention of specific learned tasks as well as by strong external cues (daily pre-programmed ring), and can increase the quality of life for patients with DAT.

Enhanced neutrophil chemotactic activity after bronchial challenge in subjects with grain dust-induced asthma.

PubMed

Park, H S; Jung, K S

1998-03-01

There have been few reports suggesting involvement of neutrophils in induction of bronchoconstriction after inhalation of grain dust. To understand the role of neutrophils in pathogenesis of grain dust-induced asthma. We observed serum neutrophil chemotactic activity during grain dust-bronchoprovocation tests in six asthmatic subjects with positive bronchial challenges (group I). They were compared with those of six symptomatic subjects from the same workplace with negative bronchial challenges (group II). After grain dust inhalation, serum neutrophil chemotactic activity significantly increased at 30 minutes (P = .028), and then decreased to baseline level at 240 minutes (P = .028) in five subjects of group I having isolated early asthmatic responses. Enhanced neutrophil chemotactic activity was persistent for up to 240 minutes in one asthmatic subject having both early and late asthmatic responses. There was, however, no significant change in serum neutrophil chemotactic activity during bronchial challenges in subjects of group II. Pre-incubation of sera with anti-interleukin-8 (IL-8) antibody did not affect the neutrophil chemotactic activity results of group I subjects. These results suggest that enhanced neutrophil chemotactic activity distinct from IL-8 may contribute to significant bronchoconstriction induced by grain dust.

Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

PubMed Central

Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

2016-01-01

Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:28239613

Salicylate-induced changes in immediate-early genes in the hippocampal CA1 area

PubMed Central

WU, HAO; XU, FENG-LEI; YIN, YONG; DA, PENG; YOU, XIAO-DONG; XU, HUI-MIN; TANG, YAN

2015-01-01

Studies have suggested that salicylate affects neuronal function via interactions with specific membrane channels/receptors. However, the effect of salicylate on activity and synaptic morphology of the hippocampal Cornu Ammonis (CA) 1 area remains to be elucidated. The activation of immediate-early genes (IEGs) was reported to correlate with neuronal activity, in particular activity-regulated cytoskeleton-associated protein and early growth response gene 1. The aim of the present study was to evaluate the expression of these IEGs, as well that of N-methyl D-aspartate (NMDA) receptor subunit 2B in rats following acute and chronic salicylate treatment. Protein and messenger RNA levels of all three genes were increased in rats following chronic administration of salicylate (300 mg/kg for 10 days), returning to baseline levels 14 days post-cessation of treatment. The transient upregulation of gene expression following treatment was accompanied by ultrastructural alterations in hippocampal CA1 area synapses. An increase in synaptic interface curvature was observed as well as an increased number of presynaptic vesicles; in addition, postsynaptic densities thickened and lengthened. In conclusion, the results of the present study indicated that chronic exposure to salicylate may lead to structural alteration of hippocampal CA1 neurons, and it was suggested that this process occurs through induced expression of IEGs via NMDA receptor activation. PMID:25873216

Spatio-temporal dynamics of brain mechanisms in aversive classical conditioning: high-density event-related potential and brain electrical tomography analyses.

PubMed

Pizzagalli, Diego A; Greischar, Lawrence L; Davidson, Richard J

2003-01-01

Social cognition, including complex social judgments and attitudes, is shaped by individual learning experiences, where affect often plays a critical role. Aversive classical conditioning-a form of associative learning involving a relationship between a neutral event (conditioned stimulus, CS) and an aversive event (unconditioned stimulus, US)-represents a well-controlled paradigm to study how the acquisition of socially relevant knowledge influences behavior and the brain. Unraveling the temporal unfolding of brain mechanisms involved appears critical for an initial understanding about how social cognition operates. Here, 128-channel ERPs were recorded in 50 subjects during the acquisition phase of a differential aversive classical conditioning paradigm. The CS+ (two fearful faces) were paired 50% of the time with an aversive noise (CS upward arrow + /Paired), whereas in the remaining 50% they were not (CS upward arrow + /Unpaired); the CS- (two different fearful faces) were never paired with the noise. Scalp ERP analyses revealed differences between CS upward arrow + /Unpaired and CS- as early as approximately 120 ms post-stimulus. Tomographic source localization analyses revealed early activation modulated by the CS+ in the ventral visual pathway (e.g. fusiform gyrus, approximately 120 ms), right middle frontal gyrus (approximately 176 ms), and precuneus (approximately 240 ms). At approximately 120 ms, the CS- elicited increased activation in the left insula and left middle frontal gyrus. These findings not only confirm a critical role of prefrontal, insular, and precuneus regions in aversive conditioning, but they also suggest that biologically and socially salient information modulates activation at early stages of the information processing flow, and thus furnish initial insight about how affect and social judgments operate.

Egg-laying environment modulates offspring responses to predation risk in an amphibian.

PubMed

Tóth, Zoltán; Hettyey, Attila

2018-05-01

Predator-induced plasticity has been in the focus of evolutionary ecological research in the last decades, but the consequences of temporal variation in the presence of cues predicting offspring environment have remained controversial. This is partly due to the fact that the role of early environmental effects has scarcely been scrutinized in this context while also controlling for potential maternal effects. In this study, we investigated how past environmental conditions, that is different combinations of risky or safe adult (prenatal) and oviposition (early post-natal) environments, affected offspring's plastic responses in hatching time and locomotor activity to predation risk during development in the smooth newt (Lissotriton vulgaris). We found that females did not adjust their reproductive investment to the perceived level of risk in the adult environment, and this prenatal environment had generally negligible effect on offspring phenotype. However, when predator cues were absent during oviposition, larvae raised in the presence of predator cues delayed their hatching and exhibited a decreased activity compared to control larvae developing without predator cues, which responses are advantageous when predators pose a threat to hatched larvae. In the presence of predator cues during oviposition, the difference in hatching time persisted, but the difference in general locomotor activity disappeared between risk-exposed and control larvae. Our findings provide clear experimental evidence that fine-scale temporal variation in a predictive cue during and after egg-laying interactively affects offspring phenotype, and highlight the importance of the early post-natal environment, which may exert a substantial influence on progeny's phenotype also under natural conditions. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

How does early maternal separation and chronic stress in adult rats affect the immunoreactivity of serotonergic neurons within the dorsal raphe nucleus?

PubMed

Pollano, Antonella; Trujillo, Verónica; Suárez, Marta M

2018-01-01

Vulnerability to emotional disorders like depression derives from interactions between early and late environments, including stressful conditions. The serotonin (5HT) system is strongly affected by stress and chronic unpredictable stress can alter the 5HT system. We evaluated the distribution of active serotonergic neurons in the dorsal raphe nucleus (DR) through immunohistochemistry in maternally separated and chronically stressed rats treated with an antidepressant, tianeptine, whose mechanism of action is still under review. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50-74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle. We found an interaction between the effects of MS and chronic unpredictable stress on Fos-5HT immunoreactive cells at mid-caudal level of the DR. MS-chronically stressed rats showed an increase of Fos-5HT immunoreactive cells compared with AFR-chronically stressed rats. The ventrolateral (DRL/VLPAG) and dorsal (DRD) subdivisions of the DR were significantly more active than the ventral part (DRV). At the rostral level of the DR, tianeptine decreased the number of Fos-5HT cells in DR in the AFR groups, both unstressed and stressed. Overall, our results support the idea of a match in phenotype exhibited when the early and the adult environment correspond.

Parkin Regulates the Activity of Pyruvate Kinase M2*

PubMed Central

Liu, Kun; Li, Fanzhou; Han, Haichao; Chen, Yue; Mao, Zebin; Luo, Jianyuan; Zhao, Yingming; Zheng, Bin; Gu, Wei; Zhao, Wenhui

2016-01-01

Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease. PMID:26975375

The not-so-bitter pill: Effects of combined oral contraceptives on peripheral physiological indicators of emotional reactivity.

PubMed

Armbruster, Diana; Kirschbaum, Clemens; Strobel, Alexander

2017-08-01

Combined oral contraceptives (COC) are used by millions of women worldwide. Although findings are not entirely consistent, COC have been found to impact on brain function and, thus, to modulate affective processes. Here, we investigated electro-physiological responses to emotional stimuli in free cycling women in both the early follicular and late luteal phase as well as in COC users. Skin conductance response (SCR), startle reflex, corrugator and zygomaticus activity were assessed. COC users showed reduced overall startle magnitude and SCR amplitude, but heightened overall zygomaticus activity, although effect sizes were small. Thus, COC users displayed reduced physiological reactions indicating negative affect and enhanced physiological responses signifying positive affect. In free cycling women, endogenous 17β-estradiol levels were associated with fear potentiated startle in both cycle phases as well as with SCR and zygomaticus activity during the follicular phase. Testosterone was associated with corrugator and zygomaticus activity during the luteal phase, while progesterone levels correlated with corrugator activity in the follicular phase. To the contrary, in COC users, endogenous hormones were not associated with electro-physiological measures. The results further underscore the importance of considering COC use in psychophysiological studies on emotional processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of genistein on early-stage cutaneous wound healing

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

Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

2011-07-08

Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected bymore » antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results suggest that genistein supplementation reduces oxidative stress by increasing antioxidant capacity and modulating proinflammatory cytokine expression during the early stage of wound healing.« less

Region-growing approach to detect microcalcifications in digital mammograms

NASA Astrophysics Data System (ADS)

Shin, Jin-Wook; Chae, Soo-Ik; Sook, Yoon M.; Park, Dong-Sun

2001-09-01

Detecting early symptoms of breast cancer is very important to enhance the possibility of cure. There have been active researches to develop computer-aided diagnosis(CAD) systems detecting early symptoms of breast cancer in digital mammograms. An expert or a CAD system can recognize the early symptoms based on microcalcifications appeared in digital mammographic images. Microcalcifications have higher gray value than surrounding regions, so these can be detected by expanding a region from a local maximum. However the resultant image contains unnecessary elements such as noise, holes and valleys. Mathematical morphology is a good solution to delete regions that are affected by the unnecessary elements. In this paper, we present a method that effectively detects microcalcifications in digital mammograms using a combination of local maximum operation and the region-growing operation.

The Effect of Early Visual Deprivation on the Neural Bases of Auditory Processing.

PubMed

Guerreiro, Maria J S; Putzar, Lisa; Röder, Brigitte

2016-02-03

Transient congenital visual deprivation affects visual and multisensory processing. In contrast, the extent to which it affects auditory processing has not been investigated systematically. Research in permanently blind individuals has revealed brain reorganization during auditory processing, involving both intramodal and crossmodal plasticity. The present study investigated the effect of transient congenital visual deprivation on the neural bases of auditory processing in humans. Cataract-reversal individuals and normally sighted controls performed a speech-in-noise task while undergoing functional magnetic resonance imaging. Although there were no behavioral group differences, groups differed in auditory cortical responses: in the normally sighted group, auditory cortex activation increased with increasing noise level, whereas in the cataract-reversal group, no activation difference was observed across noise levels. An auditory activation of visual cortex was not observed at the group level in cataract-reversal individuals. The present data suggest prevailing auditory processing advantages after transient congenital visual deprivation, even many years after sight restoration. The present study demonstrates that people whose sight was restored after a transient period of congenital blindness show more efficient cortical processing of auditory stimuli (here speech), similarly to what has been observed in congenitally permanently blind individuals. These results underscore the importance of early sensory experience in permanently shaping brain function. Copyright © 2016 the authors 0270-6474/16/361620-11$15.00/0.

INFANT EMOTIONAL WITHDRAWAL: A PRECURSOR OF AFFECTIVE AND COGNITIVE DISTURBANCE IN FETAL ALCOHOL SPECTRUM DISORDERS

PubMed Central

Molteno, Christopher D.; Jacobson, Joseph L.; Carter, R. Colin; Dodge, Neil C.; Jacobson, Sandra W.

2013-01-01

Objectives To test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. Methods The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Socio-demographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years; cognitive and affective function, at 5 and 9 years. Results Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all four infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. Conclusions This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link prenatal alcohol to a specific aspect of infant affective function not attributable to mother-infant interaction, infant temperament, or other socioemotional aspects of the infant’s environment and identify infant emotional withdrawal as an early indicator of affective disturbance, particularly in children later diagnosed with FAS and PFAS. PMID:24033350

A Developmental Shift in Black-White Differences in Depressive Affect across Adolescence and Early Adulthood: The Influence of Early Adult Social Roles and Socio-Economic Status

ERIC Educational Resources Information Center

Jager, Justin

2011-01-01

This study examined Black-White differences in growth of depressive affect using a longitudinal sample of middle-class, suburban U.S. subjects (n = 956) that spanned from adolescence to early adulthood. Specifically, this study examined whether Black-White differences in growth of depressive affect shift over time, and the extent to which that…

Concentrations of isoflavones and their metabolites in the blood of pregnant and non-pregnant heifers fed soy bean.

PubMed

Woclawek-Potocka, Izabela; Piskula, Mariusz Krzysztof; Bah, Mamadou; Siemieniuch, Marta Jolanta; Korzekwa, Anna; Brzezicka, Edyta; Skarzynski, Dariusz Jan

2008-10-01

The present study compared the changes in isoflavones (daidzein and genistein) and their metabolite (equol and para-ethyl-phenol) concentrations in the blood plasma of cyclic and pregnant heifers after feeding with soy bean. Twelve healthy heifers were divided into three groups: cyclic heifers (days 8-12 of the estrous cycle; control group; n=4), an early pregnancy group (2 months pregnant; n=4) and a late pregnancy group (8 months pregnant; n=4). All heifers were fed a single dose of 2.5 kg of soy bean and then blood samples were taken from the jugular vein for 8 h at predetermined intervals. The concentrations of soy bean-derived isoflavones and their active metabolites were measured in the blood plasma on an HPLC system. In the blood plasma of the early- and late-pregnant heifers, we found lower concentrations and time-dependent decreases in daidzein and genistein in comparison to cyclic heifers (P<0.05). Moreover, we noticed significant increases of equol and para-ethyl-phenol in the blood plasma of the early-pregnant heifers (P<0.05). In contrast, in the blood plasma of the late-pregnant heifers, we did not find an increase in the isoflavone metabolite concentrations compared with the early-pregnant heifers (P>0.05). In conclusion, physiological status (cyclicity or pregnancy) of the females influenced the concentrations of isoflavone metabolites in the blood plasma of the heifers. The stage of pregnancy affects isoflavone absorption, biotransformation and metabolism differently and results in higher concentrations of active metabolites of isoflavones during early pregnancy in comparison to their lower concentrations during late pregnancy. Therefore, we surmise that cows are more sensitive to active isoflavone metabolite actions during early pregnancy than cyclic heifers and heifers in late pregnancy.

Two Processes in Early Bimanual Motor Skill Learning

PubMed Central

Yeganeh Doost, Maral; Orban de Xivry, Jean-Jacques; Bihin, Benoît; Vandermeeren, Yves

2017-01-01

Most daily activities are bimanual and their efficient performance requires learning and retention of bimanual coordination. Despite in-depth knowledge of the various stages of motor skill learning in general, how new bimanual coordination control policies are established is still unclear. We designed a new cooperative bimanual task in which subjects had to move a cursor across a complex path (a circuit) as fast and as accurately as possible through coordinated bimanual movements. By looking at the transfer of the skill between different circuits and by looking at training with varying circuits, we identified two processes in early bimanual motor learning. Loss of performance due to the switch in circuit after 15 min of training amounted to 20%, which suggests that a significant portion of improvements in bimanual performance is specific to the used circuit (circuit-specific skill). In contrast, the loss of performance due to the switch in circuit was 5% after 4 min of training. This suggests that learning the new bimanual coordination control policy dominates early in the training and is independent of the used circuit. Finally, switching between two circuits throughout training did not affect the early stage of learning (i.e., the first few minutes), but did affect the later stage. Together, these results suggest that early bimanual motor skill learning includes two different processes. Learning the new bimanual coordination control policy predominates in the first minutes whereas circuit-specific skill improvements unfold later in parallel with further improvements in the bimanual coordination control policy. PMID:29326573

Phospho-mimicry mutant of atToc33 affects early development of Arabidopsis thaliana.

PubMed

Oreb, Mislav; Zoryan, Mikael; Vojta, Aleksandar; Maier, Uwe G; Eichacker, Lutz A; Schleiff, Enrico

2007-12-22

The precursor protein receptor at the chloroplast outer membrane atToc33 is a GTPase, which can be inactivated by phosphorylation in vitro, being arrested in the GDP loaded state. To assess the physiological function of phosphorylation, attoc33 knock out mutants were complemented with a mutated construct mimicking the constitutively phosphorylated state. Our data suggest that the reduced functionality of the mutant protein can be compensated by its upregulation. Chloroplast biogenesis and photosynthetic activity are impaired in the mutants during the early developmental stage, which is consistent with the requirement of atToc33 in young photosynthetic tissues.

The psychophysiology of parenting: Individual differences in autonomic reactivity to positive and negative mood inductions and observed parental affect during dyadic interactions with children.

PubMed

Connell, Arin M; Dawson, Glen C; Danzo, Sarah; McKillop, Hannah N

2017-02-01

Parenting is a complex activity driven, in part, by parental emotional and physiological responses. However, work examining the physiological underpinnings of parenting behavior is still in its infancy, and very few studies have examined such processes beyond early childhood. The current study examines associations between Autonomic Nervous System (ANS) indices of parents' physiological reactivity to positive and negative mood states and observed parental affect during a series of discussion tasks with their adolescent child. Respiratory Sinus Arrhythmia (RSA) was measured as an index of parasympathetic nervous system (PNS) activation while viewing film clips designed to induce neutral, sad, and amused mood states. Parental positive affect, anger, and distress were observed during a series of parent-child discussion tasks, which included an ambiguous discussion regarding adolescent growth, a conflict discussion, and a fun-activity planning discussion. Results supported the association between aspects of parental physiological reactivity and observed affect during dyadic interactions. Further, RSA interacted with maternal depression to predict observed positive affect, anger, and distress, although differences across tasks and specific emotions were found regarding the nature of the interaction effects. Overall, results suggest that such neurobiological processes may be particularly important predictors of parental behavior, particularly in at-risk populations. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice.

PubMed

Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog-Bon; Lee, Sang-Rae; Kong, Il-Keun; Ryoo, Jae-Woong; Park, Young-Il; Chang, Kyu-Tae; Lee, Dong-Seok

2014-09-15

We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle. The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection. Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased. These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span. Copyright © 2014 Elsevier Inc. All rights reserved.

AMP-Activated Protein Kinase as a Reprogramming Strategy for Hypertension and Kidney Disease of Developmental Origin.

PubMed

Tain, You-Lin; Hsu, Chien-Ning

2018-06-12

Suboptimal early-life conditions affect the developing kidney, resulting in long-term programming effects, namely renal programming. Adverse renal programming increases the risk for developing hypertension and kidney disease in adulthood. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life. AMP-activated protein kinase (AMPK) plays a key role in normal renal physiology and the pathogenesis of hypertension and kidney disease. This review discusses the regulation of AMPK in the kidney and provides hypothetical mechanisms linking AMPK to renal programming. This will be followed by studies targeting AMPK activators like metformin, resveratrol, thiazolidinediones, and polyphenols as reprogramming strategies to prevent hypertension and kidney disease. Further studies that broaden our understanding of AMPK isoform- and tissue-specific effects on renal programming are needed to ultimately develop reprogramming strategies. Despite the fact that animal models have provided interesting results with regard to reprogramming strategies targeting AMPK signaling to protect against hypertension and kidney disease with developmental origins, these results await further clinical translation.

New insights into the early steps of oil body mobilization during pollen germination

PubMed Central

Castro, Antonio Jesús

2013-01-01

In some plants, pollen grains accumulate storage lipids that serve as energy supply during germination. Here, three enzymes involved in early steps of oil body mobilization in the male gametophyte were functionally characterized for the first time. The effect of extracellular sugars on pollen performance and oil body dynamics was also analysed. Olive pollen oil bodies showed phospholipase A, lipase, and lipoxygenase activities on their surface. Enzyme activity levels increased during germination with a maximum after 3h. Removal of extracellular sugars from the germination medium did not affect pollen performance but increased enzyme activity rates and sped up oil body mobilization. Inhibitors seriously hampered pollen germination and pollen tube growth, leading to a characteristic accumulation of oil bodies in the germinative aperture. It can be concluded that storage lipids are sufficient for proper olive pollen germination. A lipase and a lipoxygenase are likely involved in oil body mobilization. Extracellular sugars may modulate their function, while a phospholipase A may promote their access to the storage lipids. PMID:23132905

Microenvironmental autophagy promotes tumour growth.

PubMed

Katheder, Nadja S; Khezri, Rojyar; O'Farrell, Fergal; Schultz, Sebastian W; Jain, Ashish; Rahman, Mohammed M; Schink, Kay O; Theodossiou, Theodossis A; Johansen, Terje; Juhász, Gábor; Bilder, David; Brech, Andreas; Stenmark, Harald; Rusten, Tor Erik

2017-01-19

As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment. Induction of autophagy is mediated by Drosophila tumour necrosis factor and interleukin-6-like signalling from metabolically stressed tumour cells, whereas tumour growth depends on active amino acid transport. We show that dormant growth-impaired tumours from autophagy-deficient animals reactivate tumorous growth when transplanted into autophagy-proficient hosts. We conclude that transformed cells engage surrounding normal cells as active and essential microenvironmental contributors to early tumour growth through nutrient-generating autophagy.

Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinson's Disease

PubMed Central

Vezoli, Julien; Fifel, Karim; Leviel, Vincent; Dehay, Colette; Kennedy, Henry; Cooper, Howard M.; Gronfier, Claude; Procyk, Emmanuel

2011-01-01

Background It is increasingly recognized that non-motor symptoms are a prominent feature of Parkinson's disease and in the case of cognitive deficits can precede onset of the characteristic motor symptoms. Here, we examine in 4 monkeys chronically treated with low doses of the neurotoxin MPTP the early and long-term alterations of rest-activity rhythms in relationship to the appearance of motor and cognitive symptoms. Methodology/Principal Findings Behavioral activity recordings as well as motor and cognitive assessments were carried out continuously and in parallel before, during and for several months following MPTP-treatment (12–56 weeks). Cognitive abilities were assessed using a task that is dependent on the functional integrity of the fronto-striatal axis. Rest-activity cycles were monitored continuously using infrared movement detectors of locomotor activity. Motor impairment was evaluated using standardized scales for primates. Results show that MPTP treatment led to an immediate alteration (within one week) of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only became apparent 3 to 5 weeks after initiating chronic MPTP administration. In three of the four animals studied, clinical scores returned to control levels 5–7 weeks following cessation of MPTP treatment. In contrast, both cognitive deficits and chronobiological alterations persisted for many months. Levodopa treatment led to an improvement of cognitive performance but did not affect rest-activity rhythms in the two cases tested. Conclusions/Significance Present results show that i) changes in the rest activity cycles constituted early detectable consequences of MPTP treatment and, along with cognitive alterations, characterize the presymptomatic stage; ii) following motor recovery there is a long-term persistence of non-motor symptoms that could reflect differential underlying compensatory mechanisms in these domains; iii) the progressive MPTP-monkey model of presymptomatic ongoing parkinsonism offers possibilities for in-depth studies of early non-motor symptoms including sleep alterations and cognitive deficits. PMID:21887350

Cyber Culture and Personnel Security: Report 2 - Ethnographic Analysis of Second Life

DTIC Science & Technology

2011-07-01

respondents reported experiencing highly stressful events during their early childhood , albeit to varying degrees. These events included divorce ...adjudication, and continuous evaluation phases. Moreover, personnel’s activities in the cyber world may negatively affect their judgment, day-to-day...described below: Behaviors That Can be Used to Negatively Influence Personnel A core concern for personnel security is that individuals might become

The Structure of Good Beginnings: The Early Experiences of Graduate Students. ASHE Annual Meeting Paper.

ERIC Educational Resources Information Center

Boyle, Peg; Boice, Bob

This paper proposes a model for graduate student success and reports the results of a study of factors affecting the success of 40 first-year graduate students. Based on a review of the literature, a four-element model for graduate success was devised that focused on: (1) immersion in research activities; (2) academic regimen and planning; (3)…

Precambrian evolution of the climate system.

PubMed

Walker, J C

1990-01-01

Climate is an important environmental parameter of the early Earth, likely to have affected the origin and evolution of life, the composition and mineralogy of sedimentary rocks, and stable isotope ratios in sedimentary minerals. There is little observational evidence constraining Precambrian climates. Most of our knowledge is at present theoretical. Factors that must have affected the climate include reduced solar luminosity, enhanced rotation rate of the Earth, an area of land that probably increased with time, and biological evolution, particularly as it affected the composition of the atmosphere and the greenhouse effect. Cloud cover is a major uncertainty about the early Earth. Carbon dioxide and its greenhouse effect are the factors that have been most extensively studied. This paper presents a new examination of the biogeochemical cycles of carbon as they may have changed between an Archean Earth deficient in land, sedimentary rocks, and biological activity, and a Proterozoic Earth much like the modern Earth, but lacking terrestrial life and carbonate-secreting plankton. Results of a numerical simulation of this transition show how increasing biological activity could have drawn down atmospheric carbon dioxide by extracting sedimentary organic carbon from the system. Increasing area of continents could further have drawn down carbon dioxide by encouraging the accumulation of carbonate sediments. An attempt to develop a numerical simulation of the carbon cycles of the Precambrian raises questions about sources and sinks of marine carbon and alkalinity on a world without continents. More information is needed about sea-floor weathering processes.

Transient Shifts of Incubation Temperature Reveal Immediate and Long-Term Transcriptional Response in Chicken Breast Muscle Underpinning Resilience and Phenotypic Plasticity.

PubMed

Naraballobh, Watcharapong; Trakooljul, Nares; Murani, Eduard; Brunner, Ronald; Krischek, Carsten; Janisch, Sabine; Wicke, Michael; Ponsuksili, Siriluck; Wimmers, Klaus

2016-01-01

Variations in egg incubation temperatures can have acute or long-term effects on gene transcription in avian species. Altered gene expression may, in turn, affect muscle traits in poultry and indirectly influence commercial production. To determine how changes in eggshell temperature affect gene expression, incubation temperatures were varied [36.8°C (low), 37.8°C (control), 38.8°C (high)] at specific time periods reflecting two stages of myogenesis [embryonic days (ED) 7-10 and 10-13]. Gene expression was compared between interventions and matching controls by microarrays in broiler breast muscle at ED10 or ED13 and post-hatch at day 35. Early (ED7-10) high incubation temperature (H10ΔC) resulted in 1370 differentially expressed genes (DEGs) in embryos. Ingenuity pathway analysis revealed temporary activation of cell maintenance, organismal development, and survival ability genes, but these effects were not maintained in adults. Late high incubation temperature (ED10-13) (H13ΔC) had slightly negative impacts on development of cellular components in embryos, but a cumulative effect was observed in adults, in which tissue development and nutrition metabolism were affected. Early low incubation temperature (L10ΔC) produced 368 DEGs, most of which were down-regulated and involved in differentiation and formation of muscle cells. In adults, this treatment down-regulated pathways of transcriptional processes, but up-regulated cell proliferation. Late low temperature incubation (L13ΔC) produced 795 DEGs in embryos, and activated organismal survival and post-transcriptional regulation pathways. In adults this treatment activated cellular and organ development, nutrition and small molecule activity, and survival rate, but deactivated size of body and muscle cells. Thermal interventions during incubation initiate immediate and delayed transcriptional responses that are specific for timing and direction of treatment. Interestingly, the transcriptional response to transiently decreased incubation temperature, which did not affect the phenotypes, prompts compensatory effects reflecting resilience. In contrast, higher incubation temperature triggers gene expression and has long-term effects on the phenotype. These mechanisms of considerable phenotypic plasticity contribute to the biodiversity and broaden the basis for managing poultry populations.

A Tribute to Charlie Chaplin: Induced Positive Affect Improves Reward-Based Decision-Learning in Parkinson’s Disease

PubMed Central

Ridderinkhof, K. Richard; van Wouwe, Nelleke C.; Band, Guido P. H.; Wylie, Scott A.; Van der Stigchel, Stefan; van Hees, Pieter; Buitenweg, Jessika; van de Vijver, Irene; van den Wildenberg, Wery P. M.

2012-01-01

Reward-based decision-learning refers to the process of learning to select those actions that lead to rewards while avoiding actions that lead to punishments. This process, known to rely on dopaminergic activity in striatal brain regions, is compromised in Parkinson’s disease (PD). We hypothesized that such decision-learning deficits are alleviated by induced positive affect, which is thought to incur transient boosts in midbrain and striatal dopaminergic activity. Computational measures of probabilistic reward-based decision-learning were determined for 51 patients diagnosed with PD. Previous work has shown these measures to rely on the nucleus caudatus (outcome evaluation during the early phases of learning) and the putamen (reward prediction during later phases of learning). We observed that induced positive affect facilitated learning, through its effects on reward prediction rather than outcome evaluation. Viewing a few minutes of comedy clips served to remedy dopamine-related problems associated with frontostriatal circuitry and, consequently, learning to predict which actions will yield reward. PMID:22707944

Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy

PubMed Central

Chacon, Jessica Ann; Sarnaik, Amod A; Chen, Jie Qing; Creasy, Caitlin; Kale, Charuta; Robinson, John; Weber, Jeffrey; Hwu, Patrick; Pilon-Thomas, Shari; Radvanyi, Laszlo

2014-01-01

Purpose Cultured tumor fragments from melanoma metastases have been used for years as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy. The expansion of tumor-reactive CD8+ T cells with IL-2 in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8+ T cells recently found to constitute the majority of tumor-specific T cells. Experimental Design We used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB co-stimulation. Results We found that addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8+ TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFκB activation and the induction of T-cell survival and memory genes, as well as enhanced IL-2 responsiveness, in the CD8+ T cells in the fragments and emerging from the fragments. Early provision of 4-1BB co-stimulation also affected the dendritic cells (DC) by activating NFκB in DC and promoting their maturation inside the tumor fragments. Blocking HLA class I prevented the enhanced outgrowth of CD8+ T cells with anti-4-1BB, suggesting that an ongoing HLA class I-mediated antigen presentation in early tumor fragment cultures plays a role in mediating tumor-specific CD8+ TIL outgrowth. Conclusions Our results highlight a previously unrecognized concept in TIL adoptive cell therapy that the tumor microenvironment can be dynamically regulated in the initial tumor fragment cultures to regulate the types of T cells expanded and their functional characteristics. PMID:25472998

Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy.

PubMed

Chacon, Jessica Ann; Sarnaik, Amod A; Chen, Jie Qing; Creasy, Caitlin; Kale, Charuta; Robinson, John; Weber, Jeffrey; Hwu, Patrick; Pilon-Thomas, Shari; Radvanyi, Laszlo

2015-02-01

Cultured tumor fragments from melanoma metastases have been used for years as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy (ACT). The expansion of tumor-reactive CD8(+) T cells with interleukin-2 (IL2) in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8(+) T cells recently found to constitute the majority of tumor-specific T cells. We used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB costimulation. We found that addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8(+) TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFκB activation and the induction of T-cell survival and memory genes, as well as enhanced IL2 responsiveness, in the CD8(+) T cells in the fragments and emerging from the fragments. Early provision of 4-1BB costimulation also affected the dendritic cells (DC) by activating NFκB in DC and promoting their maturation inside the tumor fragments. Blocking HLA class I prevented the enhanced outgrowth of CD8(+) T cells with anti-4-1BB, suggesting that an ongoing HLA class I-mediated antigen presentation in early tumor fragment cultures plays a role in mediating tumor-specific CD8(+) TIL outgrowth. Our results highlight a previously unrecognized concept in TIL ACT that the tumor microenvironment can be dynamically regulated in the initial tumor fragment cultures to regulate the types of T cells expanded and their functional characteristics. ©2014 American Association for Cancer Research.

Daily Physical Activity in Total Hip Arthroplasty Patients Undergoing Different Surgical Approaches: A Cohort Study.

PubMed

Engdal, Monika; Foss, Olav A; Taraldsen, Kristin; Husby, Vigdis S; Winther, Siri B

2017-07-01

Muscle weakness due to trauma from the surgical approach is anticipated to affect the ability of the patient to undertake daily physical activity early after total hip arthroplasty (THA). The objective of this study was to compare daily physical activity on days 1 to 4 after discharge, in patients following THA performed by 1 of 3 surgical approaches. A cohort study included 60 hip osteoarthritis patients, scheduled for THA, allocated to direct lateral approach, posterior approach, or anterior approach. Daily physical activity was measured by an accelerometer, with upright time per 24 hours as primary outcome and walking time, number of steps, and number of upright events per 24 hours as secondary outcomes. There were no statistically significant group differences in any of the measures of daily physical activity (P > 0.290) or between days of follow-up (P > 0.155). Overall, the median participant had 3.50 hours (interquartile range, 2.85-4.81 hours) of upright time, and participants showed wide variation in all outcomes of daily physical activity. There were no differences in daily physical activity between THA patients undergoing different surgical approaches. The surgical approach may not be a limiting factor for daily physical activity early after surgery in a fast-track treatment course.

Early-life Socio-economic Status and Adult Health: The Role of Positive Affect.

PubMed

Murdock, Kyle W; LeRoy, Angie S; Fagundes, Christopher P

2017-08-01

The aim of this paper is to develop a further understanding of the relationship between early-life socio-economic status (SES) and adult health disparities. This was accomplished through evaluation of state indicators of positive and negative affect as mechanisms through which early-life SES was associated with susceptibility to a rhinovirus (i.e. the common cold). Analyses were conducted among 286 adults in a viral challenge study in which participants were exposed to a rhinovirus via nasal drops and cold symptoms were evaluated over a period of 5 days. Participant age, body mass index, sex, education, ethnicity, pre-challenge virus-specific antibody titres and subjective adult SES, along with virus type and season of participation, were included as covariates. Early-life SES was associated with cold incidence through state positive affect, but not state negative affect. In addition, contrast analysis indicated that the indirect effect through state positive affect was stronger than the indirect effect through state negative affect. Findings provide further support for early-life SES being an important variable associated with adult health, and that state self-reported positive affect may be an underlying mechanism associated with susceptibility to rhinoviruses. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Big data managing in a landslide early warning system: experience from a ground-based interferometric radar application

NASA Astrophysics Data System (ADS)

Intrieri, Emanuele; Bardi, Federica; Fanti, Riccardo; Gigli, Giovanni; Fidolini, Francesco; Casagli, Nicola; Costanzo, Sandra; Raffo, Antonio; Di Massa, Giuseppe; Capparelli, Giovanna; Versace, Pasquale

2017-10-01

A big challenge in terms or landslide risk mitigation is represented by increasing the resiliency of society exposed to the risk. Among the possible strategies with which to reach this goal, there is the implementation of early warning systems. This paper describes a procedure to improve early warning activities in areas affected by high landslide risk, such as those classified as critical infrastructures for their central role in society. This research is part of the project LEWIS (Landslides Early Warning Integrated System): An Integrated System for Landslide Monitoring, Early Warning and Risk Mitigation along Lifelines. LEWIS is composed of a susceptibility assessment methodology providing information for single points and areal monitoring systems, a data transmission network and a data collecting and processing center (DCPC), where readings from all monitoring systems and mathematical models converge and which sets the basis for warning and intervention activities. The aim of this paper is to show how logistic issues linked to advanced monitoring techniques, such as big data transfer and storing, can be dealt with compatibly with an early warning system. Therefore, we focus on the interaction between an areal monitoring tool (a ground-based interferometric radar) and the DCPC. By converting complex data into ASCII strings and through appropriate data cropping and average, and by implementing an algorithm for line-of-sight correction, we managed to reduce the data daily output without compromising the capability for performing.

Short-term hyperglycaemia causes non-reversible changes in arterial gene expression in a fully 'switchable' in vivo mouse model of diabetes.

PubMed

Zervou, S; Wang, Y-F; Laiho, A; Gyenesei, A; Kytömäki, L; Hermann, R; Abouna, S; Epstein, D; Pelengaris, S; Khan, M

2010-12-01

Irreversible arterial damage due to early effects of hypo- or hyperglycaemia could account for the limited success of glucose-lowering treatments in preventing cardiovascular disease (CVD) events. We hypothesised that even brief hypo- or hyperglycaemia could adversely affect arterial gene expression and that these changes, moreover, might not be fully reversible. By controlled activation of a 'switchable' c-Myc transgene in beta cells, adult pIns-c-MycER(TAM) mice were rendered transiently hypo- and then hyperglycaemic, after which they were allowed to recover for up to 3 months. Immediate and sequential changes in aortic global gene expression from normal glycaemia through hypo- and hyperglycaemia to recovery were assessed. Gene expression was compared with that of normoglycaemic transgenic and tamoxifen-treated wild-type controls. Overall, expression of 95 genes was significantly affected by moderate hypoglycaemia (glucose down to 2.5 mmol/l), whereas over 769 genes were affected by hyperglycaemia. Genes and pathways activated included several involved in atherogenic processes, such as inflammation and arterial calcification. Although expression of many genes recovered to initial pre-exposure levels when hyperglycaemia was corrected (74.9%), in one in four genes this did not occur. Quantitative reverse transcriptase PCR and immunohistochemistry verified the gene expression patterns of key molecules, as shown by global gene arrays. Short-term exposure to hyperglycaemia can cause deleterious and persistent changes in arterial gene expression in vivo. Brief hypoglycaemia also adversely affects gene expression, although less substantially. Together, these results suggest that early correction of hyperglycaemia and avoidance of hypoglycaemia may both be necessary to avoid excess CVD risk in diabetes.

The development of cognitive empathy and concern in preschool children: A behavioral neuroscience investigation.

PubMed

Decety, Jean; Meidenbauer, Kimberly L; Cowell, Jason M

2018-05-01

This developmental neuroscience study examined the electrophysiological responses (EEG and ERPs) associated with perspective taking and empathic concern in preschool children, as well as their relation to parental empathy dispositions and children's own prosocial behavior. Consistent with a body of previous studies using stimuli depicting somatic pain in both children and adults, larger early (~200 ms) ERPs were identified when perceiving painful versus neutral stimuli. In the slow wave window (~800 ms), a significant interaction of empathy condition and stimulus type was driven by a greater difference between painful and neutral images in the empathic concern condition. Across early development, children exhibited enhanced N2 to pain when engaging in empathic concern. Greater pain-elicited N2 responses in the cognitive empathy condition also related to parent dispositional empathy. Children's own prosocial behavior was predicted by several individual differences in neural function, including larger early LPP responses during cognitive empathy and greater differentiation in late LPP and slow wave responses to empathic concern versus affective perspective taking. Left frontal activation (greater alpha suppression) while engaging in affective perspective taking was also related to higher levels of parent cognitive empathy. Together, this multilevel analysis demonstrates the important distinction between facets of empathy in children; the value of examining neurobehavioral processes in development. It provides provoking links between children's neural functioning and parental dispositions in early development. © 2017 John Wiley & Sons Ltd.

Psychological keys in the study of African American religious folk songs in the early work of Howard W. Odum (1884-1954).

PubMed

Bernal-Marcos, Marcos José; Castro-Tejerina, Jorge; Loredo-Narciandi, José Carlos

2017-02-01

This study focuses on the analysis of the early work of Howard W. Odum (1884-1954) and the examination of the psychological aspects that marked his reflection on African American music. This analysis reveals many of the aspects that were generically shared by the psychological agenda of the period when analyzing aesthetic experience and activity. Outstanding among these are the relationship of the musical phenomenon with very basic or primary affective-emotional dimensions, the conception of the musical phenomenon as an indicator of the cognitive-affective development of human groups, its expression in the form of cultural and complex intersubjective products, or its possible participation in the technoscientific design of social reform and progress. The simultaneous treatment of all of these aspects in Odum's work brings to light the interdisciplinary framework in which early psychology moved, while revealing the theoretical and ideological contradictions and controversies that enveloped the discipline, above all, at the point where it attempted to place itself at the service of the constitution of self-governed individuals. All in all, Odum's work also reflects the crucial role that early psychology attributed to art as a privileged medium to give meaning to experience and the human being's vital purposes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Parent-child relationship quality and infantile amnesia in adults.

PubMed

Peterson, Carole; Nguyen, Duyen T K

2010-11-01

The first years of life are typically shrouded by infantile amnesia, but there is enormous variability between adults in how early and how much they can remember from this period. This study examined one possible factor affecting this variability: whether the perceived quality of parent-child relationships is associated with the number of early memories young adults can retrieve, and their age at the time of their first memory. We found such associations but they were qualified by parent gender. Mother-child relationships that were more affectively intense (greater social support but also more negative interchanges) were associated with recalling more early memories, although paternal companionship was most associated with how early an individual's first memory was. Affective tone of retrieved memories was also assessed, and a greater proportion of affectively positive memories (as well as fewer affectively neutral memories for males) was associated with high parental involvement in children's lives.

The impact of early repeated pain experiences on stress responsiveness and emotionality at maturity in rats.

PubMed

Page, Gayle G; Blakely, Wendy P; Kim, Miyong

2005-01-01

The intensive care necessary for premature newborns is characterized by multiple procedures, many of which are painful. Given emerging evidence that such early pain during this time of high brain plasticity may affect long-term neurodevelopmental and social-emotional functioning, this study explored the impact of early repeated pain on emotionality and stress responsivity at maturity. From birth through postnatal day 7, Fischer 344 pups underwent either paw needle prick every day versus every other day or daily paw touch, or were left unperturbed. Each paw received the designated perturbation once per day. At maturity, some animals underwent emotionality testing: either a 4-day series of open field exposures or a single elevated plus-maze (EPM) exposure. The paw prick groups exhibited less open field habituation and occupied the EPM open arms more. Two weeks later, all animals were either subjected to forced swim or not. At 1h post-swim, animals underwent either blood withdrawal for plasma corticosterone (CS) levels and ex vivo natural killer cell activity (NKCA) or were injected intravenously with radiolabeled NK-sensitive syngeneic MADB106 tumor cells and assessed for lung tumor retention. Sex was a major factor in the manifestation of perturbation-related differences in the biologic outcomes. Whereas postnatal pain differentially affected baseline tumor retention between males and females, only males exhibited perturbation-related differences in swim stress-induced increases in tumor retention and CS. Finally, male-female differences were evident in CS, NKCA, and tumor responses to swim stress. These findings suggest that early pain affects neurodevelopmental function in the mature organism; however, these relationships are complicated by sex differences, the postnatal pain schedule, and the outcome measured.

Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

PubMed Central

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

PubMed

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

Cellular uptake mediated by epidermal growth factor receptor facilitates the intracellular activity of phosphorothioate-modified antisense oligonucleotides

PubMed Central

Wang, Shiyu; Allen, Nickolas; Vickers, Timothy A; Revenko, Alexey S; Sun, Hong; Liang, Xue-hai; Crooke, Stanley T

2018-01-01

Abstract Chemically modified antisense oligonucleotides (ASOs) with phosphorothioate (PS) linkages have been extensively studied as research and therapeutic agents. PS-ASOs can enter the cell and trigger cleavage of complementary RNA by RNase H1 even in the absence of transfection reagent. A number of cell surface proteins have been identified that bind PS-ASOs and mediate their cellular uptake; however, the mechanisms that lead to productive internalization of PS-ASOs are not well understood. Here, we characterized the interaction between PS-ASOs and epidermal growth factor receptor (EGFR). We found that PS-ASOs trafficked together with EGF and EGFR into clathrin-coated pit structures. Their co-localization was also observed at early endosomes and inside enlarged late endosomes. Reduction of EGFR decreased PS-ASO activity without affecting EGF-mediated signaling pathways and overexpression of EGFR increased PS-ASO activity in cells. Furthermore, reduction of EGFR delays PS-ASO trafficking from early to late endosomes. Thus, EGFR binds to PS-ASOs at the cell surface and mediates essential steps for active (productive) cellular uptake of PS-ASOs through its cargo-dependent trafficking processes which migrate PS-ASOs from early to late endosomes. This EGFR-mediated process can also serve as an additional model to better understand the mechanism of intracellular uptake and endosomal release of PS-ASOs. PMID:29514240

Parkin Regulates the Activity of Pyruvate Kinase M2.

PubMed

Liu, Kun; Li, Fanzhou; Han, Haichao; Chen, Yue; Mao, Zebin; Luo, Jianyuan; Zhao, Yingming; Zheng, Bin; Gu, Wei; Zhao, Wenhui

2016-05-06

Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Pathogenetic Importance and Therapeutic Implications of NF-κB in Lymphoid Malignancies

PubMed Central

Lim, Kian-Huat; Yang, Yibin; Staudt, Louis M.

2014-01-01

Summary Derangement of the nuclear factor κB (NF-κB) pathway initiates and/or sustains many types of human cancer. B-cell malignancies are particularly affected by oncogenic mutations, translocations, and copy number alterations affecting key components the NF-κB pathway, most likely owing to the pervasive role of this pathway in normal B cells. These genetic aberrations cause tumors to be ‘addicted’ to NF-κB, which can be exploited therapeutically. Since each subtype of lymphoid cancer utilizes different mechanisms to activate NF-κB, several different therapeutic strategies are needed to address this pathogenetic heterogeneity. Fortunately, a number of drugs that block signaling cascades leading to NF-κB are in early phase clinical trials, several of which are already showing activity in lymphoid malignancies. PMID:22435566

Cannabis use in early adolescence: Evidence of amygdala hypersensitivity to signals of threat.

PubMed

Spechler, Philip A; Orr, Catherine A; Chaarani, Bader; Kan, Kees-Jan; Mackey, Scott; Morton, Aaron; Snowe, Mitchell P; Hudson, Kelsey E; Althoff, Robert R; Higgins, Stephen T; Cattrell, Anna; Flor, Herta; Nees, Frauke; Banaschewski, Tobias; Bokde, Arun L W; Whelan, Robert; Büchel, Christian; Bromberg, Uli; Conrod, Patricia; Frouin, Vincent; Papadopoulos, Dimitri; Gallinat, Jurgen; Heinz, Andreas; Walter, Henrik; Ittermann, Bernd; Gowland, Penny; Paus, Tomáš; Poustka, Luise; Martinot, Jean-Luc; Artiges, Eric; Smolka, Michael N; Schumann, Gunter; Garavan, Hugh

2015-12-01

Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n=70) of 14-year olds with a history of cannabis use to a group (n=70) of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood. Copyright © 2015. Published by Elsevier Ltd.

Adenosine Triphosphate stimulates differentiation and mineralization in human osteoblast-like Saos-2 cells.

PubMed

Cutarelli, Alessandro; Marini, Mario; Tancredi, Virginia; D'Arcangelo, Giovanna; Murdocca, Michela; Frank, Claudio; Tarantino, Umberto

2016-05-01

In the last years adenosine triphosphate (ATP) and subsequent purinergic system activation through P2 receptors were investigated highlighting their pivotal role in bone tissue biology. In osteoblasts ATP can regulate several activities like cell proliferation, cell death, cell differentiation and matrix mineralization. Since controversial results exist, in this study we analyzed the ATP effects on differentiation and mineralization in human osteoblast-like Saos-2 cells. We showed for the first time the altered functional activity of ATP receptors. Despite that, we found that ATP can reduce cell proliferation and stimulate osteogenic differentiation mainly in the early stages of in vitro maturation as evidenced by the enhanced expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2) and Osteocalcin (OC) genes and by the increased ALP activity. Moreover, we found that ATP can affect mineralization in a biphasic manner, at low concentrations ATP always increases mineral deposition while at high concentrations it always reduces mineral deposition. In conclusion, we show the osteogenic effect of ATP on both early and late stage activities like differentiation and mineralization, for the first time in human osteoblastic cells. © 2016 Japanese Society of Developmental Biologists.

Anthropogenic noise playback impairs embryonic development and increases mortality in a marine invertebrate

NASA Astrophysics Data System (ADS)

Nedelec, Sophie L.; Radford, Andrew N.; Simpson, Stephen D.; Nedelec, Brendan; Lecchini, David; Mills, Suzanne C.

2014-07-01

Human activities can create noise pollution and there is increasing international concern about how this may impact wildlife. There is evidence that anthropogenic noise may have detrimental effects on behaviour and physiology in many species but there are few examples of experiments showing how fitness may be directly affected. Here we use a split-brood, counterbalanced, field experiment to investigate the effect of repeated boat-noise playback during early life on the development and survival of a marine invertebrate, the sea hare Stylocheilus striatus at Moorea Island (French Polynesia). We found that exposure to boat-noise playback, compared to ambient-noise playback, reduced successful development of embryos by 21% and additionally increased mortality of recently hatched larvae by 22%. Our work, on an understudied but ecologically and socio-economically important taxon, demonstrates that anthropogenic noise can affect individual fitness. Fitness costs early in life have a fundamental influence on population dynamics and resilience, with potential implications for community structure and function.

Gene–environment interplay in Drosophila melanogaster: Chronic food deprivation in early life affects adult exploratory and fitness traits

PubMed Central

Burns, James Geoffrey; Svetec, Nicolas; Rowe, Locke; Mery, Frederic; Dolan, Michael J.; Boyce, W. Thomas; Sokolowski, Marla B.

2012-01-01

Early life adversity has known impacts on adult health and behavior, yet little is known about the gene–environment interactions (GEIs) that underlie these consequences. We used the fruit fly Drosophila melanogaster to show that chronic early nutritional adversity interacts with rover and sitter allelic variants of foraging (for) to affect adult exploratory behavior, a phenotype that is critical for foraging, and reproductive fitness. Chronic nutritional adversity during adulthood did not affect rover or sitter adult exploratory behavior; however, early nutritional adversity in the larval period increased sitter but not rover adult exploratory behavior. Increasing for gene expression in the mushroom bodies, an important center of integration in the fly brain, changed the amount of exploratory behavior exhibited by sitter adults when they did not experience early nutritional adversity but had no effect in sitters that experienced early nutritional adversity. Manipulation of the larval nutritional environment also affected adult reproductive output of sitters but not rovers, indicating GEIs on fitness itself. The natural for variants are an excellent model to examine how GEIs underlie the biological embedding of early experience. PMID:23045644

Early trauma, negative affect, and anxious attachment: the role of metacognition.

PubMed

Myers, Samuel G; Wells, Adrian

2015-01-01

Metacognition is linked to the etiology and maintenance of negative emotions and psychological disorder in the Self-Regulatory Executive Function Model. Although there is significant evidence supporting the model, little is currently known about the situational factors for developing dysfunctional metacognitions. The current study explored the hypothesis that early aversive experiences might be important and also tested if metacognitions could mediate the relationship between such experiences and psychological symptoms. Three hundred and fifty non-clinical adults completed a retrospective early trauma measure, as well as measures of current metacognitive beliefs, negative affect, and anxious attachment. Early emotional abuse positively and significantly correlated with several metacognitive belief dimensions but other forms of early trauma did not. Metacognition fully mediated the relationship between emotional abuse and negative affect. Anxious attachment was also positively and significantly associated with metacognitive beliefs and specific relationships remained after controlling for early emotional abuse and current negative affect. Findings are consistent with the ideas that: (i) early negative experiences, and emotional abuse in particular, could be a factor in the formation of problematic metacognitions and (ii) these metacognitions may be important in determining the effects of abuse on subsequent psychological symptoms.

Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes.

PubMed

Cittaro, Davide; Lampis, Valentina; Luchetti, Alessandra; Coccurello, Roberto; Guffanti, Alessandro; Felsani, Armando; Moles, Anna; Stupka, Elia; D' Amato, Francesca R; Battaglia, Marco

2016-04-28

Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice's respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders.

Airway structural cells regulate TLR5-mediated mucosal adjuvant activity.

PubMed

Van Maele, L; Fougeron, D; Janot, L; Didierlaurent, A; Cayet, D; Tabareau, J; Rumbo, M; Corvo-Chamaillard, S; Boulenouar, S; Jeffs, S; Vande Walle, L; Lamkanfi, M; Lemoine, Y; Erard, F; Hot, D; Hussell, T; Ryffel, B; Benecke, A G; Sirard, J-C

2014-05-01

Antigen-presenting cell (APC) activation is enhanced by vaccine adjuvants. Most vaccines are based on the assumption that adjuvant activity of Toll-like receptor (TLR) agonists depends on direct, functional activation of APCs. Here, we sought to establish whether TLR stimulation in non-hematopoietic cells contributes to flagellin's mucosal adjuvant activity. Nasal administration of flagellin enhanced T-cell-mediated immunity, and systemic and secretory antibody responses to coadministered antigens in a TLR5-dependent manner. Mucosal adjuvant activity was not affected by either abrogation of TLR5 signaling in hematopoietic cells or the presence of flagellin-specific, circulating neutralizing antibodies. We found that flagellin is rapidly degraded in conducting airways, does not translocate into lung parenchyma and stimulates an early immune response, suggesting that TLR5 signaling is regionalized. The flagellin-specific early response of lung was regulated by radioresistant cells expressing TLR5 (particularly the airway epithelial cells). Flagellin stimulated the epithelial production of a small set of mediators that included the chemokine CCL20, which is known to promote APC recruitment in mucosal tissues. Our data suggest that (i) the adjuvant activity of TLR agonists in mucosal vaccination may require TLR stimulation of structural cells and (ii) harnessing the effect of adjuvants on epithelial cells can improve mucosal vaccines.

Impact of recombinant globular adiponectin on early warm ischemia-reperfusion injury in rat bile duct after liver transplantation.

PubMed

Xia, Yang; Gong, Jian-Ping

2014-09-19

Adiponectin (APN) is an adipocyte protein with anti-diabetic properties, which has been recently revealed to have anti-inflammatory activity in organ ischemia- reperfusion injury (IRI). However, little is known about its function in bile duct IRI after liver transplantation. Therefore, we investigated whether APN affects early warm IRI in rat bile duct using a liver autologous transplantation model. In our study, rats were randomly divided into three experimental groups: a sham group, a IRI group, and a APN group. The serum enzyme levels and BDISS scores of bile duct histology associated with bile duct injury, decreased after administration of APN. Subsequently, the expression of proinflammatory cytokines, such as tumor necrosis factor(TNF-α),.interleukin-6(IL-6) and myeloperoxidase (MPO) decreased. Furthermore, pretreatment with APN suppressed the activation of nuclear factor-kappa B (NF-κB) (p65), a transcription factor involved in inflammatory reactions, compared to other two groups. Administration of APN also downregulated the expression of Fas protein and attenuated caspase-3 activity to decrease bile duct apoptosis. Our results illustrate that APN protects the rat bile duct against early warm IRI by suppressing the inflammatory response and hepatocyte apoptosis, and NF-κB (p65) plays an important role in this process.

Small larvae in large rivers: observations on downstream movement of European grayling Thymallus thymallus during early life stages.

PubMed

Van Leeuwen, C H A; Dokk, T; Haugen, T O; Kiffney, P M; Museth, J

2017-06-01

Behaviour of early life stages of the salmonid European grayling Thymallus thymallus was investigated by assessing the timing of larval downstream movement from spawning areas, the depth at which larvae moved and the distribution of juvenile fish during summer in two large connected river systems in Norway. Trapping of larvae moving downstream and electrofishing surveys revealed that T. thymallus larvae emerging from the spawning gravel moved downstream predominantly during the night, despite light levels sufficient for orientation in the high-latitude study area. Larvae moved in the water mostly at the bottom layer close to the substratum, while drifting debris was caught in all layers of the water column. Few young-of-the-year still resided close to the spawning areas in autumn, suggesting large-scale movement (several km). Together, these observations show that there may be a deliberate, active component to downstream movement of T. thymallus during early life stages. This research signifies the importance of longitudinal connectivity for T. thymallus in Nordic large river systems. Human alterations of flow regimes and the construction of reservoirs for hydropower may not only affect the movement of adult fish, but may already interfere with active movement behaviour of fish during early life stages. © 2017 The Fisheries Society of the British Isles.

Isocitrate dehydrogenase 1 is downregulated during early skin tumorigenesis which can be inhibited by overexpression of manganese superoxide dismutase.

PubMed

Robbins, Delira; Wittwer, Jennifer A; Codarin, Sarah; Circu, Magdalena L; Aw, Tak Yee; Huang, Ting-Ting; Van Remmen, Holly; Richardson, Arlan; Wang, David B; Witt, Stephan N; Klein, Ronald L; Zhao, Yunfeng

2012-08-01

Isocitrate dehydrogenase 1 (IDH1), a cytosolic enzyme that converts isocitrate to alpha-ketoglutarate, has been shown to be dysregulated during tumorigenesis. However, at what stage of cancer development IDH1 is dysregulated and how IDH1 may affect cell transformation and tumor promotion during early stages of cancer development are unclear. We used a skin cell transformation model and mouse skin epidermal tissues to study the role of IDH1 in early skin tumorigenesis. Our studies demonstrate that both the tumor promoter TPA and UVC irradiation decreased expression and activity levels of IDH1, not IDH2, in the tumor promotable JB6 P+ cell model. Skin epidermal tissues treated with dimethylbenz[α]anthracene/TPA also showed decreases in IDH1 expression and activity. In non-promotable JB6 P-cells, IDH1 was upregulated upon TPA treatment, whereas IDH2 was maintained at similar levels with TPA treatment. Interestingly, IDH1 knockdown enhanced, whereas IDH1 overexpression suppressed, TPA-induced cell transformation. Finally, manganese superoxide dismutase overexpression suppressed tumor promoter induced decreases in IDH1 expression and mitochondrial respiration, while intracellular alpha-ketoglutarate levels were unchanged. These results suggest that decreased IDH1 expression in early stage skin tumorigenesis is highly correlated with tumor promotion. In addition, oxidative stress might contribute to IDH1 inactivation, because manganese superoxide dismutase, a mitochondrial antioxidant enzyme, blocked decreases in IDH1 expression and activity. © 2012 Japanese Cancer Association.

Development and Application of Advanced Ophthalmic Imaging Technology to Enhance Military Ocular Health Capabilities

DTIC Science & Technology

2009-04-01

active military personnel and veterans, are affected by three major blinding diseases of the retina and optic nerve: diabetic retinopathy , age-related...disease is detected early. New advanced detection methods are available, but are only interpretable by very experienced specialists. The goal of this...consist of several steps [1-3]: feature detection ; transform model estimation; optimization function design; and optimization strategies. We do not

Valence interacts with the early ERP old/new effect and arousal with the sustained ERP old/new effect for affective pictures.

PubMed

Van Strien, Jan W; Langeslag, Sandra J E; Strekalova, Nadja J; Gootjes, Liselotte; Franken, Ingmar H A

2009-01-28

To examine whether valence and arousal influence recognition memory during early automatic or during more sustained processes, event-related brain potentials (ERPs) of 21 women were recorded while they made old/new judgments in a continuous recognition task with pictures from the International Affective Picture System. The pictures were presented twice and differed in emotional valence and arousal. The P1 peak and four time windows were investigated: 200-300 ms, 300-400 ms, 400-600 ms, and 750-1000 ms after stimulus onset. There was a robust old/new effect starting in the 200-300 ms epoch and lasting all time windows. The valence effect was mainly present in the P1 peak and the 200-400 ms epoch, whereas the arousal effect was found in the 300-1000 ms epoch. Exploratory sLORETA analyses dissociated valence-dependent ventromedial prefrontal activity and arousal-dependent occipital activity in the 350-380 ms time window. Valence interacted with the 200-400 ms old/new effect at central and frontal sites. Arousal interacted with the 750-1000 ms old/new effect at posterior sites. It is concluded that valence influences fast recognition memory, while arousal may influence sustained encoding.

Different modes of APC/C activation control growth and neuron-glia interaction in the developing Drosophila eye.

PubMed

Neuert, Helen; Yuva-Aydemir, Yeliz; Silies, Marion; Klämbt, Christian

2017-12-15

The development of the nervous system requires tight control of cell division, fate specification and migration. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that affects different steps of cell cycle progression, as well as having postmitotic functions in nervous system development. It can therefore link different developmental stages in one tissue. The two adaptor proteins, Fizzy/Cdc20 and Fizzy-related/Cdh1, confer APC/C substrate specificity. Here, we show that two distinct modes of APC/C function act during Drosophila eye development. Fizzy/Cdc20 controls the early growth of the eye disc anlage and the concomitant entry of glial cells onto the disc. In contrast, fzr/cdh1 acts during neuronal patterning and photoreceptor axon growth, and subsequently affects neuron-glia interaction. To further address the postmitotic role of Fzr/Cdh1 in controlling neuron-glia interaction, we identified a series of novel APC/C candidate substrates. Four of our candidate genes are required for fzr/cdh1 -dependent neuron-glia interaction, including the dynein light chain Dlc90F Taken together, our data show how different modes of APC/C activation can couple early growth and neuron-glia interaction during eye disc development. © 2017. Published by The Company of Biologists Ltd.

Thymosin α1 modifies podosome architecture and promptly stimulates the expression of podosomal markers in mature macrophages.

PubMed

Serafino, Annalucia; Andreola, Federica; Pittaluga, Eugenia; Krasnowska, Ewa K; Nicotera, Giuseppe; Sferrazza, Gianluca; Sinibaldi Vallebona, Paola; Pierimarchi, Pasquale; Garaci, Enrico

2015-01-01

The immunomodulatory activity of thymosin α1 (Tα1) on innate immunity has been extensively described, but its mechanism of action is not completely understood. We explored the possibility that Tα1-stimulation could affect the formation of podosomes, the highly dynamic, actin-rich, adhesion structures involved in macrophage adhesion/chemotaxis. The following methods were used: optical and scanning electron microscopy for analyzing morphology of human monocyte-derived macrophages (MDMs); time-lapse imaging for visualizing the time-dependent modifications induced at early times by Tα1 treatment; confocal microscopy and Western blot for analyzing localization and expression of podosome components; and Matrigel Migration Assay and zymography for testing MDM invasive ability and metalloproteinase secretion. We obtained data to support that Tα1 could affect MDM motility, invasion and chemotaxis by promptly stimulating assembly and disassembly of podosomal structures. At very early times after its addition to cell culture medium and within 1 h of treatment, Tα1 induces modifications in MDM morphology and in podosomal components that are suggestive of increased podosome turnover. Since impairment of podosome formation leads to reduced innate immunity and is associated with several immunodeficiency disorders, we confirm the validity of Tα1 as a potent activator of innate immunity and suggest possible new clinical application of this thymic peptide.

Expression of CALR mutants causes mpl-dependent thrombocytosis in zebrafish.

PubMed

Lim, K-H; Chang, Y-C; Chiang, Y-H; Lin, H-C; Chang, C-Y; Lin, C-S; Huang, L; Wang, W-T; Gon-Shen Chen, C; Chou, W-C; Kuo, Y-Y

2016-10-07

CALR mutations are identified in about 30% of JAK2/MPL-unmutated myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET) and primary myelofibrosis. Although the molecular pathogenesis of CALR mutations leading to MPNs has been studied using in vitro cell lines models, how mutant CALR may affect developmental hematopoiesis remains unknown. Here we took advantage of the zebrafish model to examine the effects of mutant CALR on early hematopoiesis and model human CALR-mutated MPNs. We identified three zebrafish genes orthologous to human CALR, referred to as calr, calr3a and calr3b. The expression of CALR-del52 and CALR-ins5 mutants caused an increase in the hematopoietic stem/progenitor cells followed by thrombocytosis without affecting normal angiogenesis. The expression of CALR mutants also perturbed early developmental hematopoiesis in zebrafish. Importantly, morpholino knockdown of mpl but not epor or csf3r could significantly attenuate the effects of mutant CALR. Furthermore, the expression of mutant CALR caused jak-stat signaling activation in zebrafish that could be blocked by JAK inhibitors (ruxolitinib and fedratinib). These findings showed that mutant CALR activates jak-stat signaling through an mpl-dependent mechanism to mediate pathogenic thrombopoiesis in zebrafish, and illustrated that the signaling machinery related to mutant CALR tumorigenesis are conserved between human and zebrafish.

Interactions of non-detergent sulfobetaines with early folding intermediates facilitate in vitro protein renaturation.

PubMed

Vuillard, L; Rabilloud, T; Goldberg, M E

1998-08-15

Non-detergent sulfobetaines (NDSB) are a family of solubilizing and stabilizing agents for proteins. In a previous study [Goldberg, M. E., Expert-Bezancon, N., Vuillard, L. & Rabilloud, T. (1996) Folding & Design 1, 21-27] we showed that the amount of active protein recovered in in vitro folding experiments could be significantly increased by some NDSBS. In this work we investigated the mechanisms by which these molecules facilitate protein renaturation. Stopped-flow and manual-mixing fluorescence and enzyme activity measurements were used to compare the kinetics of protein folding in the presence and absence of N-phenyl-methyl-N,N-dimethylammonium-propane-sulfonate (NDSB 256). Hen lysozyme and the beta2 subunit of Escherichia coli tryptophan synthase were chosen as model systems since their folding pathways had been previously investigated in detail. It is shown that, massive aggregation of tryptophan synthase occurs within less than 2.5 s after dilution in the renaturation buffer, but can be prevented by NDSB 256; only very early folding phases (such as the formation of a loosely packed hydrophobic core able to bind 8-anilino-1-naphthalenesulphonic acid, and the initial burying of tryptophan 177) are significantly altered by NDSB 256; none of the later phases is affected. Furthermore, NDSB 256 did not significantly affect any of the kinetic phases observed during the refolding of denatured lysozyme retaining intact disulphide bonds. This shows that NDSB 256 only interferes with very early steps in the folding process and acts by limiting the abortive interactions that could lead to the formation of inactive aggregates.

Postprandial Metabolism of Macronutrients and Cardiometabolic Risk: Recent Developments, Emerging Concepts, and Future Directions.

PubMed

Jacome-Sosa, Miriam; Parks, Elizabeth J; Bruno, Richard S; Tasali, Esra; Lewis, Gary F; Schneeman, Barbara O; Rains, Tia M

2016-03-01

Cardiovascular disease (CVD) is the leading cause of death in the United States. Although the role of habitual lifestyle factors such as physical activity and dietary patterns in increasing CVD risk has long been appreciated, less is known about how acute daily activities may cumulatively contribute to long-term disease risk. Here, the term acute refers to metabolic responses occurring in a short period of time after eating, and the goal of this article is to review recently identified stressors that can occur after meals and during the sleep-wake cycle to affect macronutrient metabolism. It is hypothesized that these events, when repeated on a regular basis, contribute to the observed long-term behavioral risks identified in population studies. In this regard, developments in research methods have supported key advancements in 3 fields of macronutrient metabolism. The first of these research areas is the focus on the immediate postmeal metabolism, spanning from early intestinal adsorptive events to the impact of incretin hormones on these events. The second topic is a focus on the importance of meal components on postprandial vasculature function. Finally, some of the most exciting advances are being made in understanding dysregulation in metabolism early in the day, due to insufficient sleep, that may affect subsequent processing of nutrients throughout the day. Key future research questions are highlighted which will lead to a better understanding of the relations between nocturnal, basal (fasting), and early postmeal events, and aid in the development of optimal sleep and targeted dietary patterns to reduce cardiometabolic risk. © 2016 American Society for Nutrition.

Infant pain-related negative affect at 12 months of age: early infant and caregiver predictors.

PubMed

Din Osmun, Laila; Pillai Riddell, Rebecca; Flora, David B

2014-01-01

To examine the predictive relationships of early infant and caregiver variables on expressed pain-related negative affect duration at the 12-month immunization. Infants and their caregivers (N = 255) were followed during immunization appointments over the first year of life. Latent growth curve modeling in a structural equation modeling context was used. Higher levels of initial infant pain reactivity at 2 months and caregiver emotional availability averaged across 2, 4, and 6 months of age were related to larger decreases in the duration of infant negative affect over the first 6 months of life. Longer duration of infant negative affect at 2 months and poorer regulation of infant negative affect over the first 6 months of life predicted longer durations of infant negative affect by 12 months. Infant negative affect at 12 months was a function of both infant factors and the quality of caregiver interactive behaviors (emotional availability) in early infancy.

Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

PubMed

Mantovani, Alberto; Locati, Massimo

2013-07-01

Macrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases.

The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal.

PubMed

Contarino, Angelo; Papaleo, Francesco

2005-12-20

The negative affective symptoms of opiate withdrawal powerfully motivate drug-seeking behavior and may trigger relapse to heroin abuse. To date, no medications exist that effectively relieve the negative affective symptoms of opiate withdrawal. The corticotropin-releasing factor (CRF) system has been hypothesized to mediate the motivational effects of drug dependence. The CRF signal is transmitted by two distinct receptors named CRF receptor-1 (CRF1) and CRF2. Here we report that genetic disruption of CRF1 receptor pathways in mice eliminates the negative affective states of opiate withdrawal. In particular, neither CRF1 receptor heterozygous (CRF1+/-) nor homozygous (CRF1-/-) null mutant mice avoided environmental cues repeatedly paired with the early phase of opiate withdrawal. These results were not due to altered associative learning processes because CRF1+/- and CRF1-/- mice displayed reliable, conditioned place aversions to environmental cues paired with the kappa-opioid receptor agonist U-50,488H. We also examined the impact of CRF1 receptor-deficiency upon opiate withdrawal-induced dynorphin activity in the nucleus accumbens, a brain molecular mechanism thought to underlie the negative affective states of drug withdrawal. Consistent with the behavioral indices, we found that, during the early phase of opiate withdrawal, neither CRF1+/- nor CRF1-/- showed increased dynorphin mRNA levels in the nucleus accumbens. This study reveals a cardinal role for CRF/CRF1 receptor pathways in the negative affective states of opiate withdrawal and suggests therapeutic strategies for the treatment of opiate addiction.

Centennial to millennial variations of atmospheric methane during the early Holocene

NASA Astrophysics Data System (ADS)

Yang, Ji-Woong; Ahn, Jinho; Brook, Edward

2015-04-01

Atmospheric CH4 is one of the most important greenhouse gases. Ice core studies revealed strong correlations between millennial CH4 variations and Greenland climate during the last glacial period. However, millennial to sub-millennial CH4 variations during interglacial periods are not well studied. Recently, several high-resolution data sets have been produced for the late Holocene, but it is difficult to distinguish natural- from anthropogenic changes. In contrast, the methane budget of the early Holocene is not affected by anthropogenic disturbances, thus may help us better understand natural CH4 control mechanisms under interglacial climate boundary conditions. Here we present our new high-precision and high-resolution atmospheric CH4 record from Siple Dome ice core, Antarctica that covers the early Holocene. We used our new wet extraction system at Seoul National University that shows a good precision of ~1 ppb. Our data show several tens of ppb of centennial- to millennial CH4 variations and an anti-correlative evolution with Greenland climate on the millennial time scale. The CH4 record could have been affected by many different types of forcing, including temperature, precipitation (monsoon intensity), biomass burning, sea surface temperature, and solar activity. According to our data, early Holocene CH4 is well correlated with records of hematite stained grains (HSG) in North Atlantic sediment records, within age uncertainties. A red-noise spectral analysis yields peaks at frequencies of ~1270 and ~80 years, which are similar to solar frequencies, but further investigations are needed to determine major controlling factor of atmospheric CH4during the early Holocene.

Benzene-induced myelotoxicity: application of flow cytofluorometry for the evaluation of early proliferative change in bone marrow.

PubMed Central

Irons, R D

1981-01-01

A detailed description of flow cytofluorometric DNA cell cycle analysis is presented. A number of studies by the author and other investigators are reviewed in which a method is developed for the analysis of cell cycle phase in bone marrow of experimental animals. Bone marrow cell cycle analysis is a sensitive indicator of changes in bone marrow proliferative activity occurring early in chemically-induced myelotoxicity. Cell cycle analysis, used together with other hematologic methods, has revealed benzene-induced toxicity in proliferating bone marrow cells to be cycle specific, appearing to affect a population in late S phase which then accumulate in G2/M. PMID:7016521

The Large Area Crop Inventory Experiment /LACIE/ - A summary of three years' experience

NASA Technical Reports Server (NTRS)

Erb, R. B.; Moore, B. H.

1979-01-01

Aims, history and schedule of the Large Area Crop Inventory Experiment (LACIE) conducted by NASA, USDA and NOAA from 1974-1977 are described. The LACIE experiment designed to research, develop, apply and evaluate a technology to monitor wheat production in important regions throughout the world (U.S., Canada, USSR, Brasil) utilized quantitative multispectral data collected by Landsat in concert with current weather data and historical information. The experiment successfully exploited computer data and mathematical models to extract timely corp information. A follow-on activities for the early 1980's is planned focusing especially on the early warning of changes affecting production and quality of renewable resources and commodity production forecast.

Positive Affect and Inflammatory Activity in Breast Cancer Survivors: Examining the Role of Affective Arousal

PubMed Central

Moreno, Patricia I.; Moskowitz, Andrew L.; Ganz, Patricia A.; Bower, Julienne E.

2016-01-01

Objective Given the importance of positive affect and inflammation for well-being in cancer survivors, the current study examined the relationship between high and low arousal positive affect and inflammation in 186 women who completed treatment for early-stage breast cancer. Methods Measures of high and low arousal positive affect were completed within three months after treatment completion (baseline). Plasma markers of inflammation, including sTNF-RII, CRP, and IL-1ra, were assessed at baseline and 6 and 12 month follow-up assessments. Results Multilevel modeling analyses showed that high arousal positive affect was associated with lower levels of sTNF-RII, a marker of TNF activity, at treatment completion and prospectively predicted maintenance of these differences through the 6 and 12 month follow-ups controlling for biobehavioral confounds (b = −.055, t(156) = −2.40, p = .018). However, this association was no longer significant when controlling for fatigue. Exploratory analyses showed that low arousal positive affect was associated with lower levels of CRP at treatment completion and through the 6 and 12 month follow-ups; this association remained significant controlling for fatigue and other confounds (b = −.217, t(152) = −2.04, p = .043). Conclusion The relationship of high arousal positive affect (e.g., “active”) with sTNF-RII appears to be driven by the overlap of high arousal positive affect with fatigue while the relationship of low arousal positive affect (e.g., “calm”) with CRP was independent of fatigue. Future research should consider affective arousal when examining the association of positive affect with inflammation as this facet of positive affect may have important implications for interpretation of results. PMID:26867077

Social recovery therapy in combination with early intervention services for enhancement of social recovery in patients with first-episode psychosis (SUPEREDEN3): a single-blind, randomised controlled trial.

PubMed

Fowler, David; Hodgekins, Jo; French, Paul; Marshall, Max; Freemantle, Nick; McCrone, Paul; Everard, Linda; Lavis, Anna; Jones, Peter B; Amos, Tim; Singh, Swaran; Sharma, Vimal; Birchwood, Max

2018-01-01

Provision of early intervention services has increased the rate of social recovery in patients with first-episode psychosis; however, many individuals have continuing severe and persistent problems with social functioning. We aimed to assess the efficacy of early intervention services augmented with social recovery therapy in patients with first-episode psychosis. The primary hypothesis was that social recovery therapy plus early intervention services would lead to improvements in social recovery. We did this single-blind, phase 2, randomised controlled trial (SUPEREDEN3) at four specialist early intervention services in the UK. We included participants who were aged 16-35 years, had non-affective psychosis, had been clients of early intervention services for 12-30 months, and had persistent and severe social disability, defined as engagement in less than 30 h per week of structured activity. Participants were randomly assigned (1:1), via computer-generated randomisation with permuted blocks (sizes of four to six), to receive social recovery therapy plus early intervention services or early intervention services alone. Randomisation was stratified by sex and recruitment centre (Norfolk, Birmingham, Lancashire, and Sussex). By necessity, participants were not masked to group allocation, but allocation was concealed from outcome assessors. The primary outcome was time spent in structured activity at 9 months, as measured by the Time Use Survey. Analysis was by intention to treat. This trial is registered with ISRCTN, number ISRCTN61621571. Between Oct 1, 2012, and June 20, 2014, we randomly assigned 155 participants to receive social recovery therapy plus early intervention services (n=76) or early intervention services alone (n=79); the intention-to-treat population comprised 154 patients. At 9 months, 143 (93%) participants had data for the primary outcome. Social recovery therapy plus early intervention services was associated with an increase in structured activity of 8·1 h (95% CI 2·5-13·6; p=0·0050) compared with early intervention services alone. No adverse events were deemed attributable to study therapy. Our findings show a clinically important benefit of enhanced social recovery on structured activity in patients with first-episode psychosis who received social recovery therapy plus early intervention services. Social recovery therapy might be useful in improving functional outcomes in people with first-episode psychosis, particularly in individuals not motivated to engage in existing psychosocial interventions targeting functioning, or who have comorbid difficulties preventing them from doing so. National Institute for Health Research. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

A critical life stage of the Atlantic salmon Salmo salar: behaviour and survival during the smolt and initial post-smolt migration.

PubMed

Thorstad, E B; Whoriskey, F; Uglem, I; Moore, A; Rikardsen, A H; Finstad, B

2012-07-01

The anadromous life cycle of Atlantic salmon Salmo salar involves long migrations to novel environments and challenging physiological transformations when moving between salt-free and salt-rich waters. In this article, (1) environmental factors affecting the migration behaviour and survival of smolts and post-smolts during the river, estuarine and early marine phases, (2) how behavioural patterns are linked to survival and (3) how anthropogenic factors affect migration and survival are synthesized and reviewed based on published literature. The timing of the smolt migration is important in determining marine survival. The timing varies among rivers, most likely as a consequence of local adaptations, to ensure sea entry during optimal periods. Smolts and post-smolts swim actively and fast during migration, but in areas with strong currents, their own movements may be overridden by current-induced transport. Progression rates during the early marine migration vary between 0.4 and 3.0 body lengths s(-1) relative to the ground. Reported mortality is 0.3-7.0% (median 2.3) km(-1) during downriver migration, 0.6-36% (median 6.0) km(-1) in estuaries and 0.3-3.4% (median 1.4) km(-1) in coastal areas. Estuaries and river mouths are the sites of the highest mortalities, with predation being a common cause. The mortality rates varied more among studies in estuaries than in rivers and marine areas, which probably reflects the huge variation among estuaries in their characteristics. Behaviour and survival during migration may also be affected by pollution, fish farming, sea lice Lepeophtheirus salmonis, hydropower development and other anthropogenic activities that may be directly lethal, delay migration or have indirect effects by inhibiting migration. Total mortality reported during early marine migration (up to 5-230 km from the river mouths) in the studies available to date varies between 8 and 71%. Hence, the early marine migration is a life stage with high mortalities, due to both natural and human influences. Factors affecting mortality during the smolt and post-smolt stages contribute to determine the abundance of spawner returns. With many S. salar populations in decline, increased mortality at these stages may considerably contribute to limit S. salar production, and the consequences of human-induced mortality at this stage may be severe. Development of management actions to increase survival and fitness at the smolt and post-smolt stages is crucial to re-establish or conserve wild populations. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Modulation of α power and functional connectivity during facial affect recognition.

PubMed

Popov, Tzvetan; Miller, Gregory A; Rockstroh, Brigitte; Weisz, Nathan

2013-04-03

Research has linked oscillatory activity in the α frequency range, particularly in sensorimotor cortex, to processing of social actions. Results further suggest involvement of sensorimotor α in the processing of facial expressions, including affect. The sensorimotor face area may be critical for perception of emotional face expression, but the role it plays is unclear. The present study sought to clarify how oscillatory brain activity contributes to or reflects processing of facial affect during changes in facial expression. Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed videos of human faces that changed their expression from neutral to fearful, neutral, or happy expressions. Induced changes in α power during the different morphs, source analysis, and graph-theoretic metrics served to identify the role of α power modulation and cross-regional coupling by means of phase synchrony during facial affect recognition. Changes from neutral to emotional faces were associated with a 10-15 Hz power increase localized in bilateral sensorimotor areas, together with occipital power decrease, preceding reported emotional expression recognition. Graph-theoretic analysis revealed that, in the course of a trial, the balance between sensorimotor power increase and decrease was associated with decreased and increased transregional connectedness as measured by node degree. Results suggest that modulations in α power facilitate early registration, with sensorimotor cortex including the sensorimotor face area largely functionally decoupled and thereby protected from additional, disruptive input and that subsequent α power decrease together with increased connectedness of sensorimotor areas facilitates successful facial affect recognition.

Activation of cutaneous immune responses in complex regional pain syndrome

PubMed Central

Birklein, Frank; Drummond, Peter D.; Li, Wenwu; Schlereth, Tanja; Albrecht, Nahid; Finch, Philip M.; Dawson, Linda F.; Clark, J. David; Kingery, Wade S.

2014-01-01

The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but TNF-α and IL-6 are elevated in experimental skin blister fluid from CRPS affected limbs, as is tryptase, a marker for mast cells. In the rat fracture model of CRPS exaggerated sensory and sympathetic neural signaling stimulate keratinocyte and mast cell proliferation, causing the local production of high levels of inflammatory cytokines leading to pain behavior. The current investigation used CRPS patient skin biopsies to determine whether keratinocyte and mast cell proliferation occur in CRPS skin and to identify the cellular source of the up-regulated TNF-α, IL-6, and tryptase observed in CRPS experimental skin blister fluid. Skin biopsies were collected from the affected skin and the contralateral mirror site in 55 CRPS patients and the biopsy sections were immunostained for keratinocyte, cell proliferation, mast cell markers, TNF-α, and IL-6. In early CRPS keratinocytes were activated in the affected skin, resulting in proliferation, epidermal thickening, and up-regulated TNF-α and IL-6 expression. In chronic CRPS there was reduced keratinocyte proliferation with epidermal thinning in the affected skin. Acute CRPS patients also had increased mast cell accumulation in the affected skin, but there was no increase in mast cell numbers in chronic CRPS. PMID:24462502

Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses.

PubMed

Rudinskiy, Nikita; Hawkes, Jonathan M; Wegmann, Susanne; Kuchibhotla, Kishore V; Muzikansky, Alona; Betensky, Rebecca A; Spires-Jones, Tara L; Hyman, Bradley T

2014-06-10

Intraneuronal neurofibrillary tangles (NFTs) - a characteristic pathological feature of Alzheimer's and several other neurodegenerative diseases - are considered a major target for drug development. Tangle load correlates well with the severity of cognitive symptoms and mouse models of tauopathy are behaviorally impaired. However, there is little evidence that NFTs directly impact physiological properties of host neurons. Here we used a transgenic mouse model of tauopathy to study how advanced tau pathology in different brain regions affects activity-driven expression of immediate-early gene Arc required for experience-dependent consolidation of long-term memories. We demonstrate in vivo that visual cortex neurons with tangles are as likely to express comparable amounts of Arc in response to structured visual stimulation as their neighbors without tangles. Probability of experience-dependent Arc response was not affected by tau tangles in both visual cortex and hippocampal pyramidal neurons as determined postmortem. Moreover, whole brain analysis showed that network-wide activity-driven Arc expression was not affected by tau pathology in any of the brain regions, including brain areas with the highest tangle load. Our findings suggest that intraneuronal NFTs do not affect signaling cascades leading to experience-dependent gene expression required for long-term synaptic plasticity.

Evidence of an IFN-γ by early life stress interaction in the regulation of amygdala reactivity to emotional stimuli.

PubMed

Redlich, Ronny; Stacey, David; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Kugel, Harald; Heindel, Walter; Arolt, Volker; Baune, Bernhard T; Dannlowski, Udo

2015-12-01

Since numerous studies have found that exposure to early life stress leads to increased peripheral inflammation and psychiatric disease, it is thought that peripheral immune activation precedes and possibly mediates the onset of stress-associated psychiatric disease. Despite early studies, IFNγ has received little attention relative to other inflammatory cytokines in the context of the pathophysiology of affective disorders. Neuroimaging endophenotypes have emerged recently as a promising means of elucidating these types of complex relationships including the modeling of the interaction between environmental factors and genetic predisposition. Here we investigate the GxE relationship between early-life stress and genetic variants of IFNγ on emotion processing. To investigate the impact of the relationship between genetic variants of IFNγ (rs1861494, rs2069718, rs2430561) and early life stress on emotion processing, a sample of healthy adults (n=409) undergoing an emotional faces paradigm in an fMRI study were genotyped and analysed. Information on early life stress was obtained via Childhood Trauma Questionnaire (CTQ). A positive association between early life stress and amygdala reactivity was found. Specifically, the main effect of genotype of rs1861494 on amygdala reactivity indicates a higher neural response in C allele carriers compared to T homozygotes, while we did not find main effects of rs2069718 and rs2430561. Importantly, interaction analyses revealed a specific interaction between IFNγ genotype (rs1861494) and early life stress affecting amygdala reactivity to emotional faces, resulting from a positive association between CTQ scores and amygdala reactivity in C allele carriers while this association was absent in T homozygotes. Our findings indicate that firstly the genetic variant of IFNγ (rs1861494) is involved with the regulation of amygdala reactivity to emotional stimuli and secondly, that this genetic variant moderates effects of early life stress on emotion processing. These findings reiterate the importance that inflammatory genes play in the interaction with early life stress and the regulation of emotion processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease.

PubMed

Králík, L; Flachsová, E; Hansíková, H; Saudek, V; Zeman, J; Martásek, P

2017-01-01

Menkes disease is a severe X-linked recessive disorder caused by a defect in the ATP7A gene, which encodes a membrane copper-transporting ATPase. Deficient activity of the ATP7A protein results in decreased intestinal absorption of copper, low copper level in serum and defective distribution of copper in tissues. The clinical symptoms are caused by decreased activities of copper-dependent enzymes and include neurodegeneration, connective tissue disorders, arterial changes and hair abnormalities. Without therapy, the disease is fatal in early infancy. Rapid diagnosis of Menkes disease and early start of copper therapy is critical for the effectiveness of treatment. We report a molecular biology-based strategy that allows early diagnosis of copper transport defects and implementation of individual therapies before the full development of pathological symptoms. Low serum copper and decreased activity of copperdependent mitochondrial cytochrome c oxidase in isolated platelets found in three patients indicated a possibility of functional defects in copper-transporting proteins, especially in the ATPA7 protein, a copper- transporting P-type ATPase. Rapid mutational screening of the ATP7A gene using high-resolution melting analysis of DNA indicated presence of mutations in the patients. Molecular investigation for mutations in the ATP7A gene revealed three nonsense mutations: c.2170C>T (p.Gln724Ter); c.3745G>T (p.Glu1249Ter); and c.3862C>T (p.Gln1288Ter). The mutation c.3745G>T (p.Glu1249Ter) has not been identified previously. Molecular analysis of the ATOX1 gene as a possible modulating factor of Menkes disease did not reveal presence of pathogenic mutations. Molecular diagnostics allowed early onset of individual therapies, adequate genetic counselling and prenatal diagnosis in the affected families.

Reassessment of an Arabidopsis cell wall invertase inhibitor AtCIF1 reveals its role in seed germination and early seedling growth.

PubMed

Su, Tao; Wolf, Sebastian; Han, Mei; Zhao, Hongbo; Wei, Hongbin; Greiner, Steffen; Rausch, Thomas

2016-01-01

In higher plants, cell wall invertase (CWI) and vacuolar invertase (VI) are recognized as essential players in sugar metabolism and sugar signaling, thereby affecting source-sink interactions, plant development and responses to environmental cues. CWI and VI expression levels are transcriptionally controlled; however, both enzymes are also subject to posttranslational control by invertase inhibitor proteins. The physiological significances of inhibitor proteins during seed germination and early seedling development are not yet fully understood. Here, we demonstrate that the inhibitor isoform AtCIF1 impacted on seed germination and early seedling growth in Arabidopsis. The primary target of AtCIF1 was shown to be localized to the apoplast after expressing an AtCIF1 YFP-fusion construct in tobacco epidermis and transgenic Arabidopsis root. The analysis of expression patterns showed that AtCWI1 was co-expressed spatiotemporally with AtCIF1 within the early germinating seeds. Seed germination was observed to be accelerated independently of exogenous abscisic acid (ABA) in the AtCIF1 loss-of-function mutant cif1-1. This effect coincided with a drastic increase of CWI activity in cif1-1 mutant seeds by 24 h after the onset of germination, both in vitro and in planta. Accordingly, quantification of sugar content showed that hexose levels were significantly boosted in germinating seeds of the cif1-1 mutant. Further investigation of AtCIF1 overexpressors in Arabidopsis revealed a markedly suppressed CWI activity as well as delayed seed germination. Thus, we conclude that the posttranslational modulation of CWI activity by AtCIF1 helps to orchestrate seed germination and early seedling growth via fine-tuning sucrose hydrolysis and, possibly, sugar signaling.

Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I): a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial.

PubMed

Taheri, Shahrad; Chagoury, Odette; Zaghloul, Hadeel; Elhadad, Sara; Ahmed, Salma Hayder; Omar, Omar; Payra, Sherryl; Ahmed, Salma; El Khatib, Neda; Amona, Rasha Abou; El Nahas, Katie; Bolton, Matthew; Chaar, Henem; Suleiman, Noor; Jayyousi, Amin; Zirie, Mahmoud; Janahi, Ibrahim; Elhag, Wahiba; Alnaama, Abdulla; Zainel, Abduljaleel; Hassan, Dahlia; Cable, Tim; Charlson, Mary; Wells, Martin; Al-Hamaq, Abdulla; Al-Abdulla, Samya; Abou-Samra, Abdul Badi

2018-05-21

Type 2 diabetes mellitus (T2DM) and obesity are syndemic and will have a significant impact on affected individuals and healthcare services worldwide. Evidence shows that T2DM remission can be achieved with significant weight loss in those who are younger with early diabetes and requiring fewer medications for glycaemic control. DIADEM-I aims to examine the impact of an intensive lifestyle intervention (ILI) using a low-energy diet (LED) meal replacement approach combined with physical activity in younger individuals with early T2DM. The planned study is an ongoing, non-blinded, pragmatic, randomised controlled, parallel-group trial examining the impact of an LED-based ILI on body weight and diabetes remission in younger (18-50 years) T2DM individuals with early diabetes (≤ 3-year duration). The ILI will be compared to usual medical care (UMC). The primary outcome will be weight loss at 12 months. Other key outcomes of interest include diabetes remission, glycaemic control, diabetes complications, cardiovascular health, physical activity, mental health, and quality of life. It is planned for the study to include 138 subjects for assessment of the primary outcome. Safety will be assessed throughout. If DIADEM-I demonstrates a clinically significant effect for younger individuals with early T2DM, it will inform clinical guidelines and services of the future for management of T2DM. ISRCTN: ISRCTN20754766 (date assigned: 7 June 2017); ClinicalTrials.gov, ID: NCT03225339 Registered on 26 June 2017.

Stressors and affective states among professional rugby union players.

PubMed

Nicholls, A R; Backhouse, S H; Polman, R C J; McKenna, J

2009-02-01

The purpose of the present study was to examine (a) the sources of sport and non-sport stress and their associated symptoms on rest days, training days, and match days and (b) the temporal aspects of sources and symptoms of stress and affective states. Professional male rugby union players (n=16) completed the Daily Analysis of Life Demands in Athletes (DALDA) and the Activation Deactivation Adjective Check List (AD ACL) for 28 days. On match days players reported that few stressors were "worse than normal." Most stressors were "worse than normal" on training days followed by rest days and more stressors were "worse than normal" on the day after a match than on match days. Further, players reported an unpleasant, low activation state across the three analysis days, suggesting they were in an overtrained state. The findings of this study demonstrate that professional rugby players experience negative affect and a multitude of sport and non-sport stressors. Early detection of stressors and negative affective states could help prevent symptoms of overtraining and burnout and facilitate optimal training and sporting performance. Coaches and practitioners are encouraged to integrate the DALDA and AD ACL in their training and performance monitoring regimes.

Heritability of the neural response to emotional pictures: evidence from ERPs in an adult twin sample.

PubMed

Weinberg, Anna; Venables, Noah C; Proudfit, Greg Hajcak; Patrick, Christopher J

2015-03-01

Affect-modulated event-related potentials (ERPs) are increasingly used to study psychopathology and individual differences in emotion processing. Many have suggested that variation in these neural responses reflects genetically mediated risk. However, to date, no studies have demonstrated genetic contributions to affect-modulated ERPs. The present study therefore sought to examine the heritability of a range of ERPs elicited during affective picture viewing. One hundred and thirty monozygotic and 124 dizygotic twin pairs passively viewed 30 pleasant, 30 neutral and 30 unpleasant images for 6 s each. The early posterior negativity was scored for each subject; in addition, the P300/late positive potential (LPP) was scored in multiple time windows and sites. Results indicate that the centro-parietal P300 (occurring between 300 and 600 ms) is subject to substantial genetic contributions. Furthermore, variance in the P300 elicited by affective stimuli was moderately heritable even after controlling for the P300 elicited by neutral stimuli. Later and more frontal activation (i.e. between 1000 and 3000 ms) also showed evidence of heritablity. Early parietal, and perhaps later frontal portions of the P300/LPP complex, may therefore represent promising neurobehavioral markers of genetically influenced processing of emotional information. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Cortisol elevation post-hatch affects behavioural performance in zebrafish larvae.

PubMed

Best, Carol; Vijayan, Mathilakath M

2018-02-01

Maternal cortisol is essential for cortisol stress axis development and de novo production of this steroid commences only after hatch in zebrafish (Danio rerio). However, very little is known about the effect of elevated cortisol levels, during the critical period of stress axis activation, on larval performance. We tested the hypothesis that elevated cortisol levels post-hatch affect behavioural performance and this is mediated by glucocorticoid receptor (GR) activation in zebrafish larvae. The behavioural response included measuring larval activity in response to alternating light and dark cycles, as well as thigmotaxis. Zebrafish larvae at 3days post-fertilization were exposed to waterborne cortisol for 24h to mimic a steroid response to an early-life stressor exposure. Also, larvae were exposed to waterborne RU-486 (a GR antagonist) either in the presence or absence of cortisol to confirm GR activation. Co-treatment with RU-486 completely abolished the upregulation of cortisol-induced 11β-hydroxysteroid dehydrogenase type 2 transcript abundance, confirming GR signalling. Cortisol-exposed larvae displayed increased locomotor activity irrespective of light condition, but showed no changes in thigmotaxis. This cortisol-mediated behavioural response was not affected by co-treatment with RU-486. Cortisol exposure also did not modify the transcript abundances of GR and mineralocorticoid receptor (MR) in zebrafish larvae. Altogether, cortisol stress axis activation post-hatch increases locomotor activity in zebrafish larvae. Our results suggest that GR signalling may not be involved in this behavioural response, leading to the proposal that cortisol action via MR signalling may influence locomotor activity in zebrafish larvae. Copyright © 2017 Elsevier Inc. All rights reserved.

Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish

PubMed Central

Wilson, K S; Tucker, C S; Al-Dujaili, E A S; Holmes, M C; Hadoke, P W F; Kenyon, C J

2016-01-01

Glucocorticoids (GCs) in utero influence embryonic development with consequent programmed effects on adult physiology and pathophysiology and altered susceptibility to cardiovascular disease. However, in viviparous species, studies of these processes are compromised by secondary maternal influences. The zebrafish, being fertilised externally, avoids this problem and has been used here to investigate the effects of transient alterations in GC activity during early development. Embryonic fish were treated either with dexamethasone (a synthetic GC), an antisense GC receptor (GR) morpholino (GR Mo), or hypoxia for the first 120h post fertilisation (hpf); responses were measured during embryonic treatment or later, post treatment, in adults. All treatments reduced cortisol levels in embryonic fish to similar levels. However, morpholino- and hypoxia-treated embryos showed delayed physical development (slower hatching and straightening of head–trunk angle, shorter body length), less locomotor activity, reduced tactile responses and anxiogenic activity. In contrast, dexamethasone-treated embryos showed advanced development and thigmotaxis but no change in locomotor activity or tactile responses. Gene expression changes were consistent with increased (dexamethasone) and decreased (hypoxia, GR Mo) GC activity. In adults, stressed cortisol values were increased with dexamethasone and decreased by GR Mo and hypoxia pre-treatments. Other responses were similarly differentially affected. In three separate tests of behaviour, dexamethasone-programmed fish appeared ‘bolder’ than matched controls, whereas Mo and hypoxia pre-treated fish were unaffected or more reserved. Similarly, the dexamethasone group but not the Mo or hypoxia groups were heavier, longer and had a greater girth than controls. Hyperglycaemia and expression of GC responsive gene (pepck) were also increased in the dexamethasone group. We conclude that GC activity controls many aspects of early-life growth and development in the zebrafish and that, like other species, manipulating GC status pharmacologically, physiologically or genetically in early life leads to programmable metabolic and behavioural traits in adulthood. PMID:27390302

Can passive mobilization provide clinically-relevant brain stimulation? A pilot EEG and NIRS study on healthy subjects.

PubMed

Pittaccio, Simone; Garavaglia, Lorenzo; Molteni, Erika; Guanziroli, Eleonora; Zappasodi, Filippo; Beretta, Elena; Strazzer, Sandra; Molteni, Franco; Villa, Elena; Passaretti, Francesca

2013-01-01

Lower limb rehabilitation is a fundamental part of post-acute care in neurological disease. Early commencement of active workout is often prevented by paresis, thus physical treatment may be delayed until patients regain some voluntary command of their muscles. Passive mobilization of the affected joints is mostly delivered in order to safeguard tissue properties and shun circulatory problems. The present paper investigates the potential role of early passive motion in stimulating cortical areas of the brain devoted to the control of the lower limb. An electro-mechanical mobilizer for the ankle joint (Toe-Up!) was implemented utilizing specially-designed shape-memory-alloy-based actuators. This device was constructed to be usable by bedridden subjects. Besides, the slowness and gentleness of the imparted motion, make it suitable for patients in a very early stage of their recovery. The mobilizer underwent technical checks to confirm reliability and passed the required safety tests for electric biomedical devices. Four healthy volunteers took part in the pre-clinical phase of the study. The protocol consisted in measuring of brain activity by EEG and NIRS in four different conditions: rest, active dorsiflexion of the ankle, passive mobilization of the ankle, and assisted motion of the same joint. The acquired data were processed to obtain maps of cortical activation, which were then compared. The measurements collected so far show that there is a similar pattern of activity between active and passive/assisted particularly in the contralateral premotor areas. This result, albeit based on very few observations, might suggest that passive motion provides somatosensory afferences that are processed in a similar manner as for voluntary control. Should this evidence be confirmed by further trials on healthy individuals and neurological patients, it could form a basis for a clinical use of early passive exercise in supporting central functional recovery.

Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

PubMed

Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

2008-12-01

This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

Effects of Low Salinity on Adult Behavior and Larval Performance in the Intertidal Gastropod Crepipatella peruviana (Calyptraeidae)

PubMed Central

Montory, Jaime A.; Pechenik, Jan A.; Diederich, Casey M.; Chaparro, Oscar R.

2014-01-01

Shallow-water coastal areas suffer frequent reductions in salinity due to heavy rains, potentially stressing the organisms found there, particularly the early stages of development (including pelagic larvae). Individual adults and newly hatched larvae of the gastropod Crepipatella peruviana were exposed to different levels of salinity stress (32(control), 25, 20 or 15), to quantify the immediate effects of exposure to low salinities on adult and larval behavior and on the physiological performance of the larvae. For adults we recorded the threshold salinity that initiates brood chamber isolation. For larvae, we measured the impact of reduced salinity on velar surface area, velum activity, swimming velocity, clearance rate (CR), oxygen consumption (OCR), and mortality (LC50); we also documented the impact of salinity discontinuities on the vertical distribution of veliger larvae in the water column. The results indicate that adults will completely isolate themselves from the external environment by clamping firmly against the substrate at salinities ≤24. Moreover, the newly hatched larvae showed increased mortality at lower salinities, while survivors showed decreased velum activity, decreased exposed velum surface area, and decreased mean swimming velocity. The clearance rates and oxygen consumption rates of stressed larvae were significantly lower than those of control individuals. Finally, salinity discontinuities affected the vertical distribution of larvae in the water column. Although adults can protect their embryos from low salinity stress until hatching, salinities <24 clearly affect survival, physiology and behavior in early larval life, which will substantially affect the fitness of the species under declining ambient salinities. PMID:25077484

Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?

PubMed

Scott, Ian C; Rijsdijk, Frühling; Walker, Jemma; Quist, Jelmar; Spain, Sarah L; Tan, Rachael; Steer, Sophia; Okada, Yukinori; Raychaudhuri, Soumya; Cope, Andrew P; Lewis, Cathryn M

2015-07-01

Genetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA. We evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants - 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions - for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models. HLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP - rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) - associated with HAQ scores over 6-24 months. HLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.

Suppression of Familial Adenomatous Polyposis by CP-31398, a TP53 modulator, in APCmin/+ Mice1

PubMed Central

Rao, Chinthalapally V.; Swamy, Malisetty V.; Patlolla, Jagan M.R.; Kopelovich, Levy

2008-01-01

p53 mutations occur in a large number of human malignancies. Mutant p53 is unable to affect downstream genes necessary for DNA repair, cell cycle regulation, and apoptosis. The styrylquinazoline CP-31398 can rescue destabilized mutant p53 expression and promote activity of wild-type p53. The present study examines chemopreventive effects of CP-31398 on intestinal adenoma development in an animal model of familial adenomatous polyposis (FAP). Effects were examined at both early and late stages of adenoma formation. Effects of CP-31398 on early-stage adenomas were determined by feeding 7-week-old female C57B/6J-APCmin (heterozygous) and wild-type C57BL/6J mice with American Institute of Nutrition (AIN)-76A diets containing 0, 100, or 200 ppm CP-31398 for 75 days. To examine activity toward late-stage adenomas, CP31398 administration was delayed until 15 weeks of age and continued for 50 days. During early-stage intervention, dietary CP-31398 suppressed development of intestinal tumors by 36% (p < 0.001) and 75% (p < 0.0001), at low and high dose, respectively. During late-stage intervention, CP-31398 also significantly suppressed intestinal polyp formation, albeit to a lesser extent than observed with early intervention. Adenomas in treated mice showed increased apoptotic cell death and decreased proliferation in conjunction with increased expression of p53, p21WAF1/CIP, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP). These observations demonstrate for the first time that the p53-modulating agent CP-31398 possesses significant chemopreventive activity in vivo against intestinal neoplastic lesions in genetically-predisposed APCmin/+ mice. Chemopreventive activity of other agents that restore tumor suppressor functions of mutant p53 in tumor cells is currently under investigation. PMID:18794156

Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression.

PubMed

Schwarz, Jaclyn M; Hutchinson, Mark R; Bilbo, Staci D

2011-12-07

A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat nucleus accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene × early-life environment interaction on morphine-induced glial activation and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior.

Early-Life Experience Decreases Drug-Induced Reinstatement of Morphine CPP in Adulthood via Microglial-Specific Epigenetic Programming of Anti-Inflammatory IL-10 Expression

PubMed Central

Schwarz, Jaclyn M.; Hutchinson, Mark R.; Bilbo, Staci D.

2012-01-01

A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat Nucleus Accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with Ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene X early-life environment interaction on morphine-induced glial activation, and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior. PMID:22159099

The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles.

PubMed

Barrett, C E; Arambula, S E; Young, L J

2015-07-21

Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1-14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified. Neonatal social isolation impaired female PP formation, without affecting OTR density. Accumbal OTR density was, however, positively correlated with the percent of time spent huddling with the partner in neonatally isolated females. Females with high accumbal OTR binding were resilient to neonatal isolation. These results are consistent with the hypothesis that parental nurturing shapes neural systems underlying social relationships by enhancing striatal OTR signaling. Thus, we next determined whether early touch, mimicking parental licking and grooming, stimulates hypothalamic OT neuron activity. Tactile stimulation induced immediate-early gene activity in OT neurons in neonates. Finally, we investigated whether pharmacologically potentiating OT release using a melanocortin 3/4 agonist, melanotan-II (10 mg kg(-1) subcutaneously), would mitigate the social isolation-induced impairments in attachment behavior. Neonatal melanotan-II administration buffered against the effects of early isolation on partner preference formation. Thus, variation in accumbal OTR density and early OT release induced by parental nurturing may moderate susceptibility to early adverse experiences, including neglect.

Influence of early attentional modulation on working memory

PubMed Central

Gazzaley, Adam

2011-01-01

It is now established that attention influences working memory (WM) at multiple processing stages. This liaison between attention and WM poses several interesting empirical questions. Notably, does attention impact WM via its influences on early perceptual processing? If so, what are the critical factors at play in this attention-perception-WM interaction. I review recent data from our laboratory utilizing a variety of techniques (electroencephalography (EEG), functional MRI (fMRI) and transcranial magnetic stimulation (TMS)), stimuli (features and complex objects), novel experimental paradigms, and research populations (younger and older adults), which converge to support the conclusion that top-down modulation of visual cortical activity at early perceptual processing stages (100–200 ms after stimulus onset) impacts subsequent WM performance. Factors that affect attentional control at this stage include cognitive load, task practice, perceptual training, and aging. These developments highlight the complex and dynamic relationships among perception, attention, and memory. PMID:21184764

Temporally selective attention modulates early perceptual processing: event-related potential evidence.

PubMed

Sanders, Lisa D; Astheimer, Lori B

2008-05-01

Some of the most important information we encounter changes so rapidly that our perceptual systems cannot process all of it in detail. Spatially selective attention is critical for perception when more information than can be processed in detail is presented simultaneously at distinct locations. When presented with complex, rapidly changing information, listeners may need to selectively attend to specific times rather than to locations. We present evidence that listeners can direct selective attention to time points that differ by as little as 500 msec, and that doing so improves target detection, affects baseline neural activity preceding stimulus presentation, and modulates auditory evoked potentials at a perceptually early stage. These data demonstrate that attentional modulation of early perceptual processing is temporally precise and that listeners can flexibly allocate temporally selective attention over short intervals, making it a viable mechanism for preferentially processing the most relevant segments in rapidly changing streams.

A Review of High School Level Astronomy Student Research Projects Over the Last Two Decades

NASA Astrophysics Data System (ADS)

Fitzgerald, M. T.; Hollow, R.; Rebull, L. M.; Danaia, L.; McKinnon, D. H.

2014-09-01

Since the early 1990s with the arrival of a variety of new technologies, the capacity for authentic astronomical research at the high school level has skyrocketed. This potential, however, has not realised the bright-eyed hopes and dreams of the early pioneers who expected to revolutionise science education through the use of telescopes and other astronomical instrumentation in the classroom. In this paper, a general history and analysis of these attempts is presented. We define what we classify as an Astronomy Research in the Classroom (ARiC) project and note the major dimensions on which these projects differ before describing the 22 major student research projects active since the early 1990s. This is followed by a discussion of the major issues identified that affected the success of these projects and provide suggestions for similar attempts in the future.

Infant emotional withdrawal: a precursor of affective and cognitive disturbance in fetal alcohol spectrum disorders.

PubMed

Molteno, Christopher D; Jacobson, Joseph L; Carter, R Colin; Dodge, Neil C; Jacobson, Sandra W

2014-02-01

Our aim was to test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Sociodemographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years, cognitive and affective function at 5 and 9 years. Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all 4 infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link prenatal alcohol to a specific aspect of infant affective function not attributable to mother-infant interaction, infant temperament, or other socioemotional aspects of the infant's environment and identify infant emotional withdrawal as an early indicator of affective disturbance, particularly in children later diagnosed with FAS and PFAS. Copyright © 2013 by the Research Society on Alcoholism.

Understanding frailty in the geriatric population.

PubMed

Wick, Jeannette Y

2011-09-01

Clinicians who work with the frail elderly know what frailty looks like, but until recently, they have had no science-based definition of this condition. Frailty is classified as a medical syndrome, and Fried et al. were among the first to standardize the definition of frailty as a distinct syndrome with biologic underpinnings. Their definition describes a clinical phenotype of decreased reserve and resistance to stressors, with clinical manifestations of a mutually exacerbating cycle of negative energy balance, sarcopenia, diminished strength, and exertion intolerance. Age is no longer considered a defining characteristic, although frailty is still considered primarily a geriatric problem. Approximately two-thirds of affected individuals enter frailty in a slow, progressive way, while one-third become frail cataclysmically. Weakness is a common early sign, and exhaustion and weight loss are often late manifestations. Observing early behavioral changes before frailty develops could provide insight into its development and suggest early interventions. Since frailty is clearly associated with adverse outcomes, a healthy, active lifestyle is the cornerstone of prevention, and many researchers suggest that resistance training can reverse some muscle loss and improve functioning. When the health care team proposes any change in care, including a new medication, it should be prepared to describe how the intervention may affect cognition, memory, energy, or function.

Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

PubMed Central

Berghella, Libera; Ferraro, Elisabetta

2012-01-01

Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

Chloride channels in myotonia congenita assessed by velocity recovery cycles.

PubMed

Tan, S Veronica; Z'Graggen, Werner J; Boërio, Delphine; Rayan, Dipa Raja; Norwood, Fiona; Ruddy, Deborah; Howard, R; Hanna, Michael G; Bostock, Hugh

2014-06-01

Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC-1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected. MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched, normal controls. MC patients exhibited increased early supernormality, but this was prevented by treatment with sodium channel blockers. After multiple conditioning stimuli, late supernormality was enhanced in all MC patients, indicating delayed repolarization. These abnormalities were similar between the MC subtypes, but recessive patients showed a greater drop in amplitude during repetitive stimulation. MVRCs indicate that chloride conductance only becomes important when muscle fibers are depolarized. The differential responses to repetitive stimulation suggest that, in dominant MC, the affected chloride channels are activated by strong depolarization, consistent with a positive shift of the CLC-1 activation curve. Copyright © 2013 Wiley Periodicals, Inc.

CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Cav3.2 T-type calcium channel activity and reticular thalamic neuron firing.

PubMed

Rzhepetskyy, Yuriy; Lazniewska, Joanna; Blesneac, Iulia; Pamphlett, Roger; Weiss, Norbert

2016-11-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. In a recent study by Steinberg and colleagues, 2 recessive missense mutations were identified in the Cav3.2 T-type calcium channel gene (CACNA1H), in a family with an affected proband (early onset, long duration ALS) and 2 unaffected parents. We have introduced and functionally characterized these mutations using transiently expressed human Cav3.2 channels in tsA-201 cells. Both of these mutations produced mild but significant changes on T-type channel activity that are consistent with a loss of channel function. Computer modeling in thalamic reticular neurons suggested that these mutations result in decreased neuronal excitability of thalamic structures. Taken together, these findings implicate CACNA1H as a susceptibility gene in amyotrophic lateral sclerosis.

A Preliminary Investigation of Factors Affecting Appraisal of the Decision to Take Early Retirement.

ERIC Educational Resources Information Center

Gowan, Mary A.

1998-01-01

Examines why individuals elect to take the early retirement package offered by their employer, as well as factors affecting their appraisal of that decision. Results suggest that all early retirement decisions are not voluntary. Individuals who do not wish to retire and who had lower self-esteem, fewer financial resources, and plans to continue…

Body Dissatisfaction and Eating Disturbances in Early Adolescence: A Structural Modeling Investigation Examining Negative Affect and Peer Factors

ERIC Educational Resources Information Center

Hutchinson, Delyse M.; Rapee, Ronald M.; Taylor, Alan

2010-01-01

This study tested five proposed models of the relationship of negative affect and peer factors in early adolescent body dissatisfaction, dieting, and bulimic behaviors. A large community sample of girls in early adolescence was assessed via questionnaire (X[overbar] age = 12.3 years). Structural equation modeling (SEM) indicated that negative…

Attentional and affective biases for attractive females emerge early in development.

PubMed

Rennels, Jennifer Lynn; Verba, Stephanie Ann

2017-01-01

Predominant experience with females early in development results in infants developing an attractive, female-like facial representation that guides children's attention toward and affective preferences for attractive females. When combined with increased interest in the other sex at puberty, these early emerging biases might help explain the robust prosocial and financial biases men exhibit toward attractive women during adulthood.

Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes

PubMed Central

Kostopoulou, Ourania N.; Wilhelmi, Vanessa; Raiss, Sina; Ananthaseshan, Sharan; Lindström, Mikael S.; Bartek, Jiri; Söderberg-Naucler, Cecilia

2017-01-01

Human cytomegalovirus (HCMV) utilizes RNA polymerase II to transcribe viral genes and produce viral mRNAs. It can specifically target the nucleolus to facilitate viral transcription and translation. As RNA polymerase I (Pol I)-mediated transcription is active in the nucleolus, we investigated the role of Pol I, along with relative contributions of the human Pol II and Pol III, to early phases of viral transcription in HCMV infected cells, compared with Herpes Simplex Virus-1 (HSV-1) and Murine cytomegalovirus (MCMV). Inhibition of Pol I with siRNA or the Pol I inhibitors CX-5461 or Actinomycin D (5nM) resulted in significantly decreased IE and pp65 mRNA and protein levels in human fibroblasts at early times post infection. This initially delayed replication was compensated for later during the replication process, at which stage it didn’t significantly affect virus production. Pol I inhibition also reduced HSV-1 ICP0 and gB transcripts, suggesting that some herpesviruses engage Pol I for their early transcription. In contrast, inhibition of Pol I failed to affect MCMV transcription. Collectively, our results contribute to better understanding of the functional interplay between RNA Pol I-mediated nucleolar events and the Herpes viruses, particularly HCMV whose pathogenic impact ranges from congenital malformations and potentially deadly infections among immunosuppressed patients, up to HCMV’s emerging oncomodulatory role in human tumors. PMID:29228551

HepPar1-Positive Circulating Microparticles Are Increased in Subjects with Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection

PubMed Central

Abbate, Valeria; Marcantoni, Margherita; Giuliante, Felice; Vecchio, Fabio M.; Gatto, Ilaria; Mele, Caterina; Saviano, Antonio; Arciuolo, Damiano; Gaetani, Eleonora; Ferrari, Maria C.; Giarretta, Igor; Ardito, Francesco; Riccardi, Laura; Nicoletti, Alberto; Ponziani, Francesca R.; Gasbarrini, Antonio; Pompili, Maurizio; Pola, Roberto

2017-01-01

Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study, we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied 15 patients affected by HCC undergoing LR, and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and five with healthy livers) were used as controls. After LR, HCC patients underwent a follow-up to check for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p < 0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p = 0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+), were not associated with HCC, nor could they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients. PMID:28498353

Distinct plasma immune signatures in ME/CFS are present early in the course of illness.

PubMed

Hornig, Mady; Montoya, José G; Klimas, Nancy G; Levine, Susan; Felsenstein, Donna; Bateman, Lucinda; Peterson, Daniel L; Gottschalk, C Gunnar; Schultz, Andrew F; Che, Xiaoyu; Eddy, Meredith L; Komaroff, Anthony L; Lipkin, W Ian

2015-02-01

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS ( n = 52) relative to healthy controls ( n = 348) that are not present in subjects with longer duration of illness ( n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS.

HAZMAT. III. The UV Evolution of Mid- to Late-M Stars with GALEX

NASA Astrophysics Data System (ADS)

Schneider, Adam C.; Shkolnik, Evgenya L.

2018-03-01

Low-mass stars are currently the most promising targets for detecting and characterizing habitable planets in the solar neighborhood. However, the ultraviolet (UV) radiation emitted by such stars can erode and modify planetary atmospheres over time, drastically affecting their habitability. Thus, knowledge of the UV evolution of low-mass stars is critical for interpreting the evolutionary history of any orbiting planets. Shkolnik & Barman used photometry from the Galaxy Evolution Explorer (GALEX) to show how UV emission evolves for early-type M stars (>0.35 M ⊙). In this paper, we extend their work to include both a larger sample of low-mass stars with known ages as well as M stars with lower masses. We find clear evidence that mid- and late-type M stars (0.08–0.35 M ⊙) do not follow the same UV evolutionary trend as early-Ms. Lower-mass M stars retain high levels of UV activity up to field ages, with only a factor of 4 decrease on average in GALEX NUV and FUV flux density between young (<50 Myr) and old (∼5 Gyr) stars, compared to a factor of 11 and 31 for early-Ms in NUV and FUV, respectively. We also find that the FUV/NUV flux density ratio, which can affect the photochemistry of important planetary biosignatures, is mass- and age-dependent for early-Ms, but remains relatively constant for the mid- and late-type Ms in our sample.

Distinct plasma immune signatures in ME/CFS are present early in the course of illness

PubMed Central

Hornig, Mady; Montoya, José G.; Klimas, Nancy G.; Levine, Susan; Felsenstein, Donna; Bateman, Lucinda; Peterson, Daniel L.; Gottschalk, C. Gunnar; Schultz, Andrew F.; Che, Xiaoyu; Eddy, Meredith L.; Komaroff, Anthony L.; Lipkin, W. Ian

2015-01-01

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS. PMID:26079000

Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study

PubMed Central

Salustri, C.; Tecchio, F.; Zappasodi, F.; Tomasevic, L.; Ercolani, M.; Moffa, F.; Cassetta, E.; Rossini, P. M.; Squitti, R.

2013-01-01

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer's disease (AD) patients. Methods. We performed a case-control study using magnetoencephalography to detect sensorimotor fields of AD patients, at rest and during median nerve stimulation. We analyzed position and amount of neurons synchronously activated by the stimulation in both hemispheres to investigate the capability of the primary somatosensory cortex to reorganize its circuitry disrupted by the disease. We also assessed systemic levels of copper, ceruloplasmin, non-Cp copper (i.e., copper not bound to ceruloplasmin), peroxides, transferrin, and total antioxidant capacity. Results. Patients' sensorimotor generators appeared spatially shifted, despite no change of latency and strength, while spontaneous activity sources appeared unchanged. Neuronal reorganization was greater in moderately ill patients, while delta activity increased in severe patients. Non-Cp copper was the only biological variable appearing to be associated with patient sensorimotor transmission. Conclusions. Our data strengthen the notion that non-Cp copper, not copper in general, affects neuronal activity in AD. Significance. High plasticity in the disease early stages in regions controlling more commonly used body parts strengthens the notion that physical and cognitive activities are protective factors against progression of dementia. PMID:24416615

In Vitro Phytotoxicity and Antioxidant Activity of Selected Flavonoids

PubMed Central

De Martino, Laura; Mencherini, Teresa; Mancini, Emilia; Aquino, Rita Patrizia; De Almeida, Luiz Fernando Rolim; De Feo, Vincenzo

2012-01-01

The knowledge of flavonoids involved in plant-plant interactions and their mechanisms of action are poor and, moreover, the structural characteristics required for these biological activities are scarcely known. The objective of this work was to study the possible in vitro phytotoxic effects of 27 flavonoids on the germination and early radical growth of Raphanus sativus L. and Lepidium sativum L., with the aim to evaluate the possible structure/activity relationship. Moreover, the antioxidant activity of the same compounds was also evaluated. Generally, in response to various tested flavonoids, germination was only slightly affected, whereas significant differences were observed in the activity of the various tested flavonoids against radical elongation. DPPH test confirms the antioxidant activity of luteolin, quercetin, catechol, morin, and catechin. The biological activity recorded is discussed in relation to the structure of compounds and their capability to interact with cell structures and physiology. No correlation was found between phytotoxic and antioxidant activities. PMID:22754304

Distributed and opposing effects of incidental learning in the human brain.

PubMed

Hall, Michelle G; Naughtin, Claire K; Mattingley, Jason B; Dux, Paul E

2018-06-01

Incidental learning affords a behavioural advantage when sensory information matches regularities that have previously been encountered. Previous studies have taken a focused approach by probing the involvement of specific candidate brain regions underlying incidentally acquired memory representations, as well as expectation effects on early sensory representations. Here, we investigated the broader extent of the brain's sensitivity to violations and fulfilments of expectations, using an incidental learning paradigm in which the contingencies between target locations and target identities were manipulated without participants' overt knowledge. Multivariate analysis of functional magnetic resonance imaging data was applied to compare the consistency of neural activity for visual events that the contingency manipulation rendered likely versus unlikely. We observed widespread sensitivity to expectations across frontal, temporal, occipital, and sub-cortical areas. These activation clusters showed distinct response profiles, such that some regions displayed more reliable activation patterns under fulfilled expectations, whereas others showed more reliable patterns when expectations were violated. These findings reveal that expectations affect multiple stages of information processing during visual decision making, rather than early sensory processing stages alone. Copyright © 2018 Elsevier Inc. All rights reserved.

Implicit Race Bias Decreases the Similarity of Neural Representations of Black and White Faces

PubMed Central

Brosch, Tobias; Bar-David, Eyal; Phelps, Elizabeth A.

2013-01-01

Implicit race bias has been shown to affect decisions and behaviors. It may also change perceptual experience by increasing perceived differences between social groups. We investigated how this phenomenon may be expressed at the neural level by testing whether the distributed blood-oxygenation-level-dependent (BOLD) patterns representing Black and White faces are more dissimilar in participants with higher implicit race bias. We used multivoxel pattern analysis to predict the race of faces participants were viewing. We successfully predicted the race of the faces on the basis of BOLD activation patterns in early occipital visual cortex, occipital face area, and fusiform face area (FFA). Whereas BOLD activation patterns in early visual regions, likely reflecting different perceptual features, allowed successful prediction for all participants, successful prediction on the basis of BOLD activation patterns in FFA, a high-level face-processing region, was restricted to participants with high pro-White bias. These findings suggest that stronger implicit pro-White bias decreases the similarity of neural representations of Black and White faces. PMID:23300228

Exploiting mAb structure characteristics for a directed QbD implementation in early process development.

PubMed

Karlberg, Micael; von Stosch, Moritz; Glassey, Jarka

2018-03-07

In today's biopharmaceutical industries, the lead time to develop and produce a new monoclonal antibody takes years before it can be launched commercially. The reasons lie in the complexity of the monoclonal antibodies and the need for high product quality to ensure clinical safety which has a significant impact on the process development time. Frameworks such as quality by design are becoming widely used by the pharmaceutical industries as they introduce a systematic approach for building quality into the product. However, full implementation of quality by design has still not been achieved due to attrition mainly from limited risk assessment of product properties as well as the large number of process factors affecting product quality that needs to be investigated during the process development. This has introduced a need for better methods and tools that can be used for early risk assessment and predictions of critical product properties and process factors to enhance process development and reduce costs. In this review, we investigate how the quantitative structure-activity relationships framework can be applied to an existing process development framework such as quality by design in order to increase product understanding based on the protein structure of monoclonal antibodies. Compared to quality by design, where the effect of process parameters on the drug product are explored, quantitative structure-activity relationships gives a reversed perspective which investigates how the protein structure can affect the performance in different unit operations. This provides valuable information that can be used during the early process development of new drug products where limited process understanding is available. Thus, quantitative structure-activity relationships methodology is explored and explained in detail and we investigate the means of directly linking the structural properties of monoclonal antibodies to process data. The resulting information as a decision tool can help to enhance the risk assessment to better aid process development and thereby overcome some of the limitations and challenges present in QbD implementation today.

Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice.

PubMed

Kido, Tatsuo; Sun, Zhaoyu; Lau, Yun-Fai Chris

2017-06-23

Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRY ON ) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age. Pathological and molecular analyses indicate that hSRY ON pups lack innate suckling activities, and develop fatty liver disease, arrested alveologenesis in the lung, impaired neurogenesis in the brain and occasional myocardial fibrosis and minimized thymus development. Transcriptome analysis shows that, in addition to those unique to the respective organs, various cell growth and survival pathways and functions are differentially affected in the transgenic mice. These observations suggest that ectopic activation of a Y-located SRY gene could exert male-specific effects in development and physiology of multiple organs, thereby contributing to sexual dimorphisms in normal biological functions and disease processes in affected individuals.

Probiotic Lactobacillus Strains Stimulate the Inflammatory Response and Activate Human Macrophages.

PubMed

Rocha-Ramírez, L M; Pérez-Solano, R A; Castañón-Alonso, S L; Moreno Guerrero, S S; Ramírez Pacheco, A; García Garibay, M; Eslava, C

2017-01-01

Lactobacilli have been shown to promote health functions. In this study, we analyzed the mechanism by which four different strains of probiotics affected innate immunity, such as regulation of ROS, cytokines, phagocytosis, bactericidal activity, signaling by NF- κ B pp65, and TLR2 activation. The production of ROS was dependent on the concentration and species of Lactobacillus . The results obtained from the tested strains ( Lactobacillus rhamnosus GG, L. rhamnosus KLSD, L. helveticus IMAU70129, and L. casei IMAU60214) showed that strains induced early proinflammatory cytokines such as IL-8,TNF- α , IL-12p70, and IL-6. However, IL-1 β expression was induced only by L. helveticus and L. casei strains (after 24 h stimulation). Phagocytosis and bactericidal activity of macrophages against various pathogens, such as S. aureus , S. typhimurium , and E. coli , were increased by pretreatment with Lactobacillus . The nuclear translocation NF- κ B pp65 and TLR2-dependent signaling were also increased by treatment with the probiotics. Taken together, the experiments demonstrate that probiotic strains of Lactobacillus exert early immunostimulatory effects that may be directly linked to the initial inflammation of the response of human macrophages.

Association study of monoamine oxidase-A gene promoter polymorphism (MAOA-uVNTR) with self-reported anxiety and other psychopathological symptoms in a community sample of early adolescents.

PubMed

Voltas, Núria; Aparicio, Estefania; Arija, Victoria; Canals, Josefa

2015-04-01

The polymorphism upstream of the gene for monoamine oxidase A (MAOA-uVNTR) is reported to be an important enzyme involved in human physiology and behavior. With a sample of 228 early-adolescents from a community sample (143 girls) and adjusting for environmental variables, we examined the influence of MAOA-uVNTR alleles on the scores obtained in the Screen for Childhood Anxiety and Related Emotional Disorders and in the Child Symptom Inventory-4. Our results showed that girls with the high-activity MAOA allele had higher scores for generalized and total anxiety than their low-activity peers, whereas boys with the low-activity allele had higher social phobia scores than boys with the high-activity allele. Results for conduct disorder symptoms did not show a significant relationship between the MAOA alleles and the presence of these symptoms. Our findings support a possible association, depending on gender, between the MAOA-uVNTR polymorphism and psychopathological disorders such as anxiety, which affects high rates of children and adolescents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Probiotic Lactobacillus Strains Stimulate the Inflammatory Response and Activate Human Macrophages

PubMed Central

Moreno Guerrero, S. S.; Ramírez Pacheco, A.; García Garibay, M.; Eslava, C.

2017-01-01

Lactobacilli have been shown to promote health functions. In this study, we analyzed the mechanism by which four different strains of probiotics affected innate immunity, such as regulation of ROS, cytokines, phagocytosis, bactericidal activity, signaling by NF-κB pp65, and TLR2 activation. The production of ROS was dependent on the concentration and species of Lactobacillus. The results obtained from the tested strains (Lactobacillus rhamnosus GG, L. rhamnosus KLSD, L. helveticus IMAU70129, and L. casei IMAU60214) showed that strains induced early proinflammatory cytokines such as IL-8,TNF-α, IL-12p70, and IL-6. However, IL-1β expression was induced only by L. helveticus and L. casei strains (after 24 h stimulation). Phagocytosis and bactericidal activity of macrophages against various pathogens, such as S. aureus, S. typhimurium, and E. coli, were increased by pretreatment with Lactobacillus. The nuclear translocation NF-κB pp65 and TLR2-dependent signaling were also increased by treatment with the probiotics. Taken together, the experiments demonstrate that probiotic strains of Lactobacillus exert early immunostimulatory effects that may be directly linked to the initial inflammation of the response of human macrophages. PMID:28758133

Identification of functional domains of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication

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

Kim, Seong K., E-mail: skim1@lsuhsc.edu; Kim, Seongman; Dai Gan

2011-09-01

The equine herpesvirus 1 (EHV-1) negative regulatory IR2 protein (IR2P), an early 1,165-amino acid (aa) truncated form of the 1487-aa immediate-early protein (IEP), lacks the trans-activation domain essential for IEP activation functions but retains domains for binding DNA, TFIIB, and TBP and the nuclear localization signal. IR2P mutants of the N-terminal region which lack either DNA-binding activity or TFIIB-binding activity were unable to down-regulate EHV-1 promoters. In EHV-1-infected cells expressing full-length IR2P, transcription and protein expression of viral regulatory IE, early EICP0, IR4, and UL5, and late ETIF genes were dramatically inhibited. Viral DNA levels were reduced to 2.1% ofmore » control infected cells, but were vey weakly affected in cells that express the N-terminal 706 residues of IR2P. These results suggest that IR2P function requires the two N-terminal domains for binding DNA and TFIIB as well as the C-terminal residues 707 to 1116 containing the TBP-binding domain. - Highlights: > We examine the functional domains of IR2P that mediates negative regulation. > IR2P inhibits at the transcriptional level. > DNA-binding mutant or TFIIB-binding mutant fails to inhibit. > C-terminal aa 707 to 1116 are required for full inhibition. > Inhibition requires the DNA-binding domain, TFIIB-binding domain, and C-terminus.« less

Mild zinc deficiency in male and female rats: early postnatal alterations in renal nitric oxide system and morphology.

PubMed

Tomat, Analia Lorena; Veiras, Luciana Cecilia; Aguirre, Sofía; Fasoli, Héctor; Elesgaray, Rosana; Caniffi, Carolina; Costa, María Ángeles; Arranz, Cristina Teresa

2013-03-01

Fetal and postnatal zinc deficiencies induce an increase in arterial blood pressure and impair renal function in male adult rats. We therefore hypothesized that these renal alterations are present in early stages of life and that there are sexual differences in the adaptations to this nutritional injury. The aim was to study the effects of moderate zinc deficiency during fetal life and lactation on renal morphology, oxidative stress, apoptosis, and the nitric oxide system in male and female rats at 21 d of life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy to weaning. Glomerulus number, morphology, oxidative stress, apoptotic cells, nitric oxide synthase activity, and protein expression were evaluated in the kidneys of offspring at 21 d. Zinc deficiency decreased the nephron number, induced glomerular hypertrophy, increased oxidative damage, and decreased nitric oxide synthase activity in the male and female rat kidneys. Nitric oxide synthase activity was not affected by inhibitors of the neuronal or inducible isoforms, so nitric oxide was mainly generated by the endothelial isoenzyme. Gender differences were observed in glomerular areas and antioxidant enzyme activities. Zinc deficiency during fetal life and lactation induces an early decrease in renal functional units, associated with a decrease in nitric oxide activity and an increase in oxidative stress, which would contribute to increased arterial blood pressure and renal dysfunction in adulthood. The sexual differences observed in this model may explain the dissimilar development of hypertension and renal diseases in adult life. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of cognitive stimulation at home in low-income preschoolers' nutrition, physical activity and body mass index.

PubMed

den Bosch, Saskia Op; Duch, Helena

2017-08-01

Early childhood obesity disproportionately affects children of low socioeconomic status. Children attending Head Start are reported to have an obesity rate of 17.9%.This longitudinal study aimed to understand the relationship between cognitive stimulation at home and intake of junk food, physical activity and body size, for a nationally representative sample of 3- and 4-year old children entering Head Start. We used The Family and Child Experiences Survey 2006. Cognitive stimulation at home was measured for 1905 children at preschool entry using items from the Home Observation Measurement of the Environment Short Form. Junk food consumption and physical activity were obtained from parent interviews at kindergarten entry. BMI z scores were based on CDC national standards. We analyzed the association between early cognitive stimulation and junk food consumption, physical activity and BMI, using multinomial and binary logistic regression on a weighted sample. Children who received moderate levels of cognitive stimulation at home had a 1.5 increase in the likelihood of consuming low amounts of junk food compared to children from low cognitive stimulation environments. Children who received moderate and high levels of cognitive stimulation were two and three times, respectively, more likely to be physically active than those in low cognitive stimulation homes. No direct relationship was identified between cognitive stimulation and BMI. Prevention and treatment efforts to address early childhood obesity may consider strategies that support parents in providing cognitively stimulating home environments. Existing evidence-based programs can guide intervention in pediatric primary care.

Menstruation disturbances: prevalence, characteristics, and effects on the activities of daily living among adolescent girls from Brazil.

PubMed

Pitangui, Ana Carolina R; Gomes, Mayra Ruana de A; Lima, Alaine Souza; Schwingel, Paulo Adriano; Albuquerque, Ana Paula dos S; de Araújo, Rodrigo Cappato

2013-06-01

To determine the prevalence, characteristics and effects on the activities of daily living of menstruation disturbances among adolescent girls. Descriptive, cross-sectional study. A public school in the city of Petrolina, Brazil. 218 female adolescents of ages between 12 and 17 years. We used a structured questionnaire addressing the socio-demographic and menstrual characteristics of the adolescents. The intensity of menstrual pain and its effect on the activities of daily living were measured using an 11-point numeric rating scale. The mean age of adolescent girls was 13.7 ± 1.5 years. The menstrual cycles of 67% were regular, while 33% were irregular. Dysmenorrhea had a prevalence of 73%, and school absenteeism was observed among 31% of the adolescents. In addition, 66% of the participants considered that dysmenorrhea affected their activities of daily living. Associations were found between the intensity of pain and the variables: school absenteeism; affected activities of daily living; need to use medications; and between affected activities of daily living and school absenteeism (P < .05). Among the menstrual disturbances observed dysmenorrhea stood out due to its high prevalence among adolescents with a negative effect on adolescents' activities of daily living. Early diagnosis and knowledge about menstrual disturbances are essential because in addition to reiterating the importance of implementing health education actions, they also help to choose appropriate treatments, thus minimizing the negative effects of these disturbances on the lives of adolescents. Copyright © 2013 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species.

PubMed

De Milito, Angelo; Iessi, Elisabetta; Logozzi, Mariantonia; Lozupone, Francesco; Spada, Massimo; Marino, Maria Lucia; Federici, Cristina; Perdicchio, Maurizio; Matarrese, Paola; Lugini, Luana; Nilsson, Anna; Fais, Stefano

2007-06-01

Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose- and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI.

Early Iron Deficiency Has Brain and Behavior Effects Consistent with Dopaminergic Dysfunction123

PubMed Central

Lozoff, Betsy

2011-01-01

To honor the late John Beard’s many contributions regarding iron and dopamine biology, this review focuses on recent human studies that test specific hypotheses about effects of early iron deficiency on dopamine system functioning. Short- and long-term alterations associated with iron deficiency in infancy can be related to major dopamine pathways (mesocortical, mesolimbic, nigrostriatal, tuberohypophyseal). Children and young adults who had iron deficiency anemia in infancy show poorer inhibitory control and executive functioning as assessed by neurocognitive tasks where pharmacologic and neuroimaging studies implicate frontal-striatal circuits and the mesocortical dopamine pathway. Alterations in the mesolimbic pathway, where dopamine plays a major role in behavioral activation and inhibition, positive affect, and inherent reward, may help explain altered social-emotional behavior in iron-deficient infants, specifically wariness and hesitance, lack of positive affect, diminished social engagement, etc. Poorer motor sequencing and bimanual coordination and lower spontaneous eye blink rate in iron-deficient anemic infants are consistent with impaired function in the nigrostriatal pathway. Short- and long-term changes in serum prolactin point to dopamine dysfunction in the tuberohypophyseal pathway. These hypothesis-driven findings support the adverse effects of early iron deficiency on dopamine biology. Iron deficiency also has other effects, specifically on other neurotransmitters, myelination, dendritogenesis, neurometabolism in hippocampus and striatum, gene and protein profiles, and associated behaviors. The persistence of poorer cognitive, motor, affective, and sensory system functioning highlights the need to prevent iron deficiency in infancy and to find interventions that lessen the long-term effects of this widespread nutrient disorder. PMID:21346104

Early Negative Affect Predicts Anxiety, not Autism, in Preschool Boys with Fragile X Syndrome

PubMed Central

Tonnsen, Bridgette L.; Malone, Patrick S.; Hatton, Deborah D.

2012-01-01

Children with fragile X syndrome (FXS) face high risk for anxiety disorders, yet no studies have explored FXS as a high-risk sample for investigating early manifestations of anxiety outcomes. Negative affect is one of the most salient predictors of problem behaviors and has been associated with both anxiety and autistic outcomes in clinical and non-clinical pediatric samples. In light of the high comorbidity between autism and anxiety within FXS, the present study investigates the relationship between longitudinal trajectories of negative affect (between 8 and 71 months) and severity of anxiety and autistic outcomes in young males with FXS (n= 25). Multilevel models indicated associations between elevated anxiety and higher fear and sadness, lower soothability, and steeper longitudinal increases in approach. Autistic outcomes were unrelated to negative affect. These findings suggest early negative affect differentially predicts anxiety, not autistic symptoms, within FXS. Future research is warranted to determine the specificity of the relationship between negative affect and anxiety, as well as to explore potential moderators. Characterizing the relationship between early negative affect and anxiety within FXS may inform etiology and treatment considerations specific to children with FXS, as well as lend insight into precursors of anxiety disorders in other clinical groups and community samples. PMID:23011214

Adenovirus EIIA early promoter: transcriptional control elements and induction by the viral pre-early EIA gene, which appears to be sequence independent.

PubMed Central

Murthy, S C; Bhat, G P; Thimmappaya, B

1985-01-01

A molecular dissection of the adenovirus EIIA early (E) promoter was undertaken to study the sequence elements required for transcription and to examine the nucleotide sequences, if any, specific for its trans-activation by the viral pre-early EIA gene product. A chimeric gene in which the EIIA-E promoter region fused to the coding sequences of the bacterial chloramphenicol acetyltransferase (CAT) gene was used in transient assays to identify the transcriptional control regions. Deletion mapping studies revealed that the upstream DNA sequences up to -86 were sufficient for the optimal basal level transcription in HeLa cells and also for the EIA-induced transcription. A series of linker-scanning (LS) mutants were constructed to precisely identify the nucleotide sequences that control transcription. Analysis of these LS mutants allowed us to identify two regions of the promoter that are critical for the EIIA-E transcription. These regions are located between -29 and -21 (region I) and between -82 and -66 (region II). Mutations in region I affected initiation and appeared functionally similar to the "TATA" sequence of the commonly studied promoters. To examine whether or not the EIIA-E promoter contained DNA sequences specific for the trans-activation by the EIA, the LS mutants were analyzed in a cotransfection assay containing a plasmid carrying the EIA gene. CAT activity of all of the LS mutants was induced by the EIA gene in this assay, suggesting that the induction of transcription of the EIIA-E promoter by the EIA gene is not sequence-specific. Images PMID:3857577

Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse Model

PubMed Central

Wei, Ran; Hui, Edward S.; Feldon, Joram; Meyer, Urs; Chung, Sookja; Chua, Siew E.; Sham, Pak C.; Wu, Ed X.; McAlonan, Grainne M.

2009-01-01

Objectives Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. Method We used an established mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. Results PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating. Conclusions Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life. PMID:19629183

Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

PubMed Central

Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

2016-01-01

Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

Implicit and explicit categorization of natural scenes.

PubMed

Codispoti, Maurizio; Ferrari, Vera; De Cesarei, Andrea; Cardinale, Rossella

2006-01-01

Event-related potential (ERP) studies have consistently found that emotionally arousing (pleasant and unpleasant) pictures elicit a larger late positive potential (LPP) than neutral pictures in a window from 400 to 800 ms after picture onset. In addition, an early ERP component has been reported to vary with emotional arousal in a window from about 150 to 300 ms with affective, compared to neutral stimuli, prompting significantly less positivity over occipito-temporal sites. Similar early and late ERP components have been found in explicit categorization tasks, suggesting that selective attention to target features results in similar cortical changes. Several studies have shown that the affective modulation of the LPP persisted even when the same pictures are repeated several times, when they are presented as distractors, or when participants are engaged in a competing task. These results indicate that categorization of affective stimuli is an obligatory process. On the other hand, perceptual factors (e.g., stimulus size) seem to affect the early ERP component but not the affective modulation of the LPP. Although early and late ERP components vary with stimulus relevance, given that they are differentially affected by stimulus and task manipulations, they appear to index different facets of picture processing.

Early signs of geodynamic activity before the 2011-2012 El Hierro eruption

NASA Astrophysics Data System (ADS)

López, Carmen; García-Cañada, Laura; Martí, Joan; Domínguez Cerdeña, Itahiza

2017-02-01

The potential relation between mantle plume dynamics, regional tectonics and eruptive activity in the Canary Islands has not been studied yet through the analysis of long-time series of geophysical observational data. The existence of highly reliable seismic and geodetic data has enabled us to study from 1996 to 2014 the geodynamic evolution of the North Atlantic Azores-Gibraltar region (including the NW African margin) and its relationship with recent volcanic activity in El Hierro (Canary Islands). We compiled a new and unified regional seismic catalog and used long time-series of digital 3D surface displacements recorded by permanent GPS stations in the region. A joint regional- and local-scale analysis based on these data enabled us to identify signs of anomalous tectonic activity from 2003 onwards, whose intensity increased in 2007 and finally accelerated three months before the onset of the volcanic eruption on El Hierro in October 2011. Activity included the occurrence of regional extension and an uplift process affecting the southern Iberian Peninsula, NW Africa, and the Canary Islands. We interpret these observations as early signs of the geodynamic activity, which led to El Hierro eruption and the subsequent episodes of magma intrusion. Results point to the significant contribution of the mantle plume dynamics (i.e. external forces) in this renewed volcanic activity in the Canary Islands and emphasize the role of mantle dynamics in controlling regional tectonics.

Early signs of geodynamic activity before the 2011-2012 El Hierro eruption

NASA Astrophysics Data System (ADS)

López, Carmen; García-Cañada, Laura; Martí, Joan; Domínguez Cerdeña, Itahiza

2017-04-01

The potential relation between mantle plume dynamics, regional tectonics and eruptive activity in the Canary Islands has not been studied yet through the analysis of long-time series of geophysical observational data. The existence of highly reliable seismic and GNSS data has enabled us to study from 1996 to 2014 the geodynamic evolution of the North Atlantic Azores-Gibraltar region and its relationship with recent volcanic activity in El Hierro (Canary Islands, Spain). We compiled a new and unified regional seismic catalog and used long time-series of surface displacements recorded by permanent GNSS stations in the region. A regional- and local-scale analysis based on these data enabled us to identify signs of anomalous tectonic activity from 2003 onwards, whose intensity increased in 2007 and finally accelerated three months before the onset of the volcanic eruption on El Hierro in October 2011. This activity includes a regional extension and an uplift process that affects the southern Iberian Peninsula, NW Africa, and the Canary Islands. We interpret these observations as early signs of the geodynamic activity, which led to El Hierro eruption and the subsequent episodes of magma intrusion. Results point to the significant contribution of the mantle plume dynamics (i.e. external forces) in this renewed volcanic activity in the Canary Islands and emphasize the role of mantle dynamics in controlling regional tectonics.

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

PubMed Central

van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.

2017-01-01

Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA-axis hyper-reactivity in adulthood, as also found in major depression. This hyper-activity is related to increased corticotrophin-releasing hormone signaling and impaired glucocorticoid receptor-mediated negative feedback. In contrast, initial evidence for HPA-axis hypo-reactivity is observed for early social deprivation, potentially reflecting the abnormal HPA-axis function as observed in post-traumatic stress disorder, and future studies should investigate its neural/neuroendocrine foundation in further detail. Interestingly, experiencing additional (chronic) stress in adulthood seems to normalize these alterations in HPA-axis function, supporting the match/mismatch theory. PMID:28469557

Selective breeding for infant rat separation-induced ultrasonic vocalizations: developmental precursors of passive and active coping styles.

PubMed

Brunelli, Susan A; Hofer, Myron A

2007-09-04

Human depression and anxiety disorders show inherited biases across generations, as do antisocial disorders characterized by aggression. Each condition is preceded in children by behavioral inhibition or aggressive behavior, respectively, and both are characterized by separation anxiety disorders. In affected families, adults and children exhibit different forms of altered autonomic nervous system regulation and hypothalamic-pituitary-adrenal activity in response to stress. Because it is difficult to determine mechanisms accounting for these associations, animal studies are useful for studying the fundamental relationships between biological and behavioral traits. Pharmacologic and behavioral studies suggest that infant rat ultrasonic vocalizations (USV) are a measure of an early anxiety-like state related to separation anxiety. However, it was not known whether or not early ultrasound emissions in infant rats are markers for genetic risk for anxiety states later in life. To address these questions, we selectively bred two lines of rats based on high and low rates of USV to isolation at postnatal (P) 10 days of age. To our knowledge, ours is the only laboratory that has ever selectively bred on the basis of an infantile trait related to anxiety. The High and Low USV lines show two distinct sets of patterns of behavior, physiology and neurochemistry from infancy through adulthood. As adults High line rats demonstrate "anxious"/"depressed" phenotypes in behavior and autonomic nervous system (ANS) regulation to standard laboratory tests. In Lows, on the other hand, behavior and autonomic regulation are consistent with an "aggressive" phenotype. The High and Low USV lines are the first genetic animal models implicating long-term associations of contrasting "coping styles" with early attachment responses. They thus present a potentially powerful model for examining gene-environment interactions in the development of life-long affective regulation.

Fabry disease: Review and experience during newborn screening.

PubMed

Hsu, Ting-Rong; Niu, Dau-Ming

2018-05-01

Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Heterozygous females can develop vital organ damage that in turn causes severe morbidity and mortality; these symptoms may be as severe as those in affected males. For the treatable disease, this review aims to raise awareness of early recognition and further management of FD based on newborn screening. As newborn screening for FD has been implemented worldwide, it allows the early detection of individuals with Fabry mutations. Based on screening studies, the prevalence of the later-onset type FD is much higher than that of classical type FD. Newborn screening studies have also revealed that patients with FD may develop insidious but ongoing irreversible organ damage. The timing of enzyme replacement therapy, which is able to stabilize the progression of disease, is important in order to prevent irreversible organ damage. Therapies that may become available in the future include pharmacological chaperones and substrate reduction therapy, both of which are still under investigation as ways of improving the health of individuals with FD. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute Stress and Perceptual Load Consume the Same Attentional Resources: A Behavioral-ERP Study

PubMed Central

Tiferet-Dweck, Chen; Hensel, Michael; Kirschbaum, Clemens; Tzelgov, Joseph; Friedman, Alon; Salti, Moti

2016-01-01

Stress and perceptual load affect selective attention in a paradoxical manner. They can facilitate selectivity or disrupt it. This EEG study was designed to examine the reciprocal relations between stress, load and attention. Two groups of subjects, one that performed the Trier Social Stress Test (TSST), and a control group, were asked to respond to a target letter under low and high perceptual load in the absence or presence of a distractor. In the control group, the distractor increased response times (RTs) for high and low load. In the TSST group, distractor increased RTs under low load only. ERPs showed that distractor’s presentation attenuated early visual P1 component and shortened its latency. In the TSST group, distractor reduced P1 component under high load but did not affect its latency. Source localization demonstrated reduced activation in V1 in response to distractors presence in the P1 time window for the TSST group compared to the control group. A behavioral replication revealed that in the TSST group distractors were less perceived under high load. Taken together, our results show that stress and perceptual load affect selectivity through the early stages of visual processing and might increase selectivity in a manner that would block conscious perception of irrelevant stimuli. PMID:27196027

The effects of microgravity on gametogenesis, fertilization, and early embryogenesis

NASA Astrophysics Data System (ADS)

Tan, X.

Gametogenesis fertilization and early embryogenesis are crucial periods for normal development afterwards In past three decades many experiments have been conducted in space and in simulated weightlessness induced by clinostats to elucidate the issue Different animal species including Drosophila wasp shrimp fish amphibian mouse rats etc have been used for the study Oogenesis and spermatogenesis are affected by microgravity in different ways Some researches found that microgravity condition perturbed the process of oogenesis in many species A significant increased frequency of chromosomal non-disjunction was found in Drosophila females resulting the loss of chromosomes during meiosis and inhibition of cell division Studies on wasp showed a decreased hatchability and accumulation of unhatched eggs when the insects were exposed to spaceflight at different stages of oogenesis For experiments conducted on vertebrate animal models the results are somehow different however Microgravity has no significant effect for fish Medaka etc amphibian South African clawed toad Xenopus laevis or mammals mouse Spermatogenesis on the other hand is more significantly affected by microgravity condition Some researches indicated sperm are sensitive to changes in gravitational force and this sensitivity affects the ability of sperm to fertilize eggs Sperm swim with higher velocity in microgravity which is coupled with altered protein phosphorylation level in sperm under microgravity condition Microgravity also induced activation of the

Early activation of quorum sensing in Pseudomonas aeruginosa reveals the architecture of a complex regulon.

PubMed

Schuster, Martin; Greenberg, E Peter

2007-08-22

Quorum-sensing regulation of gene expression in Pseudomonas aeruginosa is complex. Two interconnected acyl-homoserine lactone (acyl-HSL) signal-receptor pairs, 3-oxo-dodecanoyl-HSL-LasR and butanoyl-HSL-RhlR, regulate more than 300 genes. The induction of most of the genes is delayed during growth of P. aeruginosa in complex medium, cannot be advanced by addition of exogenous signal, and requires additional regulatory components. Many of these late genes can be induced by addition of signals early by using specific media conditions. While several factors super-regulate the quorum receptors, others may co-regulate target promoters or may affect expression posttranscriptionally. To better understand the contributions of super-regulation and co-regulation to quorum-sensing gene expression, and to better understand the general structure of the quorum sensing network, we ectopically expressed the two receptors (in the presence of their cognate signals) and another component that affects quorum sensing, the stationary phase sigma factor RpoS, early in growth. We determined the effect on target gene expression by microarray and real-time PCR analysis. Our results show that many target genes (e.g. lasB and hcnABC) are directly responsive to receptor protein levels. Most genes (e.g. lasA, lecA, and phnAB), however, are not significantly affected, although at least some of these genes are directly regulated by quorum sensing. The majority of promoters advanced by RhlR appeared to be regulated directly, which allowed us to build a RhlR consensus sequence. The direct responsiveness of many quorum sensing target genes to receptor protein levels early in growth confirms the role of super-regulation in quorum sensing gene expression. The observation that the induction of most target genes is not affected by signal or receptor protein levels indicates that either target promoters are co-regulated by other transcription factors, or that expression is controlled posttranscriptionally. This architecture permits the integration of multiple signaling pathways resulting in quorum responses that require a "quorum" but are otherwise highly adaptable and receptive to environmental conditions.

Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. I. Multimode effect on early membrane events.

PubMed

Rocher, Françoise; Dédaldéchamp, Fabienne; Saeedi, Saed; Fleurat-Lessard, Pierrette; Chollet, Jean-Francois; Roblin, Gabriel

2014-11-01

A study of the structure-activity relationship carried out on several benzoic acid-related phenolics indicates that this type of compounds hinders the osmocontractile reaction of pulvinar cells in the range of 0-100%. Tentatively, we tried to find a way that could explain this differential action. With this aim, the relationship between the inhibitory effect and important molecular physico-chemical parameters (namely lipophilicity and degree of dissociation) was drawn. In addition, the effect of a variety of these compounds was investigated on their capacity to modify the electrical transmembrane potential and induce modifications in proton fluxes. Finally, using plasma membrane vesicles purified from pulvinar tissues, we examined the effects of some selected compounds on the proton pump activity and catalytic activity of the plasma membrane H(+)-ATPase. Taken together, the results indicate that a modification of the molecular structure of phenolics may induce important variation in the activity of the compound on these early membrane events. Among the tested phenolics, salicylic acid (SA) and acetylsalicylic acid (ASA, aspirin) are of particuler note, as they showed atypical effects on the physiological processes studied. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice

PubMed Central

Valerio, Daria G.; Xu, Haiming; Eisold, Meghan E.; Woolthuis, Carolien M.; Pandita, Tej K.

2017-01-01

K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre–induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage–specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. PMID:27827827

EARLY BUD-BREAK 1 (EBB1) is a regulator of release from seasonal dormancy in poplar trees

PubMed Central

Yordanov, Yordan S.; Ma, Cathleen; Strauss, Steven H.; Busov, Victor B.

2014-01-01

Trees from temperate latitudes transition between growth and dormancy to survive dehydration and freezing stress during winter months. We used activation tagging to isolate a dominant mutation affecting release from dormancy and identified the corresponding gene EARLY BUD-BREAK 1 (EBB1). We demonstrate through positioning of the tag, expression analysis, and retransformation experiments that EBB1 encodes a putative APETALA2/Ethylene responsive factor transcription factor. Transgenic up-regulation of the gene caused early bud-flush, whereas down-regulation delayed bud-break. Native EBB1 expression was highest in actively growing apices, undetectable during the dormancy period, but rapidly increased before bud-break. The EBB1 transcript was localized in the L1/L2 layers of the shoot meristem and leaf primordia. EBB1-overexpressing transgenic plants displayed enlarged shoot meristems, open and poorly differentiated buds, and a higher rate of cell division in the apex. Transcriptome analyses of the EBB1 transgenics identified 971 differentially expressed genes whose expression correlated with the EBB1 expression changes in the transgenic plants. Promoter analysis among the differentially expressed genes for the presence of a canonical EBB1-binding site identified 65 putative target genes, indicative of a broad regulatory context of EBB1 function. Our results suggest that EBB1 has a major and integrative role in reactivation of meristem activity after winter dormancy. PMID:24951507

Adaptation in human visual cortex as a mechanism for rapid discrimination of aversive stimuli.

PubMed

Keil, Andreas; Stolarova, Margarita; Moratti, Stephan; Ray, William J

2007-06-01

The ability to react rapidly and efficiently to adverse stimuli is crucial for survival. Neuroscience and behavioral studies have converged to show that visual information associated with aversive content is processed quickly and accurately and is associated with rapid amplification of the neural responses. In particular, unpleasant visual information has repeatedly been shown to evoke increased cortical activity during early visual processing between 60 and 120 ms following the onset of a stimulus. However, the nature of these early responses is not well understood. Using neutral versus unpleasant colored pictures, the current report examines the time course of short-term changes in the human visual cortex when a subject is repeatedly exposed to simple grating stimuli in a classical conditioning paradigm. We analyzed changes in amplitude and synchrony of large-scale oscillatory activity across 2 days of testing, which included baseline measurements, 2 conditioning sessions, and a final extinction session. We found a gradual increase in amplitude and synchrony of very early cortical oscillations in the 20-35 Hz range across conditioning sessions, specifically for conditioned stimuli predicting aversive visual events. This increase for conditioned stimuli affected stimulus-locked cortical oscillations at a latency of around 60-90 ms and disappeared during extinction. Our findings suggest that reorganization of neural connectivity on the level of the visual cortex acts to optimize early perception of specific features indicative of emotional relevance.

Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

PubMed

Dib, Tatiana; Martínez-Pinto, Jonathan; Reyes-Parada, Miguel; Torres, Gonzalo E; Sotomayor-Zárate, Ramón

2018-07-02

Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50μLs.c.) or estradiol valerate (EV: 0.1mg/50μLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost-effectiveness of a one-year coaching program for healthy physical activity in early rheumatoid arthritis.

PubMed

Brodin, Nina; Lohela-Karlsson, Malin; Swärdh, Emma; Opava, Christina H

2015-01-01

To describe cost-effectiveness of the Physical Activity in Rheumatoid Arthritis (PARA) study intervention. Costs were collected and estimated retrospectively. Cost-effectiveness was calculated based on the intervention cost per patient with respect to change in health status (EuroQol global visual analog scale--EQ-VAS and EuroQol--EQ-5D) and activity limitation (Health assessment questionnaire - HAQ) using cost-effectiveness- and cost-minimization analyses. Total cost of the one-year intervention program was estimated to be €67 317 or €716 per participant. Estimated difference in total societal cost between the intervention (IG) and control (CG) was €580 per participant. Incremental cost-effectiveness ratio (ICER) for one point (1/100) of improvement in EQ-VAS was estimated to be €116. By offering the intervention to more affected participants in the IG compared to less affected participants, 15.5 extra points of improvement in EQ-VAS and 0.13 points of improvement on HAQ were gained at the same cost. "Ordinary physiotherapy" was most cost-effective with regard to EQ-5D. The intervention resulted in improved effect in health status for the IG with a cost of €116 per extra point in VAS. The intervention was cost-effective if targeted towards a subgroup of more affected patients when evaluating the effect using VAS and HAQ. The physical activity coaching intervention resulted in an improved effect on VAS for the intervention group, to a higher cost. In order to maximize cost-effectiveness, this type of physical activity coaching intervention should be targeted towards patients largely affected by their RA. The intervention is cost-effective from the patients' point of view, but not from that of the general population.

Transcriptomic profile of leg muscle during early growth in chicken

PubMed Central

Zhang, Genxi; Li, Tingting; Ling, Jiaojiao; Zhang, Xiangqian; Wang, Jinyu

2017-01-01

The early growth pattern, especially the age of peak growth, of broilers affects the time to market and slaughter weight, which in turn affect the profitability of the poultry industry. However, the underlying mechanisms regulating chicken growth and development have rarely been studied. This study aimed to identify candidate genes involved in chicken growth and investigated the potential regulatory mechanisms of early growth in chicken. RNA sequencing was applied to compare the transcriptomes of chicken muscle tissues at three developmental stages during early growth. In total, 978 differentially expressed genes (DEGs) (fold change ≥ 2; false discovery rate < 0.05) were detected by pairwise comparison. Functional analysis showed that the DEGs are mainly involved in the processes of cell growth, muscle development, and cellular activities (such as junction, migration, assembly, differentiation, and proliferation). Many of the DEGs are well known to be related to chicken growth, such as MYOD1, GH, IGF2BP2, IGFBP3, SMYD1, CEBPB, FGF2, and IGFBP5. KEGG pathway analysis identified that the DEGs were significantly enriched in five pathways (P < 0.1) related to growth and development: extracellular matrix–receptor interaction, focal adhesion, tight junction, insulin signaling pathway, and regulation of the actin cytoskeleton. A total of 42 DEGs assigned to these pathways are potential candidate genes inducing the difference in growth among the three developmental stages, such as MYH10, FGF2, FGF16, FN1, CFL2, MAPK9, IRS1, PHKA1, PHKB, and PHKG1. Thus, our study identified a series of genes and several pathways that may participate in the regulation of early growth in chicken. These results should serve as an important resource revealing the molecular basis of chicken growth and development. PMID:28291821

Early life conditions that impact song learning in male zebra finches also impact neural and behavioral responses to song in females.

PubMed

Sewall, Kendra B; Anderson, Rindy C; Soha, Jill A; Peters, Susan; Nowicki, Stephen

2018-04-20

Early life stressors can impair song in songbirds by negatively impacting brain development and subsequent learning. Even in species in which only males sing, early life stressors might also impact female behavior and its underlying neural mechanisms, but fewer studies have examined this possibility. We manipulated brood size in zebra finches to simultaneously examine the effects of developmental stress on male song learning and female behavioral and neural response to song. Although adult male HVC volume was unaffected, we found that males from larger broods imitated tutor song less accurately. In females, early condition did not affect the direction of song preference: all females preferred tutor song over unfamiliar song in an operant test. However, treatment did affect the magnitude of behavioral response to song: females from larger broods responded less during song preference trials. This difference in activity level did not reflect boldness per se, as a separate measure of this trait did not differ with brood size. Additionally, in females we found a treatment effect on expression of the immediate early gene ZENK in response to tutor song in brain regions involved in song perception (dNCM) and social motivation (LSc.vl, BSTm, TnA), but not in a region implicated in song memory (CMM). These results are consistent with the hypothesis that developmental stressors that impair song learning in male zebra finches also influence perceptual and/or motivational processes in females. However, our results suggest that the learning of tutor song by females is robust to disturbance by developmental stress. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

Basic abnormalities in visual processing affect face processing at an early age in autism spectrum disorder.

PubMed

Vlamings, Petra Hendrika Johanna Maria; Jonkman, Lisa Marthe; van Daalen, Emma; van der Gaag, Rutger Jan; Kemner, Chantal

2010-12-15

A detailed visual processing style has been noted in autism spectrum disorder (ASD); this contributes to problems in face processing and has been directly related to abnormal processing of spatial frequencies (SFs). Little is known about the early development of face processing in ASD and the relation with abnormal SF processing. We investigated whether young ASD children show abnormalities in low spatial frequency (LSF, global) and high spatial frequency (HSF, detailed) processing and explored whether these are crucially involved in the early development of face processing. Three- to 4-year-old children with ASD (n = 22) were compared with developmentally delayed children without ASD (n = 17). Spatial frequency processing was studied by recording visual evoked potentials from visual brain areas while children passively viewed gratings (HSF/LSF). In addition, children watched face stimuli with different expressions, filtered to include only HSF or LSF. Enhanced activity in visual brain areas was found in response to HSF versus LSF information in children with ASD, in contrast to control subjects. Furthermore, facial-expression processing was also primarily driven by detail in ASD. Enhanced visual processing of detailed (HSF) information is present early in ASD and occurs for neutral (gratings), as well as for socially relevant stimuli (facial expressions). These data indicate that there is a general abnormality in visual SF processing in early ASD and are in agreement with suggestions that a fast LSF subcortical face processing route might be affected in ASD. This could suggest that abnormal visual processing is causative in the development of social problems in ASD. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Quality of life in breast cancer sufferers.

PubMed

Shouman, Ahmed Essmat; Abou El Ezz, Nahla Fawzy; Gado, Nivine; Ibrahim Goda, Amal Mahmoud

2016-08-08

Purpose - The purpose of this paper is to measure health-related quality of life (QOL) among patients with early stage cancer breast under curative treatment at department of oncology and nuclear medicine at Ain Shams University Hospitals. Identify factors affecting QOL among these patients. Design/methodology/approach - A cross-sectional study measured QOL among early stage female breast cancer (BC) patients and determined the main factors affecting their QOL. Three interviewer administered questionnaires were used. Findings - The physical domain mostly affected in BC patients and the functional domain least. Socio-demographic factors that significantly affected BC patients QOL scores were patient age, education, having children and family income. Specific patient characteristics include caregiver presence - a factor that affected different QOL scores. Age at diagnosis, affection in the side of the predominant hand, post-operative chemotherapy and difficulty in obtaining the medication were the disease-related factors that affected QOL scores. Originality/value - The final model predicting QOL for early stage female BC patients included age, education and difficulty in obtaining the medication as determinants for total QOL score. Carer presence was the specific patient characteristic that affected different QOL scores.

Early Intensive Leg Training to Enhance Walking in Children With Perinatal Stroke: Protocol for a Randomized Controlled Trial.

PubMed

Hurd, Caitlin; Livingstone, Donna; Brunton, Kelly; Teves, Michelle; Zewdie, Ephrem; Smith, Allison; Ciechanski, Patrick; Gorassini, Monica A; Kirton, Adam; Watt, Man-Joe; Andersen, John; Yager, Jerome; Yang, Jaynie F

2017-08-01

Development of motor pathways is modulated by activity in these pathways, when they are maturing (ie, critical period). Perinatal stroke injures motor pathways, including the corticospinal tracts, reducing their activity and impairing motor function. Current intervention for the lower limb emphasizes passive approaches (stretching, braces, botulinum toxin injections). The study hypothesis was that intensive, early, child-initiated activity during the critical period will enhance connectivity of motor pathways to the legs and improve motor function. The study objective was to determine whether early intervention with intensive activity is better than standard care, intervention delivered during the proposed critical period is better than after, and the outcomes are different when the intervention is delivered by a physical therapist in an institution vs. a parent at home. A prospective, delay-group, single-blind, randomized controlled trial (RCT) and a parallel, cohort study of children living beyond commuting distance and receiving an intervention delivered by their parent. The RCT intervention was provided in university laboratories, and parent training was provided in the childs home. Children 8 months to 3 years old with MRI-confirmed perinatal ischemic stroke and early signs of hemiparesis. Intensive, play-based leg activity with weights for the affected leg and foot, 1 hour/day, 4 days/week for 12 weeks. The primary outcome was the Gross Motor Function Measure-66 score. Secondary outcomes were motion analysis of walking, full-day step counts, motor evoked potentials from transcranial magnetic stimulation, and patellar tendon reflexes. Inter-individual heterogeneity in the severity of the stroke and behavioral differences are substantial but measurable. Differences in intervention delivery and assessment scoring are minimized by standardization and training. The intervention, contrary to current practice, could change physical therapy interventions for children with perinatal stroke. © 2017 American Physical Therapy Association

Vaccine Therapy for HIV: A Historical Review of the Treatment of Infectious Diseases by Active Specific Immunization with Microbe-Derived Agents

DTIC Science & Technology

1993-01-01

with tuberculosis induced an inflammatory response in affected tissues, and advocated "tuberculin therapy". Sir Almoth Wright in the early 20th...inoculation of tuberculin into patients with tuberculosis Other research groups have recently tried similar induced an inflammatory response in...THERAPY FOR TUBERCULOSIS (1890-191t) smallpox prompted searches for vaccines against other diseases. In 1850 the quixotic French physician While Pasteur

Effects of water temperature on breeding phenology, growth, and metamorphosis of foothill yellow-legged frogs (Rana boylii): a case study of the regulated mainstem and unregulated tributaries of California's Trinity River

Treesearch

Clara Wheeler; James Bettaso; Donald Ashton; Hartwell Welsh

2014-01-01

Many riverine organisms are well adapted to seasonally dynamic environments, but extreme changes in flow and thermal regimes can threaten sustainability of their populations in regulated rivers. Altered thermal regimes may limit recruitment to populations by shifting the timing of breeding activities and affecting the growth and development of early life stages. Stream...

Psychological evaluation of treated females with virilizing congenital adrenal hyperplasia.

PubMed

Hurtig, A L; Radhakrishnan, J; Reyes, H M; Rosenthal, I M

1983-12-01

The psychological development of females with congenital adrenal hyperplasia (CAH) has been previously studied by Money, et al, who found that psychological development of sex identity was consistent with sex assignment despite virilizing adrenal hormones and abnormal external genitalia requiring surgical correction. In this study, using a variety of psychological tests, we assessed the sex-dimorphic behavior, body image, cognitive functioning, and sex-role identity of nine patients ranging in age from 13 to 21, all treated with glucocorticoids and surgical correction. Four of the nine showed moderate virilization despite treatment. Psychological measures included the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Bem Sex-Role Inventory, the Draw-A-Person (DAP) and an interview with patient and family. Results indicate that patients fall within the normal expectable range for this developmental period in visual-spatial and verbal cognitive functioning, in sex-role identity, and in social interpersonal early behaviors. In two areas of functioning these patients demonstrated some variance from the norms, specifically in sexual identity and early activity levels. This suggests that sexual identity and physical activity are most prone to hormonal and psychological impact but that cognition and sex-role identity are not affected. Future studies of this sample will look at personality dimensions such as ego functioning, defense and affect to consider the impact of body image concerns and conflicts.

SEASON OF DELTAMETHRIN APPLICATION AFFECTS FLEA AND PLAGUE CONTROL IN WHITE-TAILED PRAIRIE DOG (CYNOMYS LEUCURUS) COLONIES, COLORADO, USA.

PubMed

Tripp, Daniel W; Streich, Sean P; Sack, Danielle A; Martin, Daniel J; Griffin, Karen A; Miller, Michael W

2016-07-01

In 2008 and 2009, we evaluated the duration of prophylactic deltamethrin treatments in white-tailed prairie dog ( Cynomys leucurus ) colonies and compared effects of autumn or spring dust application in suppressing flea numbers and plague. Plague occurred before and during our experiment. Overall, flea abundance tended to increase from May or June to September, but it was affected by deltamethrin treatment and plague dynamics. Success in trapping prairie dogs (animals caught/trap days) declined between June and September at all study sites. However, by September trap success on dusted sites (19%; 95% confidence interval [CI] 16-22%) was about 15-fold greater than on undusted control sites (1%; CI 0.3-4%; P≤0.0001). Applying deltamethrin dust as early as 12 mo prior seemed to afford some protection to prairie dogs. Our data showed that dusting even a portion of a prairie dog colony can prolong its persistence despite epizootic plague. Autumn dusting may offer advantages over spring in suppressing overwinter or early-spring flea activity, but timing should be adjusted to precede the annual decline in aboveground activity for hibernating prairie dog species. Large colony complexes or collections of occupied but fragmented habitat may benefit from dusting some sites in spring and others in autumn to maximize flea suppression in a portion of the complex or habitat year-round.

Lessons learned during active epidemiological surveillance of Ebola and Marburg viral hemorrhagic fever epidemics in Africa.

PubMed

Allaranga, Yokouide; Kone, Mamadou Lamine; Formenty, Pierre; Libama, Francois; Boumandouki, Paul; Woodfill, Celia J I; Sow, Idrissa; Duale, Sambe; Alemu, Wondimagegnehu; Yada, Adamou

2010-03-01

To review epidemiological surveillance approaches used during Ebola and Marburg hemorrhagic fever epidemics in Africa in the past fifteen years. Overall, 26 hemorrhagic epidemic outbreaks have been registered in 12 countries; 18 caused by the Ebola virus and eight by the Marburg virus. About 2551 cases have been reported, among which 268 were health workers (9,3%). Based on articles and epidemic management reports, this review analyses surveillance approaches, route of introduction of the virus into the population (urban and rural), the collaboration between the human health sector and the wildlife sector and factors that have affected epidemic management. Several factors affecting the epidemiological surveillance during Ebola and Marburg viruses hemorrhagic epidemics have been observed. During epidemics in rural settings, outbreak investigations have shown multiple introductions of the virus into the human population through wildlife. In contrast, during epidemics in urban settings a single introduction of the virus in the community was responsible for the epidemic. Active surveillance is key to containing outbreaks of Ebola and Marburg viruses Collaboration with those in charge of the conservation of wildlife is essential for the early detection of viral hemorrhagic fever epidemics. Hemorrhagic fever epidemics caused by Ebola and Marburg viruses are occurring more and more frequently in Sub-Saharan Africa and only an adapted epidemiological surveillance system will allow for early detection and effective response.

Active Interpersonal Touch Gives Rise to the Social Softness Illusion

PubMed Central

Gentsch, Antje; Panagiotopoulou, Elena; Fotopoulou, Aikaterini

2015-01-01

Summary Social touch plays a powerful role in human life, with important physical and mental health benefits in development and adulthood. Touch is central in building the foundations of social interaction, attachment, and cognition [1–5], and early, social touch has unique, beneficial neurophysiological and epigenetic effects [6–9]. The recent discovery of a separate neurophysiological system for affectively laden touch in humans has further kindled scientific interest in the area [10, 11]. Remarkably, however, little is known about what motivates and sustains the human tendency to touch others in a pro-social manner. Given the importance of social touch, we hypothesized that active stroking elicits more sensory pleasure when touching others’ skin than when touching one’s own skin. In a set of six experiments (total N = 133) we found that healthy participants, mostly tested in pairs to account for any objective differences in skin softness, consistently judged another’s skin as feeling softer and smoother than their own skin. We further found that this softness illusion appeared selectively when the touch activated a neurophysiological system for affective touch in the receiver. We conclude that this sensory illusion underlies a novel, bodily mechanism of socio-affective bonding and enhances our motivation to touch others. PMID:26365257

Time course of implicit processing and explicit processing of emotional faces and emotional words.

PubMed

Frühholz, Sascha; Jellinghaus, Anne; Herrmann, Manfred

2011-05-01

Facial expressions are important emotional stimuli during social interactions. Symbolic emotional cues, such as affective words, also convey information regarding emotions that is relevant for social communication. Various studies have demonstrated fast decoding of emotions from words, as was shown for faces, whereas others report a rather delayed decoding of information about emotions from words. Here, we introduced an implicit (color naming) and explicit task (emotion judgment) with facial expressions and words, both containing information about emotions, to directly compare the time course of emotion processing using event-related potentials (ERP). The data show that only negative faces affected task performance, resulting in increased error rates compared to neutral faces. Presentation of emotional faces resulted in a modulation of the N170, the EPN and the LPP components and these modulations were found during both the explicit and implicit tasks. Emotional words only affected the EPN during the explicit task, but a task-independent effect on the LPP was revealed. Finally, emotional faces modulated source activity in the extrastriate cortex underlying the generation of the N170, EPN and LPP components. Emotional words led to a modulation of source activity corresponding to the EPN and LPP, but they also affected the N170 source on the right hemisphere. These data show that facial expressions affect earlier stages of emotion processing compared to emotional words, but the emotional value of words may have been detected at early stages of emotional processing in the visual cortex, as was indicated by the extrastriate source activity. Copyright © 2011 Elsevier B.V. All rights reserved.

Antioxidant response of ridgetail white prawn Exopalaemon carinicauda to harmful dinoflagellate Prorocentrum minimum exposure and its histological change

NASA Astrophysics Data System (ADS)

Mu, Cuimin; Ren, Xianyun; Ge, Qianqian; Wang, Jiajia; Li, Jian

2017-04-01

The dinoflagellate Prorocentrum minimum, one of the most widespread red tide causing species, affects marine aquaculture and ecosystems worldwide. In this study, ridgetail white prawn Exopalaemon carinicauda were exposed to P. minimum cells (5 × 104 cells mL-1) to investigate its harmful effects on the shrimp. Antioxidant activities and histological changes were used as indicators of health status of the shrimp. In 72 hours, the mortality of E. carinicauda was not affected, but its antioxidant response and histology were statistically different from those of control. Elevated superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities and depressed catalase (CAT) activity were observed in gill; while increased SOD, glutathione S-transferase (GST), CAT activities and modulated GPX activity were observed in hepatopancreas. Thus, antioxidant activities in gill and hepatopancreas seem to respond differentially to harmful alga exposure. Increased malondialdehyde (MDA) content in early a few hours indicates the damage of the antioxidant defense system. Although MDA content recovered to a low level thereafter, a series of histological abnormalities including accumulation or infiltration of hemocytes, tissue lesions and necrosis were discovered in gill and hepatopancreas. Exposure to P. minimum induced sublethal effects on E. carinicauda, including temporary oxidative damage and histological injury.

Cosmological lepton asymmetry, primordial nucleosynthesis and sterile neutrinos

NASA Astrophysics Data System (ADS)

Abazajian, Kevork; Bell, Nicole F.; Fuller, George M.; Wong, Yvonne Y. Y.

2005-09-01

We study post weak decoupling coherent active-sterile and active-active matter-enhanced neutrino flavor transformation in the early Universe. We show that flavor conversion efficiency at Mikheyev-Smirnov-Wolfenstein resonances is likely to be high (adiabatic evolution) for relevant neutrino parameters and energies. However, we point out that these resonances cannot sweep smoothly and continuously with the expansion of the Universe. We show how neutrino flavor conversion in this way can leave both the active and sterile neutrinos with nonthermal energy spectra, and how, in turn, these distorted energy spectra can affect the neutron-to-proton ratio, primordial nucleosynthesis, and cosmological mass/closure constraints on sterile neutrinos. We demonstrate that the existence of a light sterile neutrino which mixes with active neutrinos can change fundamentally the relationship between the cosmological lepton numbers and the primordial nucleosynthesis He4 yield.

Early life stress affects mortality rate more than social behavior, gene expression or oxidative damage in honey bee workers.

PubMed

Rueppell, Olav; Yousefi, Babak; Collazo, Juan; Smith, Daniel

2017-04-01

Early life stressors can affect aging and life expectancy in positive or negative ways. Individuals can adjust their behavior and molecular physiology based on early life experiences but relatively few studies have connected such mechanisms to demographic patterns in social organisms. Sociality buffers individuals from environmental influences and it is unclear how much early life stress affects later life history. Workers of the honey bee (Apis mellifera L.) were exposed to two stressors, Varroa parasitism and Paraquat exposure, early in life. Consequences were measured at the molecular, behavioral, and demographic level. While treatments did not significantly affect levels of oxidative damage, expression of select genes, and titers of the common deformed wing virus, most of these measures were affected by age. Some of the age effects, such as declining levels of deformed wing virus and oxidative damage, were opposite to our predictions but may be explained by demographic selection. Further analyses suggested some influences of worker behavior on mortality and indicated weak treatment effects on behavior. The latter effects were inconsistent among the two experiments. However, mortality rate was consistently reduced by Varroa mite stress during development. Thus, mortality was more responsive to early life stress than our other response variables. The lack of treatment effects on these measures may be due to the social organization of honey bees that buffers the individual from the impact of stressful developmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Life Stress Affects Mortality Rate More than Social Behavior, Gene Expression or Oxidative Damage in Honey Bee Workers

PubMed Central

Rueppell, Olav; Yousefi, Babak; Collazo, Juan; Smith, Daniel

2017-01-01

Early life stressors can affect aging and life expectancy in positive or negative ways. Individuals can adjust their behavior and molecular physiology based on early life experiences but relatively few studies have connected such mechanisms to demographic patterns in social organisms. Sociality buffers individuals from environmental influences and it is unclear how much early life stress affects later life history. Workers of the honey bee (Apis mellifera L.) were exposed to two stressors, Varroa parasitism and paraquat exposure, early in life. Consequences were measured at the molecular, behavioral, and demographic level. While treatments did not significantly affect levels of oxidative damage, expression of select genes, and titers of the common deformed wing virus, most of these measures were affected by age. Some of the age effects, such as declining levels of deformed wing virus and oxidative damage, were opposite to our predictions but may be explained by demographic selection. Further analyses suggested some influences of worker behavior on mortality and indicated weak treatment effects on behavior. The latter effects were inconsistent among the two experiments. However, mortality rate was consistently reduced by Varroa mite stress during development. Thus, mortality was more responsive to early life stress than our other response variables. The lack of treatment effects on these measures may be due to the social organization of honey bees that buffers the individual from the impact of stressful developmental conditions. PMID:28122251

Ureide metabolism during seedling development in French bean (Phaseolus vulgaris).

PubMed

Quiles, Francisco Antonio; Raso, María José; Pineda, Manuel; Piedras, Pedro

2009-01-01

French bean (Phaseolus vulgaris) is a legume that transports most of the atmospheric nitrogen fixed in its nodules to the aerial parts of the plant as ureides. Changes in ureide content and in enzymatic activities involved in their metabolism were identified in the cotyledons and embryonic axes during germination and early seedling development. Accumulation of ureides (ca. 1300 nmol per pair of cotyledons) was observed in the cotyledons of dry seeds. Throughout germination, the total amount of ureides slightly decreased to about 1200 nmol, but increased both in cotyledons and in embryonic axes after radicle emergence. In the axes, the ureides were almost equally distributed in roots, hypocotyls and epicotyls. The pattern of ureide distribution was not affected by the presence of nitrate or sucrose in the media up to 6 days after imbibition. Ureides are synthesized from purines because allopurinol (a xanthine dehydrogenase inhibitor) blocks the increase of ureides. Allantoin and allantoate-degrading activities were detected in French bean dried seeds, whereas no ureidoglycolate-degrading activity was detected. During germination, the levels of the three activities remain unchanged in cotyledons. After radicle emergence, the levels of activities in cotyledons changed. Allantoin-degrading activity increased, allantoate-degrading activity decreased and ureidoglycolate-degrading activity remained undetectable in cotyledons. In developing embryonic axes, the three activities were detected throughout germination and early seedling development. The embryonic axes are able to synthesize ureides, because those compounds accumulated in axes without cotyledons.

Three-dimensional large-eddy simulations of the early phase of contrail-to-cirrus transition: effects of atmospheric turbulence and radiative transfer

DOE PAGES

Paoli, Roberto; Thouron, Odile; Cariolle, Daniel; ...

2017-12-08

Here, this article presents the results from numerical experiments of the early phase of contrail-cirrus formation using a limited set of fully three-dimensional, high-resolution large-eddy-simulations. The focus is laid on the interplay between atmospheric turbulence and the radiative transfer (and to a limited extent the ambient ice relative humidity), and how this interaction affects the contrail evolution and the characteristics of the resulting contrail-cirrus one hour after emission. Turbulence is sustained via a large-scale stochastic forcing that creates a non-uniform shear in addition to pure turbulent fluctuations. This effect manifests in the formation of vertically sheared structures of ice crystals.more » When radiative transfer is activated, ice tends to redistribute more uniformly along the vertical direction forming spotty vertical structures. For the conditions analyzed in this study, atmospheric turbulence, inclusive of non-uniform turbulent shear and turbulent fluctuations, affects primarily the contrail width whereas the microphysical properties such ice water path and ice mass are controlled by radiative transfer and relative humidity.« less

The effects of drilling muds on marine invertebrate larvae and adults

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

Raimondi, P.T.; Barnett, A.M.; Krause, P.R.

1997-06-01

A series of laboratory experiments tested the effects of drilling muds from an active platform off southern California on larvae and adults of marine invertebrates. Red abalone (Haliotis rufescens) were used to determine effects of drilling muds on fertilization, early development, survivorship, and settlement, and experiments on adult brown cup corals (Paracyathus stearnsii) tested effects on adult survivorship, viability, and tissue loss. Exposures to drilling muds did not have an effect on abalone fertilization or early development. However, several exposures to drilling muds resulted in weak, but significant, positive effects of drilling muds on settlement of competent larvae. In contrast,more » settlement of red abalone larvae on natural coralline algal crusts decreased with increasing concentrations of drilling muds. This suggests that drilling muds affect either the abalone`s ability to detect natural settlement inducers, or they affect the inducer itself. Exposure of brown cup corals to concentrations of drilling muds adversely impacted their survivorship and viability. These effects were likely caused by increased tissue mortality of the coral polyps.« less

Three-dimensional large-eddy simulations of the early phase of contrail-to-cirrus transition: effects of atmospheric turbulence and radiative transfer

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

Paoli, Roberto; Thouron, Odile; Cariolle, Daniel

Here, this article presents the results from numerical experiments of the early phase of contrail-cirrus formation using a limited set of fully three-dimensional, high-resolution large-eddy-simulations. The focus is laid on the interplay between atmospheric turbulence and the radiative transfer (and to a limited extent the ambient ice relative humidity), and how this interaction affects the contrail evolution and the characteristics of the resulting contrail-cirrus one hour after emission. Turbulence is sustained via a large-scale stochastic forcing that creates a non-uniform shear in addition to pure turbulent fluctuations. This effect manifests in the formation of vertically sheared structures of ice crystals.more » When radiative transfer is activated, ice tends to redistribute more uniformly along the vertical direction forming spotty vertical structures. For the conditions analyzed in this study, atmospheric turbulence, inclusive of non-uniform turbulent shear and turbulent fluctuations, affects primarily the contrail width whereas the microphysical properties such ice water path and ice mass are controlled by radiative transfer and relative humidity.« less

Elk Hills Endangered Species Program: environmental assessment of the blunt-nosed leopard lizard, Crotaphytus silus. Phase 2, 1980

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

Mullen, R.K.

1981-02-01

This report represents an extension of previous findings concerning the status of the endangered species, Crotaphytus silus (blunt-nosed leopard lizard) on the Naval Petroleum Reserve Number 1 (NPR-1), Elk Hills, California. Previous findings in 1979 were limited to superficial observations of the occurrence and distribution of C. silus on NPR-1. The present report details findings from more extensive field work conducted from late May to early August 1980, and complements the 1979 work. The ultimate purpose of the investigations reported here is to provide sufficient bases for making informed decisions concerning the relationships of present and possible future oil-related activitiesmore » at Elk Hills to the status of C. silus. There have been no particularly unique life history indicators of environmental impact on C. silus mediated through activities on NPR-1. Observations may be made, however, on the seasonal correlates of such activities: (1) individual C. silus may be buried or fatally exposed to the environment by construction activities occurring during the species' hibernation; (2) during periods when adult C. silus is active on the surface, construction activities may displace individuals that may not then be able to successfully occupy a new range, although it is to be noted in this regard that the home range of the species can be rather plastic; (3) construction activities bury or expose nest chambers of C. silus. This would unfavorably affect an average of three potential hatchlings with each burial or exposure; and (4) construction occurring when only (or predominantly) hatchlings are active on the surface may affect animals less able to avoid these activities than adults. In addition, hibernating adults will be affected, as previously noted.« less

Rat Stem-Cell Factor Induces Splenocytes Capable Of Regenerating The Thymus

PubMed Central

Migita, Russell T.; Trebasky, Lisa D.; Housman, Jerry M.; Elliott, Gary S.; Hendren, R. Wayne; Deprince, Randolph B.; Greiner, Dale L.

1992-01-01

Cytokine regulation of prethymic T-lymphoid progenitor-cell proliferation and/or differentiation has not been well-defined, although much is known of cytokine regulation of hemopoietic stem- and progenitor-cell development. Here we use a recently identified hemopoietic growth factor, stem-cell factor (SCF) (a form of the c-kit ligand), and a transplant model of thymocyte regeneration to assess the effect of SCF on the in vivo generation of prethymic, thymocyte progenitor-cell activity. We show that recombinant rat SCF (rrSCF164 administered to weanling rats selectively induces an increase in thymocyte progenitor activity in the spleens of treated rats as compared to rats treated with vehicle, polyethylene glycol (PEG)-conjugated rat albumin, or recombinant human granulocyte colony-stimulating factor (rhG-CSF). These data demonstrate that administration of SCF in vivo affects extrathymic-origin thymocyte regenerating cells and may influence, directly or indirectly, early prethymic stages of T-cell lymphopoiesis in addition to its known effect on early stages of myelopoiesis and erythropoiesis. PMID:1285280

Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765).

PubMed

Burger, Jan A; Buggy, Joseph J

2013-11-01

Over the past 3 years, ibrutinib (PCI-32765) has emerged as a breakthrough in targeted therapy for patients with certain types of B cell malignancies. Early stage clinical trials found ibrutinib to be particularly active in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), providing the rationale for ongoing phase 3 trials. In contrast to conventional chemo-immunotherapy, ibrutinib is not myelosuppressive, and responses are not affected by disease features that predict failure to respond to or short remission durations after chemo-immunotherapy, such as del17p. In CLL, ibrutinib characteristically causes an early redistribution of tissue-resident CLL cells into the blood, with rapid resolution of enlarged lymph nodes, along with a surge in lymphocytosis. Later, after weeks to months of continuous ibrutinib therapy, the growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients. This review discusses the discovery, preclinical and clinical development of ibrutinib, its pathophysiological basis, and outlines perspectives for future use of ibrutinib.

Meeting the challenge of new fatherhood during the early weeks.

PubMed

St John, Winsome; Cameron, Catherine; McVeigh, Carol

2005-01-01

To explore new/subsequent Australian fathers' perspectives on the experiences, processes, and life changes in the early weeks of fatherhood. Interpretive study using in-depth interviews and grounded theory analysis techniques, based on a symbolic interactionist framework. Participants were recruited from the postnatal wards of a major public hospital, early discharge program, and early childhood centers in southeast Queensland, Australia. Eighteen first-time/subsequent fathers interviewed 6 to 12 weeks after the birth. Although rewarding, fathers found new or expanding fatherhood to be a significant challenge and time of change. Major themes included making a commitment, taking responsibility, negotiating responsibilities, developing and maintaining relationships, maintaining family integrity, balancing activities, and perceiving the self as father. Work had a major impact on fathers' ability to participate with their family and newborn. To manage, fathers sought to balance the demands of work and home, deal with stressors, manage their time, develop routines, and reprioritize. Fathers developed a sense of themselves as fathers over time, building confidence and deriving satisfaction from their fathering role. A range of competing factors affected fathers' ability to participate in the home with their newborn in the early weeks after birth.

Immature Spinal Locomotor Output in Children with Cerebral Palsy.

PubMed

Cappellini, Germana; Ivanenko, Yury P; Martino, Giovanni; MacLellan, Michael J; Sacco, Annalisa; Morelli, Daniela; Lacquaniti, Francesco

2016-01-01

Detailed descriptions of gait impairments have been reported in cerebral palsy (CP), but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analyzed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2-12 years) and 33 typically developing (TD) children (1-12 years). TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children). Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behavior.

Immature Spinal Locomotor Output in Children with Cerebral Palsy

PubMed Central

Cappellini, Germana; Ivanenko, Yury P.; Martino, Giovanni; MacLellan, Michael J.; Sacco, Annalisa; Morelli, Daniela; Lacquaniti, Francesco

2016-01-01

Detailed descriptions of gait impairments have been reported in cerebral palsy (CP), but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analyzed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2–12 years) and 33 typically developing (TD) children (1–12 years). TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children). Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behavior. PMID:27826251

The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles

PubMed Central

Barrett, C E; Arambula, S E; Young, L J

2015-01-01

Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1–14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified. Neonatal social isolation impaired female PP formation, without affecting OTR density. Accumbal OTR density was, however, positively correlated with the percent of time spent huddling with the partner in neonatally isolated females. Females with high accumbal OTR binding were resilient to neonatal isolation. These results are consistent with the hypothesis that parental nurturing shapes neural systems underlying social relationships by enhancing striatal OTR signaling. Thus, we next determined whether early touch, mimicking parental licking and grooming, stimulates hypothalamic OT neuron activity. Tactile stimulation induced immediate-early gene activity in OT neurons in neonates. Finally, we investigated whether pharmacologically potentiating OT release using a melanocortin 3/4 agonist, melanotan-II (10 mg kg−1 subcutaneously), would mitigate the social isolation-induced impairments in attachment behavior. Neonatal melanotan-II administration buffered against the effects of early isolation on partner preference formation. Thus, variation in accumbal OTR density and early OT release induced by parental nurturing may moderate susceptibility to early adverse experiences, including neglect. PMID:26196439

Activation of AMP-activated protein kinase in response to temperature elevation shows seasonal variation in the zebra mussel, Dreissena polymorpha.

PubMed

Jost, Jennifer A; Keshwani, Sarah S; Abou-Hanna, Jacob J

2015-04-01

Global climate change is affecting ectothermic species, and a variety of studies are needed on thermal tolerances, especially from cellular and physiological perspectives. This study utilized AMP-activated protein kinase (AMPK), a key regulator of cellular energy levels, to examine the effects of high water temperatures on zebra mussel (Dreissena polymorpha) physiology. During heating, AMPK activity increased as water temperature increased to a point, and maximum AMPK activity was detected at high, but sublethal, water temperatures. This pattern varied with season, suggesting that cellular mechanisms of seasonal thermal acclimatization affect basic metabolic processes during sublethal heat stress. There was a greater seasonal variation in the water temperature at which maximum AMPK activity was measured than in lethal water temperature. Furthermore, baseline AMPK activity varied significantly across seasons, most likely reflecting altered metabolic states during times of growth and reproduction. In addition, when summer-collected mussels were lab-acclimated to winter and spring water temperatures, patterns of heat stress mirrored those of field-collected animals. These data suggest that water temperature is the main driver of the seasonal variation in physiology. This study concluded that AMPK activity, which reflects changes in energy supply and demand during heat stress, can serve as a sensitive and early indicator of temperature stress in mussels. Copyright © 2014 Elsevier Inc. All rights reserved.

Touchscreen typing-pattern analysis for detecting fine motor skills decline in early-stage Parkinson's disease.

PubMed

Iakovakis, Dimitrios; Hadjidimitriou, Stelios; Charisis, Vasileios; Bostantzopoulou, Sevasti; Katsarou, Zoe; Hadjileontiadis, Leontios J

2018-05-16

Parkinson's disease (PD) is a degenerative movement disorder causing progressive disability that severely affects patients' quality of life. While early treatment can produce significant benefits for patients, the mildness of many early signs combined with the lack of accessible high-frequency monitoring tools may delay clinical diagnosis. To meet this need, user interaction data from consumer technologies have recently been exploited towards unsupervised screening for PD symptoms in daily life. Similarly, this work proposes a method for detecting fine motor skills decline in early PD patients via analysis of patterns emerging from finger interaction with touchscreen smartphones during natural typing. Our approach relies on low-/higher-order statistical features of keystrokes timing and pressure variables, computed from short typing sessions. Features are fed into a two-stage multi-model classification pipeline that reaches a decision on the subject's status (PD patient/control) by gradually fusing prediction probabilities obtained for individual typing sessions and keystroke variables. This method achieved an AUC = 0.92 and 0.82/0.81 sensitivity/specificity (matched groups of 18 early PD patients/15 controls) with discriminant features plausibly correlating with clinical scores of relevant PD motor symptoms. These findings suggest an improvement over similar approaches, thereby constituting a further step towards unobtrusive early PD detection from routine activities.

Visual Circuit Development Requires Patterned Activity Mediated by Retinal Acetylcholine Receptors

PubMed Central

Burbridge, Timothy J.; Xu, Hong-Ping; Ackman, James B.; Ge, Xinxin; Zhang, Yueyi; Ye, Mei-Jun; Zhou, Z. Jimmy; Xu, Jian; Contractor, Anis; Crair, Michael C.

2014-01-01

SUMMARY The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial largely due to the inherent difficulty recording neural activity in early development. Here, we describe novel genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a de-coupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience. PMID:25466916

The Competitive Interplay between Allosteric HIV-1 Integrase Inhibitor BI/D and LEDGF/p75 during the Early Stage of HIV-1 Replication Adversely Affects Inhibitor Potency.

PubMed

Feng, Lei; Dharmarajan, Venkatasubramanian; Serrao, Erik; Hoyte, Ashley; Larue, Ross C; Slaughter, Alison; Sharma, Amit; Plumb, Matthew R; Kessl, Jacques J; Fuchs, James R; Bushman, Frederic D; Engelman, Alan N; Griffin, Patrick R; Kvaratskhelia, Mamuka

2016-05-20

Allosteric HIV-1 integrase inhibitors (ALLINIs) have recently emerged as a promising class of antiretroviral agents and are currently in clinical trials. In infected cells, ALLINIs potently inhibit viral replication by impairing virus particle maturation but surprisingly exhibit a reduced EC50 for inhibiting HIV-1 integration in target cells. To better understand the reduced antiviral activity of ALLINIs during the early stage of HIV-1 replication, we investigated the competitive interplay between a potent representative ALLINI, BI/D, and LEDGF/p75 with HIV-1 integrase. While the principal binding sites of BI/D and LEDGF/p75 overlap at the integrase catalytic core domain dimer interface, we show that the inhibitor and the cellular cofactor induce markedly different multimerization patterns of full-length integrase. LEDGF/p75 stabilizes an integrase tetramer through the additional interactions with the integrase N-terminal domain, whereas BI/D induces protein-protein interactions in C-terminal segments that lead to aberrant, higher-order integrase multimerization. We demonstrate that LEDGF/p75 binds HIV-1 integrase with significantly higher affinity than BI/D and that the cellular protein is able to reverse the inhibitor induced aberrant, higher-order integrase multimerization in a dose-dependent manner in vitro. Consistent with these observations, alterations of the cellular levels of LEDGF/p75 markedly affected BI/D EC50 values during the early steps of HIV-1 replication. Furthermore, genome-wide sequencing of HIV-1 integration sites in infected cells demonstrate that LEDGF/p75-dependent integration site selection is adversely affected by BI/D treatment. Taken together, our studies elucidate structural and mechanistic details of the interplay between LEDGF/p75 and BI/D during the early stage of HIV-1 replication.

When beggars are choosers-How nesting of a solitary bee is affected by temporal dynamics of pollen plants in the landscape.

PubMed

Persson, Anna S; Mazier, Florence; Smith, Henrik G

2018-06-01

Wild bees are declining in intensively farmed regions worldwide, threatening pollination services to flowering crops and wild plants. To halt bee declines, it is essential that conservation actions are based on a mechanistic understanding of how bee species utilize landscapes. We aimed at teasing apart how foraging resources in the landscape through the nesting season affected nesting and reproduction of a solitary bee in a farmland region. We investigated how availability of floral resources and potentially resource-rich habitats surrounding nests affected nest provisioning and reproduction in the solitary polylectic bee Osmia bicornis . The study was performed in 18 landscape sectors dominated by agriculture, but varying in agricultural intensity in terms of proportion of organic crop fields and seminatural permanent pastures. Pasture-rich sectors contained more oak ( Quercus robur ), which pollen analysis showed to be favored forage in early season. More oaks ≤100 m from nests led to higher proportions of oak pollen in nest provisions and increased speed of nest construction in early season, but this effect tapered off as flowering decreased. Late-season pollen foraging was dominated by buttercup ( Ranunculus spp.), common in various noncrop habitats. Foraging trips were longer with more oaks and increased further through the season. The opposite was found for buttercup. Oak and buttercup interacted to explain the number of offspring; buttercup had a positive effect only when the number of oaks was above the mean for the studied sectors. The results show that quality of complex and pasture-rich landscapes for O. bicornis depends on preserving existing and generating new oak trees. Lignose plants are key early-season forage resources in agricultural landscapes. Increasing habitat heterogeneity with trees and shrubs and promoting suitable late-flowering forbs can benefit O. bicornis and other wild bees active in spring and early summer, something which existing agri-environment schemes seldom target.

Application and analysis of debris-flow early warning system in Wenchuan earthquake-affected area

NASA Astrophysics Data System (ADS)

Liu, D. L.; Zhang, S. J.; Yang, H. J.; Zhao, L. Q.; Jiang, Y. H.; Tang, D.; Leng, X. P.

2016-02-01

The activities of debris flow (DF) in the Wenchuan earthquake-affected area significantly increased after the earthquake on 12 May 2008. The safety of the lives and property of local people is threatened by DFs. A physics-based early warning system (EWS) for DF forecasting was developed and applied in this earthquake area. This paper introduces an application of the system in the Wenchuan earthquake-affected area and analyzes the prediction results via a comparison to the DF events triggered by the strong rainfall events reported by the local government. The prediction accuracy and efficiency was first compared with a contribution-factor-based system currently used by the weather bureau of Sichuan province. The storm on 17 August 2012 was used as a case study for this comparison. The comparison shows that the false negative rate and false positive rate of the new system is, respectively, 19 and 21 % lower than the system based on the contribution factors. Consequently, the prediction accuracy is obviously higher than the system based on the contribution factors with a higher operational efficiency. On the invitation of the weather bureau of Sichuan province, the authors upgraded their prediction system of DF by using this new system before the monsoon of Wenchuan earthquake-affected area in 2013. Two prediction cases on 9 July 2013 and 10 July 2014 were chosen to further demonstrate that the new EWS has high stability, efficiency, and prediction accuracy.

Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus

PubMed Central

Evuarherhe, Obaro; Barker, Gareth R. I.; Savalli, Giorgia; Warburton, Elizabeth C.; Brown, Malcolm W.

2014-01-01

Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesised to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluR2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluR2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluR2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. PMID:24729442

E2F4 is required for early eye patterning.

PubMed

Ruzhynsky, Vladimir A; Furimsky, Marosh; Park, David S; Wallace, Valerie A; Slack, Ruth S

2009-01-01

Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.5 and characterized by aberrant shape of the optic cup, coloboma as well as abnormal eye pigmentation. Loss of E2F4 is associated with proximal-distal patterning defects in the optic vesicle. These defects are characterized by the expansion of optic stalk marker gene expression to the optic cup and reduced expression of ventral optic cup markers. These defects are associated with a split of Shh expression domain at the ventral midline of the forebrain and expansion of the Shh activity into the ventral optic cup. Despite these patterning defects, early neuronal differentiation and Shh expression in the retina are not affected by E2F4 deletion. Overall, the results of our studies show a novel role of E2F4 in the early eye development. 2009 S. Karger AG, Basel.

Emotional words facilitate lexical but not early visual processing.

PubMed

Trauer, Sophie M; Kotz, Sonja A; Müller, Matthias M

2015-12-12

Emotional scenes and faces have shown to capture and bind visual resources at early sensory processing stages, i.e. in early visual cortex. However, emotional words have led to mixed results. In the current study ERPs were assessed simultaneously with steady-state visual evoked potentials (SSVEPs) to measure attention effects on early visual activity in emotional word processing. Neutral and negative words were flickered at 12.14 Hz whilst participants performed a Lexical Decision Task. Emotional word content did not modulate the 12.14 Hz SSVEP amplitude, neither did word lexicality. However, emotional words affected the ERP. Negative compared to neutral words as well as words compared to pseudowords lead to enhanced deflections in the P2 time range indicative of lexico-semantic access. The N400 was reduced for negative compared to neutral words and enhanced for pseudowords compared to words indicating facilitated semantic processing of emotional words. LPC amplitudes reflected word lexicality and thus the task-relevant response. In line with previous ERP and imaging evidence, the present results indicate that written emotional words are facilitated in processing only subsequent to visual analysis.

The effect of day-neutral mutations in barley and wheat on the interaction between photoperiod and vernalization.

PubMed

Turner, Adrian S; Faure, Sébastien; Zhang, Yang; Laurie, David A

2013-09-01

Vernalization-2 (Vrn-2) is the major flowering repressor in temperate cereals. It is only expressed under long days in wild-type plants. We used two day-neutral (photoperiod insensitive) mutations that allow rapid flowering in short or long days to investigate the day length control of Vrn-2. The barley (Hordeum vulgare) early maturity8 (eam8) mutation affects the barley ELF3 gene. eam8 mutants disrupt the circadian clock resulting in elevated expression of Ppd-H1 and the floral activator HvFT1 under short or long days. When eam8 was crossed into a genetic background with a vernalization requirement Vrn-2 was expressed under all photoperiods and the early flowering phenotype was partially repressed in unvernalized (UV) plants, likely due to competition between the constitutively active photoperiod pathway and the repressing effect of Vrn-2. We also investigated the wheat (Triticum aestivum) Ppd-D1a mutation. This differs from eam8 in causing elevated levels of Ppd-1 and TaFT1 expression without affecting the circadian clock. We used genotypes that differed in "short-day vernalization". Short days were effective in promoting flowering in individuals wild type at Ppd-D1, but not in individuals that carry the Ppd-D1a mutation. The latter showed Vrn-2 expression in short days. In summary, eam8 and Ppd-D1a mimic long days in terms of photoperiod response, causing Vrn-2 to become aberrantly expressed (in short days). As Ppd-D1a does not affect the circadian clock, this also shows that clock regulation of Vrn-2 operates indirectly through one or more downstream genes, one of which may be Ppd-1.

Behavioral deficits and cholinergic pathway abnormalities in male Sanfilippo B mice.

PubMed

Kan, Shih-Hsin; Le, Steven Q; Bui, Quang D; Benedict, Braeden; Cushman, Jesse; Sands, Mark S; Dickson, Patricia I

2016-10-01

Sanfilippo B syndrome is a progressive neurological disorder caused by inability to catabolize heparan sulfate glycosaminoglycans. We studied neurobehavior in male Sanfilippo B mice and heterozygous littermate controls from 16 to 20 weeks of age. Affected mice showed reduced anxiety, with a decrease in the number of stretch-attend postures during the elevated plus maze (p=0.001) and an increased tendency to linger in the center of an open field (p=0.032). Water maze testing showed impaired spatial learning, with reduced preference for the target quadrant (p=0.01). In radial arm maze testing, affected mice failed to achieve above-chance performance in a win-shift working memory task (t-test relative to 50% chance: p=0.289), relative to controls (p=0.037). We found a 12.4% reduction in mean acetylcholinesterase activity (p<0.001) and no difference in choline acetyltransferase activity or acetylcholine in whole brain of affected male animals compared to controls. Cholinergic pathways are affected in adult-onset dementias, including Alzheimer disease. Our results suggest that male Sanfilippo B mice display neurobehavioral deficits at a relatively early age, and that as in adult dementias, they may display deficits in cholinergic pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

Sulfhydryl modification of V449C in the glutamate transporter EAAT1 abolishes substrate transport but not the substrate-gated anion conductance

PubMed Central

Seal, Rebecca P.; Shigeri, Yasushi; Eliasof, Scott; Leighton, Barbara H.; Amara, Susan G.

2001-01-01

Excitatory amino acid transporters (EAATs) buffer and remove synaptically released l-glutamate and maintain its concentrations below neurotoxic levels. EAATs also mediate a thermodynamically uncoupled substrate-gated anion conductance that may modulate cell excitability. Here, we demonstrate that modification of a cysteine substituted within a C-terminal domain of EAAT1 abolishes transport in both the forward and reverse directions without affecting activation of the anion conductance. EC50s for l-glutamate and sodium are significantly lower after modification, consistent with kinetic models of the transport cycle that link anion channel gating to an early step in substrate translocation. Also, decreasing the pH from 7.5 to 6.5 decreases the EC50 for l-glutamate to activate the anion conductance, without affecting the EC50 for the entire transport cycle. These findings demonstrate for the first time a structural separation of transport and the uncoupled anion flux. Moreover, they shed light on some controversial aspects of the EAAT transport cycle, including the kinetics of proton binding and anion conductance activation. PMID:11752470

naked cuticle targets dishevelled to antagonize Wnt signal transduction

PubMed Central

Rousset, Raphaël; Mack, Judith A.; Wharton, Keith A.; Axelrod, Jeffrey D.; Cadigan, Ken M.; Fish, Matthew P.; Nusse, Roel; Scott, Matthew P.

2001-01-01

In Drosophila embryos the protein Naked cuticle (Nkd) limits the effects of the Wnt signal Wingless (Wg) during early segmentation. nkd loss of function results in segment polarity defects and embryonic death, but how nkd affects Wnt signaling is unknown. Using ectopic expression, we find that Nkd affects, in a cell-autonomous manner, a transduction step between the Wnt signaling components Dishevelled (Dsh) and Zeste-white 3 kinase (Zw3). Zw3 is essential for repressing Wg target-gene transcription in the absence of a Wg signal, and the role of Wg is to relieve this inhibition. Our double-mutant analysis shows that, in contrast to Zw3, Nkd acts when the Wg pathway is active to restrain signal transduction. Yeast two hybrid and in vitro experiments indicate that Nkd directly binds to the basic-PDZ region of Dsh. Specially timed Nkd overexpression is capable of abolishing Dsh function in a distinct signaling pathway that controls planar-cell polarity. Our results suggest that Nkd acts directly through Dsh to limit Wg activity and thus determines how efficiently Wnt signals stabilize Armadillo (Arm)/β-catenin and activate downstream genes. PMID:11274052

Participatory ergonomics: co-developing interventions to reduce the risk of musculoskeletal symptoms in business drivers.

PubMed

Gyi, Diane; Sang, Katherine; Haslam, Cheryl

2013-01-01

The participatory process within four case study organisations with a target population of high mileage business drivers is described. The aim was to work with drivers and their managers to co-develop intervention activities to raise awareness of musculoskeletal health in drivers, including use of the car as a mobile office and manual handling from the car. Train-the-trainer sessions were delivered in each organisation, along with the co-production of training materials. The effectiveness of these activities were evaluated using three sources of data: post-intervention questionnaires, interviews with organisation 'champions' and observations from the research team's diaries. The approach raised management awareness of the risks to drivers and was successful in affecting change, and as such, participatory research should consider the early stages of a project as part of any intervention activities. The research team also reflect on conducting applied longitudinal research in the field. Raising awareness of the risks of musculoskeletal disorders in drivers who work from their vehicle is important. This paper reflects on research in the field and provides guidance on the participatory process and evaluating intervention activities. The participatory process was successful in affecting change at management level.

Combined effect of three insect growth regulators on the digestive enzymatic profiles of Callosobruchus maculatus (Coleoptera: Bruchidae).

PubMed

Khatter, Najat Aly; Abuldahb, Faten Farid

2011-12-01

Insect growth regulators (IGRs) are insecticides that mimic insect produced hormones by regulatingdevelopmental process. Theyhave little or no mammalian toxicity, and are considered reduced-risk insecticides that are often exempt from tolerance requirements of regulatory agencies. IGRs, especially, chlorfluazuron, hydroprene and hexaflumuron (benzoylphenylurea) are currently studied because of possibility of using in stored products protection. Many of IGRs compounds usedin insect pests control are known to affect digestive enzymes. Chlorfluazuron, hydroprene and hexaflumuronwere tested topically at doses of 0.25%, 0.5%&1% for chlorfluazuron and hydroprene and 0.5, 1 & 2 microg/ml of hexaflumuron to investigate its effects on the activities of the digestive enzymes protease, amylase and lipase in Callosobruchusmaculatus larvae, which were affected by IGRs individually and in combination. When combined, the effect was more sever at low concentration. There were statistically significant differences (P < or = 0.05) in enzyme activities in combined and individual treatments. Combination three IGRs caused a two-fold decrease in enzyme activity even at reduced concentration. Clear dose-response relationships were established with respect to enzyme activity. A synergistic effect of IGRs was found by combination of low doses. These effects are most pronounced in early instars.

Area Handbook Series: Sudan: A Country Study

DTIC Science & Technology

1991-06-01

major courts and mag- istrate’s courts. Special courts, under military jurisdiction, dealt with offenses affecting national security or involving...treating African southerners as a minority group. Another major factor that has affected Sudan’s evolution is the country’s relationship with Egypt. As early...civilian governments. The conflict appeared likely to continue to affect Sudan’s people and institutions for the rest of the twentieth century. Early

Sodium Butyrate Improves Locomotor Impairment and Early Mortality in a Rotenone-Induced Drosophila Model of Parkinson’s Disease

PubMed Central

St. Laurent, Robyn; O’Brien, Liam M.; Ahmad, S. Tariq

2013-01-01

Parkinson’s disease (PD) is a neurodegenerative disorder primarily affecting the dopaminergic neurons in the nigrastriatal pathway resulting in debilitating motor impairment in both familial and sporadic cases. Histone deacetylase (HDAC) inhibitors have been recently implicated as a therapeutic candidate because of their ability to correct the disrupted HDAC activity in PD and other neurodegenerative diseases. Sodium butyrate (SB), an HDAC inhibitor, reduces degeneration of dopaminergic neurons in a mutant alpha-synuclein Drosophila transgenic model of familial PD. Chronic exposure to the pesticide rotenone also causes selective degeneration of dopaminergic neurons and causes locomotor impairment and early mortality in a Drosophila model of chemically-induced PD. This study investigated the effects of sodium butyrate on locomotor impairment and early mortality in a rotenone-induced PD model. We show that treatment with 10 mM SB-supplemented food rescued the rotenone-induced locomotor impairment and early mortality in flies. Additionally, flies with the genetic knockdown of HDAC activity through Sin3A loss-of-function mutation (Sin3Alof) were resistant to rotenone-induced locomotor impairment and early mortality. Furthermore, SB-supplemented Sin3Alof flies had a modest additive effect for improving locomotor impairment. We also show SB-mediated improvement of rotenone-induced locomotor impairment was associated with elevated dopamine levels in the brain. However, the possibility of SB-mediated protective role through mechanisms independent from dopamine system is also discussed. These findings demonstrate that HDAC inhibitors like SB can ameliorate locomotor impairment in a rotenone-induced PD model. PMID:23623990

Genetic and pharmacological factors that influence reproductive aging in nematodes.

PubMed

Hughes, Stacie E; Evason, Kimberley; Xiong, Chengjie; Kornfeld, Kerry

2007-02-16

Age-related degenerative changes in the reproductive system are an important aspect of aging, because reproductive success is the major determinant of evolutionary fitness. Caenorhabditis elegans is a prominent organism for studies of somatic aging, since many factors that extend adult lifespan have been identified. However, mechanisms that control reproductive aging in nematodes or other animals are not well characterized. To use C. elegans to measure reproductive aging, we analyzed mated hermaphrodites that do not become sperm depleted and monitored the duration and level of progeny production. Mated hermaphrodites display a decline of progeny production that culminates in reproductive cessation before the end of the lifespan, demonstrating that hermaphrodites undergo reproductive aging. To identify factors that influence reproductive aging, we analyzed genetic, environmental, and pharmacological factors that extend lifespan. Dietary restriction and reduced insulin/insulin-like growth factor signaling delayed reproductive aging, indicating that nutritional status and a signaling pathway that responds to environmental stress influence reproductive aging. Cold temperature delayed reproductive aging. The anticonvulsant medicine ethosuximide, which affects neural activity, delayed reproductive aging, indicating that neural activity can influence reproductive aging. Some of these factors decrease early progeny production, but there is no consistent relationship between early progeny production and reproductive aging in strains with an extended lifespan. To directly examine the effects of early progeny production on reproductive aging, we used sperm availability to modulate the level of early reproduction. Early progeny production neither accelerated nor delayed reproductive aging, indicating that reproductive aging is not controlled by use-dependent mechanisms. The implications of these findings for evolutionary theories of aging are discussed.

Impact of Attention Biases to Threat and Effortful Control on Individual Variations in Negative Affect and Social Withdrawal in Very Young Children

PubMed Central

Zapp, Daniel J.; Fettig, Nicole B.; Pérez-Edgar, Koraly

2015-01-01

Early temperamental sensitivity may form the basis for the later development of socioemotional maladjustment. In particular, temperamental negative affect places children at risk for the development of anxiety. However, not all children who show negative affect go on to develop anxiety or extreme social withdrawal. Recent research indicates that reactive control, in the form of attention to threat, may serve as a bridge between early temperament and the development of later social difficulties. In addition, variation in effortful control may also modulate this trajectory. Children (MeanAge=5.57 years) were assessed for attention bias to threatening and pleasant faces using a dot-probe paradigm. Attention bias to threatening (but not happy) faces moderated the direct positive relation between negative affect and social withdrawal. Children with threat biases showed a significant link between negative affect and social withdrawal, while children who avoided threat did not. In contrast, effortful control did not moderate the relation between negative affect and social withdrawal. Rather, there was a direct negative relation between effortful control and social withdrawal. The findings from this short report indicate that the relation amongst temperament, attention bias, and social withdrawal appears early in life and point to early emerging specificity in reactive and regulatory functioning. PMID:26477597

Rapid and highly resolving associative affective learning: convergent electro- and magnetoencephalographic evidence from vision and audition.

PubMed

Steinberg, Christian; Bröckelmann, Ann-Kathrin; Rehbein, Maimu; Dobel, Christian; Junghöfer, Markus

2013-03-01

Various pathway models for emotional processing suggest early prefrontal contributions to affective stimulus evaluation. Yet, electrophysiological evidence for such rapid modulations is still sparse. In a series of four MEG/EEG studies which investigated associative learning in vision and audition using a novel MultiCS Conditioning paradigm, many different neutral stimuli (faces, tones) were paired with aversive and appetitive events in only two to three learning instances. Electrophysiological correlates of neural activity revealed highly significant amplified processing for conditioned stimuli within distributed prefrontal and sensory cortical networks. In both, vision and audition, affect-specific responses occurred in two successive waves of rapid (vision: 50-80 ms, audition: 25-65 ms) and mid-latency (vision: >130 ms, audition: >100 ms) processing. Interestingly, behavioral measures indicated that MultiCS Conditioning successfully prevented contingency awareness. We conclude that affective processing rapidly recruits highly elaborate and widely distributed networks with substantial capacity for fast learning and excellent resolving power. Copyright © 2012 Elsevier B.V. All rights reserved.

SLC30A9 mutation affecting intracellular zinc homeostasis causes a novel cerebro-renal syndrome

PubMed Central

Perez, Yonatan; Shorer, Zamir; Liani-Leibson, Keren; Chabosseau, Pauline; Kadir, Rotem; Volodarsky, Michael; Halperin, Daniel; Barber-Zucker, Shiran; Shalev, Hanna; Schreiber, Ruth; Gradstein, Libe; Gurevich, Evgenia; Zarivach, Raz; Rutter, Guy A.; Landau, Daniel

2017-01-01

Abstract A novel autosomal recessive cerebro-renal syndrome was identified in consanguineous Bedouin kindred: neurological deterioration was evident as of early age, progressing into severe intellectual disability, profound ataxia, camptocormia and oculomotor apraxia. Brain MRI was normal. Four of the six affected individuals also had early-onset nephropathy with features of tubulo-interstitial nephritis, hypertension and tendency for hyperkalemia, though none had rapid deterioration of renal function. Genome wide linkage analysis identified an ∼18 Mb disease-associated locus on chromosome 4 (maximal logarithm of odds score 4.4 at D4S2971; θ = 0). Whole exome sequencing identified a single mutation in SLC30A9 within this locus, segregating as expected within the kindred and not found in a homozygous state in 300 Bedouin controls. We showed that SLC30A9 (solute carrier family 30 member 9; also known as ZnT-9) is ubiquitously expressed with high levels in cerebellum, skeletal muscle, thymus and kidney. Confocal analysis of SH-SY5Y cells overexpressing SLC30A9 fused to enhanced green fluorescent protein demonstrated vesicular cytosolic localization associated with the endoplasmic reticulum, not co-localizing with endosomal or Golgi markers. SLC30A9 encodes a putative zinc transporter (by similarity) previously associated with Wnt signalling. However, using dual-luciferase reporter assay in SH-SY5Y cells we showed that Wnt signalling was not affected by the mutation. Based on protein modelling, the identified mutation is expected to affect SLC30A9’s highly conserved cation efflux domain, putatively disrupting its transmembrane helix structure. Cytosolic Zn2+ measurements in HEK293 cells overexpressing wild-type and mutant SLC30A9 showed lower zinc concentration within mutant rather than wild-type SLC30A9 cells. This suggests that SLC30A9 has zinc transport properties affecting intracellular zinc homeostasis, and that the molecular mechanism of the disease is through defective function of this novel activity of SLC30A9 rather than by a defect in its previously described role in transcriptional activation of Wnt signalling. PMID:28334855

Human Papillomavirus Types 16 and 18 Early-expressed Proteins Differentially Modulate the Cellular Redox State and DNA Damage

PubMed Central

Cruz-Gregorio, Alfredo; Manzo-Merino, Joaquín; Gonzaléz-García, María Cecilia; Pedraza-Chaverri, José; Medina-Campos, Omar Noel; Valverde, Mahara; Rojas, Emilio; Rodríguez-Sastre, María Alexandra; García-Cuellar, Claudia María; Lizano, Marcela

2018-01-01

Oxidative stress has been proposed as a risk factor for cervical cancer development. However, few studies have evaluated the redox state associated with human papillomavirus (HPV) infection. The aim of this work was to determine the role of the early expressed viral proteins E1, E2, E6 and E7 from HPV types 16 and 18 in the modulation of the redox state in an integral form. Therefore, generation of reactive oxygen species (ROS), concentration of reduced glutathione (GSH), levels and activity of the antioxidant enzymes catalase and superoxide dismutase (SOD) and deoxyribonucleic acid (DNA) damage, were analysed in epithelial cells ectopically expressing the viral proteins. Our research shows that E6 oncoproteins decreased GSH and catalase protein levels, as well as its enzymatic activity, which was associated with an increase in ROS production and DNA damage. In contrast, E7 oncoproteins increased GSH, as well as catalase protein levels and its activity, which correlated with a decrease in ROS without affecting DNA integrity. The co-expression of both E6 and E7 oncoproteins neutralized the effects that were independently observed for each of the viral proteins. Additionally, the combined expression of E1 and E2 proteins increased ROS levels with the subsequent increase in the marker for DNA damage phospho-histone 2AX (γH2AX). A decrease in GSH, as well as SOD2 levels and activity were also detected in the presence of E1 and E2, even though catalase activity increased. This study demonstrates that HPV early expressed proteins differentially modulate cellular redox state and DNA damage. PMID:29483822

Dietary vitamin A impacts DNA methylation patterns of adipogenesis-related genes in suckling rats.

PubMed

Arreguín, A; Ribot, J; Mušinović, H; von Lintig, J; Palou, A; Bonet, M L

2018-05-11

We previously showed that vitamin A supplementation in early life impacts white adipose tissue (WAT) biology. We here studied the vitamin's effects on DNA methylation of genes crucial for WAT cell development, determination and metabolism. CpG promoter methylation and mRNA expression of Pparg, Zfp423, Pcna, and Rbp4 was compared in inguinal WAT of 21-day-old rats supplemented during the suckling period with vehicle (controls) or an emulsion of vitamin A as retinyl ester (RE) or β-carotene (BC). The methylation profile of promoters was affected by vitamin A supplementation with pronounced differences between the RE and BC groups. In the RE group, hypermethylation of the Rbp4 (at multiple CpGs) and the Pparg2 (at a specific CpG) promoters and hypomethylation of the Pcna promoter (at multiple CpGs) was observed, together with inverse changes in gene expression levels. In the BC group, hypomethylation of the Rbp4 and hypermethylation of the Pcna promoter at distinct CpGs was observed, with no effects on gene expression. In both supplemention groups, hypomethylation and increased expression was found for Zfp423. Thus, modest vitamin A supplementation in early postnatal life impacts methylation marks in developing WAT. Differential epigenetic effects of RE and BC in early life may affect adipose tissue programming activity. Copyright © 2018 Elsevier Inc. All rights reserved.

[Cryptococcal meningitis as a diagnostic problem in a patient with SLE--case report].

PubMed

Bosnić, Dubravka; Cerovec, Mislav; Anić, Branimir; Mayer, Miroslav; Sentić, Mirna; Baresić, Marko; Markeljević, Jasenka; Cikes, Nada

2008-01-01

Systemic erythematosus lupus (SLE) is a disease with wide range of clinical manifestations, signs and symptoms. Disease outcome depends mostly on the affection of kidneys and central nervous system by the disease. Very important cause of death in patients with SLE is infection. Infections are very common among these patients due to aggressive immunosuppressive treatment that is needed for the disease inflammatory activity control. In this case report we have presented a patient with SLE who initially had severe renal affection, but also complications of immunosuppressive therapy that was administered. Even though the disease was accidentally diagnosed, it had a severe clinical progress. Because of lupus nephropathy, in the early phase of the disease we administered aggressive immunosuppressive therapy (combined parenteral therapy of glucocorticoides and cyclophosphamide). As an outcome of the combined effect of disease and immunosuppressive agents used in the treatment of the disease, the patient had increased infective diathesis (repeated infections caused by S. enteritidis--urinary infections and sepsis). During one of the disease flares the patient was hospitalized an opportunistic infection developed. It was meningitis caused by C. neoformans. This opportunistic mycosis infection presented with clinically totally nonspecific signs and symptoms of CNS affection. Therefore, we suspected affection of CNS with SLE. Even though all diagnostic procedures were made on time and that adequate antifungal and supportive agents were applied very early after the infection onset, the outcome was fatal. Because of infective diathesis in patients with SLE, which present with common and opportunistic infections, and due to high mortality rates caused by these infections, we have tried to emphasise the importance of taking adequate specimens early after infection outcome for these rare infective agents like C. neophormans. In recent medical literature are dominant cases reported in Asia. Reports from Europe are very rare, and this case is the one of that kind in Croatia.

A fast neural signature of motivated attention to consumer goods separates the sexes.

PubMed

Junghöfer, Markus; Kissler, Johanna; Schupp, Harald T; Putsche, Christian; Elling, Ludger; Dobel, Christian

2010-01-01

Emotional stimuli guide selective visual attention and receive enhanced processing. Previous event-related potential studies have identified an early (>120 ms) negative potential shift over occipito-temporal regions (early posterior negativity, EPN) presumed to indicate the facilitated processing of survival-relevant stimuli. The present study investigated whether this neural signature of motivated attention is also responsive to the intrinsic significance of man-made objects and consumer goods. To address this issue, we capitalized on gender differences towards specific man-made objects, shoes and motorcycles, for which the Statistical Yearbook 2005 of Germany's Federal Statistical Office (Statistisches Bundesamt, 2005) revealed pronounced differences in consumer behavior. In a passive viewing paradigm, male and female participants viewed pictures of motorcycles and shoes, while their magnetoencephalographic brain responses were measured. Source localization of the magnetic counterpart of the EPN (EPNm) revealed pronounced gender differences in picture processing. Specifically, between 130 and 180 ms, all female participants generated stronger activity in occipito-temporal regions when viewing shoes compared to motorcycles, while all men except one showed stronger activation for motorcycles than shoes. Thus, the EPNm allowed a sex-dimorphic classification of the processing of consumer goods. Self-report data confirmed gender differences in consumer behavior, which, however, were less distinct compared to the brain based measure. Considering the latency of the EPNm, the reflected automatic emotional network activity is most likely not yet affected by higher cognitive functions such as response strategies or social expectancy. Non-invasive functional neuroimaging measures of early brain activity may thus serve as objective measure for individual preferences towards consumer goods.

Disease activity in and quality of life of patients with psoriatic arthritis mutilans: the Nordic PAM Study.

PubMed

Lindqvist, U; Gudbjornsson, B; Iversen, L; Laasonen, L; Ejstrup, L; Ternowitz, T; Ståhle, M

2017-11-01

To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries. Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient's education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM. Sixty-seven patients were included. Patients with PAM had a protracted disease history (33 ± 14 years) and disease onset at a relatively early age (30 ± 12 years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60 years of age reported the most impaired quality of life in comparison to the control group. PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied.

Anatomically ordered tapping interferes more with one-digit addition than two-digit addition: a dual-task fMRI study.

PubMed

Soylu, Firat; Newman, Sharlene D

2016-02-01

Fingers are used as canonical representations for numbers across cultures. In previous imaging studies, it was shown that arithmetic processing activates neural resources that are known to participate in finger movements. Additionally, in one dual-task study, it was shown that anatomically ordered finger tapping disrupts addition and subtraction more than multiplication, possibly due to a long-lasting effect of early finger counting experiences on the neural correlates and organization of addition and subtraction processes. How arithmetic task difficulty and tapping complexity affect the concurrent performance is still unclear. If early finger counting experiences have bearing on the neural correlates of arithmetic in adults, then one would expect anatomically and non-anatomically ordered tapping to have different interference effects, given that finger counting is usually anatomically ordered. To unravel these issues, we studied how (1) arithmetic task difficulty and (2) the complexity of the finger tapping sequence (anatomical vs. non-anatomical ordering) affect concurrent performance and use of key neural circuits using a mixed block/event-related dual-task fMRI design with adult participants. The results suggest that complexity of the tapping sequence modulates interference on addition, and that one-digit addition (fact retrieval), compared to two-digit addition (calculation), is more affected from anatomically ordered tapping. The region-of-interest analysis showed higher left angular gyrus BOLD response for one-digit compared to two-digit addition, and in no-tapping conditions than dual tapping conditions. The results support a specific association between addition fact retrieval and anatomically ordered finger movements in adults, possibly due to finger counting strategies that deploy anatomically ordered finger movements early in the development.

Enhanced startle reflexivity during presentation of visual nurture cues in young adults who experienced parental divorce in early childhood.

PubMed

Hengesch, Xenia; Larra, Mauro F; Finke, Johannes B; Blumenthal, Terry D; Schächinger, Hartmut

2017-10-01

Adverse childhood experiences (ACE) may influence stress and affective processing in adulthood. Animal and human studies show enhanced startle reflexivity in adult participants with ACE. This study examined the impact of one of the most common ACE, parental divorce, on startle reflexivity in adulthood. Affective modulation of acoustically-elicited startle eye blink was assessed in a group of 23 young adults with self-reported history of parental divorce, compared to an age- and sex-matched control group (n=18). Foreground pictures were either aversive (e.g. mutilation and injury), standard appetitive (e.g. erotic, recreational sport), or nurture pictures (e.g. related to early life, parental care), intermixed with neutral pictures (e.g. household objects), and organized in three valence blocks delivered in a balanced, pseudo-randomized sequence. During picture viewing startle eye blinks were elicited by binaural white noise bursts (50ms, 105 dB) via headphones and recorded at the left orbicularis oculi muscle via EMG. A significant interaction of group×picture valence (p=0.01) was observed. Contrast with controls revealed blunted startle responsiveness of the ACE group during presentation of aversive pictures, but enhanced startle during presentation of nurture-related pictures. No group differences were found during presentation of standard appetitive pictures. ACE participants rated nurture pictures as more arousing (p=0.02) than did control participants. Results suggest that divorce in childhood led to altered affective context information processing in early adulthood. When exposed to unpleasant (vs. neutral) pictures participants with ACE showed less startle potentiation than controls. Nurture context, however, potentiated startle in ACE participants, suggesting visual cuing to activate protective behavioral responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Early sensory over-responsivity in toddlers with autism spectrum disorders as a predictor of family impairment and parenting stress.

PubMed

Ben-Sasson, A; Soto, T W; Martínez-Pedraza, F; Carter, A S

2013-08-01

Sensory over-responsivity (SOR) affects many individuals with autism spectrum disorders (ASD), often leading to stressful encounters during daily routines. This study describes the associations between early SOR symptoms and the longitudinal course of restrictions in family life activities and parenting stress across three time-points in families raising a child with ASD (n = 174). Covariates were child diagnostic severity, emotional problems, and maternal affective symptoms. At time 1 mean chronological age was 28.5 months. Children were administered the Autism Diagnostic Observation Schedule (ADOS) and Mullen Scales of Early Learning (MSEL). Parents completed the Infant Toddler Sensory Profile (ITSP), Infant-Toddler Social Emotional Assessment (ITSEA), Beck Anxiety Index (BAI), and the Center for Epidemiologic Studies Depression Inventory (CES-D) at time 1; and the Parenting Stress Index (PSI) and Family Life Impairment Scale (FLIS) at the three annual time-points. Latent Growth Curve Models indicated that higher SOR scores on the ITSP at time 1 were associated with higher initial levels of family life impairment and parenting stress and with a smaller magnitude of change over time. These associations were independent of severity of ADOS social-communication symptoms, MSEL composite score, ITSEA externalizing and anxiety symptoms, and maternal affective symptoms as measured by the BAI and CES-D. On average FLIS and PSI did not change over time, however, there was significant individual variability. Concurrently, SOR at time 1 explained 39-45% of the variance in family stress and impairment variables. An evaluation of SOR should be integrated into the assessment of toddlers with ASD considering their role in family life impairment and stress. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

PubMed

Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

2013-02-15

Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

The Epstein–Barr virus nuclear protein SM is both a post-transcriptional inhibitor and activator of gene expression

PubMed Central

Ruvolo, Vivian; Wang, Eryu; Boyle, Sarah; Swaminathan, Sankar

1998-01-01

The Epstein–Barr virus (EBV) nuclear protein BS-MLF1 (SM) is expressed early after entry of EBV into the lytic cycle. SM transactivates reporter gene constructs driven by a wide variety of promoters, but the mechanism of SM action is poorly understood. In this study, we demonstrate that the SM protein inhibits expression of intron-containing genes and activates expression of intron-less genes. We demonstrate that SM has the predicted inhibitory effect on expression of a spliced EBV gene but activates an unspliced early EBV gene. SM inhibited gene expression at the post-transcriptional level by preventing the accumulation of nuclear and cytoplasmic RNA transcripts. Conversely, SM led to increased accumulation of nuclear mRNA from intron-less genes without affecting the rate of transcription, indicating that SM enhances nuclear RNA stability. The ratio of cytoplasmic to nuclear polyadenylated mRNA was increased in the presence of SM, suggesting that SM also enhances nucleo-cytoplasmic mRNA transport. The degree of transactivation by SM was dependent on the sequence of the 3′-untranslated region of the target mRNA. Finally, we demonstrate that the amino-terminal portion of SM fused to glutathione-S-transferase binds radioactively labeled RNA in vitro, indicating that SM is a single-stranded RNA binding protein. Importantly, the latent and immediate-early genes of EBV contain introns whereas many early and late genes do not. Thus, SM may down-regulate synthesis of host cell proteins and latent EBV proteins while simultaneously enhancing expression of specific lytic EBV genes by binding to mRNA and modulating its stability and transport. PMID:9671768

The Epstein-Barr virus nuclear protein SM is both a post-transcriptional inhibitor and activator of gene expression.

PubMed

Ruvolo, V; Wang, E; Boyle, S; Swaminathan, S

1998-07-21

The Epstein-Barr virus (EBV) nuclear protein BS-MLF1 (SM) is expressed early after entry of EBV into the lytic cycle. SM transactivates reporter gene constructs driven by a wide variety of promoters, but the mechanism of SM action is poorly understood. In this study, we demonstrate that the SM protein inhibits expression of intron-containing genes and activates expression of intron-less genes. We demonstrate that SM has the predicted inhibitory effect on expression of a spliced EBV gene but activates an unspliced early EBV gene. SM inhibited gene expression at the post-transcriptional level by preventing the accumulation of nuclear and cytoplasmic RNA transcripts. Conversely, SM led to increased accumulation of nuclear mRNA from intron-less genes without affecting the rate of transcription, indicating that SM enhances nuclear RNA stability. The ratio of cytoplasmic to nuclear polyadenylated mRNA was increased in the presence of SM, suggesting that SM also enhances nucleo-cytoplasmic mRNA transport. The degree of transactivation by SM was dependent on the sequence of the 3'-untranslated region of the target mRNA. Finally, we demonstrate that the amino-terminal portion of SM fused to glutathione-S-transferase binds radioactively labeled RNA in vitro, indicating that SM is a single-stranded RNA binding protein. Importantly, the latent and immediate-early genes of EBV contain introns whereas many early and late genes do not. Thus, SM may down-regulate synthesis of host cell proteins and latent EBV proteins while simultaneously enhancing expression of specific lytic EBV genes by binding to mRNA and modulating its stability and transport.

Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

PubMed Central

Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

2016-01-01

Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced stages of Parkinson’s disease. PMID:27776130

Early Life Stress Differentially Modulates Distinct Forms of Brain Plasticity in Young and Adult Mice

PubMed Central

Reichardt, Wilfried; Clark, Kristin; Geiger, Julia; Gross, Claus M.; Heyer, Andrea; Neagu, Valentin; Bhatia, Harsharan; Atas, Hasan C.; Fiebich, Bernd L.; Bischofberger, Josef; Haas, Carola A.; Normann, Claus

2012-01-01

Background Early life trauma is an important risk factor for many psychiatric and somatic disorders in adulthood. As a growing body of evidence suggests that brain plasticity is disturbed in affective disorders, we examined the short-term and remote effects of early life stress on different forms of brain plasticity. Methodology/Principal Findings Mice were subjected to early deprivation by individually separating pups from their dam in the first two weeks after birth. Distinct forms of brain plasticity were assessed in the hippocampus by longitudinal MR volumetry, immunohistochemistry of neurogenesis, and whole-cell patch-clamp measurements of synaptic plasticity. Depression-related behavior was assessed by the forced swimming test in adult animals. Neuropeptides and their receptors were determined by real-time PCR and immunoassay. Early maternal deprivation caused a loss of hippocampal volume, which returned to normal in adulthood. Adult neurogenesis was unaffected by early life stress. Long-term synaptic potentiation, however, was normal immediately after the end of the stress protocol but was impaired in adult animals. In the forced swimming test, adult animals that had been subjected to early life stress showed increased immobility time. Levels of substance P were increased both in young and adult animals after early deprivation. Conclusion Hippocampal volume was affected by early life stress but recovered in adulthood which corresponded to normal adult neurogenesis. Synaptic plasticity, however, exhibited a delayed impairment. The modulation of synaptic plasticity by early life stress might contribute to affective dysfunction in adulthood. PMID:23071534

xCT expression reduces the early cell cycle requirement for calcium signaling

PubMed Central

Lastro, Michele; Kourtidis, Antonis; Farley, Kate; Conklin, Douglas S.

2009-01-01

Calcium has long been recognized as an important regulator of cell cycle transitions although the mechanisms are largely unknown. A functional genomic screen has identified genes involved in the regulation of early cell cycle progression by calcium. These genes when overexpressed confer the ability to bypass the G1/S arrest induced by Ca2+- channel antagonists in mouse fibroblasts. Overexpression of the cystine-glutamate exchanger, xCT, had the greatest ability to evade calcium antagonist-induced cell cycle arrest. xCT carries out the rate limiting step of glutathione synthesis in many cell types and is responsible for the uptake of cystine in most human cancer cell lines. Functional analysis indicates that the cystine uptake activity of xCT overcomes the G1/S arrest induced by Ca2+- channel antagonists by bypassing the requirement for calcium signaling. Since cells overexpressing xCT were found to have increased levels and activity of the AP-1 transcription factor in G1, redox stimulation of AP-1 activity accounts for the observed growth of these cells in the presence of calcium channel antagonists. These results suggest that reduced calcium signaling impairs AP-1 activation and that xCT expression may directly affect cell proliferation. PMID:18054200

Reward, motivation, and emotion systems associated with early-stage intense romantic love.

PubMed

Aron, Arthur; Fisher, Helen; Mashek, Debra J; Strong, Greg; Li, Haifang; Brown, Lucy L

2005-07-01

Early-stage romantic love can induce euphoria, is a cross-cultural phenomenon, and is possibly a developed form of a mammalian drive to pursue preferred mates. It has an important influence on social behaviors that have reproductive and genetic consequences. To determine which reward and motivation systems may be involved, we used functional magnetic resonance imaging and studied 10 women and 7 men who were intensely "in love" from 1 to 17 mo. Participants alternately viewed a photograph of their beloved and a photograph of a familiar individual, interspersed with a distraction-attention task. Group activation specific to the beloved under the two control conditions occurred in dopamine-rich areas associated with mammalian reward and motivation, namely the right ventral tegmental area and the right postero-dorsal body and medial caudate nucleus. Activation in the left ventral tegmental area was correlated with facial attractiveness scores. Activation in the right anteromedial caudate was correlated with questionnaire scores that quantified intensity of romantic passion. In the left insula-putamen-globus pallidus, activation correlated with trait affect intensity. The results suggest that romantic love uses subcortical reward and motivation systems to focus on a specific individual, that limbic cortical regions process individual emotion factors, and that there is localization heterogeneity for reward functions in the human brain.

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Asthma-Related Immune Responses in Youth With Asthma: Associations With Maternal Responsiveness and Expressions of Positive and Negative Affect in Daily Life.

PubMed

Tobin, Erin T; Kane, Heidi S; Saleh, Daniel J; Wildman, Derek E; Breen, Elizabeth Crabb; Secord, Elizabeth; Slatcher, Richard B

2015-10-01

Stressful family environments early in life have negative effects on physical health. However, less is known about the health effects of positive aspects of families. We examined the associations between maternal responsiveness and immune markers among youth with asthma and identified youth expressions of positive affect as a potential mechanism of these associations. Forty-three youths with asthma (26 boys; aged 10-17 years) wore the Electronically Activated Recorder for 4 days to assess maternal responsiveness and youth expressions of affect from audio-recordings of daily life. Trained coders rated Electronically Activated Recorder sound files for expressions of maternal responsiveness and affect displayed by the youth. Peripheral blood mononuclear cells were isolated, cultured, and assayed to determine stimulated levels of interleukin (IL)-5, IL-13, and interferon-γ. Greater maternal responsiveness was associated with decreased stimulated production of IL-5 (r = -0.38, p = .012) and IL-13 (r = -0.33, p = .031). Greater total positive affect in youth was linked to decreased stimulated production of IL-5 (r = -0.46, p = .002) and IL-13 (r = -0.37, p = .014). Total negative affect among youth was unrelated to immune responses. There was a significant indirect effect of maternal responsiveness via positive affect in youth on lower levels of IL-5 (95% confidence interval = -3.41 to -0.03) and IL-13 (95% confidence interval = -2.34 to -0.01) when adjusting for caregiver-youth conflict and negative affect among youth. These results indicate the importance of positive family interactions for youth and provide preliminary evidence for a mechanism through which parenting can influence immune responses in youth with asthma.

Effects of parkinsonism on health status in welding exposed workers.

PubMed

Harris, Rachel C; Lundin, Jessica I; Criswell, Susan R; Hobson, Angela; Swisher, Laura M; Evanoff, Bradley A; Checkoway, Harvey; Racette, Brad A

2011-11-01

Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was ≥15. All subjects completed a Parkinson's disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL's). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of Parkinsonism on Health Status in Welding Exposed Workers

PubMed Central

Harris, Rachel C.; Lundin, Jessica I.; Criswell, Susan R.; Hobson, Angela; Swisher, Laura M.; Evanoff, Bradley A.; Checkoway, Harvey; Racette, Brad A.

2011-01-01

Background Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Methods Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was >15. All subjects completed a Parkinson’s disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. Results Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL’s). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. Conclusion Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD. PMID:21724446

Spatiotemporal differentiation in auditory and motor regions during auditory phoneme discrimination.

PubMed

Aerts, Annelies; Strobbe, Gregor; van Mierlo, Pieter; Hartsuiker, Robert J; Corthals, Paul; Santens, Patrick; De Letter, Miet

2017-06-01

Auditory phoneme discrimination (APD) is supported by both auditory and motor regions through a sensorimotor interface embedded in a fronto-temporo-parietal cortical network. However, the specific spatiotemporal organization of this network during APD with respect to different types of phonemic contrasts is still unclear. Here, we use source reconstruction, applied to event-related potentials in a group of 47 participants, to uncover a potential spatiotemporal differentiation in these brain regions during a passive and active APD task with respect to place of articulation (PoA), voicing and manner of articulation (MoA). Results demonstrate that in an early stage (50-110 ms), auditory, motor and sensorimotor regions elicit more activation during the passive and active APD task with MoA and active APD task with voicing compared to PoA. In a later stage (130-175 ms), the same auditory and motor regions elicit more activation during the APD task with PoA compared to MoA and voicing, yet only in the active condition, implying important timing differences. Degree of attention influences a frontal network during the APD task with PoA, whereas auditory regions are more affected during the APD task with MoA and voicing. Based on these findings, it can be carefully suggested that APD is supported by the integration of early activation of auditory-acoustic properties in superior temporal regions, more perpetuated for MoA and voicing, and later auditory-to-motor integration in sensorimotor areas, more perpetuated for PoA.

Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

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

Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan

2015-06-10

As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellularmore » energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress.« less

PGC-1α, A Potential Therapeutic Target for Early Intervention in Parkinson’s Disease

PubMed Central

Zheng, Bin; Liao, Zhixiang; Locascio, Joseph J.; Lesniak, Kristen A.; Roderick, Sarah S.; Watt, Marla L.; Eklund, Aron C.; Zhang-James, Yanli; Kim, Peter D.; Hauser, Michael A.; Grünblatt, Edna; Moran, Linda B.; Mandel, Silvia A.; Riederer, Peter; Miller, Renee M.; Federoff, Howard J.; Wüllner, Ullrich; Papapetropoulos, Spyridon; Youdim, Moussa B.; Cantuti-Castelvetri, Ippolita; Young, Anne B.; Vance, Jeffery M.; Davis, Richard L.; Hedreen, John C.; Adler, Charles H.; Beach, Thomas G.; Graeber, Manuel B.; Middleton, Frank A.; Rochet, Jean-Christophe; Scherzer, Clemens R.

2011-01-01

Parkinson’s disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson’s and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and substantia nigra transcriptomes, followed by two-stage replication on three platforms. We found 10 gene sets with previously unknown associations with Parkinson’s disease. These gene sets pinpoint defects in mitochondrial electron transport, glucose utilization, and glucose sensing and reveal that they occur early in disease pathogenesis. Genes controlling cellular bioenergetics that are expressed in response to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) are underexpressed in Parkinson’s disease patients. Activation of PGC-1α results in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain and blocks the dopaminergic neuron loss induced by mutant α-synuclein or the pesticide rotenone in cellular disease models. Our systems biology analysis of Parkinson’s disease identifies PGC-1α as a potential therapeutic target for early intervention. PMID:20926834

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson’s Disease: A Critical Review

PubMed Central

Nair, Arun T; Ramachandran, Vadivelan; Joghee, Nanjan M; Antony, Shanish; Ramalingam, Gopalakrishnan

2018-01-01

Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson’s disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson’s disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson’s disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson’s disease patients. PMID:29291606

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

PubMed Central

Müller, Sören; Agnihotri, Sameer; Shoger, Karsen E.; Myers, Max I.; Chaparala, Srilakshmi; Villanueva, Clarence R.; Chattopadhyay, Ansuman; Butterfield, Lisa H.; Okada, Hideho; Pollack, Ian F.

2018-01-01

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns. PMID:29618666

Cortisol modifies extinction learning of recently acquired fear in men

PubMed Central

Hermann, Andrea; Stark, Rudolf; Wolf, Oliver Tobias

2014-01-01

Exposure therapy builds on the mechanism of fear extinction leading to decreased fear responses. How the stress hormone cortisol affects brain regions involved in fear extinction in humans is unknown. For this reason, we tested 32 men randomly assigned to receive either 30 mg hydrocortisone or placebo 45 min before fear extinction. In fear acquisition, a picture of a geometrical figure was either partially paired (conditioned stimulus; CS+) or not paired (CS−) with an electrical stimulation (unconditioned stimulus; UCS). In fear extinction, each CS was presented again, but no UCS occurred. Cortisol increased conditioned skin conductance responses in early and late extinction. In early extinction, higher activation towards the CS− than to the CS+ was found in the amygdala, hippocampus and posterior parahippocampal gyrus. This pattern might be associated with the establishment of a new memory trace. In late extinction, the placebo compared with the cortisol group displayed enhanced CS+/CS− differentiation in the amygdala, medial frontal cortex and nucleus accumbens. A change from early deactivation to late activation of the extinction circuit as seen in the placebo group seems to be needed to enhance extinction and to reduce fear. Cortisol appears to interfere with this process thereby impairing extinction of recently acquired conditioned fear. PMID:23945999

Selective early-acquired fear memories undergo temporary suppression during adolescence

PubMed Central

Pattwell, Siobhan S.; Bath, Kevin G.; Casey, B. J.; Ninan, Ipe; Lee, Francis S.

2011-01-01

Highly conserved neural circuitry between rodents and humans has allowed for in-depth characterization of behavioral and molecular processes associated with emotional learning and memory. Despite increased prevalence of affective disorders in adolescent humans, few studies have characterized how associative-emotional learning changes during the transition through adolescence or identified mechanisms underlying such changes. By examining fear conditioning in mice, as they transitioned into and out of adolescence, we found that a suppression of contextual fear occurs during adolescence. Although contextual fear memories were not expressed during early adolescence, they could be retrieved and expressed as the mice transitioned out of adolescence. This temporary suppression of contextual fear was associated with blunted synaptic activity in the basal amygdala and decreased PI3K and MAPK signaling in the hippocampus. These findings reveal a unique form of brain plasticity in fear learning during early adolescence and may prove informative for understanding endogenous mechanisms to suppress unwanted fear memories. PMID:21220344

Atherogenicity index and health-related fatty acids in different stages of lactation from Friesian, Jersey and Friesian×Jersey cross cow milk under a pasture-based dairy system.

PubMed

Nantapo, C T W; Muchenje, V; Hugo, A

2014-03-01

The objective of the study was to investigate the effect of stage of lactation on the fatty acid profiles of milk from Friesian, Jersey and Friesian×Jersey cows. Linoleic acid in pastures was highest in the second phase which coincided with mid-lactation days (p<0.05). Highest milk moisture content and lowest fat free dry matter content was seen in early lactation (p<0.05). Higher fat content was observed in late lactation than early lactation. Highest butyric, caproic, linoleic, omega-6 and polyunsaturated fatty acids were observed for milk from Friesian cows. Highest conjugated fatty acids, α-linolenic acid, linoleic acid, saturated fatty acids, polyunsaturated fatty acids, omega-6, and omega-3 were observed in early lactation. Atherogenicity index and desaturase activity indices were highest in late lactation. In conclusion, stage of lactation and genotype affected milk health-related fatty acid profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sociophysiology 25 years ago: early perspectives of an emerging discipline now part of social neuroscience.

PubMed

Barchas, Patricia R; Barchas, Jack D

2011-08-01

Sociophysiology was a term used early in the history of sociology and then again 25 years ago to describe interactions between the "social" and the "biological" worlds. Social scientists had largely viewed biology and the brain as a "black box" that was not an active aspect of their work or theories. A landmark, unpublished conference in 1986 brought together social scientists and biologists dedicated to the idea that bringing sociological conceptualizations and approaches together with those of physiology might create new ways to understand human behavior. The umbrella question for sociophysiology was dual: how do social processes impact the physiology of the organism, and how does that altered physiology affect future social behavior? This paper summarizes that conference with the goal of providing a glimpse into the early history of social neuroscience and to demonstrate the variety of individuals and interests that were present at the emergence of this new field. The late Patricia R. Barchas organized and chaired the conference. © 2011 New York Academy of Sciences.

Motor development and motor resonance difficulties in autism: relevance to early intervention for language and communication skills

PubMed Central

McCleery, Joseph P.; Elliott, Natasha A.; Sampanis, Dimitrios S.; Stefanidou, Chrysi A.

2013-01-01

Research suggests that a sub-set of children with autism experience notable difficulties and delays in motor skills development, and that a large percentage of children with autism experience deficits in motor resonance. These motor-related deficiencies, which evidence suggests are present from a very early age, are likely to negatively affect social-communicative and language development in this population. Here, we review evidence for delayed, impaired, and atypical motor development in infants and children with autism. We then carefully review and examine the current language and communication-based intervention research that is relevant to motor and motor resonance (i.e., neural “mirroring” mechanisms activated when we observe the actions of others) deficits in children with autism. Finally, we describe research needs and future directions and developments for early interventions aimed at addressing the speech/language and social-communication development difficulties in autism from a motor-related perspective. PMID:23630476

Envelopments: immersion in and emergence from drug misuse.

PubMed

Weegmann, Martin; Khantzian, Edward J

2011-01-01

Contemporary psychodynamic therapists, as contrasted with early ones, are more active and interactive, less dependent on interpretations, and more focused on affects, self-regulation, and interpersonal relations, with a premium placed on the therapeutic alliance. Evidence supports the utility and effectiveness of the psychodynamic paradigm. Two cases are presented that demonstrate how a well-trained psychodynamic therapist is able to effectively apply such an approach to individuals with substance use disorders, in one instance a client in early treatment still immersed in her addictions, and, in the second case a client in early abstinence emerging from a long standing dependency on alcohol and cocaine. The case material highlights the special sensitivities and practices required to address predisposing factors and resulting consequences associated with addictive disorders. Reflections by the therapist and the clients provide a basis to consider the nature of the clients' addictive involvements, a rationale for the therapist's interventions, and how client vulnerabilities are addressed in their attempts to recover from their addictions.

Seeing race: N170 responses to race and their relation to automatic racial attitudes and controlled processing.

PubMed

Ofan, Renana H; Rubin, Nava; Amodio, David M

2011-10-01

We examined the relation between neural activity reflecting early face perception processes and automatic and controlled responses to race. Participants completed a sequential evaluative priming task, in which two-tone images of Black faces, White faces, and cars appeared as primes, followed by target words categorized as pleasant or unpleasant, while encephalography was recorded. Half of these participants were alerted that the task assessed racial prejudice and could reveal their personal bias ("alerted" condition). To assess face perception processes, the N170 component of the ERP was examined. For all participants, stronger automatic pro-White bias was associated with larger N170 amplitudes to Black than White faces. For participants in the alerted condition only, larger N170 amplitudes to Black versus White faces were also associated with less controlled processing on the word categorization task. These findings suggest that preexisting racial attitudes affect early face processing and that situational factors moderate the link between early face processing and behavior.

Origin of the terrestrial planets and the moon.

PubMed

Taylor, S R

1996-03-01

Our ideas about the origin and evolution of the solar system have advanced significantly as a result of the past 25 years of space exploration. Metal-sulfide-silicate partitioning seems to have been present in the early dust components of the solar nebula, prior to chondrule formation. The inner solar nebula was depleted in volatile elements by early solar activity. The early formation of the gas giant, Jupiter, affected the subsequent development of inner solar system and is responsible for the existence of the asteroid belt, and the small size of Mars. The Earth and the other terrestrial planets accreted in a gas-free environment, mostly from volatile-depleted planetesimals which were already differentiated into metallic cores and silicate mantles. The origin of the Moon by a single massive impact with a body larger than Mars explains the angular momentum, orbital characteristics and unique nature of the Earth-Moon system. The density and chemical differences between the Earth and Moon are accounted for by deriving the Moon from the mantle of the impactor.

The role of affective evaluation in conflict adaptation: An LRP study.

PubMed

Fröber, Kerstin; Stürmer, Birgit; Frömer, Romy; Dreisbach, Gesine

2017-08-01

Conflict between incompatible response tendencies is typically followed by control adjustments aimed at diminishing subsequent conflicts, a phenomenon often called conflict adaptation. Dreisbach and Fischer (2015, 2016) recently proposed that it is not the conflict per se but the aversive quality of a conflict that originally motivates this kind of sequential control adjustment. With the present study we tested the causal role of aversive signals in conflict adaptation in a more direct way. To this end, after each trial of a vertical Simon task participants rated whether they experienced the last trial as rather pleasant or unpleasant. Conflict adaptation was measured via lateralized readiness potentials as a measure of early motor-related activation that were computed on the basis of event-related brain potentials. Results showed the typical suppression of automatic response activation following trials rated as unpleasant, whereas suppression was relaxed following trials rated as pleasant. That is, sequential control adaptation was not based on previous conflict but on the subjective affective experience. This is taken as evidence that negative affect even in the absence of actual conflict triggers subsequent control adjustments. Copyright © 2017 Elsevier Inc. All rights reserved.

[Motor function evaluation in merosin-deficient congenital muscular dystrophy children].

PubMed

Rocco, Fernanda M; Luz, Fernanda H Gianini; Rossato, Alexsander Junquera; Fernandes, Antônio Carlos; Oliveira, Acary S B; Betetas, Javier Toledano; Zanoteli, Edmar

2005-06-01

Congenital muscular dystrophy (CMD) is a heterogeneous group of disorders characterized by early onset of hypotonia and weakness. Almost 50% of the cases are caused by primary deficiency of a protein named merosin (MD), and present a homogenous phenotype with a severe motor and respiratory involvement. Eleven children with clinical and histological diagnosis of CMD-MD, aged of 3 to 15 years, were studied using the manual muscle testing (Medical Research Council), goniometric analysis, motor ability and day life activities (Barthel index) scales, with the objective to characterize the main motor function limitations. The muscular groups most affected were cervical flexors, paravertebral and proximal portions of limbs. The muscular groups of upper limbs were as affected as the lower limbs, and the extensors were more affected than the flexors groups. All children had severe muscular retractions on the hip, knee and elbow. Other frequent deformities were scoliosis and equinus-varum feet. No children presented the motor ability to walk, stand up and crawl; and all of them were classified as dependents or semi-dependents in the day life activities scale. Our findings confirm the severe and diffuse involvement of skeletal muscle in CMD-MD patients, producing serious motor limitations and deformities.

Contextual Variability in Personality From Significant–Other Knowledge and Relational Selves

PubMed Central

Andersen, Susan M.; Tuskeviciute, Rugile; Przybylinski, Elizabeth; Ahn, Janet N.; Xu, Joy H.

2016-01-01

We argue that the self is intrinsically embedded in an interpersonal context such that it varies in IF–THEN terms, as the relational self. We have demonstrated that representations of the significant other and the relationship with that other are automatically activated by situational cues and that this activation affects both experienced and expressed aspects of the self and personality. Here, we expand on developments of the IF–THEN cognitive-affective framework of personality system (Mischel and Shoda, 1995), by extending it to the domain of interpersonal relationships at the dyadic level (Andersen and Chen, 2002). Going beyond Mischel’s early research (Mischel, 1968), our framework combines social cognition and learning theory with a learning-based psychodynamic approach, which provides the basis for extensive research on the social-cognitive process of transference and the relational self as it arises in everyday social interactions (Andersen and Cole, 1990), evidence from which contributes to a modern conceptualization of personality that emphasizes the centrality of the situation. PMID:26779051

Contextual Variability in Personality From Significant-Other Knowledge and Relational Selves.

PubMed

Andersen, Susan M; Tuskeviciute, Rugile; Przybylinski, Elizabeth; Ahn, Janet N; Xu, Joy H

2015-01-01

We argue that the self is intrinsically embedded in an interpersonal context such that it varies in IF-THEN terms, as the relational self. We have demonstrated that representations of the significant other and the relationship with that other are automatically activated by situational cues and that this activation affects both experienced and expressed aspects of the self and personality. Here, we expand on developments of the IF-THEN cognitive-affective framework of personality system (Mischel and Shoda, 1995), by extending it to the domain of interpersonal relationships at the dyadic level (Andersen and Chen, 2002). Going beyond Mischel's early research (Mischel, 1968), our framework combines social cognition and learning theory with a learning-based psychodynamic approach, which provides the basis for extensive research on the social-cognitive process of transference and the relational self as it arises in everyday social interactions (Andersen and Cole, 1990), evidence from which contributes to a modern conceptualization of personality that emphasizes the centrality of the situation.

Effects of decomposition on gunshot wound characteristics: under moderate temperatures with insect activity.

PubMed

MacAulay, Lauren E; Barr, Darryl G; Strongman, Doug B

2009-03-01

Previous studies document characteristics of gunshot wounds shortly after they were inflicted. This study was conducted to determine if the early stages of decomposition obscure or alter the physical surface characteristics of gunshot wounds, thereby affecting the quantity and quality of information retrievable from such evidence. The study was conducted in August and September, 2005 in Nova Scotia, Canada in forested and exposed environments. Recently killed pigs were used as research models and were shot six times each at three different ranges (contact, 2.5 cm, and 1.5 m). Under these test conditions, the gunshot wounds maintained the characteristics unique to each gunshot range and changes that occurred during decomposition were not critical to the interpretation of the evidence. It was concluded that changes due to decomposition under the conditions tested would not affect the collection and interpretation of gunshot wound evidence until the skin was degraded in the late active or advanced decay stage of decomposition.

How has early testicular cancer affected your life? A study of sexual function in men attending active surveillance for stage one testicular cancer.

PubMed

Brand, Sue; Williams, Hilary; Braybrooke, Jeremy

2015-06-01

Testicular cancer is the most common cancer in young men, it is frequently diagnosed at key times in relationship formation. In early stage disease the vast majority of tumours will be cured by surgery alone with patients being offered active surveillance rather than adjuvant therapies. To date, research has not evaluated how surveillance alone impacts on sexual function. The aim of this quantitative longitudinal study was to ascertain the sexual function of men with stage one disease at 3 and 12 months post diagnosis and to compare with normative data. Additional data was collected on the information men sought regarding sexual function and media they used to access this. This study shows that men's sexual function is altered at diagnosis and improves by 3 months. At 12 months, whilst not statistically significant, sexual function improves but not to the same level as normative data comparison. Men appear to find verbal information useful at 3 months, however men appear to be seeking written and online information at 12 months. The intricacies of sexual function together with the low number of participants may have been best met with a qualitative approach. However, the information data indicates the importance of further research into the effects of early stage testicular cancer on sexual function. Therefore, further qualitative research is recommended to explore the effects of early stage testicular cancer in relation to sexual function. Copyright © 2014 Elsevier Ltd. All rights reserved.

Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice.

PubMed

Valerio, Daria G; Xu, Haiming; Eisold, Meghan E; Woolthuis, Carolien M; Pandita, Tej K; Armstrong, Scott A

2017-01-05

K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre-induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage-specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. © 2017 by The American Society of Hematology.

Identifying the Target Cell in Primary Simian Immunodeficiency Virus (SIV) Infection: Highly Activated Memory CD4+ T Cells Are Rapidly Eliminated in Early SIV Infection In Vivo

PubMed Central

Veazey, Ronald S.; Tham, Irene C.; Mansfield, Keith G.; DeMaria, MaryAnn; Forand, Amy E.; Shvetz, Daniel E.; Chalifoux, Laura V.; Sehgal, Prabhat K.; Lackner, Andrew A.

2000-01-01

It has recently been shown that rapid and profound CD4+ T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodeficiency virus (SIV)-infected macaques within days of infection. Here we demonstrate (by three- and four-color flow cytometry) that this depletion is specific to a definable subset of CD4+ T cells, namely, those having both a highly and/or acutely activated (CD69+ CD38+ HLA-DR+) and memory (CD45RA− Leu8−) phenotype. Moreover, we demonstrate that this subset of helper T cells is found primarily within the intestinal lamina propria. Viral tropism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4+ T-cell depletion occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this specific subset of activated memory CD4+ T cells may also be detected in peripheral blood and lymph nodes in early SIV infection. However, since this particular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4+ T cell counts. This finding suggests that SIV and, presumably, human immunodeficiency virus specifically infect, replicate in, and eliminate definable subsets of CD4+ T cells in vivo. PMID:10590091

Event-related potentials reveal preserved attention allocation but impaired emotion regulation in patients with epilepsy and comorbid negative affect.

PubMed

De Taeye, Leen; Pourtois, Gilles; Meurs, Alfred; Boon, Paul; Vonck, Kristl; Carrette, Evelien; Raedt, Robrecht

2015-01-01

Patients with epilepsy have a high prevalence of comorbid mood disorders. This study aims to evaluate whether negative affect in epilepsy is associated with dysfunction of emotion regulation. Event-related potentials (ERPs) are used in order to unravel the exact electrophysiological time course and investigate whether a possible dysfunction arises during early (attention) and/or late (regulation) stages of emotion control. Fifty epileptic patients with (n = 25) versus without (n = 25) comorbid negative affect plus twenty-five matched controls were recruited. ERPs were recorded while subjects performed a face- or house-matching task in which fearful, sad or neutral faces were presented either at attended or unattended spatial locations. Two ERP components were analyzed: the early vertex positive potential (VPP) which is normally enhanced for faces, and the late positive potential (LPP) that is typically larger for emotional stimuli. All participants had larger amplitude of the early face-sensitive VPP for attended faces compared to houses, regardless of their emotional content. By contrast, in patients with negative affect only, the amplitude of the LPP was significantly increased for unattended negative emotional expressions. These VPP results indicate that epilepsy with or without negative affect does not interfere with the early structural encoding and attention selection of faces. However, the LPP results suggest abnormal regulation processes during the processing of unattended emotional faces in patients with epilepsy and comorbid negative affect. In conclusion, this ERP study reveals that early object-based attention processes are not compromised by epilepsy, but instead, when combined with negative affect, this neurological disease is associated with dysfunction during the later stages of emotion regulation. As such, these new neurophysiological findings shed light on the complex interplay of epilepsy with negative affect during the processing of emotional visual stimuli and in turn might help to better understand the etiology and maintenance of mood disorders in epilepsy.

The Relationship Between Early Life Events, Parental Attachment, and Psychopathic Tendencies in Adolescent Detainees.

PubMed

Christian, Erica J; Meltzer, Christine L; Thede, Linda L; Kosson, David S

2017-04-01

Despite increasing interest in understanding psychopathic traits in youth, the role of early environmental factors in the development of psychopathic traits is not well understood. No prior studies have directly examined the relationship between early life events and psychopathic traits. We examined links between life events in the first 4 years of life and indices of the core affective and interpersonal components of psychopathy. Additionally, we examined relationships between early life events, psychopathic traits, and attachment to parents among 206 adjudicated adolescents. Results indicated that the total number of early life events was positively correlated with indices of the affective component of psychopathy. Moreover, psychopathic traits moderated the relationship between the number of early life events and later reports of attachment to parents. Findings suggest that early environmental factors could have important implications for the development of psychopathic traits and may impact attachment to parents for youth with psychopathic traits.

Activation of Protease Activated Receptor 2 by Exogenous Agonist Exacerbates Early Radiation Injury in Rat Intestine

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

Wang Junru; Boerma, Marjan; Kulkarni, Ashwini

2010-07-15

Purpose: Protease-activated receptor-2 (PAR{sub 2}) is highly expressed throughout the gut and regulates the inflammatory, mitogenic, fibroproliferative, and nociceptive responses to injury. PAR{sub 2} is strikingly upregulated and exhibits increased activation in response to intestinal irradiation. We examined the mechanistic significance of radiation enteropathy development by assessing the effect of exogenous PAR{sub 2} activation. Methods and Materials: Rat small bowel was exposed to localized single-dose radiation (16.5 Gy). The PAR{sub 2} agonist (2-furoyl-LIGRLO-NH{sub 2}) or vehicle was injected intraperitoneally daily for 3 days before irradiation (before), for 7 days after irradiation (after), or both 3 days before and 7 daysmore » after irradiation (before-after). Early and delayed radiation enteropathy was assessed at 2 and 26 weeks after irradiation using quantitative histologic examination, morphometry, and immunohistochemical analysis. Results: The PAR{sub 2} agonist did not elicit changes in the unirradiated (shielded) intestine. In contrast, in the irradiated intestine procured 2 weeks after irradiation, administration of the PAR{sub 2} agonist was associated with more severe mucosal injury and increased intestinal wall thickness in all three treatment groups (p <.05) compared with the vehicle-treated controls. The PAR{sub 2} agonist also exacerbated the radiation injury score, serosal thickening, and mucosal inflammation (p <.05) in the before and before-after groups. The short-term exogenous activation of PAR{sub 2} did not affect radiation-induced intestinal injury at 26 weeks. Conclusion: The results of the present study support a role for PAR{sub 2} activation in the pathogenesis of early radiation-induced intestinal injury. Pharmacologic PAR{sub 2} antagonists might have the potential to reduce the intestinal side effects of radiotherapy and/or as countermeasures in radiologic accidents or terrorism scenarios.« less

Activation of the Early B-Cell-Specific mb-1 (Ig-α) Gene by Pax-5 Is Dependent on an Unmethylated Ets Binding Site

PubMed Central

Maier, Holly; Colbert, Jeff; Fitzsimmons, Daniel; Clark, Dawn R.; Hagman, James

2003-01-01

Methylation of cytosine in CpG dinucleotides promotes transcriptional repression in mammals by blocking transcription factor binding and recruiting methyl-binding proteins that initiate chromatin remodeling. Here, we use a novel cell-based system to show that retrovirally expressed Pax-5 protein activates endogenous early B-cell-specific mb-1 genes in plasmacytoma cells, but only when the promoter is hypomethylated. CpG methylation does not directly affect binding of the promoter by Pax-5. Instead, methylation of an adjacent CpG interferes with assembly of ternary complexes comprising Pax-5 and Ets proteins. In electrophoretic mobility shift assays, recruitment of Ets-1 is blocked by methylation of the Ets site (5′CCGGAG) on the antisense strand. In transfection assays, selective methylation of a single CpG within the Pax-5-dependent Ets site greatly reduces mb-1 promoter activity. Prior demethylation of the endogenous mb-1 promoter is required for its activation by Pax-5 in transduced cells. Although B-lineage cells have only unmethylated mb-1 genes and do not modulate methylation of the mb-1 promoter during development, other tissues feature high percentages of methylated alleles. Together, these studies demonstrate a novel DNA methylation-dependent mechanism for regulating transcriptional activity through the inhibition of DNA-dependent protein-protein interactions. PMID:12612069

Radiologic Changes by Early Motion in Neck Fractures of the Fifth Metacarpal Treated with Antegrade Intramedullary Fixation.

PubMed

Heo, Youn Moo; Kim, Sang Bum; Yi, Jin Woong; Kim, Tae Gyun; Lim, Byoung Gu

2016-02-01

As intramedullary (IM) fixation is one of the fixation methods used in neck fractures of the fifth metacarpal, an early motion of injured finger can be allowed. The purpose of this study is to evaluate whether immediate active motion affects the stability of antegrade IM fixation in surgical treatment of neck fractures of the fifth metacarpal bone and to assess related factors. Thirty one patients treated by closed reduction and antegrade IM fixation were consecutively enrolled. All patients started active motion of the little finger since 7 postoperative days and only daily activities including writing, typing or washing were allowed until the union of fracture. All fractures were healed within four to eight weeks. The changes of angulation, fifth metacarpal length and tip to head distance of K-wire were compared between immediate postoperative radiographs and radiographs at eight weeks. In addition, the effects by age, gender, initial angulation and comminution of the metacarpal neck were assessed. The average change of angulation was 0.12°, 5th metacarpal length was 1.49mm and tip to head distance of K-wire was 1.31mm. There was no significant difference in the change of angulation (p = 0.137). But, there were significant differences in the change of 5th metacarpal length and tip to head distance of K-wire ([Formula: see text]). The change of angulation was related to a comminution of the metacarpal neck and that of 5th metacarpal length was related to age and sex. The change of 5th metacarpal length and tip to head distance of K-wire can occur by an early mobilization in the antegrade IM fixation for neck fractures of the fifth metacarpal. However, we thought that an early active motion after surgery is important to increase the patients' satisfaction, even though careful selection of candidates is necessary.

Function of the two Xenopus smad4s in early frog development.

PubMed

Chang, Chenbei; Brivanlou, Ali H; Harland, Richard M

2006-10-13

Signals from the transforming growth factor beta family members are transmitted in the cell through specific receptor-activated Smads and a common partner Smad4. Two Smad4 genes (alpha and beta/10, or smad4 and smad4.2) have been isolated from Xenopus, and conflicting data are reported for Smad4beta/10 actions in mesodermal and neural induction. To further understand the functions of the Smad4s in early frog development, we analyzed their activities in detail. We report that Smad10 is a mutant form of Smad4beta that harbors a missense mutation of a conserved arginine to histidine in the MH1 domain. The mutation results in enhanced association of Smad10 with the nuclear transcription corepressor Ski and leads to its neural inducing activity through inhibition of bone morphogenetic protein (BMP) signaling. In contrast to Smad10, both Smad4alpha and Smad4beta enhanced BMP signals in ectodermal explants. Using antisense morpholino oligonucleotides (MOs) to knockdown endogenous Smad4 protein levels, we discovered that Smad4beta was required for both activin- and BMP-mediated mesodermal induction in animal caps, whereas Smad4alpha affected only the BMP signals. Neither Smad4 was involved directly in neural induction. Expression of Smad4beta-MO in early frog embryos resulted in reduction of mesodermal markers and defects in axial structures, which were rescued by either Smad4alpha or Smad4beta. Smad4alpha-MO induced only minor deficiency at late stages. As Smad4beta, but not Smad4alpha, is expressed at high levels maternally and during early gastrulation, our data suggest that although Smad4alpha and Smad4beta may have similar activities, they are differentially utilized during frog embryogenesis, with only Smad4beta being essential for mesoderm induction.

Brain responses to food images during the early and late follicular phase of the menstrual cycle in healthy young women: relation to fasting and feeding1234

PubMed Central

Ziemke, Florencia; Magkos, Faidon; Barrios, Fernando A; Brinkoetter, Mary; Boyd, Ingrid; Rifkin-Graboi, Anne; Yannakoulia, Mary; Rojas, Rafael; Pascual-Leone, Alvaro; Mantzoros, Christos S

2011-01-01

Background: Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown. Objective: The objective was to examine whether brain activation during food visualization is affected by changes in estradiol concentration in the fasted and fed conditions. Design: Nine eumenorrheic, lean young women [mean (±SD) age: 26.2 ± 3.2 y; body mass index (in kg/m2): 22.4 ± 1.2] completed 2 visits, one in the early (low estradiol) and one in the late (high estradiol) follicular phase of their menstrual cycle. At each visit, subjects underwent functional magnetic resonance imaging while they viewed food and nonfood images, before and after a standardized meal. Region-of-interest analysis was used to examine the effect of follicular phase and prandial state on brain activation (food > nonfood contrast) and its association with estradiol concentration. Results: Differences were identified in the inferior frontal and fusiform gyri. In these areas, visualization of food elicited greater activation in the fed state than during fasting but only in the late follicular phase, when estradiol concentration was high. The change in estradiol concentration across the follicular phase (late minus early) was inversely correlated with the change in fusiform gyrus activation in the fasted state but not in the fed state. Conclusion: Our findings suggest that estradiol may reduce food intake by decreasing sensitivity to food cues in the ventral visual pathway under conditions of energy deprivation. This trial was registered at clinicaltrials.gov as NCT00130117. PMID:21593494

How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2006

2006-01-01

Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…

Factors Affecting Early Services for Children Who Are Hard of Hearing

ERIC Educational Resources Information Center

Harrison, Melody; Page, Thomas A.; Oleson, Jacob; Spratford, Meredith; Berry, Lauren Unflat; Peterson, Barbara; Welhaven, Anne; Arenas, Richard M.; Moeller, Mary Pat

2016-01-01

Purpose: To describe factors affecting early intervention (EI) for children who are hard of hearing, we analyzed (a) service setting(s) and the relationship of setting to families' frequency of participation, and (b) provider preparation, caseload composition, and experience in relation to comfort with skills that support spoken language for…

Genetic and environmental factors affecting early rooting of six Populus genomic groups: implications for tree improvement

Treesearch

Ronald S., Jr. Zalesny

2006-01-01

Genetic and environmental factors affect the early rooting of Populus planted as unrooted hardwood cuttings. Populus genotypes of six genomic groups were tested in numerous studies for the quantitative genetics of rooting, along with effects of preplanting treatments and soil temperature. Genetics data (e.g. heritabilities,...

Impact of attention biases to threat and effortful control on individual variations in negative affect and social withdrawal in very young children.

PubMed

Cole, Claire E; Zapp, Daniel J; Fettig, Nicole B; Pérez-Edgar, Koraly

2016-01-01

Early temperamental sensitivity may form the basis for the later development of socioemotional maladjustment. In particular, temperamental negative affect places children at risk for the development of anxiety. However, not all children who show negative affect go on to develop anxiety or extreme social withdrawal. Recent research indicates that reactive control, in the form of attention to threat, may serve as a bridge between early temperament and the development of later social difficulties. In addition, variation in effortful control may also modulate this trajectory. Children (mean age=5.57 years) were assessed for attention bias to threatening and pleasant faces using a dot-probe paradigm. Attention bias to threatening (but not happy) faces moderated the direct positive relation between negative affect and social withdrawal. Children with threat biases showed a significant link between negative affect and social withdrawal, whereas children who avoided threat did not. In contrast, effortful control did not moderate the relation between negative affect and social withdrawal. Rather, there was a direct negative relation between effortful control and social withdrawal. The findings from this short report indicate that the relations among temperament, attention bias, and social withdrawal appears early in life and point to early emerging specificity in reactive and regulatory functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of Affect and Cognition in Processing Messages about Early Diagnosis for Alzheimer’s Disease by Older People

PubMed Central

De Pelsmacker, Patrick; Lewi, Martine; Cauberghe, Veroline

2017-01-01

Through early diagnosis of symptoms, the Alzheimer’s disease process can be decelerated. The main concern is to encourage the population at risk to take responsible actions at the earliest stage of the onset of the disease. Persuasive communication is essential to achieve this. In an experimental study, the evaluation of awareness messages for early diagnosis containing weak and strong arguments and negative and positive images was performed on a sample of older Belgians. The mediating role of affective responses and message thoughts was explored. Strong arguments led to a more positive evaluation of the message than weak arguments directly and indirectly via the positive effect they had on message affect and thoughts, which, in turn, positively affected message evaluation. A negative message image led to a more positive message evaluation than a positive one. This effect was not mediated by either message affect or message thoughts. PMID:28604627

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

PubMed

Baselski, V S; Medina, R A; Parker, C D

1978-11-01

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12.

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

PubMed Central

Baselski, V S; Medina, R A; Parker, C D

1978-01-01

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12. PMID:730364

Effectiveness of an early mobilization protocol in a trauma and burns intensive care unit: a retrospective cohort study.

PubMed

Clark, Diane E; Lowman, John D; Griffin, Russell L; Matthews, Helen M; Reiff, Donald A

2013-02-01

Bed rest and immobility in patients on mechanical ventilation or in an intensive care unit (ICU) have detrimental effects. Studies in medical ICUs show that early mobilization is safe, does not increase costs, and can be associated with decreased ICU and hospital lengths of stay (LOS). The purpose of this study was to assess the effects of an early mobilization protocol on complication rates, ventilator days, and ICU and hospital LOS for patients admitted to a trauma and burn ICU (TBICU). This was a retrospective cohort study of an interdisciplinary quality-improvement program. Pre- and post-early mobility program patient data from the trauma registry for 2,176 patients admitted to the TBICU between May 2008 and April 2010 were compared. No adverse events were reported related to the early mobility program. After adjusting for age and injury severity, there was a decrease in airway, pulmonary, and vascular complications (including pneumonia and deep vein thrombosis) post-early mobility program. Ventilator days and TBICU and hospital lengths of stay were not significantly decreased. Using a historical control group, there was no way to account for other changes in patient care that may have occurred between the 2 periods that could have affected patient outcomes. The dose of physical activity both before and after the early mobility program were not specifically assessed. Early mobilization of patients in a TBICU was safe and effective. Medical, nursing, and physical therapy staff, as well as hospital administrators, have embraced the new culture of early mobilization in the ICU.

Behavioural response to combined insecticide and temperature stress in natural populations of Drosophila melanogaster.

PubMed

Fournier-Level, A; Neumann-Mondlak, A; Good, R T; Green, L M; Schmidt, J M; Robin, C

2016-05-01

Insecticide resistance evolves extremely rapidly, providing an illuminating model for the study of adaptation. With climate change reshaping species distribution, pest and disease vector control needs rethinking to include the effects of environmental variation and insect stress physiology. Here, we assessed how both long-term adaptation of populations to temperature and immediate temperature variation affect the genetic architecture of DDT insecticide response in Drosophila melanogaster. Mortality assays and behavioural assays based on continuous activity monitoring were used to assess the interaction between DDT and temperature on three field-derived populations from climate extremes (Raleigh for warm temperate, Tasmania for cold oceanic and Queensland for hot tropical). The Raleigh population showed the highest mortality to DDT, whereas the Queensland population, epicentre for derived alleles of the resistance gene Cyp6g1, showed the lowest. Interaction between insecticide and temperature strongly affected mortality, particularly for the Tasmanian population. Activity profiles analysed using self-organizing maps show that the insecticide promoted an early response, whereas elevated temperature promoted a later response. These distinctive early or later activity phases revealed similar responses to temperature and DDT dose alone but with more or less genetic variance depending on the population. This change in genetic variance among populations suggests that selection particularly depleted genetic variance for DDT response in the Queensland population. Finally, despite similar (co)variation between traits in benign conditions, the genetic responses across population differed under stressful conditions. This showed how stress-responsive genetic variation only reveals itself in specific conditions and thereby escapes potential trade-offs in benign environments. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Effects of dextromethorphan/quinidine on auditory event-related potentials in multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2009-10-01

The purpose of this study was to characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of laughing and/or crying in patients with multiple sclerosis before and after treatment with dextromethorphan/quinidine (DM/Q). Behavioral responses and event-related potentials (ERPs) in response to subjectively significant and neutral verbal stimuli were recorded from 2 groups: 6 multiple sclerosis patients with PBA before (PBA-preTx) and after (PBA-DM/Q) treatment with DM/Q and 6 healthy control (HC) subjects. Statistical nonparametric mapping comparisons of ERP source current density distributions between groups were conducted for subjectively significant and neutral stimuli separately before and after treatment with DM/Q. Treatment with DM/Q had a normalizing effect on the behavioral responses of PBA patients. Event-related potential waveform comparisons of PBA-preTx and PBA-DM/Q with HC, for both neutral and subjectively significant stimuli, revealed effects on early ERP components. Comparisons between PBA-preTx and HC, in response to subjectively significant stimuli, revealed both early and late effects. Source analysis comparisons between PBA-preTx and PBA-DM/Q indicated distinct activations in areas involved in emotional processing and high-level and associative visual processing in response to neutral stimuli and in areas involved in emotional, somatosensory, primary, and premotor processing in response to subjectively significant stimuli. In most cases, stimuli evoked higher current density in PBA-DM/Q compared with the other groups. In conclusion, differences in brain activity were observed before and after medication. Also, DM/Q administration resulted in normalization of behavioral and electrophysiological measures.

Maternal postpartum learned helplessness (LH) affects maternal care by dams and responses to the LH test in adolescent offspring.

PubMed

Kurata, Akiko; Morinobu, Shigeru; Fuchikami, Manabu; Yamamoto, Shigeto; Yamawaki, Shigeto

2009-06-01

It is known that the early environment affects the mental development of rodent and human offspring. However, it is not known specifically whether a postpartum depressive state influences the depressive state in offspring. Using learned helplessness (LH) in rats as an animal model of depression, we examined the influence of maternal postpartum LH on responses to the LH test of offspring. Dam rats were judged as LH or non-helpless (nLH) on postnatal days (PN) 2-3, and maternal behavior was recorded during PN2-14. On PN 45-46, offspring were subjected to the LH test. Plasma corticosterone (CORT) levels, hippocampal levels of glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) mRNA were measured before and after the LH test in offspring. Active nursing in LH dams was significantly lower than that in nLH dams. Susceptibility to LH in the offspring of LH dams was significantly higher than in those of nLH dams, and was negatively correlated with active nursing by LH dams. The GR mRNA levels before and after the LH test were lower in the offspring of LH dams than in those of nLH dams, and the reduced basal GR mRNA and protein might have resulted in the higher CORT response after the LH test. There was no significant difference in BDNF mRNA in the offspring of LH and nLH dams. These findings suggest that early postpartum LH decreased active nursing and increased depression-like behavior in the adolescent offspring via dysfunction of the hypothalamic-pituitary-adrenal axis.

Effects of soybean meal on digestive enzymes activity, expression of inflammation-related genes, and chromatin modifications in marine fish (Sparus aurata L.) larvae.

PubMed

Perera, Erick; Yúfera, Manuel

2017-04-01

The effects of soybean meal (SBM) in early diet of Sparus aurata larvae at two developmental windows were assessed. Prolonged (beyond 14 days post-hatch, dph) feeding with SBM decreased the activity of pancreatic enzymes of larvae. In the absence of SBM these larvae later resumed enzyme activities, but exhibited a significant delay in development. Larvae response to SBM involved up-regulation of extracellular matrix remodeling enzymes and pro-inflammatory cytokines, coupled with a drop in putative intestinal enzymes. Larvae receiving SBM at first feeding appear later to have lower expression of inflammation-related genes, especially those fed SBM until 14 dph. Multivariate analysis confirmed that the duration of the SBM early feeding period drives the physiology of larvae in different directions. Feeding larvae with SBM increased global histone H3 acetylation, whereas upon removal of SBM the process was reverted. A more in deep analysis revealed a dynamic interplay among several reversible histone modifications such as H3K14ac and H3K27m3. Finally, we showed that SBM feeding of larvae results in global hypomethylation that persist after SBM removal. This study is the first demonstrating an effect of diet on marine fish epigenetics. It is concluded that there are limitations for extending SBM feeding of S. aurata larvae beyond 14 dph even under co-feeding with live feed, affecting key physiological processes and normal growth. However, up to 14 dph, SBM does not affect normal development, and produces apparently lasting effects on some key enzymes, genes, and chromatin modifications.

A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity.

PubMed

Devaux, Jérôme; Abidi, Affef; Roubertie, Agathe; Molinari, Florence; Becq, Hélène; Lacoste, Caroline; Villard, Laurent; Milh, Mathieu; Aniksztejn, Laurent

2016-05-01

Mutations in the KCNQ2 gene encoding the voltage-gated potassium channel subunit Kv7.2 cause early onset epileptic encephalopathy (EOEE). Most mutations have been shown to induce a loss of function or to affect the subcellular distribution of Kv7 channels in neurons. Herein, we investigated functional consequences and subcellular distribution of the p.V175L mutation of Kv7.2 (Kv7.2(V175L) ) found in a patient presenting EOEE. We observed that the mutation produced a 25-40 mV hyperpolarizing shift of the conductance-voltage relationship of both the homomeric Kv7.2(V175L) and heteromeric Kv7.2(V175L) /Kv7.3 channels compared to wild-type channels and a 10 mV hyperpolarizing shift of Kv7.2(V175L) /Kv7.2/Kv7.3 channels in a 1:1:2 ratio mimicking the patient situation. Mutant channels also displayed faster activation kinetics and an increased current density that was prevented by 1 μm linopirdine. The p.V175L mutation did not affect the protein expression of Kv7 channels and its localization at the axon initial segment. We conclude that p.V175L is a gain of function mutation. This confirms previous observations showing that mutations having opposite consequences on M channels can produce EOEE. These findings alert us that drugs aiming to increase Kv7 channel activity might have adverse effects in EOEE in the case of gain-of-function variants. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Affective, Biological, and Cognitive Predictors of Depressive Symptom Trajectories in Adolescence

PubMed Central

Salk, Rachel; Hyde, Janet Shibley; Priess-Groben, Heather A.; Simonson, Jordan L.

2013-01-01

Heterogeneity in the longitudinal course of depressive symptoms was examined using latent growth mixture modeling among a community sample of 382 U.S. youth from ages 11 to 18 (52.1% female). Three latent trajectory classes were identified: Stable Low (51%; displayed low depressive symptoms at all assessments), Increasing (37%; reported low depressive symptoms at age 11, but then significantly higher depressive symptoms than the Stable Low class at ages 13, 15, and 18), and Early High (12%; reported high early depressive symptoms at age 11, followed by symptoms that declined over time yet remained significantly higher than those of the Stable Low class at ages 13, 15, and 18). By age 15, rates of Major Depressive Disorder diagnoses among the Early High (25.0%) and Increasing (20.4%) classes were more than twice that observed among the Stable Low class (8.8%). Affective (negative affectivity), biological (pubertal timing, sex) and cognitive (cognitive style, rumination) factors were examined as predictors of class membership. Results indicated general risk factors for both high-risk trajectories as well as specific risk factors unique to each trajectory. Being female and high infant negative affectivity predicted membership in the Increasing class. Early puberty, high infant negative affectivity for boys, and high rumination for girls predicted membership in the Early High class. Results highlight the importance of examining heterogeneity in depression trajectories in adolescence as well as simultaneously considering risk factors across multiple domains. PMID:24158642

How family members manage risk around functional decline: the autonomy management process in households facing dementia.

PubMed

Berry, Brandon; Apesoa-Varano, Ester Carolina; Gomez, Yarin

2015-04-01

Most dementia research investigates the social context of declining ability through studies of decision-making around medical treatment and end-of-life care. This study seeks to fill an important gap in research about how family members manage the risks of functional decline at home. Drawing on three waves of in-depth interviewing in 2012-2014, it investigates how family members in US households manage decline in an affected individual's natural range of daily activities over time. The findings show that early on in the study period affected individuals were perceived to have awareness of their decline and routinely drew on family members for support. Support transformed when family members detected that the individual's deficit awareness had diminished, creating a corresponding increase in risk of self-harm around everyday activities. With a loss of confidence in the individual's ability to regulate his or her own activities to avoid these risks, family members employed unilateral practices to manage the individual's autonomy around his or her activity involvements. These practices typically involved various deceits and ruses to discourage elders from engaging in activities perceived as potentially dangerous. The study concludes by discussing the implications that the social context of interpretive work around awareness and risk plays an important role in how families perceive an elder's functional ability and manage his or her activity involvements. Copyright © 2015 Elsevier Ltd. All rights reserved.

How family members manage risk around functional decline: The autonomy management process in households facing dementia

PubMed Central

Berry, Brandon; Apesoa-Varano, Ester Carolina; Gomez, Yarin

2015-01-01

Most dementia research investigates the social context of declining ability through studies of decision-making around medical treatment and end-of-life care. This study seeks to fill an important gap in research about how family members manage the risks of functional decline at home. Drawing on three waves of retrospective interviewing in 2012–2014, it investigates how family members in US households manage decline in an affected individual’s natural range of daily activities over time. The findings show that early on in the study period affected individuals were perceived to have awareness of their decline and routinely drew on family members for support. Support transformed when family members detected that the individual’s deficit awareness had diminished, creating a corresponding increase in risk of self-harm around everyday activities. With a loss of confidence in the individual’s ability to regulate his or her own activities to avoid these risks, family members employed unilateral practices to manage the individual’s autonomy around his or her activity involvements. These practices typically involved various deceits and ruses to discourage elders from engaging in activities perceived as potentially dangerous. The study concludes by discussing the implications that the social context of interpretive work around awareness and risk plays an important role in how families perceive an elder’s functional ability and manage his or her activity involvements. PMID:25697634

Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease.

PubMed

Uhlig, Holm H

2013-12-01

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, has multifactorial aetiology with complex interactions between genetic and environmental factors. Over 150 genetic loci are associated with IBD. The genetic contribution of the majority of those loci towards explained heritability is low. Recent studies have reported an increasing spectrum of human monogenic diseases that can present with IBD-like intestinal inflammation. A substantial proportion of patients with those genetic defects present with very early onset of intestinal inflammation. The 40 monogenic defects with IBD-like pathology selected in this review can be grouped into defects in intestinal epithelial barrier and stress response, immunodeficiencies affecting granulocyte and phagocyte activity, hyper- and autoinflammatory disorders as well as defects with disturbed T and B lymphocyte selection and activation. In addition, there are defects in immune regulation affecting regulatory T cell activity and interleukin (IL)-10 signalling. Related to the variable penetrance of the IBD-like phenotype, there is a likely role for modifier genes and gene-environment interactions. Treatment options in this heterogeneous group of disorders range from anti-inflammatory and immunosuppressive therapy to blockade of tumour necrosis factor α and IL-1β, surgery, haematopoietic stem cell transplantation or gene therapy. Understanding of prototypic monogenic 'orphan' diseases cannot only provide treatment options for the affected patients but also inform on immunological mechanisms and complement the functional understanding of the pathogenesis of IBD.

Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue.

PubMed

Rebolledo, Alejandro; Rebolledo, Oscar R; Marra, Carlos A; García, María E; Roldán Palomo, Ana R; Rimorini, Laura; Gagliardino, Juan J

2010-10-21

To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility. Adult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K+-induced depolarization using intact and thereafter PVAT-deprived rings. Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats. FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.

Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

PubMed

Habarou, Florence; Hamel, Yamina; Haack, Tobias B; Feichtinger, René G; Lebigot, Elise; Marquardt, Iris; Busiah, Kanetee; Laroche, Cécile; Madrange, Marine; Grisel, Coraline; Pontoizeau, Clément; Eisermann, Monika; Boutron, Audrey; Chrétien, Dominique; Chadefaux-Vekemans, Bernadette; Barouki, Robert; Bole-Feysot, Christine; Nitschke, Patrick; Goudin, Nicolas; Boddaert, Nathalie; Nemazanyy, Ivan; Delahodde, Agnès; Kölker, Stefan; Rodenburg, Richard J; Korenke, G Christoph; Meitinger, Thomas; Strom, Tim M; Prokisch, Holger; Rotig, Agnes; Ottolenghi, Chris; Mayr, Johannes A; de Lonlay, Pascale

2017-08-03

Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Modeling the impact of tuberculosis interventions on epidemiologic outcomes and health system costs.

PubMed

Oxlade, Olivia; Piatek, Amy; Vincent, Cheri; Menzies, Dick

2015-02-13

Tuberculosis (TB) programs must invest in a variety of TB specific activities in order to reach ambitious global targets. Uncertainty exists surrounding the potential impact of each of these activities. The objective of our study was to model different interventions and quantify their impact on epidemiologic outcomes and costs from the health system perspective. Decision analysis was used to define the TB patient trajectory within the health system of three different countries. We considered up to seven different interventions that could affect either the natural history of TB, or patient trajectories within the health system. The expected impact of interventions were derived from published studies where possible. Epidemiologic outcomes and associated health system costs were projected for each scenario. With no specific intervention, TB related death rates are high and less than 10% of the population starts on correct treatment. Interventions that either prevent cases or affect all patients with TB disease early in their trajectory are expected to have the biggest impact, regardless of underlying epidemiologic characteristics of the setting. In settings with a private sector, improving diagnosis and appropriate treatment across all sectors is expected to have a major impact on outcomes. In all settings, the greatest benefit will come from early diagnosis of all forms of TB. Once this has been achieved more specific interventions, such as those targeting HIV, drug resistance or the private sector can be integrated to increase impact.

Time of Day Differences in Neural Reward Functioning in Healthy Young Men.

PubMed

Byrne, Jamie E M; Hughes, Matthew E; Rossell, Susan L; Johnson, Sheri L; Murray, Greg

2017-09-13

Reward function appears to be modulated by the circadian system, but little is known about the neural basis of this interaction. Previous research suggests that the neural reward response may be different in the afternoon; however, the direction of this effect is contentious. Reward response may follow the diurnal rhythm in self-reported positive affect, peaking in the early afternoon. An alternative is that daily reward response represents a type of prediction error, with neural reward activation relatively high at times of day when rewards are unexpected (i.e., early and late in the day). The present study measured neural reward activation in the context of a validated reward task at 10.00 h, 14.00 h, and 19.00 h in healthy human males. A region of interest BOLD fMRI protocol was used to investigate the diurnal waveform of activation in reward-related brain regions. Multilevel modeling found, as expected, a highly significant quadratic time-of-day effect focusing on the left putamen ( p < 0.001). Consistent with the "prediction error" hypothesis, activation was significantly higher at 10.00 h and 19.00 h compared with 14.00 h. It is provisionally concluded that the putamen may be particularly important in endogenous priming of reward motivation at different times of day, with the pattern of activation consistent with circadian-modulated reward expectancies in neural pathways (i.e., greater activation to reward stimuli at unexpected times of day). This study encourages further research into circadian modulation of reward and underscores the methodological importance of accounting for time of day in fMRI protocols. SIGNIFICANCE STATEMENT This is one of the first studies to use a repeated-measures imaging procedure to explore the diurnal rhythm of reward activation. Although self-reported reward (most often operationalized as positive affect) peaks in the afternoon, the present findings indicate that neural activation is lowest at this time. We conclude that the diurnal neural activation pattern may reflect a prediction error of the brain, where rewards at unexpected times (10.00 h and 19.00 h) elicit higher activation in reward brain regions than at expected (14.00 h) times. These data also have methodological significance, suggesting that there may be a time of day influence, which should be accounted for in neural reward studies. Copyright © 2017 the authors 0270-6474/17/378895-06$15.00/0.

Short-Term responses of breeding birds of grassland and early successional habitat to timing of haying in Northwestern Arkansas

USGS Publications Warehouse

Luscier, J.D.; Thompson, W.L.

2009-01-01

In 2003, we evaluated nest survival and density of the Dickcissel (Spiza americana), Eastern Meadowlark (Sturnella magna), Field Sparrow (Spizella pusilla), and Red-winged Blackbird (Agelaius phoeniceus) in four unhayed, two early-hayed (26-31 May) and three late-hayed (17-25 June) fields in northwestern Arkansas. Rope dragging and observations revealed 89 nests. Daily nest-survival rates (SE) prior to haying ranged from 0.94 (0.03) to 0.97 (0.02). Early haying affected both nest-survival rates and bird densities negatively, whereas late haying had minimal effects. Fifteen nests in hayed portions of early-hayed fields were destroyed, whereas only 2 of 52 nests were affected by late haying. Density was at least 0.98 birds ha-1 higher in unhayed than in early-hayed fields and 1.03 birds ha-1 higher in late-hayed than in early-hayed fields. In northwestern Arkansas, postponing haying until mid- to late June would allow time for nestlings to fledge, would have little effect on bird densities, and would affect hay nutrition and regrowth minimally. ?? The Cooper Ornithological Society, 2009.

Postnatal TLR2 activation impairs learning and memory in adulthood.

PubMed

Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

2015-08-01

Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation[S

PubMed Central

Allende, Maria L.; Cook, Emily K.; Larman, Bridget C.; Nugent, Adrienne; Brady, Jacqueline M.; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J.

2018-01-01

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB-corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses. PMID:29358305

Role of burning season on initial understory vegetation response to prescribed fire in a mixed conifer forest

USGS Publications Warehouse

Knapp, E.E.; Schwilk, D.W.; Kane, J.M.; Keeley, J.E.

2007-01-01

Although the majority of fires in the western United States historically occurred during the late summer or early fall when fuels were dry and plants were dormant or nearly so, early-season prescribed burns are often ignited when fuels are still moist and plants are actively growing. The purpose of this study was to determine if burn season influences postfire vegetation recovery. Replicated early-season burn, late-season burn, and unburned control units were established in a mixed conifer forest, and understory vegetation was evaluated before and after treatment. Vegetation generally recovered rapidly after prescribed burning. However, late-season burns resulted in a temporary but significant drop in cover and a decline in species richness at the 1 m 2 scale in the following year. For two of the several taxa that were negatively affected by burning, the reduction in frequency was greater after late-season than early-season burns. Early-season burns may have moderated the effect of fire by consuming less fuel and lessening the amount of soil heating. Our results suggest that, when burned under high fuel loading conditions, many plant species respond more strongly to differences in fire intensity and severity than to timing of the burn relative to stage of plant growth. ?? 2007 NRC.

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.

PubMed

Allende, Maria L; Cook, Emily K; Larman, Bridget C; Nugent, Adrienne; Brady, Jacqueline M; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J; Proia, Richard L

2018-03-01

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB -corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB -corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB -corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses.

Communal nesting exerts epigenetic influences on affective and social behaviors in rats selectively bred for an infantile trait.

PubMed

Martinez, Ashley Rae; Brunelli, Susan A; Zimmerberg, Betty

2015-02-01

Communal nesting (CN) is a mouse model of early social enrichment during pregnancy and lactation. In this study, a rat model of CN was developed to determine if CN exerts an epigenetic effect in rats selectively bred for an infantile affective trait (high and low rates of ultrasonic distress calls). High and Low offspring from CN groups were compared to standard reared (SN) offspring on five measures of social and affective behavior at three critical ages. A differential effect of the CN paradigm on High and Low lines was seen in measures of anxiety and arousal, but not in measures of depression or social behavior. Neonatal CN subjects emitted fewer distress calls than SN subjects when separated from their dams, and the High line subjects were more affected by the CN procedure. As juveniles, CN subjects showed increased social behaviors in tests of juvenile parenting and play compared to SN subjects. In adulthood, CN differentially increased the activity of Low line subjects. All CN subjects displayed less anxiety behavior in an open field compared to SN subjects; High line subjects were more anxious than Lows. CN reduced immobility and increased attempts to escape on the Porsolt forced swim task relative to SN subjects. These results extend the usefulness of this early enrichment paradigm from mice to rats, and found some rodent species differences in outcomes dependent on the behavioral test. They also emphasize the importance of social contact during pregnancy and lactation on offspring's optimal development across behaviors and ages. Copyright © 2014 Elsevier Inc. All rights reserved.

Dissociable early attentional control mechanisms underlying cognitive and affective conflicts

PubMed Central

Chen, Taolin; Kendrick, Keith M.; Feng, Chunliang; Sun, Shiyue; Yang, Xun; Wang, Xiaogang; Luo, Wenbo; Yang, Suyong; Huang, Xiaoqi; Valdés-Sosa, Pedro A.; Gong, Qiyong; Fan, Jin; Luo, Yue-Jia

2016-01-01

It has been well documented that cognitive conflict is sensitive to the relative proportion of congruent and incongruent trials. However, few studies have examined whether affective conflict processing is modulated as a function of proportion congruency (PC). To address this question we recorded event-related potentials (ERP) while subjects performed both cognitive and affective face-word Stroop tasks. By varying the proportion of congruent and incongruent trials in each block, we examined the extent to which PC impacts both cognitive and affective conflict control at different temporal stages. Results showed that in the cognitive task an anteriorly localized early N2 component occurred predominantly in the low proportion congruency context, whereas in the affective task it was found to occur in the high proportion congruency one. The N2 effects across the two tasks were localized to the dorsolateral prefrontal cortex, where responses were increased in the cognitive task but decreased in the affective one. Furthermore, high proportions of congruent items produced both larger amplitude of a posteriorly localized sustained potential component and a larger behavioral Stroop effect in cognitive and affective tasks. Our findings suggest that cognitive and affective conflicts engage early dissociable attentional control mechanisms and a later common conflict response system. PMID:27892513

Early Sign Language Experience Goes Along with an Increased Cross-modal Gain for Affective Prosodic Recognition in Congenitally Deaf CI Users.

PubMed

Fengler, Ineke; Delfau, Pia-Céline; Röder, Brigitte

2018-04-01

It is yet unclear whether congenitally deaf cochlear implant (CD CI) users' visual and multisensory emotion perception is influenced by their history in sign language acquisition. We hypothesized that early-signing CD CI users, relative to late-signing CD CI users and hearing, non-signing controls, show better facial expression recognition and rely more on the facial cues of audio-visual emotional stimuli. Two groups of young adult CD CI users-early signers (ES CI users; n = 11) and late signers (LS CI users; n = 10)-and a group of hearing, non-signing, age-matched controls (n = 12) performed an emotion recognition task with auditory, visual, and cross-modal emotionally congruent and incongruent speech stimuli. On different trials, participants categorized either the facial or the vocal expressions. The ES CI users more accurately recognized affective prosody than the LS CI users in the presence of congruent facial information. Furthermore, the ES CI users, but not the LS CI users, gained more than the controls from congruent visual stimuli when recognizing affective prosody. Both CI groups performed overall worse than the controls in recognizing affective prosody. These results suggest that early sign language experience affects multisensory emotion perception in CD CI users.

Motherese, affect, and vocabulary development: dyadic communicative interactions in infants and toddlers.

PubMed

Dave, Shruti; Mastergeorge, Ann M; Olswang, Lesley B

2018-07-01

Responsive parental communication during an infant's first year has been positively associated with later language outcomes. This study explores responsivity in mother-infant communication by modeling how change in guiding language between 7 and 11 months influences toddler vocabulary development. In a group of 32 mother-child dyads, change in early maternal guiding language positively predicted child language outcomes measured at 18 and 24 months. In contrast, a number of other linguistic variables - including total utterances and non-guiding language - did not correlate with toddler vocabulary development, suggesting a critical role of responsive change in infant-directed communication. We further assessed whether maternal affect during early communication influenced toddler vocabulary outcomes, finding that dominant affect during early mother-infant communications correlated to lower child language outcomes. These findings provide evidence that responsive parenting should not only be assessed longitudinally, but unique contributions of language and affect should also be concurrently considered in future study.

First experience with early dynamic (18)F-NaF-PET/CT in patients with chronic osteomyelitis.

PubMed

Freesmeyer, Martin; Stecker, Franz F; Schierz, Jan-Henning; Hofmann, Gunther O; Winkens, Thomas

2014-05-01

This study investigates whether early dynamic positron emission tomography/computed tomography (edPET/CT) using (18)F-sodium fluoride-((18)F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed(18)F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late (18)F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUVmax, edSUVmean, respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late (18)F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed(18)F-NaF -PET offers additional information about early radiotracer distribution to standard (18)F-NaF -PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed(18)F-NaF-PET to a three-phase bone scan.

Time-course of changes in neuronal activity markers following iTBS-TMS of the rat neocortex.

PubMed

Hoppenrath, Kathrin; Funke, Klaus

2013-03-01

In a rat model of transcranial magnetic stimulation we could recently show that intermittent theta-burst stimulation (iTBS) affects the neocortical expression of the immediate early gene products c-Fos and zif268 as well as that of the two glutamic acid decarboxylase isoforms GAD65 and GAD67 and that of the calcium-binding proteins calbindin (CB) and parvalbumin (PV), known as markers of excitatory and inhibitory activity. We now analyzed in more detail the time course of changes in the expression of these proteins at 10, 20, 40, 80 and 160min following a single block of iTBS consisting of 600 stimuli. Initial increase in c-Fos, zif268 and GAD65 (20min) signals transient activation of excitatory and inhibitory neurons, thereafter first followed by a decrease in markers of activity of inhibitory neurons (GAD67, PV, CB: 20-80min) and then by a late decrease in c-Fos and GAD65 expression (160min). The results demonstrate that one iTBS block may have an after-effect of at least two different phases, an early phase with increased neuronal activity (c-Fos, zif268) but also the likelihood of increased GABA-release (GAD65), followed by a late phase (>40min) of reduced neuronal activity in excitatory and inhibitory systems which may indicate a state of reduced excitability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Alkaline phosphatase activity in blood group B or O secretors is fluctuated by the dinner intake of previous night].

PubMed

Matsushita, Makoto; Harajiri, Sanae; Tabata, Shiori; Yukimasa, Nobuyasu; Muramoto, Yoshimi; Komoda, Tsugikazu

2013-04-01

We previously reported that two intestinal alkaline phosphatase (IAP) isoforms, high molecular mass IAP (HIAP) and normal molecular mass IAP (NIAP), appear in healthy serum with our Triton-PAGE method for determination of ALP isozymes. In addition, HIAP is chiefly present in blood group B or O secretors, and a large amount of NIAP is secreted into the circulation after high-fat meal in blood group B or O secretors. In the present paper, we investigated the relationship between alkaline phosphatase (ALP) activity in early morning with the patient in a fasted state and the dinner intake of previous night. Two types of dinner were prepared; a low-fat meal (520 kcal), and a high-fat meal (1,040 kcal). Subjects ate the 2 types of dinner on different days. The mean ALP activities at 14 h after high-fat meal ingestion in blood group B or O secretors (n=14) from JSCC and IFCC methods were 8.8% and 5.2% higher than those at 14 h after low-fat meal ingestion in blood group B or O secretors, respectively. The increases in ALP activity between after high-fat meal and low-fat meal were nearly identical to the increases in NIAP activity. These results suggest that a high-fat meal is more likely to affect ALP activity at the early morning with the patient in a fasted state in blood group B or O secretors.

The non-canonical BMP and Wnt/β-catenin signaling pathways orchestrate early tooth development

PubMed Central

Yuan, Guohua; Yang, Guobin; Zheng, Yuqian; Zhu, Xiaojing; Chen, Zhi; Zhang, Zunyi; Chen, YiPing

2015-01-01

BMP and Wnt signaling pathways play a crucial role in organogenesis, including tooth development. Despite extensive studies, the exact functions, as well as if and how these two pathways act coordinately in regulating early tooth development, remain elusive. In this study, we dissected regulatory functions of BMP and Wnt pathways in early tooth development using a transgenic noggin (Nog) overexpression model (K14Cre;pNog). It exhibits early arrested tooth development, accompanied by reduced cell proliferation and loss of odontogenic fate marker Pitx2 expression in the dental epithelium. We demonstrated that overexpression of Nog disrupted BMP non-canonical activity, which led to a dramatic reduction of cell proliferation rate but did not affect Pitx2 expression. We further identified a novel function of Nog by inhibiting Wnt/β-catenin signaling, causing loss of Pitx2 expression. Co-immunoprecipitation and TOPflash assays revealed direct binding of Nog to Wnts to functionally prevent Wnt/β-catenin signaling. In situ PLA and immunohistochemistry on Nog mutants confirmed in vivo interaction between endogenous Nog and Wnts and modulation of Wnt signaling by Nog in tooth germs. Genetic rescue experiments presented evidence that both BMP and Wnt signaling pathways contribute to cell proliferation regulation in the dental epithelium, with Wnt signaling also controlling the odontogenic fate. Reactivation of both BMP and Wnt signaling pathways, but not of only one of them, rescued tooth developmental defects in K14Cre;pNog mice, in which Wnt signaling can be substituted by transgenic activation of Pitx2. Our results reveal the orchestration of non-canonical BMP and Wnt/β-catenin signaling pathways in the regulation of early tooth development. PMID:25428587

Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.

PubMed

Salari, Ali-Akbar; Bakhtiari, Amir; Homberg, Judith R

2015-08-01

Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500μg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Endothelin-1 signalling controls early embryonic heart rate in vitro and in vivo.

PubMed

Karppinen, S; Rapila, R; Mäkikallio, K; Hänninen, S L; Rysä, J; Vuolteenaho, O; Tavi, P

2014-02-01

Spontaneous activity of embryonic cardiomyocytes originates from sarcoplasmic reticulum (SR) Ca(2+) release during early cardiogenesis. However, the regulation of heart rate during embryonic development is still not clear. The aim of this study was to determine how endothelin-1 (ET-1) affects the heart rate of embryonic mice, as well as the pathway through which it exerts its effects. The effects of ET-1 and ET-1 receptor inhibition on cardiac contraction were studied using confocal Ca(2+) imaging of isolated mouse embryonic ventricular cardiomyocytes and ultrasonographic examination of embryonic cardiac contractions in utero. In addition, the amount of ET-1 peptide and ET receptor a (ETa) and b (ETb) mRNA levels were measured during different stages of development of the cardiac muscle. High ET-1 concentration and expression of both ETa and ETb receptors was observed in early cardiac tissue. ET-1 was found to increase the frequency of spontaneous Ca(2+) oscillations in E10.5 embryonic cardiomyocytes in vitro. Non-specific inhibition of ET receptors with tezosentan caused arrhythmia and bradycardia in isolated embryonic cardiomyocytes and in whole embryonic hearts both in vitro (E10.5) and in utero (E12.5). ET-1-mediated stimulation of early heart rate was found to occur via ETb receptors and subsequent inositol trisphosphate receptor activation and increased SR Ca(2+) leak. Endothelin-1 is required to maintain a sufficient heart rate, as well as to prevent arrhythmia during early development of the mouse heart. This is achieved through ETb receptor, which stimulates Ca(2+) leak through IP3 receptors. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.

PubMed

Maniam, Jayanthi; Antoniadis, Christopher P; Morris, Margaret J

2015-01-01

Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early-life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11βHSD-1), 5-α reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11βHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning.

Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics

PubMed Central

Antoni, Michael H.; Lutgendorf, Susan K.; Blomberg, Bonnie; Carver, Charles S.; Lechner, Suzanne; Diaz, Alain; Stagl, Jamie; Arevalo, Jesusa M.G.; Cole, Steven W.

2011-01-01

Background Chronic threat and anxiety are associated with pro-inflammatory transcriptional profiles in circulating leukocytes, but the causal direction of that relationship has not been established. This study tested whether a Cognitive-Behavioral Stress Management (CBSM) intervention targeting negative affect and cognition might counteract anxiety-related transcriptional alterations in people confronting a major medical threat. Methods 199 women undergoing primary treatment of Stage 0–III breast cancer were randomized to a 10-week CBSM protocol or an active control condition. 79 provided peripheral blood leukocyte samples for genome-wide transcriptional profiling and bioinformatic analyses at baseline, 6-, and 12-month follow-ups. Results Baseline negative affect was associated with > 50% differential expression of 201 leukocyte transcripts, including up-regulated expression of pro-inflammatory and metastasis-related genes. CBSM altered leukocyte expression of 91 genes by > 50% at follow-up (Group × Time interaction), including down-regulation of pro-inflammatory and metastasis-related genes and up-regulation of Type I interferon response genes. Promoter-based bioinformatic analyses implicated decreased activity of NF-κB/Rel and GATA family transcription factors and increased activity of Interferon Response Factors and the Glucocorticoid Receptor (GR) as potential mediators of CBSM-induced transcriptional alterations. Conclusions In early stage breast cancer patients, a 10-week CBSM intervention can reverse anxiety-related up-regulation of pro-inflammatory gene expression in circulating leukocytes. These findings clarify the molecular signaling pathways by which behavioral interventions can influence physical health and alter peripheral inflammatory processes that may reciprocally affect brain affective and cognitive processes. PMID:22088795

Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting.

PubMed

Sheikh, Haroon I; Joanisse, Marc F; Mackrell, Sarah M; Kryski, Katie R; Smith, Heather J; Singh, Shiva M; Hayden, Elizabeth P

2014-01-01

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent-child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps < .001). Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ≤ .05), with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations.

Early Language Development in Context: Interactions between Infant Temperament and Parenting Characteristics

ERIC Educational Resources Information Center

Laake, Lauren M.; Bridgett, David J.

2018-01-01

Research Findings: This study considered the interplay between infant temperament and maternal caregiving behaviors in relation to early language. A total of 118 mother-infant dyads participated in the study. Mothers rated infant positive affect (PA) and negative affect (NA), and maternal behaviors were coded during a free-play task when infants…

The Roles of Motivation, Affective Attitudes, and Willingness to Communicate among Chinese Students in Early English Immersion Programs

ERIC Educational Resources Information Center

Knell, Ellen; Chi, Yanping

2012-01-01

Early English immersion in China has been studied from many angles, but no research to date has investigated affective variables, which may have a profound relevance to successful English acquisition. The present study examines the roles of motivation, attitudes towards learning English, willingness to communicate, perceived competence, language…

Temperament and Parenting during the First Year of Life Predict Future Child Conduct Problems

PubMed Central

Lahey, Benjamin B.; Van Hulle, Carol A.; Keenan, Kate; Rathouz, Paul J.; D’Onofrio, Brian M.; Rodgers, Joseph Lee; Waldman, Irwin D.

2010-01-01

Predictive associations between parenting and temperament during the first year of life and child conduct problems were assessed longitudinally in 1,863 offspring of a representative sample of women. Maternal ratings of infant fussiness, activity level, predictability, and positive affect each independently predicted maternal ratings of conduct problems during ages 4–13 years. Furthermore, a significant interaction indicated that infants who were both low in fussiness and high in predictability were at very low risk for future conduct problems. Fussiness was a stronger predictor of conduct problems in boys whereas fearfulness was a stronger predictor in girls. Conduct problems also were robustly predicted by low levels of early mother-report cognitive stimulation. Interviewer-rated maternal responsiveness was a robust predictor of conduct problems, but only among infants low in fearfulness. Spanking during infancy predicted slightly more severe conduct problems, but the prediction was moderated by infant fussiness and positive affect. Thus, individual differences in risk for mother-rated conduct problems across childhood are already partly evident in maternal ratings of temperament during the first year of life and are predicted by early parenting and parenting-by-temperament interactions. PMID:18568397

Dynamic facial expressions evoke distinct activation in the face perception network: a connectivity analysis study.

PubMed

Foley, Elaine; Rippon, Gina; Thai, Ngoc Jade; Longe, Olivia; Senior, Carl

2012-02-01

Very little is known about the neural structures involved in the perception of realistic dynamic facial expressions. In the present study, a unique set of naturalistic dynamic facial emotional expressions was created. Through fMRI and connectivity analysis, a dynamic face perception network was identified, which is demonstrated to extend Haxby et al.'s [Haxby, J. V., Hoffman, E. A., & Gobbini, M. I. The distributed human neural system for face perception. Trends in Cognitive Science, 4, 223-233, 2000] distributed neural system for face perception. This network includes early visual regions, such as the inferior occipital gyrus, which is identified as insensitive to motion or affect but sensitive to the visual stimulus, the STS, identified as specifically sensitive to motion, and the amygdala, recruited to process affect. Measures of effective connectivity between these regions revealed that dynamic facial stimuli were associated with specific increases in connectivity between early visual regions, such as the inferior occipital gyrus and the STS, along with coupling between the STS and the amygdala, as well as the inferior frontal gyrus. These findings support the presence of a distributed network of cortical regions that mediate the perception of different dynamic facial expressions.

Effects of amendment of different biochars on soil physical and biological properties related to carbon mineralization

NASA Astrophysics Data System (ADS)

Zhang, Renduo; Zhu, Shuzhi; Ouyang, Lei

2014-05-01

Biochar addition to soils potentially affects various soil properties, and these effects are dependent on biochars derived from different feedstock materials and pyrolysis processes. The objective of this study was to investigate the effects of amendment of different biochars on soil physical and biological properties. Biochars were produced with dairy manure and woodchip at temperatures of 300, 500, and 700°C, respectively. Each biochar was mixed at 5% (w/w) with a forest soil and the mixture was incubated for 180 days, during which soil physical and biological properties, and soil respiration rates were measured. Results showed that the biochar addition significantly enhanced the formation of soil macroaggregates at the early incubation time. The biochar application significantly reduced soil bulk density, increased the amount of soil organic matter, and stimulated microbial activity and soil respiration rates at the early incubation stage. Biochar applications improved water retention capacity, with stronger effects by biochars produced at higher pyrolysis temperatures. At the same suction, the soil with woodchip biochars possessed higher water content than with the dairy manure biochars. Biochar addition significantly affected the soil physical and biological properties, which resulted in different soil carbon mineralization rates.

CaMKII knockdown affects both early and late phases of olfactory long-term memory in the honeybee.

PubMed

Scholl, Christina; Kübert, Natalie; Muenz, Thomas S; Rössler, Wolfgang

2015-12-01

Honeybees are able to solve complex learning tasks and memorize learned information for long time periods. The molecular mechanisms mediating long-term memory (LTM) in the honeybee Apis mellifera are, to a large part, still unknown. We approached this question by investigating the potential function of the calcium/calmodulin-dependent protein kinase II (CaMKII), an enzyme known as a 'molecular memory switch' in vertebrates. CaMKII is able to switch to a calcium-independent constitutively active state, providing a mechanism for a molecular memory and has further been shown to play an essential role in structural synaptic plasticity. Using a combination of knockdown by RNA interference and pharmacological manipulation, we disrupted the function of CaMKII during olfactory learning and memory formation. We found that learning, memory acquisition and mid-term memory were not affected, but all manipulations consistently resulted in an impaired LTM. Both early LTM (24 h after learning) and late LTM (72 h after learning) were significantly disrupted, indicating the necessity of CaMKII in two successive stages of LTM formation in the honeybee. © 2015. Published by The Company of Biologists Ltd.

Hatching late in the season requires flexibility in the timing of song learning

PubMed Central

Leitner, Stefan; Teichel, Johanna; Ter Maat, Andries; Voigt, Cornelia

2015-01-01

Most songbirds learn their songs from adult tutors, who can be their father or other male conspecifics. However, the variables that control song learning in a natural social context are largely unknown. We investigated whether the time of hatching of male domesticated canaries has an impact on their song development and on the neuroendocrine parameters of the song control system. Average age difference between early- and late-hatched males was 50 days with a maximum of 90 days. Song activity of adult tutor males decreased significantly during the breeding season. While early-hatched males were exposed to tutor songs for on average the first 99 days, late-hatched peers heard adult song only during the first 48 days of life. Remarkably, although hatching late in the season negatively affected body condition, no differences between both groups of males were found in song characteristics either in autumn or in the following spring. Similarly, hatching date had no effect on song nucleus size and circulating testosterone levels. Our data suggest that late-hatched males must have undergone accelerated song development. Furthermore, the limited tutor song exposure did not affect adult song organization and song performance. PMID:26311160

Developmental Programming and Endocrine Disruptor Effects on Reproductive Neuroendocrine Systems

PubMed Central

Gore, Andrea C.

2009-01-01

The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted. PMID:18394690

Costs of immune responses are related to host body size and lifespan

DOE PAGES

Brace, Amber J.; Lajeunesse, Marc J.; Ardia, Daniel R.; ...

2017-06-01

A central assumption in ecological immunology is that immune responses are costly, with costs manifesting directly (e.g., increases in metabolic rate and increased amino acid usage) or as tradeoffs with other life processes (e.g., reduced growth and reproductive success). Across taxa, host longevity, timing of maturity, and reproductive effort affect the organization of immune systems. It is reasonable, therefore, to expect that these and related factors should also affect immune activation costs. Specifically, species that spread their breeding efforts over a long lifetime should experience lower immune costs than those that mature and breed quickly and die comparatively early. Likewise,more » body mass should affect immune costs, as body size affects the extent to which hosts are exposed to parasites as well as how hosts can combat infections (via its effects on metabolic rates and other factors). Here in this paper, we used phylogenetic meta-regression to reveal that, in general, animals incur costs of immune activation, but small species that are relatively long-lived incur the largest costs. These patterns probably arise because of the relative need for defense when infection risk is comparatively high and fitness can only be realized over a comparatively long period. However, given the diversity of species considered here and the overall modest effects of body mass and life history on immune costs, much more research is necessary before generalizations are appropriate.« less

Costs of immune responses are related to host body size and lifespan

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

Brace, Amber J.; Lajeunesse, Marc J.; Ardia, Daniel R.

A central assumption in ecological immunology is that immune responses are costly, with costs manifesting directly (e.g., increases in metabolic rate and increased amino acid usage) or as tradeoffs with other life processes (e.g., reduced growth and reproductive success). Across taxa, host longevity, timing of maturity, and reproductive effort affect the organization of immune systems. It is reasonable, therefore, to expect that these and related factors should also affect immune activation costs. Specifically, species that spread their breeding efforts over a long lifetime should experience lower immune costs than those that mature and breed quickly and die comparatively early. Likewise,more » body mass should affect immune costs, as body size affects the extent to which hosts are exposed to parasites as well as how hosts can combat infections (via its effects on metabolic rates and other factors). Here in this paper, we used phylogenetic meta-regression to reveal that, in general, animals incur costs of immune activation, but small species that are relatively long-lived incur the largest costs. These patterns probably arise because of the relative need for defense when infection risk is comparatively high and fitness can only be realized over a comparatively long period. However, given the diversity of species considered here and the overall modest effects of body mass and life history on immune costs, much more research is necessary before generalizations are appropriate.« less

Social grooming network in captive chimpanzees: does the wild or captive origin of group members affect sociality?

PubMed

Levé, Marine; Sueur, Cédric; Petit, Odile; Matsuzawa, Tetsuro; Hirata, Satoshi

2016-01-01

Many chimpanzees throughout the world are housed in captivity, and there is an increasing effort to recreate social groups by mixing individuals with captive origins with those with wild origins. Captive origins may entail restricted rearing conditions during early infant life, including, for example, no maternal rearing and a limited social life. Early rearing conditions have been linked with differences in tool-use behavior between captive- and wild-born chimpanzees. If physical cognition can be impaired by non-natural rearing, what might be the consequences for social capacities? This study describes the results of network analysis based on grooming interactions in chimpanzees with wild and captive origins living in the Kumamoto Sanctuary in Kumamoto, Japan. Grooming is a complex social activity occupying up to 25% of chimpanzees' waking hours and plays a role in the emergence and maintenance of social relationships. We assessed whether the social centralities and roles of chimpanzees might be affected by their origin (captive vs wild). We found that captive- and wild-origin chimpanzees did not differ in their grooming behavior, but that theoretical removal of individuals from the network had differing impacts depending on the origin of the individual. Contrary to findings that non-natural early rearing has long-term effects on physical cognition, living in social groups seems to compensate for the negative effects of non-natural early rearing. Social network analysis (SNA) and, in particular, theoretical removal analysis, were able to highlight differences between individuals that would have been impossible to show using classical methods. The social environment of captive animals is important to their well-being, and we are only beginning to understand how SNA might help to enhance animal welfare.

Ceres Evolution: From Thermodynamic Modeling and Now Dawn Observation

NASA Astrophysics Data System (ADS)

McCord, T. B.; Combe, J. P.; Castillo, J. C.; Raymond, C. A.; De Sanctis, M. C.; Jaumann, R.; Ammannito, E.; Russell, C. T.

2015-12-01

Thermodynamic modeling indicated that Ceres has experienced planetary processes, including extensive melting of its ~25% water and differentiation, (McCord and Sotin, JGR, 2005; Castillo and McCord, Icarus, 2009). Early telescopic studies showed Ceres' surface to be spectrally similar to carboneous-chondrite-like material, i.e., aqueously altered silicates darkened by carbon, with a water-OH-related absorption near 3.06 µm. Later observations improved the spectra and suggested more specific interpretations: Structural water in clay minerals, phyllosilicates, perhaps ammoniated, iron-rich clays, carbonates, brucite, all implying extensive aqueous alteration, perhaps in the presence of CO2. Telescopic observations and thermodynamic models predicted Dawn would find a very different body compared to Vesta (e.g. McCord et al., SSR, 2011), as current Dawn observations are confirming. Ceres' original water ice should have melted early in its evolution, with the resulting differentiation and mineralization strongly affecting Ceres' composition, size and shape over time. The ocean should have become very salty and perhaps may still be liquid in places. The surface composition from telescopes seems to reflect this complex history. The mineralization with repeated mixing of the crust with the early liquid interior and with in-fall from space would create a complex surface that will present an interpretation challenge for Dawn. The Dawn spacecraft is currently collecting observations of Ceres' landforms, elemental and mineralogical/molecular composition and gravity field from orbit. Early results suggest a heavily cratered but distorted and lumpy body with features and composition consistent with internal activity, perhaps recent or current, associated with water and perhaps other volatiles. We will present and interpret the latest Dawn Ceres findings and how they affect our earlier understanding of Ceres evolution from modeling and telescope observations.

DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

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

Marchetti, Francesco; Wyrobek, Andrew J.

Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization.more » During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.« less

Mediterranean Storms: An Integrated Approach of Risk Management

NASA Astrophysics Data System (ADS)

Karageorgou, H.; Riza, E.; Linos, A.; Papanikolaou, D.

2010-09-01

Disaster by UN definition is "a serious disruption of the functioning of a community or a society, involving widespread human, material, economic, or environmental losses and impacts, which exceeds the ability of the affected community or society to cope using only its own resources". Mediterranean storms induce flash floods caused by excessive amounts of rainfall within a short lasting period of time. The intensity and duration of precipitation, region geomorphology, urbanization and different governmental emergency management structures trigger different consequences between Mediterranean countries. The integrated approach in management of storm risk represents a holistic perspective including interactions between government, science and technology institutions, developing agencies, private sector, NGOs and public. Local authorities and national government are responsible for the design, preparation and decision on storm risk management policies and strategies considering scientific risk identifying, assessing and understanding. Efficient governance management requires satisfied response to early warning systems, functionality of the affected systems upon which society depends and appropriate focus on variable interest, beliefs, values and ideologies between social groups. Also an appropriate balancing of benefits and costs in an efficient and equitable manner is important for the governance risk management. Natural sciences in corporation with the engineering science have developed effective early prediction, warning and monitoring systems on storm and flood risk. The health sciences use prediction systems for health related hazards and consequences and the social sciences research estimates the human resilience during disasters and the factors which affect and determine the human behavior. Also social sciences survey the response of public to early warning messages, the appropriate communicative methods to distributing messages and mechanisms to improve public response. The available and applied science and technology in prediction and early warning systems rely on the close collaboration between scientists and policy makers to achieve effective disaster prevention of human life and mitigation of damages. Developing agencies approach risk management as an integral part of development and encourage activities and measures to reduce the exposure and vulnerability to natural hazards through early warning systems, building codes, land use plans and disaster sensitive development plans. The human settlement and investment in high risk floodplains place greater numbers of people and economic assets in danger of being affected by storms and floods. Disasters and development are highly inter-related. Recurrent disasters and frequent localized disasters erode development and conversely the development processes can reduce disaster risk, or create new risks. The private sector participation in risk reduction efforts can help local communities mitigate disasters and increases the benefits of the businesses. The private insurance sector is highly involved in the prevention of disaster caused by natural hazards especially storms and floods. The collaboration between academic community and the insurance sector indicates the linkages between the mutual insurance actions and risk culture. Also tourism industry and private critical infrastructure sector get involved in prevention measures and activities against storm and flood risks to build sustainable functionality and keep public trust. NGOs focus on social, cultural, environmental, educational, or health issues in disaster management and their members are educated and experienced on their area of operations. The staff of local and national NGOs is familiar with culture, languages, governance structures, social networks, climate and geography of the affected area and holds a unique understanding of the specific problems of the affected population. Additionally, NGO’s operations do not suffer from bureaucracy and therefore are able to deploy on very short notice. The public awareness, behavior and response to disasters depend on the knowledge about the risk, the understanding of the information and the translation of what it means in their own particular circumstances. The majority of people judges the information to be credible and discusses the meaning of information with trusted family members, friends and colleagues to decide the next action. Well educated people, efficient management of previous experiences, successful communication methods and trust on government and authorities contribute towards efficient public response on disasters.

IQCB1 and PDE6B Mutations Cause Similar Early Onset Retinal Degenerations in Two Closely Related Terrier Dog Breeds

PubMed Central

Goldstein, Orly; Mezey, Jason G.; Schweitzer, Peter A.; Boyko, Adam R.; Gao, Chuan; Bustamante, Carlos D.; Jordan, Julie Ann; Aguirre, Gustavo D.; Acland, Gregory M.

2013-01-01

Purpose. To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively. Methods. Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the “MAGIC” genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease. Results. Structural photoreceptor abnormalities were observed in crd1-affected dogs as young as 11-weeks old. Rod and cone inner segment (IS) and outer segments (OS) were abnormal in size, shape, and number. In crd2-affected dogs, rod and cone IS and OS were abnormal as early as 3 weeks of age, progressing with age to severe loss of the OS, and thinning of the outer nuclear layer (ONL) by 12 weeks of age. Genome-wide association study (GWAS) identified association at the telomeric end of CFA3 in crd1-affected dogs and on CFA33 in crd2-affected dogs. Candidate gene evaluation identified a three bases deletion in exon 21 of PDE6B in crd1-affected dogs, and a cytosine insertion in exon 10 of IQCB1 in crd2-affected dogs. Conclusions. Identification of the mutations responsible for these two early-onset retinal degenerations provides new large animal models for comparative disease studies and evaluation of potential therapeutic approaches for the homologous human diseases. PMID:24045995

Effects of spray-dried Pseudomonas fluorescens, strain CL145A (Zequanox®) on reproduction and early development of the fathead minnow (Pimephales promelas).

USGS Publications Warehouse

Waller, Diane L.; Luoma, James A.

2016-01-01

The biopesticide, Zequanox®, is registered for dreissenid mussel control in open water systems. Previous toxicity trials with nontarget organisms, including young-of-the year of several fish species and invertebrates, demonstrated selectivity of Zequanox for dreissenids. However, data are lacking on its safety to reproductive and early life stages of fish. The present study evaluated the effects of Zequanox on spawning and early life stages of the fathead minnow, Pimephales promelas, at the maximum approved concentration (100 mg Zequanox active ingredient /L) and exposure duration (8 h) for open water application. The results showed no significant effect of Zequanox on survival, condition, or cumulative egg deposition (21 d) in adult fathead minnow. Eggs (<24-h old) exposed to Zequanox developed to the eyed-stage at a similar rate to that of unexposed eggs. Additionally, Zequanox did not have a significant effect on survival and growth (90 d) of newly hatched fry (<24-h old). The results indicate that Zequanox treatment will not affect survival, spawning, and early life development of fathead minnows when applied at the recommended treatment regime.

Experimental acidification of Little Rock Lake (Wisconsin): fish research approach and early responses.

PubMed

Swenson, W A; McCormick, J H; Simonson, T D; Jensen, K M; Eaton, J G

1989-01-01

One goal of research at Little Rock Lake, Wisconsin, is to enhance understanding of lake acidification effects on warm- and cool-water fishery resources. The Little Rock Lake fish assemblage is characteristic of many acid sensitive waters in North America and is dominated by yellow perch (Percidae) and sunfishes (Centrarchidae). Analyses of reproduction, early survival and growth rates in the field were designed around the differing reproductive modes of these taxa. Complementary laboratory research on early life stages was conducted to assist in isolating direct effect mechanisms and to determine the reliability of laboratory results in predicting field response. Preliminary findings suggest that lake acidification to pH 5.6 has not influenced reproductive activity of the four most abundant fish species. However, the field results suggest that year-class failure of rock bass (Ambloplites rupestris) may be occurring due to reduced survival of early life stages. Reduced growth and food conversion efficiency of Age 0 largemouth bass (Micropterus salmoides) is also suggested. The laboratory bioassays indicate rock bass is the most acid-sensitive Little Rock Lake species tested. However, rock bass fry survival was not significantly affected until pH was reduced from 5.6 to 5.0.

The effects of milking frequency on insulin-like growth factor I signaling within the mammary gland of dairy cows.

PubMed

Murney, R; Stelwagen, K; Wheeler, T T; Margerison, J K; Singh, K

2015-08-01

In dairy cows, short-term changes in milking frequency (MF) in early lactation have been shown to produce both an immediate and a long-term effect on milk yield. The effect of MF on milk yield is controlled locally within mammary glands and could be a function of changes in either number or activity of secretory mammary epithelial cells (MEC). Insulin-like growth factor I (IGF-I) signaling is one candidate factor that could mediate these effects, as it can be controlled locally within mammary glands. Both MEC number and activity can be affected by IGF-I signaling by activating the phosphoinositide 3-kinase (PI3K)/Akt and extracellular-signal-regulated kinase (ERK)1/2 pathways. To investigate the relationship between MF and IGF-I signaling, udder halves of 17 dairy cows were milked either 4 times a day (4×) or once a day (1×) for 14 d in early lactation. On d 14, between 3 and 5 h following milking, mammary biopsies were obtained from 10 cows from both udder halves, and changes in the expression of genes associated with IGF-I signaling and the activation of the PI3K/Akt and ERK1/2 pathways were measured. The mRNA abundance of IGF type I receptor, IGF binding protein (IGFBP)-3, and IGFBP-5 were lower following 4× milking relative to 1× milking. However, the mRNA abundance of IGF-I was not affected by MF. Both IGFBP3 and IGFBP5 are thought to inhibit IGF-I; therefore, decreases in their mRNA abundance may serve to stimulate the IGF-I signal in the 4×-milked mammary gland. The activation of PI3K/Akt pathway was lower in response to 4× milking relative to 1×, and the activation of the ERK1/2 was unaffected by MF, suggesting that they do not mediate the effects of MF. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Targeted Sos1 deletion reveals its critical role in early T-cell development

PubMed Central

Kortum, Robert L.; Sommers, Connie L.; Alexander, Clayton P.; Pinski, John M.; Li, Wenmei; Grinberg, Alex; Lee, Jan; Love, Paul E.; Samelson, Lawrence E.

2011-01-01

Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development. Sos1 was required for pre–T-cell receptor (pre-TCR)– but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR–stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development. PMID:21746917

Effect of chronotype and student learning time on mathematical ability based on self-regulated learning

NASA Astrophysics Data System (ADS)

Ratnaningsih, N.; El Akbar, R. R.; Hidayat, E.

2018-05-01

One of ways to improve students' learning ability is conduct a research, with purpose to obtain a method to improve students' ability. Research often carried out on the modification of teaching methods, uses of teaching media, motivation, interests and talents of students. Research related to the internal condition of students becomes very interesting to studied, including research on circadian rhythms. Every person in circadian rhythms has its own Chronotype, which divided into two types namely early type and night late type. Chronotype affects the comfort in activity, for example a person with Chronotype category of early type tends to be more comfort in daytime activities. The purpose of this study is to examine the conditions of students, related Chronotype suitable or appropriate for student learning time. This suitability then studied in relation to the ability of learning mathematics with self- regulated learning approach. This study consists of three stages; (i) student Chronotype measurement, (ii) data retrieval, and (iii) analysis of research results. The results show the relationship between the students' learning ability in mathematics to learning time corresponding to Chronotype.

[Anti-epidermal growth factor receptor treatment: a new paradigm for conducting therapeutic trials].

PubMed

Marty, Michel; Bedairia, Naima; Armand, Jean-Pierre

2003-11-01

Agents which modify biological properties of tumour tissue can target many tenths of functions over- or underexpressed in human tumours. In general these agents are cytostatic rather than cytotoxic and will affect only that fraction of human tumours where the target plays and important and unique role for the viability of the tumour tissue. Alternatively it is expected that acute toxicity will not be observed at active dose-time exposure; rather subacute or chronic toxicity can be observed with these agents. Clinical studies will have to follow the following rules: characterisation of the pharmacological target and of its functional role on tumour tissue; definition of an optimal biological dose rather than a maximum tolerated dose; importance of validated pharmacodynamic endpoints; importance and thus need for early studies of combination regimens. It is still too early to define general guidelines for the study of these different therapeutic families. Nevertheless, studies already conducted with agents interfering with EGF mediated signalization have already permitted preliminary indications on pharmacodynamics, target assessment, level of activity and conduct of clinical trials with combination regimens.

Absenteeism in schools during the 2009 influenza A(H1N1) pandemic: a useful tool for early detection of influenza activity in the community?

PubMed

Kara, E O; Elliot, A J; Bagnall, H; Foord, D G F; Pnaiser, R; Osman, H; Smith, G E; Olowokure, B

2012-07-01

Certain influenza outbreaks, including the 2009 influenza A(H1N1) pandemic, can predominantly affect school-age children. Therefore the use of school absenteeism data has been considered as a potential tool for providing early warning of increasing influenza activity in the community. This study retrospectively evaluates the usefulness of these data by comparing them with existing syndromic surveillance systems and laboratory data. Weekly mean percentages of absenteeism in 373 state schools (children aged 4-18 years) in Birmingham, UK, from September 2006 to September 2009, were compared with established syndromic surveillance systems including a telephone health helpline, a general practitioner sentinel network and laboratory data for influenza. Correlation coefficients were used to examine the relationship between each syndromic system. In June 2009, school absenteeism generally peaked concomitantly with the existing influenza surveillance systems in England. Weekly school absenteeism surveillance would not have detected pandemic influenza A(H1N1) earlier but daily absenteeism data and the development of baselines could improve the timeliness of the system.

A personal overview of causalgia and other reflex dystrophies.

PubMed Central

Shumacker, H B

1985-01-01

This is a personal assessment of true major causalgia and the other reflex dystrophies, related but distinctly separate entities. The clinical picture of causalgia differs only in minor respects from that described by Mitchell over 120 years ago. Its management has, however, been clarified, largely through the extensive experiences of World War II. It is readily recognized and can be treated effectively by sympathetic blocks or sympathectomy together with active exercise. The other reflex dystrophies are far less understood. They appear to have a similar pattern in their early phase and to respond well to a program of exercise and control of edema--a regimen which, because of pain and paresis, cannot be carried out without sympathetic blocks or occasionally sympathectomy. When not recognized early and treated properly, the sympatomatology usually changes dramatically and treatment differs. Often control of edema and active use of the affected part are all that is necessary. Sometimes, in addition to these measures, sympathetic blocks or sympathectomy is required. Guidelines found useful in management are outlined. Puzzling features are discussed. PMID:3977427

The effect of exposure to hypergravity on pregnant rat dams, pregnancy outcome and early neonatal development

NASA Astrophysics Data System (ADS)

Ladd, B.; Nguon, K.; Sajdel-Sulkowska, E. M.

2006-01-01

We previously reported that hypergravity exposure affects food intake and mass gain during pregnancy. In the present study, we explored the hypothesis that changes in maternal body mass in hypergravity-exposed pregnant rat dams affect pregnancy outcome and early offspring development. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravity and by exposure during critical developmental periods. To test this hypothesis, we compared maternal body mass gain, food consumption, birth outcome and early offspring development between Sprague Dawley rat dams exposed to graded (1.5 1.75G) chronic hypergravity (HG) or rotation (rotational control, RC) on a 24-ft centrifuge for 22.5 h starting on gestational day (G) 10 with dams housed under identical conditions but not exposed to hypergravity (SC). We also compared maternal body mass, food consumption, birth outcome and early offspring development between rat dams exposed to 1.65G during different stages of pregnancy and nursing. Exposure to hypergravity resulted in transient loss in body mass and prolonged decrease in food consumption in HG dams, but the changes observed at 1.5G were not magnified at 1.65G or 1.75G. On the other hand RC dams gained more mass and consumed more food than SC dams. Exposure to hypergravity also affected pregnancy outcome as evidenced by decreased litter size, lowered neonatal mass at birth, and higher neonatal mortality; pregnancy outcome was not affected in RC dams. Neonatal changes evidenced by impaired righting response observed at 1.5G was magnified at higher gravity and was dependent on the period of hypergravity exposure. On the other hand, righting response was improved in RC neonates. Hypergravity exposure during early postpartum affected the food consumption of nursing mothers and affected early survival of their offspring. The changes observed in dams and neonates appear to be due to hypergravity exposure since animals exposed to the rotation during the same period are not affected. This study suggests that while pregnancy can proceed under altered gravity, exposure to hypergravity affects pregnant dams, pregnancy outcome and the developing fetus as well as nursing dams and neonates and raises an important question whether the mammalian system possess a gravisensing ability.

Nonsurgical treatment and early return to activity leads to improved Achilles tendon fatigue mechanics and functional outcomes during early healing in an animal model.

PubMed

Freedman, Benjamin R; Gordon, Joshua A; Bhatt, Pankti R; Pardes, Adam M; Thomas, Stephen J; Sarver, Joseph J; Riggin, Corinne N; Tucker, Jennica J; Williams, Alexis W; Zanes, Robert C; Hast, Michael W; Farber, Daniel C; Silbernagel, Karin G; Soslowsky, Louis J

2016-12-01

Achilles tendon ruptures are common and devastating injuries; however, an optimized treatment and rehabilitation protocol has yet to be defined. Therefore, the objective of this study was to investigate the effects of surgical repair and return to activity on joint function and Achilles tendon properties after 3 weeks of healing. Sprague-Dawley rats (N = 100) received unilateral blunt transection of their Achilles tendon. Animals were then randomized into repaired or non-repaired treatments, and further randomized into groups that returned to activity after 1 week (RTA1) or after 3 weeks (RTA3) of limb casting in plantarflexion. Limb function, passive joint mechanics, and tendon properties (mechanical, organizational using high frequency ultrasound, histological, and compositional) were evaluated. Results showed that both treatment and return to activity collectively affected limb function, passive joint mechanics, and tendon properties. Functionally, RTA1 animals had increased dorsiflexion ROM and weight bearing of the injured limb compared to RTA3 animals 3-weeks post-injury. Such functional improvements in RTA1 tendons were evidenced in their mechanical fatigue properties and increased cross sectional area compared to RTA3 tendons. When RTA1 was coupled with nonsurgical treatment, superior fatigue properties were achieved compared to repaired tendons. No differences in cell shape, cellularity, GAG, collagen type I, or TGF-β staining were identified between groups, but collagen type III was elevated in RTA3 repaired tendons. The larger tissue area and increased fatigue resistance created in RTA1 tendons may prove critical for optimized outcomes in early Achilles tendon healing following complete rupture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2172-2180, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Nonsurgical treatment and early return to activity leads to improved Achilles tendon fatigue mechanics and functional outcomes during early healing in an animal model

PubMed Central

Freedman, BR; Gordon, JA; Bhatt, PB; Pardes, AM; Thomas, SJ; Sarver, JJ; Riggin, CN; Tucker, JJ; Williams, AW; Zanes, RC; Hast, MW; Farber, DC; Silbernagel, KG; Soslowsky, LJ

2016-01-01

Achilles tendon ruptures are common and devastating injuries; however, an optimized treatment and rehabilitation protocol has yet to be defined. Therefore, the objective of this study was to investigate the effects of surgical repair and return to activity on joint function and Achilles tendon properties after 3-weeks of healing. Sprague Dawley rats (N=100) received unilateral blunt transection of their Achilles tendon. Animals were then randomized into repaired or non-repaired treatments, and further randomized into groups that returned to activity after 1-week (RTA1) or after 3-weeks (RTA3) of limb casting in plantarflexion. Limb function, passive joint mechanics, and tendon properties (mechanical, organizational using high frequency ultrasound, histological, and compositional) were evaluated. Results showed that both treatment and return to activity collectively affected limb function, passive joint mechanics, and tendon properties. Functionally, RTA1 animals had increased dorsiflexion ROM and weight bearing of the injured limb compared to RTA3 animals 3-weeks post injury. Such functional improvements in RTA1 tendons were evidenced in their mechanical fatigue properties and increased cross sectional area compared to RTA3 tendons. When RTA1 was coupled with nonsurgical treatment, superior fatigue properties were achieved compared to repaired tendons. No differences in cell shape, cellularity, GAG, collagen type I, or TGF-β staining were identified between groups, but collagen type III was elevated in RTA3 repaired tendons. The larger tissue area and increased fatigue resistance created in RTA1 tendons may prove critical for optimized outcomes in early Achilles tendon healing following complete rupture. PMID:27038306

Differences in the importance of weather and weather-based decisions among campers in Ontario parks (Canada)

NASA Astrophysics Data System (ADS)

Hewer, Micah J.; Scott, Daniel J.; Gough, William A.

2017-10-01

Parks and protected areas represent an important resource for tourism in Canada, in which camping is a common recreational activity. The important relationship between weather and climate with recreation and tourism has been widely acknowledged within the academic literature. Howbeit, the need for activity-specific assessments has been identified as an on-going need for future research in the field of tourism climatology. Furthermore, very little is known about the interrelationships between personal characteristics and socio-demographics with weather preferences and behavioural thresholds. This study uses a stated climate preferences approach (survey responses) to explore differences in the importance of weather and related weather-based decisions among summer campers in Ontario parks. Statistically significant differences were found among campers for each of the four dependent variables tested in this study. Physically active campers placed greater importance on weather but were still more tolerant of adverse weather conditions. Older campers placed greater importance on weather. Campers travelling shorter distances placed greater importance on weather and were more likely to leave the park early due to adverse weather. Campers staying for longer periods of time were less likely to leave early due to weather and were willing to endure longer durations of adverse weather conditions. Beginner campers placed greater importance on weather, were more likely to leave early due to weather and recorded lower temporal weather thresholds. The results of this study contribute to the study of tourism climatology by furthering understanding of how personal characteristics such as gender, age, activity selection, trip duration, distance travelled, travel experience and life cycles affect weather preferences and decisions, focusing this time on recreational camping in a park tourism context.

The efficacy of sodium benzoate as an adjunctive treatment in early psychosis - CADENCE-BZ: study protocol for a randomized controlled trial.

PubMed

Ryan, Alex; Baker, Andrea; Dark, Frances; Foley, Sharon; Gordon, Anne; Hatherill, Sean; Stathis, Stephen; Saha, Sukanta; Bruxner, George; Beckman, Martin; Richardson, Drew; Berk, Michael; Dean, Olivia; McGrath, John; Group, Cadence Working; Scott, James

2017-04-07

Psychotic disorders affect up to 3% of the population and are often chronic and disabling. Innovation in the pharmacological treatment of psychosis has remained stagnant in recent decades. In order to improve outcomes for those with psychotic disorders, we present a protocol for the trial of a common food preservative, sodium benzoate, as an adjunctive treatment in early psychosis. Persons experiencing early psychosis (n = 160) will be recruited through hospitals and community mental health services in Queensland, Australia. Patients will be randomized to receive either 12-week treatment with 1000 mg (500 mg twice daily (BD)) sodium benzoate or placebo. Patients will undergo fortnightly outcome assessments, in addition to weekly ongoing capacity to consent, drug compliance and safety assessments. The primary outcome measure is the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes are Global Assessment of Function (GAF), Assessment of Quality of Life Scale (AQOL), the Activity and Participation Questionnaire (APQ6), International Physical Activity Questionnaires (IPAQ), Simple Physical Activity Questionnaire (SIMPAQ), Physical Activity Questionnaire, Clinical Global Impression (CGI), Hamilton Depression rating Scale-17 items (HDRS), Opiate Treatment Index (OTI) and the Patients' Global Impression of Improvement (PGI-I). As a tertiary objective, changes from baseline to endpoint in to serum markers related to D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate will be investigated. Consumers and clinicians are keen to help develop better treatments for those with psychosis. This study, part of the wider Cadence clinical trials platform will examine if a safe and accessible food preservative can help optimize outcomes in those with psychosis. Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12615000187549 . Registered on 26 February 2015.

Proinflammatory T Cell Status Associated with Early Life Adversity.

PubMed

Elwenspoek, Martha M C; Hengesch, Xenia; Leenen, Fleur A D; Schritz, Anna; Sias, Krystel; Schaan, Violetta K; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Schächinger, Hartmut; Vögele, Claus; Turner, Jonathan D; Muller, Claude P

2017-12-15

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69 + CD8 + T cells ( p = 0.022), increased numbers of HLA-DR + CD4 and HLA-DR + CD8 T cells ( p < 0.001), as well as increased numbers of CD25 + CD8 + T cells ( p = 0.036). ELA also showed a trend toward higher numbers of CCR4 + CXCR3 - CCR6 + CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells. Copyright © 2017 by The American Association of Immunologists, Inc.

Differences in the importance of weather and weather-based decisions among campers in Ontario parks (Canada).

PubMed

Hewer, Micah J; Scott, Daniel J; Gough, William A

2017-10-01

Parks and protected areas represent an important resource for tourism in Canada, in which camping is a common recreational activity. The important relationship between weather and climate with recreation and tourism has been widely acknowledged within the academic literature. Howbeit, the need for activity-specific assessments has been identified as an on-going need for future research in the field of tourism climatology. Furthermore, very little is known about the interrelationships between personal characteristics and socio-demographics with weather preferences and behavioural thresholds. This study uses a stated climate preferences approach (survey responses) to explore differences in the importance of weather and related weather-based decisions among summer campers in Ontario parks. Statistically significant differences were found among campers for each of the four dependent variables tested in this study. Physically active campers placed greater importance on weather but were still more tolerant of adverse weather conditions. Older campers placed greater importance on weather. Campers travelling shorter distances placed greater importance on weather and were more likely to leave the park early due to adverse weather. Campers staying for longer periods of time were less likely to leave early due to weather and were willing to endure longer durations of adverse weather conditions. Beginner campers placed greater importance on weather, were more likely to leave early due to weather and recorded lower temporal weather thresholds. The results of this study contribute to the study of tourism climatology by furthering understanding of how personal characteristics such as gender, age, activity selection, trip duration, distance travelled, travel experience and life cycles affect weather preferences and decisions, focusing this time on recreational camping in a park tourism context.

Natural cellular resistance of beige mice against Cryptococcus neoformans

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

Hidore, M.R.; Murphy, J.W.

Previous reports have demonstrated that natural killer (NK) cells are capable of inhibiting the growth of Cryptococcus neoformans in vitro, and recent studies indicate that adoptively transferred NK cell-enriched spleen cell populations enhance clearance of cryptococci from the tissues of cyclophosphamide-pretreated recipients. The primary objective of these studies was to confirm that NK cells participate in early clearance of C. neoformans in vivo. Secondarily, the anti-cryptococcal activities of polymorphonuclear leukocytes and macrophages were examined. Seven-week-old C57BL/6 bg/+ mice, which have normal levels of NK cell activity, were compared with their bg/bg littermates, which have impaired NK cell function. One andmore » 3 days after injecting both groups of mice i.v. with 2 x 10/sup 4/ cryptococci, the authors assessed the NK cell activities in spleens, lungs, and livers and clearance of the organism from corresponding tissues as determined by the mean log/sub 1//sup 0/ numbers of cryptococcal colony-forming units (CFU) per organ. Although the data indicated a correlation between early clearance of cryptococci from tissues and levels of NK cell activities in the corresponding tissues, it was also possible that differences in phagocytic cell function between the bg/+ and bg/bg animals could account for the observed differences in clearance of cryptococci from the tissues. These data indicate that NK cells were the effector cells responsible for enhanced early clearance of cryptococci from the tissues of bg/+ animals when compared with clearance from the tissues of the bg/bg littermates. Furthermore, they confirm the hypothesis that NK cells can affect C. neoformans under in vivo conditions.« less

Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

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

Thomas, Christine M.

2015-08-01

Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, withmore » the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in multicomponent systems.« less

Frontal fibrosing alopecia treatment options.

PubMed

Fertig, Raymond; Tosti, Antonella

2016-11-01

Frontal fibrosing alopecia (FFA) is a rare dermatologic disease that causes scarring and hair loss and is increasing in prevalence worldwide. FFA patients typically present with hair loss in the frontal scalp region and eyebrows which may be associated with sensations of itching or burning. FFA is a clinically distinct variant of lichen planopilaris (LPP) that affects predominantly postmenopausal women, although men and premenopausal women may also be affected. Early diagnosis and prompt treatment are necessary to prevent definitive scarring and permanent hair loss. Data from retrospective studies indicate that 5-alpha-reductase inhibitors (5aRIs) are effective in stabilizing the disease. In our clinical experience, we have seen optimal results treating FFA patients with oral finasteride in conjunction with hydroxychloroquine, topical calcineurin inhibitors (tacrolimus) and excimer laser in patients with signs of active inflammation.

Disentangling reward anticipation with simultaneous pupillometry / fMRI.

PubMed

Schneider, Max; Leuchs, Laura; Czisch, Michael; Sämann, Philipp G; Spoormaker, Victor I

2018-05-05

The reward system may provide an interesting intermediate phenotype for anhedonia in affective disorders. Reward anticipation is characterized by an increase in arousal, and previous studies have linked the anterior cingulate cortex (ACC) to arousal responses such as dilation of the pupil. Here, we examined pupil dynamics during a reward anticipation task in forty-six healthy human subjects and evaluated its neural correlates using functional magnetic resonance imaging (fMRI). Pupil size showed a strong increase during monetary reward anticipation, a moderate increase during verbal reward anticipation and a decrease during control trials. For fMRI analyses, average pupil size and pupil change were computed in 1-s time bins during the anticipation phase. Activity in the ventral striatum was inversely related to the pupil size time course, indicating an early onset of activation and a role in reward prediction processing. Pupil dilations were linked to increased activity in the salience network (dorsal ACC and bilateral insula), which likely triggers an increase in arousal to enhance task performance. Finally, increased pupil size preceding the required motor response was associated with activity in the ventral attention network. In sum, pupillometry provides an effective tool for disentangling different phases of reward anticipation, with relevance for affective symptomatology. Copyright © 2018 Elsevier Inc. All rights reserved.

Challenges and Limitations in Early Intervention

ERIC Educational Resources Information Center

Hadders-Algra, Mijna

2011-01-01

Research over the past three decades has shown that early intervention in infants biologically at risk of developmental disorders, irrespective of the presence of a brain lesion, is associated with improved cognitive development in early childhood without affecting motor development. However, at present it is unknown whether early intervention is…

Early Childhood Special Music Education

ERIC Educational Resources Information Center

Darrow, Alice-Ann

2011-01-01

The process of early intervention is a critical component of Early Childhood Special Music Education. Early intervention is the process of providing services, education, and support to young children who have disabilities or to children who are at-risk of developing needs that may affect their physical, cognitive, or emotional development. The…

Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study

PubMed Central

Karolis, Vyacheslav; Caldinelli, Chiara; Brittain, Philip J.; Kroll, Jasmin; Rodríguez-Toscano, Elisa; Tesse, Marcello; Colquhoun, Matthew; Howes, Oliver; Dell'Acqua, Flavio; Thiebaut de Schotten, Michel; Murray, Robin M.; Williams, Steven C.R.; Nosarti, Chiara

2015-01-01

The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI. SIGNIFICANCE STATEMENT Here we used the example of perinatal brain injury (PBI) associated with very preterm birth to study the brain's ability to adapt to injury sustained early in life. In adulthood, individuals with PBI did not show significant deficits in working memory, but exhibited less activation in typical frontoparietal working memory areas. They also showed a relative overactivation of nontask-specific brain areas (perisylvian cortex) compared with controls, and such activation was negatively correlated with the size of white matter pathways involved in working memory (dorsal cingulum). Furthermore, this “extra” activation was associated with better working memory performance and could represent a novel compensatory mechanism following PBI. Such information could inform the development of neuroscience-based cognitive interventions following PBI. PMID:26631462

The Temporal Dynamics of Two Response-Focused Forms of Emotion Regulation: Experiential, Expressive, and Autonomic Consequences

PubMed Central

Dan-Glauser, Elise S.; Gross, James J.

2011-01-01

This study examines the early affective consequences of two close forms of suppression. Participants (N=37) were shown negative, positive, and neutral pictures and cued either to attend to the pictures, or to perform expressive or physiological suppression (i.e. reduce body reactions). Continuous measures of experience, expressivity, and autonomic responses showed that both suppression strategies produced rapid response modulation. Common effects of the two strategies included a transient increase in negative feeling, a durable decrease in positive feeling, and a decrease in expressivity, cardiovascular activity, and oxygenation. The two strategies were significantly different only in response to positive stimuli, with physiological suppression showing a larger decrease in experience intensity and blood pressure. These results suggest a strong overlap between the two suppression strategies in terms of their early impact on emotional responses. PMID:21361967

Ergonomics content in the physical education teacher's guide in Rwanda.

PubMed

Nellutla, Manobhiram; Patel, Hetal; Kabanda, Aline; Nuhu, Assuman

2012-01-01

An important aspect that affects the effectiveness of ergonomic programs is that inefficient mechanical functioning start at an early age and that back pain and posture problems are already evident in children. Children, from a very early age, as well as adults spend an ever increasing amount of their time in front of computer and television screens. The cumulative effect of this sedentary lifestyle leads to improper posture, as well as inefficient and harmful movement patterns and loss of basic physical skills. Physical Education course should deal not only with sports and physical activities, but also with broader aspects of life-skills and physical functionality. It should offer a solution to the modern technology-based society. Keeping this in perspective, Ergonomics content was introduced in Physical Education Teacher's Guide in Rwandan schools with an aim in preventing musculoskeletal disorder in children.

Precipitation and the occurrence of lyme disease in the Northeastern United States

USGS Publications Warehouse

McCabe, G.J.; Bunnell, J.E.

2004-01-01

The occurrence of Lyme disease is a growing concern in the United States, and various studies have been performed to understand the factors related to Lyme disease occurrence. In the United States, Lyme disease has occurred most frequently in the northeastern United States. Positive correlations between the number of cases of Lyme disease reported in the northeastern United States during the 1992-2002 period indicate that late spring/early summer precipitation was a significant climate factor affecting the occurrence of Lyme disease. When late spring/early summer precipitation was greater than average, the occurrence of Lyme disease was above average, possibly due to increased tick activity and survival rate during wet conditions. Temperature did not seem to explain the variability in Lyme disease reports for the northeastern United States. ?? Mary Ann Liebert, Inc.

Multidisciplinary management of Paget-Schroetter syndrome. A case series of eight patients.

PubMed

Rosa Salazar, Vladimir; Otálora Valderrama, Sonia Del Pilar; Hernández Contreras, María Encarnación; García Pérez, Bartolomé; Arroyo Tristán, Andrés Del Amor; García Méndez, María Del Mar

2015-08-01

Paget-Schroetter syndrome (PSS) in the context of upper extremity deep venous thrombosis (DVT) is an uncommon but potentially very serious condition affecting young, healthy adults, in which secondary post-thrombotic syndrome (PTS) can be a complication with major implications. The best treatment option remains controversial, with current guidelines recommending anticoagulation for at least 3 months. However, an incidence of PTS of approximately 50% after 6 months, 30% after 1 year and 25% after 2 years has been found using this therapeutic approach. Consequently, specialized units recommend local thrombolysis and early decompressive surgery. We describe a series of eight cases treated in this way. None of the patients showed signs of complications, and an early return to regular activities with no PTS was observed in 90% of cases. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Work productivity is associated with disease activity and functional ability in Italian patients with early axial spondyloarthritis: an observational study from the SPACE cohort.

PubMed

de Hooge, Manouk; Ramonda, Roberta; Lorenzin, Mariagrazia; Frallonardo, Paola; Punzi, Leonardo; Ortolan, Augusta; Doria, Andrea

2016-11-16

Spondyloarthritis often affects young people, typically in their working years. The aim of our study was to investigate work productivity and its relationship with disease activity and physical functioning in Italian patients with axial spondyloarthritis (axSpA) with chronic back pain (CBP) for ≥3 months and ≤2 years, and onset  < 45 years of age. Baseline absenteeism, presenteeism, work productivity loss (assessed by the Work Productivity and Activity Impairment questionnaire (WPAI)), and disease activity (assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)/Ankylosing Spondylitis Disease Activity Score (ASDAS)) and functional ability (assessed by the Bath Ankylosing Spondylitis Disease Functional Index (BASFI)) of patients with axSpA (rheumatologist's diagnosis) included in the Italian section of the Spondyloarthritis Caught Early (SPACE) cohort were collected. Multivariate linear regression analysis was used to evaluate the associations between work productivity and disease activity/physical functioning. Absenteeism in 51 patients with axSpA was low (8.3 %). A decrease in work productivity was related to an increase in disease activity. Disease activity was strongly correlated with absenteeism (p < 0.01), presenteeism (p < 0.01) and work productivity loss (p < 0.001). In addition, decreased work productivity was related to a decrease in functional ability. Physical functioning was correlated with absenteeism (p < 0.001), presenteeism (p < 0.05) and work productivity loss (p < 0.001). Impairment of work productivity was correlated with disease activity and physical functioning in Italian patients with axSpA with CBP for ≥3 months and ≤2 years, with onset <45 years of age.

Muscle morphology and mitochondrial investigations of a family with autosomal dominant cerebellar ataxia and retinal degeneration mapped to chromosome 3p12-p21.1.

PubMed

Forsgren, L; Libelius, R; Holmberg, M; von Döbeln, U; Wibom, R; Heijbel, J; Sandgren, O; Holmgren, G

1996-12-01

The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders with ataxia and dysarthria as early and dominant signs. In ADCA type II, retinal degeneration causes severe visual impairment. ADCA type II has recently been mapped to chromosome 3p by three independent groups. In the family with ADCA type II studied here, the disease has been mapped to chromosome 3p12-p21.1. Histochemical examination of muscle biopsies in 5 cases showed slight neurogenic atrophy and irregular lobulated appearance or focal decreases of enzyme activity when staining for NADH dehydrogenase, succinic dehydrogenase and cytochrome oxidase. Ragged-red fibres were scarce. Electron microscopic examination showed uneven distribution of mitochondria with large fibre areas devoid of mitochondria and/or large subsarcolemmal accumulations of small rounded mitochondria, and frequent autophagic vacuoles. These vacuoles contained remnants of multiple small rounded organelles, possibly mitochondria, and had a remarkably consistent ultrastructural appearance. Biochemical investigation of mitochondrial function showed reduced activity of complex IV and slightly reduced activity of complex I in the respiratory chain in a severely affected child while no abnormalities were found in his affected uncle.

Auxin-Dependent Cell Division and Cell Elongation. 1-Naphthaleneacetic Acid and 2,4-Dichlorophenoxyacetic Acid Activate Different Pathways1

PubMed Central

Campanoni, Prisca; Nick, Peter

2005-01-01

During exponential phase, the tobacco (Nicotiana tabacum) cell line cv Virginia Bright Italia-0 divides axially to produce linear cell files of distinct polarity. This axial division is controlled by exogenous auxin. We used exponential tobacco cv Virginia Bright Italia-0 cells to dissect early auxin signaling, with cell division and cell elongation as physiological markers. Experiments with 1-naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D) demonstrated that these 2 auxin species affect cell division and cell elongation differentially; NAA stimulates cell elongation at concentrations that are much lower than those required to stimulate cell division. In contrast, 2,4-D promotes cell division but not cell elongation. Pertussis toxin, a blocker of heterotrimeric G-proteins, inhibits the stimulation of cell division by 2,4-D but does not affect cell elongation. Aluminum tetrafluoride, an activator of the G-proteins, can induce cell division at NAA concentrations that are not permissive for division and even in the absence of any exogenous auxin. The data are discussed in a model where the two different auxins activate two different pathways for the control of cell division and cell elongation. PMID:15734918

Early neural activation during facial affect processing in adolescents with Autism Spectrum Disorder.

PubMed

Leung, Rachel C; Pang, Elizabeth W; Cassel, Daniel; Brian, Jessica A; Smith, Mary Lou; Taylor, Margot J

2015-01-01

Impaired social interaction is one of the hallmarks of Autism Spectrum Disorder (ASD). Emotional faces are arguably the most critical visual social stimuli and the ability to perceive, recognize, and interpret emotions is central to social interaction and communication, and subsequently healthy social development. However, our understanding of the neural and cognitive mechanisms underlying emotional face processing in adolescents with ASD is limited. We recruited 48 adolescents, 24 with high functioning ASD and 24 typically developing controls. Participants completed an implicit emotional face processing task in the MEG. We examined spatiotemporal differences in neural activation between the groups during implicit angry and happy face processing. While there were no differences in response latencies between groups across emotions, adolescents with ASD had lower accuracy on the implicit emotional face processing task when the trials included angry faces. MEG data showed atypical neural activity in adolescents with ASD during angry and happy face processing, which included atypical activity in the insula, anterior and posterior cingulate and temporal and orbitofrontal regions. Our findings demonstrate differences in neural activity during happy and angry face processing between adolescents with and without ASD. These differences in activation in social cognitive regions may index the difficulties in face processing and in comprehension of social reward and punishment in the ASD group. Thus, our results suggest that atypical neural activation contributes to impaired affect processing, and thus social cognition, in adolescents with ASD.

Dihydroquercetin Does Not Affect Age-Dependent Increase in Blood Pressure and Angiotensin-Converting Enzyme Activity in the Aorta of Hypertensive Rats.

PubMed

Slashcheva, G A; Rykov, V A; Lobanov, A V; Murashev, A N; Kim, Yu A; Arutyunyan, T V; Korystova, A F; Kublik, L N; Levitman, M Kh; Shaposhnikona, V V; Korystov, Yu N

2016-09-01

We analyzed changes in angiotensin-converting enzyme activity in the aorta of hypertensive SHR rats against the background of age-related BP increase (from week 7 to 14) and the effect of dihydroquercetin on BP rise and angiotensin-converting enzyme activity. Normotensive WKY rats of the same age were used as the control. BP and activity of angiotensin-converting enzyme in the aorta of SHR rats increased with age. Dihydroquercetin in doses of 100 and 300 μg/kg per day had no effect on the increase of these parameters; dihydroquercetin administered to 14-week-old WKY rats in a dose of 300 μg/kg reduced activity of the angiotensin-converting enzyme. Thus, the early (7-14 weeks) increase in BP and angiotensin-converting enzyme activity in the aorta of SHR rats was not modified by flavonoids (dihydroquercetin) in contrast to other rat strains and humans, which is indicative of specificity of hypertension mechanism in SHR rats.

Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity.

PubMed

Kumar, Atul; Chaugule, Viduth K; Condos, Tara E C; Barber, Kathryn R; Johnson, Clare; Toth, Rachel; Sundaramoorthy, Ramasubramanian; Knebel, Axel; Shaw, Gary S; Walden, Helen

2017-05-01

RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during Parkin activation. However, current data on active RBR ligases reflect the absence of regulatory domains. Therefore, it remains unclear how individual RBR ligases are activated, and whether they share a common mechanism. We now report the crystal structure of a human Parkin-phosphoubiquitin complex, which shows that phosphoubiquitin binding induces movement in the 'in-between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding promotes cooperation between Parkin molecules, which suggests a role for interdomain association in the RBR ligase mechanism.

Scanning the horizon in a decentralized healthcare system: the Canadian experience.

PubMed

Morrison, Andra

2012-07-01

Canada has a highly decentralized health care system with 13 provinces and territories delivering health care within their own respective jurisdictions. Decisions regarding which innovative health technologies to adopt are often driven by the unique health care priorities of each jurisdiction's population. To understand these needs, the Canadian Agency for Drugs and Technologies in Health's (CADTH's) Early Awareness Service has expanded its activities. In addition to proactively scanning the horizon for new and emerging health technologies, the Early Awareness Service also scans the horizon for national and jurisdictional health policy issues. This paper looks at CADTH's process for identifying and monitoring policy issues at a national and jurisdictional level. CADTH's Early Awareness Service delivers timely information on emerging health care concerns and technologies that may affect health care finances, facilities, operations, and patient care. The identification of important policy issues can help determine which new and emerging technologies will have the most significant impact on the health care system. The information that CADTH scans can also be used to help decision-makers prepare for potential developments and events that may have an impact on health care systems. By improving its capability to identify and share policy issues across and within jurisdictions, CADTH is better situated to provide information that can be used by policy-makers to help them plan and anticipate for the introduction of new technologies and future developments affecting the unique health care needs of their jurisdictions.

Alzheimer’s and ABC transporters - new opportunities for diagnostics and treatment

PubMed Central

Pahnke, Jens; Langer, Oliver; Krohn, Markus

2014-01-01

Much has been said about the increasing number of demented patients and the main risk factor ‘age’. Frustratingly, we do not know the precise pattern and all modulating factors that provoke the pathologic changes in the brains of affected elderly. We have to diagnose early to be able to stop the progression of diseases that irreversibly destroy brain substance. Familiar AD cases have mislead some researchers for almost 20 years, which has unfortunately narrowed the scientific understanding and has, thus, lead to insufficient funding of independent approaches. Therefore, basic researchers hardly have been able to develop causative treatments and clinicians still do not have access to prognostic and early diagnostic tools. During the recent years it became clear that insufficient Aβ export, physiologically facilitated by the ABC transporter superfamily at the brain’s barriers, plays a fundamental role in disease initiation and progression. Furthermore, export mechanisms that are deficient in affected elderly are new targets for activation and, thus, treatment, but ideally also for prevention. In sporadic AD disturbed clearance of β-amyloid from the brain is so far the most important factor for its accumulation in the parenchyma and vessel walls. Here, we review findings about the contribution of ABC transporters and of the perivascular drainage/glymphatic system on β-amyloid clearance. We highlight their potential value for innovative early diagnostics using PET and describe recently described, effective ABC transporter-targeting agents as potential causative treatment for neurodegenerative proteopathies/dementias. PMID:24746857

Alzheimer's and ABC transporters--new opportunities for diagnostics and treatment.

PubMed

Pahnke, Jens; Langer, Oliver; Krohn, Markus

2014-12-01

Much has been said about the increasing number of demented patients and the main risk factor 'age'. Frustratingly, we do not know the precise pattern and all modulating factors that provoke the pathologic changes in the brains of affected elderly. We have to diagnose early to be able to stop the progression of diseases that irreversibly destroy brain substance. Familiar AD cases have mislead some researchers for almost 20 years, which has unfortunately narrowed the scientific understanding and has, thus, lead to insufficient funding of independent approaches. Therefore, basic researchers hardly have been able to develop causative treatments and clinicians still do not have access to prognostic and early diagnostic tools. During the recent years it became clear that insufficient Aβ export, physiologically facilitated by the ABC transporter superfamily at the brain's barriers, plays a fundamental role in disease initiation and progression. Furthermore, export mechanisms that are deficient in affected elderly are new targets for activation and, thus, treatment, but ideally also for prevention. In sporadic AD disturbed clearance of β-amyloid from the brain is so far the most important factor for its accumulation in the parenchyma and vessel walls. Here, we review findings about the contribution of ABC transporters and of the perivascular drainage/glymphatic system on β-amyloid clearance. We highlight their potential value for innovative early diagnostics using PET and describe recently described, effective ABC transporter-targeting agents as potential causative treatment for neurodegenerative proteopathies/dementias. Copyright © 2014 Elsevier Inc. All rights reserved.