Histamine release inhibitory activity of Piper nigrum leaf.

PubMed

Hirata, Noriko; Naruto, Shunsuke; Inaba, Kazunori; Itoh, Kimihisa; Tokunaga, Masashi; Iinuma, Munekazu; Matsuda, Hideaki

2008-10-01

Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.

Positive force feedback in human walking

PubMed Central

Grey, Michael J; Nielsen, Jens Bo; Mazzaro, Nazarena; Sinkjær, Thomas

2007-01-01

The objective of this study was to determine if load receptors contribute to the afferent-mediated enhancement of ankle extensor muscle activity during the late stance phase of the step cycle. Plantar flexion perturbations were presented in late stance while able-bodied human subjects walked on a treadmill that was declined by 4%, inclined by 4% or held level. The plantar flexion perturbation produced a transient, but marked, presumably spinally mediated decrease in soleus EMG that varied directly with the treadmill inclination. Similarly, the magnitude of the control step soleus EMG and Achilles' tendon force also varied directly with the treadmill inclination. In contrast, the ankle angular displacement and velocity were inversely related to the treadmill inclination. These results suggest that Golgi tendon organ feedback, via the group Ib pathway, is reduced when the muscle–tendon complex is unloaded by a rapid plantar flexion perturbation in late stance phase. The changes in the unload response with treadmill inclination suggest that the late stance phase soleus activity may be enhanced by force feedback. PMID:17331984

Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice

PubMed Central

Wang, Xianfeng; Buechler, Nancy L.; Martin, Ayana; Wells, Jonathan; Yoza, Barbara; McCall, Charles E.; Vachharajani, Vidula

2016-01-01

Objective Obesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis. Methods Sepsis was induced using cecal ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a “second-hit” (marker of immune function) at different time points to track phases of sepsis in ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis. Results We observed that the ob/ob-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in ob/ob mice during hypo-inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation in vivo via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65. Conclusion SIRT-2 regulates microvascular inflammation in obese mice with sepsis and may provide a novel treatment target for obesity with sepsis. PMID:27500833

Seasonal heat stress affects adipose tissue proteome toward enrichment of the Nrf2-mediated oxidative stress response in late-pregnant dairy cows.

PubMed

Zachut, M; Kra, G; Livshitz, L; Portnick, Y; Yakoby, S; Friedlander, G; Levin, Y

2017-03-31

Environmental heat stress and metabolic stress during transition from late gestation to lactation are main factors limiting production in dairy cattle, and there is a complex interaction between them. Many proteins expressed in adipose tissue are involved in metabolic responses to stress. We aimed to investigate the effects of seasonal heat stress on adipose proteome in late-pregnant cows, and to identify biomarkers of heat stress. Late pregnant cows during summer heat stress (S, n=18), or during the winter season (W, n=12) were used. Subcutaneous adipose tissue biopsies sampled 14days prepartum from S (n=10) and W (n=8) were analyzed by intensity-based, label-free, quantitative shotgun proteomics (nano-LC-MS/MS). Plasma concentrations of malondialdehyde and cortisol were higher in S than in W cows. Proteomic analysis revealed that 107/1495 proteins were differentially abundant in S compared to W (P<0.05 and fold change of at least ±1.5). Top canonical pathways in S vs. W adipose were Nrf2-mediated oxidative stress response, acute-phase response, and FXR/RXR and LXR/RXR activation. Novel biomarkers of heat stress in adipose tissue were found. These findings indicate that seasonal heat stress has a unique effect on adipose tissue in late-pregnant cows. This work shows that seasonal heat stress increases plasma concentrations of the oxidative stress marker malondialdehyde and cortisol in transition dairy cows. As many proteins expressed in the adipose tissue are involved in metabolic responses to stress, we investigated the effects of heat stress on the proteome of adipose tissue from late-pregnant cows during summer or winter seasons. We demonstrated that heat stress enriches several stress-related pathways, such as the Nrf2-mediated oxidative stress response and the acute-phase response in adipose tissues. Thus, environmental heat stress has a unique effect on adipose tissue in late-pregnant cows, as part of the regulatory adaptations to chronic heat load during the summer season. In addition, this study presents the widest available dataset of adipose tissue proteome in dairy cows, and revealed several novel biomarkers of heat stress in adipose tissue of dairy cows, the use of which awaits further validation. Copyright © 2017 Elsevier B.V. All rights reserved.

Charge Exchange Contribution to the Decay of the Ring Current, Measured by Energetic Neutral Atoms (ENAs)

NASA Technical Reports Server (NTRS)

Jorgensen, A. M.; Henderson, M. G.; Roelof, E. C.; Reeves, G. D.; Spence, H. E.

2001-01-01

In this paper we calculate the contribution of charge exchange to the decay of the ring current. Past works have suggested that charge exchange of ring current protons is primarily responsible for the decay of the ring current during the late recovery phase, but there is still much debate about the fast decay of the early recovery phase. We use energetic neutral atom (ENA) measurements from Polar to calculate the total ENA energy escape. To get the total ENA escape we apply a forward modeling technique, and to estimate the total ring current energy escape we use the Dessler-Parker-Sckopke relationship. We find that during the late recovery phase of the March 10, 1998 storm ENAs with energies greater than 17.5 keV can account for 75% of the estimated energy loss from the ring current. During the fast recovery the measured ENAs can only account for a small portion of the total energy loss. We also find that the lifetime of the trapped ions is significantly shorter during the fast recovery phase than during the late recovery phase, suggesting that different processes are operating during the two phases.

PKACs attenuate innate antiviral response by phosphorylating VISA and priming it for MARCH5-mediated degradation

PubMed Central

Yan, Bing-Ru; Zhou, Lu; Hu, Ming-Ming; Li, Mi; Lin, Heng; Yang, Yan; Wang, Yan-Yi

2017-01-01

Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes. PKACs-deficiency or inactivation by the inhibitor H89 potentiated innate immunity to RNA viruses in cells and mice. Our findings reveal a critical mechanism of attenuating innate immune response to avoid host damage at the late phase of viral infection by the house-keeping PKA kinase. PMID:28934360

PKACs attenuate innate antiviral response by phosphorylating VISA and priming it for MARCH5-mediated degradation.

PubMed

Yan, Bing-Ru; Zhou, Lu; Hu, Ming-Ming; Li, Mi; Lin, Heng; Yang, Yan; Wang, Yan-Yi; Shu, Hong-Bing

2017-09-01

Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes. PKACs-deficiency or inactivation by the inhibitor H89 potentiated innate immunity to RNA viruses in cells and mice. Our findings reveal a critical mechanism of attenuating innate immune response to avoid host damage at the late phase of viral infection by the house-keeping PKA kinase.

Sleep and Premenstrual Syndrome

PubMed Central

Jehan, Shazia; Auguste, Evan; Hussain, Mahjabeen; Pandi-Perumal, Seithikurippu R.; Brzezinski, Amon; Gupta, Ravi; Attarian, Hrayr; Jean-Louis, Giradin; McFarlane, Samy I.

2016-01-01

The etiology of premenstrual syndrome (PMS) is unknown; it may be due to the normal effect of hormones during the menstrual cycle as it occurs in the late luteal phase of the menstrual cycle.PMS affects women of childbearing age and remits with the onset of menstruation. The menstrual phase is known to influence stage 2 and REM sleep in women, irrespective of premenstrual dysphoric disorder (PMDD). Women with PMDD showed a decreased response to melatonin in their luteal phase as compared to the follicular phase of the menstrual cycle. However, melatonin duration or timing of offset in the morning has not been reported to correlate with the mood. Rather, improvement in mood-related symptoms of PMDD has been found to be influenced by sleep deprivation, be it sleep restrictions in early or late night. Sleep disturbance and decreased melatonin secretions due to hormonal fluctuations during the luteal phase of the menstrual cycle could explain the sleep complaints of PMDD. PMID:28239684

HLA-DR expression, cytokines and bioactive lipids in sepsis

PubMed Central

2014-01-01

Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock. PMID:24904669

Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear

PubMed Central

Chai, Ning; Liu, Jian-Feng; Xue, Yan-Xue; Yang, Chang; Yan, Wei; Wang, Hui-Min; Luo, Yi-Xiao; Shi, Hai-Shui; Wang, Ji-Shi; Bao, Yan-Ping; Meng, Shi-Qiu; Ding, Zeng-Bo; Wang, Xue-Yi; Lu, Lin

2014-01-01

Fear extinction has been extensively studied, but little is known about the molecular processes that underlie the persistence of extinction long-term memory (LTM). We found that microinfusion of norepinephrine (NE) into the CA1 area of the dorsal hippocampus during the early phase (0 h) after extinction enhanced extinction LTM at 2 and 14 days after extinction. Intra-CA1 infusion of NE during the late phase (12 h) after extinction selectively promoted extinction LTM at 14 days after extinction that was blocked by the β-receptor antagonist propranolol, protein kinase A (PKA) inhibitor Rp-cAMPS, and protein synthesis inhibitors anisomycin and emetine. The phosphorylation levels of PKA, cyclic adenosine monophosphate response element-binding protein (CREB), GluR1, and the membrane GluR1 level were increased by NE during the late phase after extinction that was also blocked by propranolol and Rp-cAMPS. These results suggest that the enhancement of extinction LTM persistence induced by NE requires the activation of the β-receptor/PKA/CREB signaling pathway and membrane GluR1 trafficking. Moreover, extinction increased the phosphorylation levels of Erk1/2, CREB, and GluR1, and the membrane GluR1 level during the late phase, and anisomycin/emetine alone disrupted the persistence of extinction LTM, indicating that the persistence of extinction LTM requires late-phase protein synthesis in the CA1. Propranolol and Rp-cAMPS did not completely disrupt the persistence of extinction LTM, suggesting that another β-receptor/PKA-independent mechanism underlies the persistence of extinction LTM. Altogether, our results showed that enhancing hippocampal noradrenergic activity during the late phase after extinction selectively promotes the persistence of extinction LTM. PMID:24553734

Immune response phenotype of allergic versus clinically tolerant pigs in a neonatal swine model of allergy.

PubMed

Schmied, Julie; Rupa, Prithy; Garvie, Sarah; Wilkie, Bruce

2013-07-15

The prevalence of childhood food allergy and the duration of these allergies, particularly those considered to be transient, like egg and milk allergy, are increasing. The identification of allergic individuals using minimally invasive, non-anaphylaxis-threatening methods is therefore of increasing importance. In this experiment, correlates were sought of an allergic immune response (IR) phenotype in pigs. Using pigs pre-treated with heat-killed bacteria or bacterial components before allergic sensitization with the egg white protein ovomucoid (Ovm), differences were determined in IR phenotype of pigs in the categories treated-allergic, treated-tolerant, control-allergic (CA) and control-tolerant. Phenotype was established by measuring immunoglobulin (Ig)-associated antibody activity (AbA), cytokine profiles and the proportion of blood T-regulatory cells (T-regs) and observing late-phase allergen-specific skin tests (ST). Although 100% of pigs became sensitized to Ovm, only 33% of pigs had clinical signs of allergy after oral challenge with egg white. Pigs without clinical signs were classified as clinically tolerant. Sixty-seven percent of allergic pigs had a positive, late-phase ST classified as very strong or strong, while 84% of clinically tolerant pigs did not have late-phase ST. Treated-allergic pigs and CA pigs had greater total antibody IgG (H+L), IgE and IgG1 AbA than clinically tolerant pigs. Cytokine profiles of allergic pigs and the proportion of circulating T-regs, did not differ significantly between allergic and clinically tolerant pigs. Therefore, measurement of allergen-specific IgG, IgG1 and/or IgE activity and evaluation of late-phase ID ST may be useful in identifying allergic IR phenotypes in swine models of food allergy, which may be extended toward human use. Copyright © 2013 Elsevier B.V. All rights reserved.

Antiallergic activity of unripe Citrus hassaku fruits extract and its flavanone glycosides on chemical substance-induced dermatitis in mice.

PubMed

Itoh, Kimihisa; Masuda, Megumi; Naruto, Shunsuke; Murata, Kazuya; Matsuda, Hideaki

2009-10-01

Oral administration of a 50% ethanolic extract (CH-ext) obtained from unripe Citrus hassaku fruits collected in July exhibited a potent dose-dependent inhibition of IgE (immunoglobulin E)-mediated triphasic cutaneous reaction at 1 h [immediate phase response (IPR)], 24 h [late phase response (LPR)] and 8 days [very late phase response (vLPR)] after dinitrofluorobenzene challenge in mice. Naringin, a major flavanone glycoside component of CH-ext, showed a potent dose-dependent inhibition against IPR, LPR and vLPR. Neohesperidin, another major glycoside component of CH-ext, showed an inhibition against vLPR. The effect of CH-ext on type IV allergic reaction was examined by determining inhibitory activity against ear swelling in mice by using the picryl chloride-induced contact dermatitis (PC-CD) model. Oral administration (p.o.) of CH-ext and subcutaneous administration (s.c.) of prednisolone inhibited ear swelling during the induction phase of PC-CD. The inhibitory activities of combinations of CH-ext (p.o.) and prednisolone (s.c.) against PC-CD in mice were more potent than those of CH-ext alone and prednisolone alone, without enhancing the adverse effects. Other combinations of prednisolone (s.c.) and flavanone glycoside (p.o.) components of CH-ext, i.e. naringin and neohesperidin, exerted similar synergistic effects.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex.

PubMed

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex

PubMed Central

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants. PMID:29311827

Probing the Production of Extreme-ultraviolet Late-phase Solar Flares Using the Model Enthalpy-based Thermal Evolution of Loops

NASA Astrophysics Data System (ADS)

Dai, Yu; Ding, Mingde

2018-04-01

Recent observations in extreme-ultraviolet (EUV) wavelengths reveal an EUV late phase in some solar flares that is characterized by a second peak in warm coronal emissions (∼3 MK) several tens of minutes to a few hours after the soft X-ray (SXR) peak. Using the model enthalpy-based thermal evolution of loops (EBTEL), we numerically probe the production of EUV late-phase solar flares. Starting from two main mechanisms of producing the EUV late phase, i.e., long-lasting cooling and secondary heating, we carry out two groups of numerical experiments to study the effects of these two processes on the emission characteristics in late-phase loops. In either of the two processes an EUV late-phase solar flare that conforms to the observational criteria can be numerically synthesized. However, the underlying hydrodynamic and thermodynamic evolutions in late-phase loops are different between the two synthetic flare cases. The late-phase peak due to a long-lasting cooling process always occurs during the radiative cooling phase, while that powered by a secondary heating is more likely to take place in the conductive cooling phase. We then propose a new method for diagnosing the two mechanisms based on the shape of EUV late-phase light curves. Moreover, from the partition of energy input, we discuss why most solar flares are not EUV late flares. Finally, by addressing some other factors that may potentially affect the loop emissions, we also discuss why the EUV late phase is mainly observed in warm coronal emissions.

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

Advanced Parkinson's disease effect on goal-directed and habitual processes involved in visuomotor associative learning

PubMed Central

Hadj-Bouziane, Fadila; Benatru, Isabelle; Brovelli, Andrea; Klinger, Hélène; Thobois, Stéphane; Broussolle, Emmanuel; Boussaoud, Driss; Meunier, Martine

2013-01-01

The present behavioral study re-addresses the question of habit learning in Parkinson's disease (PD). Patients were early onset, non-demented, dopa-responsive, candidates for surgical treatment, similar to those we found earlier as suffering greater dopamine depletion in the putamen than in the caudate nucleus. The task was the same conditional associative learning task as that used previously in monkeys and healthy humans to unveil the striatum involvement in habit learning. Sixteen patients and 20 age- and education-matched healthy control subjects learned sets of 3 visuo-motor associations between complex patterns and joystick displacements during two testing sessions separated by a few hours. We distinguished errors preceding vs. following the first correct response to compare patients' performance during the earliest phase of learning dominated by goal-directed actions with that observed later on, when responses start to become habitual. The disease significantly retarded both learning phases, especially in patients under 60 years of age. However, only the late phase deficit was disease severity-dependent and persisted on the second testing session. These findings provide the first corroboration in Parkinson patients of two ideas well-established in the animal literature. The first is the idea that associating visual stimuli to motor acts is a form of habit learning that engages the striatum. It is confirmed here by the global impairment in visuo-motor learning induced by PD. The second idea is that goal-directed behaviors are predominantly caudate-dependent whereas habitual responses are primarily putamen-dependent. At the advanced PD stages tested here, dopamine depletion is greater in the putamen than in the caudate nucleus. Accordingly, the late phase of learning corresponding to the emergence of habitual responses was more vulnerable to the disease than the early phase dominated by goal-directed actions. PMID:23386815

Local antinociceptive action of fluoxetine in the rat formalin assay: role of l-arginine/nitric oxide/cGMP/KATP channel pathway.

PubMed

Ghorbanzadeh, Behnam; Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Alboghobeish, Soheila

2018-02-01

The present study was conducted to evaluate the local antinociceptive actions of fluoxetine, a selective serotonin reuptake inhibitor, and the possible involvement of the l-arginine/NO/cGMP/K ATP channel pathway in this effect using the formalin test in rats. To elucidate the underlying mechanisms, animals were pre-treated with l-NAME, aminoguanidine, methylene blue, glibenclamide, l-arginine, sodium nitroprusside, or diazoxide. Local ipsilateral, but not contralateral, administration of fluoxetine (10-300 μg/paw) dose-dependently suppressed flinching number during both early and late phases of the test, and this was comparable with morphine also given peripherally. Pre-treatment with l-NAME, aminoguanidine, methylene blue, or glibenclamide dose-dependently prevented fluoxetine (100 μg/paw)-induced antinociception in the late phase. In contrast, administration of l-arginine, sodium nitroprusside, and diazoxide significantly enhanced the antinociception caused by fluoxetine in the late phase of the test. However, these treatments had no significant effect on the antinociceptive response of fluoxetine in the early phase of the formalin test. Our data demonstrate that local peripheral antinociception of fluoxetine during the late phase of the formalin test could be due to activation of l-arginine/NO/cGMP/K ATP channel pathway. The peripheral action of fluoxetine raises the possibility that topical application of this drug (e.g., as a cream, ointment, or jelly) may be a useful method for relieving the inflammatory pain states.

Dissociation of face-selective cortical responses by attention.

PubMed

Furey, Maura L; Tanskanen, Topi; Beauchamp, Michael S; Avikainen, Sari; Uutela, Kimmo; Hari, Riitta; Haxby, James V

2006-01-24

We studied attentional modulation of cortical processing of faces and houses with functional MRI and magnetoencephalography (MEG). MEG detected an early, transient face-selective response. Directing attention to houses in "double-exposure" pictures of superimposed faces and houses strongly suppressed the characteristic, face-selective functional MRI response in the fusiform gyrus. By contrast, attention had no effect on the M170, the early, face-selective response detected with MEG. Late (>190 ms) category-related MEG responses elicited by faces and houses, however, were strongly modulated by attention. These results indicate that hemodynamic and electrophysiological measures of face-selective cortical processing complement each other. The hemodynamic signals reflect primarily late responses that can be modulated by feedback connections. By contrast, the early, face-specific M170 that was not modulated by attention likely reflects a rapid, feed-forward phase of face-selective processing.

Anti-allergic activity of the Morinda citrifolia extract and its constituents

PubMed Central

Murata, Kazuya; Abe, Yumi; Shinohara, Kaito; Futamura-Masuda, Megumi; Uwaya, Akemi; Isami, Fumiyuki; Matsuda, Hideaki

2014-01-01

Background: Morinda citrifolia (Rubiaceae), commonly known as noni is distributed throughout tropical and sub-tropical regions of the world. Anti-allergic effects of noni have not been reported despite the clinical usage as an anti-allergic agent. Materials and Methods: To investigate the anti-allergic effects of the 50% ethanolic extract of M. citrifolia fruits and leaves (MCF-ext and MCL-ext), dinitrofluorobenzene (DNFB)-induced triphasic cutaneous reaction and picryl chloride-induced contact dermatitis (PC-CD) tests were performed. Results: In DNFB-induced triphasic cutaneous reaction, oral administration of MCF-ext and MCL-ext exhibited dose-dependent inhibition of cutaneous reaction at 1 h (immediate phase response) after the DNFB challenge. MCF-ext also inhibited ear swelling at 24 h (late phase response) and 8 days (very late phase response) after the DNFB challenge. The effect of MCL-ext on the immediate phase response was attributed to the anti-degranulation from RBL-2H3 cells, while MCF-ext had no significant effect on degranulation. The active components of anti-degranulation activity in MCL-ext were determined to be ursolic acid, rutin and kaempferol-3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside. In the PC-CD test, both MCF-ext and MCL-ext showed an anti-swelling effect but the potency of MCF-ext was stronger than MCL-ext. Conclusion: These data suggest that noni fruits and leaves can be a daily consumable material for the prevention of allergic symptoms. PMID:25002809

Mesozoic and Cenozoic structural evolution of North Oman: New insights from high-quality 3D seismic from the Lekhwair area

NASA Astrophysics Data System (ADS)

Bazalgette, Loïc; Salem, Hisham

2018-06-01

This paper highlights the role of Triassic-Jurassic extension and late Cretaceous compression in the Mesozoic-Cenozoic (Alpine) structuring of North Oman. The syn/post-Mesozoic regional structural evolution is usually documented as a succession of two stages of deformation. The Alpine 1 phase, late Cretaceous in age, occurred in association with two ophiolite obduction stages (Semail and Masirah ophiolites). It was characterised by strike slip to extensional deformation in the North Oman foreland basin sub-surface. The Alpine 2 phase, Miocene in age, was related to the continental collision responsible for both the Zagros orogen and the uplift of the Oman Mountains. The Alpine 2 deformation was transpressional to compressional. Observation and interpretation of good quality 3D seismic in the Lekhwair High area enabled the distinction of two earlier phases. Early Mesozoic extension occurred concomitantly with the regional Triassic to Jurassic rifting, developing Jurassic-age normal faults. Late Cretaceous compression occurred prior to the main Alpine 1 phase and triggered the inversion of Jurassic-seated normal faults as well as the initiation of compressional folds in the Cretaceous overburden. These early phases have been ignored or overlooked as part of the North Oman history although they are at the origin of structures hosting major local and regional hydrocarbon accumulations.

Analysis of plant hormone profiles in response to moderate dehydration stress.

PubMed

Urano, Kaoru; Maruyama, Kyonoshin; Jikumaru, Yusuke; Kamiya, Yuji; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2017-04-01

Plant responses to dehydration stress are mediated by highly complex molecular systems involving hormone signaling and metabolism, particularly the major stress hormone abscisic acid (ABA) and ABA-dependent gene expression. To understand the roles of plant hormones and their interactions during dehydration, we analyzed the plant hormone profiles with respect to dehydration responses in Arabidopsis thaliana wild-type (WT) plants and ABA biosynthesis mutants (nced3-2). We developed a procedure for moderate dehydration stress, and then investigated temporal changes in the profiles of ABA, jasmonic acid isoleucine (JA-Ile), salicylic acid (SA), cytokinin (trans-zeatin, tZ), auxin (indole-acetic acid, IAA), and gibberellin (GA 4 ), along with temporal changes in the expression of key genes involved in hormone biosynthesis. ABA levels increased in a bi-phasic pattern (at the early and late phases) in response to moderate dehydration stress. JA-Ile levels increased slightly in WT plants and strongly increased in nced3-2 mutant plants at 72 h after the onset of dehydration. The expression profiles of dehydration-inducible genes displayed temporal responses in an ABA-dependent manner. The early phase of ABA accumulation correlated with the expression of touch-inducible genes and was independent of factors involved in the major ABA regulatory pathway, including the ABA-responsive element-binding (AREB/ABF) transcription factor. JA-Ile, SA, and tZ were negatively regulated during the late dehydration response phase. Transcriptome analysis revealed important roles for hormone-related genes in metabolism and signaling during dehydration-induced plant responses. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Extreme late chronotypes and social jetlag challenged by Antarctic conditions in a population of university students from Uruguay.

PubMed

Tassino, Bettina; Horta, Stefany; Santana, Noelia; Levandovski, Rosa; Silva, Ana

2016-01-01

In humans, a person's chronotype depends on environmental cues and on individual characteristics, with late chronotypes prevailing in youth. Social jetlag (SJL), the misalignment between an individual׳s biological clock and social time, is higher in late chronotypes. Strong SJL is expected in Uruguayan university students with morning class schedules and very late entertainment activities. Sleep disorders have been reported in Antarctic inhabitants, that might be a response to the extreme environment or to the strictness of Antarctic life. We evaluated, for the first time in Uruguay, the chronotypes and SJL of 17 undergraduate students of the First Uruguayan Summer School on Antarctic Research, using Munich Chronotype Questionnaire (MCTQ) and sleep logs (SL) recorded during 3 phases: pre-Antarctic, Antarctic, and post-Antarctic. The midsleep point of free days corrected for sleep debt on work days (MSFsc,) was used as proxy of individuals' chronotype, whose values (around 6 a.m.) are the latest ever reported. We found a SJL of around 2 h in average, which correlated positively with MSFsc, confirming that late chronotypes generate a higher sleep debt during weekdays. Midsleep point and sleep duration significantly decreased between pre-Antarctic and Antarctic phases, and sleep duration rebounded to significant higher values in the post-Antarctic phase. Waking time, but not sleep onset time, significantly varied among phases. This evidence suggests that sleep schedules more likely depended on the social agenda than on the environmental light-dark shifts. High motivation of students towards Antarctic activities likely induced a subjective perception of welfare non-dependent on sleep duration.

Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent.

PubMed

Jha, Pawan Kumar; Bouâouda, Hanan; Gourmelen, Sylviane; Dumont, Stephanie; Fuchs, Fanny; Goumon, Yannick; Bourgin, Patrice; Kalsbeek, Andries; Challet, Etienne

2017-04-19

Circadian rhythms in nocturnal and diurnal mammals are primarily synchronized to local time by the light/dark cycle. However, nonphotic factors, such as behavioral arousal and metabolic cues, can also phase shift the master clock in the suprachiasmatic nuclei (SCNs) and/or reduce the synchronizing effects of light in nocturnal rodents. In diurnal rodents, the role of arousal or insufficient sleep in these functions is still poorly understood. In the present study, diurnal Sudanian grass rats, Arvicanthis ansorgei , were aroused at night by sleep deprivation (gentle handling) or caffeine treatment that both prevented sleep. Phase shifts of locomotor activity were analyzed in grass rats transferred from a light/dark cycle to constant darkness and aroused in early night or late night. Early night, but not late night, sleep deprivation induced a significant phase shift. Caffeine on its own induced no phase shifts. Both sleep deprivation and caffeine treatment potentiated light-induced phase delays and phase advances in response to a 30 min light pulse, respectively. Sleep deprivation in early night, but not late night, potentiated light-induced c-Fos expression in the ventral SCN. Caffeine treatment in midnight triggered c-Fos expression in dorsal SCN. Both sleep deprivation and caffeine treatment potentiated light-induced c-Fos expression in calbindin-containing cells of the ventral SCN in early and late night. These findings indicate that, in contrast to nocturnal rodents, behavioral arousal induced either by sleep deprivation or caffeine during the sleeping period potentiates light resetting of the master circadian clock in diurnal rodents, and activation of calbindin-containing suprachiasmatic cells may be involved in this effect. SIGNIFICANCE STATEMENT Arousing stimuli have the ability to regulate circadian rhythms in mammals. Behavioral arousal in the sleeping period phase shifts the master clock in the suprachiasmatic nuclei and/or slows down the photic entrainment in nocturnal animals. How these stimuli act in diurnal species remains to be established. Our study in a diurnal rodent, the Grass rat, indicates that sleep deprivation in the early rest period induces phase delays of circadian locomotor activity rhythm. Contrary to nocturnal rodents, both sleep deprivation and caffeine-induced arousal potentiate the photic entrainment in a diurnal rodent. Such enhanced light-induced circadian responses could be relevant for developing chronotherapeutic strategies. Copyright © 2017 the authors 0270-6474/17/374343-16$15.00/0.

Menstrual cycle effects on perceived exertion and pain during exercise among sedentary women.

PubMed

Hooper, Ann E Caldwell; Bryan, Angela D; Eaton, Melissa

2011-03-01

Increasing cardiovascular fitness through exercise participation among sedentary people is important for decreasing all-cause mortality. From an intervention perspective, identifying modifiable factors that maximize the successful initiation of exercise is of utmost importance. For women, cyclic hormonal variations can influence aspects of health and health behaviors, from smoking cessation efficacy to physiological responses to exercise. The purpose of this study was to examine the influence of menstrual cycle phase and hormonal contraceptive (HC) use on subjective response to an initial bout of moderate intensity exercise among previously sedentary women (n = 117). Women completed a treadmill exercise challenge session at 65% of their previously determined maximum oxygen consumption (Vo(2) max) during the early follicular, late follicular, or luteal phase. Participants reported ratings of perceived exertion and pain using Borg's Rating of Perceived Exertion (RPE) and CR10 scales at 10, 20, and 30 minutes during the exercise session. There was a significant menstrual phase x birth control interaction on change in RPE [F(2, 111) = 3.75, p < 0.05] and change in perceived pain [F(2, 110) = 3.31, p < 0.05]. Women in the early follicular phase who were not using HCs had significantly greater increases in RPE and increases in pain compared with women in the late follicular and luteal phases. Our results indicate that the use of HC and cycle phase influence sedentary women's subjective response to exercise. These results have important implications for the timing of exercise interventions aimed at increasing exercise among sedentary women.

Antinociceptive properties of N-Mannich bases derived from 3-substituted pyrrolidine-2,5-dione in the formalin model of persistent pain in mice.

PubMed

Obniska, Jolanta; Sałat, Kinga; Librowski, Tadeusz; Kamiński, Krzysztof; Lipkowska, Anna; Wiklik, Beata; Rybka, Sabina; Rapacz, Anna

2015-02-01

Accumulated data indicate that anticonvulsants possess antinociceptive properties in rodent pain models. In view of the anticonvulsant activity demonstrated previously among N-Mannich bases derived from 3-mono- (1-6) and 3,3-disubstituted pyrrolidine-2,5-diones (7-14) their analgesic activity has been investigated in the formalin model of tonic pain in mice. The compounds 1-14 were tested at doses equal to the respective ED50 values obtained earlier in the MES test. 0.5% formalin solution was given as intraplantar injections into the hind paw of the mouse and the duration of the nocifensive response was counted in drug-treated and vehicle-treated animals in the acute and the late phases of the test. A significant antinociceptive activity was observed for majority of the compounds. In the first phase of the test all the active compounds, except for 9-11, reduced the duration of the licking response up to 88% (compounds 2 and 6; p<0.001). In the late phase the 1-3, 5, 6, 9 and 14 were the most effective agents and their analgesic activities ranged from 92 to 100%. The results of the research indicate that some of the investigated compounds reduced effectively either both phases of the test or were able to attenuate pain during only the acute or late phase of the formalin test. These properties, which are particularly strong in case of the compounds 1-3, 5, 6, 9 and 14, might be relevant for the development of novel analgesic-active compounds and their possible use in neuropathic pain syndromes. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Role of the mouse retinal photoreceptor ribbon synapse in visual motion processing for optokinetic responses.

PubMed

Sugita, Yuko; Araki, Fumiyuki; Chaya, Taro; Kawano, Kenji; Furukawa, Takahisa; Miura, Kenichiro

2015-01-01

The ribbon synapse is a specialized synaptic structure in the retinal outer plexiform layer where visual signals are transmitted from photoreceptors to the bipolar and horizontal cells. This structure is considered important in high-efficiency signal transmission; however, its role in visual signal processing is unclear. In order to understand its role in visual processing, the present study utilized Pikachurin-null mutant mice that show improper formation of the photoreceptor ribbon synapse. We examined the initial and late phases of the optokinetic responses (OKRs). The initial phase was examined by measuring the open-loop eye velocity of the OKRs to sinusoidal grating patterns of various spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant mice showed significant initial OKRs with a spatiotemporal frequency tuning (spatial frequency, 0.09 ± 0.01 cycles/°; temporal frequency, 1.87 ± 0.12 Hz) that was slightly different from the wild-type mice (spatial frequency, 0.11 ± 0.01 cycles/°; temporal frequency, 1.66 ± 0.12 Hz). The late phase of the OKRs was examined by measuring the slow phase eye velocity of the optokinetic nystagmus induced by the sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and temporal frequencies of the mutant mice (spatial frequency, 0.11 ± 0.02 cycles/°; temporal frequency, 0.81 ± 0.24 Hz) were both lower than those in the wild-type mice (spatial frequency, 0.15 ± 0.02 cycles/°; temporal frequency, 1.93 ± 0.62 Hz). These results suggest that the ribbon synapse modulates the spatiotemporal frequency tuning of visual processing along the ON pathway by which the late phase of OKRs is mediated.

Role of the Mouse Retinal Photoreceptor Ribbon Synapse in Visual Motion Processing for Optokinetic Responses

PubMed Central

Sugita, Yuko; Araki, Fumiyuki; Chaya, Taro; Kawano, Kenji; Furukawa, Takahisa; Miura, Kenichiro

2015-01-01

The ribbon synapse is a specialized synaptic structure in the retinal outer plexiform layer where visual signals are transmitted from photoreceptors to the bipolar and horizontal cells. This structure is considered important in high-efficiency signal transmission; however, its role in visual signal processing is unclear. In order to understand its role in visual processing, the present study utilized Pikachurin-null mutant mice that show improper formation of the photoreceptor ribbon synapse. We examined the initial and late phases of the optokinetic responses (OKRs). The initial phase was examined by measuring the open-loop eye velocity of the OKRs to sinusoidal grating patterns of various spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant mice showed significant initial OKRs with a spatiotemporal frequency tuning (spatial frequency, 0.09 ± 0.01 cycles/°; temporal frequency, 1.87 ± 0.12 Hz) that was slightly different from the wild-type mice (spatial frequency, 0.11 ± 0.01 cycles/°; temporal frequency, 1.66 ± 0.12 Hz). The late phase of the OKRs was examined by measuring the slow phase eye velocity of the optokinetic nystagmus induced by the sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and temporal frequencies of the mutant mice (spatial frequency, 0.11 ± 0.02 cycles/°; temporal frequency, 0.81 ± 0.24 Hz) were both lower than those in the wild-type mice (spatial frequency, 0.15 ± 0.02 cycles/°; temporal frequency, 1.93 ± 0.62 Hz). These results suggest that the ribbon synapse modulates the spatiotemporal frequency tuning of visual processing along the ON pathway by which the late phase of OKRs is mediated. PMID:25955222

Cytokine expression during early and late phase of acute Puumala hantavirus infection

PubMed Central

2011-01-01

Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection. PMID:22085404

Endocrine changes in male stumptailed macaques (Macaca arctoides) as a response to odor stimulation with vaginal secretions.

PubMed

Cerda-Molina, Ana Lilia; Hernández-López, Leonor; Chavira, Roberto; Cárdenas, Mario; Paez-Ponce, Denisse; Cervantes-De la Luz, Harry; Mondragón-Ceballos, Ricardo

2006-01-01

In mammalian species, social chemosignals are important in modulating endocrine reproductive functions. In nonhuman primates, previous studies have described a high frequency of mounting behavior by females in the follicular and periovulatory phases of the menstrual cycle. Stumptailed macaque females do not signal receptivity by means of sexual swellings, as do others macaques, therefore providing a good model in which to study chemical signaling of reproductive status. We exposed anesthetized stumptailed males to vaginal secretions of either late follicular or menses phase or to saline solution to determine the endocrine changes promoting male sexual behavior. In males exposed to follicular secretions, plasma testosterone concentrations were sustained up to 120 min after exposure. Such an effect was not observed in animals exposed to menses or saline odor sources. A luteinizing hormone surge, occurring 30 minutes after exposure to late follicular phase secretion swabs, preceded this sustained testosterone effect. The fact that late follicular scents induce sustained testosterone concentrations provides support to the idea that stumptailed males draw information concerning female reproductive status from the female's vaginal odor.

Quercetin and Its Anti-Allergic Immune Response.

PubMed

Mlcek, Jiri; Jurikova, Tunde; Skrovankova, Sona; Sochor, Jiri

2016-05-12

Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase.

A review on the structural styles of deformation during Late Cretaceous and Paleocene tectonic phases in the southern North Sea area

NASA Astrophysics Data System (ADS)

Deckers, Jef; van der Voet, Eva

2018-04-01

The Mesozoic rifts in the southern North Sea area were affected by Late Cretaceous to Paleocene inversion. Two main inversion phases were traditionally identified in this interval: the Sub-Hercynian and the Laramide phases. The Sub-Hercynian phase started in the early Late Cretaceous, peaked during the Campanian and ended in the late Maastrichtian, while the Laramide phase started in the late Danian and ended in the Thanetian. The Late Cretaceous Sub-Hercynian phase was strong and occurred in several pulses. These pulses led to basin-scale uplift by large reverse movements along basin-bounding faults and resulted in large amounts of erosion (up to 2 km) of Mesozoic and older sediments. The middle Paleocene Laramide phase on the other hand resulted in mild, domal uplift of some Late Cretaceous inverted basins and subsidence (into depocenters) of others. The subsequent Cenozoic inversion phases displayed similar or lower amplitudes and wavelengths of vertical surface movements as the Laramide phase. The transition from the Sub-Hercynian to the Laramide phase in the southern North Sea area therefore coincides with the overall transition from fault-controlled inversion to broad domal vertical surface movements.

How Stress and Anxiety Can Alter Immediate and Late Phase Skin Test Responses in Allergic Rhinitis

PubMed Central

Kiecolt-Glaser, Janice K.; Heffner, Kathi L.; Glaser, Ronald; Malarkey, William B.; Porter, Kyle; Atkinson, Cathie; Laskowski, Bryon; Lemeshow, Stanley; Marshall, Gailen D.

2010-01-01

Summary Allergic rhinitis (AR) is the fifth most common chronic disease, and the association between allergic disorders and anxiety is well-documented. To investigate how anxiety and stressors modulate skin prick test (SPT) responses and associated inflammatory responses, 28 men and women with AR were selected by clinical history and skin test responses. The participants were admitted twice to a hospital research unit for 4 hours in a crossover trial. Changes in SPT wheals were assessed before and after a standardized laboratory speech stressor, as well as again the following morning; skin responses assessed twice during a lab session without a stressor and again the following morning served as the contrast condition. Anxiety heightened the magnitude of allergen-induced wheals following the stressor. As anxiety increased, SPT wheal diameters increased after the stressor, compared to a slight decrease following the control task. Anxiety also substantially enhanced the effects of stress on late phase responses: even skin tests performed the day after the stressor reflected the continuing impact of the speech stressor among the more anxious participants. Greater anxiety was associated with more IL-6 production by Con A-stimulated leukocytes following the stressor compared to the control visit. The data suggest that stress and anxiety can enhance and prolong AR symptoms. PMID:19150180

Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

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

Brown, Robert J.; Jun, Brandon J.; Advanced Imaging Laboratory, Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California

Purpose: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results: Fractional anisotropy in the spleniummore » of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic evaluations, and testing of mitigation approaches.« less

Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis.

PubMed

Sternak, Magdalena; Jakubowski, Andrzej; Czarnowska, Elzbieta; Slominska, Ewa M; Smolenski, Ryszard T; Szafarz, Malgorzata; Walczak, Maria; Sitek, Barbara; Wojcik, Tomasz; Jasztal, Agnieszka; Kaminski, Karol; Chlopicki, Stefan

2015-09-01

Exogenous 1-methylnicotinamide (MNA) displays anti-inflammatory activity. The aim of this work was to characterize the profile of release of endogenous MNA during the initiation and progression of murine hepatitis induced by Concanavalin A (ConA). In particular we aimed to clarify the role of interleukin-6 (IL-6) as well as the energy state of hepatocytes in MNA release in early and late phases of ConA-induced hepatitis in mice. Hepatitis was induced by ConA in IL-6(+/+) and IL-6(-/-) mice, and various parameters of liver inflammation and injury, as well as the energy state of hepatocytes, were analysed in relation to MNA release. The decrease in ATP/ADP and NADH/NAD ratios, cytokine release (IL-6, IFN-ɤ), acute phase response (e.g. haptoglobin) and liver injury (alanine aminotransaminase, ALT) were all blunted in ConA-induced hepatitis in IL-6(-/-) mice as compared to IL-6(+/+) mice. The release of MNA in response to Con A was also significantly blunted in IL-6(-/-) mice as compared to IL-6(+/+) mice in the early stage of ConA-induced hepatitis. In turn, nicotinamide N-methyltransferase (NNMT) and aldehyde oxidase (AO) activities were blunted in the liver and MNA plasma concentration was elevated to similar degree in the late stage after Concanavalin A in IL-6(+/+) and IL-6(-/-) mice. In conclusion, we demonstrated that in ConA-induced hepatitis, early, but not late MNA release was IL-6-dependent. Our results suggest that in the initiation and early hepatitis, MNA release is linked to the energy deficit/impaired redox status in hepatocytes, while in a later phase, MNA release is rather linked to the systemic inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

Climate change, adaptive cycles, and the persistence of foraging economies during the late Pleistocene/Holocene transition in the Levant.

PubMed

Rosen, Arlene M; Rivera-Collazo, Isabel

2012-03-06

Climatic forcing during the Younger Dryas (∼12.9-11.5 ky B.P.) event has become the theoretical basis to explain the origins of agricultural lifestyles in the Levant by suggesting a failure of foraging societies to adjust. This explanation however, does not fit the scarcity of data for predomestication cultivation in the Natufian Period. The resilience of Younger Dryas foragers is better illustrated by a concept of adaptive cycles within a theory of adaptive change (resilience theory). Such cycles consist of four phases: release/collapse (Ω); reorganization (α), when the system restructures itself after a catastrophic stimulus through innovation and social memory--a period of greater resilience and less vulnerability; exploitation (r); and conservation (K), representing an increasingly rigid system that loses flexibility to change. The Kebarans and Late Natufians had similar responses to cold and dry conditions vs. Early Natufians and the Pre-Pottery Neolithic A responses to warm and wet climates. Kebarans and Late Natufians (α-phase) shifted to a broader-based diet and increased their mobility. Early Natufian and Pre-Pottery Neolithic A populations (r- and K-phases) had a growing investment in more narrowly focused, high-yield plant resources, but they maintained the broad range of hunted animals because of increased sedentism. These human adaptive cycles interlocked with plant and animal cycles. Forest and grassland vegetation responded to late Pleistocene and early Holocene climatic fluctuations, but prey animal cycles reflected the impact of human hunting pressure. The combination of these three adaptive cycles results in a model of human adaptation, showing potential for great sustainability of Levantine foraging systems even under adverse climatic conditions.

IL-21 Is an Antitolerogenic Cytokine of the Late-Phase Alloimmune Response

PubMed Central

Petrelli, Alessandra; Carvello, Michele; Vergani, Andrea; Lee, Kang Mi; Tezza, Sara; Du, Ming; Kleffel, Sonja; Chengwen, Liu; Mfarrej, Bechara G.; Hwu, Patrick; Secchi, Antonio; Leonard, Warren J.; Young, Deborah; Sayegh, Mohamed H.; Markmann, James F.; Zajac, Allan J.; Fiorina, Paolo

2011-01-01

OBJECTIVE Interleukin-21 (IL-21) is a proinflammatory cytokine that has been shown to affect Treg/Teff balance. However, the mechanism by which IL-21 orchestrates alloimmune response and interplays with Tregs is still unclear. RESEARCH DESIGN AND METHODS The interplay between IL-21/IL-21R signaling, FoxP3 expression, and Treg survival and function was evaluated in vitro in immunologically relevant assays and in vivo in allogenic and autoimmune models of islet transplantation. RESULTS IL-21R expression decreases on T cells and B cells in vitro and increases in the graft in vivo, while IL-21 levels increase in vitro and in vivo during anti-CD3/anti-CD28 stimulation/allostimulation in the late phase of the alloimmune response. In vitro, IL-21/IL-21R signaling (by using rmIL-21 or genetically modified CD4+ T cells [IL-21 pOrf plasmid–treated or hIL-21-Tg mice]) enhances the T-cell response during anti-CD3/anti-CD28 stimulation/allostimulation, prevents Treg generation, inhibits Treg function, induces Treg apoptosis, and reduces FoxP3 and FoxP3-dependent gene transcripts without affecting FoxP3 methylation status. In vivo targeting of IL-21/IL-21R expands intragraft and peripheral Tregs, promotes Treg neogenesis, and regulates the antidonor immune response, whereas IL-21/IL-21R signaling in Doxa-inducible ROSA-rtTA-IL-21-Tg mice expands Teffs and FoxP3− cells. Treatment with a combination of mIL-21R.Fc and CTLA4-Ig (an inhibitor of the early alloimmune response) leads to robust graft tolerance in a purely alloimmune setting and prolonged islet graft survival in NOD mice. CONCLUSIONS IL-21 interferes with different checkpoints of the FoxP3 Treg chain in the late phase of alloimmune response and, thus, acts as an antitolerogenic cytokine. Blockade of the IL-21/IL-21R pathway could be a precondition for tolerogenic protocols in transplantation. PMID:22013017

Synaptic potentials in respiratory neurones during evoked phase switching after NMDA receptor blockade in the cat

PubMed Central

Pierrefiche, O; Haji, A; Foutz, A S; Takeda, R; Champagnat, J; Denavit-Saubié, M

1998-01-01

Blockade of NMDA receptors by dizocilpine impairs the inspiratory off-switch (IOS) of central origin but not the IOS evoked by stimulation of sensory afferents. To investigate whether this difference was due to the effects of different patterns of synaptic interactions on respiratory neurones, we stimulated electrically the superior laryngeal nerve (SLN) or vagus nerve in decerebrate cats before and after i.v. administration of dizocilpine, whilst recording intracellularly. Phrenic nerve responses to ipsilateral SLN or vagal stimulation were: at mid-inspiration, a transient inhibition often followed by a brief burst of activity; at late inspiration, an IOS; and at mid-expiration, a late burst of activity. In all neurones (n = 16), SLN stimulation at mid-inspiration evoked an early EPSP during phase 1 (latency to the arrest of phrenic nerve activity), followed by an IPSP in inspiratory (I) neurones (n = 8) and by a wave of EPSPs in post-inspiratory (PI) neurones (n = 8) during phase 2 (inhibition of phrenic activity). An EPSP in I neurones and an IPSP in PI neurones occurred during phase 3 (brief phrenic burst) following phase 2. Evoked IOS was associated with a fast (phase 1) activation of PI neurones, whereas during spontaneous IOS, a progressive (30-50 ms) depolarization of PI neurones preceded the arrest of phrenic activity. Phase 3 PSPs were similar to those occurring during the burst of activity seen at the start of spontaneous inspiration. Dizocilpine did not suppress the evoked phrenic inhibition and the late burst of activity. The shapes and timing of the evoked PSPs and the changes in membrane potential in I and PI neurones during the phase transition were not altered. We hypothesize that afferent sensory pathways not requiring NMDA receptors (1) terminate inspiration through a premature activation of PI neurones, and (2) evoke a late burst of phrenic activity which might be the first stage of the inspiratory on-switch. PMID:9508816

T(reg) cells may regulate interlukin-17 production by modulating TH1 responses in 1,3-β-glucan-induced lung inflammation in mice.

PubMed

Chen, Ying; Liu, Fangwei; Weng, Dong; Song, Laiyu; Li, Cuiying; Tang, Wen; Yu, Ye; Dai, Wujing; Chen, Jie

2013-01-01

1,3-β-glucan is considered a fungal biomarker and exposure to this agent can induce lung inflammation. Complement activation plays an important role in early immune responses to β-glucan. Previous studies showed that T-regulatory cells (Tregs) regulated 1,3-β-glucan-induced lung inflammation by modulating the maintenance of immune homeostasis in the lung. Both interleukin (IL)-17 and TH17 cells play pivotal roles in inflammation associated with lung disease and share reciprocal developmental pathways with Tregs. However, the effect of Tregs on IL-17 and TH17 responses in 1,3-β-glucan-induced lung inflammation remains unclear. In this study, mice were exposed to 1,3-β-glucan by intratracheal instillation. To investigate the effects of Tregs on IL-17 and TH17 cells in the induced lung inflammation, a Treg-depleted mice model was generated by administration of anti-CD25 mAb. The results indicated that Treg-depleted mice showed more severe pathological inflammatory changes in lung tissues. Tregs depletion reduced IL-17 expression in these tissues, and increased those of TH1 cytokines. The expression of IL-17 increased at the early phase of the inflammation response. There were no significant effects of the Tregs on expression of RORγt and IL-6 or the amount of CD4(+)IL-17(+) cells in the lungs. When taken together, the late phase of the 1,3-β-glucan-induced inflammatory response in the mice was primarily mediated by TH1 cytokines rather than IL-17. In contrast, the early phase of the inflammatory response might be mediated in part by IL-17 along with activated complement. Tregs might be required for IL-17 expression during the late phase inflammatory response in mice. The increased IL-17 mRNA observed during the 1,3-β-glucan induced inflammatory response were attributed to cells other than TH17 cells.

Extreme late chronotypes and social jetlag challenged by Antarctic conditions in a population of university students from Uruguay

PubMed Central

Tassino, Bettina; Horta, Stefany; Santana, Noelia; Levandovski, Rosa; Silva, Ana

2016-01-01

In humans, a person’s chronotype depends on environmental cues and on individual characteristics, with late chronotypes prevailing in youth. Social jetlag (SJL), the misalignment between an individual׳s biological clock and social time, is higher in late chronotypes. Strong SJL is expected in Uruguayan university students with morning class schedules and very late entertainment activities. Sleep disorders have been reported in Antarctic inhabitants, that might be a response to the extreme environment or to the strictness of Antarctic life. We evaluated, for the first time in Uruguay, the chronotypes and SJL of 17 undergraduate students of the First Uruguayan Summer School on Antarctic Research, using Munich Chronotype Questionnaire (MCTQ) and sleep logs (SL) recorded during 3 phases: pre-Antarctic, Antarctic, and post-Antarctic. The midsleep point of free days corrected for sleep debt on work days (MSFsc,) was used as proxy of individuals’ chronotype, whose values (around 6 a.m.) are the latest ever reported. We found a SJL of around 2 h in average, which correlated positively with MSFsc, confirming that late chronotypes generate a higher sleep debt during weekdays. Midsleep point and sleep duration significantly decreased between pre-Antarctic and Antarctic phases, and sleep duration rebounded to significant higher values in the post-Antarctic phase. Waking time, but not sleep onset time, significantly varied among phases. This evidence suggests that sleep schedules more likely depended on the social agenda than on the environmental light–dark shifts. High motivation of students towards Antarctic activities likely induced a subjective perception of welfare non-dependent on sleep duration. PMID:27226819

Menstrual Cycle Effects on Perceived Exertion and Pain During Exercise Among Sedentary Women

PubMed Central

Bryan, Angela D.; Eaton, Melissa

2011-01-01

Abstract Background Increasing cardiovascular fitness through exercise participation among sedentary people is important for decreasing all-cause mortality. From an intervention perspective, identifying modifiable factors that maximize the successful initiation of exercise is of utmost importance. For women, cyclic hormonal variations can influence aspects of health and health behaviors, from smoking cessation efficacy to physiological responses to exercise. The purpose of this study was to examine the influence of menstrual cycle phase and hormonal contraceptive (HC) use on subjective response to an initial bout of moderate intensity exercise among previously sedentary women (n = 117). Methods Women completed a treadmill exercise challenge session at 65% of their previously determined maximum oxygen consumption (Vo2 max) during the early follicular, late follicular, or luteal phase. Participants reported ratings of perceived exertion and pain using Borg's Rating of Perceived Exertion (RPE) and CR10 scales at 10, 20, and 30 minutes during the exercise session. Results There was a significant menstrual phase × birth control interaction on change in RPE [F(2, 111) = 3.75, p < 0.05] and change in perceived pain [F(2, 110) = 3.31, p < 0.05]. Women in the early follicular phase who were not using HCs had significantly greater increases in RPE and increases in pain compared with women in the late follicular and luteal phases. Conclusions Our results indicate that the use of HC and cycle phase influence sedentary women's subjective response to exercise. These results have important implications for the timing of exercise interventions aimed at increasing exercise among sedentary women. PMID:21219246

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

PubMed

Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

2012-06-25

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

Self-determined motivation in rehabilitating professional rugby union players.

PubMed

Carson, Fraser; Polman, Remco C J

2017-01-01

The aim of the present study was to explore the views of professional rugby union players during the early rehabilitation, late rehabilitation and return to play stages, following anterior cruciate ligament (ACL) injury. A qualitative dominant, mixed methodological approach was utilized with five players who had suffered an ACL injury requiring reconstructive surgery. A longitudinal approach, concurrent with each player's rehabilitation, consisting of twice monthly interviews, a self-report diary and three established questionnaires (MOS-Social Support Survey, Sherbourne & Stewart, 1991; Sport Climate Questionnaire, Deci & Ryan, n.d.; Injury Rehabilitation Questionnaire, Deci & Ryan, n.d.) were completed. Theoretical thematic analysis was conducted on three distinct phases (Early Limited Participation phase, 10 higher order themes; Late Limited Rehabilitation phase, 11 higher order themes; and Return to Play phase, 9 higher order themes) and coded relating to autonomy, competence and relatedness. The findings suggest that increased autonomy and control assist emotional and behavioral responses during rehabilitation and return to play, while development of competence increases self-confidence.

Replication in hydroxyurea: it's a matter of time.

PubMed

Alvino, Gina M; Collingwood, David; Murphy, John M; Delrow, Jeffrey; Brewer, Bonita J; Raghuraman, M K

2007-09-01

Hydroxyurea (HU) is a DNA replication inhibitor that negatively affects both the elongation and initiation phases of replication and triggers the "intra-S phase checkpoint." Previous work with budding yeast has shown that, during a short exposure to HU, MEC1/RAD53 prevent initiation at some late S phase origins. In this study, we have performed microarray experiments to follow the fate of all origins over an extended exposure to HU. We show that the genome-wide progression of DNA synthesis, including origin activation, follows the same pattern in the presence of HU as in its absence, although the time frames are very different. We find no evidence for a specific effect that excludes initiation from late origins. Rather, HU causes S phase to proceed in slow motion; all temporal classes of origins are affected, but the order in which they become active is maintained. We propose a revised model for the checkpoint response to HU that accounts for the continued but slowed pace of the temporal program of origin activation.

On the Importance of the Flare's Late Phase for the Solar Extreme Ultraviolet Irradiance

NASA Technical Reports Server (NTRS)

Woods, Thomas N.; Eparvier, Frank; Jones, Andrew R.; Hock, Rachel; Chamberlin, Phillip C.; Klimchuk, James A.; Didkovsky, Leonid; Judge, Darrell; Mariska, John; Bailey, Scott;

Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats

PubMed Central

Bernabeu, Ramon; Bevilaqua, Lia; Ardenghi, Patricia; Bromberg, Elke; Schmitz, Paulo; Bianchin, Marino; Izquierdo, Ivan; Medina, Jorge H.

1997-01-01

cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been recently proposed to participate in both the late phase of long term potentiation in the hippocampus and in the late, protein synthesis-dependent phase of memory formation. Here we report that a late memory consolidation phase of an inhibitory avoidance learning is regulated by an hippocampal cAMP signaling pathway that is activated, at least in part, by D1/D5 receptors. Bilateral infusion of SKF 38393 (7.5 μg/side), a D1/D5 receptor agonist, into the CA1 region of the dorsal hippocampus, enhanced retention of a step-down inhibitory avoidance when given 3 or 6 h, but not immediately (0 h) or 9 h, after training. In contrast, full retrograde amnesia was obtained when SCH 23390 (0.5 μg/side), a D1/D5 receptor antagonist, was infused into the hippocampus 3 or 6 h after training. Intrahippocampal infusion of 8Br-cAMP (1.25 μg/side), or forskolin (0.5 μg/side), an activator of adenylyl cyclase, enhanced memory when given 3 or 6 h after training. KT5720 (0.5 μg/side), a specific inhibitor of PKA, hindered memory consolidation when given immediately or 3 or 6 h posttraining. Rats submitted to the avoidance task showed learning-specific increases in hippocampal 3H-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h after training. In addition, PKA activity and P-CREB (phosphorylated form of cAMP responsive element binding protein) immunoreactivity increased in the hippocampus immediately and 3 and 6 h after training. Together, these findings suggest that the late phase of memory consolidation of an inhibitory avoidance is modulated cAMP/PKA signaling pathways in the hippocampus. PMID:9192688

Expression analysis of genes involved in TLR2-related signaling pathway: Inflammation and apoptosis after ischemic brain injury.

PubMed

Winters, L; Winters, T; Gorup, D; Mitrečić, D; Curlin, M; Križ, J; Gajović, S

2013-05-15

Toll-like receptor 2 (TLR2) is involved in innate immunity in the brain and in the cascade of events after ischemic stroke. The aim of this study was to get an insight into the expression of genes related to TLR2 signaling pathway and associated with inflammation and apoptosis in the later stages of brain response after ischemic injury. Middle cerebral artery occlusion was performed on both wild-type and TLR2(-/-) mice followed by real-time PCR to measure the relative expression of selected genes. In TLR2(-/-) mice expression of genes involved in proinflammatory response was decreased after cerebral ischemia. Tnf was the most prominent cytokine active in the late phase of recovery. Contrary to proinflammatory genes, the expression of Casp8, as a hallmark of apoptosis, was increased in TLR2(-/-) mice, in particular in the late phase of recovery. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Status Update on the NCRP Scientific Committee SC 5-1 Report: Decision Making for Late-Phase Recovery from Nuclear or Radiological Incidents - 13450

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

Chen, S.Y.

2013-07-01

In August 2008, the U.S. Department of Homeland Security (DHS) issued its final Protective Action Guide (PAG) for radiological dispersal device (RDD) and improvised nuclear device (IND) incidents. This document specifies protective actions for public health during the early and intermediate phases and cleanup guidance for the late phase of RDD or IND incidents, and it discusses approaches to implementing the necessary actions. However, while the PAG provides specific guidance for the early and intermediate phases, it prescribes no equivalent guidance for the late-phase cleanup actions. Instead, the PAG offers a general description of a complex process using a site-specificmore » optimization approach. This approach does not predetermine cleanup levels but approaches the problem from the factors that would bear on the final agreed-on cleanup levels. Based on this approach, the decision-making process involves multifaceted considerations including public health, the environment, and the economy, as well as socio-political factors. In an effort to fully define the process and approach to be used in optimizing late-phase recovery and site restoration following an RDD or IND incident, DHS has tasked the NCRP with preparing a comprehensive report addressing all aspects of the optimization process. Preparation of the NCRP report is a three-year (2010-2013) project assigned to a scientific committee, the Scientific Committee (SC) 5-1; the report was initially titled, Approach to Optimizing Decision Making for Late- Phase Recovery from Nuclear or Radiological Terrorism Incidents. Members of SC 5-1 represent a broad range of expertise, including homeland security, health physics, risk and decision analysis, economics, environmental remediation and radioactive waste management, and communication. In the wake of the Fukushima nuclear accident of 2011, and guided by a recent process led by the White House through a Principal Level Exercise (PLE), the optimization approach has since been expanded to include off-site contamination from major nuclear power plant accidents as well as other nuclear or radiological incidents. The expanded application under the current guidance has thus led to a broadened scope of the report, which is reflected in its new title, Decision Making for Late-Phase Recovery from Nuclear or Radiological Incidents. The NCRP report, which is due for publication in 2013, will substantiate the current DHS guidance by clarifying and elaborating on the processes required for the development and implementation of procedures for optimizing decision making for late-phase recovery, enabling the establishment of cleanup goals on a site-specific basis. The report will contain a series of topics addressing important issues related to the long-term recovery from nuclear or radiological incidents. Special topics relevant to supporting the optimization of the decision-making process will include cost-benefit analysis, radioactive waste management, risk communication, stakeholder interaction, risk assessment, and decontamination approaches and techniques. The committee also evaluated past nuclear and radiological incidents for their relevance to the report, including the emerging issues associated with the Fukushima nuclear accident. Thus, due to the commonality of the late-phase issues (such as the potential widespread contamination following an event), the majority of the information pertaining to the response in the late-phase decision-making period, including site-specific optimization framework and approach, could be used or adapted for use in case of similar situations that are not due to terrorism, such as those that would be caused by major nuclear facility accidents or radiological incidents. To ensure that the report and the NCRP recommendations are current and relevant to the effective implementation of federal guidance, SC 5-1 has actively coordinated with the agencies of interest and other relevant stakeholders throughout the duration of the project. The resulting report will be an important resource to guide those involved in late-phase recovery efforts following a nuclear or radiological incident. (authors)« less

Nuclear Translocation of MEK1 Triggers a Complex T cell Response through the Co-repressor Silencing Mediator of Retinoid and Thyroid Hormone Receptor (SMRT)

PubMed Central

Guo, Lei; Chen, Chaoyu; Liang, Qiaoling; Karim, Md. Zunayet; Gorska, Magdalena M.; Alam, Rafeul

2012-01-01

MEK1 phosphorylates ERK1/2 and regulates T cell generation, differentiation and function. MEK1 has recently been shown to translocate to the nucleus. Its nuclear function is largely unknown. By studying human CD4 T cells we demonstrate that a low level of MEK1 is present in the nucleus of CD4 T cells under basal conditions. T cell activation further increases the nuclear translocation of MEK1. MEK1 interacts with the nuclear receptor co-repressor SMRT. MEK1 reduces the nuclear level of SMRT in an activation-dependent manner. MEK1 is recruited to the promoter of c-Fos upon TCR stimulation. Conversely, SMRT is bound to the c-Fos promoter under basal conditions and is removed upon TCR stimulation. We examined the role of SMRT in regulation of T cell function. siRNA-mediated knockdown of SMRT results in a biphasic effect on cytokine production. The production of the cytokines—IL2, IL4, IL10 and IFNγ increases in the early phase (8 hr) and then decreases in the late phase (48 hr). The late phase decrease is associated with inhibition of T cell proliferation. The late phase inhibition of T cell activation is, in part, mediated by IL10 that is produced in the early phase, and in part, by β-catenin signaling. Thus, we have identified a novel nuclear function of MEK1. MEK1 triggers a complex pattern of early T cell activation followed by a late inhibition through its interaction with SMRT. This biphasic dual effect likely reflects a homeostatic regulation of T cell function by MEK1. PMID:23225884

Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17beta-treated, intact follicular and pregnant sheep.

PubMed

Magness, Ronald R; Phernetton, Terrance M; Gibson, Tiffini C; Chen, Dong-Bao

2005-05-15

Oestrogen dramatically increases uterine blood flow (UBF) in ovariectomized (Ovx) ewes. Both the follicular phase and pregnancy are normal physiological states with elevated levels of circulating oestrogen. ICI 182 780 is a pure steroidal oestrogen receptor (ER) antagonist that blocks oestrogenic actions in oestrogen-responsive tissue. We hypothesized that an ER-mediated mechanism is responsible for in vivo rises in UBF in physiological states of high oestrogen. The purpose of the study was to examine the effect of an ER antagonist on exogenous and endogenous oestradiol-17beta (E2beta)-mediated elevations in UBF. Sheep were surgically instrumented with bilateral uterine artery blood flow transducers, and uterine and femoral artery catheters. Ovx animals (n = 8) were infused with vehicle (35% ethanol) or ICI 182 780 (0.1-3.0 microg min(-1)) into one uterine artery for 10 min before and 50 min after E2beta was given (1 microg kg(-1) I.V. bolus) and UBF was recorded for an additional hour. Intact, cycling sheep were synchronized to the follicular phase using progesterone, prostaglandin F2alpha(PGF2alpha) and pregnant mare serum gonadotrophin (PMSG). When peri-ovulatory rises in UBF reached near peak levels, ICI 182 780 (1 or 2 microg (ml uterine blood flow)-1) was infused unilaterally (n = 4 sheep). Ewes in the last stages of pregnancy (late pregnant ewes) were also given ICI 182 780 (0.23-2.0 microg (ml uterine blood flow)-1; 60 min infusion) into one uterine artery (n = 8 sheep). In Ovx sheep, local infusion of ICI 182 780 did not alter systemic cardiovascular parameters, such as mean arterial blood pressure or heart rate; however, it maximally decreased ipsilateral, but not contralateral, UBF vasodilatory responses to exogenous E2beta by approximately 55-60% (P < 0.01). In two models of elevated endogenous E2beta, local ICI 182 780 infusion inhibited the elevated UBF seen in follicular phase and late pregnant ewes in a time-dependent manner by approximately 60% and 37%, respectively; ipsilateral > contralateral effects (P < 0.01). In late pregnant sheep ICI 182 780 also mildly and acutely (for 5-30 min) elevated mean arterial pressure and heart rate (P < 0.05). We conclude that exogenous E2beta-induced increases in UBF in the Ovx animal and endogenous E2beta-mediated elevations of UBF during the follicular phase and late pregnancy are partially mediated by ER-dependent mechanisms.

Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17β-treated, intact follicular and pregnant sheep

PubMed Central

Magness, Ronald R; Phernetton, Terrance M; Gibson, Tiffini C; Chen, Dong-bao

2005-01-01

Oestrogen dramatically increases uterine blood flow (UBF) in ovariectomized (Ovx) ewes. Both the follicular phase and pregnancy are normal physiological states with elevated levels of circulating oestrogen. ICI 182 780 is a pure steroidal oestrogen receptor (ER) antagonist that blocks oestrogenic actions in oestrogen-responsive tissue. We hypothesized that an ER-mediated mechanism is responsible for in vivo rises in UBF in physiological states of high oestrogen. The purpose of the study was to examine the effect of an ER antagonist on exogenous and endogenous oestradiol-17β (E2β)-mediated elevations in UBF. Sheep were surgically instrumented with bilateral uterine artery blood flow transducers, and uterine and femoral artery catheters. Ovx animals (n = 8) were infused with vehicle (35% ethanol) or ICI 182 780 (0.1–3.0 μg min−1) into one uterine artery for 10 min before and 50 min after E2β was given (1 μg kg−1i.v. bolus) and UBF was recorded for an additional hour. Intact, cycling sheep were synchronized to the follicular phase using progesterone, prostaglandin F2α(PGF2α) and pregnant mare serum gonadotrophin (PMSG). When peri-ovulatory rises in UBF reached near peak levels, ICI 182 780 (1 or 2 μg (ml uterine blood flow)−1) was infused unilaterally (n = 4 sheep). Ewes in the last stages of pregnancy (late pregnant ewes) were also given ICI 182 780 (0.23–2.0 μg (ml uterine blood flow)−1; 60 min infusion) into one uterine artery (n = 8 sheep). In Ovx sheep, local infusion of ICI 182 780 did not alter systemic cardiovascular parameters, such as mean arterial blood pressure or heart rate; however, it maximally decreased ipsilateral, but not contralateral, UBF vasodilatory responses to exogenous E2β by ∼55–60% (P < 0.01). In two models of elevated endogenous E2β, local ICI 182 780 infusion inhibited the elevated UBF seen in follicular phase and late pregnant ewes in a time-dependent manner by ∼60% and 37%, respectively; ipsilateral ≫ contralateral effects (P < 0.01). In late pregnant sheep ICI 182 780 also mildly and acutely (for 5–30 min) elevated mean arterial pressure and heart rate (P < 0.05). We conclude that exogenous E2β-induced increases in UBF in the Ovx animal and endogenous E2β-mediated elevations of UBF during the follicular phase and late pregnancy are partially mediated by ER-dependent mechanisms. PMID:15774510

Temporal Changes in Gene Expression after Injury in the Rat Retina

PubMed Central

Vázquez-Chona, Félix; Song, Bong K.; Geisert, Eldon E.

2010-01-01

Purpose The goal of this study was to define the temporal changes in gene expression after retinal injury and to relate these changes to the inflammatory and reactive response. A specific emphasis was placed on the tetraspanin family of proteins and their relationship with markers of reactive gliosis. Methods Retinal tears were induced in adult rats by scraping the retina with a needle. After different survival times (4 hours, and 1, 3, 7, and 30 days), the retinas were removed, and mRNA was isolated, prepared, and hybridized to the Affymatrix RGU34A microarray (Santa Clara, CA). Microarray results were confirmed by using RT-PCR and correlation to protein levels was determined. Results Of the 8750 genes analyzed, approximately 393 (4.5%) were differentially expressed. Clustering analysis revealed three major profiles: (1) The early response was characterized by the upregulation of transcription factors; (2) the delayed response included a high percentage of genes related to cell cycle and cell death; and (3) the late, sustained profile clustered a significant number of genes involved in retinal gliosis. The late, sustained cluster also contained the upregulated crystallin genes. The tetraspanins Cd9, Cd81, and Cd82 were also associated with the late, sustained response. Conclusions The use of microarray technology enables definition of complex genetic changes underlying distinct phases of the cellular response to retinal injury. The early response clusters genes associate with the transcriptional regulation of the wound-healing process and cell death. Most of the genes in the late, sustained response appear to be associated with reactive gliosis. PMID:15277499

"Missing links" in borderline personality disorder: loss of neural synchrony relates to lack of emotion regulation and impulse control.

PubMed

Williams, Leanne M; Sidis, Anna; Gordon, Evian; Meares, Russell A

2006-05-01

Symptoms of borderline personality disorder (BPD) may reflect distinct breakdowns in the integration of posterior and frontal brain networks. We used a high temporal resolution measure (40-Hz gamma phase synchrony) of brain activity to examine the connectivity of brain function in BPD. Unmedicated patients with BPD (n = 15) and age-and sex-matched healthy control subjects (n = 15) undertook a task requiring discrimination of salient from background tones. In response to salient stimuli, the magnitude and latency of peak gamma phase synchrony for early (0-150 ms post stimulus) and late (250-500 ms post stimulus) phases were calculated for frontal and posterior regions and for left and right hemispheres. We recorded skin conductance responses (SCRs) and reaction time (RT) simultaneously to examine the contribution of arousal and performance. Compared with controls, patients with BPD had a significant delay in early posterior gamma synchrony and a reduction in right hemisphere late gamma synchrony in response to salient stimuli. Both SCR onset and RT were also delayed in BPD, but independently from differences in synchrony. The delay in posterior synchrony was associated with cognitive symptoms, and reduced right hemisphere synchrony was associated with impulsivity. These findings suggest that distinct impairments in the functional connectivity of neural systems for orienting to salient input underlie core dimensions of cognitive disturbance and poor impulse control in BPD.

Mid-Late Miocene deformation of the northern Kuqa fold-and-thrust belt (southern Chinese Tian Shan): An apatite (U-Th-Sm)/He study

NASA Astrophysics Data System (ADS)

Chang, Jian; Tian, Yuntao; Qiu, Nansheng

2017-01-01

The Kuqa fold-and-thrust belt developed in response to Cenozoic southward shortening between the Chinese Tian Shan and the Tarim Basin. This study aims to constrain the timing of the Late Cenozoic deformation by determining the onset time of enhanced rock cooling using apatite (U-Th-Sm)/He thermochronometry. Eight sedimentary samples were collected from Triassic to Cretaceous strata exposed along a 17 km N-S transect, cross-cutting the northern Kuqa fold-and-thrust belt. Single-grain AHe ages from these samples mostly cluster around 8-16 Ma and are younger than their depositional ages. Older AHe ages show a positive relationship with [eU], a proxy for radiation damage. Modelling of the observed age-eU relationships suggest a phase of enhanced cooling and erosion initiated at Mid-Late Miocene time (10-20 Ma) in the northern Kuqa fold-and-thrust belt. This result is consistent with a coeval abrupt increase of sedimentation rate in the foreland Kuqa depression, south of the study area, indicating a Mid-Late Miocene phase of shortening in the northern Kuqa fold-and-thrust belt.

Photic Resetting and Entrainment in CLOCK-Deficient Mice

PubMed Central

Dallmann, Robert; DeBruyne, Jason P.; Weaver, David R.

2012-01-01

Mice lacking CLOCK protein have a relatively subtle circadian phenotype, including a slightly shorter period in constant darkness, differences in phase resetting after 4-hr light pulses in the early and late night, and a variably advanced phase angle of entrainment in a light-dark (LD) cycle (DeBruyne et al., Neuron 50:465–477, 2006). The present series of experiments was conducted to more fully characterize the circadian phenotype of Clock−/− mice under various lighting conditions. A phase-response curve (PRC) to 4-hour light pulses in free-running mice was conducted; the results confirm that Clock−/− mice exhibit very large phase advances after 4 hrs light pulses in the late subjective night, but have relatively normal responses to light at other phases. The abnormal shape of the PRC to light may explain the tendency of CLOCK-deficient mice to begin activity before lights-out when housed in a 12 hrs light: 12 hrs dark lighting schedule. To assess this relationship further, Clock−/− and wild-type control mice were entrained to skeleton lighting cycles (1L:23D, and 1L:10D:1L:12D). Comparing entrainment under the two types of skeleton photoperiods revealed that exposure to 1 hr light in the morning leads to a phase advance of activity onset (expressed the following afternoon) in Clock−/− mice, but not in the controls. Constant light typically causes an intensity-dependent increase in circadian period in mice, but this did not occur in CLOCK-deficient mice. The failure of Clock−/− mice to respond to the period-lengthening effect of constant light likely results from the increased functional impact of light falling in the phase advance zone of the PRC. Collectively, these experiments reveal that alterations in the response of CLOCK-deficient mice to light in several paradigms are likely due to an imbalance in the shape of the PRC to light. PMID:21921293

The Quiet Revolution that Transformed Women's Employment, Education, and Family. NBER Working Paper No. 11953

ERIC Educational Resources Information Center

Goldin, Claudia

2006-01-01

The modern economic role of women emerged in four phases. The first three were evolutionary; the last was revolutionary. Phase I occurred from the late nineteenth century to the 1920s; Phase II was from 1930 to 1950; Phase III extended from 1950 to the late 1970s; and Phase IV, the "quiet revolution," began in the late 1970s and is still ongoing.…

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

PubMed

Akram, Afia Muhammad; Iqbal, Zafar; Akhtar, Tanveer; Khalid, Ahmed Mukhtar; Sabar, Muhammad Farooq; Qazi, Mahmood Hussain; Aziz, Zeba; Sajid, Nadia; Aleem, Aamer; Rasool, Mahmood; Asif, Muhammad; Aloraibi, Saleh; Aljamaan, Khaled; Iqbal, Mudassar

2017-04-03

BCR-ABL kinase domain (K D ) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-K D mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-K D . Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-K D mutation screening in late chronic phase CML patients for improved clinical management of disease.

Quantitative Proteomic Profiling of Early and Late Responses to Salicylic Acid in Cucumber Leaves

PubMed Central

Li, Liang; Shang, Qing-Mao

2016-01-01

Salicylic acid (SA) is an important phytohormone that plays vital regulatory roles in plant growth, development, and stress responses. However, studies on the molecular mechanism of SA, especially during the early SA responses, are lagging behind. In this study, we initiated a comprehensive isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the early and late SA-responsive proteins in leaves of cucumber (Cucumis sativus L.) seedlings. Upon SA application through the roots, endogenous SA accumulated in cucumber leaves. By assaying the changes in marker gene expression and photosynthetic rate, we collected samples at 12 h and 72 h post treatment (hpt) to profile the early and late SA responsiveness, respectively. The iTRAQ assay followed by tandem mass spectrometry revealed 135 differentially expressed proteins (DEPs) at 12 hpt and 301 DEPs at 72 hpt. The functional categories for these SA-responsive proteins included in a variety of biochemical processes, including photosynthesis, redox homeostasis, carbohydrate and energy metabolism, lipid metabolism, transport, protein folding and modification, proteolysis, cell wall organization, and the secondary phenylpropanoid pathway. Conclusively, based on the abundant changes of these DEPs, together with their putative functions, we proposed a possible SA-responsive protein network. It appears that SA could elicit reactive oxygen species (ROS) production via enhancing the photosynthetic electron transferring, and then confer some growth-promoting and stress-priming effects on cells during the late phase, including enhanced photosynthesis and ROS scavenging, altered carbon metabolic flux for the biosynthesis of amino acids and nucleotides, and cell wall reorganization. Overall, the present iTRAQ assay provides higher proteome coverage and deepened our understanding of the molecular basis of SA-responses. PMID:27551830

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

PubMed Central

2012-01-01

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors. PMID:22731117

The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

PubMed

Kohen, Paulina; Castro, Olga; Palomino, Alberto; Muñoz, Alex; Christenson, Lane K; Sierralta, Walter; Carvallo, Pilar; Strauss, Jerome F; Devoto, Luigi

2003-07-01

This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in StAR mRNA (3.5-fold) and protein (1.8-fold). Collectively, these data indicate that 1) the hCG-stimulated steroidogenic response is dependent on the age of the CL; 2) the early luteal phase CL is relatively insensitive to exogenous hCG in the presence of normal pituitary gonadotropin support, but becomes responsive when the latter is withdrawn; 3) the hCG-stimulated steroidogenic response in the mid- and late luteal phase is correlated with increased StAR mRNA and protein abundance; and 4) there are differential responses of small and large luteal cells to hCG stimulation that depend upon the age of the CL.

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

PubMed

McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

2015-01-15

Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights reserved.

Adrenomedullin and adrenomedullin binding protein-1 attenuate vascular endothelial cell apoptosis in sepsis.

PubMed

Zhou, Mian; Simms, H Hank; Wang, Ping

2004-08-01

To determine whether vascular endothelial cell apoptosis occurs in the late stage of sepsis and, if so, whether administration of a potent vasodilatory peptide adrenomedullin and its newly reported specific binding protein (AM/AMBP-1) prevents sepsis-induced endothelial cell apoptosis. Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Our recent studies have shown that administration of AM/AMBP-1 delays or even prevents the transition from the hyperdynamic phase to the hypodynamic phase of sepsis, attenuates tissue injury, and decreases sepsis-induced mortality. However, the mechanisms responsible for the beneficial effects of AM/AMBP-1 in sepsis remain unknown. Polymicrobial sepsis was induced by cecal ligation and puncture in adult male rats. Human AMBP-1 (40 microg/kg body weight) was infused intravenously at the beginning of sepsis for 20 minutes and synthetic AM (12 microg/kg body weight) was continuously administered for the entire study period using an Alzert micro-osmotic pump, beginning 3 hours prior to the induction of sepsis. The thoracic aorta and pulmonary tissues were harvested at 20 hours after cecal ligation and puncture (ie, the late stage of sepsis). Apoptosis was determined using TUNEL assay, M30 Cytodeath immunostaining, and electromicroscopy. In addition, anti-apoptotic Bcl-2 and pro-apoptotic Bax gene expression and protein levels were assessed by RT-PCR and Western blot analysis, respectively. Vascular endothelial cells underwent apoptosis formation at 20 hours after cecal ligation and puncture as determined by three different methods. Moreover, partial detached endothelial cell in the aorta was observed. Bcl-2 mRNA and protein levels decreased significantly at 20 hours after the onset of sepsis while Bax was not altered. Administration of AM/AMBP-1 early after sepsis, however, significantly reduced the number of apoptotic endothelial cells. This was associated with significantly increased Bcl-2 protein levels and decreased Bax gene expression in the aortic and pulmonary tissues. The above results suggest that vascular endothelial cell apoptosis occurs in late sepsis and the anti-apoptotic effects of AM/AMBP-1 appear to be in part responsible for their beneficial effects observed under such conditions.

Multi-lobulation of the nucleus in prolonged S phase by nuclear expression of Chk tyrosine kinase.

PubMed

Nakayama, Yuji; Yamaguchi, Naoto

2005-04-01

Chk tyrosine kinase phosphorylates Src-family tyrosine kinases and suppresses their kinase activity. We recently showed that Chk localizes to the nucleus as well as the cytoplasm and inhibits cell proliferation. To investigate the role of nuclear Chk in proliferation, various Chk mutants were constructed and expressed. Nuclear localization of Chk-induced dynamic multi-lobulation of the nucleus and prolonged S phase of the cell cycle. The N-terminal domain of Chk and a portion of its kinase domain but not the kinase activity were responsible for induction of the multi-lobulation. Cell sorting analysis revealed that nuclear multi-lobulated cells were enriched in late S phase. Multi-lobulated nuclei were surrounded with lamin B1 that was particularly concentrated in concave regions of the nuclei. Furthermore, treatment with nocodazole or taxol disrupted multi-lobulation of the nucleus. These results suggest that nuclear multi-lobulation in late S phase, which is dependent on polymerization and depolymerization of microtubules, may be involved in nuclear Chk-induced inhibition of proliferation.

The temporal analysis of yeast exponential phase using shotgun proteomics as a fermentation monitoring technique

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

Huang, Eric L.; Orsat, Valerie; Shah, Manesh B

2012-01-01

System biology and bioprocess technology can be better understood using shotgun proteomics as a monitoring system during the fermentation. We demonstrated a shotgun proteomic method to monitor the temporal yeast proteome in early, middle and late exponential phases. Our study identified a total of 1389 proteins combining all 2D-LC-MS/MS runs. The temporal Saccharomyces cerevisiae proteome was enriched with proteolysis, radical detoxification, translation, one-carbon metabolism, glycolysis and TCA cycle. Heat shock proteins and proteins associated with oxidative stress response were found throughout the exponential phase. The most abundant proteins observed were translation elongation factors, ribosomal proteins, chaperones and glycolytic enzymes. Themore » high abundance of the H-protein of the glycine decarboxylase complex (Gcv3p) indicated the availability of glycine in the environment. We observed differentially expressed proteins and the induced proteins at mid-exponential phase were involved in ribosome biogenesis, mitochondria DNA binding/replication and transcriptional activator. Induction of tryptophan synthase (Trp5p) indicated the abundance of tryptophan during the fermentation. As fermentation progressed toward late exponential phase, a decrease in cell proliferation was implied from the repression of ribosomal proteins, transcription coactivators, methionine aminopeptidase and translation-associated proteins.« less

Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats.

PubMed

Safari, Fereshteh; Shekarforoosh, Shahnaz; Hashemi, Tahmineh; Namvar Aghdash, Simin; Fekri, Asefeh; Safari, Fatemeh

2017-07-01

The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection.

Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance

PubMed Central

Khare, Sangeeta; Lawhon, Sara D.; Drake, Kenneth L.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Everts, Robin E.; Lewin, Harris A.; Galindo, Cristi L.; Garner, Harold R.; Adams, Leslie Garry

2012-01-01

Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection), processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i) early (30 min and 1 hr post-infection), ii) intermediate (2, 4 and 8 hrs post-infection), and iii) late (12 hrs post-infection). We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence) that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed pathways and specifically modified mechanistic genes contributing to the colonization of Peyer's patch. PMID:22912686

Role and Importance of IGF-1 in Traumatic Brain Injuries

PubMed Central

Mangiola, Annunziato; Vigo, Vera; Anile, Carmelo; De Bonis, Pasquale; Lofrese, Giorgio

2015-01-01

It is increasingly affirmed that most of the long-term consequences of TBI are due to molecular and cellular changes occurring during the acute phase of the injury and which may, afterwards, persist or progress. Understanding how to prevent secondary damage and improve outcome in trauma patients, has been always a target of scientific interest. Plans of studies focused their attention on the posttraumatic neuroendocrine dysfunction in order to achieve a correlation between hormone blood level and TBI outcomes. The somatotropic axis (GH and IGF-1) seems to be the most affected, with different alterations between the acute and late phases. IGF-1 plays an important role in brain growth and development, and it is related to repair responses to damage for both the central and peripheral nervous system. The IGF-1 blood levels result prone to decrease during both the early and late phases after TBI. Despite this, experimental studies on animals have shown that the CNS responds to the injury upregulating the expression of IGF-1; thus it appears to be related to the secondary mechanisms of response to posttraumatic damage. We review the mechanisms involving IGF-1 in TBI, analyzing how its expression and metabolism may affect prognosis and outcome in head trauma patients. PMID:26417600

Analysis of the temporal program of replication initiation in yeast chromosomes.

PubMed

Friedman, K L; Raghuraman, M K; Fangman, W L; Brewer, B J

1995-01-01

The multiple origins of eukaryotic chromosomes vary in the time of their initiation during S phase. In the chromosomes of Saccharomyces cerevisiae the presence of a functional telomere causes nearby origins to delay initiation until the second half of S phase. The key feature of telomeres that causes the replication delay is the telomeric sequence (C(1-3)A/G(1-3)T) itself and not the proximity of the origin to a DNA end. A second group of late replicating origins has been found at an internal position on chromosome XIV. Four origins, spanning approximately 140 kb, initiate replication in the second half of S phase. At least two of these internal origins maintain their late replication time on circular plasmids. Each of these origins can be separated into two functional elements: those sequences that provide origin function and those that impose late activation. Because the assay for determining replication time is costly and laborious, it has not been possible to analyze in detail these 'late' elements. We report here the development of two new assays for determining replication time. The first exploits the expression of the Escherichia coli dam methylase in yeast and the characteristic period of hemimethylation that transiently follows the passage of a replication fork. The second uses quantitative hybridization to detect two-fold differences in the amount of specific restriction fragments as a function of progress through S phase. The novel aspect of this assay is the creation in vivo of a non-replicating DNA sequence by site-specific pop-out recombination. This non-replicating fragment acts as an internal control for copy number within and between samples. Both of these techniques are rapid and much less costly than the more conventional density transfer experiments that require CsCl gradients to detect replicated DNA. With these techniques it should be possible to identify the sequences responsible for late initiation, to search for other late replicating regions in the genome, and to begin to analyze the effect that altering the temporal program has on chromosome function.

Decrease in early right alpha band phase synchronization and late gamma band oscillations in processing syntax in music.

PubMed

Ruiz, María Herrojo; Koelsch, Stefan; Bhattacharya, Joydeep

2009-04-01

The present study investigated the neural correlates associated with the processing of music-syntactical irregularities as compared with regular syntactic structures in music. Previous studies reported an early ( approximately 200 ms) right anterior negative component (ERAN) by traditional event-related-potential analysis during music-syntactical irregularities, yet little is known about the underlying oscillatory and synchronization properties of brain responses which are supposed to play a crucial role in general cognition including music perception. First we showed that the ERAN was primarily represented by low frequency (<8 Hz) brain oscillations. Further, we found that music-syntactical irregularities as compared with music-syntactical regularities, were associated with (i) an early decrease in the alpha band (9-10 Hz) phase synchronization between right fronto-central and left temporal brain regions, and (ii) a late ( approximately 500 ms) decrease in gamma band (38-50 Hz) oscillations over fronto-central brain regions. These results indicate a weaker degree of long-range integration when the musical expectancy is violated. In summary, our results reveal neural mechanisms of music-syntactic processing that operate at different levels of cortical integration, ranging from early decrease in long-range alpha phase synchronization to late local gamma oscillations. 2008 Wiley-Liss, Inc.

Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial.

PubMed

Magnano, Laura; Montoto, Silvia; González-Barca, Eva; Briones, Javier; Sancho, Juan Manuel; Muntañola, Ana; Salar, Antonio; Besalduch, Joan; Escoda, Lourdes; Moreno, Carol; Domingo-Domenech, Eva; Estany, Cristina; Oriol, Albert; Altés, Albert; Pedro, Carmen; Gardella, Santiago; Asensio, Antoni; Vivancos, Pilar; Fernández de Sevilla, Alberto; Ribera, Josep María; Colomer, Dolors; Campo, Elias; López-Guillermo, Armando

2017-04-01

Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.

Thermodynamic Spectrum of Solar Flares Based on SDO/EVE Observations: Techniques and First Results

NASA Technical Reports Server (NTRS)

Wang, Yuming; Zhou, Zhenjun; Zhang, Jie; Liu, Kai; Liu, Rui; Shen, Chenglong; Chamberlin, Phillip C.

2016-01-01

The Solar Dynamics Observatory (SDO)/EUV Variability Experiment (EVE) provides rich information on the thermodynamic processes of solar activities, particularly on solar flares. Here, we develop a method to construct thermodynamic spectrum (TDS) charts based on the EVE spectral lines. This tool could potentially be useful for extreme ultraviolet (EUV) astronomy to learn about the eruptive activities on distant astronomical objects. Through several cases, we illustrate what we can learn from the TDS charts. Furthermore, we apply the TDS method to 74 flares equal to or greater than the M5.0 class, and reach the following statistical results. First, EUV peaks are always behind the soft X-ray (SXR) peaks and stronger flares tend to have faster cooling rates. There is a power-law correlation between the peak delay times and the cooling rates, suggesting a coherent cooling process of flares from SXR to EUV emissions. Second, there are two distinct temperature drift patterns, called Type I and Type II. For Type I flares, the enhanced emission drifts from high to low temperature like a quadrilateral, whereas for Type II flares the drift pattern looks like a triangle. Statistical analysis suggests that Type II flares are more impulsive than Type I flares. Third, for late-phase flares, the peak intensity ratio of the late phase to the main phase is roughly correlated with the flare class, and the flares with a strong late phase are all confined. We believe that the re-deposition of the energy carried by a flux rope, which unsuccessfully erupts out, into thermal emissions is responsible for the strong late phase found in a confined flare. Furthermore, we show the signatures of the flare thermodynamic process in the chromosphere and transition region in the TDS charts. These results provide new clues to advance our understanding of the thermodynamic processes of solar flares and associated solar eruptions, e.g., coronal mass ejections.

THERMODYNAMIC SPECTRUM OF SOLAR FLARES BASED ON SDO/EVE OBSERVATIONS: TECHNIQUES AND FIRST RESULTS

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

Wang, Yuming; Zhou, Zhenjun; Liu, Kai

2016-03-15

The Solar Dynamics Observatory (SDO)/EUV Variability Experiment (EVE) provides rich information on the thermodynamic processes of solar activities, particularly on solar flares. Here, we develop a method to construct thermodynamic spectrum (TDS) charts based on the EVE spectral lines. This tool could potentially be useful for extreme ultraviolet (EUV) astronomy to learn about the eruptive activities on distant astronomical objects. Through several cases, we illustrate what we can learn from the TDS charts. Furthermore, we apply the TDS method to 74 flares equal to or greater than the M5.0 class, and reach the following statistical results. First, EUV peaks are always behind the soft X-raymore » (SXR) peaks and stronger flares tend to have faster cooling rates. There is a power-law correlation between the peak delay times and the cooling rates, suggesting a coherent cooling process of flares from SXR to EUV emissions. Second, there are two distinct temperature drift patterns, called Type I and Type II. For Type I flares, the enhanced emission drifts from high to low temperature like a quadrilateral, whereas for Type II flares the drift pattern looks like a triangle. Statistical analysis suggests that Type II flares are more impulsive than Type I flares. Third, for late-phase flares, the peak intensity ratio of the late phase to the main phase is roughly correlated with the flare class, and the flares with a strong late phase are all confined. We believe that the re-deposition of the energy carried by a flux rope, which unsuccessfully erupts out, into thermal emissions is responsible for the strong late phase found in a confined flare. Furthermore, we show the signatures of the flare thermodynamic process in the chromosphere and transition region in the TDS charts. These results provide new clues to advance our understanding of the thermodynamic processes of solar flares and associated solar eruptions, e.g., coronal mass ejections.« less

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.

PubMed

Ryge, Jesper; Winther, Ole; Wienecke, Jacob; Sandelin, Albin; Westerdahl, Ann-Charlotte; Hultborn, Hans; Kiehn, Ole

2010-06-09

Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury

PubMed Central

2010-01-01

Background Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Results Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. Conclusions This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability. PMID:20534130

Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

PubMed Central

Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

2015-01-01

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

Processing emotions: Effects of menstrual cycle phase and premenstrual symptoms on the startle reflex, facial EMG and heart rate.

PubMed

Armbruster, Diana; Grage, Tobias; Kirschbaum, Clemens; Strobel, Alexander

2018-10-01

Emotional reactivity varies across the menstrual cycle although physiological findings are not entirely consistent. We assessed facial EMG and heart rate (HR) changes in healthy free cycling women (N = 45) with an emotional startle paradigm both during the early follicular and the late luteal phase, verified by repeated salivary 17β-estradiol, progesterone and testosterone assessments. Cycle phase impacted startle responses with larger magnitudes during the luteal phase. Notably, this effect was only present when premenstrual symptoms and sequence of lab sessions were included as co-variates. At rest, participants showed a tendency towards higher HR and reduced high frequency (HF) power during the luteal phase indicating reduced parasympathetic tone. HF power was also negatively associated with startle magnitudes. HR changes in response to emotional images differed between the two cycle phases. Initial HR deceleration was more marked during the follicular phase particularly when viewing negative pictures. However, cycle phase did not significantly impact corrugator and zygomaticus activity in response to emotional pictures. Among the three gonadal steroids, correlation patterns were most consistent for testosterone. During the follicular phase, testosterone was associated with zygomaticus activity while viewing neutral or positive pictures and with less pronounced HR deceleration in response to negative images. During the luteal phase, testosterone was negatively associated with fear potentiated startle. The findings underscore the importance of considering menstrual cycle phase when investigating physiological indicators of emotion. However, the modulating effect of premenstrual symptoms also emphasizes potential inter-individual differences. Copyright © 2018 Elsevier B.V. All rights reserved.

Induction of endoplasmic reticulum stress under endotoxin tolerance increases inflammatory responses and decreases Pseudomonas aeruginosa pneumonia.

PubMed

Kim, Sena; Joe, Yeonsoo; Park, Se-Ung; Jeong, Sun Oh; Kim, Jin-Kyung; Park, Seong Hoon; Pae, Hyun-Ock; Surh, Young-Joon; Shin, Jaekyoon; Chung, Hun Taeg

2018-06-20

Endotoxin tolerance develops in the late phase of sepsis to protect cells from an early hyperinflammatory response. Nonetheless, because it induces an immunosuppressive environment, patients with sepsis in its late phase are affected by secondary infections, particularly bacterial pneumonia. Here, we showed that induction of endoplasmic reticulum (ER) stress leads to activation of glycogen synthase kinase 3β (GSK-3β) and X-box-binding protein 1 (XBP-1) in an inositol-requiring enzyme 1α (IRE1α)-mediated manner, which in turn restores the inflammatory response in endotoxin-tolerant macrophages. Animal and in vitro models of endotoxin tolerance were studied along with a model of LPS-induced endotoxin tolerance and a model of cecal ligation and puncture (CLP)-induced endotoxin tolerance. To detect the suppressed inflammatory response during endotoxin tolerance, inflammatory-cytokine expression levels were measured by quantitative real-time PCR and an ELISA. Our research revealed that induction of ER stress alleviated lung injury in a septic host infected with Pseudomonas aeruginosa via the activation of GSK-3β and XBP-1 in an IRE1α-mediated manner. Consequently, in the lungs of the septic host infected with P. aeruginosa, symptoms of pneumonia improved and the infecting bacteria were cleared. Thus, for septic patients, determination of immune status may guide the selection of appropriate immunomodulation, and ER stress can be a novel therapeutic strategy restoring the immune response in patients with endotoxin tolerance. ©2018 Society for Leukocyte Biology.

Brain Korea 21 Phase II: A New Evaluation Model. Monograph

ERIC Educational Resources Information Center

Seong, Somi; Popper, Steven W.; Goldman, Charles A.; Evans, David K.

2008-01-01

In the late 1990s, the Korea Ministry of Education and Human Resources, in response to concern over the relatively low standing of the nation's universities and researchers, launched the Brain Korea 21 program BK21). BK21 seeks to make Korean research universities globally competitive and to produce more high-quality researchers in Korea. It…

Abiotic and biotic responses to Milankovitch-forced megamonsoon and glacial cycles recorded in South China at the end of the Late Paleozoic Ice Age

NASA Astrophysics Data System (ADS)

Fang, Qiang; Wu, Huaichun; Hinnov, Linda A.; Tian, Wenqian; Wang, Xunlian; Yang, Tianshui; Li, Haiyan; Zhang, Shihong

2018-04-01

At the end of the Late Paleozoic Ice Age (LPIA) from late Early Permian to early Late Permian, the global climate was impacted by a prevailing megamonsoon and Gondwanan deglaciation. To better understand the abiotic and biotic responses to Milankovitch-forced climate changes during this time period, multi-element X-ray fluorescence (XRF) geochemistry analyses were conducted on 948 samples from the late Early-late Middle Permian Maokou Formation at Shangsi, South China. The Fe/Ti, S/Ti, Ba/Ti and Ca time series, which were calibrated with an existing "floating" astronomical time scale (ATS), show the entire suite of Milankovitch rhythms including 405 kyr long eccentricity, 128 and 95 kyr short eccentricity, 33 kyr obliquity and 20 kyr precession. Spectral coherency and cross-phase analysis reveals that chemical weathering (monitored by Fe/Ti) and upwelling (captured by S/Ti and Ba/Ti) are nearly antiphase in the precession band, which suggests a contrast between summer and winter monsoon intensities. Strong obliquity signal in the Ba/Ti series is proposed to derive from changes in thermohaline circulation intensity from glaciation dynamics in southern Gondwana. The abundance of foraminifer, brachiopod and ostracod faunas within the Maokou Formation were mainly controlled by the 1.1 Myr obliquity modulation cycle. The obliquity-forced high-nutrient and oxygen-depleted conditions generally produced a benthic foraminifer bloom, but threatened the brachiopod and ostracod faunas.

Cdc7 is required throughout the yeast S phase to activate replication origins.

PubMed

Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

CLB5-dependent activation of late replication origins in S. cerevisiae.

PubMed

Donaldson, A D; Raghuraman, M K; Friedman, K L; Cross, F R; Brewer, B J; Fangman, W L

1998-08-01

Replication origins in chromosomes are activated at specific times during the S phase. We show that the B-type cyclins are required for proper execution of this temporal program. clb5 cells activate early origins but not late origins, explaining the previously described long clb5 S phase. Origin firing appears normal in cIb6 mutants. In clb5 clb6 double mutant cells, the late origin firing defect is suppressed, accounting for the normal duration of the phase despite its delayed onset. Therefore, Clb5p promotes the timely activation of early and late origins, but Clb6p can activate only early origins. In clb5 clb6 mutants, the other B-type cyclins (Clb1-4p) promote an S phase during which both early and late replication origins fire.

PPARα autocrine regulation of Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: NO and cGMP accumulation.

PubMed

Tanaka, Saori; Sugiyama, Nanae; Takahashi, Yuko; Mantoku, Daiki; Sawabe, Yukinori; Kuwabara, Hiroko; Nakano, Takashi; Shimamoto, Chikao; Matsumura, Hitoshi; Marunaka, Yoshinori; Nakahari, Takashi

2014-12-15

In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca(2+)-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N(5)-[imino(propylamino)methyl]-L-ornithine hydrochloride (N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca(2+)-regulated exocytosis in antral mucous cells. Copyright © 2014 the American Physiological Society.

Heat export from the tropics drives mid to late Holocene palaeoceanographic changes offshore southern Australia

NASA Astrophysics Data System (ADS)

Perner, Kerstin; Moros, Matthias; De Deckker, Patrick; Blanz, Thomas; Wacker, Lukas; Telford, Richard; Siegel, Herbert; Schneider, Ralph; Jansen, Eystein

2018-01-01

The Leeuwin Current (LC), an eastern boundary current, transports tropical waters from the Indo-Pacific Warm Pool (IPWP) towards southern latitudes and modulates oceanic conditions offshore southern Australia. New, high-resolution planktic foraminifer assemblage data and alkenone-derived sea surface temperatures (SST) provide an in-depth view on LC variability and mechanisms driving the current's properties during the mid to late Holocene (last c. 7.4 ka BP). Our marine reconstructions highlight a longer-term mid to late Holocene reduction of tropical heat export from the IPWP area into the LC. Mid Holocene (c. 7.4 to 3.5 ka BP) occurrence of high SSTs (>19.5 °C), tropical planktic foraminifera and a well-stratified water column document an enhanced heat export from the tropics. From c. 3.5 ka BP onwards, a weaker LC and a notably reduced tropical heat export cause oceanic cooling offshore southern Australia. The observed mid to late Holocene trends likely result from large-scale changes in the IPWP's heat storage linked to the El Niño-Southern Oscillation (ENSO) phenomenon. We propose that a strong and warm LC occurs in response to a La Niña-like state of ENSO during the mid Holocene. The late Holocene LC cooling, however, results from a shift towards an El Niño-like state and a more variable ENSO system that causes cooling of the IPWP. Superimposed on these longer-term trends we find evidence of distinct late Holocene millennial-scale phases of enhanced El Niño/La Niña development, which appear synchronous with northern hemispheric climatic variability. Phases of dominant El Niño-like states occur parallel to North Atlantic cold phases: the '2800 years BP cooling event', the 'Dark Ages' and the 'Little Ice Age', whereas the 'Roman Warm Period' and the 'Medieval Climate Anomaly' parallel periods of a predominant La Niña-like state. Our findings provide further evidence of coherent interhemispheric climatic and oceanic conditions during the mid to late Holocene, suggesting ENSO as a potential mediator.

Phase Shifting Capacity of the Circadian Pacemaker Determined by the SCN Neuronal Network Organization

PubMed Central

vanderLeest, Henk Tjebbe; Rohling, Jos H. T.; Michel, Stephan; Meijer, Johanna H.

2009-01-01

Background In mammals, a major circadian pacemaker that drives daily rhythms is located in the suprachiasmatic nuclei (SCN), at the base of the hypothalamus. The SCN receive direct light input via the retino-hypothalamic tract. Light during the early night induces phase delays of circadian rhythms while during the late night it leads to phase advances. The effects of light on the circadian system are strongly dependent on the photoperiod to which animals are exposed. An explanation for this phenomenon is currently lacking. Methodology and Principal Findings We recorded running wheel activity in C57 mice and observed large amplitude phase shifts in short photoperiods and small shifts in long photoperiods. We investigated whether these different light responses under short and long days are expressed within the SCN by electrophysiological recordings of electrical impulse frequency in SCN slices. Application of N-methyl-D-aspartate (NMDA) induced sustained increments in electrical activity that were not significantly different in the slices from long and short photoperiods. These responses led to large phase shifts in slices from short days and small phase shifts in slices from long days. An analysis of neuronal subpopulation activity revealed that in short days the amplitude of the rhythm was larger than in long days. Conclusions The data indicate that the photoperiodic dependent phase responses are intrinsic to the SCN. In contrast to earlier predictions from limit cycle theory, we observed large phase shifting responses in high amplitude rhythms in slices from short days, and small shifts in low amplitude rhythms in slices from long days. We conclude that the photoperiodic dependent phase responses are determined by the SCN and propose that synchronization among SCN neurons enhances the phase shifting capacity of the circadian system. PMID:19305510

Time-dependent distinct roles of Toll-like receptor 4 in a house dust mite-induced asthma mouse model.

PubMed

Ishii, T; Niikura, Y; Kurata, K; Muroi, M; Tanamoto, K; Nagase, T; Sakaguchi, M; Yamashita, N

2018-03-01

House dust mites (HDMs) are a common source of allergens that trigger both allergen-specific and innate immune responses in humans. Here, we examined the effect of allergen concentration and the involvement of Toll-like receptor 4 (TLR4) in the process of sensitization to house dust mite allergens in an HDM extract-induced asthma mouse model.　Intranasal administration of HDM extract induced an immunoglobulin E response and eosinophilic inflammation in a dose-dependent manner from 2.5 to 30 μg/dose. In TLR4-knockout mice, the infiltration of eosinophils and neutrophils into the lung was decreased compared with that in wild-type mice in the early phase of inflammation (total of three doses). However, in the late phase of inflammation (total of seven doses), eosinophil infiltration was significantly greater in TLR4-knockout mice than in wild-type mice. This suggests that the roles of TLR4 signaling are different between the early phase and the later phase of HDM allergen-induced inflammation. Thus, innate immune response through TLR4 regulated the response to HDM allergens, and the regulation was altered during the phase of inflammation. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Differences in activation properties of the hamstring muscles during overground sprinting.

PubMed

Higashihara, Ayako; Nagano, Yasuharu; Ono, Takashi; Fukubayashi, Toru

2015-09-01

The purpose of this study was to quantify activation of the biceps femoris (BF) and medial hamstring (MH) during overground sprinting. Lower-extremity kinematics and electromyography (EMG) of the BF and MH were recorded in 13 male sprinters performing overground sprinting at maximum effort. Mean EMG activity was calculated in the early stance, late stance, mid-swing, and late-swing phases. Activation of the BF was significantly greater during the early stance phase than the late stance phase (p<0.01). Activation of the BF muscle was significantly lower during the first half of the mid-swing phase than the other phases (p<0.05). The MH had significantly greater EMG activation relative to its recorded maximum values compared to that for the BF during the late stance (p<0.05) and mid-swing (p<0.01) phases. These results indicate that the BF shows high activation before and after foot contact, while the MH shows high activation during the late stance and mid-swing phases. We concluded that the activation properties of the BF and MH muscles differ within the sprinting gait cycle. Copyright © 2015 Elsevier B.V. All rights reserved.

Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles.

PubMed

Esteves, Sandro C; Khastgir, Gautam; Shah, Jatin; Murdia, Kshitiz; Gupta, Shweta Mittal; Rao, Durga G; Dash, Soumyaroop; Ingale, Kundan; Patil, Milind; Moideen, Kunji; Thakor, Priti; Dewda, Pavitra

2018-01-01

Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. Patients with high ovarian response to control ovarian stimulation are more prone to exhibit PE at the late follicular phase. However, in studies showing an overall detrimental effect of PE on pregnancy rates, the adverse effect of PE on endometrial receptivity seems to be offset, at least in part, by the availability of good quality embryo for transfer in women with a high ovarian response. Given the limitations of the currently available assays to measure progesterone at low ranges, caution should be applied to adopt specific cutoff values above which the effect of progesterone rise could be considered detrimental and to recommend "freeze-all" based solely on pre-defined cutoff points.

Sense of agency is related to gamma band coupling in an inferior parietal-preSMA circuitry

PubMed Central

Ritterband-Rosenbaum, Anina; Nielsen, Jens B.; Christensen, Mark S.

2014-01-01

In the present study we tested whether sense of agency (SoA) is reflected by changes in coupling between right medio-frontal/supplementary motor area (SMA) and inferior parietal cortex (IPC). Twelve healthy adult volunteers participated in the study. They performed a variation of a line-drawing task (Nielsen, 1963; Fourneret and Jeannerod, 1998), in which they moved a cursor on a digital tablet with their right hand without seeing the hand. Visual feedback displayed on a computer monitor was either in correspondence with or deviated from the actual movement. This made participants uncertain as to the agent of the movement and they reported SoA in approximately 50% of trials when the movement was computer-generated. We tested whether IPC-preSMA coupling was associated with SoA, using dynamic causal modeling (DCM) for induced responses (Chen et al., 2008; Herz et al., 2012). Nine different DCMs were constructed for the early and late phases of the task, respectively. All models included two regions: a superior medial gyrus (preSMA) region and a right supramarginal gyrus (IPC) region. Bayesian models selection (Stephan et al., 2009) favored a model with input to IPC and modulation of the forward connection to SMA in the late task phase, and a model with input to preSMA and modulation of the backward connection was favored for the early task phase. The analysis shows that IPC source activity in the 50–60 Hz range modulated preSMA source activity in the 40–70 Hz range in the presence of SoA compared with no SoA in the late task phase, but the test of the early task phase did not reveal any differences between presence and absence of SoA. We show that SoA is associated with a directionally specific between frequencies coupling from IPC to preSMA in the higher gamma (ɣ) band in the late task phase. This suggests that SoA is a retrospective perception, which is highly dependent on interpretation of the outcome of the performed action. PMID:25076883

Evoked potentials in immobilized cats to a combination of clicks with painful electrocutaneous stimuli

NASA Technical Reports Server (NTRS)

Gilinskiy, M. A.; Korsakov, I. A.

1979-01-01

Averaged evoked potentials in the auditory, somatosensory, and motor cortical zones, as well as in the mesencephalic reticular formation were recorded in acute experiments on nonanesthetized, immobilized cats. Omission of the painful stimulus after a number of pairings resulted in the appearance of a delayed evoked potential, often resembling the late phases of the response to the painful stimulus. The characteristics of this response are discussed in comparison with conditioned changes of the sensory potential amplitudes.

Phase distribution of spliceosomal introns: implications for intron origin

PubMed Central

Nguyen, Hung D; Yoshihama, Maki; Kenmochi, Naoya

2006-01-01

Background The origin of spliceosomal introns is the central subject of the introns-early versus introns-late debate. The distribution of intron phases is non-uniform, with an excess of phase-0 introns. Introns-early explains this by speculating that a fraction of present-day introns were present between minigenes in the progenote and therefore must lie in phase-0. In contrast, introns-late predicts that the nonuniformity of intron phase distribution reflects the nonrandomness of intron insertions. Results In this paper, we tested the two theories using analyses of intron phase distribution. We inferred the evolution of intron phase distribution from a dataset of 684 gene orthologs from seven eukaryotes using a maximum likelihood method. We also tested whether the observed intron phase distributions from 10 eukaryotes can be explained by intron insertions on a genome-wide scale. In contrast to the prediction of introns-early, the inferred evolution of intron phase distribution showed that the proportion of phase-0 introns increased over evolution. Consistent with introns-late, the observed intron phase distributions matched those predicted by an intron insertion model quite well. Conclusion Our results strongly support the introns-late hypothesis of the origin of spliceosomal introns. PMID:16959043

Ghrelin clearance is reduced at the late stage of polymicrobial sepsis.

PubMed

Wu, Rongqian; Zhou, Mian; Cui, Xiaoxuan; Simms, H Hank; Wang, Ping

2003-11-01

The cardiovascular response to sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Ghrelin, a newly-identified endogenous ligand for growth hormone secretagogue receptor (i.e., ghrelin receptor), was recently demonstrated to be a potent vasoactive peptide in addition to its effects on growth hormone release and energy homeostasis. We have shown that ghrelin (via its receptor) may play an important role in regulating cardiovascular responses in the progression of polymicrobial sepsis. However, it remains unknown whether the clearance of this peptide is altered in sepsis. To determine this, male adult rats were injected with 125I-ghrelin through the jugular vein at 5 or 20 h after cecal ligation and puncture (CLP, i.e., sepsis model) or sham operation. The blood sample was collected every 2 min for 30 min for determining half-life (t1/2). Tissue samples (i.e., kidneys, liver, brain, heart, lungs, spleen, stomach, small intestine, large intestine, skin and muscle) were then harvested. The radioactivities of samples were counted. The results indicate that 125I-ghrelin's t1/2 and its distribution were not significantly altered in early sepsis (5 h after CLP). However, the t1/2 increased significantly in late sepsis (20 h after CLP). Tissue distribution of 125I-ghrelin was far greater in the kidneys than in any other tissues tested in both sham and septic animals. Moreover, the kidneys and liver had significantly less radioactive uptake at 20 h after CLP, but the radioactivity in blood was much higher at the same time point. There were no significant changes in 125I-ghrelin distribution in other organs at the late stage of sepsis. These results indicate that the kidneys are the primary site of ghrelin clearance, which is significantly diminished in late sepsis. In addition, the liver also plays a role in the clearance of ghrelin, which was also reduced in late sepsis. The decreased clearance of ghrelin by the kidneys and liver may be due to renal and hepatic dysfunctions under such conditions.

Cortisol levels during prolonged exercise: the influence of menstrual phase and menstrual status.

PubMed

Kanaley, J A; Boileau, R A; Bahr, J M; Misner, J E; Nelson, R A

1992-05-01

The purpose of this study was to determine the influence of menstrual phase and menstrual status on the cortisol response during 90 minutes of treadmill running at 60% VO2max. Eight eumenhorrheic athletes were tested in the early follicular (EF) (day 3-5), late follicular (LF) (day 13-15) and mid-luteal (ML) (day 22-24) phases. Six amenorrheic athletes were tested on two separate occasions. The resting cortisol levels were similar in each menstrual phase and overall a decreasing pattern of cortisol response to exercise was observed in all menstrual phases (P greater than .05). The amenorrheic athletes had a significantly greater (P less than .01) pattern of cortisol response than was observed in eumenorrheic athletes. The net increment in cortisol levels during exercise were distinctly greater (P less than .01) in amenorrheic than eumenorrheic athletes (amenorrheic: 413.8 +/- 113.1, eumenorrheic: EF: -482.8 +/- 88.3, LF: -311.8 +/- 102.1, ML: -386.3 +/- 146.2 nmol.l-1). In conclusion the cortisol levels are independent of menstrual phase. Also a larger cortisol increment is observed in amenorrheic athletes in response to prolonged submaximal exercise. The elevated cortisol levels in amenorrheics at rest and throughout exercise provides further evidence that disturbances in the hypothalamic-pituitary-adrenal function are associated with exercise-induced amenorrhea, although the site(s) of physiological disturbance have not been identified.

Anticipatory phase correction in sensorimotor synchronization.

PubMed

Repp, Bruno H; Moseley, Gordon P

2012-10-01

Studies of phase correction in sensorimotor synchronization often introduce timing perturbations that are unpredictable with regard to direction, magnitude, and position in the stimulus sequence. If participants knew any or all of these parameters in advance, would they be able to anticipate perturbations and thus regain synchrony more quickly? In Experiment 1, we asked musically trained participants to tap in synchrony with short isochronous tone sequences containing a phase shift (PS) of -100, -40, 40, or 100 ms and provided advance information about its direction, position, or both (but not about its magnitude). The first two conditions had little effect, but in the third condition participants shifted their tap in anticipation of the PS, though only by about ±40 ms on average. The phase correction response to the residual PS was also enhanced. In Experiment 2, we provided complete advance information about PSs of various magnitudes either at the time of the immediately preceding tone ("late") or at the time of the tone one position back ("early") while also varying sequence tempo. Anticipatory phase correction was generally conservative and was impeded by fast tempo in the "late" condition. At fast tempi in both conditions, advancing a tap was more difficult than delaying a tap. The results indicate that temporal constraints on anticipatory phase correction resemble those on reactive phase correction. While the latter is usually automatic, this study shows that phase correction can also be controlled consciously for anticipatory purposes. Copyright © 2011 Elsevier B.V. All rights reserved.

Diurnal thermoregulatory responses in pregnant Yankasa ewes to the dry season in a tropical Savannah.

PubMed

Yaqub, Lukuman Surakat; Ayo, Joseph Olusegun; Kawu, Muhammad Umar; Rekwot, Peter Ibrahim

2017-08-01

The study investigated concomitant effect of gestation and high ambient temperature under a tropical environment on rectal temperature (RT), respiratory rate (RR) and heart rate (HR) responses in Yankasa ewes. Twenty Yankasa ewes, consisting of ten pregnant and ten non-pregnant ewes, were used for the study. Ewes were synchronised and bred, such that each gestation phase coincided with different periods of the dry-seasons, early-gestation (cold/harmattan), mid-gestation (peak hot-dry) and late-gestation (late hot-dry). The RT, RR and HR were recorded thrice, 2 days apart at middle of each gestation period at 06:00, 14:00 and 18:00 h, concurrently with dry- (DBT) and wet-bulb temperatures of the experimental pen. The DBT was positively correlated with RT, RR during the different gestation stages. The RT significantly (P < 0.001) increased with the hour of day, regardless of the physiological status of the ewes, with peak at 14:00 h. Values of RT and RR were higher (P < 0.05) in pregnant than non-pregnant ewes at mid- and late-gestation, respectively. Mean RT was lower (P < 0.001) at 06:00 h in pregnant than non-pregnant ewes at early-gestation (cold-dry). The HR was (P < 0.05) higher in pregnant than non-pregnant ewes during the different gestation phases. In conclusion, ambient temperature and gestation concomitantly modulate diurnal thermoregulatory responses of the ewes to hot-dry season. Adequate measures should be adopted to mitigate adverse impact of prolonged high RR on the dam and the foetus during the peak of ambient temperature prevailing in the tropical Savannah environment.

Investigating gas-phase defect formation in late-stage solidification using a novel phase-field crystal alloy model

NASA Astrophysics Data System (ADS)

Wang, Nan; Smith, Nathan; Provatas, Nikolas

2017-09-01

We study late-stage solidification and the associated formation of defects in alloy materials using a novel model based on the phase-field-crystal technique. It is shown that our model successfully captures several important physical phenomena that occur in the late stages of solidification, including solidification shrinkage, liquid cavitation and microsegregation, all in a single framework. By examining the interplay of solidification shrinkage and solute segregation, this model reveals that the formation of gas pore defects at the late stage of solidification can lead to nucleation of second phase solid particles due to solute enrichment in the eutectic liquid driven by gas-phase nucleation and growth. We also predict a modification of the Gulliver-Scheil equation in the presence of gas pockets in confined liquid pools.

Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice.

PubMed

Leon, L R; Kozak, W; Peschon, J; Kluger, M J

1997-02-01

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.

Menstrual cycle, pregnancy and oral contraceptive use alter attraction to apparent health in faces.

PubMed

Jones, B C; Perrett, D I; Little, A C; Boothroyd, L; Cornwell, R E; Feinberg, D R; Tiddeman, B P; Whiten, S; Pitman, R M; Hillier, S G; Burt, D M; Stirrat, M R; Law Smith, M J; Moore, F R

2005-02-22

Previous studies demonstrating changes in women's face preferences have emphasized increased attraction to cues to possible indirect benefits (e.g. heritable immunity to infection) that coincides with periods of high fertility (e.g. the late follicular phase of the menstrual cycle). By contrast, here we show that when choosing between composite faces with raised or lowered apparent health, women's preferences for faces that are perceived as healthy are (i) stronger during the luteal phase of the menstrual cycle than during the late follicular, fertile phase, (ii) stronger in pregnant women than in non-pregnant women and (iii) stronger in women using oral contraceptives than in women with natural menstrual cycles. Change in preference for male faces was greater for short- than long-term relationships. These findings indicate raised progesterone level is associated with increased attraction to facial cues associated with possible direct benefits (e.g. low risk of infection) and suggest that women's face preferences are influenced by adaptations that compensate for weakened immune system responses during pregnancy and reduce the risk of infection disrupting foetal development.

Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin.

PubMed

Carhart-Harris, R L; Leech, R; Williams, T M; Erritzoe, D; Abbasi, N; Bargiotas, T; Hobden, P; Sharp, D J; Evans, J; Feilding, A; Wise, R G; Nutt, D J

2012-03-01

Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences. To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo. Ten healthy participants received two functional magnetic resonance imaging scans (2 mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis. Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective well-being at follow-up (P<0.01). Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.

Mental stress induces sustained elevation of blood pressure and lipid peroxidation in postmenopausal women.

PubMed

Morimoto, Keiko; Morikawa, Mayuko; Kimura, Hiroko; Ishii, Nobuko; Takamata, Akira; Hara, Yasuko; Uji, Masami; Yoshida, Ken-Ichi

2008-01-02

Mental stress is thought to underlie cardiovascular events, but there is information on oxidative stress induced by mental stress in association with cardiovascular responses in women. Using a sensitive assay for plasma 4-hydroxy-2-nonenal (HNE), as a marker for oxidative stress, we addressed the relation between pressor responses and oxidative stress induced by mental or physical stress in premenopausal and postmenopausal women. Healthy subjects (7 postmenopausal and 8 premenopausal women, in early and late follicular phases) were subjected to mental and physical stress evoked by a Color Word Test (CWT) and isometric handgrip, respectively. The CWT induced a rapid elevation of diastolic blood pressure (DBP), at a higher level in the postmenopausal than in the premenopausal women (p<0.01), and this higher DBP was sustained during the CWT and recovery (p<0.01). The CWT induced a significant elevation in plasma noradrenaline in premenopausal women in the early follicular phase and in postmenopausal women (p<0.05). Plasma nitric oxide metabolites were higher in postmenopausal than in the premenopausal women in the late follicular phase (p<0.05), but did not change during exposure to the two types of stress in either group. Plasma HNE was increased during recovery from the CWT, but not the handgrip, in postmenopausal women (2.4 times, p<0.05). There was a significant difference in the time course of the CWT-induced HNE response between the postmenopausal and premenopausal women (p<0.05). These findings suggest that mental, but not physical, stress causes sustained diastolic blood pressure elevation in postmenopausal women, accompanied by heightened oxidative stress.

Age-Related Enhancement of a Protein Synthesis-Dependent Late Phase of LTP Induced by Low Frequency Paired-Pulse Stimulation in Hippocampus

ERIC Educational Resources Information Center

Huang, Yan-You; Kandel, Eric R.

2006-01-01

Protein synthesis-dependent late phase of LTP (L-LTP) is typically induced by repeated high-frequency stimulation (HFS). This form of L-LTP is reduced in the aged animal and is positively correlated with age-related memory loss. Here we report a novel form of protein synthesis-dependent late phase of LTP in the CA1 region of hippocampus induced by…

Fluctuations of estradiol during women's menstrual cycle: Influences on reactivity towards erotic stimuli in the late positive potential.

PubMed

Munk, Aisha J L; Zoeller, Aaron C; Hennig, Juergen

2018-05-01

While several studies examined the reactivity towards negative emotional stimuli across women's menstrual cycle, only few investigated responses to positive emotional cues in association with sexual hormones on a neural level. Therefore, the aim of the current EEG-experiment was to study the differential reactivity towards positive (erotic) words during the menstrual cycle (i.e. with fluctuations in the steroids estradiol and progesterone) in the late positive potential (LPP). Regarding reactivity towards erotic stimuli, the LPP is seen as the most relevant ERP-component, as more positive amplitudes in the LPP reflect larger incentive salience and higher arousal. The LPP towards erotic words was expected to be more pronounced during fertile phases of the menstrual cycle (around ovulation). Furthermore, associations with hormonal concentrations of estradiol and progesterone were investigated. 19 young, free cycling women were tested in an Erotic Stroop paradigm during the follicular phase, ovulation, and the luteal phase in a balanced cross-over design, while electroencephalogram (EEG) was recorded. LPPs in reaction to erotic compared to neutral words were larger in every phase. During the follicular phase and ovulation, higher estradiol-concentrations were associated with more positive LPP-amplitudes towards erotic- than to neutral words. No effects of progesterone, as well as no effects of cycle phase, were evident. Results are being discussed regarding implications for further research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Response to Alcohol in Women: Role of the Menstrual Cycle and a Family History of Alcoholism

PubMed Central

Evans, Suzette M.; Levin, Frances R.

2010-01-01

The present study determined whether: 1) the response to alcohol varied as a function of menstrual cycle phase and 2) women with a paternal history of alcoholism (FHP) were less sensitive to the effects of alcohol compared to women without a family history of alcoholism (FHN). The behavioral effects of alcohol (0.00, 0.25, 0.75 g/kg) were evaluated in 21 FHN and 24 FHP women; each dose was tested during both the midfollicular and late luteal phases of the menstrual cycle. Baseline negative mood was increased during the luteal phase compared to the follicular phase (increased Beck Depression scores and decreased Vigor, Arousal, and Friendly scores). Alcohol increased ratings of Drug Liking and Good Drug Effect more in the luteal phase than the follicular phase. FHP women had greater negative mood during the luteal phase and some of these dysphoric effects were increased by alcohol more in FHP women than FHN women. Alcohol impaired performance, with no group or menstrual cycle differences. However, consistent with previous studies, FHP women were less impaired by alcohol than FHN women on the balance task. These data indicate that 1) the differences in response to alcohol across the menstrual cycle are subtle, although alcohol is liked more during the luteal phase; 2) increases in dysphoric mood during the luteal phase are more pronounced in FHP women compared to FHN women, particularly after alcohol; and 3) the differences observed in response to alcohol between FHP and FHN women are less pronounced than previously shown in men. PMID:20888148

Cooperation between Epstein-Barr Virus Immune Evasion Proteins Spreads Protection from CD8+ T Cell Recognition across All Three Phases of the Lytic Cycle

PubMed Central

Quinn, Laura L.; Zuo, Jianmin; Abbott, Rachel J. M.; Shannon-Lowe, Claire; Tierney, Rosemary J.; Hislop, Andrew D.; Rowe, Martin

2014-01-01

CD8+ T cell responses to Epstein-Barr virus (EBV) lytic cycle expressed antigens display a hierarchy of immunodominance, in which responses to epitopes of immediate-early (IE) and some early (E) antigens are more frequently observed than responses to epitopes of late (L) expressed antigens. It has been proposed that this hierarchy, which correlates with the phase-specific efficiency of antigen presentation, may be due to the influence of viral immune-evasion genes. At least three EBV-encoded genes, BNLF2a, BGLF5 and BILF1, have the potential to inhibit processing and presentation of CD8+ T cell epitopes. Here we examined the relative contribution of these genes to modulation of CD8+ T cell recognition of EBV lytic antigens expressed at different phases of the replication cycle in EBV-transformed B-cells (LCLs) which spontaneously reactivate lytic cycle. Selective shRNA-mediated knockdown of BNLF2a expression led to more efficient recognition of immediate-early (IE)- and early (E)-derived epitopes by CD8+ T cells, while knock down of BILF1 increased recognition of epitopes from E and late (L)-expressed antigens. Contrary to what might have been predicted from previous ectopic expression studies in EBV-negative model cell lines, the shRNA-mediated inhibition of BGLF5 expression in LCLs showed only modest, if any, increase in recognition of epitopes expressed in any phase of lytic cycle. These data indicate that whilst BNLF2a interferes with antigen presentation with diminishing efficiency as lytic cycle progresses (IE>E>>L), interference by BILF1 increases with progression through lytic cycle (IE

Application of high-salinity stress for enhancing the lipid productivity of Chlorella sorokiniana HS1 in a two-phase process.

PubMed

Kakarla, Ramesh; Choi, Jung-Woon; Yun, Jin-Ho; Kim, Byung-Hyuk; Heo, Jina; Lee, Sujin; Cho, Dae-Hyun; Ramanan, Rishiram; Kim, Hee-Sik

2018-01-01

Increased lipid accumulation of algal cells as a response to environmental stress factors attracted much attention of researchers to incorporate this stress response into industrial algal cultivation process with the aim of enhancing algal lipid productivity. This study applies high-salinity stress condition to a two-phase process in which microalgal cells are initially grown in freshwater medium until late exponential phase and subsequently subjected to high-salinity condition that induces excessive lipid accumulation. Our initial experiment revealed that the concentrated culture of Chlorella sorokiniana HS1 exhibited the intense fluorescence of Nile red at the NaCl concentration of 60 g/L along with 1 g/L of supplemental bicarbonate after 48 h of induction period without significantly compromising cultural integrity. These conditions were further verified with the algal culture grown for 7 days in a 1 L bottle reactor that reached late exponential phase; a 12% increment in the lipid content of harvested biomass was observed upon inducing high lipid accumulation in the concentrated algal culture at the density of 5.0 g DW/L. Although an increase in the sum of carbohydrate and lipid contents of harvested biomass indicated that the external carbon source supplemented during the induction period increased overall carbon assimilation, a decrease in carbohydrate content suggested the potential reallocation of cellular carbon that promoted lipid droplet formation under high-salinity stress. These results thus emphasize that the two-phase process can be successfully implemented to enhance algal lipid productivity by incorporating high-salinity stress conditions into the pre-concentrated sedimentation ponds of industrial algal production system.

Anti-IL-17 therapy restricts and reverses late-term corneal allo-rejection

PubMed Central

Yin, Xiao-Tang; Zobell, Stephanie; Jarosz, Jason G.; Stuart, Patrick M.

2015-01-01

Corneal allograft rejection has been described as a Th1-mediated process involving IFN-γ production. However, recent evidence has also implicated IL-17 as being involved during acute corneal allograft responses. Our data supports those that maintain that IL-17 is involved in early acute corneal allograft acceptance. However, we decided to extend these studies to include a later phase of rejection in which there is a peak of IL-17 production that is >15 fold higher than seen during acute rejection that occurs >45 days post-engraftment at the onset of late-term rejection. We demonstrate that neutralizing IL-17A at this time significantly reduced corneal graft rejection. Surprisingly, when corneal grafts that are undergoing this later phase of rejection are treated with anti-IL17A there is a reversal of both opacity and neovascularization. When compared to the early phase of rejection, the cellular infiltrate is significantly less with a greatly reduced presence of Gr-1+ neutrophils with a relative increase in CD4+ T cells and macrophages. We went on to identify that the cells expressing IL-17 were CD4+ IL-17+ T cells and somewhat surprisingly, IL-17+ F4/80+ macrophages within the rejecting corneal allografts. Taken together, these findings describe a distinct late phase of corneal allograft rejection which is likely mediated by Th17 cells and that therapeutic neutralization of IL-17A reverses this rejection. This further suggests that IL-17 might serve as an excellent therapeutic target to reduce this form of corneal allograft rejection. PMID:25754737

Concatenation of Observed Grasp Phases with Observer’s Distal Movements: A Behavioural and TMS Study

PubMed Central

De Stefani, Elisa; Innocenti, Alessandro; De Marco, Doriana; Gentilucci, Maurizio

2013-01-01

The present study aimed at determining how actions executed by two conspecifics can be coordinated with each other, or more specifically, how the observation of different phases of a reaching-grasping action is temporary related to the execution of a movement of the observer. Participants observed postures of initial finger opening, maximal finger aperture, and final finger closing of grasp after observation of an initial hand posture. Then, they opened or closed their right thumb and index finger (experiments 1, 2 and 3). Response times decreased, whereas acceleration and velocity of actual finger movements increased when observing the two late phases of grasp. In addition, the results ruled out the possibility that this effect was due to salience of the visual stimulus when the hand was close to the target and confirmed an effect of even hand postures in addition to hand apparent motion due to the succession of initial hand posture and grasp phase. In experiments 4 and 5, the observation of grasp phases modulated even foot movements and pronunciation of syllables. Finally, in experiment 6, transcranial magnetic stimulation applied to primary motor cortex 300 ms post-stimulus induced an increase in hand motor evoked potentials of opponens pollicis muscle when observing the two late phases of grasp. These data suggest that the observation of grasp phases induced simulation which was stronger during observation of finger closing. This produced shorter response times, greater acceleration and velocity of the successive movement. In general, our data suggest best concatenation between two movements (one observed and the other executed) when the observed (and simulated) movement was to be accomplished. The mechanism joining the observation of a conspecific’s action with our own movement may be precursor of social functions. It may be at the basis for interactions between conspecifics, and related to communication between individuals. PMID:24278395

The mediation effect of menstrual phase on negative emotion processing: evidence from N2.

PubMed

Wu, Haiyan; Chen, Chunping; Cheng, Dazhi; Yang, Suyong; Huang, Ruiwang; Cacioppo, Stephanie; Luo, Yue-Jia

2014-01-01

Numerous studies have shown a 'negativity bias' in emotion processing and effect of menstrual phase on emotion processing. Most of these results, however, did not match the arousal of different types of stimuli. The present study examined the time course of negative emotion processing across different menstrual phases (e.g., late luteal/premenstrual phase and follicular phase) when the arousal level of negative and neutral stimuli was equal. Following previous studies, an oddball paradigm was utilized in present study. Participants viewed neutral and negative (highly (HN) and moderately negative (MN)) stimuli with matched arousal and were asked to make deviant vs. standard judgments. The behavioral results showed a higher accuracy for HN stimuli than neutral stimuli, and the other comparisons were not significant. The major event-related potential (ERP) finding was that N2 amplitude was larger for MN than neutral in the late luteal phase, whereas such difference was absent during the follicular phase. Moreover, The N2 for HN stimuli was larger in late luteal phase than in follicular phase. Therefore, female may be with higher sensitivity to MN stimuli during late luteal phase than during follicular phase when the arousal of stimuli was well controlled. These results provide additional insight to premenstrual affective syndrome and affective disorder.

A phenology of the evolution of endothermy in birds and mammals.

PubMed

Lovegrove, Barry G

2017-05-01

Recent palaeontological data and novel physiological hypotheses now allow a timescaled reconstruction of the evolution of endothermy in birds and mammals. A three-phase iterative model describing how endothermy evolved from Permian ectothermic ancestors is presented. In Phase One I propose that the elevation of endothermy - increased metabolism and body temperature (T b ) - complemented large-body-size homeothermy during the Permian and Triassic in response to the fitness benefits of enhanced embryo development (parental care) and the activity demands of conquering dry land. I propose that Phase Two commenced in the Late Triassic and Jurassic and was marked by extreme body-size miniaturization, the evolution of enhanced body insulation (fur and feathers), increased brain size, thermoregulatory control, and increased ecomorphological diversity. I suggest that Phase Three occurred during the Cretaceous and Cenozoic and involved endothermic pulses associated with the evolution of muscle-powered flapping flight in birds, terrestrial cursoriality in mammals, and climate adaptation in response to Late Cenozoic cooling in both birds and mammals. Although the triphasic model argues for an iterative evolution of endothermy in pulses throughout the Mesozoic and Cenozoic, it is also argued that endothermy was potentially abandoned at any time that a bird or mammal did not rely upon its thermal benefits for parental care or breeding success. The abandonment would have taken the form of either hibernation or daily torpor as observed in extant endotherms. Thus torpor and hibernation are argued to be as ancient as the origins of endothermy itself, a plesiomorphic characteristic observed today in many small birds and mammals. © 2016 Cambridge Philosophical Society.

A late phase II study of RP56976 (docetaxel) in patients with advanced or recurrent breast cancer.

PubMed Central

Adachi, I.; Watanabe, T.; Takashima, S.; Narabayashi, M.; Horikoshi, N.; Aoyama, H.; Taguchi, T.

1996-01-01

A late phase II clinical trial of RP56976 (docetaxel), derived from Taxus baccata was performed to evaluate anti-tumour activity, time to progression and clinical toxicity in patients with advanced or recurrent breast cancer. The patients, between 15 and 80 years old with performance status (PS) of 0-2, received at least two cycles of docetaxel 60 mg m-2 intravenously at 3-4 week intervals. Of the 81 patients enrolled, the 72 eligible for the study were given a total of 327 cycles, with a median of four cycles each. Five patients obtained a complete response (CR) and 27 a partial response (PR); the response rate (RR) was 44.4% (95% confidence interval 32.7-56.6%). A relatively high RR of 9/28 (32.1%) was observed in patients who had received prior chemotherapy involving anthracyclines. The dose-limiting toxicity was grade 3-4 leucocytopenia or neutropenia, found in 78.9% and 85.9% patients respectively. Other severe (grade > 3) toxicities included alopecia (38%), anorexia (18.3%), nausea/vomiting (11.3%), and fatigue (9.9%). Hypersensitivity reactions, oedema and skin toxicity were not severe and were reversible. One therapy-related death occurred 10 days after the initial dose was given. These findings indicate that docetaxel has potent activity against metastatic breast cancer, and that the dose of 60 mg m-2 is safe. PMID:8546908

Synoviocyte-packaged Chlamydia trachomatis induces a chronic aseptic arthritis.

PubMed Central

Inman, R D; Chiu, B

1998-01-01

The basic mechanisms underlying reactive arthritis and specifically the joint injury that follows intra-articular Chlamydia trachomatis infection have not been defined. The present study addresses this question through the development of an experimental model. Stable cell lines were generated from synoviocytes harvested from the knee joints of Lewis rats. The synoviocytes were cocultivated with C. trachomatis to allow invasion by the microbe and were then transferred by intra-articular injection into the knee joints of Lewis rats. The ensuing arthritis could be subdivided into an early phase (

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.

Vascular Repair After Menstruation Involves Regulation of Vascular Endothelial Growth Factor-Receptor Phosphorylation by sFLT-1

PubMed Central

Graubert, Michael D.; Asuncion Ortega, Maria; Kessel, Bruce; Mortola, Joseph F.; Iruela-Arispe, M. Luisa

2001-01-01

Regeneration of the endometrium after menstruation requires a rapid and highly organized vascular response. Potential regulators of this process include members of the vascular endothelial growth factor (VEGF) family of proteins and their receptors. Although VEGF expression has been detected in the endometrium, the relationship between VEGF production, receptor activation, and endothelial cell proliferation during the endometrial cycle is poorly understood. To better ascertain the relevance of VEGF family members during postmenstrual repair, we have evaluated ligands, receptors, and activity by receptor phosphorylation in human endometrium throughout the menstrual cycle. We found that VEGF is significantly increased at the onset of menstruation, a result of the additive effects of hypoxia, transforming growth factor-α, and interleukin-1β. Both VEGF receptors, FLT-1 and KDR, followed a similar pattern. However, functional activity of KDR, as determined by phosphorylation studies, revealed activation in the late menstrual and early proliferative phases. The degree of KDR phosphorylation was inversely correlated with the presence of sFLT-1. Endothelial cell proliferation analysis in endometrium showed a peak during the late menstrual and early proliferative phases in concert with the presence of VEGF, VEGF receptor phosphorylation, and decrease of sFLT-1. Together, these results suggest that VEGF receptor activation and the subsequent modulation of sFLT-1 in the late menstrual phase likely contributes to the onset of angiogenesis and endothelial repair in the human endometrium. PMID:11290558

The nature and time-course of medial temporal lobe contributions to semantic retrieval: an fMRI study on verbal fluency.

PubMed

Sheldon, Signy; Moscovitch, Morris

2012-06-01

Recent investigations have shown that the medial temporal lobe (MTL), a region thought to be exclusive to episodic memory, can also influence performance on tests of semantic memory. The present study examined further the nature of MTL contributions to semantic memory tasks by tracking MTL activation as participants performed category fluency, a traditional test of semantic retrieval. For categories that were inherently autobiographical (e.g. names of friends), the MTLs were activated throughout the time period in which items were generated, consistent with the MTLs role in retrieving autobiographical memories. For categories that could not benefit from autobiographical or spatial/context information (e.g. governmental offices), the MTL was not implicated at any time point. For categories for which both prototypical and episodically-related information exists (e.g. kitchen utensils), there was more robust MTL activity for the open-ended, late generation periods compared with the more well-defined, early item generation time periods. We interpret these results as suggesting that early in the generation phase, responses are based on well-rehearsed prototypical knowledge whereas later performance relies more on open-ended strategies, such as deriving exemplars from personally relevant contextual information (e.g. imagining one's own kitchen). These findings and interpretation were consistent with the results of an initial, separate behavioral study (Expt 1), that used the distinctiveness of responses as a measure of open-endedness across the generation phase: Response distinctiveness corresponded to the predicted open-endedness of the various tasks at early and late phases. Overall, this is consistent with the view that as generation of semantic information becomes open-ended, it recruits processes from other domains, such as episodic memory, to support performance. Copyright © 2011 Wiley Periodicals, Inc.

Delayed pituitary adenylate cyclase-activating polypeptide delivery after brain stroke improves functional recovery by inducing m2 microglia/macrophage polarization.

PubMed

Brifault, Coralie; Gras, Marjorie; Liot, Donovan; May, Victor; Vaudry, David; Wurtz, Olivier

2015-02-01

Until now, except thrombolysis, the therapeutical strategies targeting the acute phase of cerebral ischemia have been proven ineffective, and no approach is available to attenuate the delayed cell death mechanisms and the resulting functional deficits in the late phase. Then, we investigated whether a targeted and delayed delivery of pituitary adenylate cyclase-activating polypeptide (PACAP), a peptide known to exert neuroprotective activities, may dampen delayed pathophysiological processes improving functional recovery. Three days after permanent focal ischemia, PACAP-producing stem cells were transplanted intracerebro ventricularly in nonimmunosuppressed mice. At 7 and 14 days post ischemia, the effects of this stem cell-based targeted delivery of PACAP on functional recovery, volume lesions, and inflammatory processes were analyzed. The delivery of PACAP in the vicinity of the infarct zone 3 days post stroke promotes fast, stable, and efficient functional recovery. This was correlated with a modulation of the postischemic inflammatory response. Transcriptomic and Ingenuity Pathway Analysis-based bioinformatic analyses identified several gene networks, functions, and key transcriptional factors, such as nuclear factor-κB, C/EBP-β, and Notch/RBP-J as PACAP's potential targets. Such PACAP-dependent immunomodulation was further confirmed by morphometric and phenotypic analyses of microglial cells showing increased number of Arginase-1(+) cells in mice treated with PACAP-expressing cells specifically, demonstrating the redirection of the microglial response toward a neuroprotective M2 phenotype. Our results demonstrated that immunomodulatory strategies capable of redirecting the microglial response toward a neuroprotective M2 phenotype in the late phase of brain ischemia could represent attractive options for stroke treatment in a new and unexploited therapeutical window. © 2014 American Heart Association, Inc.

Precipitation change and its effects on prehistorical human activities in the Gonghe Basin, Northeastern Qinghai-Tibet Plateau during middle and late Holocene

NASA Astrophysics Data System (ADS)

Hou, Xiaoqing; Hou, Guangliang; Wang, Fangfang; Wang, Qingbo

2018-02-01

Northeastern Qinghai-tibet Plateau is considered as the ideal region for study of the climate change during the Holocene. Based on the meteorological data, the surface & fossil pollen data, this paper reconstructed the precipitation series of the region since middle Holocene with the GIS and MAT techniques, and discussed its relationship with prehistorical human activities. The results indicate that there are four major climatic phases: (I) Middle Holocene Humid Phase (6300-5000 aBP), with the primitive millet-farming first imported into the region; (II) Late Middle Holocene Sub-humid Phase (5000-3900 aBP), with the millet-farming spread rapidly within the region; (III) Late Holocene Fluctuation Phase (3900-2900 aBP), with the mean annual precipitation dropped down to lower than 240 mm, and a production mode-shift to a combination of cropping and husbandry; (IV) Late Holocene Stationary Phase (2900-0 aBP), with a precipitation alike the modern time, and a steady farming-pastoral economic pattern.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain.

PubMed

Whitehead, John; Valdés-Márquez, Elsa; Lissmats, Agneta

2009-01-01

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright 2008 John Wiley & Sons, Ltd.

Molecular regulation of sex change induced by methyltestosterone -feeding and methyltestosterone -feeding withdrawal in the protogynous orange-spotted grouper.

PubMed

Wang, Qing; Liu, Yun; Peng, Cheng; Wang, Xiang; Xiao, Ling; Wang, Dengdong; Chen, Jiaxing; Zhang, Haifa; Zhao, Huihong; Li, Shuisheng; Zhang, Yong; Lin, Haoran

2017-08-01

The sex identity of fish can be easily manipulated by exogenous hormones. Treatment with 17-methyltestosterone (MT) has been widely used to induce a male fate, but the molecular and cellular processes underlying sex changes induced by MT treatments and the withdrawal of MT are not well studied. In this study, we systematically investigated gonadal histology, gene expression profiles, sex steroid hormone levels, and cellular changes during sex changes induced by MT-feeding and MT-feeding withdrawal in the protogynous orange-spotted grouper, Epinephelus coioides. Based on gonadal histology, we demonstrated that MT-feeding-induced sex reversal can be divided into early and late phases: in the early phase, male and female germ cells coexist, and MT-feeding withdrawal leads to a female fate; in the late phase, only male germ cells are observed, and MT-feeding withdrawal does not reverse the process, leading to a male fate. In both the early and late phases, cytochrome P450 family19 subfamily A member 1 (cyp19a1a) gene expression increased in response to MT-feeding withdrawal. Finally, by tracing doublesex- and Mab-3-related transcription factor 1 (dmrt1)-expressing cells, we found that gonia-like cells in the germinal epithelium might be the major germ cell sources for developing testes during sex reversal. Collectively, our findings provide insights into the molecular and cellular mechanisms underlying sex changes induced by exogenous hormones. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modeling the imprint of Milankovitch cycles on early Pleistocene ice volume

NASA Astrophysics Data System (ADS)

Roychowdhury, R.; DeConto, R.; Pollard, D.

2017-12-01

Global climate during Quaternary and Late Pliocene (present-3.1 Ma) is characterized by alternating glacial and interglacial conditions. Several proposed theories associate these cycles with variations in the Earth's orbital configuration. In this study, we attempt to address the anomalously strong obliquity forcing in the Late Pliocene/Early Pleistocene ice volume records (41 kyr world), which stands in sharp contrast to the primary cyclicity of insolation, which is at precessional periods (23 kyr). Model results from GCM simulations show that at low eccentricities (e<0.015), the effect of precession is minimal, and the integrated insolation metrics (such as summer metric, PDD, etc.) vary in-phase between the two hemispheres. At higher eccentricities (e>0.015), precessional response is important, and the insolation metrics vary out-of-phase between the two hemispheres. Using simulations from a GCM-driven ice sheet model, we simulate time continuous ice volume changes from Northern and Southern Hemispheres. Under eccentricities lower than 0.015, ice sheets in both hemispheres respond only to obliquity cycle, and grow and melt together (in-phase). If the ice sheet is simulated with eccentricity higher than 0.015, both hemispheres become more sensitive to precessional variation, and vary out-of-phase with each other, which is consistent with proxy observations from the late Pleistocene glaciations. We use the simulated ice volumes from 2.0 to 1.0 ma to empirically calculate global benthic δ18O variations based on the assumption that relationships between collapse and growth of ice-sheets and sea level is linear and symmetric and that the isotopic signature of the individual ice-sheets has not changed with time. Our modeled global benthic δ18O values are broadly consistent with the paleoclimate proxy records such as the LR04 stack.

Primordial standing waves

NASA Astrophysics Data System (ADS)

Gubitosi, Giulia; Magueijo, João

2018-03-01

We consider the possibility that the primordial fluctuations (scalar and tensor) might have been standing waves at their moment of creation, whether or not they had a quantum origin. We lay down the general conditions for spatial translational invariance, and isolate the pieces of the most general such theory that comply with, or break translational symmetry. We find that, in order to characterize statistically translationally invariant standing waves, it is essential to consider the correlator ⟨c0(k )c0(k')⟩ in addition to the better known ⟨c0(k )c0†(k')⟩ [where c0(k ) are the complex amplitudes of traveling waves]. We then examine how the standard process of "squeezing" (responsible for converting traveling waves into standing waves while the fluctuations are outside the horizon) reacts to being fed primordial standing waves. For translationally invariant systems only one type of standing wave, with the correct temporal phase (the "sine wave"), survives squeezing. Primordial standing waves might therefore be invisible at late times—or not—depending on their phase. Theories with modified dispersion relations behave differently in this respect, since only standing waves with the opposite temporal phase survive at late times.

Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles

PubMed Central

Esteves, Sandro C.; Khastgir, Gautam; Shah, Jatin; Murdia, Kshitiz; Gupta, Shweta Mittal; Rao, Durga G.; Dash, Soumyaroop; Ingale, Kundan; Patil, Milind; Moideen, Kunji; Thakor, Priti; Dewda, Pavitra

2018-01-01

Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. Patients with high ovarian response to control ovarian stimulation are more prone to exhibit PE at the late follicular phase. However, in studies showing an overall detrimental effect of PE on pregnancy rates, the adverse effect of PE on endometrial receptivity seems to be offset, at least in part, by the availability of good quality embryo for transfer in women with a high ovarian response. Given the limitations of the currently available assays to measure progesterone at low ranges, caution should be applied to adopt specific cutoff values above which the effect of progesterone rise could be considered detrimental and to recommend “freeze-all” based solely on pre-defined cutoff points. PMID:29755412

Cyclic Nucleotide-Gated Channels, Calmodulin, Adenylyl Cyclase, and Calcium/Calmodulin-Dependent Protein Kinase II Are Required for Late, but Not Early, Long-Term Memory Formation in the Honeybee

ERIC Educational Resources Information Center

Matsumoto, Yukihisa; Sandoz, Jean-Christophe; Devaud, Jean-Marc; Lormant, Flore; Mizunami, Makoto; Giurfa, Martin

2014-01-01

Memory is a dynamic process that allows encoding, storage, and retrieval of information acquired through individual experience. In the honeybee "Apis mellifera," olfactory conditioning of the proboscis extension response (PER) has shown that besides short-term memory (STM) and mid-term memory (MTM), two phases of long-term memory (LTM)…

GPR30 Activation Opposes Estrogen-Dependent Uterine Growth via Inhibition of Stromal ERK1/2 and Estrogen Receptor Alpha (ERα) Phosphorylation Signals

PubMed Central

Gao, Fei; Ma, Xinghong; Ostmann, Alicia B.

2011-01-01

Although estradiol-17β (E2)-regulated early and late phase uterine responses have been well defined, the molecular mechanisms linking the phases remain poorly understood. We have previously shown that E2-regulated early signals mediate cross talk with estrogen receptor (ER)-α to elicit uterine late growth responses. G protein-coupled receptor (GPR30) has been implicated in early nongenomic signaling mediated by E2, although its role in E2-dependent uterine biology is unclear. Using selective activation of GPR30 by G-1, we show here a new function of GPR30 in regulating early signaling events, including the inhibition of ERK1/2 and ERα (Ser118) phosphorylation signals and perturbation of growth regulation under the direction of E2 in the mouse uterus. We observed that GPR30 primarily localizes in the uterine epithelial cells, and its activation alters gene expression and mediates inhibition of ERK1/2 and ERα (Ser118) phosphorylation signals in the stromal compartment, suggesting a paracrine signaling is involved. Importantly, viral-driven manipulation of GPR30 or pharmacological inhibition of ERK1/2 activation effectively alters E2-dependent uterine growth responses. Overall, GPR30 is a negative regulator of ERα-dependent uterine growth in response to E2. Our work has uncovered a novel GPR30-regulated inhibitory event, which may be physiologically relevant in both normal and pathological situations to negatively balance ERα-dependent uterine growth regulatory functions induced by E2. PMID:21303939

Comparison of Timothy grass pollen extract- and single major allergen-induced gene expression and mediator release in airway epithelial cells: a meta-analysis.

PubMed

Röschmann, K I L; van Kuijen, A-M; Luiten, S; Jonker, M J; Breit, T M; Fokkens, W J; Petersen, A; van Drunen, C M

2012-10-01

Seasonal allergic rhinitis (AR) is a global health problem and its prevalence has increased considerably in the last decades. As the allergic response with its clinical manifestations is triggered by only a few proteins within natural extracts, there is an increasing tendency for single-component-resolved diagnosis and immunotherapy. As natural exposure is not to single proteins, but to complex mixtures of molecules, we were interested in comparing the activation of respiratory epithelial cells induced by the purified major allergen Phl p 1 with the induction caused by a complete extract of Timothy grass pollen (GPE). NCI-H292 cells were exposed to GPE or Ph1 p 1 for 24 h, isolated RNA and cell culture supernatants were used for microarray analysis, multiplex enzyme-linked immunosorbant assay (ELISA) and subsequent analysis. We found 262 genes that showed a GPE-induced change of at least 3-fold, whereas Ph1 p 1-stimulation resulted in 71 genes with a fold induction of more than 3-fold. Besides genes that were regulated by both stimuli, we also detected genes displaying an opposite response after stimulation, suggesting that GPE might be more than purified major allergens with regard to induced immune responses. Additional components within GPE and the resulting modulation of general processes affecting gene transcription and signalling pathways might be crucial to maintain/overcome the diseased phenotype and to induce the influx of cells contributing to late-phase allergic responses. When the initial process of sensitization is the matter of interest or late-phase allergic responses, one might miss important immune modulatory molecules and their interaction with allergens by applying single components only. © 2012 Blackwell Publishing Ltd.

ENSO and hydrologic extremes in the western United States

USGS Publications Warehouse

Cayan, D.R.; Redmond, K.T.; Riddle, L.G.

1999-01-01

Frequency distributions of daily precipitation in winter and daily stream flow from late winter to early summer, at several hundred sites in the western United States, exhibit strong and systematic responses to the two phases of ENSO. Most of the stream flows considered are driven by snowmelt. The Southern Oscillation index (SOI) is used as the ENSO phase indicator. Both modest (median) and larger (90th percentile) events were considered. In years with negative SOI values (El Nino), days with high daily precipitation and stream flow are more frequent than average over the Southwest and less frequent over the Northwest. During years with positive SOI values (La Nina), a nearly opposite pattern is seen. A more pronounced increase is seen in the number of days exceeding climatological 90th percentile values than in the number exceeding climatological 50th percentile values, for both precipitation and stream flow. Stream flow responses to ENSO extremes are accentuated over precipitation responses. Evidence suggests that the mechanism for this amplification involves ENSO-phase differences in the persistence and duration of wet episodes, affecting the efficiency of the process by which precipitation is converted to runoff. The SOI leads the precipitation events by several months, and hydrologic lags (mostly through snowmelt) dealy the stream flow response by several more months. The combined 6-12 month predictive aspect of this relationship should be of significant benefit in responding to flood (or drought) risk and in improving overall water management in the western states.Frequency distributions of daily precipitation in winter and daily stream flow from late winter to early summer, at several hundred sites in the western United States, exhibit strong and systematic responses to the two phases of ENSO. Most of the stream flows considered are driven by snowmelt. The Southern Oscillation index (SOI) is used as the ENSO phase indicator. Both modest (median) and larger (90th percentile) events were considered. In years with negative SOI values (El Nino), days with high daily precipitation and stream flow are more frequent than average over the Southwest and less frequent over the Northwest. During years with positive SOI values (La Nina), a nearly opposite pattern is seen. A more pronounced increase is seen in the number of days exceeding climatological 90th percentile values than in the number exceeding climatological 50th percentile values, for both precipitation and stream flow. Stream flow responses to ENSO extremes are accentuated over precipitation responses. Evidence suggests that the mechanism for this amplification involves ENSO-phase differences in the persistence and duration of wet episodes, affecting the efficiency of the process by which precipitation is converted to runoff. The SOI leads the precipitation events by several months, and hydrologic lags (mostly through snowmelt) delay the stream flow response by several more months. The combined 6-12-month predictive aspect of this relationship should be of significant benefit in responding to flood (or drought) risk and in improving overall water management in the western states.

A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

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

Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.

2012-11-01

Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a highmore » VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black-Right-Pointing-Pointer Endothelial VEGFR levels are modulated during this response. Black-Right-Pointing-Pointer The cell regulates VEGF-A bioavailability and cell survival. Black-Right-Pointing-Pointer This may partly underlie endothelial dysfunction seen in many pathologies.« less

Transcriptomic responses to wounding: meta-analysis of gene expression microarray data.

PubMed

Sass, Piotr Andrzej; Dąbrowski, Michał; Charzyńska, Agata; Sachadyn, Paweł

2017-11-07

A vast amount of microarray data on transcriptomic response to injury has been collected so far. We designed the analysis in order to identify the genes displaying significant changes in expression after wounding in different organisms and tissues. This meta-analysis is the first study to compare gene expression profiles in response to wounding in as different tissues as heart, liver, skin, bones, and spinal cord, and species, including rat, mouse and human. We collected available microarray transcriptomic profiles obtained from different tissue injury experiments and selected the genes showing a minimum twofold change in expression in response to wounding in prevailing number of experiments for each of five wound healing stages we distinguished: haemostasis & early inflammation, inflammation, early repair, late repair and remodelling. During the initial phases after wounding, haemostasis & early inflammation and inflammation, the transcriptomic responses showed little consistency between different tissues and experiments. For the later phases, wound repair and remodelling, we identified a number of genes displaying similar transcriptional responses in all examined tissues. As revealed by ontological analyses, activation of certain pathways was rather specific for selected phases of wound healing, such as e.g. responses to vitamin D pronounced during inflammation. Conversely, we observed induction of genes encoding inflammatory agents and extracellular matrix proteins in all wound healing phases. Further, we selected several genes differentially upregulated throughout different stages of wound response, including established factors of wound healing in addition to those previously unreported  in this context such as PTPRC and AQP4. We found that transcriptomic responses to wounding showed similar traits in a diverse selection of tissues including skin, muscles, internal organs and nervous system. Notably, we distinguished transcriptional induction of inflammatory genes not only in the initial response to wounding, but also later, during wound repair and tissue remodelling.

Analysis of the Hippocampal Proteome in ME7 Prion Disease Reveals a Predominant Astrocytic Signature and Highlights the Brain-restricted Production of Clusterin in Chronic Neurodegeneration*

PubMed Central

Asuni, Ayodeji A.; Gray, Bryony; Bailey, Joanne; Skipp, Paul; Perry, V. Hugh; O'Connor, Vincent

2014-01-01

Prion diseases are characterized by accumulation of misfolded protein, gliosis, synaptic dysfunction, and ultimately neuronal loss. This sequence, mirroring key features of Alzheimer disease, is modeled well in ME7 prion disease. We used iTRAQTM/mass spectrometry to compare the hippocampal proteome in control and late-stage ME7 animals. The observed changes associated with reactive glia highlighted some specific proteins that dominate the proteome in late-stage disease. Four of the up-regulated proteins (GFAP, high affinity glutamate transporter (EAAT-2), apo-J (Clusterin), and peroxiredoxin-6) are selectively expressed in astrocytes, but astrocyte proliferation does not contribute to their up-regulation. The known functional role of these proteins suggests this response acts against protein misfolding, excitotoxicity, and neurotoxic reactive oxygen species. A recent convergence of genome-wide association studies and the peripheral measurement of circulating levels of acute phase proteins have focused attention on Clusterin as a modifier of late-stage Alzheimer disease and a biomarker for advanced neurodegeneration. Since ME7 animals allow independent measurement of acute phase proteins in the brain and circulation, we extended our investigation to address whether changes in the brain proteome are detectable in blood. We found no difference in the circulating levels of Clusterin in late-stage prion disease when animals will show behavioral decline, accumulation of misfolded protein, and dramatic synaptic and neuronal loss. This does not preclude an important role of Clusterin in late-stage disease, but it cautions against the assumption that brain levels provide a surrogate peripheral measure for the progression of brain degeneration. PMID:24366862

Phases of New Physics in the BAO Spectrum

NASA Astrophysics Data System (ADS)

Baumann, Daniel; Green, Daniel; Zaldarriaga, Matias

2017-11-01

We show that the phase of the spectrum of baryon acoustic oscillations (BAO) is immune to the effects of nonlinear evolution. This suggests that any new physics that contributes to the initial phase of the BAO spectrum, such as extra light species in the early universe, can be extracted reliably at late times. We provide three arguments in support of our claim: first, we point out that a phase shift of the BAO spectrum maps to a characteristic sign change in the real space correlation function and that this feature cannot be generated or modified by nonlinear dynamics. Second, we confirm this intuition through an explicit computation, valid to all orders in cosmological perturbation theory. Finally, we provide a nonperturbative argument using general analytic properties of the linear response to the initial oscillations. Our result motivates measuring the phase of the BAO spectrum as a robust probe of new physics.

Targeting congestion in allergic rhinitis: the importance of intranasal corticosteroids.

PubMed

Marple, Bradley F

2008-01-01

The cardinal nasal symptoms of allergic rhinitis (AR) are sustained by an underlying inflammatory process. Congestion is one of the most prominent and distressing symptoms for patients and is strongly associated with a broadly deteriorated quality of life and significant losses in productivity. The purpose of this study was to explore the role of intranasal corticosteroids (INSs) in down-regulating the inflammatory response to allergen and their clinical efficacy on AR symptoms, particularly congestion. AR is characterized by an influx of inflammatory cells and mediators into the nasal mucosa after antigen exposure. The response is biphasic, encompassing an early and a late phase. Antigen exposure has a priming effect, decreasing the threshold for subsequent allergic reaction on rechallenge and increasing the responsiveness of the nasal mucosa. INSs are a mainstay of therapy for AR and the most effective intervention for nasal congestion and other nasal symptoms, with established superiority to antihistamines, decongestants, and leukotriene antagonists. In addition to symptom relief, INSs suppress numerous stages of the inflammatory cascade, inhibiting the influx of inflammatory cells and mediators. Topical nasal corticosteroids have a low incidence of local adverse effects, negligible systemic absorption, and excellent safety. Congestion is one of the most bothersome symptoms of AR. INS therapy improves AR symptoms, with particular efficacy in relieving congestion, by attenuating nasal hyperresponsiveness. Pretreatment with INSs has been shown to relieve early and late-phase clinical symptoms of AR. Modification of the disease process results in significant relief of symptoms and leads to fewer disease exacerbations.

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

Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease.

PubMed

Jacek, Elzbieta; Tang, Kevin S; Komorowski, Lars; Ajamian, Mary; Probst, Christian; Stevenson, Brian; Wormser, Gary P; Marques, Adriana R; Alaedini, Armin

2016-02-01

Most immunogenic proteins of Borrelia burgdorferi, the causative agent of Lyme disease, are known or expected to contain multiple B cell epitopes. However, the kinetics of the development of human B cell responses toward the various epitopes of individual proteins during the course of Lyme disease has not been examined. Using the highly immunogenic VlsE as a model Ag, we investigated the evolution of humoral immune responses toward its immunodominant sequences in 90 patients with a range of early to late manifestations of Lyme disease. The results demonstrate the existence of asynchronous, independently developing, Ab responses against the two major immunogenic regions of the VlsE molecule in the human host. Despite their strong immunogenicity, the target epitopes were inaccessible to Abs on intact spirochetes, suggesting a lack of direct immunoprotective effect. These observations document the association of immune reactivity toward specific VlsE sequences with different phases of Lyme disease, demonstrating the potential use of detailed epitope mapping of Ags for staging of the infection, and offer insights regarding the pathogen's possible immune evasion mechanisms. Copyright © 2016 by The American Association of Immunologists, Inc.

Multiple determinants controlling activation of yeast replication origins late in S phase.

PubMed

Friedman, K L; Diller, J D; Ferguson, B M; Nyland, S V; Brewer, B J; Fangman, W L

1996-07-01

Analysis of a 131-kb segment of the left arm of yeast chromosome XIV beginning 157 kb from the telomere reveals four highly active origins of replication that initiate replication late in S phase. Previous work has shown that telomeres act as determinants for late origin activation. However, at least two of the chromosome XIV origins maintain their late activation time when located on large circular plasmids, indicating that late replication is independent of telomeres. Analysis of the replication time of plasmid derivatives containing varying amounts of chromosome XIV DNA show that a minimum of three chromosomal elements, distinct from each tested origin, contribute to late activation time. These late determinants are functionally equivalent, because duplication of one set of contributing sequences can compensate for the removal of another set. Furthermore, insertion of an origin that is normally early activated into this domain results in a shift to late activation, suggesting that the chromosome XIV origins are not unique in their ability to respond to the late determinants.

MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.

PubMed

Zhou, Yu; Song, Yan; Shaikh, Zahir; Li, Hui; Zhang, Haiju; Caudle, Yi; Zheng, Shouhua; Yan, Hui; Hu, Dan; Stuart, Charles; Yin, Deling

2017-07-18

Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.

Mesozoic strike-slip movement of the Dunhua-Mishan Fault Zone in NE China: A response to oceanic plate subduction

NASA Astrophysics Data System (ADS)

Liu, Cheng; Zhu, Guang; Zhang, Shuai; Gu, Chengchuan; Li, Yunjian; Su, Nan; Xiao, Shiye

2018-01-01

The NE-striking Dunhua-Mishan Fault Zone (DMFZ) is one of two branches of the continental-scale sinistral Tan-Lu Fault Zone in NE China. The field data presented here indicate that the ca. 1000 km long DMFZ records two phases of sinistral faulting. The structures produced by these two phases of faulting include NE-SW-striking ductile shear belts and brittle faults, respectively. Mylonite-hosted microstructures and quartz c-axis fabrics suggest deformation temperatures of 450 °C-500 °C for the ductile shear belts. Combining new zircon U-Pb dates for 14 igneous rock samples analyzed during this study with the geology of this region indicates these shear belts formed during the earliest Early Cretaceous. This phase of sinistral displacement represents the initial formation of the DMFZ in response to the northward propagation of the Tan-Lu Fault Zone into NE China. A phase of Early Cretaceous rifting was followed by a second phase of sinistral faulting at 102-96 Ma, as evidenced by our new U-Pb ages for associated igneous rocks. Combining our new data with the results of previous research indicates that the DFMZ records a four-stage Cretaceous evolutionary history, where initial sinistral faulting at the beginning of the Early Cretaceous gave way to rifting during the rest of the Early Cretaceous. This was followed by a second phase of sinistral faulting at the beginning of the Late Cretaceous and a second phase of local rifting during the rest of the Late Cretaceous. The Cretaceous evolution of the DMFZ records the synchronous tectonic evolution of the NE China continent bordering the Pacific Ocean. Two phases of regional N-S compression generated the two phases of sinistral faulting within the DMFZ, whereas two-stage regional extension generated the two phases of rifting. The two compressive events were the result of the rapid low-angle subduction of the Izanagi and Pacific plates, whereas the two-stage extension was caused by the roll-back of these respective plates. The final closure of the Mongol-Okhotsk Ocean at the beginning of the Early Cretaceous intensified the synchronous compression in NE China, causing the northward propagation of the Tan-Lu Fault Zone.

Methylenetetrahydrofolate reductase C677T polymorphism: association with risk for childhood acute lymphoblastic leukemia and response during the initial phase of chemotherapy in greek patients.

PubMed

Chatzidakis, Konstantinos; Goulas, Antonis; Athanassiadou-Piperopoulou, Fani; Fidani, Liana; Koliouskas, Dimitrios; Mirtsou, Vassiliki

2006-08-01

As of late, a number of studies have focused on the association of the gene for methyletetrahydrofolate reductase (MTHFR) with risk for acute lymphoblastic leukemia (ALL) in children and in adults, as well as with response to chemotherapy. The degree of this association may vary according to the ethnic background and geographic localization of the population under study, or the phase of treatment when response to chemotherapy is concerned. We have analyzed the MTHFR C677T polymorphism in 52 patients and 88 control individuals, all ethnic Greek residents of northern Greece, and examined the association of this polymorphism with (a) susceptibility to childhood ALL and (b) the distribution of average plasma alanine aminotransferase (ALT) levels, white blood cell counts (WBC), and hemoglobin levels (Hb) during the induction and consolidation phases of treatment. We were able to detect a statistically significant protective effect, with respect to ALL, associated with carriage of the MTHFR 677T allele [OR = 0.387 (95% CI = 0.193-0.776)]. In addition, we observed a general tendency towards lower values in all three parameters studied, associated with the MTHFR 677CC genotype, which was more evident in the transition from the induction to the consolidation phase, indicating that MTHFR genotyping may be of prognostic value in the early phase of treatment for childhood ALL, in our population.

CHRONOLOGICAL CONSTRAINTS ON FLUID CIRCULATION IN MESOZOIC FORMATIONS OF THE EASTERN PART OF THE PARIS BASIN INFERRED FROM U-Pb DATING OF SECONDARY INFILLING CARBONATES

NASA Astrophysics Data System (ADS)

Pisapia, C.; Deschamps, P.; Hamelin, B.; Buschaert, S.

2009-12-01

The French agency for nuclear waste management (ANDRA) developed an Underground Research Laboratory in the Mesozoic formations of Eastern part of the Paris Basin (France) to assess the feasibility of a high-level radioactive wastes repository in sedimentary formations. The target host formation is a low-porosity detrital argillite (Callovo-Oxfordian) embedded between two shelf limestones formations (of Bajocian-Bathonian and Oxfordian-Kimmeridgian ages). These formations are affected by fracture networks, likely inherited mainly from the Eocene-Oligocene extension tectonics, also responsible of the Rhine graben formation in the same region. The limestones have very low permeability, the primary and secondary porosity being infilled by secondary carbonated minerals. The inter-particle porosity is filled with euhedral calcite spar cements. Similarly, macro-cavities and connected micro-fractures are almost sealed by euhedral calcite. Geochemical evidences (δ18O) suggest that the secondary carbonates likely derived from a common parent fluid (Buschaert et al., 2004, Appl. Geochem. (19) 1201-1215p). This late carbonated precipitation phase is responsible for the intense cementation of the limestone formations and bears witness of a major phase of fluids circulation that marked the late diagenetic evolution of the system. Knowledge of the chronology of the different precipitation phases of secondary minerals is thus of critical importance in order to determine the past hydrological conditions of the geological site. The aim of this study is to provide chronological constraints on the secondary carbonate mineral precipitation using U/Th and U/Pb methods. Analyses are performed on millimeter to centimeter scale secondary calcites collected within fractures outcropping in the regional fault zone of Gondrecourt and in cores from the ANDRA exploration-drilling program. Preliminary U-Th analyses obtained on secondary carbonates from surface fractures infillings yield secular equilibrium composition, indicating that the precipitation phase was older than 650 ky. U-Pb measurements were performed on a VG sector Thermal Ionization Mass Spectrometer (TIMS) using a 205Pb-236U-233U-229Th spike. Pb contents are generally very low, between 3 and 20 ppb, while U contents are more variable, leading to μ = 238U/204Pb up to ~600. Sub-samples with high μ show radiogenic 206Pb/204Pb ratio, but at this stage isochrons generally show high scatter. These U-Pb data however are consistent with an Eocene-Oligocene period for the late carbonates precipitation phase. We will discuss the different processes that may be responsible for these errorchrons (i.e. heterogeneities in the initial isotopic composition; multi-stage growth) as well as the chronological constraints that can be drawn from these data.

Wind disasters: A comprehensive review of current management strategies

PubMed Central

Marchigiani, Raffaele; Gordy, Stephanie; Cipolla, James; Adams, Raeanna C; Evans, David C; Stehly, Christy; Galwankar, Sagar; Russell, Sarah; Marco, Alan P; Kman, Nicholas; Bhoi, Sanjeev; Stawicki, Stanislaw P A; Papadimos, Thomas J

2013-01-01

Wind disasters are responsible for tremendous physical destruction, injury, loss of life and economic damage. In this review, we discuss disaster preparedness and effective medical response to wind disasters. The epidemiology of disease and injury patterns observed in the early and late phases of wind disasters are reviewed. The authors highlight the importance of advance planning and adequate preparation as well as prompt and well-organized response to potential damage involving healthcare infrastructure and the associated consequences to the medical response system. Ways to minimize both the extent of infrastructure damage and its effects on the healthcare system are discussed, focusing on lessons learned from recent major wind disasters around the globe. Finally, aspects of healthcare delivery in disaster zones are reviewed. PMID:23961458

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

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

Marchetti, Francesco; Marchetti, Francesco; Wryobek, Andrew J

The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-inducedmore » heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7- 1 dbf). Analysis of chromosomalaberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.« less

DNA Repair Decline During Mouse Spermiogenesis Results in the Accumulation of Heritable DNA Damage

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

Marchetti, Francesco; Marchetti, Francesco; Wyrobek, Andrew J.

The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-inducedmore » heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.« less

Treatment of nonneovascular idiopathic macular telangiectasia type 2 with intravitreal ranibizumab: results of a phase II clinical trial.

PubMed

Toy, Brian C; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2012-05-01

To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for nonneovascular idiopathic macular telangiectasia Type 2. Single-center, open-label Phase II clinical trial enrolling five participants with bilateral nonneovascular idiopathic macular telangiectasia Type 2. Intravitreal ranibizumab (0.5 mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in best-corrected visual acuity, area of late-phase leakage on fluorescein angiography, and retinal thickness on optical coherence tomography. The study treatment was well tolerated and associated with few adverse events. Change in best-corrected visual acuity at 12 months was not significantly different between treated study eyes (0.0 ± 7.5 letters) and control fellow eyes (+2.2 ± 1.9 letters). However, decreases in the area of late-phase fluorescein angiography leakage (-33 ± 20% for study eyes, +1 ± 8% for fellow eyes) and in optical coherence tomography central subfield retinal thickness (-11.7 ± 7.0% for study eyes and -2.9 ± 3.5% for fellow eyes) were greater in study eyes compared with fellow eyes. Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with nonneovascular idiopathic macular telangiectasia Type 2.

Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: a systematic review.

PubMed

Toffoletto, Simone; Lanzenberger, Rupert; Gingnell, Malin; Sundström-Poromaa, Inger; Comasco, Erika

2014-12-01

Ovarian hormones are pivotal for the physiological maintenance of the brain function as well as its response to environmental stimuli. There is mounting evidence attesting the relevance of endogenous ovarian hormones as well as exogenous estradiol and progesterone for emotional and cognitive processing. The present review systematically summarized current knowledge on sex steroid hormonal modulation of neural substrates of emotion and cognition revealed by functional magnetic resonance imaging (fMRI). Twenty-four studies of healthy naturally cycling and combined oral contraceptives (COC) user women, or women undergoing experimental manipulations, during their reproductive age, were included. Furthermore, six studies of premenstrual dysphoric disorder (PMDD), a hormonally based mood disorder, and three of gender dysphoria (GD), which provides an intriguing opportunity to examine the effect of high-dose cross-sex hormone therapy (CSHT) on brain functioning, were included. Globally, low (early follicular and the entire follicular phase for estrogen and progesterone, respectively) and high (COC, CSHT, late follicular and luteal phase for estrogen; COC, mid- and late-luteal phase for progesterone) hormonal milieu diversely affected the response of several brain regions including the amygdala, anterior cingulate cortex, and inferior frontal gyrus, but their functional recruitment across groups and domains was scattered. The constellation of findings provides initial evidence of the influence of sex steroid hormones on cortical and subcortical regions implicated in emotional and cognitive processing. Further well-powered and multimodal neuroimaging studies will be needed to identify the neural mechanism of functional brain alterations induced by sex steroid hormones. Copyright © 2014 Elsevier Ltd. All rights reserved.

Different phase delays of peripheral input to primate motor cortex and spinal cord promote cancellation at physiological tremor frequencies

PubMed Central

Koželj, Saša

2014-01-01

Neurons in the spinal cord and motor cortex (M1) are partially phase-locked to cycles of physiological tremor, but with opposite phases. Convergence of spinal and cortical activity onto motoneurons may thus produce phase cancellation and a reduction in tremor amplitude. The mechanisms underlying this phase difference are unknown. We investigated coherence between spinal and M1 activity with sensory input. In two anesthetized monkeys, we electrically stimulated the medial, ulnar, deep radial, and superficial radial nerves; stimuli were timed as independent Poisson processes (rate 10 Hz). Single units were recorded from M1 (147 cells) or cervical spinal cord (61 cells). Ninety M1 cells were antidromically identified as pyramidal tract neurons (PTNs); M1 neurons were additionally classified according to M1 subdivision (rostral/caudal, M1r/c). Spike-stimulus coherence analysis revealed significant coupling over a broad range of frequencies, with the strongest coherence at <50 Hz. Delays implied by the slope of the coherence phase-frequency relationship were greater than the response onset latency, reflecting the importance of late response components for the transmission of oscillatory inputs. The spike-stimulus coherence phase over the 6–13 Hz physiological tremor band differed significantly between M1 and spinal cells (phase differences relative to the cord of 2.72 ± 0.29 and 1.72 ± 0.37 radians for PTNs from M1c and M1r, respectively). We conclude that different phases of the response to peripheral input could partially underlie antiphase M1 and spinal cord activity during motor behavior. The coordinated action of spinal and cortical feedback will act to reduce tremulous oscillations, possibly improving the overall stability and precision of motor control. PMID:24572094

Different phase delays of peripheral input to primate motor cortex and spinal cord promote cancellation at physiological tremor frequencies.

PubMed

Koželj, Saša; Baker, Stuart N

2014-05-01

Neurons in the spinal cord and motor cortex (M1) are partially phase-locked to cycles of physiological tremor, but with opposite phases. Convergence of spinal and cortical activity onto motoneurons may thus produce phase cancellation and a reduction in tremor amplitude. The mechanisms underlying this phase difference are unknown. We investigated coherence between spinal and M1 activity with sensory input. In two anesthetized monkeys, we electrically stimulated the medial, ulnar, deep radial, and superficial radial nerves; stimuli were timed as independent Poisson processes (rate 10 Hz). Single units were recorded from M1 (147 cells) or cervical spinal cord (61 cells). Ninety M1 cells were antidromically identified as pyramidal tract neurons (PTNs); M1 neurons were additionally classified according to M1 subdivision (rostral/caudal, M1r/c). Spike-stimulus coherence analysis revealed significant coupling over a broad range of frequencies, with the strongest coherence at <50 Hz. Delays implied by the slope of the coherence phase-frequency relationship were greater than the response onset latency, reflecting the importance of late response components for the transmission of oscillatory inputs. The spike-stimulus coherence phase over the 6-13 Hz physiological tremor band differed significantly between M1 and spinal cells (phase differences relative to the cord of 2.72 ± 0.29 and 1.72 ± 0.37 radians for PTNs from M1c and M1r, respectively). We conclude that different phases of the response to peripheral input could partially underlie antiphase M1 and spinal cord activity during motor behavior. The coordinated action of spinal and cortical feedback will act to reduce tremulous oscillations, possibly improving the overall stability and precision of motor control. Copyright © 2014 the American Physiological Society.

Contrasting basin architecture and rifting style of the Vøring Basin, offshore mid-Norway and the Faroe-Shetland Basin, offshore United Kingdom

NASA Astrophysics Data System (ADS)

Schöpfer, Kateřina; Hinsch, Ralph

2017-04-01

The Vøring and the Faroe-Shetland basins are offshore deep sedimentary basins which are situated on the outer continental margin of the northeast Atlantic Ocean. Both basins are underlain by thinned continental crust whose structure is still debated. In particular the nature of the lower continental crust and the origin of high velocity bodies located at the base of the lower crust are a subject of discussion in recent literature. Regional interpretation of 2D and 3D seismic reflection data, combined with well data, suggest that both basins share several common features: (i) Pre-Cretaceous faults that are distributed across the entire basin width. (ii) Geometries of pre-Jurassic strata reflecting at least two extensional phases. (iii) Three common rift phases, Late Jurassic, Campanian-Maastrichtian and Palaeocene. (iv) Large pre-Cretaceous fault blocks that are buried by several kilometres of Cretaceous and Cenozoic strata. (iii). (v) Latest Cretaceous/Palaeocene inversion. (vi) Occurrence of partial mantle serpentinization during Early Cretaceous times, as proposed by other studies, seems improbable. The detailed analysis of the data, however, revealed significant differences between the two basins: (i) The Faroe-Shetland Basin was a fault-controlled basin during the Late Jurassic but also the Late Cretaceous extensional phase. In contrast, the Vøring Basin is dominated by the late Jurassic rifting and subsequent thermal subsidence. It exhibits only minor Late Cretaceous faults that are localised above intra-basinal and marginal highs. In addition, the Cretaceous strata in the Vøring Basin are folded. (ii) In the Vøring Basin, the locus of Late Cretaceous rifting shifted westwards, affecting mainly the western basin margin, whereas in the Faroe-Shetland Basin Late Cretaceous rifting was localised in the same area as the Late Jurassic phase, hence masking the original Jurassic geometries. (iii) Devono-Carboniferous and Aptian/Albian to Cenomanian rift phases are present in the Faroe-Shetland Basin, but are not recognisable in the Vøring Basin. (iv) Based on seismic data only, a Permian/Triassic rift phase can be suggested for the Vøring Basin, but the evidence for an equivalent rift phase in the Faroe-Shetland Basin is inconclusive. The present study demonstrates that basins developing above a complex mosaic of basement terrains accreted during orogenic phases can exhibit significant differences in their architecture. The origin of these differences may be considered to be a result of inherited pre-existing large-scale structures (e.g. pre-existing fault blocks) and/or a non-uniform crustal thickness prior to rifting.

A late wake time phase delays the human dim light melatonin rhythm.

PubMed

Burgess, Helen J; Eastman, Charmane I

2006-03-13

Short sleep/dark durations, due to late bedtimes or early wake times or both, are common in modern society. We have previously shown that a series of days with a late bedtime phase delays the human dim light melatonin rhythm, as compared to a series of days with an early bedtime, despite a fixed wake time. Here we compared the effect of an early versus late wake time with a fixed bedtime on the human dim light melatonin rhythm. Fourteen healthy subjects experienced 2 weeks of short 6h nights with an early wake time fixed at their habitual weekday wake time and 2 weeks of long 9 h nights with a wake time that occurred 3h later than the early wake time, in counterbalanced order. We found that after 2 weeks with the late wake time, the dim light melatonin onset delayed by 2.4 h and the dim light melatonin offset delayed by 2.6 h (both p < 0.001), as compared to after 2 weeks with the early wake time. These results highlight the substantial influence that wake time, likely via the associated morning light exposure, has on the timing of the human circadian clock. Furthermore, the results suggest that when people truncate their sleep by waking early their circadian clocks phase advance and when people wake late their circadian clocks phase delay.

Human Adolescent Phase Response Curves to Bright White Light.

PubMed

Crowley, Stephanie J; Eastman, Charmane I

2017-08-01

Older adolescents are particularly vulnerable to circadian misalignment and sleep restriction, primarily due to early school start times. Light can shift the circadian system and could help attenuate circadian misalignment; however, a phase response curve (PRC) to determine the optimal time for receiving light and avoiding light is not available for adolescents. We constructed light PRCs for late pubertal to postpubertal adolescents aged 14 to 17 years. Participants completed 2 counterbalanced 5-day laboratory sessions after 8 or 9 days of scheduled sleep at home. Each session included phase assessments to measure the dim light melatonin onset (DLMO) before and after 3 days of free-running through an ultradian light-dark (wake-sleep) cycle (2 h dim [~20 lux] light, 2 h dark). In one session, intermittent bright white light (~5000 lux; four 20-min exposures) was alternated with 10 min of dim room light once per day for 3 consecutive days. The time of light varied among participants to cover the 24-h day. For each individual, the phase shift to bright light was corrected for the free-run derived from the other laboratory session with no bright light. One PRC showed phase shifts in response to light start time relative to the DLMO and another relative to home sleep. Phase delay shifts occurred around the hours corresponding to home bedtime. Phase advances occurred during the hours surrounding wake time and later in the afternoon. The transition from delays to advances occurred at the midpoint of home sleep. The adolescent PRCs presented here provide a valuable tool to time bright light in adolescents.

Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

PubMed

García-Gutiérrez, Valentin; Puerta, Jose Manuel; Maestro, Begoña; Casado Montero, Luis Felipe; Muriel, Alfonso; Molina Hurtado, Jose Ramon; Perez-Encinas, Manuel; Moreno Romero, Maria Victoria; Suñol, Pere Barba; Sola Garcia, Ricardo; De Paz, Raquel; Ramirez Sanchez, Maria Jose; Osorio, Santiago; Mata Vazquez, Maria Isabel; Martinez López, Joaquin; Sastre, Jose Luis; Portero, Maria de Los Angles; Bautista, Guiomar; Duran Nieto, Maria Soledad; Giraldo, Pilar; Jimenez Jambrina, Margarita; Burgaleta, Carmen; Ruiz Aredondo, Joaquin; Peñarrubia, Maria Jesús; Requena, Maria José; Fernández Valle, María Del Carmen; Calle, Carmen; Paz Coll, Antonio; Hernández-Rivas, Jose Ángel; Franco Osorio, Rafael; Cano, Pilar; Tallón Pérez, David; Fernández de la Mata, Margarita; Garrido, Pilar López; Steegmann, Juan Luis

2014-11-01

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival. © 2014 Wiley Periodicals, Inc.

Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.

PubMed

Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki

2002-12-30

Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity.

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease

PubMed Central

Uhde, Melanie; Ajamian, Mary; Li, Xueting; Wormser, Gary P.; Marques, Adriana; Alaedini, Armin

2016-01-01

Background. Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis. Methods. Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups. Results. CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome. Conclusions. These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection. PMID:27585799

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease.

PubMed

Uhde, Melanie; Ajamian, Mary; Li, Xueting; Wormser, Gary P; Marques, Adriana; Alaedini, Armin

2016-12-01

 Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis.  Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups.  CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome.  These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Role of Macrophages in the Repair Process during the Tissue Migrating and Resident Helminth Infections

PubMed Central

Faz-López, Berenice

2016-01-01

The Th1/Th2/Th17 balance is a fundamental feature in the regulation of the inflammatory microenvironment during helminth infections, and an imbalance in this paradigm greatly contributes to inflammatory disorders. In some cases of helminthiasis, an initial Th1 response could occur during the early phases of infection (acute), followed by a Th2 response that prevails in chronic infections. During the late phase of infection, alternatively activated macrophages (AAMs) are important to counteract the inflammation caused by the Th1/Th17 response and larval migration, limiting damage and repairing the tissue affected. Macrophages are the archetype of phagocytic cells, with the primary role of pathogen destruction and antigen presentation. Nevertheless, other subtypes of macrophages have been described with important roles in tissue repair and immune regulation. These types of macrophages challenge the classical view of macrophages activated by an inflammatory response. The role of these subtypes of macrophages during helminthiasis is a controversial topic in immunoparasitology. Here, we analyze some of the studies regarding the role of AAMs in tissue repair during the tissue migration of helminths. PMID:27648452

Activation of the cerebellar cortex and the dentate nucleus in a prism adaptation fMRI study.

PubMed

Küper, Michael; Wünnemann, Meret J S; Thürling, Markus; Stefanescu, Roxana M; Maderwald, Stefan; Elles, Hans G; Göricke, Sophia; Ladd, Mark E; Timmann, Dagmar

2014-04-01

During prism adaptation two types of learning processes can be distinguished. First, fast strategic motor control responses are predominant in the early course of prism adaptation to achieve rapid error correction within few trials. Second, slower spatial realignment occurs among the misaligned visual and proprioceptive sensorimotor coordinate system. The aim of the present ultra-highfield (7T) functional magnetic resonance imaging (fMRI) study was to explore cerebellar cortical and dentate nucleus activation during the course of prism adaptation in relation to a similar visuomotor task without prism exposure. Nineteen young healthy participants were included into the study. Recently developed normalization procedures were applied for the cerebellar cortex and the dentate nucleus. By means of subtraction analysis (early prism adaptation > visuomotor, early prism adaptation > late prism adaptation) we identified ipsilateral activation associated with strategic motor control responses within the posterior cerebellar cortex (lobules VIII and IX) and the ventro-caudal dentate nucleus. During the late phase of adaptation we observed pronounced activation of posterior parts of lobule VI, although subtraction analyses (late prism adaptation > visuomotor) remained negative. These results are in good accordance with the concept of a representation of non-motor functions, here strategic control, within the ventro-caudal dentate nucleus. Copyright © 2013 Wiley Periodicals, Inc.

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

Zhang, Chundong; Zhang, Ying; Li, Yi

Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent withmore » those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited cell proliferation.« less

Late-phase synthesis of IκBα insulates the TLR4-activated canonical NF-κB pathway from noncanonical NF-κB signaling in macrophages

PubMed Central

Mukherjee, Tapas; Taye, Nandaraj; Vijayaragavan, Bharath; Chattopadhyay, Samit; Gomes, James; Basak, Soumen

2017-01-01

The nuclear factor κB (NF-κB) transcription factors coordinate the inflammatory immune response during microbial infection. Pathogenic substances engage canonical NF-κB signaling through the heterodimer RelA:p50, which is subjected to rapid negative feedback by inhibitor of κBα (IκBα). The noncanonical NF-κB pathway is required for the differentiation of immune cells; however, crosstalk between both pathways can occur. Concomitantly activated noncanonical signaling generates p52 from the p100 precursor. The synthesis of p100 is induced by canonical signaling, leading to formation of the late-acting RelA:p52 heterodimer. This crosstalk prolongs inflammatory RelA activity in epithelial cells to ensure pathogen clearance. We found that the Toll-like receptor 4 (TLR4)–activated canonical NF-κB signaling pathway is insulated from lymphotoxin β receptor (LTβR)–induced noncanonical signaling in mouse macrophage cell lines. Combined computational and biochemical studies indicated that the extent of NF-κB–responsive expression of Nfkbia, which encodes IκBα, inversely correlated with crosstalk. The Nfkbia promoter showed enhanced responsiveness to NF-κB activation in macrophages compared to that in fibroblasts. We found that this hyperresponsive promoter engaged the RelA:p52 dimer generated during costimulation of macrophages through TLR4 and LTβR to trigger synthesis of IκBα at late time points, which prevented the late-acting RelA crosstalk response. Together, these data suggest that despite the presence of identical signaling networks in cells of diverse lineages, emergent crosstalk between signaling pathways is subject to cell type–specific regulation. We propose that the insulation of canonical and noncanonical NF-κB pathways limits the deleterious effects of macrophage-mediated inflammation. PMID:27923915

Public health activities for mitigation of radiation exposures and risk communication challenges after the Fukushima nuclear accident

PubMed Central

Shimura, Tsutomu; Yamaguchi, Ichiro; Terada, Hiroshi; Robert Svendsen, Erik; Kunugita, Naoki

2015-01-01

Herein we summarize the public health actions taken to mitigate exposure of the public to radiation after the Fukushima accident that occurred on 11 March 2011 in order to record valuable lessons learned for disaster preparedness. Evacuations from the radiation-affected areas and control of the distribution of various food products contributed to the reduction of external and internal radiation exposure resulting from the Fukushima incident. However, risk communication is also an important issue during the emergency response effort and subsequent phases of dealiing with a nuclear disaster. To assist with their healing process, sound, reliable scientific information should continue to be disseminated to the radiation-affected communities via two-way communication. We will describe the essential public health actions following a nuclear disaster for the early, intermediate and late phases that will be useful for radiological preparedness planning in response to other nuclear or radiological disasters. PMID:25862700

cGMP-Phosphodiesterase Inhibition Enhances Photic Responses and Synchronization of the Biological Circadian Clock in Rodents

PubMed Central

Plano, Santiago A.; Agostino, Patricia V.; de la Iglesia, Horacio O.; Golombek, Diego A.

2012-01-01

The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN) and is synchronized by several environmental stimuli, mainly the light-dark (LD) cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2). The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC), cGMP and its related protein kinase (PKG). Pharmacological manipulation of cGMP by phosphodiesterase (PDE) inhibition (e.g., sildenafil) increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux) light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil) also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions. PMID:22590651

Measuring comfort in caregivers and patients during late end-of-life care.

PubMed

Novak, B; Kolcaba, K; Steiner, R; Dowd, T

2001-01-01

The purpose of this study was to test several formats of end-of-life comfort instruments for patients and closely involved caregivers. Kolcaba's Comfort Theory was the theoretical framework utilized. Different response formats for two end-of-life (EOL) comfort questionnaires (for patients and caregivers, respectively), and horizontal and vertical visual analog scales for total comfort (TC) lines were compared in two phases. Evaluable data were collected from both members of 38 patient-caregiver dyads in each phase. Suitable dyads were recruited from two hospice agencies in northeastern Ohio. Cronbach's alpha for the EOL comfort questionnaire (six response Likert-type format) tested during phase I for patients was .98 and for caregivers was .97. Test-retest reliability for the vertical TC line tested during phase I for patients was .64 and for caregivers was .79. The implications of this study for nursing practice and research are derived from the American Nursing Association (ANA) position statement about EOL care, which states that comfort is the goal of nursing for this population. These instruments will be useful for assessing comfort in actively dying patients and comfort of their caregivers as well as for developing evidence-based practice for this population.

Soft-sediment deformation structures from an ice-marginal storm-tide interactive system, Permo-Carboniferous Talchir Formation, Talchir Coalbasin, India

NASA Astrophysics Data System (ADS)

Bhattacharya, H. N.; Bhattacharya, Biplab

2010-01-01

Permo-Carboniferous Talchir Formation, Talchir Coalbasin, India, records sedimentation during a phase of climatic amelioration in an ice-marginal storm-affected shelf. Evidences of subtidal processes are preserved only under thick mud drapes deposited during waning storm phases. Various soft-sediment deformation structures in some sandstone/siltstone-mudstone interbeds, like syn-sedimentary faults, deformed laminations, sand-silt flows, convolute laminations and various flame structures, suggest liquefaction and fluidization of the beds due to passage of syn-depositional seismic shocks. In the Late Paleozoic ice-marginal shelf, such earthquake tremors could be generated by crustal movements in response to glacioisostatic adjustments of the basin floor.

Effects of growth phase on the membrane lipid composition of the thaumarchaeon Nitrosopumilus maritimus and their implications for archaeal lipid distributions in the marine environment

NASA Astrophysics Data System (ADS)

Elling, Felix J.; Könneke, Martin; Lipp, Julius S.; Becker, Kevin W.; Gagen, Emma J.; Hinrichs, Kai-Uwe

2014-09-01

The characteristic glycerol dibiphytanyl glycerol tetraether membrane lipids (GDGTs) of marine ammonia-oxidizing archaea (AOA) are widely used as biomarkers for studying their occurrence and distribution in marine environments and for reconstructing past sea surface temperatures using the TEX86 index. Despite an increasing use of GDGT biomarkers in microbial ecology and paleoceanography, the physiological and environmental factors influencing lipid composition in AOA, in particular the cyclization of GDGTs, remain unconstrained. We investigated the effect of metabolic state on the composition of intact polar and core lipids and the resulting TEX86 paleothermometer in pure cultures of the marine AOA Nitrosopumilus maritimus as a function of growth phase. The cellular lipid content ranged from 0.9 to 1.9 fg cell-1 and increased during growth but was lower in the stationary phases, indicating changes in average cell size in response to metabolic status. The relative abundances of monoglycosidic GDGTs increased from 27% in early growth phase to 60% in late stationary phase, while monohydroxylated GDGTs increased only slightly. The proportions of characteristic hexose-phosphohexose GDGTs were up to 7-fold higher during growth than in stationary phase, suggesting that they are valuable biomarkers for the metabolically active fraction of AOA assemblages in the environment. Methoxy archaeol was identified as novel, genuine archaeal lipid of yet unknown function; it is one of the most abundant single compounds in the lipidome of N. maritimus. TEX86 values of individual intact GDGTs and total GDGTs differed substantially, were generally lower during early and late growth phases than in stationary phase, and did not reflect growth temperature. Consequently, our results strongly suggest that biosynthesis is at least partially responsible for the systematic offsets in TEX86 values between different intact polar GDGT classes observed previously in environmental samples. Nevertheless, differences in degradation rates of intact polar GDGTs may influence the TEX86 index because the intact polar lipid precursors differ for individual core GDGTs and moreover their relative abundances change with growth stage, which may result in distinct release rates of core GDGTs from their polar precursors. Overall, our findings stress the need to accurately describe the factors influencing GDGT cyclization in thaumarchaea and thus paleotemperature reconstructions.

Stress within a Restricted Time Window Selectively Affects the Persistence of Long-Term Memory

PubMed Central

Fang, Qin; Chai, Ning; Zhao, Li-Yan; Xue, Yan-Xue; Luo, Yi-Xiao; Jian, Min; Han, Ying; Shi, Hai-Shui; Lu, Lin; Wu, Ping; Wang, Ji-Shi

2013-01-01

The effects of stress on emotional memory are distinct and depend on the stages of memory. Memory undergoes consolidation and reconsolidation after acquisition and retrieval, respectively. Stress facilitates the consolidation but disrupts the reconsolidation of emotional memory. Previous research on the effects of stress on memory have focused on long-term memory (LTM) formation (tested 24 h later), but the effects of stress on the persistence of LTM (tested at least 1 week later) are unclear. Recent findings indicated that the persistence of LTM requires late-phase protein synthesis in the dorsal hippocampus. The present study investigated the effect of stress (i.e., cold water stress) during the late phase after the acquisition and retrieval of contextual fear memory in rats. We found that stress and corticosterone administration during the late phase (12 h) after acquisition, referred to as late consolidation, selectively enhanced the persistence of LTM, whereas stress during the late phase (12 h) after retrieval, referred to as late reconsolidation, selectively disrupted the restabilized persistence of LTM. Moreover, the effects of stress on the persistence of LTM were blocked by the corticosterone synthesis inhibitor metyrapone, which was administered before stress, suggesting that the glucocorticoid system is involved in the effects of stress on the persistence of LTM. We conclude that stress within a restricted time window after acquisition or retrieval selectively affects the persistence of LTM and depends on the glucocorticoid system. PMID:23544051

The Effect of Gabapentin and Ketorolac on Allodynia and Conditioned Place Preference in Antibody-Induced Inflammation

PubMed Central

Park, HJ; Sandor, K; McQueen, J; Woller, SA; Svensson, CI; Corr, MP; Yaksh, TL

2018-01-01

Background Glucose-6-phosphate isomerase and collagen type II antibody induced arthritis models (K/BxN and CAIA, respectively) have an inflammatory and a post-inflammatory phase. Both phases display robust tactile allodynia. In previous work, inflammatory phase allodynia was reversed by gabapentin and ketorolac, whereas in late phase only gabapentin was effective. Here we sought to determine if the effects of these two drugs during the early and late phases of the two arthritis models were observed in the conditioned place preference (CPP) paradigm, indicating a differential drug effect on the aversive state. Methods Male C57BL/6 mice received K/BxN serum intraperitoneally, while male BALB/c mice received collagen type II antibody cocktail intravenously. After onset of inflammation and allodynia, we assessed effects of i.p. gabapentin (100 mg/kg) or ketorolac (15 mg/kg) using a CPP paradigm: 2 days adaptation, 2 days conditioning (vehicle in morning and drug in afternoon), preference testing on day 5. Results Consistent with the effects upon allodynia, both gabapentin and ketorolac produced a preference for the drug-paired compartment in the early phase of the K/BxN model, while gabapentin, but not ketorolac, resulted in a place preference during late phase. In the CAIA model, consistent with differential effects upon allodynia, gabapentin produced a preference in the early phase and a trend in the late phase, whereas ketorolac was ineffective at either time. Conclusions CPP validated the aversive state in the inflammatory and post-inflammatory phases of the K/BxN and CAIA arthritis models and correspondence between the anti-hyperpathic pharmacology as defined by thresholds and CPP. PMID:26517300

The effect of gabapentin and ketorolac on allodynia and conditioned place preference in antibody-induced inflammation.

PubMed

Park, H J; Sandor, K; McQueen, J; Woller, S A; Svensson, C I; Corr, M; Yaksh, T L

2016-07-01

Glucose-6-phosphate isomerase and collagen type II antibody-induced arthritis models (K/BxN and CAIA, respectively) have an inflammatory and a post-inflammatory phase. Both phases display robust tactile allodynia. In previous work, inflammatory phase allodynia was reversed by gabapentin and ketorolac, whereas in late phase only gabapentin was effective. Here, we sought to determine if the effects of these two drugs during the early and late phases of the two arthritis models were observed in the conditioned place preference (CPP) paradigm, indicating a differential drug effect on the aversive state. Male C57BL/6 mice received K/BxN serum intraperitoneally, while male BALB/c mice received collagen type II antibody cocktail intravenously. After onset of inflammation and allodynia, we assessed effects of i.p. gabapentin (100 mg/kg) or ketorolac (15 mg/kg) using a CPP paradigm: 2 days adaptation, 2 days conditioning (vehicle in morning and drug in afternoon), preference testing on day 5. Consistent with the effects upon allodynia, both gabapentin and ketorolac produced a preference for the drug-paired compartment in the early phase of the K/BxN model, while gabapentin, but not ketorolac, resulted in a place preference during late phase. In the CAIA model, consistent with differential effects upon allodynia, gabapentin produced a preference in the early phase and a trend in the late phase, whereas ketorolac was ineffective at either time. CPP validated the aversive state in the inflammatory and post-inflammatory phases of the K/BxN and CAIA arthritis models and correspondence between the anti-hyperpathic pharmacology as defined by thresholds and CPP. © 2015 European Pain Federation - EFIC®

Differences in grip force control between young and late middle-aged adults.

PubMed

Zheng, Lianrong; Li, Kunyang; Wang, Qian; Chen, Wenhui; Song, Rong; Liu, Guanzheng

2017-09-01

Grip force control is a crucial function for human to guarantee the quality of life. To examine the effects of age on grip force control, 10 young adults and 11 late middle-aged adults participated in visually guided tracking tasks using different target force levels (25, 50, and 75% of the subject's maximal grip force). Multiple measures were used to evaluate the tracking performance during force rising phase and force maintenance phase. The measurements include the rise time, fuzzy entropy, mean force percentage, coefficient of variation, and target deviation ratio. The results show that the maximal grip force was significantly lower in the late middle-aged adults than in the young adults. The time of rising phase was systematically longer among late middle-aged adults. The fuzzy entropy is a useful indicator for quantitating the force variability of the grip force signal at higher force levels. These results suggest that the late middle-aged adults applied a compensatory strategy that allow allows for sufficient time to reach the required grip force and reduce the impact of the early and subtle degenerative changes in hand motor function.

The Effect of Gender and Menstrual Phase on Serum Creatine Kinase Activity and Muscle Soreness Following Downhill Running

PubMed Central

Oosthuyse, Tanja; Bosch, Andrew N.

2017-01-01

Serum creatine kinase (CK) activity reflects muscle membrane disruption. Oestrogen has antioxidant and membrane stabilising properties, yet no study has compared the CK and muscle soreness (DOMS) response to unaccustomed exercise between genders when all menstrual phases are represented in women. Fifteen eumenorrhoeic women (early follicular, EF (n = 5); late follicular, LF (n = 5); mid-luteal, ML (n = 5) phase) and six men performed 20 min of downhill running (−10% gradient) at 9 km/h. Serum CK activity and visual analogue scale rating of perceived muscle soreness were measured before, immediately, 24-h, 48-h and 72-h after exercise. The 24-h peak CK response (relative to pre-exercise) was similar between women and men (mean change (95% confidence interval): 58.5 (25.2 to 91.7) IU/L; 68.8 (31.3 to 106.3) IU/L, respectively). However, serum CK activity was restored to pre-exercise levels quicker in women (regardless of menstrual phase) than men; after 48-h post exercise in women (16.3 (−4.4 to 37.0) IU/L; 56.3 (37.0 to 75.6) IU/L, respectively) but only after 72-h in men (14.9 (−14.8 to 44.6) IU/L). Parallel to the CK response, muscle soreness recovered by 72-h in men. Conversely, the women still reported muscle soreness at 72-h despite CK levels being restored by 48-h; delayed recovery of muscle soreness appeared mainly in EF and LF. The CK and DOMS response to downhill running is gender-specific. The CK response recovers quicker in women than men. The CK and DOMS response occur in concert in men but not in women. The DOMS response in women is prolonged and may be influenced by menstrual phase. PMID:28241459

Brain stem stimulation and the acetylcholine-evoked inhibition of neurones in the feline nucleus reticularis thalami

PubMed Central

Dingledine, Raymond; Kelly, J. S.

1977-01-01

1. In cats anaesthetized with halothane and nitrous oxide, the responses to iontophoretically applied acetylcholine (ACh) and to high-frequency stimulation of the mid-brain reticular formation (MRF) were tested on spontaneously active neurones in the nucleus reticularis thalami and underlying ventrobasal complex. 2. The initial response to MRF stimulation of 90% of the ACh-inhibited neurones found in the region of the dorsolateral nucleus reticularis was an inhibition. Conversely, the initial response of 82% of the ACh-excited neurones in the ventrobasal complex was an excitation. Neurones in the rostral pole of the nucleus reticularis were inhibited by both ACh and RMF stimulation. 3. The mean latency (and s.e. of mean) for the MRF-evoked inhibition was 13·7 ± 3·2 ms (n = 42) and that for the MRF-evoked excitation, 44.1 ± 4.2 ms (n = 35). 4. The ACh-evoked inhibitions were blocked by iontophoretic atropine, in doses that did not block amino acid-evoked inhibition. In twenty-four ACh-inhibited neurones the effect of iontophoretic atropine was tested on MRF-evoked inhibition. In all twenty-four neurones atropine had no effect on the early phase of MRF-evoked inhibition but weakly antagonized the late phase of inhibition in nine of fourteen neurones. 5. Interspike-interval histograms showed that the firing pattern of neurones in the nucleus reticularis was characterized by periods of prolonged, high-frequency bursting. Both the ACh-evoked inhibitions and the late phase of MRF-evoked inhibitions were accompanied by an increased burst activity. In contrast, iontophoretic atropine tended to suppress burst activity. 6. The possibility is discussed that electrical stimulation of the MRF activates an inhibitory cholinergic projection to the nucleus reticularis. Since neurones of the nucleus reticularis have been shown to inhibit thalamic relay cells, activation of this inhibitory pathway may play a role in MRF-evoked facilitation of thalamo-cortical relay transmission and the associated electrocortical desynchronization. PMID:915830

Concerted activities of Mcm4, Sld3, and Dbf4 in control of origin activation and DNA replication fork progression

PubMed Central

Sheu, Yi-Jun; Kinney, Justin B.; Stillman, Bruce

2016-01-01

Eukaryotic chromosomes initiate DNA synthesis from multiple replication origins in a temporally specific manner during S phase. The replicative helicase Mcm2-7 functions in both initiation and fork progression and thus is an important target of regulation. Mcm4, a helicase subunit, possesses an unstructured regulatory domain that mediates control from multiple kinase signaling pathways, including the Dbf4-dependent Cdc7 kinase (DDK). Following replication stress in S phase, Dbf4 and Sld3, an initiation factor and essential target of Cyclin-Dependent Kinase (CDK), are targets of the checkpoint kinase Rad53 for inhibition of initiation from origins that have yet to be activated, so-called late origins. Here, whole-genome DNA replication profile analysis is used to access under various conditions the effect of mutations that alter the Mcm4 regulatory domain and the Rad53 targets, Sld3 and Dbf4. Late origin firing occurs under genotoxic stress when the controls on Mcm4, Sld3, and Dbf4 are simultaneously eliminated. The regulatory domain of Mcm4 plays an important role in the timing of late origin firing, both in an unperturbed S phase and in dNTP limitation. Furthermore, checkpoint control of Sld3 impacts fork progression under replication stress. This effect is parallel to the role of the Mcm4 regulatory domain in monitoring fork progression. Hypomorph mutations in sld3 are suppressed by a mcm4 regulatory domain mutation. Thus, in response to cellular conditions, the functions executed by Sld3, Dbf4, and the regulatory domain of Mcm4 intersect to control origin firing and replication fork progression, thereby ensuring genome stability. PMID:26733669

Effect of anabolic implants on adrenal cortisol synthesis in feedlot beef cattle implanted early or late in the finishing phase.

PubMed

Gifford, C A; Branham, K A; Ellison, J O; Gómez, B I; Lemley, C O; Hart, C G; Krehbiel, C R; Bernhard, B C; Maxwell, C L; Goad, C L; Hallford, D M; Hernandez Gifford, J A

2015-01-01

Implantation of anabolic steroids to increase growth rate in beef cattle impacts adrenal glucocorticoid production. The mechanism by which combination androgen and estrogen implants reduce cortisol biosynthesis in heifers is not clear. The objective of this study was to identify whether pituitary or adrenal gene expression and liver enzyme activity may contribute to altered serum cortisol concentrations in heifers receiving a combination implant. On d 0 of a 122-d finishing phase, 187 predominantly Angus heifers (361 kg) approximately 14 months old were randomly assigned to one of three implant groups: (1) non-implanted control, (2) implanted at the beginning of the finishing phase (d 0; early implant) with a combination implant (200mg TBA+20mg E2; Revalor 200®), and (3) implanted during the late stage of the finishing phase (d 56; late implant) with Revalor 200®. At d 56, body weight (BW) was greater (P<0.0001) for the early implanted heifers (456 ± 1.9 kg) compared to 437 and 435 (± 1.8) kg for control and late implanted heifers, respectively. Final BW (d 122) was similar between both implanted groups and heavier than non-implanted controls (P<0.0001). Serum cortisol was similar among groups at d 0 (P=0.86) however, by d 28 heifers receiving the combination implant had reduced (P<0.05) serum cortisol concentrations (31.2 ng/mL) compared to controls (49.4 ng/mL) and late (48.2 ng/mL) groups. On d 84 cortisol was similar (P=0.75) among implanted heifers and was less (P<0.01) than non-implanted heifers. Expression of pituitary and adrenal genes involved in glucocorticoid synthesis was evaluated at d 28/29 or 84/85; however, despite decreased serum cortisol in implanted heifers, no change in mRNA expression was demonstrated. Liver CYP3A enzyme activity at d 28/29 was decreased 59% in early implanted heifers compared to control heifers (P=0.01). Additionally, at d 84/85 AKR1C activity was greatest (P=0.01) in control heifers compared to both implanted groups. Data suggest that components of hypothalamic-pituitary-adrenal axis are influenced by exposure to exogenous hormones and this should be recognized when considering cortisol levels as a marker for stress response. Copyright © 2014 Elsevier Inc. All rights reserved.

Holocene and late glacial palaeoceanography and palaeolimnology of the Black Sea: Changing sediment provenance and basin hydrography over the past 20,000 years

USGS Publications Warehouse

Piper, David Z.; Calvert, S.E.

2011-01-01

The elemental geochemistry of Late Pleistocene and Holocene sediments of the Black Sea, recovered in box cores from the basin margins and a 5-m gravity core from the central abyssal region of the basin, identifies two terrigenous sediment sources over the last 20 kyrs. One source region includes Anatolia and the southern Caucasus; the second region is the area drained by rivers entering the Black Sea from Eastern Europe. Alkali metal:Al and heavy:light rare-earth element ratios reveal that the relative contribution of the two sources shifted abruptly every few thousand years during the late glacial and early Holocene lacustrine phase of the basin. The shifts in source were coeval with changes in the lake level as determined from the distribution of quartz and the heavy mineral-hosted trace elements Ti and Zr.The geochemistry of the abyssal sediments further recorded a sequence of changes to the geochemistry of the water column following the lacustrine phase, when high salinity Mediterranean water entered the basin beginning 9.3 kyrs BP. Bottom water that had been oxic throughout the lake phase became anoxic at approximately 8.4 kyrs BP, as recorded by the accumulation from the water column of several redox-sensitive trace metals (Mo, Re, U). The accumulation of organic carbon and several trace nutrients (Cd, Cu, Ni, Zn) increased sharply ca. 0.4 kyrs later, at 8.0 kyrs BP, reflecting an increase of primary productivity. Its increase was coeval with a shift in the dinoflagellate ecology from stenohaline to euryhaline assemblages. During this profound environmental change from the lacustrine to the marine phase, the accumulation rate of the lithogenous sediment fraction decreased as much as 10-fold in response to the rise of the water level in the basin from a low stand ca. 9.3 ka to its current level.

Holocene and late glacial palaeoceanography and palaeolimnology of the Black Sea: Changing sediment provenance and basin hydrography over the past 20,000 years

USGS Publications Warehouse

Piper, D.Z.; Calvert, S.E.

2011-01-01

The elemental geochemistry of Late Pleistocene and Holocene sediments of the Black Sea, recovered in box cores from the basin margins and a 5-m gravity core from the central abyssal region of the basin, identifies two terrigenous sediment sources over the last 20. kyrs. One source region includes Anatolia and the southern Caucasus; the second region is the area drained by rivers entering the Black Sea from Eastern Europe. Alkali metal:Al and heavy:light rare-earth element ratios reveal that the relative contribution of the two sources shifted abruptly every few thousand years during the late glacial and early Holocene lacustrine phase of the basin. The shifts in source were coeval with changes in the lake level as determined from the distribution of quartz and the heavy mineral-hosted trace elements Ti and Zr. The geochemistry of the abyssal sediments further recorded a sequence of changes to the geochemistry of the water column following the lacustrine phase, when high salinity Mediterranean water entered the basin beginning 9.3. kyrs BP. Bottom water that had been oxic throughout the lake phase became anoxic at approximately 8.4. kyrs BP, as recorded by the accumulation from the water column of several redox-sensitive trace metals (Mo, Re, U). The accumulation of organic carbon and several trace nutrients (Cd, Cu, Ni, Zn) increased sharply ca. 0.4. kyrs later, at 8.0. kyrs BP, reflecting an increase of primary productivity. Its increase was coeval with a shift in the dinoflagellate ecology from stenohaline to euryhaline assemblages. During this profound environmental change from the lacustrine to the marine phase, the accumulation rate of the lithogenous sediment fraction decreased as much as 10-fold in response to the rise of the water level in the basin from a low stand ca. 9.3. ka to its current level.

Treatment of Non-neovascular Idiopathic Macular Telangiectasia Type 2 with Intravitreal Ranibizumab: Results of a Phase II Clinical Trial

PubMed Central

Toy, Brian C.; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

2015-01-01

Purpose To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for non-neovascular idiopathic macular telangiectasia, type 2 (IMT2). Methods Single-center, open-label phase II clinical trial enrolling 5 participants with bilateral non-neovascular IMT2. Intravitreal ranibizumab (0.5mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in: best corrected visual acuity (BCVA), area of late-phase leakage on fluorescein angiography (FA), and retinal thickness on optical coherence tomography (OCT). Results The study treatment was well-tolerated and associated with few adverse events. Change in BCVA at 12 months was not significantly different between treated study eyes (0.0±7.5 letters) and control fellow eyes (+2.2±1.9 letters). However, decreases in the area of late-phase FA leakage (−33±20% for study eyes, +1±8% for fellow eyes) and in OCT central subfield retinal thickness (−11.7±7.0% for study eyes and −2.9±3.5% for fellow eyes) were greater in study eyes compared to fellow eyes. Conclusions Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with non-neovascular IMT2. PMID:22266930

Scalar perturbation in symmetric Lee-Wick bouncing universe

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

Cho, Inyong; Kwon, O-Kab, E-mail: iycho@seoultech.ac.kr, E-mail: okab@skku.edu

2011-11-01

We investigate the scalar perturbation in the Lee-Wick bouncing universe driven by an ordinary scalar field plus a ghost field. We consider only a symmetric evolution of the universe and the scalar fields about the bouncing point. The gauge invariant Sasaki-Mukhanov variable is numerically solved in the spatially flat gauge. We find a new form of the initial perturbation growing during the contracting phase. After the bouncing, this growing mode stabilizes to a constant mode which is responsible for the late-time power spectrum.

Inter-decadal modulation of ENSO teleconnections to the Indian Ocean in a coupled model: Special emphasis on decay phase of El Niño

NASA Astrophysics Data System (ADS)

Chowdary, J. S.; Parekh, Anant; Gnanaseelan, C.; Sreenivas, P.

2014-01-01

Inter-decadal modulation of El Niño-Southern Oscillation (ENSO) teleconnections to tropical Indian Ocean (TIO) is investigated in the coupled general circulation model Climate Forecast System (CFS) using a hundred year integration. The model is able to capture the periodicity of El Niño variability, which is similar to that of the observations. The maximum TIO/north Indian Ocean (NIO) SST warming (during spring following the decay phase of El Niño) associated with El Niño is well captured by the model. Detailed analysis reveals that the surface heat flux variations mainly contribute to the El Niño forced TIO SST variations both in observations and model. However, spring warming is nearly stationary throughout the model integration period, indicating poor inter-decadal El Niño teleconnections. The observations on the other hand displayed maximum SST warming with strong seasonality from epoch to epoch. The model El Niño decay delayed by more than two seasons, results in persistent TIO/NIO SST warming through the following December unlike in the observations. The ocean wave adjustments and persistent westerly wind anomalies over the equatorial Pacific are responsible for late decay of El Niño in the model. Consistent late decay of El Niño, throughout the model integration period (low variance), is mainly responsible for the poor inter-decadal ENSO teleconnections to TIO/NIO. This study deciphers that the model needs to produce El Niño decay phase variability correctly to obtain decadal-modulations in ENSO teleconnection.

Late Mesolithic and early Neolithic forest disturbance: a high resolution palaeoecological test of human impact hypotheses

NASA Astrophysics Data System (ADS)

Innes, James B.; Blackford, Jeffrey J.; Rowley-Conwy, Peter A.

2013-10-01

The transition in north-west Europe from the hunter-gatherer societies of the Late Mesolithic to the pioneer farming societies of the early Neolithic is not well understood, either culturally or palaeoecologically. In Britain the final transition was rapid but it is unclear whether novel Neolithic attributes were introduced by immigrants who supplanted the native hunter-gatherers, or whether the latest Mesolithic foragers gradually adopted elements of the Neolithic economic package. In this study, relatively coarse- (10 mm interval) and fine-resolution (2 mm), multi-proxy palaeoecological data including pollen, charcoal and NPPs including fungi, have been used to investigate two phases of vegetation disturbance of (a) distinctly Late Mesolithic and (b) early Neolithic age, at an upland site in northern England in a region with both a Neolithic and a Late Mesolithic archaeological presence. We identify and define the palaeoecological characteristics of these two disturbance phases, about a millennium apart, in order to investigate whether differing land-use techniques can be identified and categorised as of either foraging or early farming cultures. The Late Mesolithic phase is defined by the repetitive application of fire to the woodland to encourage a mosaic of productive vegetation regeneration patches, consistent with the promotion of Corylus and to aid hunting. In this phase, weed species including Plantago lanceolata, Rumex and Chenopodiaceae are frequent, taxa which are normally associated with the first farmers. The early Neolithic phase, including an Ulmus decline, has characteristics consistent with 'forest farming', possibly mainly for domestic livestock, with an inferred succession of tree girdling, fire-prepared cultivation, and coppice-woodland management. Such fine-resolution, potentially diagnostic land-use signatures may in future be used to recognise the cultural complexion of otherwise enigmatic woodland disturbance phases during the centuries of the Mesolithic-Neolithic transition.

A Dual-Stage Two-Phase Model of Selective Attention

ERIC Educational Resources Information Center

Hubner, Ronald; Steinhauser, Marco; Lehle, Carola

2010-01-01

The dual-stage two-phase (DSTP) model is introduced as a formal and general model of selective attention that includes both an early and a late stage of stimulus selection. Whereas at the early stage information is selected by perceptual filters whose selectivity is relatively limited, at the late stage stimuli are selected more efficiently on a…

Proteasome Inhibition Enhances the Induction and Impairs the Maintenance of Late-Phase Long-Term Potentiation

ERIC Educational Resources Information Center

Dong, Chenghai; Upadhya, Sudarshan C.; Ding, Lan; Smith, Thuy K.; Hegde, Ashok N.

2008-01-01

Protein degradation by the ubiquitin-proteasome pathway plays important roles in synaptic plasticity, but the molecular mechanisms by which proteolysis regulates synaptic strength are not well understood. We investigated the role of the proteasome in hippocampal late-phase long-term potentiation (L-LTP), a model for enduring synaptic plasticity.…

Effects of temperature and salinity on larval survival and development in the invasive shrimp Palaemon macrodactylus (Caridea: Palaemonidae) along the reproductive season

NASA Astrophysics Data System (ADS)

Guadalupe Vázquez, M.; Bas, Claudia C.; Kittlein, Marcelo; Spivak, Eduardo D.

2015-05-01

The invasive shrimp Palaemon macrodactylus is associated mainly with brackish waters. Previous studies raised the question if tolerance to low salinities differs between larvae and adults. To answer this question, the combined effects of two temperatures (20 and 25 °C) and four salinities (5, 12, 23 and 34 psu) on survival and development of larvae that hatched at the beginning, in the midpoint and near the end of a reproductive season (denoted early, middle season and late larvae respectively) were examined. The three types of larvae were able to survive and reach juvenile phase at salinities between 12 and 34 psu and at both temperatures. At 5 psu all larvae died, but 45% molted at least once. Temperature and salinity to a lesser extent, had effects on the duration of development and on the number of larval stages in all larval types. Development was longer at the lower temperature, especially in middle season and late larvae. Most early larvae reached the juvenile phase through 5 larval stages; the number of larval stages of middle season and late larvae was higher at 20 °C and in late larvae also low salinity produced extra stages. Low salinity (12 psu) and, in early and middle season larvae, low temperature produced lighter and smaller individuals. Response of larvae to environmental factors seems to be related in part to the previous conditions (maternal effects and/or embryo development conditions). The narrower salinity tolerance of larvae compared to adults and the ability of zoea I to survive at least some days at 5 psu may be related with an export larval strategy.

Deformation events in the Andean orogenic cycle in the Altiplano and Western Cordillera, southern Peru

NASA Astrophysics Data System (ADS)

Ellison, R. A.; Klinck, B. A.; Hawkins, M. P.

A regional mapping program associated with radiometric age dating has provided evidence of seven deformation pulses in the Andean orogenic cycle in part of southern Peru. These are the Peruvian (Late Cretaceous), Incaic (Eocene), and five Quechua phases defined as D1 to D5. The D1 phase (early Oligocene) folded molasse deposits in the Western Cordillera; the D2 phase (late Oligocene to early Miocene) folded volcanics of the Western Cordillera; the D3 phase (middle Miocene) folded the molasse deposits in the Altiplano; the D4 (late Miocene) folded lacustrine sediments in the central part of the Western Cordillera; and the D5 phase was a major gravity slide in the Altiplano. Several faults and fault zones, known as the Chupa, Calapuja, Lagunillas, and Laraqueri Faults, are identified. They form the boundaries to Paleozoic basement blocks which appear to have acted as buttresses or barriers to the penetration of some deformation events. In the case of the D5 phase, the gravity slide was preceded by uplift and tilting of a Paleozoic block.

Innate Immune Responses in ALV-J Infected Chicks and Chickens with Hemangioma In Vivo.

PubMed

Feng, Min; Dai, Manman; Xie, Tingting; Li, Zhenhui; Shi, Meiqing; Zhang, Xiquan

2016-01-01

Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Since the precise mechanism of the innate immune response induced by ALV-J is unknown, we investigated the antiviral innate immune responses induced by ALV-J in chicks and chickens that had developed tumors. Spleen levels of interleukin-6 (IL-6), IL-10, IL-1β, and interferon-β (IFN-β) were not significantly different between the infected chick groups and the control groups from 1 day post hatch to 7 days post hatch. However, IL-6, IL-1β, and IFN-β protein levels in the three clinical samples with hemangiomas were dramatically increased compared to the healthy samples. In addition, the anti-inflammatory cytokine IL-10 increased sharply in two of three clinical samples. We also found a more than 20-fold up-regulation of ISG12-1 mRNA at 1 day post infection (d.p.i.) and a twofold up-regulation of ZC3HAV1 mRNA at 4 d.p.i. However, there were no statistical differences in ISG12-1 and ZC3HAV1 mRNA expression levels in the tumorigenesis phase. ALV-J infection induced a significant increase of Toll-like receptor 7 (TLR-7) at 1 d.p.i. and dramatically increased the mRNA levels of melanoma differentiation-associated gene 5 (MDA5) in the tumorigenesis phase. Moreover, the protein levels of interferon regulatory factor 1 (IRF-1) and signal transducer and activator of transcription 1 (STAT1) were decreased in chickens with tumors. These results suggest that ALV-J was primarily recognized by chicken TLR7 and MDA5 at early and late in vivo infection stages, respectively. ALV-J strain SCAU-HN06 did not induce any significant antiviral innate immune response in 1 week old chicks. However, interferon-stimulated genes were not induced normally during the late phase of ALV-J infection due to a reduction of IRF1 and STAT1 expression.

Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

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

Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng

2013-11-01

Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays,more » were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.« less

The RY/Sph element mediates transcriptional repression of maturation genes from late maturation to early seedling growth.

PubMed

Guerriero, Gea; Martin, Nathalie; Golovko, Anna; Sundström, Jens F; Rask, Lars; Ezcurra, Ines

2009-11-01

In orthodox seeds, the transcriptional activator ABI3 regulates two major stages in embryo maturation: a mid-maturation (MAT) stage leading to accumulation of storage compounds, and a late maturation (LEA) stage leading to quiescence and desiccation tolerance. Our aim was to elucidate mechanisms for transcriptional shutdown of MAT genes during late maturation, to better understand phase transition between MAT and LEA stages. Using transgenic and transient approaches in Nicotiana, we examined activities of two ABI3-dependent reporter genes driven by multimeric RY and abscisic acid response elements (ABREs) from a Brassica napus napin gene, termed RY and ABRE, where the RY reporter requires ABI3 DNA binding. Expression of RY peaks during mid-maturation and drops during late maturation, mimicking the MAT gene program, and in Arabidopsis thaliana RY elements are over-represented in MAT, but not in LEA, genes. The ABI3 transactivation of RY is inhibited by staurosporine, by a PP2C phosphatase, and by a repressor of maturation genes, VAL1/HSI2. The RY element mediates repression of MAT genes, and we propose that transcriptional shutdown of the MAT program during late maturation involves inhibition of ABI3 DNA binding by dephosphorylation. Later, during seedling growth, VAL1/HSI2 family repressors silence MAT genes by binding RY elements.

Phase Transitions in the Early Universe: The Cosmology of Non-Minimal Scalar Sectors

NASA Astrophysics Data System (ADS)

Kost, Jeffrey D.

Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically--such as during cosmological mass-generating phase transitions--the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this thesis, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system--often by many orders of magnitude--but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "re-overdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings. In the second part of this thesis, we proceed to study the early-universe cosmology of a Kaluza-Klein (KK) tower of scalar fields in the presence of a mass-generating phase transition, focusing on the time-development of the total tower energy density (or relic abundance) as well as its distribution across the different KK modes. We find that both of these features are extremely sensitive to the details of the phase transition and can behave in a variety of ways significant for late-time cosmology. In particular, we find that the interplay between the temporal properties of the phase transition and the mixing it generates are responsible for both enhancements and suppressions in the late-time abundances, sometimes by many orders of magnitude. We map out the complete model parameter space and determine where traditional analytical approximations are valid and where they fail. In the latter cases we also provide new analytical approximations which successfully model our results. Finally, we apply this machinery to the example of an axion-like field in the bulk, mapping these phenomena over an enlarged axion parameter space that extends beyond those accessible to standard treatments. An important by-product of our analysis is the development of an alternate "UV-based" effective truncation of KK theories which has a number of interesting theoretical properties that distinguish it from the more traditional "IR-based" truncation typically used in the literature.

Mechanisms underlying hemodynamic and neuroendocrine stress reactivity at different phases of the menstrual cycle

PubMed Central

Gordon, Jennifer L.; Girdler, Susan S.

2014-01-01

This study examined the association of menstrual cycle phase with stress reactivity as well as the hormonal and neuroendocrine mechanisms contributing to cycle effects. Fifty-seven women underwent a modified Trier Social Stress Test (TSST) during the early follicular, late follicular and luteal phases of the menstrual cycle. Greater increases in cardiac index (CI) and greater decreases in vascular resistance index (VRI) during speech were observed in the luteal phase relative to other phases, while greater increases in epinephrine (EPI) was observed during the late follicular and luteal phases compared to the early follicular phase. Luteal phase estradiol predicted luteal EPI reactivity but not CI or VRI reactivity while luteal phase EPI reactivity predicted luteal phase CI and VRI reactivity. Thus, cycle-related changes in EPI reactivity may be a stronger determinant of cycle effects on hemodynamic reactivity than sex hormones per se. PMID:24397365

Association of a trait-like bias towards the perception of negative subjective life events with risk of developing premenstrual symptoms.

PubMed

Gonda, Xenia; Fountoulakis, Konstantinos N; Csukly, Gabor; Telek, Tamas; Pap, Dorottya; Rihmer, Zoltan; Bagdy, Gyorgy

2010-04-16

Premenstrual symptoms affect the majority of healthy women. Premenstrual symptomatology has earlier been linked to stress and a state-like alteration in the perception of life events in the late-luteal phase of the menstrual cycle. We hypothesised that there is also a trait-like negative bias in the perception of life events evident throughout the whole cycle which is associated with the likelihood to manifest more marked symptoms in the late-luteal phase of the cycle. 88 healthy women completed the PRISM calendar for three consecutive cycles and the Objective and Subjective Event Checklist during the follicular phase of the first cycle. Association between PRISM score change from the follicular through the late-luteal phase and life event variables was investigated by Generalized Linear Model Analysis (GENMOD). The PRISM score change showed a significant negative association with the ratio of positive subjective life events and a significant positive association with the ratio of negative subjective life events. There were no significant results in case of the objective life events. Our results indicate that women manifesting a more marked increase of symptoms from the late follicular through the late-luteal phase of the menstrual cycle are more likely to notice negative subjective life events and less likely to notice positive subjective life events. This suggest a trait-like negative bias in the perception of life events present throughout the whole reproductive cycle which may play an important role in the emergence of premenstrual symptoms. Copyright 2010 Elsevier Inc. All rights reserved.

[Late respiratory function complications following burns].

PubMed

Ernesto, S; Marduel, Y; Freymond, N; Pacheco, Y; Devouassoux, G

2008-03-01

Twenty five per cent of thermal injuries are associated with secondary respiratory events linked to several mechanisms. In the acute phase of the accident oedema of the airways, the fume inhalation syndrome and ARDS are the most common causes responsible for death in 60% of cases. Late respiratory complications are little known and neglected. They comprise obstructive ventilatory defects due to the inhalation syndrome and restrictive defects secondary to ARDS or to dermal injury. We report the case of a female patient, extensively burnt 2 years previously, admitted to hospital with severe acute respiratory failure complicating COPD. The presence of both restrictive and obstructive defects led to the suggestion of alternative underlying mechanisms such as the pulmonary consequences of ARDS and extensive dermal scars. The latter were responsible for an armour like thickening of the skin of the thorax compatible with the restrictive defect. These functional abnormalities and the potential severity of acute respiratory failure are indications for regular pulmonary follow-up of patients with severe circumferential scarring of the thorax who are at high risk for respiratory complications.

HSP70.1 AND -70.3 ARE REQUIRED FOR LATE-PHASE PROTECTION INDUCED BY ISCHEMIC PRECONDITIONING OF MOUSE HEARTS

EPA Science Inventory

Heat-Shock Proteins 70.1 and 70.3 Are Required for Late-phase Protection
Induced by Ischemic Preconditioning of the Mouse Heart
Craig R. Hampton 1 , Akira Shimamoto 1 , Christine L. Rothnie 1 , Jeaneatte Griscavage-Ennis 1 ,
Albert Chong 1 , David J. Dix 2 , Edward D. Ve...

Food cravings and food cue responding across the menstrual cycle in a non-eating disordered sample.

PubMed

McVay, Megan Apperson; Copeland, Amy L; Newman, Hannah S; Geiselman, Paula J

2012-10-01

The study aim was to examine changes in food cue-elicited cravings and the macronutrient content of craved foods across menstrual cycle phases in a non-eating disordered sample. Thirty-five college females attended laboratory sessions in the late follicular and late luteal phases. In each session they completed a measure of state food craving before and after exposure to preferred, high fat/high sugar chocolate candy. Candy consumption following cue exposure was measured during an ad libitum "taste test." Additionally, participants rated their desire to eat foods differing systematically and significantly in macronutrient content. Ovulation was confirmed with luteinizing hormone detection kits. Results show that whereas the food cue increased cravings, this effect did not differ between cycle phases examined. The macronutrient content of foods desired also did not differ significantly between cycle phases, however, a non-significant trend suggested that high fat/high complex carbohydrate and low fat/high protein foods were more strongly desired in the late luteal phase. Amount of chocolate candy eaten did not differ between cycle phases. These results suggest that cravings for high fat/high sugar foods do not differ between menstrual cycle phases examined, whereas cravings for other foods may fluctuate across cycle phases in non-eating disordered women. Copyright © 2012 Elsevier Ltd. All rights reserved.

Context and explicit threat cue modulation of the startle reflex: Preliminary evidence of distinctions between adolescents with principal fear disorders versus distress disorders

PubMed Central

Waters, Allison M.; Nazarian, Maria; Mineka, Susan; Zinbarg, Richard E.; Griffith, James W.; Naliboff, Bruce; Ornitz, Edward M.; Craske, Michelle G.

2014-01-01

Anxiety and depression are prevalent, impairing disorders. High comorbidity has raised questions about how to define and classify them. Structural models emphasise distinctions between “fear” and “distress” disorders while other initiatives propose they be defined by neurobiological indicators that cut across disorders. This study examined startle reflex (SR) modulation in adolescents with principal fear disorders (specific phobia; social phobia) (n = 20), distress disorders (unipolar depressive disorders, dysthymia, generalized anxiety disorder; post-traumatic stress disorder) (n = 9), and controls (n = 29) during (a) baseline conditions, (b) threat context conditions (presence of contraction pads over the biceps muscle), and (c) an explicit threat cue paradigm involving phases that signalled safety from aversive stimuli (early and late stages of safe phases; early stages of danger phases) and phases that signalled immediate danger of an aversive stimulus (late stages of danger phases). Adolescents with principal fear disorders showed larger SRs than other groups throughout safe phases and early stages of danger phases. SRs did not differ between groups during late danger phases. Adolescents with principal distress disorders showed attenuated SRs during baseline and context conditions compared to other groups. Preliminary findings support initiatives to redefine emotional disorders based on neurobiological functioning. PMID:24679992

Mind over motor mapping: Driver response to changing vehicle dynamics.

PubMed

Bruno, Jennifer L; Baker, Joseph M; Gundran, Andrew; Harbott, Lene K; Stuart, Zachary; Piccirilli, Aaron M; Hosseini, S M Hadi; Gerdes, J Christian; Reiss, Allan L

2018-06-08

Improvements in vehicle safety require understanding of the neural systems that support the complex, dynamic task of real-world driving. We used functional near infrared spectroscopy (fNIRS) and pupilometry to quantify cortical and physiological responses during a realistic, simulated driving task in which vehicle dynamics were manipulated. Our results elucidate compensatory changes in driver behavior in response to changes in vehicle handling. We also describe associated neural and physiological responses under different levels of mental workload. The increased cortical activation we observed during the late phase of the experiment may indicate motor learning in prefrontal-parietal networks. Finally, relationships among cortical activation, steering control, and individual personality traits suggest that individual brain states and traits may be useful in predicting a driver's response to changes in vehicle dynamics. Results such as these will be useful for informing the design of automated safety systems that facilitate safe and supportive driver-car communication. © 2018 Wiley Periodicals, Inc.

Effects of late quaternary climate change on Palearctic shrews.

PubMed

Prost, Stefan; Klietmann, Johannes; van Kolfschoten, Thijs; Guralnick, Robert P; Waltari, Eric; Vrieling, Klaas; Stiller, Mathias; Nagel, Doris; Rabeder, Gernot; Hofreiter, Michael; Sommer, Robert S

2013-06-01

The Late Quaternary was a time of rapid climatic oscillations and drastic environmental changes. In general, species can respond to such changes by behavioral accommodation, distributional shifts, ecophenotypic modifications (nongenetic), evolution (genetic) or ultimately face local extinction. How those responses manifested in the past is essential for properly predicting future ones especially as the current warm phase is further intensified by rising levels of atmospheric carbon dioxide. Here, we use ancient DNA (aDNA) and morphological features in combination with ecological niche modeling (ENM) to investigate genetic and nongenetic responses of Central European Palearctic shrews to past climatic change. We show that a giant form of shrew, previously described as an extinct Pleistocene Sorex species, represents a large ecomorph of the common shrew (Sorex araneus), which was replaced by populations from a different gene-pool and with different morphology after the Pleistocene Holocene transition. We also report the presence of the cold-adapted tundra shrew (S. tundrensis) in Central Europe. This species is currently restricted to Siberia and was hitherto unknown as an element of the Pleistocene fauna of Europe. Finally, we show that there is no clear correlation between climatic oscillations within the last 50 000 years and body size in shrews and conclude that a special nonanalogous situation with regard to biodiversity and food supply in the Late Glacial may have caused the observed large body size. © 2013 Blackwell Publishing Ltd.

Climate Teleconnections and Recent Patterns of Human and Animal Disease Outbreaks

NASA Technical Reports Server (NTRS)

Anyamba, Assaf; Linthicum, Kenneth J.; Small, Jennifer L.; Collins, Katherine M.; Tucker, Compton J.; Pak, Edwin W.; Britch, Seth C.; Eastman, James Ronald; Pinzon, Jorge E.; Russell, Kevin L.

2011-01-01

Recent clusters of outbreaks of mosquito-borne diseases (Rift Valley fever and chikungunya) in Africa and parts of the Indian Ocean islands illustrate how interannual climate variability influences the changing risk patterns of disease outbreaks. Extremes in rainfall (drought and flood) during the period 2004 - 2009 have privileged different disease vectors. Chikungunya outbreaks occurred during the severe drought from late 2004 to 2006 over coastal East Africa and the western Indian Ocean islands and in the later years India and Southeast Asia. The chikungunya pandemic was caused by a Central/East African genotype that appears to have been precipitated and then enhanced by global-scale and regional climate conditions in these regions. Outbreaks of Rift Valley fever occurred following excessive rainfall period from late 2006 to late 2007 in East Africa and Sudan, and then in 2008 - 2009 in Southern Africa. The shift in the outbreak patterns of Rift Valley fever from East Africa to Southern Africa followed a transition of the El Nino/Southern Oscillation (ENSO) phenomena from the warm El Nino phase (2006-2007) to the cold La Nina phase (2007-2009) and associated patterns of variability in the greater Indian Ocean basin that result in the displacement of the centres of above normal rainfall from Eastern to Southern Africa. Understanding the background patterns of climate variability both at global and regional scale and their impacts on ecological drivers of vector borne-diseases is critical in long-range planning of appropriate response and mitigation measures.

Circadian Phase-Shifting Effects of Bright Light, Exercise, and Bright Light + Exercise.

PubMed

Youngstedt, Shawn D; Kline, Christopher E; Elliott, Jeffrey A; Zielinski, Mark R; Devlin, Tina M; Moore, Teresa A

2016-02-26

Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210-2340 h, (2) treadmill exercise alone from 2210-2340 h, or (3) bright light (2210-2340 h) followed by exercise from 0410-0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect.

Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia.

PubMed

Singh, Anju; Periasamy, Sivakumar; Malik, Meenakshi; Bakshi, Chandra Shekhar; Stephen, Laurie; Ault, Jeffrey G; Mannella, Carmen A; Sellati, Timothy J

2017-01-01

Infection with Francisella tularensis ssp. tularensis ( Ft ) strain SchuS4 causes an often lethal disease known as tularemia in rodents, non-human primates, and humans. Ft subverts host cell death programs to facilitate their exponential replication within macrophages and other cell types during early respiratory infection (⩽72 h). The mechanism(s) by which cell death is triggered remains incompletely defined, as does the impact of Ft on mitochondria, the host cell's organellar 'canary in a coal mine'. Herein, we reveal that Ft infection of host cells, particularly macrophages and polymorphonuclear leukocytes, drives necroptosis via a receptor-interacting protein kinase 1/3-mediated mechanism. During necroptosis mitochondria and other organelles become damaged. Ft -induced mitochondrial damage is characterized by: (i) a decrease in membrane potential and consequent mitochondrial oncosis or swelling, (ii) increased generation of superoxide radicals, and (iii) release of intact or damaged mitochondria into the lung parenchyma. Host cell recognition of and response to released mitochondria and other damage-associated molecular patterns engenders a sepsis-like syndrome typified by production of TNF, IL-1 β , IL-6, IL-12p70, and IFN- γ during late-phase tularemia (⩾72 h), but are absent early during infection.

Factors associated with failure of oncology drugs in late-stage clinical development: A systematic review.

PubMed

Jardim, Denis L; Groves, Eric S; Breitfeld, Philip P; Kurzrock, Razelle

2017-01-01

We aimed to describe the reasons for failure of experimental anticancer drugs in late-stage clinical development. We searched the PharmaProjects database (https://citeline.com/products/pharmaprojects/) for anticancer drugs discontinued between 01/01/2009 and 06/30/2014. Drug programs that reached phase III trials, but never gained Food and Drug Administration (FDA) approval were compared to 37 anti-cancer drugs achieving FDA approval in this time period. Forty-two drugs fit our criteria for development failures. These failed drugs (49% targeted, 23% cytotoxics, and 28% other) were tested in 43 cancer indications (drug programs). Only 16% (7/43) of failed drug programs adopted a biomarker-driven rationale for patient selection versus 57% (21/37) of successful drug programs (P<0.001). Phase II trial information was available in 32 of 43 failed drug programs and in 32 of 37 successful programs. Nine of the 32 trials (28%) of failed drugs versus 28 of 32 trials (87%) of successful drugs (P<0.001) achieved proof of concept (single agent response rate (RR) ⩾20% or combination therapy showing a ⩾20% RR increase above the median historical RR without the experimental agent (with a minimal absolute increase of 5%) or a randomized phase II trial showing significance (P⩽0.05) for its primary outcome). No pattern of study sites, trial design or funding characteristics emerged from the failed drug analysis. For drugs that reached Phase III, lack of a biomarker-driven strategy and failure to attain proof of concept in phase II are potential risk factors for later discontinuation, especially for targeted agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased plasmacytoid dendritic cells in Guillain-Barré syndrome.

PubMed

Wang, Yu-Zhong; Feng, Xun-Gang; Wang, Qian; Xing, Chun-Ye; Shi, Qi-Guang; Kong, Qing-Xia; Cheng, Pan-Pan; Zhang, Yong; Hao, Yan-Lei; Yuki, Nobuhiro

2015-06-15

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease. Dendritic cells (DCs) can recognize the pathogen and modulate the host immune response. Exploring the role of DCs in GBS will help our understanding of the disease development. In this study, we aimed to analyze plasmacytoid and conventional DCs in peripheral blood of patients with GBS at different stages of the disease: acute phase as well as early and late recovery phases. There was a significant increase of plasmacytoid DCs in the acute phase (p=0.03 vs healthy donors). There was a positive correlation between percentage of plasmacytoid DCs and the clinical severity of patients with GBS (r=0.61, p<0.001). Quantitative polymerase chain reaction and flow cytometry confirmed the aberrant plasmacytoid DCs in GBS. Thus, plasmacytoid DCs may participate in the development of GBS. Copyright © 2015 Elsevier B.V. All rights reserved.

Therapist adherence is associated with outcome in cognitive-behavioral therapy for bulimia nervosa.

PubMed

Folke, Sofie; Daniel, Sarah I F; Gondan, Matthias; Lunn, Susanne; Tækker, Louise; Poulsen, Stig

2017-06-01

Studies of therapist adherence in relation to treatment outcome have produced mixed results. The aim of the present study was to investigate change in therapist adherence to cognitive-behavioral therapy (CBT) for bulimia nervosa over time, and to investigate the relationship between adherence and client outcome in early, middle, and late phases of treatment. Thirty-six clients received the focused form of "enhanced" CBT (CBT-E) for bulimia nervosa. Trained observers rated audiotapes of 92 full-length therapy sessions from early (Session 3), middle (Session 11), and late phases (Session 20) of treatment using the Cognitive-Behavioral Therapy Treatment Protocol Adherence Scale. Change in adherence across the 3 treatment phases was examined using multilevel analysis. The relationship between early, middle, and late adherence levels and end-of-treatment binging frequency was examined using multilevel Poisson regression analysis. Adherence decreased significantly over the course of treatment. Higher levels of therapist adherence in early and middle phases of treatment were associated with reduced binging frequency, whereas higher levels of adherence measured late in treatment was not. Results indicate that therapists' adherence to the CBT-E treatment protocol decreases over time and that high levels of protocol adherence in early and middle phases of treatment are more important for positive client outcomes than high levels of adherence in the end of treatment. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Inter-decadal change in potential predictability of the East Asian summer monsoon

NASA Astrophysics Data System (ADS)

Li, Jiao; Ding, Ruiqiang; Wu, Zhiwei; Zhong, Quanjia; Li, Baosheng; Li, Jianping

2018-05-01

The significant inter-decadal change in potential predictability of the East Asian summer monsoon (EASM) has been investigated using the signal-to-noise ratio method. The relatively low potential predictability appears from the early 1950s through the late 1970s and during the early 2000s, whereas the potential predictability is relatively high from the early 1980s through the late 1990s. The inter-decadal change in potential predictability of the EASM can be attributed mainly to variations in the external signal of the EASM. The latter is mostly caused by the El Niño-Southern Oscillation (ENSO) inter-decadal variability. As a major external signal of the EASM, the ENSO inter-decadal variability experiences phase transitions from negative to positive phases in the late 1970s, and to negative phases in the late 1990s. Additionally, ENSO is generally strong (weak) during a positive (negative) phase of the ENSO inter-decadal variability. The strong ENSO is expected to have a greater influence on the EASM, and vice versa. As a result, the potential predictability of the EASM tends to be high (low) during a positive (negative) phase of the ENSO inter-decadal variability. Furthermore, a suite of Pacific Pacemaker experiments suggests that the ENSO inter-decadal variability may be a key pacemaker of the inter-decadal change in potential predictability of the EASM.

MCM-BP regulates unloading of the MCM2–7 helicase in late S phase

PubMed Central

Nishiyama, Atsuya; Frappier, Lori; Méchali, Marcel

2011-01-01

Origins of DNA replication are licensed by recruiting MCM2–7 to assemble the prereplicative complex (pre-RC). How MCM2–7 is inactivated or removed from chromatin at the end of S phase is still unclear. Here, we show that MCM-BP can disassemble the MCM2–7 complex and might function as an unloader of MCM2–7 from chromatin. In Xenopus egg extracts, MCM-BP exists in a stable complex with MCM7, but is not associated with the MCM2–7 hexameric complex. MCM-BP accumulates in nuclei in late S phase, well after the loading of MCM2–7 onto chromatin. MCM-BP immunodepletion in Xenopus egg extracts inhibits replication-dependent MCM dissociation without affecting pre-RC formation and DNA replication. When excess MCM-BP is incubated with Xenopus egg extracts or immunopurified MCM2–7, it binds to MCM proteins and promotes disassembly of the MCM2–7 complex. Recombinant MCM-BP also releases MCM2–7 from isolated late-S-phase chromatin, but this activity is abolished when DNA replication is blocked. MCM-BP silencing in human cells also delays MCM dissociation in late S phase. We propose that MCM-BP plays a key role in the mechanism by which pre-RC is cleared from replicated DNA in vertebrate cells. PMID:21196493

The tectonometamorphic evolution of the Apuseni Mountains (Romania): Geodynamic constraints for the evolution of the Alps-Carpathians-Dinaride system of orogens

NASA Astrophysics Data System (ADS)

Reiser, Martin; Schuster, Ralf; Fügenschuh, Bernhard

2015-04-01

New structural, thermobarometric and geochronological data allow integrating kinematics, timing and intensity of tectonic phases into a geodynamic model of the Apuseni Mountain, which provides new constraints for the evolution of the Alps-Carpathians-Dinaride system of orogens. Strong differences in terms of deformation directions between Early and Late Cretaceous events provide new constraints on the regional geodynamic evolution during the Cretaceous. Geochronological and structural data evidence a Late Jurassic emplacement of the South Apuseni Ophiolites on top of the Biharia Nappe System (Dacia Mega-Unit), situated in an external position at the European margin. Following the emplacement of the ophiolites, three compressive deformation phases affected the Apuseni Mountains during Alpine orogeny: a) NE-directed in-sequence nappe stacking and regional metamorphic overprinting under amphibolite-facies conditions during the Early Cretaceous ("Austrian Phase"), b) NW-directed thrusting and folding, associated with greenschist-facies overprinting, during the early Late Cretaceous ("Turonian Phase") and c) E-W internal folding together with brittle thrusting during the latest Cretaceous ("Laramian Phase"). Major tectonic unroofing and exhumation at the transition from Early to Late Cretaceous times is documented through new Sm-Nd Grt, Ar-Ar Ms and Rb-Sr Bt ages from the study area and resulted in a complex thermal structure with strong lateral and vertical thermal gradients. Nappe stacking and medium-grade metamorphic overprinting during the Early Cretaceous exhibits striking parallels between the evolution of the Tisza-Dacia Mega-Units and the Austroalpine Nappes (ALCAPA Mega-Unit) and evidences a close connection. However, Late Cretaceous tectonic events in the study area exhibit strong similarities with the Dinarides. Thus, the Apuseni Mountains represent the "missing link" between the Early Cretaceous Meliata subduction (associated with obduction of ophiolites) and the Neotethys subduction during Late Cretaceous times.

Mice lacking the PACAP type I receptor have impaired photic entrainment and negative masking.

PubMed

Hannibal, Jens; Brabet, Philippe; Fahrenkrug, Jan

2008-12-01

The retinohypothalamic tract (RHT) is a retinofugal neuronal pathway which, in mammals, mediates nonimage-forming vision to various areas in the brain involved in circadian timing, masking behavior, and regulation of the pupillary light reflex. The RHT costores the two neurotransmitters glutamate and pituitary adenylate cyclase activating peptide (PACAP), which in a rather complex interplay are mediators of photic adjustment of the circadian system. To further characterize the role of PACAP/PACAP receptor type 1 (PAC1) receptor signaling in light entrainment of the clock and in negative masking behavior, we extended previous studies in mice lacking the PAC1 receptor (PAC1 KO) by examining their phase response to single light pulses using Aschoff type II regime, their ability to entrain to non-24-h light-dark (LD) cycles and large phase shifts of the LD cycle (jet lag), as well as their negative masking response during different light intensities. A prominent finding in PAC1 KO mice was a significantly decreased phase delay of the endogenous rhythm at early night. In accordance, PAC1 KO mice had a reduced ability to entrain to T cycles longer than 26 h and needed more time to reentrain to large phase delays, which was prominent at low light intensities. The data obtained at late night indicated that PACAP/PAC1 receptor signaling is less important during the phase-advancing part of the phase-response curve. Finally, the PAC1 KO mice showed impaired negative masking behavior at low light intensities. Our findings substantiate a role for PACAP/PAC1 receptor signaling in nonimage-forming vision and indicate that the system is particularly important at lower light intensities.

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

Słonina, Dorota, E-mail: z5slonin@cyfronet.pl; Biesaga, Beata; Janecka, Anna

Purpose: In our previous study, using the micronucleus assay, a low-dose hyper-radiosensitivity (HRS)-like phenomenon was observed for normal fibroblasts of 2 of the 40 cancer patients investigated. In this article we report, for the first time, the survival response of primary fibroblasts from 25 of these patients to low-dose irradiation and answer the question regarding the effect of G2-phase enrichment on HRS elicitation. Methods and Materials: The clonogenic survival of asynchronous as well as G2-phase enriched fibroblast populations was measured. Separation of G2-phase cells and precise cell counting was performed using a fluorescence-activated cell sorter. Sorted and plated cells weremore » irradiated with single doses (0.1-4 Gy) of 6-MV x-rays. For each patient, at least 4 independent experiments were performed, and the induced-repair model was fitted over the whole data set to confirm the presence of HRS effect. Results: The HRS response was demonstrated for the asynchronous and G2-phase enriched cell populations of 4 patients. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, G2-phase enrichment had no effect on HRS elicitation. Conclusions: The fact that low-dose hyper-radiosensitivity is not a common effect in normal human fibroblasts implies that HRS may be of little consequence in late-responding connective tissues with regard to radiation fibrosis.« less

Social provocation modulates decision making and feedback processing: Examining the trajectory of development in adolescent participants.

PubMed

Pincham, Hannah L; Wu, Claire; Killikelly, Clare; Vuillier, Laura; Fearon, R M Pasco

2015-10-01

Increasingly, research is turning to the ways in which social context impacts decision making and feedback processing in adolescents. The current study recorded electroencephalography to examine the trajectory of development across adolescence, with a focus on how social context impacts cognition and behaviour. To that end, younger (10-12 years) and older (14-16 years) adolescents played a modified Taylor Aggression Paradigm against two virtual opponents: a low-provoker and a high-provoker. During the task's decision phase (where participants select punishment for their opponent), we examined two event-related potentials: the N2 and the late positive potential (LPP). During the outcome phase (where participants experience win or loss feedback), we measured the feedback related negativity (FRN). Although N2 amplitudes did not vary with provocation, LPP amplitudes were enhanced under high provocation for the younger group, suggesting that emotional reactivity during the decision phase was heightened for early adolescents. During the outcome phase, the FRN was reduced following win outcomes under high provocation for both groups, suggesting that a highly provocative social opponent may influence the reward response. Collectively, the data argue that social context is an important factor modulating neural responses in adolescent behavioural and brain development. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The influence of the North Atlantic Ocean variability on the atmosphere in the cold season at seasonal to multidecadal time scales

NASA Astrophysics Data System (ADS)

Frankignoul, C.

2017-12-01

Observational evidence of an atmospheric response to the North Atlantic horseshoe SST anomalies has been accumulating since the late 90's, suggesting that it drives a negative NAO response during late fall/early winter. The North Atlantic horseshoe SST anomaly is in part stochastically driven by the atmosphere, but at low frequency it is correlated with the Atlantic Multidecadal Oscillation (AMO). Correspondingly, an atmospheric response to the AMO has been detected at low frequency in winter, with a positive AMO phase leading a negative NAO-like pattern, consistent with sensitivity studies with atmospheric general circulation models. Both the subpolar and tropical components of the AMO seem to contribute to its influence on the atmosphere. As North Atlantic SST changes reflects internally-generated SST fluctuations as well the response to anthropogenic and other external forcing, the AMO is sensitive to the way the forced SST signal is removed; estimates of the natural variability of the AMO vary by as much as a factor of two between estimation methods, leading to possible biases in its alleged impacts. Since an intensification of the Atlantic meridional overturning circulation (AMOC) leads the AMO and drives a negative NAO in many climate models, albeit with different lead times, the relation between AMO and AMOC will be discussed, as well as possible links with the North Pacific and sea ice variability.

Targeting the host immune system: PD-1 and PD-L1 antibodies and breast cancer.

PubMed

Dawood, Shaheenah; Rugo, Hope S

2016-12-01

This article describes the role of the PD-1 axis and reviews current data and future directions inhibiting PD-1 and PD-L1 in breast cancer. Four phase I monotherapy expansion trials in patients with metastatic breast cancer have demonstrated low but durable single agent responses to PD-1 and PD-L1 inhibitors, ranging from 4.8 to 19%. Higher response rates are seen in triple negative breast cancer, compared with hormone receptor positive disease. Variability in requirements for tumor PD-L1 expression, and variations in testing complicate cross trial comparisons. A fifth phase Ib trial reported a 38% response rate in metastatic triple negative breast cancer treated with the combination of a PD-L1 inhibitor and nab-paclitaxel chemotherapy. Treatment is generally well tolerated, with low rates of immune toxicity including hypothyroidism, pneumonitis, hepatitis, colitis, and hypophysitis, occurring even months after the end of therapy. Immune checkpoint inhibitor therapy has recently been shown to have clinical efficacy in the treatment of breast cancer. The most compelling data are in the triple negative subtype, with responses documented in hormone receptor positive disease as well. Numerous trials are evaluating various combination strategies and biomarkers in early and late stage disease to enhance immunogenicity and response.

Evaluating the role of phage-shock protein A in Burkholderia pseudomallei.

PubMed

Southern, Stephanie J; Male, Abigail; Milne, Timothy; Sarkar-Tyson, Mitali; Tavassoli, Ali; Oyston, Petra C F

2015-11-01

The phage-shock protein (Psp) response is an extracytoplasmic response system that is vital for maintenance of the cytoplasmic membrane when the cell encounters stressful conditions. The paradigm of the Psp response has been established in Escherichia coli. The response has been shown to be important for survival during the stationary phase, maintenance of the proton motive force across membranes and implicated in virulence. In this study, we identified a putative PspA homologue in Burkholderia pseudomallei, annotated as BPSL2105. Similar to the induction of PspA in E. coli, the expression of B. pseudomallei BPSL2105 was induced by heat shock. Deletion of BPSL2105 resulted in a survival defect in the late stationary phase coincident with dramatic changes in the pH of the culture medium. The B. pseudomallei BPSL2105 deletion mutant also displayed reduced survival in macrophage infection - the first indication that the Psp response plays a role during intracellular pathogenesis in this species. The purified protein formed large oligomeric structures similar to those observed for the PspA protein of E. coli, and PspA homologues in Bacillus, cyanobacteria and higher plants, providing further evidence to support the identification of BPSL2105 as a PspA-like protein in B. pseudomallei.

The effect of learning on feedback-related potentials in adolescents with dyslexia: an EEG-ERP study.

PubMed

Kraus, Dror; Horowitz-Kraus, Tzipi

2014-01-01

Individuals with dyslexia exhibit associated learning deficits and impaired executive functions. The Wisconsin Card Sorting Test (WCST) is a learning-based task that relies heavily on executive functioning, in particular, attention shift and working memory. Performance during early and late phases of a series within the task represents learning and implementation of a newly learned rule. Here, we aimed to examine two event-related potentials associated with learning, feedback-related negativity (FRN)-P300 complex, in individuals with dyslexia performing the WCST. Adolescents with dyslexia and age-matched typical readers performed the Madrid card sorting test (MCST), a computerized version of the WCST. Task performance, reading measures, and cognitive measures were collected. FRN and the P300 complex were acquired using the event-related potentials methodology and were compared in early vs late errors within a series. While performing the MCST, both groups showed a significant reduction in average reaction times and a trend toward decreased error rates. Typical readers performed consistently better than individuals with dyslexia. FRN amplitudes in early phases were significantly smaller in dyslexic readers, but were essentially equivalent to typical readers in the late phase. P300 amplitudes were initially smaller among readers with dyslexia and tended to decrease further in late phases. Differences in FRN amplitudes for early vs late phases were positively correlated with those of P300 amplitudes in the entire sample. Individuals with dyslexia demonstrate a behavioral and electrophysiological change within single series of the MCST. However, learning patterns seem to differ between individuals with dyslexia and typical readers. We attribute these differences to the lower baseline performance of individuals with dyslexia. We suggest that these changes represent a fast compensatory mechanism, demonstrating the importance of learning strategies on reading among individuals with dyslexia.

Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline.

PubMed

Halbreich, Uriel; Kahn, Linda S

2003-11-01

Sertraline (Zoloft, Pfizer Inc.) is a selective serotonin re-uptake inhibitor (SSRI) which has been approved by the US FDA for the treatment of premenstrual dysphoric disorder (PMDD). PMDD is a severe form of premenstrual syndrome (PMS) which affects at least 5 - 8% of women of reproductive age. It is characterised by cyclic appearance at the late luteal phase of the menstrual cycle, and disappearance following the beginning of menses, with no symptoms during at least 1 week of the cycle - usually during the mid-follicular phase. Due to the cyclic luteal occurrence of PMDD, luteal phase dosing of SSRIs has been suggested and proven effective for sertraline as well as several other SSRIs. The clinical response of sertraline is reported to be within several days following initiation of treatment. Despite repeated cyclic discontinuation, no significant discontinuation adverse effects have been reported. In addition to its proven clinical efficacy, luteal-phase dosing may offer the advantages of minimising adverse effects of SSRIs while reducing the personal and economic burden of taking a prescription medication continuously for long periods and thus increasing compliance.

Design considerations and analysis planning of a phase 2a proof of concept study in rheumatoid arthritis in the presence of possible non-monotonicity.

PubMed

Liu, Feng; Walters, Stephen J; Julious, Steven A

2017-10-02

It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA), a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC) trial for a follow-on compound using the lessons learnt from the lead compound. The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid "S" shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM) is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response follows a placebo like curve, an Emax like curve, or log linear shape curve under fixed dose allocation, no adaptive allocation, half adaptive and adaptive scenarios. The bias though is significantly increased for the Emax model if the true dose response follows a U-shaped curve. In most cases the Bayesian Emax model works effectively and efficiently, with low bias and good probability of success in case of monotonic dose response. However, if there is a belief that the dose response could be non-monotonic then the NDLM is the superior model to assess the dose response.

Inhibition of Late and Early Phases of Cancer Metastasis by the NF-κB Inhibitor DHMEQ Derived from Microbial Bioactive Metabolite Epoxyquinomicin: A Review.

PubMed

Lin, Yinzhi; Ukaji, Tamami; Koide, Naoki; Umezawa, Kazuo

2018-03-03

We previously designed and synthesized dehydroxyepoxyquinomicin (DHMEQ) as an inhibitor of NF-κB based on the structure of microbial secondary metabolite epoxyquinomicin C. DHMEQ showed anti-inflammatory and anticancer activity in various in vivo disease models without toxicity. On the other hand, the process of cancer metastasis consists of cell detachment from the primary tumor, invasion, transportation by blood or lymphatic vessels, invasion, attachment, and formation of secondary tumor. Cell detachment from the primary tumor and subsequent invasion are considered to be early phases of metastasis, while tumor cell attachment to the tissue and secondary tumor formation the late phases. The assay system for the latter phase was set up with intra-portal-vein injection of pancreatic cancer cells. Intraperitoneal administration of DHMEQ was found to inhibit liver metastasis possibly by decreasing the expression of MMP-9 and IL-8. Also, when the pancreatic cancer cells treated with DHMEQ were inoculated into the peritoneal cavity of mice, the metastatic foci formation was inhibited. These results indicate that DHMEQ is likely to inhibit the late phase of metastasis. Meanwhile, we have recently employed three-dimensional (3D) culture of breast cancer cells for the model of early phase metastasis, since the 3D invasion just includes cell detachment and invasion into the matrix. DHMEQ inhibited the 3D invasion of breast cancer cells at 3D-nontoxic concentrations. In this way, DHMEQ was shown to inhibit the late and early phases of metastasis. Thus, DHMEQ is likely to be useful for the suppression of cancer metastasis.

Hepatic Hemangiomas: Factors Associated with Pseudo Washout Sign on Gd-EOB-DTPA-enhanced MR Imaging.

PubMed

Tateyama, Akihiro; Fukukura, Yoshihiko; Takumi, Koji; Shindo, Toshikazu; Kumagae, Yuichi; Nakamura, Fumihiko

2016-01-01

Our study aim was to clarify the characteristics of hemangiomas with pseudo washout sign (PWS) by comparing their features with those of hemangiomas without PWS on gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging. We evaluated the features of hemangiomas on Gd-EOB-DTPA-enhanced MR imaging of 70 hepatic hemangiomas in 31 patients, investigating the presence of peripheral or central nodular enhancement, diffuse enhancement, and arterioportal shunt during the arterial phase, fill-in enhancement during the portal venous phase, and PWS, which is low signal intensity during the late phase. We visually assessed the intensity of contrast enhancement of the lesion during the arterial, portal venous, late, and hepatobiliary phases using a 4-grade scale and used the Fisher exact and Mann-Whitney U tests to compare hemangiomas with and without PWS. We observed PWS in 33 (47%) of 70 hemangiomas, which were significantly smaller than the hemangiomas without PWS (17.4 mm ± 20.3 versus 30.1 mm ± 28.5; P = 0.005); more frequent diffuse enhancement in hemangiomas with PWS than those without (21.2% versus 2.7%; P = 0.026); and no significant differences in nodular enhancement (P = 0.231), arterioportal shunt (P = 0.403), or fill-in enhancement (P = 0.357) between hemangiomas with and without PWS. Visually determined grades of tumor contrast enhancement were significantly lower in hemangiomas with PWS during the portal venous (P = 0.007) and late (P < 0.001) phases. Small hemangiomas tend to decrease in signal intensity during the portal venous phase and show PWS during the late phase.

Arctic-North Pacific Coupled Impacts on the Late Autumn Cold in North America

NASA Technical Reports Server (NTRS)

Sung, Mi-Kyung; Kim, Baek-Min; Baik, Eun-Hyuk; Lim, Young-Kwon; Kim, Seong-Joong

2016-01-01

The Pacific Decadal Oscillation (PDO) is known to bring an anomalously cold (warm) period to southeastern (northwestern) North America during the cold season of its positive phase through a Rossby wave linkage. This study provides evidence that the remote connection between the North Pacific and the downstream temperature over central North America is strengthened by the warm arctic conditions over the Chukchi and East Siberian Sea, especially in the late autumn season. The modulation effect of the Arctic manifests itself as an altered Rossby wave response to a transient vorticity forcing that results from an equatorward storm track shift, which is induced collaboratively by the PDO and the warm Arctic. This observational finding is supported by two independent modeling experiments: 1) an idealized coupled GCM experiment being nudged toward the warm arctic surface condition and 2) a simple stationary wave model (SWM) experiment forced by transient eddy forcing.

Variation in forearc basin development along the Sunda Arc, Indonesia

NASA Astrophysics Data System (ADS)

van der Werff, W.

The present forearc basin configuration along the Sunda Arc initially appears to have been controlled by extension and differential subsidence of basement blocks in response to the late Eocene collision of India with Asia. The late Oligocene increase in convergence between the South-east Asian and Indian Plates associated with a new pulse of subduction, resulted in basement uplift and the formation of a regional unconformity that can be recognized along the entire Sunda Arc. From the early to late Miocene, the Sumba and Savu forearc sectors along the eastern Sunda Arc may have been characterized by forearc extension. Submarine fan deposition on the arcward side of the evolving accretionary prism represents the first phase in forearc basin deposition. These fans were subsequently covered by basin and slope sediments derived from the evolving magmatic arc. Structural response to increased late Miocene compression varied along strike of the Sunda Arc. North of Bali, Lombok and Sumbawa, the incipient collision between Australia and the western Banda Arc caused back-arc thrusting and basin inversion. Towards the south of Java, an increase in both the size of the accretionary prism and convergence rates resulted in uplift and large scale folding of the outer forearc basin strata. Along the west coast of Sumatra, increased compression resulted in uplift along the inner side of the forearc along older transcurrent faults. Uplift of West Sumatra was followed by the deposition of a westward prograding sequence of terrigenous sediments that resulted in the development of a broad shelf. Initial forearc basin subsidence relates to the age of the subducting oceanic lithosphere, on top of which the basin is situated. Along the western Sunda Arc, both fexural loading of the evolving accretionary prism, and across arc strike-slip faulting represent additional factors that result in forearc subsidence.

Modeling the Climatic Effect of Convergent Tectonics During the Middle to Late Miocene: Effective Closure of the Indonesian Seaway, Himalayan Uplift and the East Asian Monsoon

NASA Astrophysics Data System (ADS)

DeConto, R. M.; MacConnell, A.; Leckie, R.

2001-05-01

During the middle to late Miocene, the northward drift of Australia and New Guinea progressively restricted Indonesian throughflow (ITF). Today, ITF plays an important role in modulating inter-basin fresh water flux, heat transport, and the volume of the Western Pacific Warm Pool (WPWP). Today's WPWP is a center for deep convection that contributes considerable diabatic heating to the tropical atmosphere, affecting both the Walker and Hadley circulation. The WPWP fuels the East Asian Monsoon with moisture and latent heat and is an important component of ENSO. As the Indonesian Seaway became restricted, India was impinging on Asia. Asian continentality was increased and Himalayan/Tibetan uplift begun affecting zonal atmospheric flow and land-surface albedo. In order to better understand the climate system's response to changing Miocene paleogeography (horizontal and vertical tectonics), we have begun a series of climate model experiments using atmosphere, ocean, and coupled atmosphere-ocean general circulation models (GCMs). The GCM experiments are designed to isolate the possible response to effective Indonesian gateway closure within the framework of evolving Miocene Paleogeography between 11 and 7 Ma. In the first phase of our modeling study, an AGCM was used to test the sensitivity of tropical Indo-Pacific and Asian climate (including monsoonal intensity) to the presence of a WPWP in a pre and post Himalayan/Tibetan Plateau world. The results of the GCM simulations will be discussed in the context of the hypotheses that 1) a proto-WPWP became established as the Indonesian Seaway became increasingly restricted during the late middle to late Miocene; and 2) the growth of the WPWP had a first order affect on tropical Pacific climate and the East Asian monsoon.

Theta Frequency Stimulation Induces a Local Form of Late Phase LTP in the CA1 Region of the Hippocampus

ERIC Educational Resources Information Center

Huang, Yan-You; Kandel, Eric R.

2005-01-01

The late phase of LTP (L-LTP) is typically induced by repeated high-frequency stimulation. This form of LTP requires activation of transcription and translation and results in the cell-wide distribution of gene products that can be captured by other marked synapses. Here we report that theta frequency stimulation (5 Hz, 30 sec) applied to the…

Late-time cosmological phase transitions

NASA Technical Reports Server (NTRS)

Schramm, David N.

1991-01-01

It is shown that the potential galaxy formation and large scale structure problems of objects existing at high redshifts (Z approx. greater than 5), structures existing on scales of 100 M pc as well as velocity flows on such scales, and minimal microwave anisotropies ((Delta)T/T) (approx. less than 10(exp -5)) can be solved if the seeds needed to generate structure form in a vacuum phase transition after decoupling. It is argued that the basic physics of such a phase transition is no more exotic than that utilized in the more traditional GUT scale phase transitions, and that, just as in the GUT case, significant random Gaussian fluctuations and/or topological defects can form. Scale lengths of approx. 100 M pc for large scale structure as well as approx. 1 M pc for galaxy formation occur naturally. Possible support for new physics that might be associated with such a late-time transition comes from the preliminary results of the SAGE solar neutrino experiment, implying neutrino flavor mixing with values similar to those required for a late-time transition. It is also noted that a see-saw model for the neutrino masses might also imply a tau neutrino mass that is an ideal hot dark matter candidate. However, in general either hot or cold dark matter can be consistent with a late-time transition.

Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Ding, Nan; Chang, Jianbo; Jian, Qiliang; Liang, Xuefei; Liang, Zhongzhen; Wang, Fang

2016-11-01

To assess the efficacy of late luteal phase clomiphene citrate (CC) administration relative to early follicular phase CC for ovulation induction for polycystic ovary syndrome (PCOS). Review. A complete electronic databases including PubMed, Embase, The Cochrane Library, Web of Science, and CBM were searched for relevant randomized controlled trials (RCTs). The search was not restricted by language and publication time. Two reviewers selected trials and assessed trial quality by the Cochrane Handbook 5.1.0 independently. Four eligible RCT studies involving 708 women (934 cycles) were included. The results of the Meta-analysis: Late luteal phase group was associated with a number of higher total follicles (MD 1.82; 95% CI 0.86-2.78, p < 0.00001) and significant higher endometrial thickness on the day of HCG (MD 0.88; 95% CI 0.78-0.99, p < 0.00001) compared with early follicular group. There were no significant differences in the rate of pregnancy (RR 1.29; 95% CI 0.83-2.01, p = 0.26), ovulation rate (RR 0.99; 95% CI 0.86-1.14, p = 0.87), and abortion rate (RR 1.12; 95% CI 0.38 to 3.29, p = 0.84) between the two groups. It appeared that late luteal phase CC for ovulation induction might be an effective method for ovulation induction in women with PCOS compared to conventional CC administration. Further intensive randomized-controlled studies should be warranted to define the efficacy of CC used in late luteal phase.

Circadian Phase-Shifting Effects of Bright Light, Exercise, and Bright Light + Exercise

PubMed Central

Kline, Christopher E.; Elliott, Jeffrey A.; Zielinski, Mark R.; Devlin, Tina M.; Moore, Teresa A.

2016-01-01

Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210–2340 h, (2) treadmill exercise alone from 2210–2340 h, or (3) bright light (2210–2340 h) followed by exercise from 0410–0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect. PMID:27103935

Effects of regular away travel on training loads, recovery, and injury rates in professional Australian soccer players.

PubMed

Fowler, Peter; Duffield, Rob; Waterson, Adam; Vaile, Joanna

2015-07-01

The current study examined the acute and longitudinal effects of regular away travel on training load (TL), player wellness, and injury surrounding competitive football (soccer) matches. Eighteen male professional football players, representing a team competing in the highest national competition in Australia, volunteered to participate in the study. Training loads, player wellness and injury incidence, rate, severity, and type, together with the activity at the time of injury, were recorded on the day before, the day of, and for 4 d after each of the 27 matches of the 2012-13 season. This included 14 home and 13 away matches, further subdivided based on the midpoint of the season into early (1-13) and late competition (14-27) phases. While TLs were significantly greater on day 3 at home compared with away during the early competition phase (P=.03), no other significant effects of match location were identified (P>.05). Total TL and mean wellness over the 6 d surrounding matches and TL on day 3 were significantly reduced during the late compared with the early competition phase at home and away (P<.05). Although not significantly (P>.05), training missed due to injury was 60% and 50% greater during the late than during the early competition phase at home and away, respectively. In conclusion, no significant interactions between match location and competition phase were evident during the late competition phase, which suggests that away travel had negligible cumulative effects on the reduction in player wellness in the latter half of the season.

Effect of bodily fluids from honey bee (Apis mellifera) larvae on growth and genome-wide transcriptional response of the causal agent of American Foulbrood disease (Paenibacillus larvae).

PubMed

De Smet, Lina; De Koker, Dieter; Hawley, Alyse K; Foster, Leonard J; De Vos, Paul; de Graaf, Dirk C

2014-01-01

Paenibacillus larvae, the causal agent of American Foulbrood disease (AFB), affects honey bee health worldwide. The present study investigates the effect of bodily fluids from honey bee larvae on growth velocity and transcription for this Gram-positive, endospore-forming bacterium. It was observed that larval fluids accelerate the growth and lead to higher bacterial densities during stationary phase. The genome-wide transcriptional response of in vitro cultures of P. larvae to larval fluids was studied by microarray technology. Early responses of P. larvae to larval fluids are characterized by a general down-regulation of oligopeptide and sugar transporter genes, as well as by amino acid and carbohydrate metabolic genes, among others. Late responses are dominated by general down-regulation of sporulation genes and up-regulation of phage-related genes. A theoretical mechanism of carbon catabolite repression is discussed.

Accelerated middle Miocene exhumation of the Talesh Mountains constrained by U-Th/He thermochronometry: Evidence for the Arabia-Eurasia collision in the NW Iranian Plateau

NASA Astrophysics Data System (ADS)

Madanipour, Saeed; Ehlers, Todd A.; Yassaghi, Ali; Enkelmann, Eva

2017-08-01

The Talesh Mountains at the NW margin of the Iranian Plateau curve around the southwestern corner of the South Caspian Block and developed in response to the collision of the Arabian-Eurasian Plates. The timing, rates, and regional changes in late Cenozoic deformation of the Talesh Mountains are not fully understood. In this study, we integrate 23 new apatite and zircon bedrock U-Th/He ages and structurally restored geologic cross sections with previously published detrital apatite fission track data to reconstruct the deformation history of the Talesh Mountains. Our results reveal that slow rock exhumation initiated during the late Oligocene ( 27-23 Ma) and then accelerated in the middle Miocene ( 12 Ma). These events resulted in the present-day high-elevation and curved geometry of the mountains. The spatial and temporal distribution of cooling ages suggest that the Oligocene bending of the Talesh Mountains was earlier than in the eastern Alborz, Kopeh Dagh, and central Alborz Mountains that initiated during the late Cenozoic. Late Oligocene and middle Miocene deformation episodes recorded in the Talesh Mountains can be related to the collisional phases of the Arabian and Eurasian Plates. The lower rate of exhumation recorded in the Talesh Mountains occurred during the initial soft collision of the Arabian-Eurasian Plates in the late Oligocene. The accelerated exhumation that occurred during final collision since the middle Miocene resulted from collision of the harder continental margin.

Timing of the endometrial biopsy may be critical for the accurate diagnosis of luteal phase deficiency.

PubMed

Castelbaum, A J; Wheeler, J; Coutifaris, C B; Mastroianni, L; Lessey, B A

1994-03-01

To determine the optimal time to perform the endometrial biopsy for the detection of "out-of-phase" endometrium. Two endometrial biopsies were performed during a single menstrual cycle in each subject. The patient's chronological day was determined by counting forward from the midcycle LH surge, as assessed by urinary LH detection. The "early" biopsy was done on day LH + 7.4 +/- 0.8, and the "late" biopsy on day LH + 11.6 +/- 0.7. Each biopsy was independently read by two pathologists and was considered out of phase if the histologic date was > or = 3 days delayed compared with the chronological date. Infertility practice of an academic teaching hospital. Thirty-three ovulatory women seeking evaluation for infertility. Number of patients with out-of-phase endometrium detected by the early versus the late biopsy. There was a significantly greater detection rate for out-of-phase endometrium using the early biopsy (12.1% to 18.2% incidence depending on the observer) compared with the later biopsy (6.1% to 9.1% incidence). A majority of the early out-of-phase biopsies corrected by the time of the later biopsy. Our findings indicate that an endometrial biopsy performed in the midluteal phase may detect a greater number of women with delayed endometrial maturation during the temporal window of embryo implantation. The observation that most of the women with out-of-phase midluteal biopsies had normal late luteal endometrium may represent a cryptic form of luteal phase deficiency.

Earthquake potential in California-Nevada implied by correlation of strain rate and seismicity

USGS Publications Warehouse

Zeng, Yuehua; Petersen, Mark D.; Shen, Zheng-Kang

2018-01-01

Rock mechanics studies and dynamic earthquake simulations show that patterns of seismicity evolve with time through (1) accumulation phase, (2) localization phase, and (3) rupture phase. We observe a similar pattern of changes in seismicity during the past century across California and Nevada. To quantify these changes, we correlate GPS strain rates with seismicity. Earthquakes of M > 6.5 are collocated with regions of highest strain rates. By contrast, smaller magnitude earthquakes of M ≥ 4 show clear spatiotemporal changes. From 1933 to the late 1980s, earthquakes of M ≥ 4 were more diffused and broadly distributed in both high and low strain rate regions (accumulation phase). From the late 1980s to 2016, earthquakes were more concentrated within the high strain rate areas focused on the major fault strands (localization phase). In the same time period, the rate of M > 6.5 events also increased significantly in the high strain rate areas. The strong correlation between current strain rate and the later period of seismicity indicates that seismicity is closely related to the strain rate. The spatial patterns suggest that before the late 1980s, the strain rate field was also broadly distributed because of the stress shadows from previous large earthquakes. As the deformation field evolved out of the shadow in the late 1980s, strain has refocused on the major fault systems and we are entering a period of increased risk for large earthquakes in California.

Earthquake Potential in California-Nevada Implied by Correlation of Strain Rate and Seismicity

NASA Astrophysics Data System (ADS)

Zeng, Yuehua; Petersen, Mark D.; Shen, Zheng-Kang

2018-02-01

Rock mechanics studies and dynamic earthquake simulations show that patterns of seismicity evolve with time through (1) accumulation phase, (2) localization phase, and (3) rupture phase. We observe a similar pattern of changes in seismicity during the past century across California and Nevada. To quantify these changes, we correlate GPS strain rates with seismicity. Earthquakes of M > 6.5 are collocated with regions of highest strain rates. By contrast, smaller magnitude earthquakes of M ≥ 4 show clear spatiotemporal changes. From 1933 to the late 1980s, earthquakes of M ≥ 4 were more diffused and broadly distributed in both high and low strain rate regions (accumulation phase). From the late 1980s to 2016, earthquakes were more concentrated within the high strain rate areas focused on the major fault strands (localization phase). In the same time period, the rate of M > 6.5 events also increased significantly in the high strain rate areas. The strong correlation between current strain rate and the later period of seismicity indicates that seismicity is closely related to the strain rate. The spatial patterns suggest that before the late 1980s, the strain rate field was also broadly distributed because of the stress shadows from previous large earthquakes. As the deformation field evolved out of the shadow in the late 1980s, strain has refocused on the major fault systems and we are entering a period of increased risk for large earthquakes in California.

Post-collisional magmatism in the central East African Orogen: The Maevarano Suite of north Madagascar

NASA Astrophysics Data System (ADS)

Goodenough, K. M.; Thomas, R. J.; De Waele, B.; Key, R. M.; Schofield, D. I.; Bauer, W.; Tucker, R. D.; Rafahatelo, J.-M.; Rabarimanana, M.; Ralison, A. V.; Randriamananjara, T.

2010-04-01

Late tectonic, post-collisional granite suites are a feature of many parts of the Late Neoproterozoic to Cambrian East African Orogen (EAO), where they are generally attributed to late extensional collapse of the orogen, accompanied by high heat flow and asthenospheric uprise. The Maevarano Suite comprises voluminous plutons which were emplaced in some of the tectonostratigraphic terranes of northern Madagascar, in the central part of the EAO, following collision and assembly during a major orogeny at ca. 550 Ma. The suite comprises three main magmatic phases: a minor early phase of foliated gabbros, quartz diorites, and granodiorites; a main phase of large batholiths of porphyritic granitoids and charnockites; and a late phase of small-scale plutons and sheets of monzonite, syenite, leucogranite and microgranite. The main phase intrusions tend to be massive, but with variably foliated margins. New U-Pb SHRIMP zircon data show that the whole suite was emplaced between ca. 537 and 522 Ma. Geochemically, all the rocks of the suite are enriched in the LILE, especially K, and the LREE, but are relatively depleted in Nb, Ta and the HREE. These characteristics are typical of post-collisional granitoids in the EAO and many other orogenic belts. It is proposed that the Maevarano Suite magmas were derived by melting of sub-continental lithospheric mantle that had been enriched in the LILE during earlier subduction events. The melting occurred during lithospheric delamination, which was associated with extensional collapse of the East African Orogen.

Origins and Transport of Ions during Magnetospheric Substorms

NASA Technical Reports Server (NTRS)

Ashour-Abdalla, Maha; El-Alaoui, Mostafa; Peroomian, Vahe; Raeder, Joachim; Walker, Ray J.; Frank, L. A.; Paterson, W. R.

1999-01-01

We investigate the origins and the transport of ions observed in the near-Earth plasma sheet during the growth and expansion phases of a magnetospheric substorm that occurred on November 24, 1996. Ions observed at Geotail were traced backward in time in time-dependent magnetic and electric fields to determine their origins and the acceleration mechanisms responsible for their energization. Results from this investigation indicate that, during the growth phase of the substorm, most of the ions reaching Geotail had origins in the low latitude boundary layer (LLBL) and had alread@, entered the magnetosphere when the growth phase began. Late in the growth phase and in the expansion phase a higher proportion of the ions reaching Geotail had their origin in the plasma mantle. Indeed, during the expansion phase more than 90% of the ions seen by Geotail were from the mantle. The ions were accelerated enroute to the spacecraft; however, most of the ions' energy gain was achieved by non-adiabatic acceleration while crossing the equatorial current sheet just prior to their detection by Geotail. In general, the plasma mantle from both southern and northern hemispheres supplied non-adiabatic ions to Geotail, whereas the LLBL supplied mostly adiabatic ions to the distributions measured by the spacecraft.

The Origin of the EUV Late Phase: A Case Study of the C8.8 Flare on 2010 May 5

NASA Technical Reports Server (NTRS)

Hock, R. A.; Woods, T. N.; Klimchuk, J. A.; Eparvier, F. G.; Jones, A. R.

2012-01-01

Since the launch of NASA's Solar Dynamics Observatory on 2010 February 11, the Extreme ultraviolet Variability Experiment (EVE) has observed numerous flares. One interesting feature observed by EVE is that a subset of flares exhibit an additional enhancement of the 2-3 million K emission several hours after the flares soft X-ray emission. From the Atmospheric Imaging Assembly (AIA) images, we observe that this secondary emission, dubbed the EUV late phase, occurs in the same active region as the flare but not in the same coronal loops. Here, we examine the C8.8 flare that occurred on 2010 May 5 as a case study of EUV late phase flares. In addition to presenting detailed observations from both AIA and EVE, we develop a physical model of this flare and test it using the Enthalpy Based Thermal Evolution of Loops (EBTEL) model.

How Synchronous was the Transition into the Younger Dryas across the Euro-Atlantic Region?

NASA Astrophysics Data System (ADS)

Schenk, F.; Muschitiello, F.; Heikkilä, M. P.; Väliranta, M.; Tarasov, L.; Brandefelt, J.; Johansson, A. V.; Naslund, J. O.; Wohlfarth, B.

2015-12-01

Observations of a currently weakening subpolar gyre south of Greenland has again increased scientific attention regarding the role of the Atlantic Meridional Overturning Circulation (AMOC) for the regional to global climate. The rapid climate shift of the Younger Dryas (YD, GS-1) cold reversal during the last deglaciation is attributed to an abrupt slowdown or collapse of the AMOC due to a strong meltwater pulse and/or the rapid disintegration of the Laurentide Ice sheet. Although such a dramatic event is not expected for the future, the spatiotemporal climatic response to such a slowdown is an interesting test case. Two recently well dated proxy records around the North Sea region suggest a non-synchronous early cooling/onset of the YD compared to Greenland (NGRIP). Presentation #61803 discusses the hypothesis of a local cooling as a response to increased ice berg calving and/or meltwater from Fenno-Scandinavian Ice Sheet (FIS) during the late Alleröd warm phase (GI-1a). Here we study CCSM3 model output from the quasi-transient atmosphere-ocean simulation (TraCE) where no strong contribution from FIS is considered from the late Alleröd into the YD. We evaluate to which extent the spatiotemporal temperature response to the AMOC slowdown of the simulation is synchronous over the Euro-Atlantic region and how atmospheric teleconnections reorganize during the rapid shift into the YD. In addition, we run time-slice experiments at high spatial resolution of around 100 km with the Community Earth System Model CESM1.0.5 for the late Alleröd and YD to compare spatial climatic differences for both periods taking into account the regional influence from continental ice sheets in more detail.

Proteomic Analysis of Stationary Phase in the Marine Bacterium "Candidatus Pelagibacter ubique"

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

Sowell, S. M.; Norbeck, A. D.; Lipton, M. S.

2008-05-09

The α-proteobacterium ‘Candidatus Pelagibacter ubique’ str. HTCC1062, and most other members of the SAR11 clade, lack genes for assimilatory sulfate reduction, making them dependent on organosulfur compounds that occur naturally in seawater. To investigate how these cells adapt to sulfur limitation, batch cultures were grown in defined media containing either limiting or non-limiting amounts of dimethylsulfoniopropionate (DMSP) as the sole sulfur source. Protein and mRNA expression were measured during exponential growth, immediately prior to stationary phase, and in late stationary phase. Two distinct responses were observed: one as DMSP became exhausted, and another as cells acclimated to a sulfur-limited environment.more » The first response was characterized by increased transcription and translation of all Ca. P. ubique genes downstream of previously confirmed S-adenosyl methionine (SAM) riboswitches: bhmT, mmuM, and metY. Proteins encoded by these genes were up to 33 times more abundant as DMSP became limiting. Their predicted function is to shunt all available sulfur to methionine. The secondary response, observed during sulfur-depleted stationary phase, was a 6-10 fold increase in transcription of the heme c shuttle ccmC and two small genes of unknown function (SAR11_1163 and SAR11_1164). This bacterium's strategy for coping with sulfur stress appears to be intracellular redistribution to support methionine biosynthesis, rather than increasing organosulfur import. Many of the genes and SAM riboswitches involved in this response are located in a hypervariable genome region (HVR). One of these HVR genes, ordL, is located downstream of a conserved motif that evidence suggests is a novel riboswitch.« less

Stratospheric Response to Intraseasonal Changes in Incoming Solar Radiation

NASA Astrophysics Data System (ADS)

Garfinkel, Chaim; silverman, vered; harnik, nili; Erlich, caryn

2016-04-01

Superposed epoch analysis of meteorological reanalysis data is used to demonstrate a significant connection between intraseasonal solar variability and temperatures in the stratosphere. Decreasing solar flux leads to a cooling of the tropical upper stratosphere above 7hPa, while increasing solar flux leads to a warming of the tropical upper stratosphere above 7hPa, after a lag of approximately six to ten days. Late winter (February-March) Arctic stratospheric temperatures also change in response to changing incoming solar flux in a manner consistent with that seen on the 11 year timescale: ten to thirty days after the start of decreasing solar flux, the polar cap warms during the easterly phase of the Quasi-Biennal Oscillation. In contrast, cooling is present after decreasing solar flux during the westerly phase of the Quasi-Biennal Oscillation (though it is less robust than the warming during the easterly phase). The estimated composite mean changes in Northern Hemisphere upper stratospheric (~ 5hPa) polar temperatures exceed 8K, and are potentially a source of intraseasonal predictability for the surface. These changes in polar temperature are consistent with the changes in wave driving entering the stratosphere. Garfinkel, C.I., V. Silverman, N. Harnik, C. Erlich, Y. Riz (2015), Stratospheric Response to Intraseasonal Changes in Incoming Solar Radiation, J. Geophys. Res. Atmos., 120, 7648-7660. doi: 10.1002/2015JD023244.

G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

PubMed Central

Bajrami, Besnik; Zhu, Haiyan; Zhang, Yu C.

2016-01-01

Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID:27551153

Frequency modulation reveals the phasing of orbital eccentricity during Cretaceous Oceanic Anoxic Event II and the Eocene hyperthermals

NASA Astrophysics Data System (ADS)

Laurin, Jiří; Meyers, Stephen R.; Galeotti, Simone; Lanci, Luca

2016-05-01

Major advances in our understanding of paleoclimate change derive from a precise reconstruction of the periods, amplitudes and phases of the 'Milankovitch cycles' of precession, obliquity and eccentricity. While numerous quantitative approaches exist for the identification of these astronomical cycles in stratigraphic data, limitations in radioisotopic dating, and instability of the theoretical astronomical solutions beyond ∼50 Myr ago, can challenge identification of the phase relationships needed to constrain climate response and anchor floating astrochronologies. Here we demonstrate that interference patterns accompanying frequency modulation (FM) of short eccentricity provide a robust basis for identifying the phase of long eccentricity forcing in stratigraphic data. One- and two-dimensional models of sedimentary distortion of the astronomical signal are used to evaluate the veracity of the FM method, and indicate that pristine eccentricity FM can be readily distinguished in paleo-records. Apart from paleoclimatic implications, the FM approach provides a quantitative technique for testing and calibrating theoretical astronomical solutions, and for refining chronologies for the deep past. We present two case studies that use the FM approach to evaluate major carbon-cycle perturbations of the Eocene and Late Cretaceous. Interference patterns in the short-eccentricity band reveal that Eocene hyperthermals ETM2 ('Elmo'), H2, I1 and ETM3 (X; ∼52-54 Myr ago) were associated with maxima in the 405-kyr cycle of orbital eccentricity. The same eccentricity configuration favored regional anoxic episodes in the Mediterranean during the Middle and Late Cenomanian (∼94.5-97 Myr ago). The initial phase of the global Oceanic Anoxic Event II (OAE II; ∼93.9-94.5 Myr ago) coincides with maximum and falling 405-kyr eccentricity, and the recovery phase occurs during minimum and rising 405-kyr eccentricity. On a Myr scale, the event overlaps with a node in eccentricity amplitudes. Both studies underscore the importance of seasonality in pacing major climatic perturbations during greenhouse times.

Transgenic tomato expressing interleukin-12 has a therapeutic effect in a murine model of progressive pulmonary tuberculosis

PubMed Central

Elías-López, A L; Marquina, B; Gutiérrez-Ortega, A; Aguilar, D; Gomez-Lim, M; Hernández-Pando, R

2008-01-01

Host control of mycobacterial infection, in both human and mouse models, has been shown to be associated with the production of interferon (IFN)-γ by CD4+ T cells. Interleukin (IL)-12 is known to be a crucial cytokine in the differentiation of IFN-γ-producing T helper 1 (Th1) cells. To determine whether continuous administration of IL-12 expressed in transgenic tomato (TT–IL-12) has therapeutic efficacy in a murine model of pulmonary tuberculosis, BALB/c mice were infected with either Mycobacterium tuberculosis H37Rv strain or a multi-drug-resistant clinical isolate (MDR) and treated with a daily oral dose of TT-IL12 crude fruit extracts. For the early H37Rv infection, TT–IL-12 administration was started 1 day before infection and continued for 60 days. In the H37Rv or MDR late infection, treatment was started 60 days after infection and continued for another 60 days. In both phases of infection, TT–IL-12 administration resulted in a reduction of bacterial loads and tissue damage compared with wild-type tomato (non-TT). The Th1 response was increased and the Th2 response was reduced. In the late infection, a long-term treatment with TT–IL-12 was necessary. We demonstrate that TT–IL-12 increases resistance to infection and reduces lung tissue damage during early and late drug-sensitive and drug-resistant mycobacterial infection. PMID:18727633

Bidirectional plasticity of pontine pneumotaxic postinspiratory drive: implication for a pontomedullary respiratory central pattern generator.

PubMed

Poon, Chi-Sang; Song, Gang

2014-01-01

The "pneumotaxic center" in the rostral dorsolateral pons as delineated by Lumsden nine decades ago is known to play an important role in promoting the inspiratory off-switch (IOS) for inspiratory-expiratory phase transition as a fail-safe mechanism for preventing apneusis in the absence of vagal input. Traditionally, the pontine pneumotaxic mechanism has been thought to contribute a tonic descending input that lowers the IOS threshold in medullary respiratory central pattern generator (rCPG) circuits, but otherwise does not constitute part of the rCPG. Recent evidence indicates that descending input from the Kölliker-Fuse nucleus (KFN) within the pneumotaxic center is essential for gating the postinspiratory phase of the three-phase respiratory rhythm to control the IOS in vagotomized animals. A critical question arising is whether such a descending pneumotaxic input from KFN that drives postinspiratory activity is tonic (null hypothesis) or rhythmic with postinspiratory phase modulation (alternative hypothesis). Here, we show that multifarious evidence reported in the literature collectively indicates that the descending pneumotaxic input may exhibit NMDA receptor-dependent short-term plasticity in the form of a biphasic neural differentiator that bidirectionally and phase-selectively modulates postinspiratory phase duration in response to vagal and peripheral chemoreceptor inputs independent of the responses in inspiratory and late-expiratory activities. The phase-selectivity property of the descending pneumotaxic input implicates a population of pontine early-expiratory (postinspiratory/expiratory-decrementing) neurons as the most likely neural correlate of the pneumotaxic mechanism that drives post-I activity, suggesting that the pontine pneumotaxic mechanism may be an integral part of a pontomedullary rCPG that underlies the three-phase respiratory rhythm. © 2014 Elsevier B.V. All rights reserved.

Dentition phase and chronological age in relation to gingival crevicular fluid alkaline phosphatase activity in growing subjects.

PubMed

Perinetti, Giuseppe; Baccetti, Tiziano; Di Leonardo, Bruno; Di Lenarda, Roberto; Contardo, Luca

2011-11-01

Identification of skeletal maturation phases is of primary importance in terms of individual responsiveness to nearly all dentofacial orthopaedic treatments. In this regard, dentition phase and chronological age are still widely used to define the timing of and responsiveness to orthodontic treatments. Recently, gingival crevicular fluid (GCF) alkaline phosphatase (ALP) activity has been shown to be a reliable biomarker of skeletal maturation in growing subjects. Here, for the first time, circumpubertal dentition phases and chronological age were evaluated for correlations with GCF ALP activity, as a biomarker of skeletal maturation. Eighty-five healthy growing subjects (51 females, 34 males; mean age, 11.7±2.3 years) were enrolled into this double-blind, prospective, cross-sectional-design study. Samples of GCF were collected from each subject at the mesial and distal sites of both of the central incisors, at the maxillary and mandibular arches. Their dentition phases were recorded as intermediate mixed, late mixed, or permanent. GCF ALP enzymatic activity was determined spectrophotometrically. The dentition phases showed median GCF ALP activities from 42.0 to 67.5 mU/sample. Although these were slightly greater for the permanent dentition, no significant differences were seen. Also, the chronological age did not correlate significantly with GCF ALP activity, and no significant differences were seen between maxillary and mandibular sites in any of the comparisons. Assessment for treatment timing of dentofacial disharmonies in individual patients that require monitoring of their skeletal maturation phases should not rely on their circumpubertal dentition phase and chronological age. Copyright © 2011 Società Italiana di Ortodonzia SIDO. Published by Elsevier Srl. All rights reserved.

Climate-driven sediment aggradation and incision phases since the Late Pleistocene in the NW Himalaya, India

NASA Astrophysics Data System (ADS)

Dey, Saptarshi; Thiede, Rasmus C.; Schildgen, Taylor F.; Wittmann, Hella; Bookhagen, Bodo; Scherler, Dirk; Jain, Vikrant; Strecker, Manfred R.

2016-04-01

Deciphering the response of sediment routing systems to climatic forcing is fundamental for understanding the impacts of climate change on landscape evolution and depositional systems. In the Sub-Himalaya, late Pleistocene to Holocene alluvial fills and fluvial terraces record periodic fluctuations of sediment supply and transport capacity on timescale of 103 to 105 years, most likely related to past climatic fluctuations. To evaluate the climatic control on sediment supply and transport capacity, we analyze remnant alluvial fans and terraces in the Kangra Basin of the northwestern Sub-Himalaya. Based on field observations and OSL and CRN-dating, we recognized two sedimentary cycles with major sediment aggradation and subsequent re-incision phases. The large one developed over the entire last glacial period with ˜200 m high alluvial fan (AF1) and the second one during the latest Pleistocene/Holocene with ˜50 m alluvial fan (AF2) and its re-incision . Surface-exposure dating of six terrace levels with in-situ cosmogenic nuclides (10Be) indicates the onset of channel abandonment and ensuing incision phases. Two terrace surfaces from the highest level (T1) sculpted into the oldest-preserved AF1 dates back to 48.9 ± 4.1 ka and 42.1 ± 2.7 ka (2σ error). T2 surfaces sculpted into the remnants of AF1 have exposure ages of 16.8 ± 2 ka and 14.1 ± 0.9 ka, while terraces sculpted into the late Pleistocene- Holocene fan (AF2) provide ages of 8.4± 0.8 ka, 6.6± 0.7 ka, 4.9± 0.4 ka and 3.1± 0.3 ka. Together with previously-published ages on the timing of aggradation, we find a correlation between variations in sediment transport with oxygen-isotope records from regions affected by Indian Summer Monsoon. During stronger monsoon phases and post-LGM glacial retreat manifested by increased sediment delivery (moraines and hillslope-derived) to the trunk streams, causing aggradation in the basin; whereas, weakened monsoon phases characterized by reduced sediment-delivery from the hillslope or moraines resulted into incision of the transiently-stored sediments. Sediment cycles in the Kangra Basin are largely synchronous with those documented from other NW Himalayan valleys.

Late Neoproterozoic metamorphic assemblages along the Pan-African Hamisana Shear Zone, southeastern Egypt: Metamorphism, geochemistry and petrogenesis

NASA Astrophysics Data System (ADS)

Ali-Bik, Mohamed W.; Sadek, Mohamed F.; Ghabrial, Doris Sadek

2014-11-01

A variety of Late Neoproterozoic gneisses and amphibolites are distributed along the N-S trending Hamisana Shear Zone (HSZ), in southeastern Egypt. The HSZ originated after the accretion of the Arabian-Nubian Shield (ANS) and covers an area of about 1500 km2 in southeastern Egypt and northeastern Sudan. The architecture of the northern part of the HSZ is best explained as a tectono-stratigraphic column, in which allochthonous ophiolitic mélange was thrusted onto metamorphosed island-arc assemblages (gneisses and amphibolites). The latter rock units were generally subjected to two successive phases of amphibolite facies metamorphism, followed by a thermal phase and retrograde overprint. The early penetrative, low- to medium-pressure metamorphism (M1) was synchronous with D1-gneissosity and N-S trending lineation, demarcating the high strain HSZ. The mineral assemblages formed during the M1 phase include quartz + andesine + hornblende (I) + biotite (I) in hornblende-biotite gneiss, quartz + andesine + pargasitic hornblende (I) + ferroan pargasitic hornblende (I) + edenitic hornblende (I) in hornblende-schist, quartz + plagioclase + biotite + muscovite in psammopelitic gneiss, and diopside + tremolite + calcite + sphene ± garnet in calc-silicates, being characteristic for amphibolite facies with metamorphic conditions of 600 ± 50 °C and 5-6.5 kbar. The second metamorphic phase (M2) is related to the crystallization of biotite and/or hornblende in S2 foliation demarcating the NE-SW trending dextral shear deformation (D2). The calculated temperature for this M2 phase is about 592 °C. Subsequent thermal events are documented by growth of spinel and scapolite in calc-silicate rocks and of cordierite in psammopelitic gneiss in response to uplift, decomposition and heat provided by the nearby late-formed igneous intrusions. Finally, the rocks reached a temperature of about 530 °C during the cooling retrogressive stage. Based on geological, petrological and geochemical investigations, the island arc assemblages are grouped into: (a) meta-igneous rocks (hornblende-biotite gneiss, biotite gneiss and amphibolites) and (b) metasedimentary rocks (psammopelitic gneiss, hornblende-schist and calc-silicates). Geochemical inspection revealed the non-consanguineous nature of these rock units. They represent subduction-related, theoleiitic and calc-alkaline magmatic rocks and their concomitant sedimentary derivations as well as minor continental shelf calcareous sediments. In terms of maturity, the geochemical signatures of these subduction-related rocks point to an immature volcanic arc origin.

Chemistry, Dynamics, and Radiation of Ozone Loss: Airborne Measurements of OH, HO2, N02, Cl0, BrO, IO, ClON02, BrON02, CIOOCl, and H2O

NASA Technical Reports Server (NTRS)

Anderson, James G.

2005-01-01

This research addresses, through a combination of in situ and remote aircraft-borne Which mechanisms are responsible for the continuing erosion of ozone over midlatitudes of the Northern Hemisphere? Will the rapid loss of ozone over the Arctic in late winter continue to worsen over the next two decades? Are these large losses dynamically coupled to midlatitudes? Which mechanisms dictate the rate of exchange of material between the troposphere and stratosphere? How will these processes change in response to changes in climate? Will regional scale pollution episodes, that are emerging as predictable seasonal events, significantly affect the middle-to-upper troposphere chemical composition. If so, how will these changes alter the chemical composition of the middle world? What changes are predicted for the overworld? Why has the arctic stratosphere become colder in the late winter phase in recent years? Have increases in tropical upper troposphere temperatures increased the temperature gradient such as to change the trajectories of vertically propagating waves, thus reducing the effectiveness of the meridional circulation for transport of heat, momentum and ozone from the tropics to high latitudes?

Short-term cropland responses to temperature extreme events during late winter

NASA Astrophysics Data System (ADS)

De Simon, G.; Alberti, G.; Delle Vedove, G.; Peressotti, A.; Zaldei, A.; Miglietta, F.

2013-04-01

In recent years, several studies have focused on terrestrial ecosystem response to extreme events. Most of this research has been conducted in natural ecosystems, but few have considered agro-ecosystems. In this study, we investigated the impact of a manipulated warmer or cooler late winter-early spring on the carbon budget and final harvest of a soybean crop (Glycine max (L.) Merr.). Soil temperature was altered by manipulating soil albedo by covering the soil surface with a layer of inert silica gravel. We tested three treatments: cooling (Co), warming (W), mix (M) and control (C). An automated system continuously measured soil heterotrophic respiration (Rh), soil temperature profiles, and soil water content across the entire year in each plot. Phenological phases were periodically assessed and final harvest was measured in each plot. Results showed that treatments had only a transient effect on daily Rh rates which did not result in a total annual carbon budget significantly different from control, even though cooling showed a significant reduction in final harvest. We also observed anticipation in seed germination in both W and M treatments and a delay in germination for Co. Moreover, plant density and growth increased in W and M and decreased in Co.

Oldest human occupation of Wallacea at Laili Cave, Timor-Leste, shows broad-spectrum foraging responses to late Pleistocene environments

NASA Astrophysics Data System (ADS)

Hawkins, Stuart; O'Connor, Sue; Maloney, Tim Ryan; Litster, Mirani; Kealy, Shimona; Fenner, Jack N.; Aplin, Ken; Boulanger, Clara; Brockwell, Sally; Willan, Richard; Piotto, Elena; Louys, Julien

2017-09-01

The Wallacea Archipelago provides an extraordinary laboratory for the study of human colonisation and adaptation, yet few detailed archaeological studies have been conducted in the region that span the earliest phase of human settlement. Laili Cave, in northern Timor-Leste, preserves the oldest human occupation in this insular region with a cultural sequence spanning 11,200 to 44,600 cal BP. Small-bodied vertebrates and invertebrates were recovered to the lowest excavated levels, associated with highly concentrated stone artefacts. We report on human behavioural adaptations within the context of Pleistocene environments and changing landscapes using zooarchaeological, stone artefact, bathymetric, and experimental isotopic analyses. Results indicate that Pleistocene humans used the abundant local chert liberally and engaged in mobile broad-spectrum exploitation of invertebrates and fishes from marine, estuarine, and freshwater environments within close proximity of Laili Cave. The faunal assemblage indicates heterogeneous but relatively stable environments during the late Pleistocene. Variability in subsistence strategies over time appears to be a response to changing landscapes and concomitant local resources. This record contrasts with marine specialisations evident from other sites in Timor-Leste and within the broader Wallacean region.

Late Quaternary landscape evolution in the Great Karoo, South Africa: Processes and drivers.

NASA Astrophysics Data System (ADS)

Oldknow, Chris; Hooke, Janet; Lang, Andreas

2016-04-01

The Great Karoo spans the north-central part of South Africa at a major climatic boundary. The characteristics, sequences, spatial patterns and drivers of river response to Late Quaternary climate changes in this region remain unclear due to the fragmentary alluvial/colluvial stratigraphic record and the lack of dated palaeoclimatic archives. Dendritic gully networks incised into deep deposits (up to 6 m) of colluvium and alluvium in the upper Sundays River catchment expose a legacy of "cut and fill" features. In 1st order tributaries, these are predominantly discontinuous palaeochannels and flood-outs with localised palaeosols, whereas in 2nd & 3rd order tributaries there are: 1) incised palaeo-geomorphic surfaces, 2) semi-continuous inset terrace sequences, 3) buried palaeo-gully topography. Using a combination of field mapping, logging of sediment outcrops, soil micromorphological and grain size analysis, mineral magnetic measurements and radiometric dating (OSL & 14C), we derive a stratigraphic evolution model which demonstrates a) the number of phases of incision, aggradation and pedogenesis, b) the spatial and temporal extent of each phase and c) the drivers of alluviation and associated feedbacks. Our reconstruction of regional valley alluviation indicates four distinct terrace units of contrasting depositional age. The base of the succession reflects slow aggradation under periglacial conditions associated with the Last Glacial Maximum. Subsequent channel entrenchment, causing terrace abandonment (T1) occurred in the deglacial period when vegetation and rainfall were in anti-phase. Re-instatement of connectivity with deep upland colluvial stores resulted in the injection of a pulse of sediment to valley floors, triggering compartmentalised backfilling (aggradation of T2) which propagated upstream as far as the second order drainage lines. This backfilling restructured the local hydrology, which, in concert with enhanced summer-rainfall, contributed to a major increase in the palaeo-water table, enhanced vegetation productivity and led to the formation of extensive calcified root-mats. Soil micromorphological evidence from this calcrete unit and burial of T2 by up to 1.5 m of alluvium (T3) indicates subsequent aridification, but depth of channel entrenchment was retarded by the blanketing effect of the underlying calcrete. The final terrace (T4) is much younger (Late Holocene), reflecting slow aggradation in a wetland setting. Wider segments of valley preserve a 'cut and fill' phase intermediate in age between regional T3 and T4 which appears to be a function of varying alluvial preservation potential. The research demonstrates that phases of alluviation and pedogenesis in these valleys reflect a complex interplay between Late Quaternary climate change and autogenic-feedbacks relating to abrupt changes in sediment supply and connectivity.

Food-anticipatory activity and liver per1-luc activity in diabetic transgenic rats

NASA Technical Reports Server (NTRS)

Davidson, Alec J.; Stokkan, Karl-Arne; Yamazaki, Shin; Menaker, Michael

2002-01-01

The mammalian Per1 gene is an important component of the core cellular clock mechanism responsible for circadian rhythms. The rodent liver and other tissues rhythmically express Per1 in vitro but typically damp out within a few cycles. In the liver, the peak of this rhythm occurs in the late subjective night in an ad lib-fed rat, but will show a large phase advance in response to restricted availability of food during the day. The relationship between this shift in the liver clock and food-anticipatory activity (FAA), the circadian behavior entrained by daily feeding, is currently unknown. Insulin is released during feeding in mammals and could serve as an entraining signal to the liver. To test the role of insulin in the shift in liver Per1 expression and the generation of FAA, per-luciferase transgenic rats were made diabetic with a single injection of streptozotocine. Following 1 week of restricted feeding and locomotor activity monitoring, liver was collected for per-luc recording. In two separate experiments, FAA emerged and liver Per1 phase-shifted in response to daytime 8-h food restriction. The results rule out insulin as a necessary component of this system.

Antinociceptive activities of 70% methanol extract of evodiae fructus (fruit of Evodia rutaecarpa var. bodinieri) and its alkaloidal components.

PubMed

Matsuda, H; Wu, J X; Tanaka, T; Iinuma, M; Kubo, M

1997-03-01

The effects of 70% methanol extract (EA-ext) from Evodiae Fructus (EA) consisting of dried fruits of Evodia rutaecarpa var. bodinieri (Rutaceae) on nociceptive responses were investigated. Oral administration of 50 or 200 mg/kg EA-ext had the same antinociceptive effect on writhing responses as induced by acetic acid. Its major alkaloidal constituents, evodiamine and rutaecarpine also had the antinociceptive effect. EA-ext significantly decreased the frequency of licking behavior within a unit of time at the late phase without affecting that of the early phase in the formalin test. EA-ext also increased nociceptive threshold of the inflamed paw without increasing that in the non-inflamed paw in the Randall-Selitto test. Although EA-ext inhibited the rise of vascular permeability induced by acetic acid and the increase of paw edema induced by carrageenin, it was ineffective on nociceptive response in the hot plate test and on locomotor activity. These results suggest that EA possesses antinociceptive effects and its mode of action may be mediated by anti-inflammatory action, and that the antinociceptive constituents are only partially attributable to alkaloidal components mentioned above.

Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

PubMed

Soules, M R; Clifton, D K; Cohen, N L; Bremner, W J; Steiner, R A

1989-10-01

Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P secretion in LPD is decreased P pulse amplitude; 3) the finding of similar serum FSH levels in the two groups in both the early and late follicular phases did not support compromised folliculogenesis as an etiological factor for LPD.

Thermal Emissions Spanning the Prompt and the Afterglow Phases of the Ultra-long GRB 130925A

NASA Astrophysics Data System (ADS)

Basak, Rupal; Rao, A. R.

2015-07-01

GRB 130925A is an ultra-long gamma-ray burst (GRB), and it shows clear evidence for thermal emission in the soft X-ray data of the Swift/X-ray Telescope (XRT; ∼0.5 keV), lasting until the X-ray afterglow phase. Due to the long duration of the GRB, the burst could be studied in hard X-rays with high-resolution focusing detectors (NuSTAR). The blackbody temperature, as measured by the Swift/XRT, shows a decreasing trend until the late phase (Piro et al.) whereas the high-energy data reveal a significant blackbody component during the late epochs at an order of magnitude higher temperature (∼5 keV) compared to contemporaneous low energy data (Bellm et al.). We resolve this apparent contradiction by demonstrating that a model with two black bodies and a power law (2BBPL) is consistent with the data right from the late prompt emission to the afterglow phase. Both blackbodies show a similar cooling behavior up to late times. We invoke a structured jet, having a fast spine and a slower sheath layer, to identify the location of these blackbodies. Independent of the physical interpretation, we propose that the 2BBPL model is a generic feature of the prompt emission of all long GRBs, and the thermal emission found in the afterglow phase of different GRBs reflects the lingering thermal component of the prompt emission with different timescales. We strengthen this proposal by pointing out a close similarity between the spectral evolutions of this GRB and GRB 090618, a source with significant wide band data during the early afterglow phase.

Motor evoked responses from the thigh muscles to the stimulation of the upper limb nerves in patients with late poliomyelitis.

PubMed

Ertekin, Cumhur; On, Arzu Yagiz; Kirazli, Yeşim; Kurt, Tülay; Gürgör, Nevin

2002-04-01

To demonstrate a clear-cut M response recorded from the severely affected thigh muscles to the stimulation of the upper limb nerves in a serial of patients with late poliomyelitis. Fifteen patients with late poliomyelitis, 7 patients with spinal cord disorders and 11 control subjects were included. Evoked muscle responses were investigated in quadriceps femoris and/or thigh adductor muscles to the stimulation of the brachial plexus, median and ulnar nerves. Evoked muscle responses were obtained from the thigh muscles in all 12 late polio patients with proximal lower extremity involvement. The response could not be recorded from the thigh muscles neither in the 3 polio patients with upper extremity involvement nor in the healthy control subjects and in patients with other spinal cord disorders of anterior horn cell. It is proposed that the electrical stimulation of the arm nerves produce interlimb descending muscle responses in the severely affected atrophic thigh muscles of the patients with late polio. This finding suggests that there might be a focal and/or specific loss of inhibitory interneurons between injured and normal motor neurons and increased facilitatory synaptic action at the end of long propriospinal descending fibers in the case of late poliomyelitis.

Assertive and Responsive Conversational Skills of Italian-Speaking Late Talkers

ERIC Educational Resources Information Center

Bonifacio, Serena; Girolametto, Luigi; Bulligan, Manuela; Callegari, Monica; Vignola, Sandra; Zocconi, Elisabetta

2007-01-01

Background: Previous research on the pragmatic abilities of late talkers at 24 months of age indicates that they have difficulties initiating conversational interactions, but possess intact responsiveness skills. This study uses a parent-administered questionnaire for evaluating the conversational skills of late talkers and suggesting pragmatic…

Regional hardening of Upper Cretaceous Chalk in eastern England, UK: trace element and stable isotope patterns in the Upper Cenomanian and Turonian Chalk and their significance

NASA Astrophysics Data System (ADS)

Jeans, Christopher V.; Long, Dee; Hu, Xiu-Fang; Mortimore, Rory N.

2014-12-01

The regional hardening of the Late Cenomanian to Early Turonian Chalk of the Northern Province of eastern England has been investigated by examining the pattern of trace elements and stable carbon and oxygen isotopes in the bulk calcite of two extensive and stratigraphically adjacent units each 4 to 5 m thick of hard chalk in Lincolnshire and Yorkshire. These units are separated by a sequence, 0.3-1.3 m thick, of variegated marls and clayey marls. Modelling of the geochemistry of the hard chalk by comparison with the Standard Louth Chalk, combined with associated petrographic and geological evidence, indicates that (1) the hardening is due to the precipitation of a calcite cement, and (2) the regional and stratigraphical patterns of geochemical variation in the cement are largely independent of each other and have been maintained by the impermeable nature of the thin sequence of the clay-rich marls that separate them. Two phases of calcite cementation are recognised. The first phase was microbially influenced and did not lithify the chalk. It took place predominantly in oxic and suboxic conditions under considerable overpressure in which the Chalk pore fluids circulated within the units, driven by variations in compaction, temperature, pore fluid pressure and local tectonics. There is evidence in central and southern Lincolnshire of the loss of Sr and Mgenriched pore fluids to the south during an early part of this phase. The second phase of calcite precipitation was associated with the loss of overpressure in probably Late Cretaceous and in Cenozoic times as the result of fault movement in the basement penetrating the overlying Chalk and damaging the seal between the two chalk units. This greatly enhanced grain pressures, resulting in grain welding and pressure dissolution, causing lithification with the development of stylolites, marl seams, and brittle fractures. Associated with this loss of overpressure was the penetration of the chalk units by allochthonous fluids, rich in sulphate and hydrocarbons, derived probably from the North Sea Basin. Microbial sulphate-reduction under anoxic conditions within these allochthonous fluids has been responsible for dissolving the fine-grained iron and manganese oxides within the chalk, locally enriching the Fe and Mn content of the calcite cement. The possibility is discussed that the pattern of cementation preserved in these regionally hard chalks of Late Cenomanian and Early Turonian age may be different from that preserved in the younger (late Turonian to Campanian) more basinal chalks of eastern England.

Bulk viscous quintessential inflation

NASA Astrophysics Data System (ADS)

Haro, Jaume; Pan, Supriya

In a spatially-flat Friedmann-Lemaître-Robertson-Walker universe, the incorporation of bulk viscous process in general relativity leads to an appearance of a nonsingular background of the universe that both at early and late times depicts an accelerated universe. These early and late scenarios of the universe can be analytically calculated and mimicked, in the context of general relativity, by a single scalar field whose potential could also be obtained analytically where the early inflationary phase is described by a one-dimensional Higgs potential and the current acceleration is realized by an exponential potential. We show that the early inflationary universe leads to a power spectrum of the cosmological perturbations which match with current observational data, and after leaving the inflationary phase, the universe suffers a phase transition needed to explain the reheating of the universe via gravitational particle production. Furthermore, we find that at late times, the universe enters into the de Sitter phase that can explain the current cosmic acceleration. Finally, we also find that such bulk viscous-dominated universe attains the thermodynamical equilibrium, but in an asymptotic manner.

Role of Imaging in the Staging and Response Assessment of Lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group

PubMed Central

Barrington, Sally F.; Mikhaeel, N. George; Kostakoglu, Lale; Meignan, Michel; Hutchings, Martin; Müeller, Stefan P.; Schwartz, Lawrence H.; Zucca, Emanuele; Fisher, Richard I.; Trotman, Judith; Hoekstra, Otto S.; Hicks, Rodney J.; O'Doherty, Michael J.; Hustinx, Roland; Biggi, Alberto; Cheson, Bruce D.

2014-01-01

Purpose Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET) –computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely. Methods An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma. Results A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods. Conclusion This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials. PMID:25113771

Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality.

PubMed

Osuchowski, Marcin F; Welch, Kathy; Siddiqui, Javed; Remick, Daniel G

2006-08-01

Mortality in sepsis remains unacceptably high and attempts to modulate the inflammatory response failed to improve survival. Previous reports postulated that the sepsis-triggered immunological cascade is multimodal: initial systemic inflammatory response syndrome (SIRS; excessive pro-, but no/low anti-inflammatory plasma mediators), intermediate homeostasis with a mixed anti-inflammatory response syndrome (MARS; both pro- and anti-inflammatory mediators) and final compensatory anti-inflammatory response syndrome (CARS; excessive anti-, but no/low proinflammatory mediators). To verify this, we examined the evolution of the inflammatory response during the early phase of murine sepsis by repetitive blood sampling of septic animals. Increased plasma concentrations of proinflammatory (IL-6, TNF, IL-1beta, KC, MIP-2, MCP-1, and eotaxin) and anti-inflammatory (TNF soluble receptors, IL-10, IL-1 receptor antagonist) cytokines were observed in early deaths (days 1-5). These elevations occurred simultaneously for both the pro- and anti-inflammatory mediators. Plasma levels of IL-6 (26 ng/ml), TNF-alpha (12 ng/ml), KC (33 ng/ml), MIP-2 (14 ng/ml), IL-1 receptor antagonist (65 ng/ml), TNF soluble receptor I (3 ng/ml), and TNF soluble receptor II (14 ng/ml) accurately predicted mortality within 24 h. In contrast, these parameters were not elevated in either the late-deaths (day 6-28) or survivors. Surprisingly, either pro- or anti-inflammatory cytokines were also reliable in predicting mortality up to 48 h before outcome. These data demonstrate that the initial inflammatory response directly correlates to early but not late sepsis mortality. This multifaceted response questions the use of a simple proinflammatory cytokine measurement for classifying the inflammatory status during sepsis.

Geomorphic response to sea level and climate changes during Late Quaternary in a humid tropical coastline: Terrain evolution model from Southwest India.

PubMed

K, Maya; S, Vishnu Mohan; Limaye, Ruta B; Padmalal, Damodaran; Kumaran, Navnith K P

2017-01-01

The coastal lands of southern Kerala, SW India in the vicinity of Achankovil and Thenmala Shear Zones reveal a unique set of geomorphic features like beach ridges, runnels, chain of wetlands, lakes, estuaries, etc. The chain of wetlands and water bodies that are seen in the eastern periphery of the coastal lands indicates the remnants of the upper drainage channels of the previously existed coastal plain rivers of Late Pleistocene age that are later broadened due to coastal erosion under the transgressive phase. The terrain evolutionary model developed from the results of the study shows that the Late Pleistocene transgressive events might have carved out a major portion of the land areas drained by the coastal plain rivers and as a result the coastal cliff has been retreated several kilometers landwards. The NNE-SSW trending beach ridges located close to the inland wetlands indicate the extent of shoreline shift towards eastwards during Late Pleistocene period. The present beach parallel ridges in the younger coastal plain indicate the limit of the Mid Holocene shoreline as the transgression was not so severe compared to Late Pleistocene event. The zone of convergence of the two sets of beach ridges coincides with the areas of economically viable heavy mineral placers that resulted from the size and density based sorting under the repeated transgressive events to which the coast had subjected to. The chain of wetlands in the eastern side of the study area has been evolved from a mega lagoon existed during Late Pleistocene. The Pallikkal River that links discrete eastern wetland bodies has been evolved into its present form during Early Holocene.

Late-onset anaphylaxis due to poly (γ-glutamic acid) in the soup of commercial cold Chinese noodles in a patient with allergy to fermented soybeans (natto).

PubMed

Inomata, Naoko; Chin, Keishi; Nagashima, Mayumi; Ikezawa, Zenro

2011-09-01

Fermented soybeans (natto) have been reported to induce IgE-mediated, late-onset anaphylaxis without early-phase responses. However, the relevant allergens of natto allergy have never been identified. A 38-year-old man developed an anaphylactic reaction accompanied by flashing, generalized urticaria, conjunctival redness, and dyspnea 3 hours after ingestion of commercial cold Chinese noodles. He had avoided natto for the past year due to developing several anaphylactic reactions half a day after natto ingestion. The results of skin prick tests (SPTs) were strongly positive for natto and the soup of cold Chinese noodles. Furthermore, SPTs showed positive for poly (γ-glutamic acid) (PGA), which is a major constituent of natto mucilage, alone among all the ingredients of the cold Chinese noodle soup. Therefore, he was diagnosed with late-onset anaphylaxis to PGA contained in natto and the cold Chinese noodle soup. These results indicated that in the present case, the relevant allergen of late-onset anaphylaxis may have been PGA in all episodes and that the patient had been sensitized by PGA through natto ingestion. PGA is produced by Bacillus subtilis during fermentation and is a high-molecular, biodegradable polymer. The late onset is therefore, hypothesized to be due to a delayed absorption of PGA, as PGA biodegrades to peptides sufficiently small to be absorbed in the bowel. PGA has recently been applied to a wide range of fields such as foods, cosmetics, and medicine. Therefore, patients with late-onset anaphylaxis to PGA of natto should avoid not only natto but also other materials containing PGA.

Geomorphic response to sea level and climate changes during Late Quaternary in a humid tropical coastline: Terrain evolution model from Southwest India

PubMed Central

K., Maya; S., Vishnu Mohan; Limaye, Ruta B.; Padmalal, Damodaran

2017-01-01

The coastal lands of southern Kerala, SW India in the vicinity of Achankovil and Thenmala Shear Zones reveal a unique set of geomorphic features like beach ridges, runnels, chain of wetlands, lakes, estuaries, etc. The chain of wetlands and water bodies that are seen in the eastern periphery of the coastal lands indicates the remnants of the upper drainage channels of the previously existed coastal plain rivers of Late Pleistocene age that are later broadened due to coastal erosion under the transgressive phase. The terrain evolutionary model developed from the results of the study shows that the Late Pleistocene transgressive events might have carved out a major portion of the land areas drained by the coastal plain rivers and as a result the coastal cliff has been retreated several kilometers landwards. The NNE—SSW trending beach ridges located close to the inland wetlands indicate the extent of shoreline shift towards eastwards during Late Pleistocene period. The present beach parallel ridges in the younger coastal plain indicate the limit of the Mid Holocene shoreline as the transgression was not so severe compared to Late Pleistocene event. The zone of convergence of the two sets of beach ridges coincides with the areas of economically viable heavy mineral placers that resulted from the size and density based sorting under the repeated transgressive events to which the coast had subjected to. The chain of wetlands in the eastern side of the study area has been evolved from a mega lagoon existed during Late Pleistocene. The Pallikkal River that links discrete eastern wetland bodies has been evolved into its present form during Early Holocene. PMID:28467465

Quantitative Interaction Effects of Carbon Dioxide, Sodium Chloride, and Sodium Nitrite on Neurotoxin Gene Expression in Nonproteolytic Clostridium botulinum Type B

PubMed Central

Lövenklev, Maria; Artin, Ingrid; Hagberg, Oskar; Borch, Elisabeth; Holst, Elisabet; Rådström, Peter

2004-01-01

The effects of carbon dioxide, sodium chloride, and sodium nitrite on type B botulinum neurotoxin (BoNT/B) gene (cntB) expression in nonproteolytic Clostridium botulinum were investigated in a tryptone-peptone-yeast extract (TPY) medium. Various concentrations of these selected food preservatives were studied by using a complete factorial design in order to quantitatively study interaction effects, as well as main effects, on the following responses: lag phase duration (LPD), growth rate, relative cntB expression, and extracellular BoNT/B production. Multiple linear regression was used to set up six statistical models to quantify and predict these responses. All combinations of NaCl and NaNO2 in the growth medium resulted in a prolonged lag phase duration and in a reduction in the specific growth rate. In contrast, the relative BoNT/B gene expression was unchanged, as determined by the cntB-specific quantitative reverse transcription-PCR method. This was confirmed when we measured the extracellular BoNT/B concentration by an enzyme-linked immunosorbent assay. CO2 was found to have a major effect on gene expression when the cntB mRNA levels were monitored in the mid-exponential, late exponential, and late stationary growth phases. The expression of cntB relative to the expression of the 16S rRNA gene was stimulated by an elevated CO2 concentration; the cntB mRNA level was fivefold greater in a 70% CO2 atmosphere than in a 10% CO2 atmosphere. These findings were also confirmed when we analyzed the extracellular BoNT/B concentration; we found that the concentrations were 27 ng · ml−1 · unit of optical density−1 in the 10% CO2 atmosphere and 126 ng · ml−1 · unit of optical density−1 in the 70% CO2 atmosphere. PMID:15128553

Membrane depolarization and aberrant lipid distributions in the neonatal rat brain following hypoxic-ischaemic insult.

PubMed

Luptakova, Dominika; Baciak, Ladislav; Pluhacek, Tomas; Skriba, Anton; Sediva, Blanka; Havlicek, Vladimir; Juranek, Ivo

2018-05-03

Neonatal hypoxic-ischaemic (HI) encephalopathy is among the most serious complications in neonatology. In the present study, we studied the immediate (0 hour), subacute (36 hours) and late (144 hours) responses of the neonatal brain to experimental HI insult in laboratory rats. At the striatal level, the mass spectrometry imaging revealed an aberrant plasma membrane distribution of Na + /K + ions in the oedema-affected areas. The failure of the Na + /K + gradients was also apparent in the magnetic resonance imaging measurements, demonstrating intracellular water accumulation during the acute phase of the HI insult. During the subacute phase, compared with the control brains, an incipient accumulation of an array of N-acylphosphatidylethanolamine (NAPE) molecules was detected in the HI-affected brains, and both the cytotoxic and vasogenic types of oedema were detected. In the severely affected brain areas, abnormal distributions of the monosialogangliosides GM2 and GM3 were observed in two-thirds of the animals exposed to the insult. During the late stage, a partial restoration of the brain tissue was observed in most rats in both the in vivo and ex vivo studies. These specific molecular changes may be further utilized in neonatology practice in proposing and testing novel therapeutic strategies for the treatment of neonatal HI encephalopathy.

Self-assembled structural color in nature

NASA Astrophysics Data System (ADS)

Parnell, Andrew

The vibrancy and variety of structural color found in nature has long been well-known; what has only recently been discovered is the sophistication of the physics that underlies these effects. In the talk I will discuss some of our recent studies of the structures responsible for color in bird feathers and beetle elytra, based on structural characterization using small angle x-ray scattering, x-ray tomography and optical modeling. These have enabled us to study a large number of structural color exhibiting materials and look for trends in the structures nature uses to provide these optical effects. In terms of creating the optical structure responsible for the color of the Eurasian Jay feathers (Garrulus glandarius) the nanostructure is produced by a phase-separation process that is arrested at a late stage; mastery of the color is achieved by control over the duration of this phase-separation process. Our analysis shows that nanostructure in single bird feather barbs can be varied continuously by controlling the time the keratin network is allowed to phase separate before mobility in the system is arrested. Dynamic scaling analysis of the single barb scattering data implies that the phase separation arrest mechanism is rapid and also distinct from the spinodal phase separation mechanism i.e. it is not gelation or intermolecular re-association. Any growing lengthscale using this spinodal phase separation approach must first traverse the UV and blue wavelength regions, growing the structure by coarsening, resulting in a broad distribution of domain sizes. AJP acknowledges financial support via the APS/DPOLY exchange lectureship 2017.

Where Is ELSA? The Early to Late Shift in Aging

PubMed Central

Buchler, Norbou; Dobbins, Ian G.; Cabeza, Roberto

2012-01-01

Studies of cognitive and neural aging have recently provided evidence of a shift from an early- to late-onset cognitive control strategy, linked with temporally extended activity in the prefrontal cortex (PFC). It has been uncertain, however, whether this age-related shift is unique to PFC and executive control tasks or whether the functional location might vary depending on the particular cognitive processes that are altered. The present study tested whether an early-to-late shift in aging (ELSA) might emerge in the medial temporal lobes (MTL) during a protracted context memory task comprising both anticipatory cue (retrieval preparation) and retrieval probe (retrieval completion) phases. First, we found reduced MTL activity in older adults during the early retrieval preparation phase coupled with increased MTL activity during the late retrieval completion phase. Second, we found that functional connectivity between MTL and PFC regions was higher during retrieval preparation in young adults but higher during retrieval completion in older adults, suggesting an important interactive relationship between the ELSA pattern in MTL and PFC. Taken together, these results critically suggest that aging results in temporally lagged activity even in regions not typically associated with cognitive control, such as the MTL. PMID:22114083

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

PubMed Central

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

2011-01-01

It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes. PMID:21960964

The scaffold protein Nde1 safeguards the brain genome during S phase of early neural progenitor differentiation

PubMed Central

Houlihan, Shauna L; Feng, Yuanyi

2014-01-01

Successfully completing the S phase of each cell cycle ensures genome integrity. Impediment of DNA replication can lead to DNA damage and genomic disorders. In this study, we show a novel function for NDE1, whose mutations cause brain developmental disorders, in safeguarding the genome through S phase during early steps of neural progenitor fate restrictive differentiation. Nde1 mutant neural progenitors showed catastrophic DNA double strand breaks concurrent with the DNA replication. This evoked DNA damage responses, led to the activation of p53-dependent apoptosis, and resulted in the reduction of neurons in cortical layer II/III. We discovered a nuclear pool of Nde1, identified the interaction of Nde1 with cohesin and its associated chromatin remodeler, and showed that stalled DNA replication in Nde1 mutants specifically occurred in mid-late S phase at heterochromatin domains. These findings suggest that NDE1-mediated heterochromatin replication is indispensible for neuronal differentiation, and that the loss of NDE1 function may lead to genomic neurological disorders. DOI: http://dx.doi.org/10.7554/eLife.03297.001 PMID:25245017

Stable, Metastable, and Kinetically Trapped Amyloid Aggregate Phases

PubMed Central

2015-01-01

Self-assembly of proteins into amyloid fibrils plays a key role in a multitude of human disorders that range from Alzheimer’s disease to type II diabetes. Compact oligomeric species, observed early during amyloid formation, are reported as the molecular entities responsible for the toxic effects of amyloid self-assembly. However, the relation between early-stage oligomeric aggregates and late-stage rigid fibrils, which are the hallmark structure of amyloid plaques, has remained unclear. We show that these different structures occupy well-defined regions in a peculiar phase diagram. Lysozyme amyloid oligomers and their curvilinear fibrils only form after they cross a salt and protein concentration-dependent threshold. We also determine a boundary for the onset of amyloid oligomer precipitation. The oligomeric aggregates are structurally distinct from rigid fibrils and are metastable against nucleation and growth of rigid fibrils. These experimentally determined boundaries match well with colloidal model predictions that account for salt-modulated charge repulsion. The model also incorporates the metastable and kinetic character of oligomer phases. Similarities and differences of amyloid oligomer assembly to metastable liquid–liquid phase separation of proteins and to surfactant aggregation are discussed. PMID:25469942

Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin.

PubMed

Sims, Jennifer K; Wade, Paul A

2011-09-01

During chromosome duplication, it is essential to replicate not only the DNA sequence, but also the complex nucleoprotein structures of chromatin. Pericentric heterochromatin is critical for silencing repetitive elements and plays an essential structural role during mitosis. However, relatively little is understood about its assembly and maintenance during replication. The Mi2/NuRD chromatin remodeling complex tightly associates with actively replicating pericentric heterochromatin, suggesting a role in its assembly. Here we demonstrate that depletion of the catalytic ATPase subunit CHD4/Mi-2β in cells with a dampened DNA damage response results in a slow-growth phenotype characterized by delayed progression through S phase. Furthermore, we observe defects in pericentric heterochromatin maintenance and assembly. Our data suggest that chromatin assembly defects are sensed by an ATM-dependent intra-S phase chromatin quality checkpoint, resulting in a temporal block to the transition from early to late S phase. These findings implicate Mi-2β in the maintenance of chromatin structure and proper cell cycle progression.

Stable, metastable, and kinetically trapped amyloid aggregate phases.

PubMed

Miti, Tatiana; Mulaj, Mentor; Schmit, Jeremy D; Muschol, Martin

2015-01-12

Self-assembly of proteins into amyloid fibrils plays a key role in a multitude of human disorders that range from Alzheimer's disease to type II diabetes. Compact oligomeric species, observed early during amyloid formation, are reported as the molecular entities responsible for the toxic effects of amyloid self-assembly. However, the relation between early-stage oligomeric aggregates and late-stage rigid fibrils, which are the hallmark structure of amyloid plaques, has remained unclear. We show that these different structures occupy well-defined regions in a peculiar phase diagram. Lysozyme amyloid oligomers and their curvilinear fibrils only form after they cross a salt and protein concentration-dependent threshold. We also determine a boundary for the onset of amyloid oligomer precipitation. The oligomeric aggregates are structurally distinct from rigid fibrils and are metastable against nucleation and growth of rigid fibrils. These experimentally determined boundaries match well with colloidal model predictions that account for salt-modulated charge repulsion. The model also incorporates the metastable and kinetic character of oligomer phases. Similarities and differences of amyloid oligomer assembly to metastable liquid-liquid phase separation of proteins and to surfactant aggregation are discussed.

Thick strings, the liquid crystal blue phase, and cosmological large-scale structure

NASA Technical Reports Server (NTRS)

Luo, Xiaochun; Schramm, David N.

1992-01-01

A phenomenological model based on the liquid crystal blue phase is proposed as a model for a late-time cosmological phase transition. Topological defects, in particular thick strings and/or domain walls, are presented as seeds for structure formation. It is shown that the observed large-scale structure, including quasi-periodic wall structure, can be well fitted in the model without violating the microwave background isotropy bound or the limits from induced gravitational waves and the millisecond pulsar timing. Furthermore, such late-time transitions can produce objects such as quasars at high redshifts. The model appears to work with either cold or hot dark matter.

IPAD II (Integrated Programs for Aerospace-Vehicle Design) Advances in Distributed Data Base Management for CAD/CAM (Computer-Aided Design and Manufacturing Technology). Proceedings of a National Symposium Held in Denver, Colorado, April 17-19, 1984.

DTIC Science & Technology

1984-01-01

working drawings, lists, and miscellaneous information needed for construction and testing (fig. 4). Detail design and construction in- cludes...still in test and evaluation phases, and is currently operational on a CDC computer. Its approach to management of geometric data is a unique and...been to provide the high degree of engineering user flexibility and yet achieve acceptable response times. In late 1983, a test system which has user

On the timing and forcing mechanisms of late Pleistocene glacial terminations: Insights from a new high-resolution benthic stable oxygen isotope record of the eastern Mediterranean

NASA Astrophysics Data System (ADS)

Konijnendijk, T. Y. M.; Ziegler, M.; Lourens, L. J.

2015-12-01

Benthic oxygen isotope records of deep marine sedimentary archives have yielded a wealth of information regarding ice sheet dynamics and climate change during the Pleistocene. However, since they often lack independent age control, these records are generally bound by a fixed phase relationship between orbital forcing and the climate response, e.g. ice volume changes. We present the first long (∼1.2 Ma) benthic oxygen isotope record from the eastern Mediterranean, based on ODP Sites 967 and 968, which clearly reflects the behavior of global climate on a glacial-interglacial scale throughout the late Pleistocene time period. The age model for our record is based on tuning the elemental ratio of titanium versus aluminum (Ti/Al) against insolation. The Ti/Al record is dominated by the precession-related changes in northern African climate, i.e. monsoonal forcing, and hence largely independent of glacial-interglacial variability. We found the largest offset between our chronology and that of the widely applied, open ocean stacked record LR04 (Lisiecki and Raymo, 2005) for TVII (∼624 ka), which occurred ∼9 kyr earlier according to our estimates, though in agreement with the AICC2012 δDice chronology of EPICA Dome C (Bazin et al., 2013). Spectral cross-correlation analysis between our benthic δ18O record and 65°N summer insolation reveals significant amounts of power in the obliquity and precession range, with an average lag of 5.5 ± 0.8 kyr for obliquity, and 6.0 ± 1.0 kyr for precession. In addition, our results show that the obliquity-related time lag was smaller (3.0 ± 3.3 kyr) prior to ∼900 ka than after (5.7 ± 1.1 kyr), suggesting that on average the glacial response time to obliquity forcing increased during the mid-Pleistocene transition, much later than assumed by Lisiecki and Raymo (2005). Finally, we found that almost all glacial terminations have a consistent phase relationship of ∼45 ± 45° with respect to the precession and obliquity-driven increases in 65°N summer insolation, consistent with the general consensus that both obliquity and precession are important for deglaciation during the Late Pleistocene. Exceptions are glacial terminations TIIIb, T36 and potentially T32 (and TVII T24 and T34), which show this consistent phase relationship only with precession (only with obliquity). Our findings point towards an early (>1200 ka) onset of the Mid Pleistocene Transition. Vice versa, the timing of TVII, which can only be explained as a response to obliquity forcing, indicates that the transition lasted until at least after MIS 15.

Sexual reproduction as a response to H sub 2 O sub 2 damage in Schizosaccharomyces pombe

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

Bernstein, C.; Johns, V.

1989-04-01

Although sexual reproduction is widespread, its adaptive advantage over asexual reproduction is unclear. One major advantage of sex may be its promotion of recombinational repair of DNA damage during meiosis. This idea predicts that treatment of the asexual form of a facultatively sexual-asexual eucaryote with a DNA-damaging agent may cause it to enter the sexual cycle more frequently. Endogenous hydrogen peroxide is a major natural source of DNA damage. Thus, the authors treated vegetative cells of Schizosaccharomyces pombe with hydrogen peroxide to test if sexual reproduction increases. Among untreated stationary-phase S. pombe populations the sexual spores produced by meiosis representedmore » about 1% of the total cells. However, treatment of late-exponential-phase vegetative cells with hydrogen peroxide increased the percentage of meiotic spores in the stationary phase by 4- to 18-fold. Oxidative damage therefore induces sexual reproduction in a facultatively sexual organism, a result expected by the hypothesis that sex promotes DNA repair.« less

Anaphase-promoting complex/cyclosome-CDH1-mediated proteolysis of the forkhead box M1 transcription factor is critical for regulated entry into S phase.

PubMed

Park, Hyun Jung; Costa, Robert H; Lau, Lester F; Tyner, Angela L; Raychaudhuri, Pradip

2008-09-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G(1) phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G(1) phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G(1) phase and that its proteolysis is important for regulated entry into S phase.

Multiorgan failure in the serious trauma patient.

PubMed

Llompart-Pou, J A; Talayero, M; Homar, J; Royo, C

2014-10-01

Multiorgan failure remains one of the leading causes of late morbidity and mortality after severe trauma. In the early phase, it is related with an uncontrolled hyper-inflammation state, whereas in the late phase (>72 h), septic complications play a major role. We review the underlying pathophysiology, the evaluation with different scales and the clinical factors associated with multiorgan failure, as well as potential treatment options. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Accurate Modeling of Stability and Control Properties for Fighter Aircraft from CFD

DTIC Science & Technology

2012-03-01

first an aircraft to flight test which is not until late in the design phase where millions if not billions of dollars have already been invested. It...of an aircraft and even late in the design phase there are often large gaps in data due to budget cuts to flight testing and limitations to maneuvers...early in the design cycle has been the source of many costly fixes to fighter aircraft after flight testing begins. Early prediction of these nonlinear

Post-glucose load changes of plasma key metabolite and insulin concentrations during pregnancy and lactation in ewes with different susceptibility to pregnancy toxaemia.

PubMed

Duehlmeier, R; Fluegge, I; Schwert, B; Ganter, M

2013-10-01

Insulin resistance during late gestation may act as a predisposing factor of ovine pregnancy toxaemia (OPT). To evaluate the insulin action on energy metabolism in ewes with different susceptibilities to OPT, intravenous glucose tolerance tests (1 mmol glucose/kg body weight) were performed in 5.6 ± 0.7 year old, slightly underfed German Blackheaded Mutton ewes [high-risk (HR) ewes] and 2.5 year old, overnourished Finnish Landrace ewes [low-risk (LR) ewes] during mid and late pregnancy, during early lactation and during the dry period. Plasma samples were analysed for glucose, insulin, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (β-HB). The glucose elimination rate and the glucose-stimulated first-phase insulin secretion were significantly (p < 0.05) lower in the HR, in relation to the LR group combining the data of all gestational stages. The basal rate of lipolysis was significantly increased in the HR ewes during late pregnancy, but the NEFA clearance after the glucose load was similar in both groups during all reproductive stages. Plasma β-HB concentrations decreased only in the LR ewes after the glucose load during late pregnancy. Results indicate an insulin resistance in the HR ewes regarding the glucose utilization and the ketone body formation during late pregnancy. The insulin resistance in the HR ewes may represent one predisposing factor responsible for the susceptibility to OPT. Further scientific work is necessary to elucidate whether this insulin resistance was due to breed, age or nutritional state. © 2012 Blackwell Verlag GmbH.

Tissue responses to low protracted doses of high let radiations or photons - Early and late damage relevant to radio-protective countermeasures

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

1989-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Two Late Pleistocene climate-driven incision/aggradation rhythms in the middle Dnieper River basin, west-central Russian Plain

NASA Astrophysics Data System (ADS)

Panin, Andrei; Adamiec, Grzegorz; Buylaert, Jan-Pieter; Matlakhova, Ekaterina; Moska, Piotr; Novenko, Elena

2017-06-01

In valleys of the River Seim and its tributaries in the middle Dnieper basin (west-central Russian Plain), two low terraces (T1, 10-16 m, and T0, 5-7 m above the river) and a floodplain (2-4 m) with characteristic large and small palaeochannels exist. A range of field and laboratory techniques was applied and ∼30 new numerical ages (OSL and 14C dates) were obtained to establish a chronology of incision and aggradation events that resulted in the current valley morphology. Two full incision/aggradation rhythms and one additional aggradation phase from the previous rhythm were recognized in the Late Pleistocene - Holocene climate cycle. The following events were detected. (1) Late MIS 5 - early MIS 4: aggradation of Terrace T1 following the deep incision at the end of MIS 6. (2) Late MIS 4 (40-30 ka): incision into Terrace T1 below the present-day river, formation of the main scarp in the bottom of the valley between Terrace T1 and Terrace T0/Floodplain levels. (3) MIS 2: aggradation of Terrace T0, lateral migrations of a shallow braided channel located few meters above the present-day river since ∼25 ka through the LGM. (4) 18-13 ka: incision into Terrace T0 below the modern river. Multiple-thread channels concentrated in a single flow that at some places formed large meanders. In the period 15-13 ka, high floods that rose above the present-day floods left large levees and overbank loams on Terrace T0. (5) Younger Dryas - Holocene transition: aggradation up to the modern channel level, transformation of large Late Glacial to small Holocene meanders. The established incision/aggradation rhythms are believed to be manifested over the Central Russian Plain outside the influence of ice sheets in the north and base level changes in the south. The two-phase deepening of the valley occurred in the last quarter of the last glacial epoch but can not be attributed directly to the glacial-interglacial transition. Both the detected incision events correspond to relatively warm climate phases - late MIS 3, post-LGM warming including the Bølling-Allerød interstadial. Anomalously large size of the preserved river palaeochannels prove that the post-LGM incision phase was induced by a climatically forced large increase of water runoff. Considerable increase of water discharges is considered the most probably cause for the late MIS 4 incision phase also. Therefore river incision seems to have been governed rather by changing water runoff that oscillated in phase shift with the thermal regime.

Public health activities for mitigation of radiation exposures and risk communication challenges after the Fukushima nuclear accident.

PubMed

Shimura, Tsutomu; Yamaguchi, Ichiro; Terada, Hiroshi; Robert Svendsen, Erik; Kunugita, Naoki

2015-05-01

Herein we summarize the public health actions taken to mitigate exposure of the public to radiation after the Fukushima accident that occurred on 11 March 2011 in order to record valuable lessons learned for disaster preparedness. Evacuations from the radiation-affected areas and control of the distribution of various food products contributed to the reduction of external and internal radiation exposure resulting from the Fukushima incident. However, risk communication is also an important issue during the emergency response effort and subsequent phases of dealiing with a nuclear disaster. To assist with their healing process, sound, reliable scientific information should continue to be disseminated to the radiation-affected communities via two-way communication. We will describe the essential public health actions following a nuclear disaster for the early, intermediate and late phases that will be useful for radiological preparedness planning in response to other nuclear or radiological disasters. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

iRhom2 is essential for innate immunity to RNA virus by antagonizing ER- and mitochondria-associated degradation of VISA.

PubMed

Luo, Wei-Wei; Li, Shu; Li, Chen; Zheng, Zhou-Qin; Cao, Pan; Tong, Zhen; Lian, Huan; Wang, Su-Yun; Shu, Hong-Bing; Wang, Yan-Yi

2017-11-01

VISA (also known as MAVS, IPS-1 and Cardif) is an essential adaptor protein in innate immune response to RNA virus. The protein level of VISA is delicately regulated before and after viral infection to ensure the optimal activation and timely termination of innate antiviral response. It has been reported that several E3 ubiquitin ligases can mediate the degradation of VISA, but how the stability of VISA is maintained before and after viral infection remains enigmatic. In this study, we found that the ER-associated inactive rhomboid protein 2 (iRhom2) plays an essential role in mounting an efficient innate immune response to RNA virus by maintaining the stability of VISA through distinct mechanisms. In un-infected and early infected cells, iRhom2 mediates auto-ubiquitination and degradation of the E3 ubiquitin ligase RNF5 and impairs the assembly of VISA-RNF5-GP78 complexes, thereby antagonizes ER-associated degradation (ERAD) of VISA. In the late phase of viral infection, iRhom2 mediates proteasome-dependent degradation of the E3 ubiquitin ligase MARCH5 and impairs mitochondria-associated degradation (MAD) of VISA. Maintenance of VISA stability by iRhom2 ensures efficient innate antiviral response at the early phase of viral infection and ready for next round of response. Our findings suggest that iRhom2 acts as a checkpoint for the ERAD/MAD of VISA, which ensures proper innate immune response to RNA virus.

iRhom2 is essential for innate immunity to RNA virus by antagonizing ER- and mitochondria-associated degradation of VISA

PubMed Central

Luo, Wei-Wei; Li, Shu; Cao, Pan; Tong, Zhen; Lian, Huan; Wang, Su-Yun; Shu, Hong-Bing

2017-01-01

VISA (also known as MAVS, IPS-1 and Cardif) is an essential adaptor protein in innate immune response to RNA virus. The protein level of VISA is delicately regulated before and after viral infection to ensure the optimal activation and timely termination of innate antiviral response. It has been reported that several E3 ubiquitin ligases can mediate the degradation of VISA, but how the stability of VISA is maintained before and after viral infection remains enigmatic. In this study, we found that the ER-associated inactive rhomboid protein 2 (iRhom2) plays an essential role in mounting an efficient innate immune response to RNA virus by maintaining the stability of VISA through distinct mechanisms. In un-infected and early infected cells, iRhom2 mediates auto-ubiquitination and degradation of the E3 ubiquitin ligase RNF5 and impairs the assembly of VISA-RNF5-GP78 complexes, thereby antagonizes ER-associated degradation (ERAD) of VISA. In the late phase of viral infection, iRhom2 mediates proteasome-dependent degradation of the E3 ubiquitin ligase MARCH5 and impairs mitochondria-associated degradation (MAD) of VISA. Maintenance of VISA stability by iRhom2 ensures efficient innate antiviral response at the early phase of viral infection and ready for next round of response. Our findings suggest that iRhom2 acts as a checkpoint for the ERAD/MAD of VISA, which ensures proper innate immune response to RNA virus. PMID:29155878

Current therapy for laser-induced retinal injury: overview of clinical and experimental approaches

NASA Astrophysics Data System (ADS)

Schuschereba, Steven T.; Scales, David K.

1997-05-01

Adequate treatment strategies do not exist for retinal laser injuries. To gain a better understanding of available treatments, data form a variety of human laser accident cases and relevant experimental work was evaluated. Most laser eye injury cases are not attended by an ophthalmologist for several hours to days after injury and most patients are not treated.Of the few cases receiving treatment; only the FDA approved glucocortocoids are available for use. Their use, however, is still controversial. Experimental animal work during the acute phase of injury indicates that productive efforts have targeted neuroprotection, inflammation, ischemia- reperfusion, and lipid peroxidation. Late stage issues for treatment are scarring, retinal hole persistence and expansion, and traction. In summary, treatments for acute and late phase injury are currently inadequate. Preserving existing neural elements should be the top priority in these injuries. We recommend that relevant treatments begin immediately after injury. Other approaches are necessary to target early and late phase secondary damage events that are entrenched.

Delayed neovascularization in free skin flap transfer to irradiated beds in rats

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

Clarke, H.M.; Howard, C.R.; Pynn, B.R.

1985-04-01

A model for the study of neovascularization with a normal epigastric free flap set into an irradiated defect in the Fischer F344 rat is presented. In this model, both the administration of radiation and the flap transfer mimic the clinical situation. Significantly less tissue survives loss of the complete vascular pedicle at the second to fourth days following flap creation in rats with an irradiated bed. Later survival is not different from controls. Delayed neovascularization is proposed as the mechanism responsible for this effect during the period corresponding to the onset of the late phase of the response to skinmore » radiation in rats. That neovascularization does occur, although delayed, suggests that the induced endarteritis may not be as important as previously suggested.« less

The anatomy of a major late-stage thrust and implications for models of late-stage collisional orogenesis in the Caledonian crust of northern Scandinavia

NASA Astrophysics Data System (ADS)

Anderson, Mark; Hames, Willis; Stokes, Alison

2010-05-01

Within the stack of Caledonian crystalline thrust sheets of northern Scandinavia, a single amphibolite facies lithotectonic unit, the Småtinden nappe, is identified as a major, basement-coupled ("stretching") shear zone. This dominantly pelitic unit achieved peak metamorphic conditions of 535-550°C and 8-9kbars, and the stretching geometry suggests that this most likely occurred in response to overthrusting of a hot, pre-assembled Caledonian thrust stack. Along-strike variations in microstructural geometries and patterns of mineral zoning in widely developed porphyroblast phases suggest, however, subsequent strain partitioning within the zone during late-stage decoupling of the thrust stack from the basement along major out-of-sequence thrusts. Large parts of the nappe are characterised by relatively late, static growth preserving concordant Si-Se relationships, and typically symmetrical external fabrics consistent with formation under dominantly pure shear conditions. In the Salangen area, however, the nappe is characterised by early garnet growth, with discordant Si-Se relationships and asymmetric external fabric geometries consistent with formation during ESE-directed simple shear. Remarkably consistent thermometric estimates from chlorites in both regimes (post- and syn-shearing) suggest that out-of-sequence ramping occurred at temperatures in the range 370-400 ̊C, within the typical range of blocking temperatures for argon retention in muscovite. 40Ar-39Ar dating of muscovites from S-C fabrics in the out-of-sequence shear zone suggest that late-stage thrusting occurred during the middle-late Devonian (ca. 395-375 Ma). Hanging-wall and footwall geometries coupled with these radiometric dates indicate that the development of these late thrusts closely relates to reactivation of pre-Caledonian Baltic basement during the Devonian (400-370 Ma). East-west contraction during the upper end of this time frame is peculiar considering that this was the period of large magnitude and rapid extension in western Norway.

Therapy response assessment after radioembolization of patients with hepatocellular carcinoma--comparison of MR imaging with gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid and gadobutrol.

PubMed

Schelhorn, Juliane; Best, Jan; Reinboldt, Marcus P; Gerken, Guido; Ruhlmann, Marcus; Lauenstein, Thomas C; Antoch, Gerald; Kinner, Sonja

2015-07-01

To compare the utility of gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA), a liver-specific magnetic resonance (MR) imaging contrast agent, versus gadobutrol for treatment response evaluation of hepatocellular carcinoma (HCC) after radioembolization. This prospective study included 50 patients with HCC undergoing radioembolization. All patients underwent contrast-enhanced computed tomography (CT) and MR imaging with gadobutrol and Gd-EOB-DTPA on 2 consecutive days before radioembolization and 30 days, 90 days, 180 days, and 270 days after radioembolization. The standard of reference indicating tumor progression was CT combined with either α-fetoprotein or γ-glutamyltransferase. Gadobutrol-enhanced MR imaging, Gd-EOB-DTPA-enhanced MR imaging without late phase imaging (Gd-EOB-DTPA-), and Gd-EOB-DTPA-enhanced MR imaging with late phase imaging (Gd-EOB-DTPA+) were evaluated by 2 radiologists in consensus using a 4-point scale: 1 = definitely no tumor progression; 2 = probably no tumor progression; 3 = probably tumor progression; 4 = definitely tumor progression. Diagnostic accuracy was assessed with receiver operating characteristic analysis. Tumor progression was detected in 14 of 82 study visits according to the reference standard. Pairwise comparison of the area under the curve showed a tendency toward a larger area under the curve for Gd-EOB-DTPA+ compared with gadobutrol (P = .056). Sensitivity and specificity were higher in Gd-EOB-DTPA+ (0.929 and 0.971) than in Gd-EOB-DTPA- (0.786 and 0.941) or gadobutrol (0.643 and 0.956). In 2 cases, tumor progression was detected by Gd-EOB-DTPA+ and by an increase in α-fetoprotein, but not by CT, gadobutrol, or Gd-EOB-DTPA-. Gd-EOB-DTPA+ MR imaging was not inferior to gadobutrol-enhanced MR imaging in therapy response evaluation after radioembolization and may allow a more accurate detection of early HCC recurrence in single cases. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Psychological factors as predictors of early postoperative pain after open nephrectomy

PubMed Central

Mimic, Ana; Bantel, Carsten; Jovicic, Jelena; Mimic, Branko; Kisic-Tepavcevic, Darija; Durutovic, Otas; Ladjevic, Nebojsa

2018-01-01

Purpose There is an increasing interest in the identification of predictors for individual responses to analgesics and surgical pain. In this study, we aimed to determine psychological factors that might contribute to this response. We hence investigated patients undergoing a standardized surgical intervention (open nephrectomy). Patients and methods Between May 2014 and April 2015, we conducted a prospective observational cohort study. The following psychological tests were administered preoperatively: Mini-Mental State Examination, Amsterdam Preoperative Anxiety and Information Scale (APAIS), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Pain Catastrophizing Scale. The primary outcome, postoperative pain intensity (11-point numerical rating scale, [NRS]), was assessed in the “immediate early” (first 8 hours), “early” (12 and 24 hours), and “late early” periods (48 and 72 hours). Results A total of 196 patients were assessed, and 150 were finally included in the study. NRS scores improved from 4.9 (95% confidence interval [CI]: 4.7–5.1) in the “immediate early” to 3.1 (95% CI: 2.9–3.3) in the “early” and 2.3 (95% CI: 2.1–2.5) in the “late early” postoperative period. Most (87%) patients received intravenous opioids, while 13% received analgesics epidurally. Repeated measures analysis of variance indicated better pain management with epidural analgesia in the first two postoperative periods (F=15.01, p<0.00). Postoperative pain correlated strongly with analgesic strategy and preoperative psychological assessment. Multiple linear regression analysis showed “expected pain” was the only predictor in the “immediate early” phase, and “anxiety” was most important in the “early” postoperative period. In the “late early” phase, catastrophizing was the predominant predictor, alongside “preoperative analgesic usage” and “APAIS anxiety”. Conclusion After open nephrectomy, epidural analgesia conveys a clear advantage for pain management only within the first 24 hours. Moreover, as the psychological phenotype of patients changes distinctively in the first 72 postoperative hours, psychological variables increasingly determine pain intensity, even surpassing employed analgesic strategy as its main predictor. PMID:29785136

Multidisciplinary approach for fault detection: Integration of PS-InSAR, geomorphological, stratigraphic and structural data in the Venafro intermontane basin (Central-Southern Apennines, Italy)

NASA Astrophysics Data System (ADS)

Amato, Vincenzo; Aucelli, Pietro P. C.; Bellucci Sessa, Eliana; Cesarano, Massimo; Incontri, Pietro; Pappone, Gerardo; Valente, Ettore; Vilardo, Giuseppe

2017-04-01

A multidisciplinary methodology, integrating stratigraphic, geomorphological and structural data, combined with GIS-aided analysis and PS-InSAR interferometric data, was applied to characterize the relationships between ground deformations and the stratigraphic and the morphostructural setting of the Venafro intermontane basin. This basin is a morphostructural depression related to NW-SE and NE-SW oriented high angle normal faults bordering and crossing it. In particular, a well-known active fault crossing the plain is the Aquae Juliae Fault, whose recent activity is evidenced by archeoseismological data. The approach applied here reveals new evidence of possible faulting, acting during the Lower to Upper Pleistocene, which has driven the morphotectonic and the environmental evolution of the basin. In particular, the tectonic setting emerging from this study highlights the influence of the NW-SE oriented extensional phase during the late Lower Pleistocene - early Middle Pleistocene, in the generation of NE-SW trending, SE dipping, high-angle faults and NW-SE trending, high-angle transtensive faults. This phase has been followed by a NE-SW extensional one, responsible for the formation of NW-SE trending, both NW and SE dipping, high-angle normal faults, and the reactivation of the oldest NE-SW oriented structures. These NW-SE trending normal faults include the Aquae Juliae Fault and a new one, unknown until now, crossing the plain between the Venafro village and the Colle Cupone Mt. (hereinafter named the Venafro-Colle Cupone Fault, VCCF). This fault has controlled deposition of the youngest sedimentary units (late Middle Pleistocene to late Upper Pleistocene) suggesting its recent activity and it is well constrained by PS-InSAR data, as testified by the increase of the subsidence rate in the hanging wall block.

The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity.

PubMed

Kent, D

2015-11-01

This review summarises our current understanding of the molecular basis of subretinal neovascularisation (SRNV) in age-related macular degeneration (AMD). The term neovascular AMD (NVAMD) is derived from the dominant early clinical features of haemorrhage, fluid, and lipid in the subretinal space (SRS) and the historical role of fluorescein angiography in detecting the presence of NV tissue. However, at the cellular level, SRNV resembles an aberrant but stereotypical tissue repair response that incorporates both an early inflammatory phase and a late fibrotic phase in addition to the neovascular (NV) component that dominates the early clinical presentation. This review will seek not only to highlight the important molecules involved in each of these components but to demonstrate that the development of SRNV has its origins in the earliest events in non-NV AMD pathogenesis. Current evidence suggests that this early-stage pathogenesis is characterised by complement-mediated immune dysregulation, leading to a state of chronic inflammation in the retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. These initial events can be seamlessly and inextricably linked to late-stage development of SRNV in AMD by the process of dynamic reciprocity (DyR), the ongoing bidirectional communication between cells, and their surrounding matrix. Moreover, this correlation between disease onset and eventual outcome is reflected in the temporal and spatial correlation between chronic inflammation, NV, and fibrosis within the reparative microenvironment of the SRS. In summary, the downstream consequences of the earliest dysfunctional molecular events in AMD can result in the late-stage entity we recognize clinically as SRNV and is characterized by a spectrum of predictable, related, and stereotypical processes referred to as DyR.

Dynamic accommodation responses following adaptation to defocus.

PubMed

Cufflin, Matthew P; Mallen, Edward A H

2008-10-01

Adaptation to defocus is known to influence the subjective sensitivity to blur in both emmetropes and myopes. Blur is a major contributing factor in the closed-loop dynamic accommodation response. Previous investigations have examined the magnitude of the accommodation response following blur adaptation. We have investigated whether a period of blur adaptation influences the dynamic accommodation response to step and sinusoidal changes in target vergence. Eighteen subjects (six emmetropes, six early onset myopes, and six late onset myopes) underwent 30 min of adaptation to 0.00 D (control), +1.00 D or +3.00 D myopic defocus. Following this adaptation period, accommodation responses to a 2.00 D step change and 2.00 D sinusoidal change (0.2 Hz) in target vergence were recorded continuously using an autorefractor. Adaptation to defocus failed to influence accommodation latency times, but did influence response times to a step change in target vergence. Adaptation to both +1.00 and +3.00 D induced significant increases in response times (p = 0.002 and p = 0.012, respectively) and adaptation to +3.00 D increased the change in accommodation response magnitude (p = 0.014) for a 2.00 D step change in demand. Blur adaptation also significantly increased the peak-to-peak phase lag for accommodation responses to a sinusoidally oscillating target, although failed to influence the accommodation gain. These changes in accommodative response were equivalent across all refractive groups. Adaptation to a degraded stimulus causes an increased level of accommodation for dynamic targets moving towards an observer and increases response times and phase lags. It is suggested that the contrast constancy theory may explain these changes in dynamic behavior.

Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury.

PubMed

Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle; Summer, Ross

2014-01-01

Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5'-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI.

Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury

PubMed Central

Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle

2013-01-01

Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5′-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI. PMID:24285266

Anaphase-Promoting Complex/Cyclosome-Cdh1-Mediated Proteolysis of the Forkhead Box M1 Transcription Factor Is Critical for Regulated Entry into S Phase▿

PubMed Central

Park, Hyun Jung; Costa, Robert H.; Lau, Lester F.; Tyner, Angela L.; Raychaudhuri, Pradip

2008-01-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G1 phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G1 phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G1 phase and that its proteolysis is important for regulated entry into S phase. PMID:18573889

The use of lipids as phase change materials for thermal energy storage

USDA-ARS?s Scientific Manuscript database

Phase change materials (PCMs) are substances capable of absorbing and releasing large 2 amounts of thermal energy (heat or cold) as latent heat over constant temperature as they 3 undergo a change in state of matter (phase transition), commonly, between solid and 4 liquid phases. Since the late 194...

Fluctuating serotonergic function in premenstrual dysphoric disorder and premenstrual syndrome: findings from neuroendocrine challenge tests.

PubMed

Inoue, Y; Terao, T; Iwata, N; Okamoto, K; Kojima, H; Okamoto, T; Yoshimura, R; Nakamura, J

2007-02-01

Premenstrual dysphoric disorder (PMDD) has been assumed to be a subtype of premenstrual syndrome (PMS) with depressive symptoms, such as depressive mood, tension, anxiety, and mood liability during luteal phase. At present, no conclusion has been established about serotonergic function in PMDD. The purpose of this study was to investigate the serotonergic function of PMDD subjects in comparison to PMS without PMDD subjects and normal controls via neuroendocrine challenge tests. Twenty-four women (seven with PMDD, eight with PMS without PMDD, and nine normal controls) were tested on three occasions (follicular phase, early luteal phase, and late luteal phase) receiving paroxetine 20 mg orally as a serotonergic probe at 8:00 A: .M: . Plasma ACTH and cortisol were measured prior to the administration and every hour for 6 h thereafter. As a whole, there were significant differences in serotonergic function measured by ACTH and cortisol responses to paroxetine challenge across these three groups. PMDD subjects showed higher serotonergic function in follicular phase but lower serotonergic function in luteal phase, compared with women with PMS without PMDD and normal controls. The present findings suggest that PMDD women have fluctuating serotonergic function across their menstrual cycles and that the pattern may be different from PMS without PMDD.

Evidence for a Dual Antiviral Role of the Major Nuclear Domain 10 Component Sp100 during the Immediate-Early and Late Phases of the Human Cytomegalovirus Replication Cycle ▿

PubMed Central

Tavalai, Nina; Adler, Martina; Scherer, Myriam; Riedl, Yvonne; Stamminger, Thomas

2011-01-01

In recent studies, the nuclear domain 10 (ND10) components PML and hDaxx were identified as cellular restriction factors that inhibit the initiation of human cytomegalovirus (HCMV) replication. The antiviral function of ND10, however, is antagonized by the IE1 protein, which induces ND10 disruption. Here we show that IE1 not only de-SUMOylates PML immediately upon infection but also directly targets Sp100. IE1 expression alone was sufficient to downregulate endogenous Sp100 independently of the presence of PML. Moreover, cotransfection experiments revealed that IE1 negatively interferes with the SUMOylation of all Sp100 isoforms. The modulation of Sp100 at immediate-early (IE) times of infection, indeed, seemed to have an in vivo relevance for HCMV replication, since knockdown of Sp100 resulted in more cells initiating the viral gene expression program. In addition, we observed that Sp100 was degraded in a proteasome-dependent manner at late times postinfection, suggesting that Sp100 may play an additional antiviral role during the late phase. Infection experiments conducted with Sp100 knockdown human foreskin fibroblasts (HFFs) confirmed this hypothesis: depletion of Sp100 resulted in augmented release of progeny virus particles compared to that from control cells. Consistent with this observation, we noted increased amounts of viral late gene products in the absence of Sp100. Importantly, this elevated late gene expression was not dependent on enhanced viral IE gene expression. Taken together, our data provide evidence that Sp100 is the first ND10-related factor identified that not only possesses the potential to restrict the initial stage of infection but also inhibits HCMV replication during the late phase. PMID:21734036

Posttraining transcranial magnetic stimulation of striate cortex disrupts consolidation early in visual skill learning.

PubMed

De Weerd, Peter; Reithler, Joel; van de Ven, Vincent; Been, Marin; Jacobs, Christianne; Sack, Alexander T

2012-02-08

Practice-induced improvements in skilled performance reflect "offline " consolidation processes extending beyond daily training sessions. According to visual learning theories, an early, fast learning phase driven by high-level areas is followed by a late, asymptotic learning phase driven by low-level, retinotopic areas when higher resolution is required. Thus, low-level areas would not contribute to learning and offline consolidation until late learning. Recent studies have challenged this notion, demonstrating modified responses to trained stimuli in primary visual cortex (V1) and offline activity after very limited training. However, the behavioral relevance of modified V1 activity for offline consolidation of visual skill memory in V1 after early training sessions remains unclear. Here, we used neuronavigated transcranial magnetic stimulation (TMS) directed to a trained retinotopic V1 location to test for behaviorally relevant consolidation in human low-level visual cortex. Applying TMS to the trained V1 location within 45 min of the first or second training session strongly interfered with learning, as measured by impaired performance the next day. The interference was conditional on task context and occurred only when training in the location targeted by TMS was followed by training in a second location before TMS. In this condition, high-level areas may become coupled to the second location and uncoupled from the previously trained low-level representation, thereby rendering consolidation vulnerable to interference. Our data show that, during the earliest phases of skill learning in the lowest-level visual areas, a behaviorally relevant form of consolidation exists of which the robustness is controlled by high-level, contextual factors.

Characteristics of time-activity curves obtained from dynamic 11C-methionine PET in common primary brain tumors.

PubMed

Nomura, Yuichi; Asano, Yoshitaka; Shinoda, Jun; Yano, Hirohito; Ikegame, Yuka; Kawasaki, Tomohiro; Nakayama, Noriyuki; Maruyama, Takashi; Muragaki, Yoshihiro; Iwama, Toru

2018-07-01

The aim of this study was to assess whether dynamic PET with 11 C-methionine (MET) (MET-PET) is useful in the diagnosis of brain tumors. One hundred sixty patients with brain tumors (139 gliomas, 9 meningiomas, 4 hemangioblastomas and 8 primary central nervous system lymphomas [PCNSL]) underwent dynamic MET-PET with a 3-dimensional acquisition mode, and the maximum tumor MET-standardized uptake value (MET-SUV) was measured consecutively to construct a time-activity curve (TAC). Furthermore, receiver operating characteristic (ROC) curves were generated from the time-to-peak (TTP) and the slope of the curve in the late phase (SLOPE). The TAC patterns of MET-SUVs (MET-TACs) could be divided into four characteristic types when MET dynamics were analyzed by dividing the MET-TAC into three phases. MET-SUVs were significantly higher in early and late phases in glioblastoma compared to anaplastic astrocytoma, diffuse astrocytoma and the normal frontal cortex (P < 0.05). The SLOPE in the late phase was significantly lower in tumors that included an oligodendroglial component compared to astrocytic tumors (P < 0.001). When we set the cutoff of the SLOPE in the late phase to - 0.04 h -1 for the differentiation of tumors that included an oligodendroglial component from astrocytic tumors, the diagnostic accuracy was 74.2% sensitivity and 64.9% specificity. The area under the ROC curve was 0.731. The results of this study show that quantification of the MET-TAC for each brain tumor identified by a dynamic MET-PET study could be helpful in the non-invasive discrimination of brain tumor subtypes, in particular gliomas.

Cercarial dermatitis caused by bird schistosomes comprises both immediate and late phase cutaneous hypersensitivity reactions.

PubMed

Kourilová, Pavlína; Hogg, Karen G; Kolárová, Libuse; Mountford, Adrian P

2004-03-15

Avian schistosomes are the primary causative agent of cercarial dermatitis in humans, but despite its worldwide occurrence, little is known of the immune mechanism of this disease. Using a murine model, hosts were exposed to primary (1x) and multiple (4x) infections of Trichobilharzia regenti via the pinna. Penetration of larvae into the skin evoked immediate edema, thickening of the exposure site, and an influx of leukocytes, including neutrophils, macrophages, CD4+ lymphocytes, and mast cells. A large proportion of the latter were in the process of degranulating. After 1x infection, inflammation was accompanied by the release of IL-1beta, IL-6, and IL-12p40. In contrast, in 4x reinfected animals the production of histamine, IL-4, and IL-10 was dramatically elevated within 1 h of infection. Analysis of Ag-stimulated lymphocytes from the skin-draining lymph nodes revealed that cells from 1x infected mice produced a mixed Th1/Th2 cytokine response, including abundant IFN-gamma, whereas cells from 4x reinfected mice were Th2 polarized, dominated by IL-4 and IL-5. Serum Abs confirmed this polarization, with elevated levels of IgG1 and IgE after multiple infections. Infection with radiolabeled cercariae revealed that almost 90% of larvae remained in the skin, and the majority died within 8 days after infection, although parasites were cleared more rapidly in 4x reinfected mice. Our results are the first demonstration that cercarial dermatitis, caused by bird schistosomes, is characterized by an early type I hypersensitivity reaction and a late phase of cutaneous inflammation, both associated with a polarized Th2-type acquired immune response.

Oral Glucose Tolerance Test Glucose Peak Time Is Most Predictive of Prediabetes and Hepatic Steatosis in Obese Girls

PubMed Central

Cree-Green, Melanie; Xie, Danielle; Rahat, Haseeb; Garcia-Reyes, Yesenia; Bergman, Bryan C; Scherzinger, Ann; Diniz Behn, Cecilia; Chan, Christine L; Kelsey, Megan M; Pyle, Laura; Nadeau, Kristen J

2018-01-01

Abstract Obese adolescent girls are at increased risk for type 2 diabetes, characterized by defects in insulin secretion and action. We sought to determine if later glucose peak timing (>30 minutes), 1-hour glucose >155 mg/dl, or monophasic pattern of glucose excursion during an oral glucose tolerance test (OGTT) reflect a worse cardiometabolic risk profile. Post-pubertal overweight/obese adolescent girls without diabetes were studied (N = 88; age, 15.2 ± 0.2 years; body mass index percentile, 97.7 ± 0.5). All participants completed an OGTT and body composition measures. Thirty-two girls had a four-phase hyperinsulinemic euglycemic clamp with isotope tracers, vascular imaging, and muscle mitochondrial assessments. Participants were categorized by glucose peak timing (≤30 min = early; >30 min = late), 1-hour glucose concentration (±155 mg/dL) and glucose pattern (monophasic, biphasic). Girls with a late (N = 54) vs earlier peak (n = 34) timing had higher peak glucose (P < 0.001) and insulin (P = 0.023), HbA1c (P = 0.021); prevalence of hepatic steatosis (62% vs 26%; P = 0.003) and lower oral disposition index (P < 0.001) and glucagon-like peptide-1 response (P = 0.037). When classified by 1-hour glucose, group differences were similar to peak timing, but minimal when classified by glucose pattern. In the >155 mg/dL group only, peripheral insulin sensitivity and fasting free fatty acids were worse. A later glucose peak or >155 mg/dL 1-hour glucose predicts metabolic disease risk in obese adolescent girls. This may defect incretin effects and first phase insulin response, and muscle and adipose insulin resistance.

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases

PubMed Central

Rhodes, Lesley E.; Gledhill, Karl; Masoodi, Mojgan; Haylett, Ann K.; Brownrigg, Margaret; Thody, Anthony J.; Tobin, Desmond J.; Nicolaou, Anna

2009-01-01

Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI-MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and leukocyte markers, while quantifying clinical erythema. We show that vasodilatory prostaglandins (PGs) PGE2, PGF2α, and PGE3 accompany the erythema in the first 24–48 h, associated with increased COX-2 expression at 24 h. Novel, potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Sunburn is characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.—Rhodes, L. E., Gledhill, K., Masoodi, M., Haylett, A. K., Brownrigg, M., Thody, A. J., Tobin, D. J., Nicolaou, A. The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases. PMID:19584301

Immuno-histochemical localization of LH-RH during different phases of estrus cycle of rat, with reference to the preoptic and arcuate neurons, and the ependymal cells.

PubMed

Naik, D V

1976-10-06

Immunohistochemical localization of luteinizing hormone-releasing hormone (LH-RH), during different phases of the estrus cycle, in the preoptic, suprachiasmatic and arcuate nuclei, and in the OVLT of rats, with special emphasis on the ependymal cells, was studied by light, fluorescent and electron microscopy, by using rabbit anti serum to synthetic LH-RH. The LH-RH neurons in the above mentioned areas, were very active during late diestrus and early proestrus phases. Specialized ependymal cells bordering the 3rd ventricle also showed varied LH-RH positive reaction during different phases of the estrus cycle. Immunofluorescent studies showed cyclic variations in the LH-RH material in the CSF of the preoptic and infundibular recesses, as well as in the 3rd ventricle near OVLT, in that, it was maximum during late diestrus and early proestrus phases. Immediately after this, the LH-RH late proestrus was reached. We have also observed that during the proestrus phase, as the LH-RH material started declining in the CSF, it had started building up in the specialized ependyma. Estrus, metaestrus and early diestrus phases showed very weak immunofluorescent LH-RH material in the lumen of the infundibular recess and in the specialized ependyma. Our immuno-electron microscopic observations showed pleomorphic LH-RH granules in the specialized ependyma during late kiestrus and proestrus phases. All these observations lead us to believe that LH-RH is not synthesized in the ependymal cells,but is phagocytosed from the CSF of the 3rd ventricle by the specialized ependyma, which transports it to the ME portal system. In males, the fluorescent LH-RH material did not show any noticeable changes. With the present and previous work,it is concluded that the neurons in differentnuclei synthesize LH-RH and transport it to the ME portal system,primarily through the nerve fibers and secondarily by the ventricular route. It is also suggested that the ependymal transport of LH-RH to the ME portal system is cyclic and thus controls the gonadotropin secretion.

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.

The hyper-fluorescent transitional bands in ultra-late phase of indocyanine green angiography in chronic central serous chorioretinopathy.

PubMed

Hua, Rui; Yao, Kai; Xia, Fan; Li, Jun; Guo, Lei; Yang, Guoxing; Tao, Jun

2016-03-01

Chronic central serous chorioretinopathy (CSCR) is regarded as a type of severe diffuse retinal pigment epitheliopathy. There is an atrophic tract at level of retinal pigment epithelium (RPE) due to hyper-permeability of choroidal vessels, along with photoreceptor (PR) atrophy. Indocyanine green angiography (ICGA) is considered a gold standard for diagnosis. The purpose of this work is to investigate the hyper-fluorescent transitional bands (HFTB) between hypo-fluorescent and normal regions of the retina in the ultra-late phase of ICGA in CSCR. 26 chronic CSCR eyes and 12 relative normal eyes received spectral domain optical coherence tomography (SD-OCT), and ICGA at the 24th hour after indocyanine green (ICG) intravenous injection. In the ultra-late phase, images showed homogenous fluorescence in all normal eyes. On the contrary, geographical hypofluorescent lesions with atrophy of RPE was noted in 26 chronic CSCR eyes. Moreover, HFTB with intact RPE and disrupted PR was detected in 20 out of 26 chronic CSCR eyes (76.9%). The HFTB may indicate the early damage in chronic CSCR. Ultra-late ICGA can monitor not only metabolic status by endogenous melanin, but also membrane function in RPE by exogenous ICG molecule. © 2015 Wiley Periodicals, Inc.

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011–2012 season in Spain, among population targeted for vaccination

PubMed Central

2013-01-01

Background In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011–2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. Results The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0–69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions The 2011–2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season. PMID:24053661

Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase

PubMed Central

Carroll, Marilyn E.; Kohl, Emily A.; Johnson, Krista M.; LaNasa, Rachel M.

2013-01-01

Background In previous studies with male and female rhesus monkeys withdrawal of access to oral phencyclidine (PCP) self administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer. Impulsive choice for SACC increased during PCP withdrawal more than females. Objectives The goal of the present study was to examine the effect of PCP (0.25 or 0.5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle. Materials and methods In Component 1 PCP and water were available from 2 drinking spouts for 1.5 h sessions under concurrent FR 16 schedules. In Component 2 a SACC solution was available for 45 min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6 ml) or 6 delayed SACC deliveries, and the delay was increased by 1 sec after a response on the delayed lever and decreased by 1 sec after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP-withdrawal, that occurred during the mid-folllicular phase (Days 7–11) or the late-luteal (Days 24–28) phase of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases. Results PCP deliveries were higher during the luteal vs the follicular phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration. Conclusions PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys. PMID:23344553

Change in the plasmid copy number in acetic acid bacteria in response to growth phase and acetic acid concentration.

PubMed

Akasaka, Naoki; Astuti, Wiwik; Ishii, Yuri; Hidese, Ryota; Sakoda, Hisao; Fujiwara, Shinsuke

2015-06-01

Plasmids pGE1 (2.5 kb), pGE2 (7.2 kb), and pGE3 (5.5 kb) were isolated from Gluconacetobacter europaeus KGMA0119, and sequence analyses revealed they harbored 3, 8, and 4 genes, respectively. Plasmid copy numbers (PCNs) were determined by real-time quantitative PCR at different stages of bacterial growth. When KGMA0119 was cultured in medium containing 0.4% ethanol and 0.5% acetic acid, PCN of pGE1 increased from 7 copies/genome in the logarithmic phase to a maximum of 12 copies/genome at the beginning of the stationary phase, before decreasing to 4 copies/genome in the late stationary phase. PCNs for pGE2 and pGE3 were maintained at 1-3 copies/genome during all phases of growth. Under a higher concentration of ethanol (3.2%) the PCN for pGE1 was slightly lower in all the growth stages, and those of pGE2 and pGE3 were unchanged. In the presence of 1.0% acetic acid, PCNs were higher for pGE1 (10 copies/genome) and pGE3 (6 copies/genome) during the logarithmic phase. Numbers for pGE2 did not change, indicating that pGE1 and pGE3 increase their PCNs in response to acetic acid. Plasmids pBE2 and pBE3 were constructed by ligating linearized pGE2 and pGE3 into pBR322. Both plasmids were replicable in Escherichia coli, Acetobacter pasteurianus and G. europaeus, highlighting their suitability as vectors for acetic acid bacteria. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Effect of sex and ovarian hormones on carotid baroreflex resetting and function during dynamic exercise in humans

PubMed Central

Kim, Areum; Deo, Shekhar H.; Fisher, James P.

2012-01-01

To date, no studies have examined whether there are either sex- or ovarian hormone-related alterations in arterial baroreflex resetting and function during dynamic exercise. Thus we studied 16 young men and 18 young women at rest and during leg cycling at 50% heart rate (HR) reserve. In addition, 10 women were studied at three different phases of the menstrual cycle. Five-second pulses of neck pressure (NP) and neck suction (NS) from +40 to −80 Torr were applied to determine full carotid baroreflex (CBR) stimulus response curves. An upward and rightward resetting of the CBR function curve was observed during exercise in all groups with a similar magnitude of CBR resetting for mean arterial pressure (MAP) and HR between sexes (P > 0.05) and at different phases of the menstrual cycle (P > 0.05). For CBR control of MAP, women exhibited augmented pressor responses to NP at rest and exercise during mid-luteal compared with early and late follicular phases. For CBR control of HR, there was a greater bradycardic response to NS in women across all menstrual cycle phases with the operating point (OP) located further away from centering point (CP) on the CBR-HR curve during rest (OP-CP; in mmHg: −13 ± 3 women vs. −3 ± 3 men; P < 0.05) and exercise (in mmHg: −31 ± 2 women vs. −15 ± 3 men; P < 0.05). Collectively, these findings suggest that sex and fluctuations in ovarian hormones do not influence exercise resetting of the baroreflex. However, women exhibited greater CBR control of HR during exercise, specifically against acute hypertension, an effect that was present throughout the menstrual cycle. PMID:22267388

EEG phase reset due to auditory attention: an inverse time-scale approach.

PubMed

Low, Yin Fen; Strauss, Daniel J

2009-08-01

We propose a novel tool to evaluate the electroencephalograph (EEG) phase reset due to auditory attention by utilizing an inverse analysis of the instantaneous phase for the first time. EEGs were acquired through auditory attention experiments with a maximum entropy stimulation paradigm. We examined single sweeps of auditory late response (ALR) with the complex continuous wavelet transform. The phase in the frequency band that is associated with auditory attention (6-10 Hz, termed as theta-alpha border) was reset to the mean phase of the averaged EEGs. The inverse transform was applied to reconstruct the phase-modified signal. We found significant enhancement of the N100 wave in the reconstructed signal. Analysis of the phase noise shows the effects of phase jittering on the generation of the N100 wave implying that a preferred phase is necessary to generate the event-related potential (ERP). Power spectrum analysis shows a remarkable increase of evoked power but little change of total power after stabilizing the phase of EEGs. Furthermore, by resetting the phase only at the theta border of no attention data to the mean phase of attention data yields a result that resembles attention data. These results show strong connections between EEGs and ERP, in particular, we suggest that the presentation of an auditory stimulus triggers the phase reset process at the theta-alpha border which leads to the emergence of the N100 wave. It is concluded that our study reinforces other studies on the importance of the EEG in ERP genesis.

Neuroimaging Evidence of Cerebellar Involvement in Premenstrual Dysphoric Disorder

PubMed Central

Rapkin, Andrea J.; Berman, Steven M.; Mandelkern, Mark A.; Silverman, Daniel H. S.; Morgan, Melinda; London, Edythe D.

2010-01-01

Background Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic disorder that is characterized by affective symptoms, including irritability, depression, and anxiety which arise in the luteal phase of the menstrual cycle and resolve soon after the onset of menses. Despite a prevalence of up to 8% in women of reproductive age, few studies have investigated the brain mechanisms that underlie this disorder. Methods We used positron emission tomography with [18F] fluorodeoxyglucose and self-report questionnaires to assess cerebral glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison subjects in the follicular and late luteal phases of the menstrual cycle. The primary biological endpoint was incorporated regional cerebral radioactivity (scaled to the global mean) as an index of glucose metabolism. Relationships between regional brain activity and mood ratings were assessed. Blood samples were taken before each session for assay of plasma estradiol and progesterone concentrations. Results There were no group differences in hormone levels in either the follicular or late luteal phase, but the groups differed in the effect of menstrual phase on cerebellar activity. Women with PMDD, but not comparison subjects, showed an increase in cerebellar activity (particularly in the right cerebellar vermis) from the follicular phase to the late luteal phase (p = 0.003). In the PMDD group, this increase in cerebellar activity was correlated with worsening of mood (p = 0.018). Conclusions These findings suggest that the midline cerebellar nuclei, which have been implicated in other mood disorders, also contribute to negative mood in PMDD. PMID:21092938

Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms.

PubMed

Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

2016-06-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors. Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule. High dose of harmaline (15mg/kg, ip) alone caused an early-phase (0-45min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20mg/kg, ip) alone induced biphasic effects, an early-phase (0-45min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15mg/kg) with a subthreshold dose of 5-MeO-DMT (2mg/kg) induced excessive hyperactivities at late phase (45-180min) that could be abolished by either WAY-100635 or MDL-100907. Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms

PubMed Central

Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

2016-01-01

Background 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors. Methods Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule. Results High dose of harmaline (15 mg/kg, ip) alone caused an early-phase (0–45 min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45–180 min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20 mg/kg, ip) alone induced biphasic effects, an early-phase (0–45 min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45–180 min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2–15 mg/kg) with a subthreshold dose of 5-MeO-DMT (2 mg/kg) induced excessive hyperactivities at late phase (45–180 min) that could be abolished by either WAY-100635 or MDL-100907. Conclusions Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors. PMID:26977821

On- and off-response ERGs elicited by sawtooth stimuli in normal subjects and glaucoma patients.

PubMed

Pangeni, Gobinda; Lämmer, Robert; Tornow, Ralf P; Horn, Folkert K; Kremers, Jan

2012-06-01

The aim of this study is to measure the on- and off-responses and their response asymmetries elicited by sawtooth stimuli in normal subjects and glaucoma patients. Furthermore, the correlation between the ERGs and other functional and structural parameters are investigated. Full-field stimuli were produced using a Ganzfeld bowl with Light Emitting Diodes (LEDs) as light sources. On- and off-response ERGs were recorded from 17 healthy subjects, 12 pre-perimetric and 15 perimetric glaucoma patients using 4-Hz luminance rapid-on and rapid-off sawtooth stimuli (white light; mean luminance 55 cd/m(2)) at 100% contrast. The on- and off-responses were added to study response asymmetries. In addition, flash ERGs were elicited by red stimuli (200 cd/m(2)) on a blue background (10 cd/m(2)). The mean deviations (MD) of the visual field defects were obtained by standard automated perimetry. The retinal nerve fibre layer thickness (RNFLT) was measured with Spectral Domain Optical Coherence Tomography (SOCT). We studied the correlation between ERG response amplitudes, visual field mean deviation (MDs) and RNFLT values. The on-responses showed an initial negative (N-on) followed by a positive (P-on), a late positive (LP-on) and a late negative responses (LN-on). The off-responses showed an initial positive (P-off) a late positive (LP-off) and a late negative response (LN-off). The addition of on- and off-responses revealed an initial positive (P-add) and a late negative response (LN-add). The on-response components (N-on, P-on and LN-on) in the glaucoma patients were relatively similar to those of the control subjects. However, the LP-on was significantly elevated (p = 0.03) in perimetric patients. The LP-off was significantly elevated (p < 0.001), and the amplitude of LN-off was significantly reduced in perimetric patients (p = 0.02). The LN-add amplitude was significantly reduced (p < 0.001) and delayed (p = 0.03) in perimetric patients. The amplitudes of the LN-off and LN-add ERG components were significantly correlated with the PhNR in the flash ERG (LN-off: p = 0.01; LN-add: p < 0.001) and with RNFLT (LN-off: p = 0.006; LN-add: p = 0.001). On- and off-response ERGs and their response asymmetries, elicited by sawtooth stimuli, are altered in the glaucoma patients. The late components are affected. Changes in the late negative components are correlated with structural and other functional changes.

Chemistry, Dynamics, and Radiation of Ozone Loss: Airborne Measurements of OH, HO2, NO2, ClO, BrO, IO, ClONO2, BrONO2, ClOOCl, and H2O

NASA Technical Reports Server (NTRS)

Anderson, James G.

2005-01-01

This grant continued the research initially funded under NAG1-01095. This research addresses, through a combination of in situ and remote aircraft-borne instruments, the following scientific questions: Which mechanisms are responsible for the continuing erosion of ozone over midlatitudes of the Northern Hemisphere? Will the rapid loss of ozone over the Arctic in late winter continue to worsen over the next two decades? Are these large losses dynamically coupled to midlatitudes? Which mechanisms dictate the rate of exchange of material between the troposphere and stratosphere? How will these processes change in response to changes in climate? Will regional scale pollution episodes, that are emerging as predictable seasonal events, significantly affect the middle-to-upper troposphere chemical composition. If so, how will these changes alter the chemical composition of the middle world? What changes are predicted for the overworld? Why has the arctic stratosphere become colder in the late winter phase in recent years? Have increases in tropical upper troposphere temperatures increased the temperature gradient such as to change the trajectories of vertically propagating waves, thus reducing the effectiveness of the meridional circulation for transport of heat, momentum and ozone from the tropics to high latitudes?

The Southeast Asian Influenza Clinical Research Network: development and challenges for a new multilateral research endeavor.

PubMed

Higgs, Elizabeth S; Hayden, Frederick G; Chotpitayasunondh, Tawee; Whitworth, Jimmy; Farrar, Jeremy

2008-04-01

The Southeast Asia Influenza Clinical Research Network (SEA ICRN) (www.seaclinicalresearch.org) is a recently developed multilateral, collaborative partnership that aims to advance scientific knowledge and management of human influenza through integrated clinical investigation. The partnership of hospitals and institutions in Indonesia, Thailand, United Kingdom, United States, and Viet Nam was established in late 2005 after agreement on the general principles and mission of the initiative and after securing initial financial support. The establishment of the SEA ICRN was both a response to the re-emergence of the highly pathogenic avian influenza A(H5N1) virus in Southeast Asia in late 2003 and an acknowledgment that clinical trials on emerging infectious diseases require prepared and coordinated research capacity. The objectives of the Network also include building sustainable research capacity in the region, compliance with international standards, and prompt dissemination of information and sharing of samples. The scope of research includes diagnosis, pathogenesis, treatment and prevention of human influenza due to seasonal or novel viruses. The Network has overcome numerous logistical and scientific challenges but has now successfully initiated several clinical trials. The establishment of a clinical research network is a vital part of preparedness and an important element during an initial response phase to a pandemic.

Concurrent chemoradiotherapy with elective lymph node irradiation for esophageal cancer: a systemic review and pooled analysis of the literature.

PubMed

Du, Dexi; Song, Tao; Liang, Xiaodong; Fang, Min; Wu, Shixiu

2017-02-01

Concurrent chemoradiotherapy (CCRT) has been accepted as the standard non-surgical treatment for esophageal cancer. However, no consistent conclusions have been reached whether elective lymph node irradiation (ENI) should be delivered. Therefore, we performed a systematic review and pooled analysis to evaluate the value of CCRT with ENI. A literature search based on PubMed, Embase and Google Scholar was carried out and all of the studies were evaluated carefully regarding with survival outcomes, response rates, patterns of failure rates and acute/late toxicities. Twenty-two studies were identified based on the criteria: median overall survival time was 21.0 months; pooled response rates were 56.8% (CR) and 85.8% (CR+PR), respectively; residual disease rate, local-regional recurrence rate, distant failure rate and both (local-regional recurrence plus distant failure) rate was 28%, 21%, 11%, and 7%, respectively; hematologic toxicities were the most sever acute toxicities and esophagus-related toxicity was the most common radiation-related toxicity both in acute (15.7%) and late (6.2%) phase. In conclusion, ENI is feasible with acceptable toxicities in esophageal carcinoma and the efficacy should be verified in randomized trials. © 2016 International Society for Diseases of the Esophagus.

Metabolic and miRNA Profiling of TMV Infected Plants Reveals Biphasic Temporal Changes

PubMed Central

Bazzini, Ariel A.; Manacorda, Carlos A.; Tohge, Takayuki; Conti, Gabriela; Rodriguez, Maria C.; Nunes-Nesi, Adriano; Villanueva, Sofía; Fernie, Alisdair R.; Carrari, Fernando; Asurmendi, Sebastian

2011-01-01

Plant viral infections induce changes including gene expression and metabolic components. Identification of metabolites and microRNAs (miRNAs) differing in abundance along infection may provide a broad view of the pathways involved in signaling and defense that orchestrate and execute the response in plant-pathogen interactions. We used a systemic approach by applying both liquid and gas chromatography coupled to mass spectrometry to determine the relative level of metabolites across the viral infection, together with a miRs profiling using a micro-array based procedure. Systemic changes in metabolites were characterized by a biphasic response after infection. The first phase, detected at one dpi, evidenced the action of a systemic signal since no virus was detected systemically. Several of the metabolites increased at this stage were hormone-related. miRs profiling after infection also revealed a biphasic alteration, showing miRs alteration at 5 dpi where no virus was detected systemically and a late phase correlating with virus accumulation. Correlation analyses revealed a massive increase in the density of correlation networks after infection indicating a complex reprogramming of the regulatory pathways, either in response to the plant defense mechanism or to the virus infection itself. Our data propose the involvement of a systemic signaling on early miRs alteration. PMID:22174812

Caffeine-enhanced survival of radiation-sensitive, repair-deficient Chinese hamster cells

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

Utsumi, H.; Elkind, M.M.

1983-11-01

A clone of V79 Chinese hamster cells (V79-AL162/S-10) with unique properties has been isolated after a challenge of parental cells (V79-AL162) with 1 mM ouabain. Compared with parental cells, or with other clones isolated after the ouabain challenge, these cells form smaller colonies, are more sensitive to both x rays and fission-spectrum neutrons, and respond atypically to a postirradiation treatment with caffeine. Their enhanced response to x rays results mainly from a large reduction in the shoulder of their survival curve, probably because in late S phase, the most resistant phase in the cell cycle, the survival curve of thesemore » cells has a reduced shoulder width. Caffeine, and to a lesser extent theophylline, added to the colony-forming medium immediately after exposure appreciably increases the width of the shoulder of these sensitive cells, whereas caffeine has the opposite effect on the response of normal V79 cells. Thus the unique response of the V79-AL162/S-10 cells to a radiation posttreatment with caffeine (increased survival) results from a net increase in their ability to repair damage that is otherwise lethal; caffeine treatment ordinarly prevents normal V79 cells from repairing damage that is only potentially lethal.« less

Serum levels of inhibin A and inhibin B in women with normal and abnormal luteal function.

PubMed

Yamoto, M; Imai, M; Otani, H; Nakano, R

1997-05-01

To determine whether serum inhibin A and inhibin B concentrations are lower in patients with luteal dysfunction than in women with normal luteal function. Serum samples were collected from seven healthy women with regular menstrual cycles. Serum samples on days +5 to +9 after the LH surge were collected from patients with luteal dysfunction. The diagnosis of luteal dysfunction was based on a luteal phase duration less than 11 days and a single midluteal progesterone level below 10 ng/mL. Serum levels of inhibin A, inhibin B, progesterone, estradiol (E2), FSH, and LH were measured. The serum inhibin A levels were increased toward the late follicular phase. The levels reached a maximum during the midluteal phase, followed by a fall during the late luteal phase. The serum inhibin B levels were high during the follicular phases and the early luteal phase. The levels decreased during the midluteal and late luteal phases. Serum levels (mean +/- standard error of the mean) of inhibin A in patients with luteal dysfunction were significantly lower than those in women during the midluteal phase (26.2 +/- 2.9 compared to 41.9 +/- 2.8 pg/mL; P < .01) in addition to the expected decrease in serum progesterone levels (6.3 +/- 0.7 compared to 14.7 +/- 1.2 ng/mL; P < .01). Serum inhibin B levels did not differ significantly between normal women and those with luteal dysfunction. There also were no significant differences in the E2, FSH, and LH levels. Levels of inhibin A, but not of inhibin B, may reflect the human luteal function.

Metastable Amyloid Phases and their Conversion to Mature Fibrils

NASA Astrophysics Data System (ADS)

Muschol, Martin; Miti, Tatiana; Mulaj, Mentor; Schmit, Jeremy

Self-assembly of proteins into amyloid fibrils plays a key role in both functional biological responses and pathogenic disorders which include Alzheimer's disease and type II diabetes. Amyloid fibril assembly frequently generates compact oligomeric and curvilinear polymeric intermediates which are implicated to be toxic to cells. Yet, the relation between these early-stage oligomeric aggregates and late-stage rigid fibrils, which are the hallmark structure of amyloid plaques, has remained unclear. Our measurements indicate that lysozyme amyloid oligomers and their curvilinear fibrils only form after crossing a salt and protein concentration dependent threshold. These oligomeric aggregates are structurally distinct from rigid fibrils and are metastable against nucleation and growth of rigid fibrils. Our experimental transition boundaries match well with colloidal model predictions accounting for salt-modulated charge repulsion. We also report our preliminary findings on the mechanism by which these metastable oligomeric phases are converted into stable amyloid fibrils.

Amount of fear extinction changes its underlying mechanisms.

PubMed

An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

2017-07-03

There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.

Evaluation of a compact tinnitus therapy by electrophysiological tinnitus decompensation measures.

PubMed

Low, Yin Fen; Argstatter, Heike; Bolay, Hans Volker; Strauss, Daniel J

2008-01-01

Large-scale neural correlates of the tinnitus decompensation have been identified by using wavelet phase stability criteria of single sweep sequences of auditory late responses (ALRs). Our previous work showed that the synchronization stability in ALR sequences might be used for objective quantification of the tinnitus decompensation and attention which link to Jastreboff tinnitus model. In this study, we intend to provide an objective evaluation for quantifying the effect of music therapy in tinnitus patients. We examined neural correlates of the attentional mechanism in single sweep sequences of ALRs in chronic tinnitus patients who underwent compact therapy course by using the maximum entropy auditory paradigm. Results by our measure showed that the extent of differentiation between attended and unattended conditions improved significantly after the therapy. It is concluded that the wavelet phase synchronization stability of ALRs single sweeps can be used for the objective evaluation of tinnitus therapies, in this case the compact tinnitus music therapy.

Influence of dopaminergic medication on automatic postural responses and balance impairment in Parkinson's disease.

PubMed

Bloem, B R; Beckley, D J; van Dijk, J G; Zwinderman, A H; Remler, M P; Roos, R A

1996-09-01

It is still unclear why balance impairment in Parkinson's disease (PD) often responds insufficiently to dopaminergic medication. We have studied this issue in 23 patients with idiopathic PD and 24 healthy controls. Our specific purposes were (a) to investigate the contribution of abnormal automatic postural responses to balance impairment in PD and (b) to assess the influence of dopaminergic medication on abnormal automatic postural responses and balance impairment. Standing subjects received 4 degrees "toe-up" rotational perturbations of a supporting forceplate. We bilaterally recorded posturally destabilizing medium latency (ML) responses from the stretched gastrocnemius muscles and functionally corrective long latency (LL) responses from the shortened tibialis anterior (TA) muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). All patients were tested in the "off" and "on" phases. All controls were tested and retested after 1 h. During the off phase, we found enlarged ML amplitudes and diminished LL amplitudes in patients, together with a markedly increased posterior displacement of the COG. The abnormal ML and LL responses were partially responsible for the increased body sway in patients because the initial forward (destabilizing) displacement of the CFP was increased, while the subsequent backward displacement of the CFP (a measure of the corrective braking action of LL responses) was delayed. Abnormal late automatic or possibly more voluntary postural corrections also contributed substantially to the increased body sway. During the on phase, ML amplitudes were reduced in patients but remained increased compared with controls. LL amplitudes no longer differed between both groups due to a modest, possibly dopamine-related increase in patients and a simultaneous decrease in controls. The abnormal CFP displacement was only partially improved by dopaminergic medication. The later postural corrections were not improved at all. Consequently, the increased posterior COG displacement was not ameliorated during the on phase. We conclude that (a) a combination of abnormal automatic and perhaps more voluntary postural corrections contributes to increased body sway in PD and (b) dopaminergic medication fails to improve balance impairment in PD because early automatic postural responses are only partially corrected, while later occurring postural corrections are not improved at all. These electrophysiological results support clinical observations and suggest that nondopaminergic lesions play a significant role in the pathophysiology of postural abnormalities in PD.

Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

PubMed Central

Foss, Jason D.; Fink, Gregory D.

2015-01-01

Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

The DNA damage response activates HPV16 late gene expression at the level of RNA processing.

PubMed

Nilsson, Kersti; Wu, Chengjun; Kajitani, Naoko; Yu, Haoran; Tsimtsirakis, Efthymios; Gong, Lijing; Winquist, Ellenor B; Glahder, Jacob; Ekblad, Lars; Wennerberg, Johan; Schwartz, Stefan

2018-06-01

We show that the alkylating cancer drug melphalan activated the DNA damage response and induced human papillomavirus type 16 (HPV16) late gene expression in an ATM- and Chk1/2-dependent manner. Activation of HPV16 late gene expression included inhibition of the HPV16 early polyadenylation signal that resulted in read-through into the late region of HPV16. This was followed by activation of the exclusively late, HPV16 splice sites SD3632 and SA5639 and production of spliced late L1 mRNAs. Altered HPV16 mRNA processing was paralleled by increased association of phosphorylated BRCA1, BARD1, BCLAF1 and TRAP150 with HPV16 DNA, and increased association of RNA processing factors U2AF65 and hnRNP C with HPV16 mRNAs. These RNA processing factors inhibited HPV16 early polyadenylation and enhanced HPV16 late mRNA splicing, thereby activating HPV16 late gene expression.

The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial

PubMed Central

2012-01-01

Background Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted. Methods/Design A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain. Current status A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014. Discussion This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke. Trial registration Clinical Trials.gov Identifier: NCT01372059 PMID:23171380

Inducible nitric oxide synthase during the late phase of sepsis is associated with hypothermia and immune cell migration.

PubMed

Takatani, Yudai; Ono, Kenji; Suzuki, Hiromi; Inaba, Masato; Sawada, Makoto; Matsuda, Naoyuki

2018-02-14

Hypothermia is a significant sign of sepsis, which is associated with poor prognosis, but few mechanisms underlying the regulation of hypothermia are known. Inducible nitric oxide synthase (iNOS) is a key inflammatory mediator of sepsis. However, the therapeutic benefit of iNOS inhibition in sepsis is still controversial, and requires elucidation in an accurate model system. In this study, wild-type (WT) mice showed temperature drops in a biphasic manner at the early and late phase of sepsis, and all mice died within 48 h of sepsis. In contrast, iNOS-knockout (KO) mice never showed the second temperature drop and exhibited improved mortality. Plasma nitric oxide (NO) levels of WT mice increased in the late phase of sepsis and correlated to hypothermia. The results indicate that iNOS-derived NO during the late phase of sepsis caused vasodilation-induced hypothermia and a lethal hypodynamic state. The expression of the iNOS mRNA was high in the lung of WT mice with sepsis, which reflects the pathology of acute respiratory distress syndrome (ARDS). We obtained the results in a modified keyhole-type cecal ligation and puncture model of septic shock induced by minimally invasive surgery. In this accurate and reproducible model system, we transplanted the bone marrow cells of GFP transgenic mice into WT and iNOS-KO mice, and evaluated the role of increased pulmonary iNOS expression in cell migration during the late phase of sepsis. We also investigated the quantity and type of bone marrow-derived cells (BMDCs) in the lung. The number of BMDCs in the lung of iNOS-KO mice was less than that in the lung of WT mice. The major BMDCs populations were CD11b-positive, iNOS-negative cells in WT mice, and Gr-1-positive cells in iNOS-KO mice that expressed iNOS. These results suggest that sustained hypothermia may be a beneficial guide for future iNOS-targeted therapy of sepsis, and that iNOS modulated the migratory efficiency and cell type of BMDCs in septic ARDS.

The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial.

PubMed

Bunketorp Käll, Lina; Lundgren-Nilsson, Åsa; Blomstrand, Christian; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

2012-11-21

Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted. A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain. A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014. This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke. Clinical Trials.gov Identifier: NCT01372059.

The murine polyomavirus microRNA locus is required to promote viruria during the acute phase of infection.

PubMed

Burke, James M; Bass, Clovis R; Kincaid, Rodney P; Ulug, Emin T; Sullivan, Christopher S

2018-06-06

Polyomaviruses (PyVs) can cause serious disease in immunosuppressed hosts. Several pathogenic PyVs encode microRNAs (miRNAs), small RNAs that regulate gene expression via RNA silencing. Despite recent advances in understanding the activities of PyV miRNAs, the biological functions of PyV miRNAs during in vivo infections are mostly unknown. Studies presented here use murine polyomavirus (MuPyV) as a model to assess the roles of the PyV miRNAs in a natural host. This analysis reveals that a MuPyV mutant that is unable to express miRNAs has enhanced viral DNA loads in select tissues at late times after infection. This is consistent with the PyV miRNAs functioning to reduce viral replication during the persistent phase of infection in a natural host. Additionally, the MuPyV miRNA locus promotes viruria during the acute phase of infection as evidenced by a defect in shedding during infection with the miRNA mutant virus. The viruria defect of the miRNA mutant virus could be rescued by infecting Rag2-/- mice. These findings implicate the miRNA locus as functioning in both the persistent and acute phases of infection and suggest a role for MuPyV miRNA in evading the adaptive immune response. IMPORTANCE MicroRNAs are expressed by diverse viruses, but for only a few is there any understanding of their in vivo function. PyVs can cause serious disease in immunocompromised hosts. Therefore, increased knowledge of how these viruses interact with the immune response is of clinical relevance. Here we show a novel activity for a viral miRNA locus in promoting virus shedding. This work indicates that in addition to any role for the PyV miRNA locus in long-term persistence, that it also has biological activity during the acute phase. As this mutant phenotype is alleviated by infection of mice lacking an adaptive immune response, our work also connects the in vivo activity of the PyV miRNA locus to the immune response. Given that PyV-associated disease is associated with alterations in the immune response, our findings help to better understand how the balance between PyVs and the immune response becomes altered in pathogenic states. Copyright © 2018 American Society for Microbiology.

Neural Correlates of Task Cost for Stance Control with an Additional Motor Task: Phase-Locked Electroencephalogram Responses

PubMed Central

Hwang, Ing-Shiou; Huang, Cheng-Ya

2016-01-01

With appropriate reallocation of central resources, the ability to maintain an erect posture is not necessarily degraded by a concurrent motor task. This study investigated the neural control of a particular postural-suprapostural procedure involving brain mechanisms to solve crosstalk between posture and motor subtasks. Participants completed a single posture task and a dual-task while concurrently conducting force-matching and maintaining a tilted stabilometer stance at a target angle. Stabilometer movements and event-related potentials (ERPs) were recorded. The added force-matching task increased the irregularity of postural response rather than the size of postural response prior to force-matching. In addition, the added force-matching task during stabilometer stance led to marked topographic ERP modulation, with greater P2 positivity in the frontal and sensorimotor-parietal areas of the N1-P2 transitional phase and in the sensorimotor-parietal area of the late P2 phase. The time-frequency distribution of the ERP primary principal component revealed that the dual-task condition manifested more pronounced delta (1–4 Hz) and beta (13–35 Hz) synchronizations but suppressed theta activity (4–8 Hz) before force-matching. The dual-task condition also manifested coherent fronto-parietal delta activity in the P2 period. In addition to a decrease in postural regularity, this study reveals spatio-temporal and temporal-spectral reorganizations of ERPs in the fronto-sensorimotor-parietal network due to the added suprapostural motor task. For a particular set of postural-suprapostural task, the behavior and neural data suggest a facilitatory role of autonomous postural response and central resource expansion with increasing interregional interactions for task-shift and planning the motor-suprapostural task. PMID:27010634

Validation of Rapid Radiochemical Method for Californium ...

EPA Pesticide Factsheets

Technical Brief In the event of a radiological/nuclear contamination event, the response community would need tools and methodologies to rapidly assess the nature and the extent of contamination. To characterize a radiologically contaminated outdoor area and to inform risk assessment, large numbers of environmental samples would be collected and analyzed over a short period of time. To address the challenge of quickly providing analytical results to the field, the U.S. EPA developed a robust analytical method. This method allows response officials to characterize contaminated areas and to assess the effectiveness of remediation efforts, both rapidly and accurately, in the intermediate and late phases of environmental cleanup. Improvement in sample processing and analysis leads to increased laboratory capacity to handle the analysis of a large number of samples following the intentional or unintentional release of a radiological/nuclear contaminant.

Early- and Late-Onset Depression in Late Life: A Prospective Study on Clinical and Structural Brain Characteristics and Response to Electroconvulsive Therapy.

PubMed

Dols, Annemiek; Bouckaert, Filip; Sienaert, Pascal; Rhebergen, Didi; Vansteelandt, Kristof; Ten Kate, Mara; de Winter, Francois-Laurent; Comijs, Hannie C; Emsell, Louise; Oudega, Mardien L; van Exel, Eric; Schouws, Sigfried; Obbels, Jasmien; Wattjes, Mike; Barkhof, Frederik; Eikelenboom, Piet; Vandenbulcke, Mathieu; Stek, Max L

2017-02-01

The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset <55 and ≥55 years). Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT-treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study. Clinical profile and somatic health were assessed. Magnetic resonance imaging (MRI) scans were performed before the first ECT and visually rated. Response rate was 78.2% and similar between the two sites but significantly higher in LOD compared with EOD (86.9 versus 67.3%). Clinical, somatic, and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

[Disturbed respiratory cycle accompanying hypoxic-ischemic encephalopathy].

PubMed

Saito, Yoshiaki; Masuko, Kaori; Kaneko, Kaori; Saito, Kazuyo; Chikumaru, Yuri; Iwamoto, Hiroko; Matsui, Akira; Kimura, Seiji

2005-09-01

We report the case of a 2-year-old boy who experienced total asphyxia at 4 months of age, and suffered abnormalities at specific phases of the respiratory cycle. The patient was bedridden due to severe tetraplegia and showed little response to external stimuli. He has been tube-fed since the initial asphyxia and a tracheotomy was performed after recurrent hypoxic episodes as a result of the respiratory dysfunction. Upon examination, his respiratory pattern was characterized by arrest during the inspiratory phase with a possible over-riding secondary inspiration. The respiratory pause at the inspiratory phase was markedly prolonged during an episode of pulmonary infection, resulting in recurrent cyanosis that necessitated artificial ventilation. The "second" inspiration typically occurred during the mid- or late-inspiratory phases, with this pattern often shown to be variable after epileptic seizures. The characteristic breathing of this patient suggested that difficulty in forming a normal respiratory cycle, other than during periods of hypoventilation or apnoea, could be a significant respiratory dysfunction following asphyxiation. Strategies for the management of such patients should be carefully designed after close observation of breathing patterns within the respiratory cycle, and with consideration for the influence of epileptic seizures and other inputs from somatic afferents.

Synthesis of Pt 3Y and Other Early–Late Intermetallic Nanoparticles by Way of a Molten Reducing Agent

DOE PAGES

Kanady, Jacob S.; Leidinger, Peter; Haas, Andreas; ...

2017-03-29

Early–late intermetallic phases have garnered increased attention recently for their catalytic properties. To achieve the high surface areas needed for industrially relevant applications, these phases must be synthesized as nanoparticles in a scalable fashion. Herein, Pt 3Y—targeted as a prototypical example of an early–late intermetallic—has been synthesized as nanoparticles approximately 5–20 nm in diameter via a solution process and characterized by XRD, TEM, EDS, and XPS. The key development is the use of a molten borohydride (MEt 3BH, M = Na, K) as both the reducing agent and reaction medium. Readily available halide precursors of the two metals are used.more » Accordingly, no organic ligands are necessary, as the resulting halide salt byproduct prevents sintering, which further permits dispersion of the nanoscale intermetallic onto a support. The versatility of this approach was validated by the synthesis of other intermetallic phases such as Pt 3Sc, Pt 3Lu, Pt 2Na, and Au 2Y.« less

Synthesis of Pt 3Y and Other Early–Late Intermetallic Nanoparticles by Way of a Molten Reducing Agent

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

Kanady, Jacob S.; Leidinger, Peter; Haas, Andreas

Early–late intermetallic phases have garnered increased attention recently for their catalytic properties. To achieve the high surface areas needed for industrially relevant applications, these phases must be synthesized as nanoparticles in a scalable fashion. Herein, Pt 3Y—targeted as a prototypical example of an early–late intermetallic—has been synthesized as nanoparticles approximately 5–20 nm in diameter via a solution process and characterized by XRD, TEM, EDS, and XPS. The key development is the use of a molten borohydride (MEt 3BH, M = Na, K) as both the reducing agent and reaction medium. Readily available halide precursors of the two metals are used.more » Accordingly, no organic ligands are necessary, as the resulting halide salt byproduct prevents sintering, which further permits dispersion of the nanoscale intermetallic onto a support. The versatility of this approach was validated by the synthesis of other intermetallic phases such as Pt 3Sc, Pt 3Lu, Pt 2Na, and Au 2Y.« less

Relative role of pre-monsoon conditions and intraseasonal oscillations in determining early-vs-late indian monsoon intensity in a GCM

NASA Astrophysics Data System (ADS)

Ghosh, Rohit; Chakraborty, Arindam; Nanjundiah, Ravi S.

2018-01-01

The aim of this paper is to identify relative roles of different land-atmospheric conditions, apart from sea surface temperature (SST), in determining early vs. late summer monsoon intensity over India in a high resolution general circulation model (GCM). We find that in its early phase (June-July; JJ), pre-monsoon land-atmospheric processes play major role to modulate the precipitation over Indian region. These effects of pre-monsoon conditions decrease substantially during its later phase (August-September; AS) for which the interannual variation is mainly governed by the low frequency northward propagating intraseasonal oscillations. This intraseasonal variability which is related to mean vertical wind shear has a significant role during the early phase of monsoon as well. Further, using multiple linear regression, we show that interannual variation of early and late monsoon rainfall over India is best explained when all these land-atmospheric parameters are taken together. Our study delineates the relative role of different processes affecting early versus later summer monsoon rainfall over India that can be used for determining its subseasonal predictability.

σK of Clostridium acetobutylicum Is the First Known Sporulation-Specific Sigma Factor with Two Developmentally Separated Roles, One Early and One Late in Sporulation

PubMed Central

Al-Hinai, Mohab A.; Jones, Shawn W.

2014-01-01

Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σH (early), σF, σE, σG, and σK (late). Here we show that the Clostridium acetobutylicum σK acts both early, prior to Spo0A expression, and late, past σG activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σG proteins were not detectable by Western analysis, while σF protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σK is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σF, σE, and σG, but not sporulation, which was blocked past the σG stage of development, thus demonstrating that σK is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles. PMID:24187083

σK of Clostridium acetobutylicum is the first known sporulation-specific sigma factor with two developmentally separated roles, one early and one late in sporulation.

PubMed

Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T

2014-01-01

Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σ(H) (early), σ(F), σ(E), σ(G), and σ(K) (late). Here we show that the Clostridium acetobutylicum σ(K) acts both early, prior to Spo0A expression, and late, past σ(G) activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σ(G) proteins were not detectable by Western analysis, while σ(F) protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σ(K) is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σ(F), σ(E), and σ(G), but not sporulation, which was blocked past the σ(G) stage of development, thus demonstrating that σ(K) is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles.

Birth timing and behavioral responsiveness predict individual differences in the mother-infant relationship and infant behavior during weaning and maternal breeding

PubMed Central

Vandeleest, Jessica J.; Capitanio, John P.

2012-01-01

There is a great deal of variability in mother-infant interactions and infant behavior across the first year of life in rhesus monkeys. The current paper has two specific aims: 1) to determine if birth timing predicts variability in the mother-infant relationship and infant behavior during weaning and maternal breeding, and 2) to identify predictors of infant behavior during a period of acute challenge, maternal breeding. Forty-one mother-infant pairs were observed during weaning when infants were 4.5 months old, and 33 were followed through maternal breeding. Subjective ratings of 16 adjectives reflecting qualities of maternal attitude, mother-infant interactions, and infant attitude were factor analyzed to construct factors relating to the mother-infant relationship (Relaxed and Aggressive), and infant behavior (Positive Engagement and Distress). During weaning, late born infants were more Positively Engaged than peak born infants (ANOVA, P < 0.05); however, birth timing did not affect the mother-infant relationship factors Relaxed and Aggressive or the infant attitude factor Distress. During maternal breeding early born infants had less Relaxed relationships with their mothers than peak or late born infants, higher Positive Engagement scores than peak or late born infants, and tended to have higher Distress scores than peak born infants (Repeated-measures ANOVA, P < 0.05). In addition, Distress scores were higher during maternal breeding than during the pre- and post-breeding phases. Finally, multiple regression (P < 0.05) indicated that while infant behavioral responsiveness predicted infant Positive Engagement during the acute challenge of maternal breeding, qualities of the mother-infant relationship predicted infant Distress. These data suggest that birth timing influences the patterns of mother-infant interactions during weaning and maternal breeding. Additionally, infant behavioral responsiveness and mother-infant relationship quality impact infant social engagement and affect expression, respectively. PMID:24436198

Sex Differences in Stress Response Circuitry Activation Dependent on Female Hormonal Cycle

PubMed Central

Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

2010-01-01

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this fMRI study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right-handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry (amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal and medial prefrontal cortices (OFC and mPFC), and anterior cingulate gyrus (ACG). Women were scanned twice based on normal variation in menstrual cycle hormones (i.e., early follicular (EF) compared with late follicular-midcycle menstrual phases (LF/MC)). Using SPM8b, there were few significant differences in BOLD signal changes in men compared to EF women, except ventromedial (VMN) and lateral (LHA) hypothalamus, left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males. PMID:20071507

The CD3-Zeta Chimeric Antigen Receptor Overcomes TCR Hypo-Responsiveness of Human Terminal Late-Stage T Cells

PubMed Central

Awerkiew, Sabine; Schmidt, Annette; Hombach, Andreas A.; Pfister, Herbert; Abken, Hinrich

2012-01-01

Adoptive therapy of malignant diseases with tumor-specific cytotoxic T cells showed remarkable efficacy in recent trials. Repetitive T cell receptor (TCR) engagement of target antigen, however, inevitably ends up in hypo-responsive cells with terminally differentiated KLRG-1+ CD57+ CD7− phenotype limiting their therapeutic efficacy. We here revealed that hypo-responsiveness of CMV-specific late-stage CD8+ T cells is due to reduced TCR synapse formation compared to younger cells. Membrane anchoring of TCR components contributes to T cell hypo-responsiveness since dislocation of galectin-3 from the synapse by swainsonine restored both TCR synapse formation and T cell response. Transgenic expression of a CD3-zeta signaling chimeric antigen receptor (CAR) recovered hypo-responsive T cells to full effector functions indicating that the defect is restricted to TCR membrane components while synapse formation of the transgenic CAR was not blocked. CAR engineered late-stage T cells released cytokines and mediated redirected cytotoxicity as efficiently as younger effector T cells. Our data provide a rationale for TCR independent, CAR mediated activation in the adoptive cell therapy to avoid hypo-responsiveness of late-stage T cells upon repetitive antigen encounter. PMID:22292024

Non-chemosensitive parafacial neurons simultaneously regulate active expiration and airway patency under hypercapnia in rats.

PubMed

de Britto, Alan A; Moraes, Davi J A

2017-03-15

Hypercapnia or parafacial respiratory group (pFRG) disinhibition at normocapnia evokes active expiration in rats by recruitment of pFRG late-expiratory (late-E) neurons. We show that hypercapnia simultaneously evoked active expiration and exaggerated glottal dilatation by late-E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic expiratory activity in previously silent pFRG late-E neurons, which did not express the marker of ventral medullary CO 2 -sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. Hypercapnia-evoked active expiration, neural and neuronal late-E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. Hypercapnia produces disinhibition of non-chemosensitive pFRG late-E neurons to evoke active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency. Hypercapnia produces active expiration in rats and the recruitment of late-expiratory (late-E) neurons located in the parafacial respiratory group (pFRG) of the ventral medullary brainstem. We tested the hypothesis that hypercapnia produces active expiration and concomitant cranial respiratory motor responses controlling the oropharyngeal and upper airway patency by disinhibition of pFRG late-E neurons, but not via synaptic excitation. Phrenic nerve, abdominal nerve (AbN), cranial respiratory motor nerves, subglottal pressure, and medullary and spinal neurons/motoneurons were recorded in in situ preparations of juvenile rats. Hypercapnia evoked AbN active expiration, exaggerated late-E discharges in cranial respiratory motor outflows, and glottal dilatation via late-E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic late-E activity in previously silent pFRG neurons, which did not express the marker of ventral medullary CO 2 -sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. In addition, hypercapnia-evoked AbN active expiration, neural and neuronal late-E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. On the other hand, pFRG inhibition did not affect either hypercapnia-induced inspiratory increases in respiratory motor outflows or CO 2 sensitivity of the more medial Phox2b-positive neurons in the retrotrapezoid nucleus (RTN). Our data suggest that neither RTN Phox2b-positive nor other CO 2 -sensitive brainstem neurons activate Phox2b-negative pFRG late-E neurons under hypercapnia to produce AbN active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency. Hypercapnia produces disinhibition of non-chemosensitive pFRG late-E neurons in in situ preparations of juvenile rats to activate abdominal, hypoglossal and laryngeal motoneurons. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

AMPK is activated early in cerebellar granule cells undergoing apoptosis and influences VADC1 phosphorylation status and activity.

PubMed

Bobba, A; Casalino, E; Amadoro, G; Petragallo, V A; Atlante, A

2017-09-01

The neurodegeneration of cerebellar granule cells, after low potassium induced apoptosis, is known to be temporally divided into an early and a late phase. Voltage-dependent anion channel-1 (VDAC1) protein, changing from the closed inactive state to the active open state, is central to the switch between the early and late phase. It is also known that: (i) VDAC1 can undergo phosphorylation events and (ii) AMP-activated protein kinase (AMPK), the sensor of cellular stress, may have a role in neuronal homeostasis. In the view of this, the involvement of AMPK activation and its correlation with VDAC1 status and activity has been investigated in the course of cerebellar granule cells apoptosis. The results reported in this study show that an increased level of the phosphorylated, active, isoform of AMPK occurs in the early phase, peaks at 3 h and guarantees an increase in the phosphorylation status of VDCA1, resulting in a reduced activity of this latter. However this situation is transient in nature, since, in the late phase, AMPK activation decreases as well as the level of phosphorylated VDAC1. In a less phosphorylated status, VDAC1 fully recovers its gating activity and drives cells along the death route.

Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

PubMed

Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

2018-03-01

Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication. IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly associated with the replicating single-stranded DNA viral genome and played a critical role in viral DNA replication. In contrast, the DNA damage response-induced phosphorylated forms of RPA32 were dispensable for viral DNA replication. Copyright © 2018 American Society for Microbiology.

Machine learning approaches for integrating clinical and imaging features in late-life depression classification and response prediction.

PubMed

Patel, Meenal J; Andreescu, Carmen; Price, Julie C; Edelman, Kathryn L; Reynolds, Charles F; Aizenstein, Howard J

2015-10-01

Currently, depression diagnosis relies primarily on behavioral symptoms and signs, and treatment is guided by trial and error instead of evaluating associated underlying brain characteristics. Unlike past studies, we attempted to estimate accurate prediction models for late-life depression diagnosis and treatment response using multiple machine learning methods with inputs of multi-modal imaging and non-imaging whole brain and network-based features. Late-life depression patients (medicated post-recruitment) (n = 33) and older non-depressed individuals (n = 35) were recruited. Their demographics and cognitive ability scores were recorded, and brain characteristics were acquired using multi-modal magnetic resonance imaging pretreatment. Linear and nonlinear learning methods were tested for estimating accurate prediction models. A learning method called alternating decision trees estimated the most accurate prediction models for late-life depression diagnosis (87.27% accuracy) and treatment response (89.47% accuracy). The diagnosis model included measures of age, Mini-mental state examination score, and structural imaging (e.g. whole brain atrophy and global white mater hyperintensity burden). The treatment response model included measures of structural and functional connectivity. Combinations of multi-modal imaging and/or non-imaging measures may help better predict late-life depression diagnosis and treatment response. As a preliminary observation, we speculate that the results may also suggest that different underlying brain characteristics defined by multi-modal imaging measures-rather than region-based differences-are associated with depression versus depression recovery because to our knowledge this is the first depression study to accurately predict both using the same approach. These findings may help better understand late-life depression and identify preliminary steps toward personalized late-life depression treatment. Copyright © 2015 John Wiley & Sons, Ltd.

Late response to patient-reported outcome questionnaires after surgery was associated with worse outcome.

PubMed

Hutchings, Andrew; Grosse Frie, Kirstin; Neuburger, Jenny; van der Meulen, Jan; Black, Nick

2013-02-01

Nonresponse to patient-reported outcome (PRO) questionnaires after surgery might bias the results. Our aim was to gauge the potential impact of nonresponse bias by comparing the outcomes of early and late responders. This study compares 59,565 early and 20,735 late responders who underwent a hip or knee replacement, hernia repair, or varicose vein (VV) surgery. The association between timeliness of response and three outcomes (the mean postoperative disease-specific PRO and generic PRO scores and the proportion reporting a fair or poor result) was examined by regression analysis. Late responders were slightly more likely to be young, nonwhite, deprived, and have a more severe preoperative condition with poorer quality of life. Late response was associated with a slightly poorer outcome in all four procedures although not statistically significant (P < 0.05) for VV surgery. Adjusting for preoperative characteristics reduced the strength of the associations, but they remained statistically significant. As nonresponse to PRO questionnaires introduces slight bias, differences in response rates between hospitals should be taken into account when making comparisons so as to avoid overestimating the performance of those with lower response rates and failing to detect poor performing hospitals. Copyright © 2013 Elsevier Inc. All rights reserved.

Variation in responses of late-seral herbs to disturbance and environmental stress.

Treesearch

Cara R. Nelson; Charles B. Halpern; Joseph A. Antos

2007-01-01

Clonal herbs that attain maximum development in late-seral forest are often assumed to have similar responses to disturbance and to be functionally equivalent. However, little is known about the demographic or physiological responses of these plants to disturbance or to the altered conditions of the post-disturbance environment. Following harvest of a mature coniferous...

Endogenous inhibition of pain and spinal nociception in women with premenstrual dysphoric disorder

PubMed Central

Palit, Shreela; Bartley, Emily J; Kuhn, Bethany L; Kerr, Kara L; DelVentura, Jennifer L; Terry, Ellen L; Rhudy, Jamie L

2016-01-01

Purpose Premenstrual dysphoric disorder (PMDD) is characterized by severe affective and physical symptoms, such as increased pain, during the late-luteal phase of the menstrual cycle. The mechanisms underlying hyperalgesia in women with PMDD have yet to be identified, and supraspinal pain modulation has yet to be examined in this population. The present study assessed endogenous pain inhibitory processing by examining conditioned pain modulation (CPM, a painful conditioning stimulus inhibiting pain evoked by a test stimulus at a distal body site) of pain and the nociceptive flexion reflex (NFR, a spinally-mediated withdrawal reflex) during the mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle. Methods Participants were regularly-cycling women (14 without PMDD; 14 with PMDD). CPM was assessed by delivering electrocutaneous test stimuli to the sural nerve before, during, and after a painful conditioning ischemia task. Participants rated their pain to electrocutaneous stimuli, and NFR magnitudes were measured. A linear mixed model analysis was used to assess the influence of group and menstrual phase on CPM. Results Compared with controls, women with PMDD experienced greater pain during the late-luteal phase and enhanced spinal nociception during the ovulation phase, both of which were independent of CPM. Both groups showed CPM inhibition of pain that did not differ by menstrual phase. Only women with PMDD evidenced CPM inhibition of NFR. Conclusion Endogenous modulation of pain and spinal nociception is not disrupted in women with PMDD. Additionally, greater NFR magnitudes during ovulation in PMDD may be due to tonically-engaged descending mechanisms that facilitate spinal nociception, leading to enhanced pain during the premenstrual phase. PMID:26929663

Role of asymmetric meridional circulation in producing north-south asymmetry in a solar cycle dynamo model

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

Belucz, Bernadett; Dikpati, Mausumi

2013-12-10

Solar cycles in the north and south hemispheres differ in cycle length, amplitude, profile, polar fields, and coronal structure. To show what role differences in meridional flow could play in producing these differences, we present the results of three sets of numerical simulations from a flux transport dynamo in which one property of meridional circulation has been changed in the south only. The changes are in amplitude and the presence of a second cell in latitude or in depth. An ascending phase speedup causes weakening of polar and toroidal fields; a speed decrease in a late descending phase does notmore » change amplitudes. A long-duration speed increase leads to lower toroidal field peaks but unchanged polar field peaks. A second high-latitude circulation cell in an ascending phase weakens the next polar and toroidal field peaks, and the ascending phase is lengthened. A second cell in a late descending phase speeds up the cycle. A long-duration second cell leads to a poleward branch of the butterfly diagram and weaker polar fields. A second cell in depth reverses the tilt of the butterfly wing, decreasing polar fields when added during an ascending phase and increasing them during a late descending phase. A long-duration presence of a second cell in radius evolves the butterfly diagram far away from the observed one, with different dynamo periods in low and high latitudes. Thus, a second cell in depth is unlikely to persist more than a few years if the solar dynamo is advection-dominated. Our results show the importance of time variation and north-south asymmetry in meridional circulation in producing differing cycles in the north and south.« less

Synaptic Tagging, Evaluation of Memories, and the Distal Reward Problem

ERIC Educational Resources Information Center

Papper, Marc; Kempter, Richard; Leibold, Christian

2011-01-01

Long-term synaptic plasticity exhibits distinct phases. The synaptic tagging hypothesis suggests an early phase in which synapses are prepared, or "tagged," for protein capture, and a late phase in which those proteins are integrated into the synapses to achieve memory consolidation. The synapse specificity of the tags is consistent with…

7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

PubMed

van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

2015-01-01

The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Bacteriophage T4 Infection of Stationary Phase E. coli: Life after Log from a Phage Perspective

PubMed Central

Bryan, Daniel; El-Shibiny, Ayman; Hobbs, Zack; Porter, Jillian; Kutter, Elizabeth M.

2016-01-01

Virtually all studies of phage infections investigate bacteria growing exponentially in rich media. In nature, however, phages largely encounter non-growing cells. Bacteria entering stationary phase often activate well-studied stress defense mechanisms that drastically alter the cell, facilitating its long-term survival. An understanding of phage-host interactions in such conditions is of major importance from both an ecological and therapeutic standpoint. Here, we show that bacteriophage T4 can efficiently bind to, infect and kill E. coli in stationary phase, both in the presence and absence of a functional stationary-phase sigma factor, and explore the response of T4-infected stationary phase cells to the addition of fresh nutrients 5 or 24 h after that infection. An unexpected new mode of response has been identified. “Hibernation” mode is a persistent but reversible dormant state in which the infected cells make at least some phage enzymes, but halt phage development until appropriate nutrients become available before producing phage particles. Our evidence indicates that the block in hibernation mode occurs after the middle-mode stage of phage development; host DNA breakdown and the incorporation of the released nucleotides into phage DNA indicate that the enzymes of the nucleotide synthesizing complex, under middle-mode control, have been made and assembled into a functional state. Once fresh glucose and amino acids become available, the standard lytic infection process rapidly resumes and concentrations of up to 1011 progeny phage (an average of about 40 phage per initially present cell) are produced. All evidence is consistent with the hibernation-mode control point lying between middle mode and late mode T4 gene expression. We have also observed a “scavenger” response, where the infecting phage takes advantage of whatever few nutrients are available to produce small quantities of progeny within 2 to 5 h after infection. The scavenger response seems able to produce no more than an average of one phage per originally available cell, and few if any further progeny are produced by cells in this mode even if fresh nutrients are made available later. PMID:27660625

Late Paleozoic closure of the Ob-Zaisan Ocean along the Irtysh/Chara shear zone and implications for arc amalgamation and oroclinal bending in the western Central Asian Orogenic Belt

NASA Astrophysics Data System (ADS)

Li, Pengfei; Sun, Min; Rosenbaum, Gideon

2016-04-01

The Irtysh/Chara Shear Zone is one of the largest strike-slip systems in the Central Asian Orogenic Belt (CAOB). It records collisional processes of the peri-Siberian orogenic system with the West Junggar-Kazakhstan-Tianshan orogenic system following the closure of the Ob-Zaisan Ocean, but the exact timing of these events remains enigmatic. We conducted detailed structural analysis along the Irtysh Shear Zone (NW China), which together with new geochronological data allows us to reconstruct the tectonic evolution during the final closure of the Ob-Zaisan Ocean. Our results showed that subduction-accretion processes lasted at least until the Late Carboniferous in the Chinese Altai and the East/West Junggar. The subsequent arc amalgamation is characterized by a cycle of crustal thickening, orogenic collapse and transpressional thickening. On a larger scale, the West Junggar- Kazakhstan -Tianshan orogenic system defines a U-shape oroclinal structure (e.g. Xiao et al., 2010). A major phase of oroclinal bending that involved ~110° rotation may have occurred during the Late Devonian to Early Carboniferous (Levashova et al., 2012). Previous authors have linked oroclinal bending with the late Paleozoic amalgamation of the western CAOB, and proposed that a quasi-linear West Junggar- Kazakhstan -Tianshan orogenic system was buckled during the convergence of the Siberian and Tarim cratons following the closure of the Ob-Zaisan Ocean (in the north) and the South Tianshan Ocean (in the south) (e.g. Abrajevitch et al., 2008). This model, however, is not supported by our new data that constrain the closure of the Ob-Zaisan Ocean to the Late Carboniferous. Alternatively, we propose that oroclinal bending may have involved two phases of bending, with the ~110° rotation in the Late Devonian to Early Carboniferous possibly associated with trench retreat. Further tightening may have occurred in response to the convergence of the Siberian and Tarim cratons during the Late Carboniferous to Permian. References: Abrajevitch, A., Van der Voo, R., Bazhenov, M.L., Levashova, N.M., McCausland, P.J.A., 2008. The role of the Kazakhstan orocline in the late Paleozoic amalgamation of Eurasia. Tectonophysics 455, 61-76. Levashova, N., Degtyarev, K., Bazhenov, M., 2012. Oroclinal bending of the Middle and Late Paleozoic volcanic belts in Kazakhstan: Paleomagnetic evidence and geological implications. Geotectonics 46, 285-302. Xiao, W., Huang, B., Han, C., Sun, S., Li, J., 2010. A review of the western part of the Altaids: A key to understanding the architecture of accretionary orogens. Gondwana Research 18, 253-273. Acknowledgements: This study was financially supported by the Major Basic Research Project of the Ministry of Science and Technology of China (Grant: 2014CB448000 and 2014CB440801), Hong Kong Research Grant Council (HKU705311P, HKU704712P and HKU17303415), National Science Foundation of China (41273048), HKU seed funding (201111159137) and HKU CRCG grants. This work is a contribution of the Joint Laboratory of Chemical Geodynamics between HKU and CAS (Guangzhou Institute of Geochemistry), IGCP 592 and PROCORE France/Hong Kong Joint Research Scheme.

Delayed CO2 emissions from mid-ocean ridge volcanism as a possible cause of late-Pleistocene glacial cycles

NASA Astrophysics Data System (ADS)

Huybers, P. J.

2016-12-01

The coupled variations in ice volume, temperature, and atmospheric CO2 during the late Pleistocene are most often represented as involving some combination of orbital forcing, ice dynamics, and ocean circulation. Also previously argued is that changes in glaciation influence atmospheric CO2 concentrations through modifying subaerial volcanic eruptions and CO2 emissions. Building on recent evidence that ocean ridge volcanism responds to changes in sea level, a conceptual model is presented wherein ocean ridges play an important role in generating late-Pleistocene 100 ky glacial cycles on account of an inherent delay in their feedback response. If all volcanic CO2 emissions responded immediately to changes in pressure, subaerial and ocean-ridge volcanic emissions anomalies would merely oppose one another. At ocean ridges, however, the egress of CO2 from the mantle is delayed by tens-of-thousands of years, or longer, owing to ascent time. The simple model involves temperature, ice, and CO2 and is shown to oscillates at 100 ky time scales when incorporating a delayed CO2 contribution from ocean ridge volcanism, even if the feedback accounts for only a small fraction of total changes in CO2. Features of the model that are consistent with observations include that it readily become phase-locked with insolation forcing associated with changes in Earth's orbit, and that temperature variations lead changes in CO2 by several centuries during deglaciation. Under certain parameterizations, a transition from 41 ky to larger 100 ky oscillations occurs during the middle Pleistocene in response to modulations in orbital forcing. This novel description of Pleistocene glaciation should be testable through ongoing advances in understanding the circulation of carbon through the solid earth.

Radial transport of high-energy oxygen ions into the deep inner magnetosphere observed by Van Allen Probes

NASA Astrophysics Data System (ADS)

Mitani, K.; Seki, K.; Keika, K.; Gkioulidou, M.; Lanzerotti, L. J.; Mitchell, D. G.; Kletzing, C.

2017-12-01

It is known that proton is main contributor of the ring current and oxygen ions can make significant contribution during major magnetic storms. Ions are supplied to the ring current by radial transport from the plasma sheet. Convective transport of lower-energy protons and diffusive transport of higher-energy protons were reported to contribute to the storm-time and quiet-time ring current respectively [e.g., Gkioulidou et al., 2016]. However, supply mechanisms of the oxygen ions are not clear. To characterize the supply of oxygen ions to the ring current during magnetic storms, we studied the properties of energetic proton and oxygen ion phase space densities (PSDs) for specific magnetic moment (μ) during the April 23-25, 2013, geomagnetic storm observed by the Van Allen Probes mission. We here report on radial transport of high-energy (μ ≥ 0.5 keV/nT) oxygen ions into the deep inner magnetosphere during the late main phase of the magnetic storm. Since protons show little change during this period, this oxygen radial transport is inferred to cause the development of the late main phase. Enhancement of poloidal magnetic fluctuations is simultaneously observed. We estimated azimuthal mode number ≤5 by using cross wavelet analysis with ground-based observation of IMAGE ground magnetometers. The fluctuations can resonate with drift and bounce motions of the oxygen ions. The results suggest that combination of the drift and drift-bounce resonances is responsible for the radial transport of high-energy oxygen ions into the deep inner magnetosphere. We also report on the radial transport of the high-energy oxygen ions into the deep inner magnetosphere during other magnetic storms.

Effects of Exercise Intensity on Postprandial Improvement in Glucose Disposal and Insulin Sensitivity in Prediabetic Adults

PubMed Central

Rynders, Corey A.; Weltman, Judy Y.; Jiang, Boyi; Breton, Marc; Patrie, James; Barrett, Eugene J.

2014-01-01

Background: A single bout of exercise improves postprandial glycemia and insulin sensitivity in prediabetic patients; however, the impact of exercise intensity is not well understood. The present study compared the effects of acute isocaloric moderate (MIE) and high-intensity (HIE) exercise on glucose disposal and insulin sensitivity in prediabetic adults. Methods: Subjects (n = 18; age 49 ± 14 y; fasting glucose 105 ± 11 mg/dL; 2 h glucose 170 ± 32 mg/dL) completed a peak O2 consumption/lactate threshold (LT) protocol plus three randomly assigned conditions: 1) control, 1 hour of seated rest, 2) MIE (at LT), and 3) HIE (75% of difference between LT and peak O2 consumption). One hour after exercise, subjects received an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and C-peptide concentrations were sampled at 5- to 10-minute intervals at baseline, during exercise, after exercise, and for 3 hours after glucose ingestion. Total, early-phase, and late-phase area under the glucose and insulin response curves were compared between conditions. Indices of insulin sensitivity (SI) were derived from OGTT data using the oral minimal model. Results: Compared with control, SI improved by 51% (P = .02) and 85% (P < .001) on the MIE and HIE days, respectively. No differences in SI were observed between the exercise conditions (P = .62). Improvements in SI corresponded to significant reductions in the glucose, insulin, and C-peptide area under the curve values during the late phase of the OGTT after HIE (P < .05), with only a trend for reductions after MIE. Conclusion: These results suggest that in prediabetic adults, acute exercise has an immediate and intensity-dependent effect on improving postprandial glycemia and insulin sensitivity. PMID:24243632

The Oligocene-Miocene stratigraphic evolution of the Majella carbonate platform (Central Apennines, Italy)

NASA Astrophysics Data System (ADS)

Brandano, Marco; Cornacchia, Irene; Raffi, Isabella; Tomassetti, Laura

2016-03-01

The stratigraphic architecture of the Bolognano Formation documents the evolution of the Majella carbonate platform in response to global and local changes that affected the Mediterranean area during the Oligocene-Miocene interval. The Bolognano Formation consists of a homoclinal ramp that developed in a warm, subtropical environment. Five different lithofacies associations have been identified: Lepidocyclina calcarenites, cherty marly limestones, bryozon calcarenites, hemipelagic marls and marly limestones, and Lithothamnion limestones. Each association corresponds to a single lithostratigraphic unit except for the Lepidocyclina calcarenites that form two distinct lithostratigraphic units (Lepidocyclina calcarenites 1 and 2). These six units reflect alternation of shallow-water carbonate production and drowning. Specifically, two of the three stages of shallow-water carbonate production regard the development of wide dune fields within the middle ramp, one stage dominated by red algae and a sea-grass carbonate factory, whereas the two drowning phases are represented by marly cherty limestones and calcareous marls. A new biostratigraphic framework for Bolognano Formation is presented, based on high-resolution analysis of calcareous nannofossil assemblages, which proved to be very useful for biostratigraphic constraints also in shallow-water settings. Using this approach, we have linked the first drowning phase, late Chattian-Aquitanian p.p. in age, to western Mediterranean volcanism and the Mi-1 event, and the second drowning phase, late Burdigalian-Serravallian in age, to the closure of the Indo-Pacific passage and the occurrence of the global Monterey event. These results permit a new deciphering, in terms of sequence stratigraphy, of the Bolognano Formation that is interpreted as a 2nd-order super-sequence that can be subdivided into 3 transgressive-regressive sequences.

Paleoenvironmental and Paleoclimate Changes Since 21,000 Cal Years BP in the Northeastern part of Brazil Inferred From Sediment Records in Lagoa do Caco (Maranhao State, Brazil)

NASA Astrophysics Data System (ADS)

Sifeddine, A.; Meyers, P. A.; Gustavo, A.; Spadano Albuquerque, A. L.; Turcq, B.; Campbello Cordeiro, R.; Abrao, J. J.

2004-12-01

Two cores from Caco Lake, Maranhao State (North Brazil) record different histories of sediment accumulation on the margin and center of the lake that reflect changes in lake level. Seismic profiles, mineralogy and organic geochemical studies, backed by radiocarbon dating, reveal variable climatic and environmental conditions over the last 21 Cal Kyr BP. During the Last Glacial Maximum, regional climate was predominantly dry but was interrupted by short humid phases as reflected by a succession of very thin layers of sand and organic matter. The late glacial climate was relatively wet and included two rapid lake-level increases accompanied by forest expansion. The two wet phases were separated by a phase where the lake level remained stable and the forest changes were marked by the development of cool "Podocarpus" forest. These humid climate periods differed significantly from present warm tropical conditions.. The Holocene period is characterized by progressive increase of lake level, which reaches his maximum at around 7,000 Cal years BP. The period between 4,000 Cal years BP and the present shows high variability in lake level. Comparing with other South American and African records, we conclude that Late Glacial humid conditions were controlled by intensification of the ITCZ or shifts of its position, resulting in southeasterly trade wind variations and in interconnection between northern South America and the Atlantic tropical ocean-atmosphere system. The climatic variability during the Holocene is probably the result of sub-Milankovitch solar cycles and regional responses to these global forcings that are related to Atlantic and Pacific variability and their interconnections.

The roles of auxeticity and volume fraction on γ‧ precipitate microstructures in nickel-base alloys

NASA Astrophysics Data System (ADS)

Ardell, Alan J.

2017-01-01

New correlations are found between the elastic constants and late-stage precipitate microstructures in Ni-Al, Ni-Ga, Ni-Ge and Ni-Si alloys. The auxetic behaviour of Poisson's ratio, ν, measured parallel to [0 0 1] or ? in response to [1 1 0] loading, favours the amalgamation of Ni3Al and Ni3Ga precipitates into non-equilibrium shapes along cube directions when δν = (νγ‧ - νγ)/νγ‧ > 0, the superscripts referring to the γ‧ (Ni3X) and γ (Ni-X) phases, respectively. When δν < 0 amalgamation of Ni3Ge and Ni3Si precipitates does not occur and the particles retain cuboidal shapes. When δν > 0 amalgamation of Ni3Al and Ni3Ga occurs readily, primarily producing laths of both phases. The γ‧ volume fraction, f, is also shown to play a role in the late-stage microstructures of Ni-Al alloys, with an increasing tendency to form Ni3Al laths, rather than plates, as f increases. The shapes of elastically soft γ precipitates in inverse Ni-Al and Ni-Ge alloys are different; Ni-Al precipitates are lath shaped, but Ni-Ge precipitates are plate shaped. The Ni-Ge plate shape, in a non-auxetic Ni3Ge matrix (Ni3Ge being the sole non-auxetic Ni3X phase of the four studied), is the only example of persistent plates in any of the Ni-base alloys investigated to date. The combination of an elastically soft precipitate (Ni-Ge) in a non-auxetic matrix suggests a connection between auxeticity and shape.

IL-22 from T cells: better late than never.

PubMed

Honda, Kenya

2012-12-14

Interleukin-22 (IL-22) enhances mucosal barrier function and is important in antimicrobial host defense. In this issue of Immunity, Basu et al. (2012) reveal that Th22 cells are the critical adaptive source of IL-22 during late-phase infection by Citrobacter rodentium. Copyright © 2012 Elsevier Inc. All rights reserved.

A possible abrupt change in summer precipitation over eastern China around 2009

NASA Astrophysics Data System (ADS)

Ren, Yongjian; Song, Lianchun; Wang, Zunya; Xiao, Ying; Zhou, Bing

2017-04-01

Historical studies have shown that summer rainfall in eastern China undergoes decadal variations, with three apparent changes in the late 1970s, 1992, and the late 1990s. The present observational study indicates that summer precipitation over eastern China likely underwent a change in the late 2000s, during which the main spatial pattern changed from negative-positive-negative to positive-negative in the meridional direction. This change in summer precipitation over eastern China may have been associated with circulation anomalies in the middle/upper troposphere. A strong trough over Lake Baikal created a southward flow of cold air during 2009-15, compared with 1999-2008, while the westward recession of the western Pacific subtropical high strengthened the moisture transport to the north, creating conditions that were conducive for more rainfall in the north during this period. The phase shift of the Pacific Decadal Oscillation in the late 2000s led to the Pacific-Japan-type teleconnection wave train shifting from negative to positive phases, resulting in varied summer precipitation over eastern China.

Monitoring the recovery of Juncus roemerianus marsh burns with the normalized difference vegetation index and Landsat Thematic Mapper data

USGS Publications Warehouse

Ramsey, Elijah W.; Sapkota, S.K.; Barnes, F.G.; Nelson, G.A.

2002-01-01

Nine atmospherically corrected Landsat Thematic Mapper images were used to generate mean normalized difference vegetation indices (NDVI) at 11 burn sites throughout a coastal Juncus roemerianus marsh in St. Marks National Wildlife Refuge, Florida. Time-since-burn, the time lapse from the date of burn to the date of image collection, was related to variation in mean NDVI over time. Regression analysis showed that NDVI increased for about 300 to 400 days immediately after the burn, overshooting the typical mean NDVI of a nonburned marsh. For about another 500 to 600 days NDVI decreased until reaching a nearly constant NDVI of about 0.40. During the phase of increasing NDVI the ability to predict time-since-burn was within about ??60 days. Within the decreasing phase this dropped to about ??88 days. Examination of each burn site revealed some nonburn related influences on NDVI (e.g., seasonality). Normalization of burn NDVI by site-specific nonburn control NDVI eliminated most influences. However, differential responses at the site-specific level remained related to either storm impacts or secondary burning. At these sites, collateral data helped clarify the abnormal changes in NDVI. Accounting for these abnormalities, site-specific burn recovery trends could be broadly standardized into four general phases: Phase 1-preburn, Phase 2-initial recovery (increasing NDVI), Phase 3-late recovery (decreasing NDVI), and Phase 4-final coalescence (unchanging NDVI). Phase 2 tended to last about 300 to 500 days, Phase 3 an additional 500 to 600 days, and finally reaching Phase 4, 900 to 1,000 days after burn.

Deciphering natural to anthropogenic control on sedimentation: the Late Holocene Magdala (Kinneret Lake, Israel) harbour hystory

NASA Astrophysics Data System (ADS)

Sarti, G.; Rossi, V.; Amorosi, A.; Bertoni, D.; Ribolini, A.; Sammartino, I.; Zanchetta, G.

2012-04-01

Using a multidisciplinary approach involving geologists, geomorphologists and archeologists, the late Holocene sedimentary succession buried beneath the ancient Magdala harbour area (Kinneret Lake, Israel) was studied, in order to highlight the strict relationships among harbour evolutive phases (e.g. foundation, siltation, abandonment), natural events (e.g. sea-level variations, climatic changes and earthquakes among the most important) and, obviously, archaeological history. Recent excavations performed within the "Magdala Project" have discovered a harbour structure with late Hellenistic-Roman mooring stones at altitudes of 208.100 m and 208.320 m bsl respectively, suggestive of a higher lake-level (about 212 m bsl) than previously hypothesized. Along the most representative sections of trenches, integrated sedimentological, micropalaeontological (benthic meiofauna and pollen) and geochemical analyses were carried out on sedimentary deposits underlying and overlying the harbour structures, to define the main depositional facies and evolution phases that took place during the last millennia. Spatial variability of coeval palaeoenvironments across the archaeological site allowed to reconstruct a comprehensive picture of the harbour complex, evidencing the occurrence of three main evolution phases, similar to those reported from several Mediterranean Sea harbour systems: 1) a pre-harbor foundation phase; 2) a sin-harbor activity phase and 3) an harbor-abandonment phase. The first phase corresponds to the development of a natural lacustrine sandy beach barren in archaeological remains and containing an ostracod fauna very similar to the one observed within the present-day lake basin at ca. 5 m water depth. The second phase was characterized by the formation of an early Hellenistic sheltered lacustrine basin, recording the first anthropogenic control exerted on coastal sedimentation by the construction of harbour structures ("anthropogenically forced sheltered basin"). Dark, fine-grained deposits formed during the sin-harbour activity phase are rich in osteological remains (sheep, cattles) and archaeological artifacts (coins, pottery etc.). Moreover, the very high proportion of noded forms of Cyprideis torosa with respect to the smooth ones reflects stressed conditions, possibly connected to high pollution levels induced by harbor activities or, more generally, to a dense human frequentation. According to this interpretation, a sharp increase in concentration of trace metals Zn, Pb and Cu, along with P2O5, is recorded at the very base of the sin-harbour sequence on which Late Hellenistic and early Roman harbour structures rest on. The third phase, dated to the middle Roman period onwards, marks the siltation of the harbour basin and the end of Magdala harbour activities. The harbour-abandonment sequence is constituted by shoreface sands sharply overlain by foreshore-backshore well-sorted pebble conglomerates bearing middle Roman age remains. Another very similar conglomerate layer crops out in the sequence and covers Byzantine anthropogenic structures. From a sedimentological point of view the abrupt transition from sands to conglomerates indicates that major changes in sediment supply occurred after the late Roman age. We tentatively correlate this lithofacies change to climatic fluctuations (from a rainy to an arid phase) or to tectonic events, such as the destructive earthquakes occurred in the 349 AD and in 749 AD.

Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection

PubMed Central

Huang, Yongsheng; Zaas, Aimee K.; Rao, Arvind; Dobigeon, Nicolas; Woolf, Peter J.; Veldman, Timothy; Øien, N. Christine; McClain, Micah T.; Varkey, Jay B.; Nicholson, Bradley; Carin, Lawrence; Kingsmore, Stephen; Woods, Christopher W.; Ginsburg, Geoffrey S.; Hero, Alfred O.

2011-01-01

Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza. PMID:21901105

Physiology-phenology interactions in a productive semi-arid pine forest.

PubMed

Maseyk, Kadmiel S; Lin, Tongbao; Rotenberg, Eyal; Grünzweig, José M; Schwartz, Amnon; Yakir, Dan

2008-01-01

This study explored possible advantages conferred by the phase shift between leaf phenology and photosynthesis seasonality in a semi-arid Pinus halepensis forest system, not seen in temperate sites. Leaf-scale measurements of gas exchange, nitrogen and phenology were used on daily, seasonal and annual time-scales. Peak photosynthesis was in late winter, when high soil moisture, mild temperatures and low leaf vapour pressure deficit (D(L)) allowed high rates associated with high water- and nitrogen-use efficiencies. Self-sustained new needle growth through the dry and hot summer maximized photosynthesis in the following wet season, without straining carbon storage. Low rates of water loss were associated with increasing sensitivity of stomatal conductance (g(s)) to soil moisture below a relative extractable water (REW) of 0.4, and decreased g(s )sensitivity to D(L) below REW of approx. 0.2. This response was captured by the modified Ball-Berry (Leuning) model. While most physiological parameters and responses measured were typical of temperate pines, the photosynthesis-phenological phasing contributed to high productivity under warm-dry conditions. This contrasts with reported effects of short-term periodical droughts and could lead to different predictions of the effect of warming and drying climate on pine forest productivity.

Field-Aligned Current at Plasma Sheet Boundary Layers During Storm Time: Cluster Observation

NASA Astrophysics Data System (ADS)

Shi, J.; Cheng, Z.; Zhang, T.; Dunlop, M.; Liu, Z.

2007-05-01

The magnetic field data from the FGM instruments on board the four Cluster spacecrafts were used to study Field Aligned Current (FAC) at the Plasma Sheet Boundary Layers (PSBLs) with the so called "curlometer technique". We analyzed the date obtained in 2001 in the magnetotail and only two cases were found in the storm time. One (August 17, 2001) occurred from sudden commencement to main phase, and the other (October 1, 2001) lay in the main phase and recovery phase. The relationship between the FAC density and the AE index was studied and the results are shown as follows. (1) In the sudden commencement and the main phase the density of the FAC increases obviously, in the recovery phase the density of the FAC increases slightly. (2) From the sudden commencement to the initial stage of the main phase the FAC increases with decreasing AE index and decreases with increasing AE index. From the late stage of the main phase to initial stage of the recovery phase, the FAC increases with increasing AE index and decreases with decreasing AE index. In the late stage of the recovery phase the disturbance of the FAC is not so violent, so that the FAC varying with the AE index is not very obvious.

Lake System Development on the northern Tibetan Plateau during the last 12 ka

NASA Astrophysics Data System (ADS)

Ramisch, A. C.; Lockot, G.; Kasper, T.; Schulte, P.; Zhang, Y.; Daut, G.; Haberzettl, T.; Stauch, G.; Hartmann, K.; Zhu, L.; Lehmkuhl, F.; Maeusbacher, R.; Wuennemann, B.; Diekmann, B.

2013-12-01

Lake systems and their drainage basins provide valuable information of late Quaternary palaeo-environmental conditions on the Tibetan Plateau (TP). This information is often difficult to interpret because of a complex forcing-response mechanism of lake systems and their environment. Here we present an analysis of the endogenic mineral precipitation of Lake Heihai (northern TP) and its environmental constrains expressed by the exogenic mineral input. The mineralogical analysis of carbonate phases by means of X-ray diffraction revealed three distinct stages of carbonate precipitation: Aragonite (late Glacial), Monohydrocalcite (early to mid-Holocene) and Mg bearing Calcite (late Holocene). Each phase precipitates under steady state conditions of exogenic mineral input, as determined by a phase space analysis. This suggests a self-organized precipitation process driven by interactions of different ions. Hence, under steady environmental conditions carbonate precipitation is strongly dependent on the ionic compositions of the lake water and thus controlled by sources of the exogenic mineral input. To analyze the provenance of the exogenic mineral input, a Fuzzy C-Means (FCM) Clustering algorithm was performed on the minerogenic detrital fraction of the total mineral content of 57 surface reference samples. Three major sources can be distinguished: (a) glacially mediated, far distant transport originating from SE catchment (b) precipitation generated, close distant runoff originating from the SW catchment and (c) close distant transport of granite weathering products in the northern parts of the drainage basin. A change from the compositional dominance of (b) over (a) to (a) over (b) in lake sediments suggests a transition from rainfall to glacier dominated runoff production and hence drier climate conditions in the study area during the late Holocene. The environmentally controlled changes in the exogenic mineral input are compared to two different lake systems: Lake Donggi Cona (northern Tibetan Plateau) and Lake Nam Co (southern Tibetan Plateau). Major differences occur during two broad Holocene episodes: Until ~6 ka cal BP the differences reach their maximum with a peak around 9.5 cal ka BP. An intensification of the Indian Summer Monsoon (ISM) led to wetter conditions and an increased minerogenic input into Lake Nam Co. Subsequently, the aridification on the TP led to decreased minerogenic input in all three lakes especially since ~2 ka cal BP. Short term divergences from this trend are caused by dry spells on the northern TP. Their timing is quasi synchronous to Holocene Bond events, suggesting a teleconnection of northern TP climate to the circulation of the North Atlantic Ocean.

Critical phases in the seed development of common juniper (Juniperus communis).

PubMed

Gruwez, R; Leroux, O; De Frenne, P; Tack, W; Viane, R; Verheyen, K

2013-01-01

Common juniper (Juniperus communis L.) populations in northwest European lowlands are currently declining in size and number. An important cause of this decline is a lack of natural regeneration. Low seed viability seems to be one of the main bottlenecks in this process. Previous research revealed a negative relation between seed viability and both temperature and nitrogen deposition. Additionally, the seeds of common juniper have a variable ripening time, which possibly influences seed viability. However, the underlying mechanisms remain unresolved. In order to elucidate this puzzle, it is important to understand in which phases of seed production the main defects are situated, together with the influence of ripening time. In this study, we compared seed viability of populations with and without successful recruitment. We examined three seed phases: (i) gamete development; (ii) fertilisation and early-embryo development; and (iii) late-embryo development. After the first two phases, we found no difference in the percentage viable seeds between populations with or without recruitment. After late-embryo development, populations without recruitment showed a significantly lower percentage of viable seeds. These results suggest that late-embryo development is a bottleneck in seed development. However, the complex interaction between seed viability and ripening time suggest that the causes should be in the second seed phase, as the accelerated development of male and female gametophytes may disturb the male-female synchrony for successful mating. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

Embodiment and Emotional Memory in First vs. Second Language

PubMed Central

Baumeister, Jenny C.; Foroni, Francesco; Conrad, Markus; Rumiati, Raffaella I.; Winkielman, Piotr

2017-01-01

Language and emotions are closely linked. However, previous research suggests that this link is stronger in a native language (L1) than in a second language (L2) that had been learned later in life. The present study investigates whether such reduced emotionality in L2 is reflected in changes in emotional memory and embodied responses to L2 in comparison to L1. Late Spanish/English bilinguals performed a memory task involving an encoding and a surprise retrieval phase. Facial motor resonance and skin conductance (SC) responses were recorded during encoding. The results give first indications that the enhanced memory for emotional vs. neutral content (EEM effect) is stronger in L1 and less present in L2. Furthermore, the results give partial support for decreased facial motor resonance and SC responses to emotional words in L2 as compared to L1. These findings suggest that embodied knowledge involved in emotional memory is associated to increased affective encoding and retrieval of L1 compared to L2. PMID:28386240

Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle

PubMed Central

Hombach, Andreas A.; Abken, Hinrich

2013-01-01

Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient’s T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1+ CD57+ CD7− CCR7− phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy. PMID:23761793

Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle.

PubMed

Hombach, Andreas A; Abken, Hinrich

2013-01-01

Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1(+) CD57(+) CD7(-) CCR7(-) phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy.

Hürthle cell tumor dwelling in hot thyroid nodules: preoperative detection with technetium-99m-MIBI dual-phase scintigraphy.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A; Lazzi, S

1998-05-01

Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc-MIBI was used to differentiate benign and malignant hot thyroid nodules. Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN) underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late image and the washout rates (WO) from the nodule and thyroidal tissue were measured. All patients underwent thyroid surgery. Histopathology revealed a Hürthle cell tumor in three nodules, a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma without oxyphilic cells in the remaining 10 nodules. The Hürthle cell tumor nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/- 0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign nodules showed intense uptake in the early image and intense uptake to absent retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the thyroidal tissue was 20.33 +/- 2.92). Single injection dual-phase 99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result of the activity of a Hürthle cell tumor, since these tumors cause intense and persistent tracer uptake in contrast with a benign AFTN.

FMRFamide produces biphasic modulation of the LFS motor neurons in the neural circuit of the siphon withdrawal reflex of Aplysia by activating Na+ and K+ currents.

PubMed

Belkin, K J; Abrams, T W

1993-12-01

The molluscan neuropeptide FMRFamide has an inhibitory effect on transmitter release from the presynaptic sensory neurons in the neural circuit for the siphon withdrawal reflex. We have explored whether FMRFamide also acts postsynaptically in motor neurons in this circuit, focusing on the LFS motor neurons. FMRFamide typically produces a biphasic response in LFS neurons: a fast excitatory response followed by a prolonged inhibitory response. We have analyzed these postsynaptic actions and compared them with the mechanism of FMRFamide's inhibition of the presynaptic sensory neurons. The transient excitatory effect of FMRFamide, which desensitizes rapidly, is due to activation of a TTX-insensitive, Na(+)-dependent inward current. The late hyperpolarizing phase of the FMRFamide response results from activation of at least two K+ currents. One component of the hyperpolarizing response is active at rest and at more hyperpolarized membrane potentials, and is blocked by 5 mM 4-aminopyridine, suggesting that it differs from the previously described FMRFamide-modulated K+ currents in the presynaptic sensory neurons. In addition, FMRFamide increases a 4-aminopyridine-insensitive K+ current. Presynaptically, FMRFamide increases K+ conductance, acting via release of arachidonic acid. In the LFS motor neurons, application of arachidonic acid mimicked the prolonged, hyperpolarizing phase of the FMRFamide response; 4-bromophenacyl bromide, an inhibitor of phospholipase A2, selectively blocked this component of the FMRFamide response. Thus, FMRFamide may act in parallel pre- and post-synaptically to inhibit the output of the siphon withdrawal reflex circuit, producing this inhibitory effect via the same second messenger in the sensory neurons and motor neurons, though a number of the K+ currents modulated in these two types of neurons are different.

Long-Term Improvements After Multimodal Rehabilitation in Late Phase After Stroke: A Randomized Controlled Trial.

PubMed

Bunketorp-Käll, Lina; Lundgren-Nilsson, Åsa; Samuelsson, Hans; Pekny, Tulen; Blomvé, Karin; Pekna, Marcela; Pekny, Milos; Blomstrand, Christian; Nilsson, Michael

2017-07-01

Treatments that improve function in late phase after stroke are urgently needed. We assessed whether multimodal interventions based on rhythm-and-music therapy or horse-riding therapy could lead to increased perceived recovery and functional improvement in a mixed population of individuals in late phase after stroke. Participants were assigned to rhythm-and-music therapy, horse-riding therapy, or control using concealed randomization, stratified with respect to sex and stroke laterality. Therapy was given twice a week for 12 weeks. The primary outcome was change in participants' perception of stroke recovery as assessed by the Stroke Impact Scale with an intention-to-treat analysis. Secondary objective outcome measures were changes in balance, gait, grip strength, and cognition. Blinded assessments were performed at baseline, postintervention, and at 3- and 6-month follow-up. One hundred twenty-three participants were assigned to rhythm-and-music therapy (n=41), horse-riding therapy (n=41), or control (n=41). Post-intervention, the perception of stroke recovery (mean change from baseline on a scale ranging from 1 to 100) was higher among rhythm-and-music therapy (5.2 [95% confidence interval, 0.79-9.61]) and horse-riding therapy participants (9.8 [95% confidence interval, 6.00-13.66]), compared with controls (-0.5 [-3.20 to 2.28]); P =0.001 (1-way ANOVA). The improvements were sustained in both intervention groups 6 months later, and corresponding gains were observed for the secondary outcomes. Multimodal interventions can improve long-term perception of recovery, as well as balance, gait, grip strength, and working memory in a mixed population of individuals in late phase after stroke. URL: http//www.ClinicalTrials.gov. Unique identifier: NCT01372059. © 2017 American Heart Association, Inc.

Curcumin Inhibits CD4+ T Cell Activation, but Augments CD69 Expression and TGF-β1-Mediated Generation of Regulatory T Cells at Late Phase

PubMed Central

Kim, Girak; Jang, Mi Seon; Son, Young Min; Seo, Min Ji; Ji, Sang Yun; Han, Seung Hyun; Jung, In Duk; Park, Yeong-Min; Jung, Hyun Jung; Yun, Cheol-Heui

2013-01-01

Background Curcumin is a promising candidate for a natural medicinal agent to treat chronic inflammatory diseases. Although CD4+ T cells have been implicated in the pathogenesis of chronic inflammation, whether curcumin directly regulates CD4+ T cells has not been definitively established. Here, we showed curcumin-mediated regulation of CD2/CD3/CD28-initiated CD4+ T cell activation in vitro. Methodology/Principal Findings Primary human CD4+ T cells were stimulated with anti-CD2/CD3/CD28 antibody-coated beads as an in vitro surrogate system for antigen presenting cell-T cell interaction and treated with curcumin. We found that curcumin suppresses CD2/CD3/CD28-initiated CD4+ T cell activation by inhibiting cell proliferation, differentiation and cytokine production. On the other hand, curcumin attenuated the spontaneous decline of CD69 expression and indirectly increased expression of CCR7, L-selectin and Transforming growth factor-β1 (TGF-β1) at the late phase of CD2/CD3/CD28-initiated T cell activation. Curcumin-mediated up-regulation of CD69 at late phase was associated with ERK1/2 signaling. Furthermore, TGF-β1 was involved in curcumin-mediated regulation of T cell activation and late-phase generation of regulatory T cells. Conclusions/Significance Curcumin not merely blocks, but regulates CD2/CD3/CD28-initiated CD4+ T cell activation by augmenting CD69, CCR7, L-selectin and TGF-β1 expression followed by regulatory T cell generation. These results suggest that curcumin could directly reduce T cell-dependent inflammatory stress by modulating CD4+ T cell activation at multiple levels. PMID:23658623

Synchronization of the astronomical time scales in the Early Toarcian: A link between anoxia, carbon-cycle perturbation, mass extinction and volcanism

NASA Astrophysics Data System (ADS)

Ait-Itto, Fatima-Zahra; Martinez, Mathieu; Price, Gregory D.; Ait Addi, Abdellah

2018-07-01

The Late Pliensbachian-Early Toarcian is a pivotal time in the Mesozoic era, marked by pronounced carbon-isotope excursions, biotic crises and major climatic and oceanographic changes. Here we present new high-resolution carbon-isotope and magnetic-susceptibility measurements from an expanded hemipelagic Late Pliensbachian-Early Toarcian section from the Middle Atlas Basin (Morocco). Our new astronomical calibration allows the construction of an orbital time scale based on the 100-kyr eccentricity cycle. The Early Toarcian Polymorphum Zone contains 10 to 10.5 repetitions of the 100-kyr eccentricity both in the carbon-isotope and the magnetic-susceptibility data, leading to an average duration of 1.00 ± 0.08 myr. We also show that the Late Pliensbachian-Early Toarcian global carbon-cycle perturbation has an average duration of 0.24 ± 0.02 myr. These durations are comparable to previous astrochronological time scales provided for this time interval in the most complete sections of the Tethyan area, and longer than what has been provided in condensed sections. Anchoring this framework on published radiometric ages and astrochronological time scales, we estimate that the carbon-cycle perturbation of the Late Pliensbachian-Early Toarcian corresponds with the early phase of the Karoo and Chonke Aike large igneous provinces. Likewise, our new age constraints confirm that the Toarcian oceanic anoxic event is synchronous to the main phase of the Ferrar volcanic activity. Thus, these successive and short phases of the volcanic activity may have been at the origin of the successive phases of the mass extinctions observed in marine biotas in the Pliensbachian and Toarcian times.

Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice.

PubMed

Shamsi, Bilal Haider; Ma, Chaofeng; Naqvi, Saima; Xiao, Yanfeng

2014-01-01

Obesity is a metabolic disorder that can lead to high blood pressure, increased blood cholesterol and triglycerides, insulin resistance, and diabetes mellitus. The aim was to study the effects of pioglitazone mediated sensitization of peroxisome proliferator-activated receptor gamma (PPAR-γ) on the relationship of Cell death-inducing DFFA-like effector C (CIDEC) with obesity related changes in mice. Sixty C57B/L6 mice weighing 10-12g at 3 weeks of age were randomly divided into 3 groups. Mice in Group 1 were fed on normal diet (ND) while Group 2 mice were given high fat diet (HFD), and Group 3 mice were given high fat diet and treated with Pioglitazone (HFD+P). Body weight, length and level of blood sugar were measured weekly. Quantitative real-time PCR, fluorescence microscopy, and ELISA were performed to analyze the expression of CIDEC and PPAR-γ in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Body weight and length of mice increased gradually with time in all groups. Blood sugar in HFD mice started to increase significantly from the mid of late phase of obesity while pioglitazone attenuated blood sugar level in HFD+P mice. The mRNA expressions and protein levels of PPAR-γ and CIDEC genes started to increase in HFD mice as compared to ND mice and decreased gradually during the late phase of obesity in VAT. Pioglitazone enhanced the expression of PPAR-γ and CIDEC genes in HFD+P mice even during the late phase of obesity. It is insinuated that VAT is associated with late phase obesity CIDEC decrease and insulin resistance, while pioglitazone enhances CIDEC through activation of PPAR-γ, increases its expression, and decreases lipolysis, hence preventing an increase of blood sugar in mice exposed to HFD.

Molecular Genetic Analysis of Midgut Serine Proteases in Aedes aegypti Mosquitoes

PubMed Central

Isoe, Jun; Rascón, Alberto A.; Kunz, Susan; Miesfeld, Roger L.

2009-01-01

Digestion of blood meal proteins by midgut proteases provides anautogenous mosquitoes with the nutrients required to complete the gonotrophic cycle. Inhibition of protein digestion in the midgut of blood feeding mosquitoes could therefore provide a strategy for population control. Based on recent reports indicating that the mechanism and regulation of protein digestion in blood fed female Aedes aegypti mosquitoes is more complex than previously thought, we used a robust RNAi knockdown method to investigate the role of four highly expressed midgut serine proteases in blood meal metabolism. We show by Western blotting that the early phase trypsin protein (AaET) is maximally expressed at 3 h post blood meal (PBM), and that AaET is not required for the protein expression of three late phase serine proteases, AaLT (late trypsin), AaSPVI (5G1), and AaSPVII. Using the trypsin substrate analog BApNA to analyze in vitro enzyme activity in midgut extracts from single mosquitoes, we found that knockdown of AaSPVI expression caused a 77.6% decrease in late phase trypsin-like activity, whereas, knockdown of AaLT and AaSPVII expression had no significant effect on BApNA activity. In contrast, injection of AaLT, AaSPVI, and AaSPVII dsRNA inhibited degradation of endogenous serum albumin protein using an in vivo protease assay, as well as, significantly decreased egg production in both the first and second gonotrophic cycles (p<0.001). These results demonstrate that AaLT, AaSPVI, and AaSPVII all contribute to blood protein digestion and oocyte maturation, even though AaSPVI is the only abundant midgut late phase serine protease that appears to function as a classic trypsin enzyme. PMID:19883761

Circadian Periods of Sensitivity for Ramelteon on the onset of Running-wheel Activity and the Peak of Suprachiasmatic Nucleus Neuronal Firing Rhythms in C3H/HeN Mice

PubMed Central

Rawashdeh, Oliver; Hudson, Randall L.; Stepien, Iwona; Dubocovich, Margarita L.

2016-01-01

Ramelteon, an MT1/MT2 melatonin receptor agonist, is used for the treatment of sleep-onset insomnia and circadian sleep disorders. Ramelteon phase shifts circadian rhythms in rodents and humans when given at the end of the subjective day; however, its efficacy at other circadian times is not known. Here, the authors determined in C3H/ HeN mice the maximal circadian sensitivity for ramelteon in vivo on the onset of circadian running-wheel activity rhythms, and in vitro on the peak of circadian rhythm of neuronal firing in suprachiasmatic nucleus (SCN) brain slices. The phase response curve (PRC) for ramelteon (90 μg/mouse, subcutaneous [sc]) on circadian wheel-activity rhythms shows maximal sensitivity during the late mid to end of the subjective day, between CT8 and CT12 (phase advance), and late subjective night and early subjective day, between CT20 and CT2 (phase delay), using a 3-day-pulse treatment regimen in C3H/HeN mice. The PRC for ramelteon resembles that for melatonin in C3H/ HeN mice, showing the same magnitude of maximal shifts at CT10 and CT2, except that the range of sensitivity for ramelteon (CT8–CT12) during the subjective day is broader. Furthermore, in SCN brain slices in vitro, ramelteon (10 pM) administered at CT10 phase advances (5.6 ± 0.29 h, n = 3) and at CT2 phase delays (−3.2 ± 0.12 h, n = 6) the peak of circadian rhythm of neuronal firing, with the shifts being significantly larger than those induced by melatonin (10 pM) at the same circadian times (CT10: 2.7 ± 0.15 h, n = 4, p < .05; CT2: −1.13 ± 0.08 h, n = 6, p < .001, respectively). The phase shifts induced by both melatonin and ramelteon in the SCN brain slice at either CT10 or CT2 corresponded with the period of sensitivity observed in vivo. In conclusion, melatonin and ramelteon showed identical periods of circadian sensitivity at CT10 (advance) and CT2 (delay) to shift the onset of circadian activity rhythms in vivo and the peak of SCN neuronal firing rhythms in vitro. PMID:21182402

The He-rich stripped-envelope core-collapse supernova 2008ax

NASA Astrophysics Data System (ADS)

Taubenberger, S.; Navasardyan, H.; Maurer, J. I.; Zampieri, L.; Chugai, N. N.; Benetti, S.; Agnoletto, I.; Bufano, F.; Elias-Rosa, N.; Turatto, M.; Patat, F.; Cappellaro, E.; Mazzali, P. A.; Iijima, T.; Valenti, S.; Harutyunyan, A.; Claudi, R.; Dolci, M.

2011-05-01

Extensive optical and near-infrared (NIR) observations of the Type IIb supernova (SN IIb) 2008ax are presented, covering the first year after the explosion. The light curve is mostly similar in shape to that of the prototypical SN IIb 1993J, but shows a slightly faster decline rate at late phases and lacks the prominent narrow early-time peak of SN 1993J. From the bolometric light curve and ejecta expansion velocities, we estimate that about 0.07-0.15 M⊙ of 56Ni was produced during the explosion and that the total ejecta mass was between 2 and 5 M⊙, with a kinetic energy of at least 1051 erg. The spectral evolution of SN 2008ax is similar to that of SN Ib/IIb 2007Y, exhibiting high-velocity Ca II features at early phases and signs of ejecta-wind interaction from Hα observations at late times. NIR spectra show strong He I lines similar to SN Ib 1999ex and a large number of emission features at late times. Particularly interesting are the strong, double-peaked He I lines in late NIR spectra, which - together with the double-peaked [O I] emission in late optical spectra - provide clues for the asymmetry and large-scale Ni mixing in the ejecta. a Phase in days with respect to the explosion date (JD =245 4528.80 ± 0.15). B-band maximum light occurred on day 18.3. b Average seeing in arcsec over all filter bands. c CAFOS = Calar Alto 2.2m Telescope + CAFOS; DOLORES = 3.58m Telescopio Nazionale Galileo + DOLORES; AFOSC = Asiago 1.82m Copernico Telescope + AFOSC.

Predictive value of serum bradykinin and desArg9-bradykinin levels for chemotherapeutic responses in active tuberculosis patients: A retrospective case series.

PubMed

Qian, Xu; Nguyen, Duc T M; Li, Yaojun; Lyu, Jianxin; Graviss, Edward A; Hu, Tony Y

2016-12-01

There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg 9 -bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases. Nanotrap Mass-Spectrometry (MS) was used to analyze serial blood specimens from 13 HIV-negative adults with microbiologically confirmed active TB who were treated with first-line anti-TB chemotherapy. MS signal for BK (m/z 1060.5) and DABK (m/z 904.5) serum peptides were evaluated at multiple time-points (before, during, and after treatment) to evaluate how BK and DABK levels corresponded with disease status. Serum BK levels declined from pretreatment baseline levels during the early stage anti-TB therapy (induction phase) and tended to remain below baseline levels during extended treatment (consolidation phase) and after therapy completion. BK levels were consistent with induction phase sputum culture conversions indicative of decreased Mtb burden reflecting good treatment responses. Serum DABK levels tended to increase during the induction phase and decrease at consolidation and post-therapy time points, which may indicate a shift from active disease to chronic inflammation to a disease free state. Elevated BK and DABK levels after treatment completion in one patient may be related to the subsequent recurrent TB disease. Our pilot data suggests that changes in the circulating BK and DABK levels in adult TB patients can be used as potential surrogate markers of the host response both early and late in anti-TB treatment for both pulmonary and extrapulmonary TB patients. We will further exploit these host-response signatures in the future as biomarkers in combination with other clinical and microbiologic tools which may improve treatment efficacy and facilitate the development of host-directed therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of the innate immune response in the periparturient cow.

PubMed

Trevisi, Erminio; Minuti, Andrea

2018-02-01

The transition period is the most critical phase in the life of high yielding dairy cows. Within a few weeks, cows are submitted to many challenges (physiological, nutritional, psychological, management) that require prompt and effective adaptive responses. The immune system is involved in this process, and many changes of the cow's immune system components have been observed around calving. Cows are considered to be immunosuppressed in late lactation, and available data suggest that the immune system is dysregulated around parturition. Significant attention has been focused on modification of cellular functions (e.g. the reduction of phagocytosis and diapedesis), but growing interest concerns the components of the innate immune system, which often exhibits increased responses such as susceptibility to inflammatory events and the related acute phase response (APR). Systemic inflammation plays a significant role in early lactation, affects many liver functions and has been associated with the impairment of cow performance (i.e. reduced feed intake, milk yield, fertility, welfare). The assessment of variations in immune-metabolic indices offers opportunities to predict the onset of the health troubles and to anticipate the proper therapies needed to guarantee health, good welfare and fertility in the following lactation. The frequency of diseases (metabolic and infectious) before calving is rare, but several clues suggest that various metabolic and immune variations can begin during the dry period. Interesting preliminary results encourage this perspective and possible candidates are suggested. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the importance of processing conditions, product thickness and egg addition for the glycaemic and hormonal responses to pasta: a comparison with bread made from 'pasta ingredients'.

PubMed

Granfeldt, Y; Björck, I; Hagander, B

1991-10-01

The importance of processing conditions, product thickness and effect of egg addition for the glycaemic and hormonal responses to pasta was studied. Healthy subjects were given test meals with an equivalent amount of available carbohydrate from extruded high-temperature dried spaghetti and three varieties of fresh roll-sheeted linguine (thick, thin, thin with egg) made from the same ingredients (durum wheat, water and monoglycerides). As a reference bread was baked from the same ingredients as in the pasta products. Glucose, insulin and C-peptide levels were measured over a 3 h period. Glycaemic, insulin and C-peptide indexes (GI, II, CI) were calculated using 120 min areas under the curves. Glycaemic index was also calculated using the 90 min area. Also studied were the rates of in vitro starch digestion. The four pasta products produced significantly lower peak values (glucose, insulin, C-peptide) and lower GI (90 min), II (120 min) and CI (120 min) than the corresponding bread. The rate of in vitro starch digestion in pasta was also slower than in bread. In contrast to the pasta products, bread resulted in a prominent hypoglycaemia in the late phase, that is a drop below fasting blood glucose level. Minor differences in metabolic responses also appeared in the pasta products. In particular, the insulin and C-peptide response to the thin linguine was accentuated in the phase around 120 min.

Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India

PubMed Central

Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

2014-01-01

In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). PMID:25008901

Oligocene to Recent tectonic history of the Central Solomon intra-arc basin as determined from marine seismic reflection data and compilation of onland geology

NASA Astrophysics Data System (ADS)

Cowley, Shane; Mann, Paul; Coffin, M. F.; Shipley, Thomas H.

2004-10-01

Systematic analysis of a grid of 3450 km of multichannel seismic reflection lines from the Solomon Islands constrains the late Tertiary sedimentary and tectonic history of the Solomon Island arc and its convergent interaction with the Cretaceous Ontong Java oceanic plateau (OJP). The OJP, the largest oceanic plateau on Earth, subducted beneath the northern edge of the Solomon arc in the late Neogene, but the timing and consequences of this obliquely convergent event and its role in the subduction polarity reversal process remain poorly constrained. The Central Solomon intra-arc basin (CSB), which developed in Oligocene to Recent time above the Solomon arc, provides a valuable record of the tectonic environment prior to and accompanying the OJP convergent event and the subsequent arc polarity reversal. Recognition of regionally extensive stratigraphic sequences—whose ages can be inferred from marine sedimentary sections exposed onland in the Solomon Islands—indicate four distinct tectonic phases affecting the Solomon Island arc. Phase 1: Late Oligocene-Late Miocene rifting of the northeast-facing Solomon Island arc produced basal, normal-fault-controlled, asymmetrical sequences of the CSB; the proto-North Solomon trench was probably much closer to the CSB and is inferred to coincide with the trace of the present-day Kia-Kaipito-Korigole (KKK) fault zone; this protracted period of intra-arc extension shows no evidence for interruption by an early Miocene period of convergent "soft docking" of the Ontong Java Plateau as proposed by previous workers. Phase 2: Late Miocene-Pliocene oblique convergence of the Ontong Java Plateau at the proto-North Solomon trench (KKK fault zone) and folding of the CSB and formation of the Malaita accretionary prism (MAP); the highly oblique and diachronous convergence between the Ontong Java plateau and the Solomon arc terminates intra-arc extension first in the southeast (Russell subbasin of the CSB) during the Late Miocene and later during the Pliocene in the northwest (Shortland subbasin of the CSB); folds in the CSB form by inversion of normal faults formed during Phase 1; Phinney et al. [Sequence stratigraphy, structural style, and age of deformation of the Malaita accretionary prism (Solomon arc-Ontong Java Plateau convergent zone)] show a coeval pattern of southeast to northwest younging in folding and faulting of the MAP. Phase 3: Late Pliocene-early Pleistocene arc polarity reversal and subduction initiation at the San Cristobal trench. Effects of this event in the CSB include the formation of a chain of volcanoes above the subducting Australia plate at the San Cristobal trench, the formation of the broad synclinal structure of the CSB with evidence for truncation at the uplifted flanks, and widespread occurrence of slides and "seismites" (deposits formed by seismic shaking). Phase 4: Pleistocene to Recent continued shortening and synclinal subsidence of the CSB. Continued Australia-Pacific oblique plate convergence has led to deepening of the submarine, elongate basin axis of the synclinal CSB and uplift of the dual chain of the islands on its flanks.

Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression

PubMed Central

Posadas, Inmaculada; Bucci, Mariarosaria; Roviezzo, Fiorentina; Rossi, Antonietta; Parente, Luca; Sautebin, Lidia; Cirino, Giuseppe

2004-01-01

Injection of carrageenan 1% (50 μl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7- or 8-week old, weighing 32–34 g, displayed a consistent response in both phases. In 8-week-old mice, myeloperoxidase (MPO) levels are significantly elevated in the early phase at 6 h and reach their maximum at 24 h to decline to basal value at 48 h. Nitrate+nitrite (NOx) levels in the paw are maximal after 2 h and slowly decline thereafter in contrast to prostaglandin E2 levels that peak in the second phase at the 72 h point. Western blot analysis showed that inducible nitric oxide synthase (iNOS) is detectable at 6 h and cyclooxygenase 2 (COX-2) at 24 h point, respectively. Analysis of endothelial nitric oxide synthase (eNOS), iNOS and COX-2 expression at 6 and 24 h in 3–8-week-old mice demonstrated that both eNOS and iNOS expressions are dependent upon the age–weight of mice, as opposite to COX-2 that is present only in the second phase of the oedema and is not linked to mouse age–weight. Subplantar injection of carrageenan to C57BL/6J causes a biphasic oedema that is significantly reduced by about 20% when compared to CD1 mice. Interestingly, in these mice, iNOS expression is absent up to 6 h, as opposite to CD1, and becomes detectable at the 24 h point. Cyclooxygenase (COX-1) expression is upregulated between 4 and 24 h after carrageenan injection, whereas in CD1 mice COX-1 remains unchanged after irritant agent injection. MPO levels are maximal at the 24 h point and they are significantly lower, at 6 h point, than MPO levels detected in CD1 mice. In conclusion, mouse paw oedema is biphasic and age-weight dependent. The present results are the first report on the differential expressions of eNOS, iNOS, COX-1 and COX-2 in response to carrageenan injection in the two phases of the mouse paw oedema. PMID:15155540

Intrinsic vs. extrinsic controls on channel evolution in a sub-tropical river, Australia

NASA Astrophysics Data System (ADS)

Daley, James; Croke, Jacky; Thompson, Chris; Cohen, Tim; Macklin, Mark; Sharma, Ashneel

2016-04-01

Palaeohydrological research provides valuable insights to the understanding of short- and long-term fluvial dynamics in response to climate change and tectonic activity. In landscapes where tectonic activity is minimal fluvial archives record long-term changes in sediment and discharge dynamics related to either intrinsic or extrinsic controls. Isolating the relative controls of these factors is an important frontier in this area of research. Advances in geochronology, the acquisition of high resolution topographic data and geomorphological techniques provide an opportunity to assess the relative importance of intrinsic and extrinsic controls on terrace and floodplain formation. This study presents the results of detailed chrono-stratigraphic research in a partly confined river valley in subtropical southeast Queensland. River systems within this region are characterized by high hydrological variability and have a near-ubiquitous compound channel morphology (macrochannel) where Holocene deposits are inset within late Pleistocene terraces. These macrochannels can accommodate floods up to and beyond the predicted 100-year flood. Using single grain optically stimulated luminescence and radiocarbon analyses, combined with high resolution spatial datasets, we demonstrate the nature of fluvial response to major late Quaternary climate change. A large proportion of the valley floor is dominated by terrace alluvium deposited after the Last Glacial Maximum (LGM) (17 - 13 ka) and overlies basal older Pleistocene alluvium. Preliminary results suggest a phase of incision occurred at 10 ka with the formation of the large alluvial trench. The Holocene floodplain is dominated by processes of catastrophic vertical accretion and erosion (cut-and-fill) and oblique accretion at the macrochannel margins. The consistency in ages for the terraces and subsequent incision suggests a uniform network response. Alluvial sediments and channel configuration in this compound and complex landscape represent a discernable response to long-term climate change, high climate variability and extreme weather events.

The effects of cleared larch canopy and nitrogen supply on gas exchange and leaf traits in deciduous broad-leaved tree seedlings.

PubMed

Kitaoka, Satoshi; Watanabe, Yoko; Koike, Takayoshi

2009-12-01

To understand the leaf-level responses of successional tree species to forest gap formation and nitrogen deposition, we performed canopy clearing and nitrogen-amendment treatments in larch plantations and investigated the changes in the light-use characteristics and the leaf structure of the invading deciduous broad-leaved tree seedlings. We hypothesized that the responses of the tree seedlings to clearing and nitrogen input would reflect specific traits in the shoot development that would be related to the species-specific successional characteristics. The gap phase species Magnolia hyporeuca Siebold et Zucc. and the mid-late successional tree species Quercus mongolica Fischer ex Ledeb. var. crispula (Blume) Ohashi., which grow in or near the forest gaps, had higher light-saturated photosynthetic rates (Psat), enhanced mesophyll surface area (Smes) and increased leaf mass per area (LMA) under both the clearing treatment and the clearing with nitrogen-amendment treatment. These two species therefore increased their Psat via an increase in Smes and LMA. The LMA values of the late successional tree species Prunus ssiori F. Schmidt and Carpinus cordata Blume, which grow in the forest understory, were enhanced by the clearing treatment. However, they displayed lesser responses to the clearing treatment under which there were no marked increases in Psat or Smes values in the second year. These results indicate distinct and varied responses to disturbance regimes among the four seral tree seedlings. The Psat value largely increased in line with the increase in Smes value during the second year in M. hyporeuca and Q. mongolica. The nitrogen supply accelerated the change in LMA and increased the Smes value in the leaves of Q. mongolica.

Differential cellular responses to prolonged LDR-IR in MLH1-proficient and MLH1-deficient colorectal cancer HCT116 cells.

PubMed

Yan, Tao; Seo, Yuji; Kinsella, Timothy J

2009-11-15

MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining genomic stability by participating in the repair of endogenous and exogenous mispairs in the daughter strands during S phase. Exogenous mispairs can result following treatment with several classes of chemotherapeutic drugs, as well as with ionizing radiation. In this study, we investigated the role of the MLH1 protein in determining the cellular and molecular responses to prolonged low-dose rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer brachytherapy. An isogenic pair of MMR(+) (MLH1(+)) and MMR(-) (MLH1(-)) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR (1.3-17 cGy/h x 24-96 h). The clonogenic survival and gene mutation rates were examined. Cell cycle distribution was analyzed with flow cytometry. Changes in selected DNA damage repair proteins, DNA damage response proteins, and cell death marker proteins were examined with Western blotting. MLH1(+) HCT116 cells showed greater radiosensitivity with enhanced expression of apoptotic and autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell cycle alterations (increased late-S population and a G(2)/M arrest) following LDR-IR compared with MLH1(-) HCT116 cells. Importantly, a progressive increase in MLH1 protein levels was found in MLH1(+) cells during prolonged LDR-IR, which was temporally correlated with a progressive decrease in Rad51 protein (involved in homologous recombination) levels. MLH1 status significantly affects cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to prolonged LDR-IR through inhibition of homologous recombination (through inhibition of Rad51).

Contraceptive use during the reproductive lifecycle as reported by 46-year-old women in Sweden.

PubMed

Sköld, Annelie; Larsson, Margareta

2012-03-01

The aim of this study was to investigate the contraceptive methods 46-year-old women in Sweden had chosen during different phases of their reproductive lifecycle and, the factors affecting their choice. The design was a retrospective cross-sectional study and targeted 46-year-old women. Five hundred Swedish women were randomly selected from a national population-based register and sent a questionnaire with 18 multiple response questions: the response rate was 47%. The women used different contraceptive methods during different phases of their reproductive lifecycle. Women mainly used oral contraceptive pills and condoms before pregnancy, copper-IUD between pregnancies and, hormonal- and copper IUD after pregnancy. Condoms were used during all phases of women's fertile period. Women with early sexual debut were more likely to have used condom as their first contraceptive method than women with late sexual debut, and women who had children were more likely to use IUD as current contraception than women without children. High efficacy, accessibility and advice from a counselor were the most cited reasons for choosing a particular method. The most common reasons for discontinuing contraceptive use were a wish to be pregnant and concerns about side effects. The partner had little or no influence on choice of method, but advice from a gynecologist or midwife was influential. 46-year-old women in Sweden had chosen different contraceptive methods during different phases of their reproductive lifecycle. Partners appear to have limited influence over this choice. Individualized counseling by health care providers seems important. Copyright © 2011 Elsevier B.V. All rights reserved.

Global dynamics of the Escherichia coli proteome and phosphoproteome during growth in minimal medium.

PubMed

Soares, Nelson C; Spät, Philipp; Krug, Karsten; Macek, Boris

2013-06-07

Recent phosphoproteomics studies have generated relatively large data sets of bacterial proteins phosphorylated on serine, threonine, and tyrosine, implicating this type of phosphorylation in the regulation of vital processes of a bacterial cell; however, most phosphoproteomics studies in bacteria were so far qualitative. Here we applied stable isotope labeling by amino acids in cell culture (SILAC) to perform a quantitative analysis of proteome and phosphoproteome dynamics of Escherichia coli during five distinct phases of growth in the minimal medium. Combining two triple-SILAC experiments, we detected a total of 2118 proteins and quantified relative dynamics of 1984 proteins in all measured phases of growth, including 570 proteins associated with cell wall and membrane. In the phosphoproteomic experiment, we detected 150 Ser/Thr/Tyr phosphorylation events, of which 108 were localized to a specific amino acid residue and 76 were quantified in all phases of growth. Clustering analysis of SILAC ratios revealed distinct sets of coregulated proteins for each analyzed phase of growth and overrepresentation of membrane proteins in transition between exponential and stationary phases. The proteomics data indicated that proteins related to stress response typically associated with the stationary phase, including RpoS-dependent proteins, had increasing levels already during earlier phases of growth. Application of SILAC enabled us to measure median occupancies of phosphorylation sites, which were generally low (<12%). Interestingly, the phosphoproteome analysis showed a global increase of protein phosphorylation levels in the late stationary phase, pointing to a likely role of this modification in later phases of growth.

Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

PubMed

Paris, K J; Spanos, W J; Lindberg, R D; Jose, B; Albrink, F

1993-03-15

To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

Hierarchical neurocomputations underlying concurrent sound segregation: connecting periphery to percept.

PubMed

Bidelman, Gavin M; Alain, Claude

2015-02-01

Natural soundscapes often contain multiple sound sources at any given time. Numerous studies have reported that in human observers, the perception and identification of concurrent sounds is paralleled by specific changes in cortical event-related potentials (ERPs). Although these studies provide a window into the cerebral mechanisms governing sound segregation, little is known about the subcortical neural architecture and hierarchy of neurocomputations that lead to this robust perceptual process. Using computational modeling, scalp-recorded brainstem/cortical ERPs, and human psychophysics, we demonstrate that a primary cue for sound segregation, i.e., harmonicity, is encoded at the auditory nerve level within tens of milliseconds after the onset of sound and is maintained, largely untransformed, in phase-locked activity of the rostral brainstem. As then indexed by auditory cortical responses, (in)harmonicity is coded in the signature and magnitude of the cortical object-related negativity (ORN) response (150-200 ms). The salience of the resulting percept is then captured in a discrete, categorical-like coding scheme by a late negativity response (N5; ~500 ms latency), just prior to the elicitation of a behavioral judgment. Subcortical activity correlated with cortical evoked responses such that weaker phase-locked brainstem responses (lower neural harmonicity) generated larger ORN amplitude, reflecting the cortical registration of multiple sound objects. Studying multiple brain indices simultaneously helps illuminate the mechanisms and time-course of neural processing underlying concurrent sound segregation and may lead to further development and refinement of physiologically driven models of auditory scene analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Installation Restoration Program. Phase 1. Records Search 15th ABW Satellite Installations, Hawaii

DTIC Science & Technology

1984-09-01

Hickam POL Storage Facilities and Pipeline The POL storage facilities remotely located from Hickam Air Force Base (AFB...airfield with less activity than nearby Wheeler and Hickam Air Force Bases . Aircraft activity was significantly reduced in the late 1940’s and the...United States Air Force to conduct the Phase I Records Search at the 15th Air Base Wing 1-2 ES ENGINEERING-SCIENCE PHASE I PHASE 11 PHASE IV

Emotion regulation in social anxiety disorder: behavioral and neural responses to three socio-emotional tasks

PubMed Central

2013-01-01

Background Social anxiety disorder (SAD) is thought to involve deficits in emotion regulation, and more specifically, deficits in cognitive reappraisal. However, evidence for such deficits is mixed. Methods Using functional magnetic resonance imaging (fMRI) of blood oxygen-level dependent (BOLD) signal, we examined reappraisal-related behavioral and neural responses in 27 participants with generalized SAD and 27 healthy controls (HC) during three socio-emotional tasks: (1) looming harsh faces (Faces); (2) videotaped actors delivering social criticism (Criticism); and (3) written autobiographical negative self-beliefs (Beliefs). Results Behaviorally, compared to HC, participants with SAD had lesser reappraisal-related reduction in negative emotion in the Beliefs task. Neurally, compared to HC, participants with SAD had lesser BOLD responses in reappraisal-related brain regions when reappraising faces, in visual and attention related regions when reappraising criticism, and in the left superior temporal gyrus when reappraising beliefs. Examination of the temporal dynamics of BOLD responses revealed late reappraisal-related increased responses in HC, compared to SAD. In addition, the dorsomedial prefrontal cortex (DMPFC), which showed reappraisal-related increased activity in both groups, had similar temporal dynamics in SAD and HC during the Faces and Criticism tasks, but greater late response increases in HC, compared to SAD, during the Beliefs task. Reappraisal-related greater late DMPFC responses were associated with greater percent reduction in negative emotion ratings in SAD patients. Conclusions These results suggest a dysfunction of cognitive reappraisal in SAD patients, with overall reduced late brain responses in prefrontal regions, particularly when reappraising faces. Decreased late activity in the DMPFC might be associated with deficient reappraisal and greater negative reactivity. Trial registration ClinicalTrials.gov identifier: NCT00380731 PMID:24517388

Stem Cell Therapy for Autism

PubMed Central

Ichim, Thomas E; Solano, Fabio; Glenn, Eduardo; Morales, Frank; Smith, Leonard; Zabrecky, George; Riordan, Neil H

2007-01-01

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism. PMID:17597540

[Strategies, actors, promises and fears in the smallpox vaccinations campaigns in Mexico: from the Porfiriato to the Post-revolution (1880-1940)].

PubMed

Agostoni, Claudia

2011-02-01

The article examines some of the strategies employed by the Mexican health authorities that led to the organization of massive and obligatory smallpox vaccination campaigns from the late 1880s to the 1940s, a period of Mexican history that corresponds to the Porfirio Díaz regime (1877-1911), to the armed phase of the Mexican Revolution (1910-1920), and to the first two decades of the Post-revolutionary governments (1920-1940). Attention will be placed of the vaccination programs in the main urban settings, notably in Mexico City, as well as the gradual but decisive organization and regulation of vaccination campaigns in the heterogeneous rural milieu. Furthermore, the importance that hygienic education acquired will be explored, as well as the divergent and contested responses that emerged due to the obligatory vaccination campaigns, responses that included resistance, fear, uncertainty and widespread acceptance.

Endogenous antipyretics.

PubMed

Roth, Joachim

2006-09-01

The febrile increase of body temperature is regarded as a component of the complex host response to infection or inflammation that accompanies the activation of the immune system. Late phases of fever appear mediated by pro-inflammatory cytokines called endogenous pyrogens. The rise of body temperature is beneficial because it accelerates several components of the activated immune system. To prevent an excessive and dangerous rise of body temperature the febrile response is controlled, limited in strength and duration, and sometimes even prevented by the actions of endogenous antipyretic substances liberated systemically or within the brain during fever. In most cases the antipyretic effects are achieved by an inhibitory influence on the formation or action of endogenous pyrogens, or by effects on neuronal thermoregulatory circuits that are activated during fever. Endogenous antipyretic substances include steroid hormones, neuropeptides, cytokines and other molecules. It is the purpose of this review to consider the current state in the research on endogenous antipyretic systems.

Basin fill evolution and paleotectonic patterns along the Samfrau geosyncline: the Sauce Grande basin-Ventana foldbelt (Argentina) and Karoo basin-Cape foldbelt (South Africa) revisited

NASA Astrophysics Data System (ADS)

López-Gamundí, O. R.; Rossello, E. A.

As integral parts of du Toit's (1927) ``Samfrau Geosyncline'', the Sauce Grande basin-Ventana foldbelt (Argentina) and Karoo basin-Cape foldbelt (South Africa) share similar paleoclimatic, paleogeographic, and paleotectonic aspects related to the Late Paleozoic tectono-magmatic activity along the Panthalassan continental margin of Gondwanaland. Late Carboniferou-earliest Permian glacial deposits were deposited in the Sauce Grande (Sauce Grande Formation) and Karoo (Dwyka Formation) basins and Falkland-Malvinas Islands (Lafonia Formation) during an initial (sag) phase of extension. The pre-breakup position of the Falkland (Malvinas) Islands on the easternmost part of the Karoo basin (immediately east of the coast of South Africa) is supported by recent paleomagnetic data, lithofacies associations, paleoice flow directions and age similarities between the Dwyka and the Lafonia glacial sequences. The desintegration of the Gondwanan Ice Sheet (GIS) triggered widespread transgressions, reflected in the stratigraphic record by the presence of inter-basinally correlatable, open marine, fine-grained deposits (Piedra Azul Formation in the Sauce Grande basin, Prince Albert Formation in the Karoo basin and Port Sussex Formation in the Falkland Islands) capping glacial marine sediments. These early postglacial transgressive deposits, characterised by fossils of the Eurydesma fauna and Glossopteris flora, represent the maximum flooding of the basins. Cratonward foreland subsidence was triggered by the San Rafael orogeny (ca. 270 Ma) in Argentina and propogated along the Gondwanan margin. This subsidence phase generated sufficient space to accommodate thick synorogenic sequences derived from the orogenic flanks of the Sauce Grande and Karoo basins. Compositionally, the initial extensional phase of these basins was characterized by quartz-rich, craton-derived detritus and was followed by a compressional (foreland) phase characterized by a paleocurrent reversal and dominance of arc/foldbelt-derived material. In the Sauce Grande basin, tuffs are interbedded in the upper half of the synorogenic, foldbelt-derived Tunas Formation (Early-early Late? Permian). Likewise, the first widespread appearance of tuffs in the Karoo basin is in the Whitehill Formation, of late Early Permian (260 Ma) age. Silicic volcanism along the Andes and Patagonia (Choiyoi magmatic province) peaked between the late Early Permian and Late Permian. A link between these volcanics and the consanguineous airborne tuffs present in the Sauce Grande and Karoo basins is suggested on the basis of their similar compositions and ages.

Remune trial will stop; new trials planned.

PubMed

James, J S

1999-05-21

A clinical trial using remune, the anti-HIV vaccine developed by the late Dr. Jonas Salk, has been ended. The study is a clinical-endpoint trial which looks for statistically significant differences in AIDS sickness or death between patients who add remune to their treatment regimens versus those who use a placebo. Agouron Pharmaceuticals and the Immune Response Corporation who were conducting the trial announced their decision to stop it after an analysis by the Data Safety Monitoring Board. No differences in clinical endpoints were found and it was projected that continuing the trial would likely not find any. The companies are now planning two new Phase III trials using viral load testing rather than clinical endpoints as study criteria.

Dynamical mechanisms of Arctic amplification.

PubMed

Dethloff, Klaus; Handorf, Dörthe; Jaiser, Ralf; Rinke, Annette; Klinghammer, Pia

2018-05-12

The Arctic has become a hot spot of climate change, but the nonlinear interactions between regional and global scales in the coupled climate system responsible for Arctic amplification are not well understood and insufficiently described in climate models. Here, we compare reanalysis data with model simulations for low and high Arctic sea ice conditions to identify model biases with respect to atmospheric Arctic-mid-latitude linkages. We show that an appropriate description of Arctic sea ice forcing is able to reproduce the observed winter cooling in mid-latitudes as result of improved tropospheric-stratospheric planetary wave propagation triggering a negative phase of the Arctic Oscillation/North Atlantic Oscillation in late winter. © 2018 New York Academy of Sciences.

Hypofractionated Image-guided Radiation Therapy (3Gy/fraction) in Patients Affected by Inoperable Advanced-stage Non-small Cell Lung Cancer After Long-term Follow-up.

PubMed

Agolli, Linda; Valeriani, Maurizio; Bracci, Stefano; Nicosia, Luca; DE Sanctis, Vitaliana; Enrici, Riccardo Maurizi; Osti, Mattia Falchetto

2015-10-01

We conducted long-term follow-up analysis of the outcomes for patients affected by advanced-stage non-small cell lung cancer (NSCLC) treated with hypofractionated radiotherapy (RT). Sixty patients with advanced-stage NSCLC (IIIA-IV) treated with hypofractionated radiotherapy (60Gy/20 fractions) were analyzed. Radiation was delivered using an image-guided RT technique to verify the correct position. Toxicities were graded according to the Common Toxicity Criteria for Adverse Effects v4.0 scale. Overall, six patients achieved a complete response and 46 patients had a partial response (tumor response rate 86%). After a median follow-up of 30 months, locoregional progression occurred in 23 patients and distant progression occurred in 38. The 1-year and 2-years overall survival were 57% and 40%, respectively. The 1-year and 2-years progression-free survival (PFS) were 47.1% and 33.5%, respectively. The median duration of OS and PFS was 13 months and 12 months, respectively. The 2-year local PFS and metastases-free survival (MFS) were 53% and 40.3%, respectively. On univariate analysis, the T-size (≥5 cm), and type of response to RT (non-response/progressive disease) were significantly associated with worse OS. Type of response was identified as significant prognostic factors for PFS (p<0.01) local PFS (p=0.015) and MFS (p<0.01). Acute grade 3 esophagitis and pneumonitis occurred in three patients (5%) and four patients (6%), respectively. Late grade 3 esophagitis and pneumonitis occurred in 2% (one patient) and 3% (two patients), respectively. No patient experienced grade 4 acute or late RT-related toxicities. Hypofractionated RT offers good disease control for patients with advanced-stage NSCLC with acceptable toxicity rates. Phase III randomized trials are necessary to compare hypofractionated RT with conventional RT. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Glacial geology of the Shingobee River headwaters area, north-central Minnesota

USGS Publications Warehouse

Melchior, Robert C.

2014-01-01

During middle and late Wisconsin time in the Shingobee River headwaters area, the Laurentide Wadena lobe, Hewitt and Itasca phases, produced terminal and ground moraine along with a variety of associated glacial features. The stratigraphic record is accessible and provides details of depositional mode as well as principal glacial events during the advance and retreat of middle and late Wisconsin ice tongues. Geomorphic features such as tunnel valleys, stream terraces, and postglacial stream cuts formed by erosional events persist to the present day. Middle Wisconsin Hewitt phase deposits are the oldest and include drumlins, ground moraine, boulder pavements, and outwash. Together, these deposits suggest a wet-based, periodically surging glacier in a subpolar thermal state. Regional permafrost and deposition from retreating ice are inferred between the end of the Hewitt phase and the advance of late Wisconsin Itasca phase ice. Itasca phase glaciation occurred as a contemporaneous pair of adjacent ice tongues whose contrasting moraine styles suggest independent flow modes. The western (Shingobee) portion of the Itasca moraine contains composite ridges, permafrost phenomena, hill-hole pairs, and debris flows. By contrast, eastern (Onigum) moraine deposits generally lack glaciotectonic features and consist almost exclusively of mud and debris flows. Near the end of the Itasca phase, large-scale hill-hole pairs developed in the Shingobee division, and debris flows from the Onigum division blocked the preexisting Shingobee tunnel valley to form glacial lake Willobee. Postglacial streams formed deep valleys as glacial lake Willobee catastrophically drained. Dates based on temperature trends in Greenland ice cores are proposed for prominent glacial events in the Shingobee area. This report proposes that Hewitt phase glaciation occurred between 27.2 and 23.6 kiloannum and Itasca phase glaciation between 22.8 and 14.7 kiloannum. Des Moines lobe (Younger Dryas) glaciation, which had only secondary effects on the Shingobee headwaters area, occurred between 13.5 and 11.6 kiloannum.

Clomiphene citrate before and after withdrawal bleeding for induction of ovulation in women with polycystic ovary syndrome: Randomized cross-over trial.

PubMed

Elbohoty, Ahmed E H; Amer, Mohamed; Abdelmoaz, Mohamed

2016-08-01

To compare the ovarian response to early versus late clomiphene citrate (CC) in women with polycystic ovary syndrome (PCOS). This cross-over randomized controlled clinical trial included 90 infertile amenorrheic women with PCOS. After inducing withdrawal bleeding, patients were randomly divided into two equal groups to receive ovulation induction with CC 100 mg/day for 5 days. Group I started treatment the next day after finishing medroxyprogesterone acetate course for a menstrual cycle, and after a washout period of another menstrual cycle, the treatment was shifted to start on day 2 of withdrawal bleeding. Group II received a reversed protocol: late then early treatment. Women were followed up on transvaginal ultrasonography to monitor follicular growth, endometrial thickness and evidence of ovulation. Human chorionic gonadotropin 10 000 IU was given i.m. to trigger ovulation when at least one mature follicle measured ≥18 mm at day 14. In all cases, early induction protocol resulted in significantly higher proportion of ovulating patients, thicker endometrium and higher number of follicles 14-17 mm in diameter, ≥ 18 mm in diameter and total number of follicles (P < 0.001 for all comparisons). In women with PCOS, early initiation of CC before withdrawal bleeding or during the last days of the luteal phase can achieve a better ovulatory response. © 2016 Japan Society of Obstetrics and Gynecology.

Mechanisms involved in regulating DNA replication origins during the cell cycle and in response to DNA damage.

PubMed Central

Early, Anne; Drury, Lucy S; Diffley, John F X

2004-01-01

Replication origins in eukaryotic cells never fire more than once in a given S phase. Here, we summarize the role of cyclin-dependent kinases in limiting DNA replication origin usage to once per cell cycle in the budding yeast Saccharomyces cerevisiae. We have examined the role of different cyclins in the phosphorylation and regulation of several replication/regulatory factors including Cdc6, Sic1, ORC and DNA polymerase alpha-primase. In addition to being regulated by the cell cycle machinery, replication origins are also regulated by the genome integrity checkpoint kinases, Mec1 and Rad53. In response to DNA damage or drugs which interfere with the progression of replication forks, the activation of late-firing replication origins is inhibited. There is evidence indicating that the temporal programme of origin firing depends upon the local histone acetylation state. We have attempted to test the possibility that checkpoint regulation of late-origin firing operates through the regulation of the acetylation state. We found that overexpression of the essential histone acetylase, Esal, cannot override checkpoint regulation of origin firing. We have also constructed a temperature-sensitive esa1 mutant. This mutant is unable to resume cell cycle progression after alpha-factor arrest. This can be overcome by overexpression of the G1 cyclin, Cln2, revealing a novel role for Esal in regulating Start. PMID:15065654

Genomic Analysis of the DNA Replication Timing Program during Mitotic S Phase in Maize (Zea mays) Root Tips[OPEN

PubMed Central

LeBlanc, Chantal; Lee, Tae-Jin; Mulvaney, Patrick; Allen, George C.; Martienssen, Robert A.; Thompson, William F.

2017-01-01

All plants and animals must replicate their DNA, using a regulated process to ensure that their genomes are completely and accurately replicated. DNA replication timing programs have been extensively studied in yeast and animal systems, but much less is known about the replication programs of plants. We report a novel adaptation of the “Repli-seq” assay for use in intact root tips of maize (Zea mays) that includes several different cell lineages and present whole-genome replication timing profiles from cells in early, mid, and late S phase of the mitotic cell cycle. Maize root tips have a complex replication timing program, including regions of distinct early, mid, and late S replication that each constitute between 20 and 24% of the genome, as well as other loci corresponding to ∼32% of the genome that exhibit replication activity in two different time windows. Analyses of genomic, transcriptional, and chromatin features of the euchromatic portion of the maize genome provide evidence for a gradient of early replicating, open chromatin that transitions gradually to less open and less transcriptionally active chromatin replicating in mid S phase. Our genomic level analysis also demonstrated that the centromere core replicates in mid S, before heavily compacted classical heterochromatin, including pericentromeres and knobs, which replicate during late S phase. PMID:28842533

Late time cosmological phase transitions 1: Particle physics models and cosmic evolution

NASA Technical Reports Server (NTRS)

Frieman, Joshua A.; Hill, Christopher T.; Watkins, Richard

1991-01-01

We described a natural particle physics basis for late-time phase transitions in the universe. Such a transition can seed the formation of large-scale structure while leaving a minimal imprint upon the microwave background anisotropy. The key ingredient is an ultra-light pseudo-Nambu-Goldstone boson with an astronomically large (O(kpc-Mpc)) Compton wavelength. We analyze the cosmological signatures of and constraints upon a wide class of scenarios which do not involve domain walls. In addition to seeding structure, coherent ultra-light bosons may also provide unclustered dark matter in a spatially flat universe, omega sub phi approx. = 1.

Reconstruction of Middle Eocene - Late Oligocene Southern Ocean paleoclimate through calcareous nannofossils and stable isotopes

NASA Astrophysics Data System (ADS)

Villa, Giuliana; Fioroni, Chiara; Persico, Davide; Pea, Laura; Bohaty, Steve

2010-05-01

The transition from the ice free early Paleogene world to the glaciated conditions of the early Oligocene has been matter of discussion in the last years. This transition has not been monotonic but punctuated by numerous transient cooling and warming events. Here we present a summary of recent studies based on Nannofossil response to climatic changes during the Eocene and Oligocene. Collected data issue from high latitudes ODP Sites 748, 738, 744, 689 and 690. Based on a detailed revision of the biostratigraphy carried out through quantitative analysis, we conducted paleoecological studies on calcareous nannofossils through the late middle Eocene to the - late Oligocene interval to identify abundance variations of selected taxa in response to changes in sea surface temperature (SST) and trophic conditions. The nannofossil-based interpretation has been compared with detailed oxygen and carbon stable isotope stratigraphy confirming the climate variability in the Southern Ocean for this time interval. We identify the Middle Eocene Climatic optimum (MECO) event, related with the regional exclusion of Paleogenic warm-water taxa from the Southern Ocean, followed by the progressive cooling trend particularly emphasized during the cooling events at about 39 Ma, 37 Ma and 35.5 Ma. In the earliest Oligocene, marked changes in calcareous nannofossil assemblages are strikingly associated with the Oi-1 event recorded in perfect accordance with the oxygen isotope records. For most of the Oligocene we recorded a cold phase, while a warming trend is detected in the late Oligocene. In addiction, a marked increase of taxa thriving in eutrophic conditions coupled with a decrease in oligotrophic taxa, suggests the presence of a time interval (from about 36 Ma to about 26 Ma) with prevailing eutrophic conditions that correspond to an increase of the carbon stable isotope curve. This interval well corresponds with the clay mineral concentration that shows at Site 738 a higher concentration in illite (Ehrmann and Mackensen, 1992). This result can be interpreted as a major influx of weathering in the basin, bringing more nutrients to the surface water. Our data confirm a strong climate variability in the Southern Ocean during the middle Eocene - late Oligocene and nannofossils demonstrate to be useful tools for paleoclimatic and paleoceanographic reconstructions.

Automated Detection of P. falciparum Using Machine Learning Algorithms with Quantitative Phase Images of Unstained Cells.

PubMed

Park, Han Sang; Rinehart, Matthew T; Walzer, Katelyn A; Chi, Jen-Tsan Ashley; Wax, Adam

2016-01-01

Malaria detection through microscopic examination of stained blood smears is a diagnostic challenge that heavily relies on the expertise of trained microscopists. This paper presents an automated analysis method for detection and staging of red blood cells infected by the malaria parasite Plasmodium falciparum at trophozoite or schizont stage. Unlike previous efforts in this area, this study uses quantitative phase images of unstained cells. Erythrocytes are automatically segmented using thresholds of optical phase and refocused to enable quantitative comparison of phase images. Refocused images are analyzed to extract 23 morphological descriptors based on the phase information. While all individual descriptors are highly statistically different between infected and uninfected cells, each descriptor does not enable separation of populations at a level satisfactory for clinical utility. To improve the diagnostic capacity, we applied various machine learning techniques, including linear discriminant classification (LDC), logistic regression (LR), and k-nearest neighbor classification (NNC), to formulate algorithms that combine all of the calculated physical parameters to distinguish cells more effectively. Results show that LDC provides the highest accuracy of up to 99.7% in detecting schizont stage infected cells compared to uninfected RBCs. NNC showed slightly better accuracy (99.5%) than either LDC (99.0%) or LR (99.1%) for discriminating late trophozoites from uninfected RBCs. However, for early trophozoites, LDC produced the best accuracy of 98%. Discrimination of infection stage was less accurate, producing high specificity (99.8%) but only 45.0%-66.8% sensitivity with early trophozoites most often mistaken for late trophozoite or schizont stage and late trophozoite and schizont stage most often confused for each other. Overall, this methodology points to a significant clinical potential of using quantitative phase imaging to detect and stage malaria infection without staining or expert analysis.

Automated Detection of P. falciparum Using Machine Learning Algorithms with Quantitative Phase Images of Unstained Cells

PubMed Central

Park, Han Sang; Rinehart, Matthew T.; Walzer, Katelyn A.; Chi, Jen-Tsan Ashley; Wax, Adam

2016-01-01

Malaria detection through microscopic examination of stained blood smears is a diagnostic challenge that heavily relies on the expertise of trained microscopists. This paper presents an automated analysis method for detection and staging of red blood cells infected by the malaria parasite Plasmodium falciparum at trophozoite or schizont stage. Unlike previous efforts in this area, this study uses quantitative phase images of unstained cells. Erythrocytes are automatically segmented using thresholds of optical phase and refocused to enable quantitative comparison of phase images. Refocused images are analyzed to extract 23 morphological descriptors based on the phase information. While all individual descriptors are highly statistically different between infected and uninfected cells, each descriptor does not enable separation of populations at a level satisfactory for clinical utility. To improve the diagnostic capacity, we applied various machine learning techniques, including linear discriminant classification (LDC), logistic regression (LR), and k-nearest neighbor classification (NNC), to formulate algorithms that combine all of the calculated physical parameters to distinguish cells more effectively. Results show that LDC provides the highest accuracy of up to 99.7% in detecting schizont stage infected cells compared to uninfected RBCs. NNC showed slightly better accuracy (99.5%) than either LDC (99.0%) or LR (99.1%) for discriminating late trophozoites from uninfected RBCs. However, for early trophozoites, LDC produced the best accuracy of 98%. Discrimination of infection stage was less accurate, producing high specificity (99.8%) but only 45.0%-66.8% sensitivity with early trophozoites most often mistaken for late trophozoite or schizont stage and late trophozoite and schizont stage most often confused for each other. Overall, this methodology points to a significant clinical potential of using quantitative phase imaging to detect and stage malaria infection without staining or expert analysis. PMID:27636719

Development of novel force-limiting grasping forceps with a simple mechanism.

PubMed

Sakaguchi, Yasuto; Sato, Toshihiko; Yutaka, Yojiro; Muranishi, Yusuke; Komatsu, Teruya; Yoshizawa, Akihiko; Nakajima, Naoki; Nakamura, Tatsuo; Date, Hiroshi

2018-06-06

In endoscopic surgery, fragile tissues may be damaged by the application of excessive force. Thus, we developed novel endoscopic forceps with a simple force-limiting mechanism. The novel forceps were constructed with a leaf spring, and the spring thickness determines grasping pressure. We established an evaluation system (maximum score is 11 points) for lung tissue damage leading to complications. We tested the conventional forceps (186.8 kPa) and 3 novel spring forceps with the following thicknesses: 1.3 mm (53.0 kPa), 2.2 mm (187.7 kPa) and 2.8 mm (369.2 kPa). After grasping, peripheral canine lung tissues were microscopically examined for acute- and late-phase damages. In the acute phase (20 sites), the novel forceps caused capillary congestion and haemorrhage in the subpleural tissue, whereas the conventional forceps caused deep tissue and pleural damages. In the late phase (30 sites), both forceps caused fibroblast formation and interstitial thickening, which progressed to the deeper tissues as grasping pressure increased. In the acute phase, the median scores were 2.0 and 6.0 for the novel and conventional forceps, respectively (P = 0.003). In the late phase, the median scores were 2.0, 2.5 and 5.0 for 1.3-, 2.2- and 2.8-mm thick forceps, respectively, and 5.0 for the conventional forceps (P < 0.001). In both phases, the novel forceps with grasping pressure set below 187.7 kPa (2.2 mm) caused significantly less lung tissue damage than the conventional forceps. The novel endoscopic forceps are able to regulate the tissue-grasping pressure and induce less damage in lung tissues than conventional forceps.

Jointing patterns and tectonic evolution of the Maciço Calcário Estremenho, Lusitanian Basin, Portugal

NASA Astrophysics Data System (ADS)

Carvalho, Jorge M. F.

2018-05-01

The Maciço Calcário Estremenho (MCE) is an uplifted Jurassic limestone massif unit of the Lusitanian Basin, Portugal, where five main joint sets trending NNE-SSW, WSW-ENE, WNW-ESE, NW-SE, and NNW-SSE are recognized. Except for the NNW-SSE set, all the other sets host calcite veins and barren joints, evidencing a multistage development by several deformation episodes, including shear reactivation. Orthogonal patterns defined by the NNE-SSW/WNW-ESE and NNW-SSE/WSW-ENE systems are characteristic of some tectonostratigraphic units of the MCE, but the sets of each one of the systems are genetically independent. They result from specific deformation episodes undergone by the studied area in the course of its Meso-Cenozoic evolution. NNE-SSW calcite veins were the first to form during Middle Jurassic fault-controlled subsidence. A renewal of this set as barren joints took place during the Eocene Pyrenean compressive phase. The WSW-ENE and WNW-ESE sets have a restricted spatial distribution and relate to transient compressive episodes of the Middle - Late Jurassic and Jurassic - Cretaceous transitions, respectively. The NW-SE set, also characteristic of a specific region, formed during the Late Jurassic rifting and is related to local NE-SW tension dependent on block tilting towards a major NW-SE fault. The Miocene Betic compressive phase is responsible for the formation of the NNW-SSE set, which is widespread throughout the MCE.

NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules

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

Shen, Qi; Zheng, Xingzheng; McNutt, Michael A.

2009-06-10

The midbody is a structural organelle formed in late phase mitosis which is responsible for completion of cytokinesis. Although various kinds of proteins have been found to distribute or immigrate to this organelle, their functions have still not been completely worked out. In this study, we demonstrated that NAT10 (N-acetyltransferase 10, NAT10) is not only predominantly distributed in the nucleolus in interphase, but is also concentrated in the mitotic midbody during telophase. The domain in N-terminal residues 549-834 of NAT10 specifically mediated its subcellular localization. Treatment with genotoxic agents or irradiation increased concentration of NAT10 in both the nucleolus andmore » midbody. Moreover, DNA damage induced increase of NAT10 in the midbody apparently accompanied by in situ elevation of the level of acetylated {alpha}-tubulin, suggesting that it plays a role in maintaining or enhancing stability of {alpha}-tubulin. The depletion of NAT10 induced defects in nucleolar assembly, cytokinesis and decreased acetylated {alpha}-tubulin, leading to G2/M cell cycle arrest or delay of mitotic exit. In addition, over-expression of NAT10 was found in a variety of soft tissue sarcomas, and correlated with tumor histological grading. These results indicate that NAT10 may play an important role in cell division through facilitating reformation of the nucleolus and midbody in the late phase of cell mitosis, and stabilization of microtubules.« less

Paleoclimatic analyses of middle Eocene through Oligocene planktic foraminiferal faunas

USGS Publications Warehouse

Keller, G.

1983-01-01

Quantitative faunal analyses and oxygen isotope ranking of individual planktic foraminiferal species from deep sea sequences of three oceans are used to make paleoceanographic and paleoclimatic inferences. Species grouped into surface, intermediate and deep water categories based on ??18O values provide evidence of major changes in water-mass stratification, and individual species abundances indicate low frequency cool-warm oscillations. These data suggest that relatively stable climatic phases with minor cool-warm oscillations of ???0.5 m.y. frequency are separated by rapid cooling events during middle Eocene to early Oligocene time. Five major climatic phases are evident in the water-mass stratification between middle Eocene through Oligocene time. Phase changes occur at P14/P15, P15/P16, P20/P21 and P21/P22 Zone boundaries and are marked by major faunal turnovers, rapid cooling in the isotope record, hiatuses and changes in the eustatic sea level. A general cooling trend between middle Eocene to early late Oligocene is indicated by the successive replacement of warm middle Eocene surface water species by cooler late Eocene intermediate water species and still cooler Oligocene intermediate and deep water species. Increased water-mass stratification in the latest Eocene (P17), indicated by the coexistence of surface, intermediate and deep dwelling species groups, suggest that increased thermal gradients developed between the equator and poles nearly coincident with the development of the psychrosphere. This pattern may be related to significant ice accumulation between late Eocene and early late Oligocene time. ?? 1983.

The screening Horndeski cosmologies

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

Starobinsky, Alexei A.; Department of General Relativity and Gravitation, Institute of Physics,Kazan Federal University,Kremlevskaya street 18, 420008 Kazan; Sushkov, Sergey V.

2016-06-06

We present a systematic analysis of homogeneous and isotropic cosmologies in a particular Horndeski model with Galileon shift symmetry, containing also a Λ-term and a matter. The model, sometimes called Fab Five, admits a rich spectrum of solutions. Some of them describe the standard late time cosmological dynamic dominated by the Λ-term and matter, while at the early times the universe expands with a constant Hubble rate determined by the value of the scalar kinetic coupling. For other solutions the Λ-term and matter are screened at all times but there are nevertheless the early and late accelerating phases. The modelmore » also admits bounces, as well as peculiar solutions describing “the emergence of time”. Most of these solutions contain ghosts in the scalar and tensor sectors. However, a careful analysis reveals three different branches of ghost-free solutions, all showing a late time acceleration phase. We analyse the dynamical stability of these solutions and find that all of them are stable in the future, since all their perturbations stay bounded at late times. However, they all turn out to be unstable in the past, as their perturbations grow violently when one approaches the initial spacetime singularity. We therefore conclude that the model has no viable solutions describing the whole of the cosmological history, although it may describe the current acceleration phase. We also check that the flat space solution is ghost-free in the model, but it may acquire ghost in more general versions of the Horndeski theory.« less

Meeting the Late-Career Needs of Faculty Transitioning Through Retirement: One Institution's Approach.

PubMed

Cain, Joanna M; Felice, Marianne E; Ockene, Judith K; Milner, Robert J; Congdon, John L; Tosi, Stephen; Thorndyke, Luanne E

2018-03-01

Medical school faculty are aging, but few academic health centers are adequately prepared with policies, programs, and resources (PPR) to assist late-career faculty. The authors sought to examine cultural barriers to successful retirement and create alignment between individual and institutional needs and tasks through PPR that embrace the contributions of senior faculty while enabling retirement transitions at the University of Massachusetts Medical School, 2013-2017. Faculty 50 or older were surveyed, programs at other institutions and from the literature (multiple fields) were reviewed, and senior faculty and leaders, including retired faculty, were engaged to develop and implement PPR. Cultural barriers were found to be significant, and a multipronged, multiyear strategy to address these barriers, which sequentially added PPR to support faculty, was put in place. A comprehensive framework of sequenced PPR was developed to address the needs and tasks of late-career transitions within three distinct phases: pre-retirement, retirement, and post-retirement. This sequential introduction approach has led to important outcomes for all three of the retirement phases, including reduction of cultural barriers, a policy that has been useful in assessing viability of proposed phased retirement plans, transparent and realistic discussions about financial issues, and consideration of roles that retired faculty can provide. The authors are tracking the issues mentioned in consultations and efficacy of succession planning, and will be resurveying faculty to further refine their work. This framework approach could serve as a template for other academic health centers to address late-career faculty development.

The screening Horndeski cosmologies

NASA Astrophysics Data System (ADS)

Starobinsky, Alexei A.; Sushkov, Sergey V.; Volkov, Mikhail S.

2016-06-01

We present a systematic analysis of homogeneous and isotropic cosmologies in a particular Horndeski model with Galileon shift symmetry, containing also a Λ-term and a matter. The model, sometimes called Fab Five, admits a rich spectrum of solutions. Some of them describe the standard late time cosmological dynamic dominated by the Λ-term and matter, while at the early times the universe expands with a constant Hubble rate determined by the value of the scalar kinetic coupling. For other solutions the Λ-term and matter are screened at all times but there are nevertheless the early and late accelerating phases. The model also admits bounces, as well as peculiar solutions describing ``the emergence of time''. Most of these solutions contain ghosts in the scalar and tensor sectors. However, a careful analysis reveals three different branches of ghost-free solutions, all showing a late time acceleration phase. We analyse the dynamical stability of these solutions and find that all of them are stable in the future, since all their perturbations stay bounded at late times. However, they all turn out to be unstable in the past, as their perturbations grow violently when one approaches the initial spacetime singularity. We therefore conclude that the model has no viable solutions describing the whole of the cosmological history, although it may describe the current acceleration phase. We also check that the flat space solution is ghost-free in the model, but it may acquire ghost in more general versions of the Horndeski theory.

Short-term soil responses to late-seeded cover crops in a semi-arid environment

USDA-ARS?s Scientific Manuscript database

Cover crops can expand ecosystem services, though sound management recommendations for their use within semi-arid cropping systems is currently constrained by a lack of information. This study was conducted to determine agroecosystem responses to late-summer seeded cover crops under no-till managem...

VizieR Online Data Catalog: Cobalt emission in nebular phase spectra (Childress+, 2015)

NASA Astrophysics Data System (ADS)

Childress, M. J.; Hillier, D. J.; Seitenzahl, I.; Sullivan, M.; Maguire, K.; Taubenberger, S.; Scalzo, R.; Ruiter, A.; Blagorodnova, N.; Camacho, Y.; Castillo, J.; Elias-Rosa, N.; Fraser, M.; Gal-Yam, A.; Graham, M.; Howell, D. A.; Inserra, C.; Jha, S. W.; Kumar, S.; Mazzali, P. A.; McCully, C.; Morales-Garoffolo, A.; Pandya, V.; Polshaw, J.; Schmidt, B.; Smartt, S.; Smith, K. W.; Sollerman, J.; Spyromilio, J.; Tucker, B.; Valenti, S.; Walton, N.; Wolf, C.; Yaron, O.; Young, D. R.; Yuan, F.; Zhang, B.

2018-01-01

The analysis in this work relies on a compilation of SN Ia nebular spectra from the literature as well as new observations. We obtained new late-phase (+50==+150 d) spectra of several nearby SNe Ia from numerous telescopes. Several late-phase spectra of very nearby SNe Ia were collected with the Wide Field Spectrograph (WiFeS; Dopita et al. 2007Ap&SS.310..255D, 2010Ap&SS.327..245D) on the Australian National University (ANU) 2.3 m telescope at Siding Spring Observatory in northern New South Wales, Australia. New nebular spectra for three nearby SNe Ia were collected with DEIMOS (Faber et al. 2003SPIE.4841.1657F) on the Keck-II telescope on Mauna Kea, Hawaii. (4 data files).

Alteration of carotid body chemoreflexes after neonatal intermittent hypoxia and caffeine treatment in rat pups.

PubMed

Julien, Cécile A; Joseph, Vincent; Bairam, Aida

2011-08-15

In human neonates, caffeine therapy for apnoea of prematurity, especially when associated with hypoxemia, is maintained for several weeks after birth. In the present study, we used newborn rats and whole-body plethysmography to test whether chronic exposure to neonatal caffeine treatment (NCT), alone or combined with neonatal intermittent hypoxia (n-IH) alters: (1) baseline ventilation and response to hypoxia (12% O(2), 20 min); and (2) response to acute i.p. injection of caffeine citrate (20 mg/kg) or domperidone, a peripheral dopamine D2 receptor antagonist (1 mg/kg). Four groups of rats were studied as follows: raised under normal conditions with daily gavage with water (NWT) or NCT, or exposed to n-IH (n-IH+NWT and n-IH+NCT) from postnatal days 3 to 12. In n-IH+NCT rats, baseline ventilation was higher than in the other groups. Caffeine or domperidone enhanced baseline ventilation only in NWT and n-IH+NWT rats, but neither caffeine nor domperidone affected the hypoxic ventilatory response in these groups. In n-IH+NWT rats, the response during the early phase of hypoxia (<10 min) was higher than in other groups. During the late response phase to hypoxia (20 min), ventilation was lower in n-IH+NWT and n-IH+NCT rats compared to NWT or NCT, and were not affected by caffeine or domperidone injection. NCT or caffeine injection decreased baseline apnoea frequency in all groups. These data suggest that chronic exposure to NCT alters both carotid body dopaminergic and adenosinergic systems and central regulation of breathing under baseline conditions and in response to hypoxia. Copyright © 2011 Elsevier B.V. All rights reserved.

Sex differences in stress response circuitry activation dependent on female hormonal cycle.

PubMed

Goldstein, Jill M; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

2010-01-13

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i.e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.

Structure and Evolution of the Central Andes of Peru

NASA Astrophysics Data System (ADS)

Gonzalez, L.; Pfiffner, O. A.

2009-04-01

Three major units make up the Andes in Peru: (1) The Western Cordillera consists of the Cretaceous Coastal Batholith intruding Jurassic to Cretaceous volcaniclastics (Casma group) in the west, and a fold-and-thrust belt of Mesozoic sediments in the east. Eocene and Miocene volcanics (Calipuy group and equivalents) overly all of these rock types. (2) The Central Highland contains a folded Paleozoic-Mesozoic sedimentary sequence overlain by thick Quaternary deposits. A major fault puts Neoproterozoic basement rocks of the Eastern Cordillera next to these units. (3) In the Eastern Cordillera, Late Paleozoic clastic successions unconformably overly folded Early Paleozoic sediments and a Neoproterozoic basement in the east. Permian (locally Triassic) granitoids intruded these units and were affected by folding and thrusting. In the core of the Eastern Cordillera, Early Cretaceous overly Early or Late Paleozoic strata. To the west, a thrust belt of Paleozoic to Cenozoic strata forms the transition to the foreland of the Brasilian shield. The most external part of this thrust belt involves Pliocene sediments and is referred to as Subandine zone. The Coastal Batholith is internally undeformed. The adjacent fold-and-thrust belt to the east is characterized by tight, nearly isoclinal upright folds with amplitudes of up to 1000 m. At the surface only Cretaceous rocks are observed. Using balancing techniques, a detachment horizon at the base of the Lowermost Cretaceous (Goyallarisquizga group - Oyon Formation) can be proposed. Further east, folds are more open, asymmetric and east verging, Jurassic sediments appear in the cores of the anticlines. The abrupt change in style from upright tight folding in the west to more open folding in the east is explained by a primary difference in the depositional sequence, most probably associated with synsedimentary faulting. The overlying volcanics of the Calipuy group and equivalents are, in turn, only slightly folded. In the Northern part of the Western Cordillera, near Huaraz, a vertical fault puts a Late Miocene to Early Pliocene batholith (Cordillera Blanca) in direct contact to Miocene volcanics (Calipuy group, Cordillera Negra). The structure of the Central Highlands is characterized by relatively open folds in the Paleozoic to Mesozoic strata. Overlying Quaternary deposits are tilted and locally even folded. Eocene to Miocene undeformed granitoids intrude these structures. A swarm of NNW-SSE striking and steeply dipping faults separate the Eastern Cordillera from the Highlands. Some of these faults suggest block faulting. However, near Huancayo a clear indication of strike-slip motion could be found. The Neoproterozoic basement rocks and the Early Paleozoic sediments are unconformably overlain by Late Paleozoic sediments which in turn are folded. Within the Subandine zone, the structural style is characterized by east directed imbricate thrusting. The thrust faults cut down into the crystalline basement going west, suggesting a detachment within upper crustal crystalline basement rocks. In the Central Peruvian Andes, compressional deformation events progressed from west to east. Early Cretaceous plutons of the coast batholith intruded folded Jurassic to Early Cretaceous volcaniclastic rocks of the Casma group and suggest an Early Cretaceous phase of shortening in the Pacific coastal area of the Western Cordillera (referred to as Mochica phase in the literature). Within the Western Cordillera, a major phase of pre-Eocene erosion removed a substantial amount of the tight upright folds. The youngest strata folded are of Late Cretaceous to Early Paleocene age (Red Beds). The overlying volcanics are slightly younger (middle Eocene) and bracket the tight folding, referred to as Inca phase, to Late Paleocene to Early Eocene times. This is corroborated by Eocene to Miocene granitic intrusions in the adjacent fold-and-thrust belt. Still younger deformations, referred to as Quechua Phase, produced gentle folds within the Eocene volcanics. Vertical motions in the Cordillera Blanca juxtaposed a Late Miocene-Pliocene batholith to Late Miocene volcanics. These movements are post-Pleistonce in age and still active. In the Central High Zone, even Pleistocene deposits were tilted and locally folded. Timing of the steeply dipping faults bordering the Eastern Cordillera is more difficult to assess. Cretaceous strata in tectonic contact with Neoproterozoic basement indicate a Cenozoic age. But within the fold-and-thrust belt of the Subandine zone in the east, youngest strata affected by thrusting are progressively younger toward the east. They suggest thrust propagation ranging from Oligocene to Pliocene age. These young thrust faults were responsible for the uplift of the Central Highland to their present elevation.

Relative timing of last glacial maximum and late-glacial events in the central tropical Andes

NASA Astrophysics Data System (ADS)

Bromley, Gordon R. M.; Schaefer, Joerg M.; Winckler, Gisela; Hall, Brenda L.; Todd, Claire E.; Rademaker, Kurt M.

2009-11-01

Whether or not tropical climate fluctuated in synchrony with global events during the Late Pleistocene is a key problem in climate research. However, the timing of past climate changes in the tropics remains controversial, with a number of recent studies reporting that tropical ice age climate is out of phase with global events. Here, we present geomorphic evidence and an in-situ cosmogenic 3He surface-exposure chronology from Nevado Coropuna, southern Peru, showing that glaciers underwent at least two significant advances during the Late Pleistocene prior to Holocene warming. Comparison of our glacial-geomorphic map at Nevado Coropuna to mid-latitude reconstructions yields a striking similarity between Last Glacial Maximum (LGM) and Late-Glacial sequences in tropical and temperate regions. Exposure ages constraining the maximum and end of the older advance at Nevado Coropuna range between 24.5 and 25.3 ka, and between 16.7 and 21.1 ka, respectively, depending on the cosmogenic production rate scaling model used. Similarly, the mean age of the younger event ranges from 10 to 13 ka. This implies that (1) the LGM and the onset of deglaciation in southern Peru occurred no earlier than at higher latitudes and (2) that a significant Late-Glacial event occurred, most likely prior to the Holocene, coherent with the glacial record from mid and high latitudes. The time elapsed between the end of the LGM and the Late-Glacial event at Nevado Coropuna is independent of scaling model and matches the period between the LGM termination and Late-Glacial reversal in classic mid-latitude records, suggesting that these events in both tropical and temperate regions were in phase.

Analysis of Dibenzothiophene Desulfurization in a Recombinant Pseudomonas putida Strain▿

PubMed Central

Calzada, Javier; Zamarro, María T.; Alcón, Almudena; Santos, Victoria E.; Díaz, Eduardo; García, José L.; Garcia-Ochoa, Felix

2009-01-01

Biodesulfurization was monitored in a recombinant Pseudomonas putida CECT5279 strain. DszB desulfinase activity reached a sharp maximum at the early exponential phase, but it rapidly decreased at later growth phases. A model two-step resting-cell process combining sequentially P. putida cells from the late and early exponential growth phases was designed to significantly increase biodesulfurization. PMID:19047400

Phase II Study of Chemoradiotherapy With 5-Fluorouracil and Cisplatin for Stage II-III Esophageal Squamous Cell Carcinoma: JCOG Trial (JCOG 9906)

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

Kato, Ken, E-mail: kenkato@ncc.go.jp; Muro, Kei; Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi

Purpose: In this Phase II study, we evaluated the efficacy and toxicity of chemoradiotherapy (CRT) with cisplatin (CDDP) and 5-fluorouracil (5-FU) for Stage II-III esophageal squamous cell carcinoma (ESCC). Patients and Methods: Patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) thoracic ESCC were enrolled between April 2000 and March 2002. Chemotherapy comprised two courses of protracted infusion of 5-FU (400 mg/m{sup 2}/day) on Days 1-5 and 8-12, and 2-h infusion of CDDP (40 mg/m{sup 2}) on Days 1 and 8; this regimen was repeated every 5 weeks. Concurrent radiotherapy involved 60-Gy irradiation (30 fractions) for 8 weeks with a 2-weekmore » break. Responders received two courses of 5-FU (800 mg/m{sup 2}/day) on Days 1-5 and CDDP (80 mg/m{sup 2}) on Day 1. Final analysis was conducted in March 2007. Survival and late toxicities were monitored for 5 years. Results: The characteristics of the 76 patients enrolled were as follows: median age, 61 years; male/female, 68/8; performance status 0/1, 59/17 patients; Stage IIA/IIB/III, 26/12/38 patients. Of the 74 eligible patients, 46 (62.2%) achieved complete response. Median survival time was 29 months, with 3- and 5-year survival rates of 44.7% and 36.8%, respectively. Acute toxicities included Grade 3/4 esophagitis (17%), nausea (17%), hyponatremia (16%), and infection without neutropenia (12%). Late toxicities comprised Grade 3/4 esophagitis (13%), pericardial (16%) and pleural (9%) effusion, and radiation pneumonitis (4%), causing 4 deaths. Conclusions: CRT is effective for Stage II-III ESCC with manageable acute toxicities and can provide a nonsurgical treatment option. However, further improvement is required for reduction in late toxicity.« less

Cell cycle progression is regulated by intertwined redox oscillators.

PubMed

da Veiga Moreira, Jorgelindo; Peres, Sabine; Steyaert, Jean-Marc; Bigan, Erwan; Paulevé, Loïc; Nogueira, Marcel Levy; Schwartz, Laurent

2015-05-29

The different phases of the eukaryotic cell cycle are exceptionally well-preserved phenomena. DNA decompaction, RNA and protein synthesis (in late G1 phase) followed by DNA replication (in S phase) and lipid synthesis (in G2 phase) occur after resting cells (in G0) are committed to proliferate. The G1 phase of the cell cycle is characterized by an increase in the glycolytic metabolism, sustained by high NAD+/NADH ratio. A transient cytosolic acidification occurs, probably due to lactic acid synthesis or ATP hydrolysis, followed by cytosolic alkalinization. A hyperpolarized transmembrane potential is also observed, as result of sodium/potassium pump (NaK-ATPase) activity. During progression of the cell cycle, the Pentose Phosphate Pathway (PPP) is activated by increased NADP+/NADPH ratio, converting glucose 6-phosphate to nucleotide precursors. Then, nucleic acid synthesis and DNA replication occur in S phase. Along with S phase, unpublished results show a cytosolic acidification, probably the result of glutaminolysis occurring during this phase. In G2 phase there is a decrease in NADPH concentration (used for membrane lipid synthesis) and a cytoplasmic alkalinization occurs. Mitochondria hyperfusion matches the cytosolic acidification at late G1/S transition and then triggers ATP synthesis by oxidative phosphorylation. We hypothesize here that the cytosolic pH may coordinate mitochondrial activity and thus the different redox cycles, which in turn control the cell metabolism.

Upregulation of Zinc Absorption Matches Increases in Physiologic Requirements for Zinc in Women Consuming High- or Moderate-Phytate Diets during Late Pregnancy and Early Lactation.

PubMed

Hambidge, K Michael; Miller, Leland V; Mazariegos, Manolo; Westcott, Jamie; Solomons, Noel W; Raboy, Victor; Kemp, Jennifer F; Das, Abhik; Goco, Norman; Hartwell, Ty; Wright, Linda; Krebs, Nancy F

2017-06-01

Background: Estimated physiologic requirements (PRs) for zinc increase in late pregnancy and early lactation, but the effect on dietary zinc requirements is uncertain. Objective: The aim of this study was to determine changes in daily fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of differing phytate contents in relation to physiologic zinc requirements during pregnancy and lactation. Methods: This was a prospective observational study of zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3) and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of childbearing age whose major food staple was maize and who had been randomly assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined from duplicate diets and fractional absorption (FAZ) by dual isotope ratio technique (TAZ = TDZ × FAZ). All variables were examined longitudinally and by group and compared with PRs. TAZ values at later phases were compared with phase 1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating (NPNL) women. Results: TAZ was greater in the LP group than in the C group at all phases. All variables increased from phase 1 to phases 2 and 3 and declined at phase 4. TAZ increased by 1.25 mg/d ( P = 0.045) in the C group and by 0.81 mg/d ( P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d ( P = 0.002) in the C group and 2.28 mg/d ( P = 0.0004) in the LP group, compared with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values in phases 2-4. Conclusions: Upregulation of zinc absorption in late pregnancy and early lactation matches increases in PRs of pregnant and lactating women, regardless of dietary phytate, which has implications for dietary zinc requirements of pregnant and lactating women. © 2017 American Society for Nutrition.

Clinical effects of laser immunotherapy on metastatic cancer patients

NASA Astrophysics Data System (ADS)

Naylor, Mark F.; Lam, Anh K.; Bahavar, Cody F.; Nordquist, Robert E.; Chen, Wei R.

2016-03-01

Clinical trials of late-stage breast cancer patients and late-stage melanoma patients treated by laser immunotherapy (LIT) have shown promising results. In a 2010 study of Li et al, eleven late-stage melanoma patients received LIT in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. Long-term, positive response was observed in six patients. All lesions in the treatment area of the patients responded to LIT, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%.2 In 2011, Li et al, treated ten late stage breast cancer patients with LIT.1 In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%.1 This review demonstrates that LIT is safe and well tolerated, so it can be easily applied on an outpatient basis and can be combined with other pharmaceutical modalities to improve the therapeutic response of metastatic cancers.

Identification of T-Waves in the Alboran Sea

NASA Astrophysics Data System (ADS)

Carmona, Enrique; Almendros, Javier; Alguacil, Gerardo; Soto, Juan Ignacio; Luzón, Francisco; Ibáñez, Jesús M.

2015-11-01

Analyses of seismograms from ~1,100 north-Moroccan earthquakes recorded at stations of the Red Sísmica de Andalucía (Southern Spain) reveal the systematic presence of late phases embedded in the earthquake codas. These phases have distinctive frequency contents, similar to the P and S spectra and quite different to the frequency contents of the earthquake codas. They are best detected at near-shore stations. Their amplitudes decay significantly with distance to the shoreline. The delays with respect to the P-wave onsets of the preceding earthquakes are consistently around 85 s. Late phases are only detected for earthquakes located in a small region of about 100 × 60 km centered at 35.4°N, 4.0°W near the northern coast of Morocco. Several hypotheses could, in principle, explain the presence of these late phases in the seismograms, for example, the occurrence of low-energy aftershocks, efficient wave reflections, or Rayleigh waves generated along the source-station paths. However, we conclude that the most-likely origin of these phases corresponds to the incidence of T-waves (generated by conversion from elastic to acoustic energy in the north-Moroccan coast) in the southern coast of the Iberian Peninsula. T-waves are thought to be generated by energy trapping in low-velocity channels along long oceanic paths; in this case, we demonstrate that they can be produced in much shorter paths as well. Although T-waves have been already documented in other areas of the Mediterranean Sea, this is the first time that they have been identified in the Alboran Sea.

Carboniferous Proto-type Basin Evolution of Junggar Basin in Northwest China: Implications for the Growth Models of Central Asia Orogenic Belt

NASA Astrophysics Data System (ADS)

He, D.

2016-12-01

The Junggar Basin locates in the central part of Paleo-Asian Ocean tectonic domain, and records the dynamic processes of the Central Asian Orogenic Belt from subduction-accretion-collision to later intracontinental deformations. Carboniferous is the key period from subduction to closure in the tectonic evolution of Paleo-Asian Ocean. Based on the borehole, outcrop, seismic and gravity and magnetic anomaly data, the paper made analysis of the Carboniferous basin evolution.Geo-chronological results for the borehole volcanic rocks suggest that the Junggar Basin and adjacent area had five periods of volcanic activities, including two periods in the Early Carboniferous (359-347Ma 347-331Ma and 331-324Ma) and three periods in the Late Carboniferous (323-307Ma and 307-300Ma). Regional unconformities divided the Carboniferous into two tectono-stratigraphic sequences: Lower Carboniferous and Upper Carboniferous. The former is characterized by compressional structures and involves massive calc-alkaline basalts, andesites, dacites and rhyolites, whereas the later is mainly controlled by extensional faults and dominated by intermediate-mafic volcanic rocks, with bimodal volcanic rocks in parts. The paper determined four Carboniferous arc-basin belts in the Junggar Basin and adjacent area from north to south: the Saur-Fuhai-Dulate, Heshituoluogai-Wulungu-Yemaquan, Darbut-Luliang-Karamaili, and Zhongguai-Mosuowan-Baijiahai-Qitai, and identified multi-type basins, such as fore-arc basin, retro-arc basin, intra-arc rift basin, foreland basin and passive continental margin basin,etc.. The Carboniferous proto-type basin evolution of the Junggar Basin can be divided into three phases such as, the early to middle Early Carboniferous subduction-related compressional phase, the late Early Carboniferous to middle Late Carboniferous subduction-related extensional phase and the late Late Carboniferous intra-continental fault-sag phase. The study discloses that the Junggar Basin is likely underlain by juvenile continental crust rather than unified Precambrian basement, and also implies that the Junggar Basin and adjacent area, even the entire CAOB, were built by successively northward amalgamation of multiple linear arc-basin systems characterized by southward accretion.

Neural activation in the orbitofrontal cortex in response to male faces increases during the follicular phase

PubMed Central

Rupp, Heather A.; James, Thomas W.; Ketterson, Ellen D.; Sengelaub, Dale R.; Janssen, Erick; Heiman, Julia R.

2009-01-01

Women’s sexual interest changes with hormonal fluctuations across the menstrual cycle. It is unclear how hormones modify women’s sexual behavior and desire, but one possibility is that they alter women’s positive appraisals of stimuli and thus their sexual interest. Using 3 T fMRI, we measured neural activation in women at two time points in their menstrual cycle (late follicular, luteal) while they evaluated photos of men presented as potential sexual partners. Participants were ten heterosexual women aged 23–28 none of who was using hormonal contraceptives or in a committed relationship. In an event-related design, the women were presented with as series of photos of male faces and asked questions to assess their degree of sexual interest in the men depicted. Results demonstrate an overall effect of menstrual cycle phase on neural activation. During their follicular versus luteal phase, women demonstrated increased activation in the right medial orbitofrontal cortex (OFC), suggesting increased positive appraisal. Activation in the OFC was positively correlated with women’s estradiol to progesterone ratios. There were no areas that demonstrated increased activation during the luteal versus follicular phase. The observed increase in activation in the OFC during the follicular phase may reflect a hormonally mediated increase in appetitive motivation and may prime women towards increased sexual interest and behavior around ovulation. PMID:19306881

Assessing the duration of drowning episodes during the Early Cretaceous

NASA Astrophysics Data System (ADS)

Godet, A.; Föllmi, K. B.

2013-12-01

Drowning unconformities are stratigraphic key surfaces in the history of carbonate platforms. They mostly consist in the deposition of deep marine facies on top of shallow marine limestones. Although large-scale depositional geometries mimic lowstand systems track architecture, these sedimentary turnovers are developed in relation with major sea level rise, inducing an increase in the rate of creation of accommodation space that outpaces the capacity of carbonate to keep up. This so-called paradox of carbonate platform drowning implies that other parameters than purely eustatic fluctuations are involved in the demise of shallow marine ecosystems. Worldwide and at different time during Earth history, in-depth studies of drowning unconformities revealed that changes in nutrient input, clastic delivery, temperature, or a combination of them may be responsible for a decrease in light penetration in the water column and the progressive suffocation and poisoning of photosynthetic carbonate producers. The examination of such case examples from various stratigraphic intervals and palaeogeographical settings thus helps in identifying and hierarchizing potential triggering mechanisms for drowning unconformities. This is complemented by new data from Early Cretaceous successions from the Helvetic Alps. During this time period, the Helvetic carbonate platform developed along the northern Tethyan margin using both photozoan and heterozoan communities. Phases of healthy production were interrupted by several drowning episodes. The latter are marked in the sedimentary record by condensation and associated phosphogenesis and glauconitisation. From the earliest Valanginian to the early to late Barremian, three drowning unconformities reflect the intermittent installation of a more humid climate and subsequent enhanced trophic conditions, which first induced a switch from photozoan to heterozoan communities and then to long-lasting drowning phases. The latter encompass several sea level rise and fall cycles, and may be linked to strengthened upwelling currents. Moreover during the late Hauterivian - early Barremian time period, the correlation of platform carbonates with basinal sediments, by means of bio-, chemo- and sequence stratigraphy, allows to estimate the duration of a drowning episode. With the return to more oligotrophic conditions during the late Barremian, photozoan, Urgonian-type communities took up again. Their development has been abruptly stopped at the end of the early Aptian by a major emersion phase. The subsequent drowning is documented in various peritethyan areas. This initial crisis is followed by three other drowning phases that ultimately led to the replacement of shallow ecosystems by a deeper marine sedimentation in the Cenomanian. This long-term trend in the evolution of the Helvetic carbonate platform and of other peritethyan ecosystems may have been driven by more global phenomena.

Sensitivity of the Atmospheric Response to Warm Pool El Nino Events to Modeled SSTs and Future Climate Forcings

NASA Technical Reports Server (NTRS)

Hurwitz, Margaret M.; Garfinkel, Chaim I.; Newman, Paul A.; Oman, Luke D.

2013-01-01

Warm pool El Nino (WPEN) events are characterized by positive sea surface temperature (SST) anomalies in the central equatorial Pacific. Under present-day climate conditions, WPEN events generate poleward propagating wavetrains and enhance midlatitude planetary wave activity, weakening the stratospheric polar vortices. The late 21st century extratropical atmospheric response to WPEN events is investigated using the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM), version 2. GEOSCCM simulations are forced by projected late 21st century concentrations of greenhouse gases (GHGs) and ozone-depleting substances (ODSs) and by SSTs and sea ice concentrations from an existing ocean-atmosphere simulation. Despite known ocean-atmosphere model biases, the prescribed SST fields represent a best estimate of the structure of late 21st century WPEN events. The future Arctic vortex response is qualitatively similar to that observed in recent decades but is weaker in late winter. This response reflects the weaker SST forcing in the Nino 3.4 region and subsequently weaker Northern Hemisphere tropospheric teleconnections. The Antarctic stratosphere does not respond to WPEN events in a future climate, reflecting a change in tropospheric teleconnections: The meridional wavetrain weakens while a more zonal wavetrain originates near Australia. Sensitivity simulations show that a strong poleward wavetrain response to WPEN requires a strengthening and southeastward extension of the South Pacific Convergence Zone; this feature is not captured by the late 21st century modeled SSTs. Expected future increases in GHGs and decreases in ODSs do not affect the polar stratospheric responses to WPEN.

Amount of fear extinction changes its underlying mechanisms

PubMed Central

An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

2017-01-01

There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that. DOI: http://dx.doi.org/10.7554/eLife.25224.001 PMID:28671550

Habit learning and the genetics of the dopamine D3 receptor: evidence from patients with schizophrenia and healthy controls.

PubMed

Kéri, Szabolcs; Juhász, Anna; Rimanóczy, Agnes; Szekeres, György; Kelemen, Oguz; Cimmer, Csongor; Szendi, István; Benedek, György; Janka, Zoltán

2005-06-01

In this study, the authors investigated the relationship between the Ser9Gly (SG) polymorphism of the dopamine D3 receptor (DRD3) and striatal habit learning in healthy controls and patients with schizophrenia. Participants were given the weather prediction task, during which probabilistic cue-response associations were learned for tarot cards and weather outcomes (rain or sunshine). In both healthy controls and patients with schizophrenia, participants with Ser9Ser (SS) genotype did not learn during the early phase of the task (1-50 trials), whereas participants with SG genotype did so. During the late phase of the task (51-100 trials), both participants with SS and SG genotype exhibited significant learning. Learning rate was normal in patients with schizophrenia. These results suggest that the DRD3 variant containing glycine is associated with more efficient striatal habit learning in healthy controls and patients with schizophrenia. (c) 2005 APA, all rights reserved.

48 CFR 1815.208 - Submission, modification, revision, and withdrawal of proposals. (NASA supplements paragraph (b))

Code of Federal Regulations, 2010 CFR

2010-10-01

... late proposal criteria do not apply to Announcements of Opportunity, NASA Research Announcements, and Small Business Innovative Research (SBIR) Phase I and Phase II solicitations, and Small Business... Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CONTRACTING METHODS AND CONTRACT...

Recovery of cat retinal ganglion cell sensitivity following pigment bleaching.

PubMed Central

Bonds, A B; Enroth-Cugell, C

1979-01-01

1. The threshold illuminance for small spot stimulation of on-centre cat retinal ganglion cells was plotted vs. time after exposure to adapting light sufficiently strong to bleach significant amounts of rhodopsin. 2. When the entire receptive field of an X- or Y-type ganglion cell is bleached by at most 40%, recovery of the cell's rod-system proceeds in two phases: an early relatively fast one during which the response appears transient, and a late, slower one during which responses become more sustained. Log threshold during the later phase is well fit by an exponential in time (tau = 11.5-38 min). 3. After bleaches of 90% of the underlying pigment, threshold is cone-determined for as long as 40 min. Rod threshold continues to decrease for at least 85 min after the bleach. 4. The rate of recovery is slower after strong than after weak bleaches; 10 and 90% bleaches yield time constants for the later phase of 11.5 and 38 min, respectively. This contrasts with an approximate time constant of 11 min for rhodopsin regeneration following any bleach. 5. The relationship between the initial elevation of log rod threshold extrapolated from the fitted exponential curves and the initial amount of pigment bleached is monotonic, but nonlinear. 6. After a bleaching exposure, the maintained discharge is initially very regular. The firing rate first rises, then falls to the pre-bleach level, with more extended time courses of change in firing rate after stronger exposures. The discharge rate is restored before threshold has recovered fully. 7. The change in the response vs. log stimulus relationship after bleaching is described as a shift of the curve to the right, paired with a decrease in slope of the linear segment of the curve. PMID:521963

Light at night acutely impairs glucose tolerance in a time-, intensity- and wavelength-dependent manner in rats.

PubMed

Opperhuizen, Anne-Loes; Stenvers, Dirk J; Jansen, Remi D; Foppen, Ewout; Fliers, Eric; Kalsbeek, Andries

2017-07-01

Exposure to light at night (LAN) has increased dramatically in recent decades. Animal studies have shown that chronic dim LAN induced obesity and glucose intolerance. Furthermore, several studies in humans have demonstrated that chronic exposure to artificial LAN may have adverse health effects with an increased risk of metabolic disorders, including type 2 diabetes. It is well-known that acute exposure to LAN affects biological clock function, hormone secretion and the activity of the autonomic nervous system, but data on the effects of LAN on glucose homeostasis are lacking. This study aimed to investigate the acute effects of LAN on glucose metabolism. Male Wistar rats were subjected to i.v. glucose or insulin tolerance tests while exposed to 2 h of LAN in the early or late dark phase. In subsequent experiments, different light intensities and wavelengths were used. LAN exposure early in the dark phase at ZT15 caused increased glucose responses during the first 20 min after glucose infusion (p < 0.001), whereas LAN exposure at the end of the dark phase, at ZT21, caused increased insulin responses during the first 10 min (p < 0.01), indicating that LAN immediately induces glucose intolerance in rats. Subsequent experiments demonstrated that the effect of LAN was both intensity- and wavelength-dependent. White light of 50 and 150 lx induced greater glucose responses than 5 and 20 lx, whereas all intensities other than 5 lx reduced locomotor activity. Green light induced glucose intolerance, but red and blue light did not, suggesting the involvement of a specific retina-brain pathway. Together, these data show that exposure to LAN has acute adverse effects on glucose metabolism in a time-, intensity- and wavelength-dependent manner.

Breakup of Pangaea and plate kinematics of the central Atlantic and Atlas regions

NASA Astrophysics Data System (ADS)

Schettino, Antonio; Turco, Eugenio

2009-08-01

A new central Pangaea fit (type A) is proposed for the late Ladinian (230 Ma), together with a plate motions model for the subsequent phases of rifting, continental breakup and initial spreading in the central Atlantic. This model is based on: (1) a reinterpretation of the process of formation of the East Coast Magnetic Anomaly along the eastern margin of North America and the corresponding magnetic anomalies at the conjugate margins of northwest Africa and the Moroccan Meseta; (2) an analysis of major rifting events in the central Atlantic, Atlas and central Mediterranean and (3) a crustal balancing of the stretched margins of North America, Moroccan Meseta and northwest Africa. The process of fragmentation of central Pangaea can be described by three major phases spanning the time interval from the late Ladinian (230 Ma) to the Tithonian (147.7 Ma). During the first phase, from the late Ladinian (230 Ma) to the latest Rhaetian (200 Ma), rifting proceeded along the eastern margin of North America, the northwest African margin and the High, Saharan and Tunisian Atlas, determining the formation of a separate Moroccan microplate at the interface between Gondwana and Laurasia. During the second phase, from the latest Rhaetian (200 Ma) to the late Pliensbachian (185 Ma), oceanic crust started forming between the East Coast and Blake Spur magnetic anomalies, whereas the Morrocan Meseta simply continued to rift away from North America. During this time interval, the Atlas rift reached its maximum extent. Finally, the third phase, encompassing the time interval from the late Pliensbachian (185 Ma) to chron M21 (147.7 Ma), was triggered by the northward jump of the main plate boundary connecting the central Atlantic with the Tethys area. Therefore, as soon as rifting in the Atlas zone ceased, plate motion started along complex fault systems between Morocco and Iberia, whereas a rift/drift transition occurred in the northern segment of the central Atlantic, between Morocco and the conjugate margin of Nova Scotia. The inversion of the Atlas rift and the subsequent formation of the Atlas mountain belt occurred during the Oligocene-early Miocene time interval. In the central Atlantic, this event was associated with higher spreading rates of the ridge segments north of the Atlantis FZ. An estimate of 170 km of dextral offset of Morocco relative to northwest Africa, in the central Atlantic, is required by an analysis of marine magnetic anomalies. Five plate tectonic reconstructions and a computer animation are proposed to illustrate the late Triassic and Jurassic process of breakup of Pangaea in the central Atlantic and Atlas regions.

Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing's disease: 12-month, Phase III pasireotide study.

PubMed

Findling, James W; Fleseriu, Maria; Newell-Price, John; Petersenn, Stephan; Pivonello, Rosario; Kandra, Albert; Pedroncelli, Alberto M; Biller, Beverly M K

2016-11-01

Measuring salivary cortisol is a simple, convenient and accurate technique with potential value in monitoring patients with hypercortisolism. This analysis reports changes in late-night salivary cortisol (LNSC) during a 12-month, multicentre, Phase III study of patients with Cushing's disease who were randomized to pasireotide 600 or 900 μg sc bid. LNSC assessment was an exploratory objective based on a single, optional measurement at midnight ± 1 h on the same day as one of the 24-h urinary free cortisol (UFC) measurements. Of 162 enrolled patients, baseline LNSC was measured in 93. Sixty-seven patients had levels above the upper limit of normal (ULN); median baseline levels were 19.7 and 20.7 nmol/L in the groups subsequently randomized to 600 μg (n = 40) and 900 μg (n = 27), respectively. Median LNSC levels decreased from baseline to month 12; median changes in patients who had baseline LNSC > ULN in the 600 and 900 μg groups were -13.4 nmol/L (-52.6 %; n = 19) and -11.8 nmol/L (-56.1 %; n = 14), respectively. LNSC normalized at months 6 and 12 in 25/67 (37.3 %) and 13/67 (19.4 %) patients, respectively; 10/25 and 8/13 patients also had normalized UFC, and 7/25 and 4/13 had partial UFC control (UFC > ULN and ≥50 % decrease from baseline). There was a moderate correlation (r = 0.55) on the log scale between individual patient LNSC and UFC values when all time points were pooled. Pasireotide decreased LNSC levels during 12 months of treatment. Salivary cortisol may be a simple, convenient biomarker for assessing treatment response in patients with Cushing's disease.

The Effect of Low Survey Response Rates on Estimates of Alcohol Consumption in a General Population Survey

PubMed Central

Meiklejohn, Jessica; Connor, Jennie; Kypri, Kypros

2012-01-01

Background Response rates for surveys of alcohol use are declining for all modes of administration (postal, telephone, face-to-face). Low response rates may result in estimates that are biased by selective non-response. We examined non-response bias in the NZ GENACIS survey, a postal survey of a random electoral roll sample, with a response rate of 49.5% (n = 1924). Our aim was to estimate the magnitude of non-response bias in estimating the prevalence of current drinking and heavy episodic (binge) drinking. Methods We used the “continuum of resistance” model to guide the investigation. In this model the likelihood of response by sample members is related to the amount of effort required from the researchers to elicit a response. First, the demographic characteristics of respondents and non-respondents were compared. Second, respondents who returned their questionnaire before the first reminder (early), before the second reminder (intermediate) or after the second reminder (late) were compared by demographic characteristics, 12-month prevalence of drinking and prevalence of binge drinking. Results Demographic characteristics and prevalence of binge drinking were significantly different between late respondents and early/intermediate respondents, with the demographics of early and intermediate respondents being similar to people who refused to participate while late respondents were similar to all other non-respondents. Assuming non-respondents who did not actively refuse to participate had the same drinking patterns as late respondents, the prevalence of binge drinking amongst current drinkers was underestimated. Adjusting the prevalence of binge drinkers amongst current drinkers using population weights showed that this method of adjustment still resulted in an underestimate of the prevalence. Conclusions The findings suggest non-respondents who did not actively refuse to participate are likely to have similar or more extreme drinking behaviours than late respondents, and that surveys of health compromising behaviours such as alcohol use are likely to underestimate the prevalence of these behaviours. PMID:22532858

Addition of m6A to SV40 late mRNAs enhances viral structural gene expression and replication

PubMed Central

Courtney, David G.

2018-01-01

Polyomaviruses are a family of small DNA tumor viruses that includes several pathogenic human members, including Merkel cell polyomavirus, BK virus and JC virus. As is characteristic of DNA tumor viruses, gene expression in polyomaviruses is temporally regulated into an early phase, consisting of the viral regulatory proteins, and a late phase, consisting of the viral structural proteins. Previously, the late transcripts expressed by the prototypic polyomavirus simian virus 40 (SV40) were reported to contain several adenosines bearing methyl groups at the N6 position (m6A), although the precise location of these m6A residues, and their phenotypic effects, have not been investigated. Here, we first demonstrate that overexpression of the key m6A reader protein YTHDF2 induces more rapid viral replication, and larger viral plaques, in SV40 infected BSC40 cells, while mutational inactivation of the endogenous YTHDF2 gene, or the m6A methyltransferase METTL3, has the opposite effect, thus suggesting a positive role for m6A in the regulation of SV40 gene expression. To directly test this hypothesis, we mapped sites of m6A addition on SV40 transcripts and identified two m6A sites on the viral early transcripts and eleven m6A sites on the late mRNAs. Using synonymous mutations, we inactivated the majority of the m6A sites on the SV40 late mRNAs and observed that the resultant viral mutant replicated more slowly than wild type SV40. Alternative splicing of SV40 late mRNAs was unaffected by the reduction in m6A residues and our data instead suggest that m6A enhances the translation of viral late transcripts. Together, these data argue that the addition of m6A residues to the late transcripts encoded by SV40 plays an important role in enhancing viral gene expression and, hence, replication. PMID:29447282

Linking Late Miocene Magmatism and Exhumation of the Pamir-West Kunlun Mountains to Lithospheric Thinning

NASA Astrophysics Data System (ADS)

Cao, K.; Wang, G.; Zeng, Z.; Replumaz, A.

2016-12-01

In this study, we report newly-discovered potassic plutons emplaced at 11 Ma in the SE Pamir. Together with recently-reported volcanism at 12 Ma in the West Kunlun Mts. (Cao et al., 2015), it can be inferred that Late Miocene magmas extend from the north-central Tibet to the central Pamir. Furthermore, our new apatite fission-track analysis in the SE Pamir-West Kunlun Mountains present uniform ages clustering at 11-6 Ma. Forward and inverse modeling indicate Late Miocene ( 11-6 Ma) rapid exhumation of the SE Pamir-West Kunlun Mountains, concurrent with accelerated exhumation of the Shakhdara dome (Stübner et al., 2013), initial doming of the Muztagata massif (Robinson et al., 2007; Sobel et al., 2011; Cao et al., 2013), and thrusting of the front faults along Pamir-West Kunlun Mts. (Bershaw et al., 2012; Cao et al., 2013, 2015). The simultaneous doming and potassic magmatism could attributed to stress relaxation of the upper crust at that time, possibly driven by the thinning of lower lithosphere beneath Pamir-West Kunlun Mts.. Such plausible mechanisms could be responsible for Neogene magmatism, rock exhumation and plateau growth in northwestern Tibet. At the continental scale, our results support that the Tibetan Plateau underwent a Late Miocene phase of deformation and developed outward and upward since then (Molnar et al., 2012). Three representative models are proposed to account for Late Miocene magmatism and crustal deformation in northern Tibet, including 1) southward subduction of the Tarim lithosphere mantle (Matte et al., 1996; Wittlinger et al., 2004), 2) convective removal of lower lithosphere (Molnar et al., 1993; Turner et al., 1993, 1996), and 3) penetration of molten crust into Kunlun terrane (Le Pape et al., 2012; Wang et al., 2012). Our results allow to discuss these competing models in the western Tibet, to better understand the intracontinent orogenesis in central Asia, in which the lithospheric processes have led to upper crust deformation.

BDNF is essential to promote persistence of long-term memory storage

PubMed Central

Bekinschtein, Pedro; Cammarota, Martín; Katche, Cynthia; Slipczuk, Leandro; Rossato, Janine I.; Goldin, Andrea; Izquierdo, Ivan; Medina, Jorge H.

2008-01-01

Persistence is a characteristic attribute of long-term memories (LTMs). However, little is known about the molecular mechanisms that mediate this process. We recently showed that persistence of LTM requires a late protein synthesis- and BDNF-dependent phase in the hippocampus. Here, we show that intrahippocampal delivery of BDNF reverses the deficit in memory persistence caused by inhibition of hippocampal protein synthesis. Importantly, we demonstrate that BDNF induces memory persistence by itself, transforming a nonlasting LTM trace into a persistent one in an ERK-dependent manner. Thus, BDNF is not only necessary, but sufficient to induce a late postacquisition phase in the hippocampus essential for persistence of LTM storage. PMID:18263738

Oncogenic transformation through the cell cycle and the LET dependent inverse dose rate effect

NASA Technical Reports Server (NTRS)

Geard, C. R.; Miller, R. C.; Brenner, D. J.; Hall, E. J.; Wachholz, B. W. (Principal Investigator)

1994-01-01

Synchronised populations of mouse C3H/10T-1/2 cells were obtained by a stringent mitotic dislodgment procedure. Mitotic cells rapidly attach and progress sequentially through the cell cycle. Irradiation (3 Gy of X rays) was carried out at intervals from 0 to 18 h after initiating cell cycle progression of the mitotic cells. Oncogenic transformation was enhanced 10-fold over cells irradiated soon after replating (G1 and S phases) for cells in a near 2 h period corresponding to cells in G2 phase but not in mitosis. The cell surviving fraction had a 2-1/2-fold variation with resistant peaks corresponding to the late G1 and late S phases. These findings provide experimental support for the hypothesis initiated by Rossi and Kellerer and developed by Brenner and Hall to explain the LET dependent inverse dose rate effect for oncogenic transformation.

78 FR 58123 - Migratory Bird Hunting; Final Frameworks for Late-Season Migratory Bird Hunting Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

... recommended changing Indiana's experimental late Canada goose season status to operational. Service Response: We concur with the Mississippi Flyway Council's recommendation to make Indiana's experimental late Canada goose season in the Terre Haute region operational. In 2007, Indiana initiated an experimental...

Growing supermassive black holes in the late stages of galaxy mergers are heavily obscured

NASA Astrophysics Data System (ADS)

Ricci, C.; Bauer, F. E.; Treister, E.; Schawinski, K.; Privon, G. C.; Blecha, L.; Arevalo, P.; Armus, L.; Harrison, F.; Ho, L. C.; Iwasawa, K.; Sanders, D. B.; Stern, D.

2017-06-01

Mergers of galaxies are thought to cause significant gas inflows to the inner parsecs, which can activate rapid accretion on to supermassive black holes (SMBHs), giving rise to active galactic nuclei (AGN). During a significant fraction of this process, SMBHs are predicted to be enshrouded by gas and dust. Studying 52 galactic nuclei in infrared-selected local luminous and ultraluminous infrared galaxies in different merger stages in the hard X-ray band, where radiation is less affected by absorption, we find that the amount of material around SMBHs increases during the last phases of the merger. We find that the fraction of Compton-thick (CT, N H ≥ 1024 cm- 2) AGN in late-merger galaxies is higher (f_ CT=65^{+12}_{-13}{per cent}) than in local hard X-ray selected AGN (f CT = 27 ± 4 per cent), and that obscuration reaches its maximum when the nuclei of the two merging galaxies are at a projected distance of D12 ≃ 0.4-10.8 kpc (f_ CT=77_{-17}^{+13}{per cent}). We also find that all AGN of our sample in late-merger galaxies have N H > 1023 cm- 2, which implies that the obscuring material covers 95^{+4}_{-8}{per cent} of the X-ray source. These observations show that the material is most effectively funnelled from the galactic scale to the inner tens of parsecs during the late stages of galaxy mergers, and that the close environment of SMBHs in advanced mergers is richer in gas and dust with respect to that of SMBHs in isolated galaxies, and cannot be explained by the classical AGN unification model in which the torus is responsible for the obscuration.

Transforming Growth Factor β1 (TGFβ1) and Progesterone Regulate Matrix Metalloproteinases (MMP) in Human Endometrial Stromal Cells

PubMed Central

Itoh, Hiroko; Kishore, Annavarapu Hari; Lindqvist, Annika; Rogers, David E.

2012-01-01

Context: Menstruation is preceded by progesterone withdrawal and endometrial matrix remodeling predominantly through induction of matrix metalloproteinases (MMP) and recruitment of invading neutrophils. Design: Using endometrial tissues from women during various phases of the menstrual cycle, we found that MMP2, MMP9, and MMP11 were up-regulated in the late secretory phase/premenstrual phase. Because TGFβ-responsive genes were also up-regulated in endometrium during this time, we tested the hypothesis that TGFβ1 and progesterone regulate expression of MMP in human endometrial stromal cells (HESC). Results: Treatment of HESC with TGFβ1 resulted in marked increases in MMP2 and MMP11 mRNA and pro- and active MMP2 activity. Progesterone inhibited TGFβ1-induced stimulation of MMP2 and MMP11 through its nuclear hormone receptors. Interestingly, TGFβ1 also decreased progesterone receptor (PR)-A and PR-B in HESC with a more pronounced effect on PR-A. Conclusions: These data support the hypothesis that TGFβ1 has endogenous anti-progestational effects in HESC and that the opposing effects of progesterone and TGFβ1 are important in regulation of matrix integrity in human endometrium. PMID:22466340

A tissue engineered human endometrial stroma that responds to cues for secretory differentiation, decidualization and menstruation

PubMed Central

Schutte, Stacey C.; Taylor, Robert N.

2012-01-01

Objective To show the responsiveness of a tissue engineered human endometrial stroma to combinations of hormones mimicking the secretory and menstrual phases of the cycle. Design In vitro experimental study Setting University uterine biology research laboratory Cells Telomerase immortalized human endometrial stromal cells Interventions The stromal cells were cultured in monolayers (2D) or encapsulated in a collagen I hydrogel (3D) to create a simplified tissue engineered stroma. The cells and tissues were exposed to hormone treatments mimicking early and late secretory phases, decidualization and steroid withdrawal conditions to recapitulate menstruation. Main Outcome Measure(s) Morphological and biochemical markers of decidualization and collagenase activity Result(s) The 3D tissue is capable of manifesting changes in morphology and biochemical markers of decidualization similar to 2D culture and characteristic of endometrial stroma in vivo. Unlike 2D culture, the 3D tissue responded to steroid withdrawal by increased collagenase activity and tissue breakdown. Conclusion(s) 3D tissue engineered endometrial stroma can mimic secretory and menstrual phases of the cycle and may be useful for studying uterine receptivity and menstruation in a physiological endocrine environment. PMID:22306710

Development of anticipatory postural adjustments during locomotion in children.

PubMed

Hirschfeld, H; Forssberg, H

1992-08-01

1. Anticipatory postural adjustments were studied in children (6-14 yr of age) walking on a treadmill while pulling a handle. Electromyographs (EMGs) and movements were recorded from the left arm and leg. 2. Postural activity in the leg muscles preceded voluntary arm muscle activity in all age groups, including the youngest children (6 yr of age). The latency to both leg and arm muscle activity, from a triggering audio signal, decreased with age. 3. In older children the latency to both voluntary and postural activity was influenced by the phase of the step cycle. The shortest latency to the first activated postural muscle occurred during single support phase in combination with a long latency to arm muscle activity. 4. In the youngest children, there was no phase-dependent modulation of the latency to the activation of the postural muscles. The voluntary activity was delayed during the beginning of the support phase resulting in a long delay between leg and arm muscle activity. 5. The postural muscle activation pattern was modified in a phase-dependent manner in all children. Lateral gastrocnemius (LG) and hamstring muscles (HAM) were activated during the early support phase, whereas tibialis anterior (TA) and quadriceps (Q) muscles were activated during the late support phase and during the swing phase. However, in the 6-yr-old children, LG was also activated in the swing phase. LG was activated before the HAM activity in the youngest children but after HAM in 14-yr-old children and adults. 6. The occurrence of LG activity in postural responses before heel strike suggests an immature (nonplantigrade) gating of postural activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Specific Reaction Patterns to Distinct Positive Emotional Cues Related to Incentive Motivation in Dependence of the Taq1A-Polymorphism: Molecular Genetic Associations of Early and Late Event-Related Potentials.

PubMed

Munk, Aisha J L; Wielpuetz, Catrin; Osinsky, Roman; Müller, Erik M; Grant, Phillip; Hennig, Jürgen

2016-01-01

Early and late event-related potential (ERP) responses, representing early subconscious and late motivational processes, were recorded for positive emotional words related to 'wanting' and 'liking', in dependence of the dopamine-related Taq1A genotype (ANKK1/DRD2). Research suggests that 'wanting' as opposed to 'liking' is related to dopaminergic processes. Therefore, it was hypothesized that risk allele carriers of the Taq1A polymorphism exhibit late ERP changes in reaction to words representing incentive motivation, i.e. 'wanting' (word categories 'lust' and 'anticipation'), but not to words representing 'liking' ('closeness'). Seventy-two male participants performed an emotional-word Stroop task during EEG recording and were genotyped according to the Taq1A polymorphism of ANKK1/DRD2. Positive emotional words related to anticipation and lust revealed blunted responses in the late positive potential (LPP) in carriers of the A1 allele, an effect absent in response to 'liking'-related words. These differences were not evident in the earlier posterior negativity (EPN). As no differences in dependence of the Taq1A genotype were observed in reaction to 'wanting'- and 'liking'-related words in the EPN, but merely in the LPP, it can be assumed that incentive-motivational stimuli only modify motivation-related ERP responses in carriers of the A1 allele of the Taq1A polymorphism, indicating the role of dopamine in late ERP components. © 2016 S. Karger AG, Basel.

Curcumin's Neuroprotective Efficacy in Drosophila Model of Idiopathic Parkinson's Disease Is Phase Specific: Implication of its Therapeutic Effectiveness

PubMed Central

Phom, Limamanen; Achumi, Bovito; Alone, Debasmita P.; Muralidhara

2014-01-01

Abstract Selective degeneration of dopaminergic neurons in the substantia nigra underlies the basic motor impairments of Parkinson's disease (PD). Curcumin has been used for centuries in traditional medicines in India. Our aim is to understand the efficacy of genotropic drug curcumin as a neuroprotective agent in PD. Analysis of different developmental stages in model organisms revealed that they are characterized by different patterns of gene expression which is similar to that of developmental stages of human. Genotropic drugs would be effective only during those life cycle stages for which their target molecules are available. Hence there exists a possibility that targets of genotropic compounds such as curcumin may not be present in all life stages. However, no reports are available in PD models illustrating the efficacy of curcumin in later phases of adult life. This is important because this is the period during which late-onset disorders such as idiopathic PD set in. To understand this paradigm, we tested the protective efficacy of curcumin in different growth stages (early, late health stage, and transition phase) in adult Drosophila flies. Results showed that it can rescue the motor defects during early stages of life but is ineffective at later phases. This observation was substantiated with the finding that curcumin treatment could replenish depleted brain dopamine levels in the PD model only during early stages of life cycle, clearly suggesting its limitation as a therapeutic agent in late-onset neurodegenerative disorders such as PD. PMID:25238331

Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection

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

Zhao, Hongxing, E-mail: Hongxing.Zhao@igp.uu.se; Chen, Maoshan; Lind, Sara Bergström

The deregulation of cellular long non-coding RNA (lncRNA) expression during a human adenovirus infection was studied by deep sequencing. Expression of lncRNAs increased substantially following the progression of the infection. Among 645 significantly expressed lncRNAs, the expression of 398 was changed more than 2-fold. More than 80% of them were up-regulated and 80% of them were detected during the late phase. Based on the genomic locations of the deregulated lncRNAs in relation to known mRNAs and miRNAs, they were predicted to be involved in growth, structure, apoptosis and wound healing in the early phase, cell proliferation in the intermediate phasemore » and protein synthesis, modification and transport in the late phase. The most significant functions of cellular RNA-binding proteins, previously shown to interact with the deregulated lncRNAs identified here, are involved in RNA splicing, nuclear export and translation events. We hypothesize that adenoviruses exploit the lncRNA network to optimize their reproduction. - Highlights: • The expression of 398 lncRNAs showed a distinct temporal pattern during Ad2 infection. • 80% of the deregulated lncRNAs were up-regulated during the late phase of infection. • The deregulated lncRNAs potentiallyinteract with 33 cellular RNA binding proteins. • These RBPs are involved in RNA splicing, nuclear export and translation. • Adenovirus exploits the cellular lncRNA network to optimize its replication.« less

Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid.

PubMed

Clemmensen, Anders; Andersen, Klaus E; Clemmensen, Ole; Tan, Qihua; Petersen, Thomas K; Kruse, Torben A; Thomassen, Mads

2010-09-01

The pathogenesis of irritant contact dermatitis (ICD) is poorly understood, and genes participating in the epidermal response to chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies ((1/2), 4, and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to either sodium lauryl sulfate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays (representing 47,000 transcripts) revealed essentially different pathway responses (1/2)hours after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen-activated signaling cascades including extracellular signal-regulated kinase and growth factor receptor signaling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed, whereas we identified 23 suggested common biomarkers for ICD. In conclusion, we bring new insights into two hitherto less well-elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative mild exposures, respectively.

Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

PubMed Central

Liu, Zhongwu; Chopp, Michael

2015-01-01

Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

Neural correlates of appetitive extinction in humans

PubMed Central

Tapia León, Isabell; Stark, Rudolf; Klucken, Tim

2017-01-01

Abstract Appetitive extinction receives attention as an important model for the treatment of psychiatric disorders. However, in humans, its underlying neural correlates remain unknown. To close this gap, we investigated appetitive acquisition and extinction with fMRI in a 2-day monetary incentive delay paradigm. During appetitive conditioning, one stimulus (CS+) was paired with monetary reward, while another stimulus (CS−) was never rewarded. Twenty-four hours later, subjects underwent extinction, in which neither CS was reinforced. Appetitive conditioning elicited stronger skin conductance responses to the CS+ as compared with the CS−. Regarding subjective ratings, the CS+ was rated more pleasant and arousing than the CS− after conditioning. Furthermore, fMRI-results (CS+ − CS−) showed activation of the reward circuitry including amygdala, midbrain and striatal areas. During extinction, conditioned responses were successfully extinguished. In the early phase of extinction, we found a significant activation of the caudate, the hippocampus, the dorsal and ventral anterior cingulate cortex (dACC and vACC). In the late phase, we found significant activation of the nucleus accumbens (NAcc) and the amygdala. Correlational analyses with subjective ratings linked extinction success to the vACC and the NAcc, while associating the dACC with reduced extinction. The results reveal neural correlates of appetitive extinction in humans and extend assumptions from models for human extinction learning. PMID:27803289

Ectoine and 5-hydroxyectoine accumulation in the halophile Virgibacillus halodenitrificans PDB-F2 in response to salt stress.

PubMed

Tao, Ping; Li, Hui; Yu, Yunjiang; Gu, Jidong; Liu, Yongdi

2016-08-01

The moderately halophilic bacterium Virgibacillus halodenitrificans PDB-F2 copes with salinity by synthesizing or taking up compatible solutes. The main compatible solutes in this strain were ectoine and hydroxyectoine, as determined by (1)H nuclear magnetic resonance spectroscopy ((1)H-NMR). A high-performance liquid chromatography (HPLC) analysis showed that ectoine was the major solute that was synthesized in response to elevated salinity, while hydroxyectoine was a minor solute. However, the hydroxyectoine/ectoine ratio increased from 0.04 at 3 % NaCl to 0.45 at 15 % NaCl in the late exponential growth phase. A cluster of ectoine biosynthesis genes was identified, including three genes in the order of ectA, ectB, and ectC. The hydroxyectoine biosynthesis gene ectD was not part of the ectABC gene cluster. Reverse transcription-quantitative polymerase chain reactions (RT-qPCR) showed that the expression of the ect genes was salinity dependent. The expression of ectABC reached a maximum at 12 % NaCl, while ectD expression increased up to 15 % NaCl. Ectoine and hydroxyectoine production was growth phase dependent. The hydroxyectoine/ectoine ratio increased from 0.018 in the early exponential phase to 0.11 in the stationary phase at 5 % NaCl. Hydroxyectoine biosynthesis started much later than ectoine biosynthesis after osmotic shock, and the temporal expression of the ect genes differed under these conditions, with the ectABC genes being expressed first, followed by ectD gene. Increased culture salinity triggered ectoine or hydroxyectoine uptake when they were added to the medium. Hydroxyectoine was accumulated preferentially when both ectoine and hydroxyectoine were provided exogenously.

Controlling the Mesostructure Formation within the Shell of Novel Cubic/Hexagonal Phase Cetyltrimethylammonium Bromide-Poly(acrylamide-acrylic acid) Capsules for pH Stimulated Release.

PubMed

Tangso, Kristian J; Patel, Hetika; Lindberg, Seth; Hartley, Patrick G; Knott, Robert; Spicer, Patrick T; Boyd, Ben J

2015-11-11

The self-assembly of ordered structures in mixtures of oppositely charged surfactant and polymer systems has been exploited in various cleaning and pharmaceutical applications and continue to attract much interest since their discovery in the late twentieth century. The ability to control the electrostatic and hydrophobic interactions that dictate the formation of liquid crystalline phases in these systems is advantageous in manipulation of structure and rendering them responsive to external stimuli. Nanostructured capsules comprised of the cationic surfactant, cetyltrimethylammonium bromide (CTAB), and the diblock copolymer poly(acrylamide-acrylic acid) (PAAm-AA) were prepared to assess their potential as pH responsive nanomaterials. Crossed-polarizing light microscopy (CPLM) and small-angle X-ray scattering (SAXS) identified coexisting Pm3n cubic and hexagonal phases at the surfactant-polymer interface. The hydrophobic and electrostatic interactions between the oppositely charged components were studied by varying temperature and solution pH, respectively, and were found to influence the liquid crystalline nanostructure formed. The lattice parameter of the mesophases and the fraction of cubic phase in the system decreased upon heating. Acidic conditions resulted in the loss of the highly ordered structures due to protonation of the carboxylic acid group, and subsequent reduction of attractive forces previously present between the oppositely charged molecules. The rate of release of the model hydrophilic drug, Rhodamine B (RhB), from nanostructured macro-sized capsules significantly increased when the pH of the solution was adjusted from pH 7 to pH 2. This allowed for immediate release of the compound of interest "on demand", opening new options for structured materials with increased functionality over typical layer-by-layer capsules.

Prolonged hypothalamic-pituitary-adrenal axis activation after acute coronary syndrome in the GENESIS-PRAXY cohort.

PubMed

Tang, Andrew R; Rabi, Doreen M; Lavoie, Kim L; Bacon, Simon L; Pilote, Louise; Kline, Gregory A

2018-01-01

Background Glucocorticoid excess has been linked with cardiovascular disease. Little is known about the long-term cortisol response in patients after acute coronary syndrome. Design The objective of this study was to describe the distribution of salivary cortisol in the post-acute phase of acute coronary syndrome and to describe the association of late-night salivary cortisol with cardiovascular risk factors. Methods We used late-night salivary cortisol measurements post-discharge to estimate hypothalamic-pituitary-adrenal axis activity in 309 patients aged 18-55 years enrolled in the GENESIS-PRAXY study from January 2009-April 2013. We evaluated hypothalamic-pituitary-adrenal axis activity and its association with hypertension, dyslipidemia, diabetes, smoking, family history, prior acute coronary syndrome, psychiatric diseases, acute coronary syndrome severity, as well as mortality and rate of rehospitalization at 12 months. Results Persistently elevated late-night salivary cortisol>2.92 nmol/l was seen in 99 (32.0%) patients: within the range of what may be seen in Cushing's disease. Elevated late-night salivary cortisol was associated with previous acute coronary syndrome (13.3% vs 24.2%, p = 0.02), peripheral vascular disease (3.8% vs 13.1%, p = 0.002), and smoking (32.9% vs 46.5% p = 0.02). Elevated late-night salivary cortisol was associated with higher hemoglobin A1c values (5.6 ± 3.0 vs 6.1 ± 2.9, p = 0.008) and lower high density lipoprotein values (0.94 ± 0.53 vs 0.86 ± 0.50, p = 0.01). There were no differences in psychiatric symptom scores, acute coronary syndrome severity or mortality, and rate of rehospitalization at 12 months. Conclusions Many patients post-acute coronary syndrome have prolonged, marked activation of the hypothalamic-pituitary-adrenal axis. Late-night salivary cortisol co-associates with several cardiovascular risk factors. Further studies are needed to confirm the exact role of hypothalamic-pituitary-adrenal axis activity in the pathophysiology of cardiovascular disease.

The Effective Regulation of Pro- and Anti-inflammatory Cytokines Induced by Combination of PA-MSHA and BPIFB1 in Initiation of Innate Immune Responses.

PubMed

Zhou, Weiqiang; Duan, Zhiwen; Yang, Biao; Xiao, Chunling

2017-01-01

PA-MSHA and BPIFB1 play especially important roles in triggering innate immune responses by inducing production of pro- or anti-inflammatory cytokines in the oral cavity and upper airway. We found that PA-MSHA had a strong ability to activate pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. However, BPIFB1 alone did not express a directly inductive effect. With incubation of PA-MSHA and BPIFB1, the combination can activate the CD14/TLR4/MyD88 complex and induce secretion of subsequent downstream cytokines. We used a proteome profiler antibody array to evaluate the phosphokinases status with PA-MSHA and BPIFB1 treatment. The results showed that the activation of MAPK, STAT, and PI-3K pathways is involved in PA-MSHA-BPIFB1 treatment, and that the related pathways control the secretion of targeting cytokines in the downstream. When we assessed the content changes of cytokines, we found that PA-MSHA-BPIFB1 treatment increased the production of pro-inflammatory cytokines in the early phase of treatment and induced the increase of IL-4 in the late phase. Our observations suggest that PA-MSHA-BPIFB1 stimulates the release of pro-inflammatory cytokines, and thereby initiates the innate immune system against inflammation. Meanwhile, the gradual release of anti-inflammatory cytokine IL-4 by PA-MSHA-BPIFB1 can also regulate the degree of inflammatory response; thus the host can effectively resist the environmental risks, but also manipulate inflammatory response in an appropriate and adjustable manner.

Complex response of a midcontinent north America drainage system to late Wisconsinan sedimentation

USGS Publications Warehouse

Bettis, E. Arthur; Autin, W.J.

1997-01-01

The geomorphic evolution of Mud Creek basin in eastern Iowa, U.S.A. serves to illustrate how geomorphic influences such as sediment supply, valley gradient, climate, and vegetation are recorded in the alluvial stratigraphic record. Sediment supply to the fluvial system increased significantly during the late Wisconsinan through a combination of periglacial erosion and loess accumulation. Subsequent evolution of the Holocene alluvial stratigraphic record reflects long-term routing of the late Wisconsinan sediment through the drainage basin in a series of cut-and-fill cycles whose timing was influenced by hydrologic response to change in climate and vegetation. When viewed in a regional context, the alluvial stratigraphic record appears to reflect a long-term complex response of the fluvial system to increased sediment supply during the late Wisconsinan. Hydrologic and sediment-supply changes accompanying the spread of Euroamerican agriculture to the basin in the 180Os dramatically upset trends in sedimentation and channel behavior established during the Holocene. Copyright ?? 1997, SEPM (Society for Sedimentary Geology).

Continuous oral levonorgestrel/ethinyl estradiol for treating premenstrual dysphoric disorder.

PubMed

Halbreich, Uriel; Freeman, Ellen W; Rapkin, Andrea J; Cohen, Lee S; Grubb, Gary S; Bergeron, Richard; Smith, Lynne; Mirkin, Sebastian; Constantine, Ginger D

2012-01-01

The study was conducted to investigate continuous daily levonorgestrel 90 mcg/ethinyl estradiol 20 mcg (LNG/EE) on premenstrual dysphoric disorder (PMDD). In this multicenter, randomized, double-blind, placebo-controlled study, women with PMDD received LNG/EE (n=186) or placebo (n=181) daily for 112 days and completed the Daily Record of Severity of Problems (DRSP). Mean DRSP change from baseline to late luteal phase was significantly greater with LNG/EE than placebo at the late luteal phase of the first estimated cycle (-30.52±1.73 [SE] vs. -22.47±1.77; p<.001) and the worst 5 days during the last on-therapy estimated cycle (-26.77±1.83 vs. -20.89±1.82; p=.016). Other primary end points were not statistically significant. Significantly more subject taking LNG/EE (52%) than placebo (40%) responded (≥50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of ≥1 improvement) at last on-therapy cycle (p=.025). Continuous daily LNG 90 mcg/EE 20 mcg was well tolerated and may be useful for managing the physical, psychological and behavioral symptoms and loss of work productivity related to PMDD. Copyright © 2012 Elsevier Inc. All rights reserved.

Seedlings of subtropical rainforest species from similar successional guild show different photosynthetic and morphological responses to varying light levels.

PubMed

Lestari, D Puji; Nichols, J Doland

2017-02-01

Restoration using rainforest species in Australia and elsewhere has been limited to a small number of widely known species, mainly pioneer or early successional species, Using the presumed successional status as a guideline for species selection in reforestation should be taken with a caveat since a species' capacity to adjust to light gradients is not easily predicted. This study examined the photosynthetic and growth responses of four Australian subtropical rainforest species in the context of using late successional species in restoration programs. Since the selected species [Sloanea australis ((Benth.) F. Muell.), Cinnamomum oliveri (F. M. Bailey),Caldcluvia paniculosa ((F. Muell.) Hoogland) and Geissois benthamiana (F. Muell.)] are considered late-successional species, this study also discussed the possibility of separating these species according to their acclimation level towards light gradients. Seedlings of four species were grown under four light treatments using neutral density shade cloth (5, 33, 64 and 80% irradiance) during summer November 2014 to February 2015. All species demonstrated a narrow range of photosynthetic acclimation to different light levels, experienced photoinhibition and photodamage in 80% irradiance and allocated more biomass to leaves in 5% irradiance, supporting their classification as late successional species. Cinnamomum oliveri was the only species able to utilize higher irradiance, with a higher light saturated rate of photosynthesis than the other species. Canonical analysis of principal coordinates revealed that the degree of plasticity of each species in response to contrasting irradiance levels varied. This analysis separated the species into three light tolerance classes: obligate shade-adapted species (S. australis and G. benthamiana), high light-adapted species (C. paniculosa) and the generalist (C. oliveri). Overall, this study suggests that the four species can be planted and will grow well under 33-64% irradiance since either lower or higher irradiance inhibits growth, and additionally that C. paniculosa and C. oliveri can be possibly planted in early phase of restoration planting with other early-successional species. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Incubation temperature alters thermal preference and response to heat stress of broiler chickens along the rearing phase.

PubMed

Morita, V S; Almeida, V R; Matos Junior, J B; Vicentini, T I; van den Brand, H; Boleli, I C

2016-08-01

The current study aimed to investigate whether embryonic temperature manipulation may alter thermal preference throughout the rearing phase of broiler chickens and how this manipulation may affect response to thermal challenge, metabolism, growth rate and feed intake rate. Eggs were exposed to a constant incubation temperature [machine temperatures: 36°C (Low), 37.5°C (Control), and 39°C (High); eggshell temperature of 37.4 ± 0.08°C, 37.8 ± 0.15°C, and 38.8 ± 0.33°C, respectively] from d 13 till hatching. Low treatment chickens showed lower plasma T3 and GH levels at d 1 of age and lower T3 level at d 42 of age compared to the Control treatment. Preferred ambient, rectal temperature, T4 level, growth rate, food intake rate, and response to thermal challenge were not altered in these chickens. On the other hand, High-treatment chickens exhibited high preferred ambient temperature and rectal temperature during the first 2 wk post-hatch, lower plasma T3 level at d 21 and 42 and a delayed increase in respiratory movement in response to thermal challenge compared to the Control treatment. However, chickens subjected to the Control and High treatments did not differ in T4 and GH level and performance. We conclude that exposure to high temperature during late embryonic development has long-lasting effects on the thermoregulatory system of broiler chickens by affecting the heat tolerance of these chickens. Moreover, the preferred ambient temperature of the chickens from heat-treated eggs correspond to those recommended for the strain under study, whereas for the cold-treated and control-chickens it was 1°C below, indicating that incubation temperature might have consequences on the ambient temperature chickens require during the rearing phase. © 2016 Poultry Science Association Inc.

Geometry and kinematics of Majiatan Fold-and-thrust Belt, Western Ordos Basin: implication for Tectonic Evolution of North-South Tectonic Belt

NASA Astrophysics Data System (ADS)

He, D.

2017-12-01

The Helan-Chuandian North-South Tectonic Belt crossed the central Chinese mainland. It is a boundary of geological, geophysical, and geographic system of Chinese continent tectonics from shallow to deep, and a key zone for tectonic and geomorphologic inversion during Mesozoic to Cenozoic. It is superimposed by the southeastward and northeastward propagation of Qinghai-Tibet Plateau in late Cenozoic. It is thus the critical division for West and East China since Mesozoic. The Majiatan fold-and-thrust belt (MFTB), locating at the central part of HCNSTB and the western margin of Ordos Basin, is formed by the tectonic evolution of the Helan-Liupanshan Mountains. Based on the newly-acquired high-resolution seismic profiles, deep boreholes, and surface geology, the paper discusses the geometry, kinematics, and geodynamic evolution of MFTB. With the Upper Carboniferous coal measures and the pre-Sinian ductile zone as the detachments, MFTB is a multi-level detached thrust system. The thrusting was mainly during latest Jurassic to Late Cretaceous, breaking-forward in the foreland, and resulting in a shortening rate of 25-29%. By structural restoration, this area underwent extension in Middle Proterozoic to Paleozoic, which can be divided into three phases of rifting such as Middle to Late Proterozoic, Cambiran to Ordovician, and Caboniferous to early Permian. It underwent compression since Late Triassic, including such periods as Latest Triassic, Late Jurassic to early Cretaceous, Late Cretaceous to early Paleogene, and Pliocene to Quaternary, with the largest shortening around Late Jurassic to early Cretaceous period (i.e. the mid-Yanshanian movement by the local name). However, trans-extension since Eocene around the Ordos Basin got rise to the formation the Yingchuan, Hetao, and Weihe grabens. It is concluded that MFTB is the leading edge of the intra-continental Helan orogenic belt, and formed by multi-phase breaking-forward thrusting during Late Jurassic to Cretaceous. During Cenozoic, MFTB is moderately modified by the northeastward compression due to the NE propagation of Qinghai-Tibet Plateau, and distinctly superimposed by the Yingchuan half-graben. North-South Tectonic Belt underwent a full cycle from extension during Middle Proterozoic to Paleozoic to compression since late Triassic.

Using experimental petrology to constrain genesis of wet, silicic magmas in the Tonga-Kermadec island arc

NASA Astrophysics Data System (ADS)

Brens, R.; Rushmer, T. A.; Turner, S.; Adam, J.

2012-12-01

The Tongan arc system is comprised of a pair of island chains, where the western chain is the active volcanic arc. A range of rock suites, from basaltic andesites (53-56% SiO2) to dacites (64-66% SiO2), has been recovered from Late, Tofua and Fonualei in the Tonga-Kermadec primitive island arc system. For which the question arises: What is the mechanism that allows for silicic magmas to develop in a primitive island arc system? Caufield et al. (2012) suggest that fractional crystallization of a multi magma chamber process, with varying depth, is responsible for the silicic magma generation in this arc. Models such as this one have been proposed and experimentally tested in other systems (Novarupta, Alaska) to explain the origin of these silicic rocks. Our Tongan suite of rocks has had a full geochemical analysis for majors, traces and isotopes. The lavas from Tofua and Late are Fe-rich and have low concentrations of K, Rb, Ba, Zr, REE, Pb and U. However, experimental studies are needed to complement the extensive geochemical analysis done on the Tongan arc. Former geochemical work done on the igneous rocks from both of these volcanic suites from this arc suggests that the source of these rocks extend from 1.5-5.5 km in depth (Caulfield et al., 2012). Here, we present an experimental study of the phase equilibria on a natural andesitic sample (Late 1, from Ewart et al., 1975) from the island of Late. Experiments were run using the temperature constraints between 900 to 1220oC, pressure from 5 to 25 kbars and H2O addition of mostly 5wt% (but some results were obtained at 2wt% in the rocks). In the presence of 5 wt% water, phase equilibria of these experiments show the garnet stability field at >10 kb for 900 oC and increases with increasing temperature, while plagioclase enters at lower pressures when garnet exits. Experimental results currently suggests, at lower temperatures (900-950oC), a fractional crystallization relationship due to shallow level pressures of these rocks and further reinforcing Brophy's (2009) model of crystal fractionation of basalt to dacite in the presence of water, as an important process for which silica-rich magmas are produced within a primitive oceanic island arc.

The early Barremian warm pulse and the late Barremian cooling: a high resolution geochemical record of the Boreal Realm

NASA Astrophysics Data System (ADS)

Mutterlose, J.; Malkoc, M.

2009-04-01

A high resolution geochemical study of seven Barremian (lower Cretaceous) sections in NW Europe documents warming and cooling periods throughout the investigated interval. A total of 289 belemnite guards from localities in NE England and NW Germany were analysed for their trace elements (Mg, Sr, Fe and Mn) and their stable isotope composition (δ13C, δ18O) in order to reconstruct the palaeotemperature record and to better understand different palaeotemperature proxies (δ18O, Mg/Ca). The material has been collected bed-by-bed from bio- and lithostratigraphically well studied outcrops with a palaeolatitude of 36-38°N. The carbon isotope curve of the Barremian is described by a long term (5my) increase from 1‰ in the early Barremian to 3‰ in the late Barremian. This long term trend is thought to reflect the global signal of the carbon budget of the Barremian oceans. Superimposed on this signature is a short termed peak (~ 105kyrs) of 2.5‰ in the late early Barremian Aulacoteuthis zone. This "Aulacoteuthis peak", which goes along with the widespread deposition of TOC rich mudstones, was caused by increased productivity. It is seen as a regional signal related to warm-humid conditions and palaeoceanographically a quasi lagoonal setting. δ13C shifts of 1.5‰ from specimens collected from one horizon may reflect high resolution seasonal changes of run-off and nutrient supply. The oxygen isotope signature clearly shows similar palaeotemperature variations of the approx. 5my lasting Barremian for all sections investigated. The climatic evolution allows to recognize three different phases. An earliest Barremian cool phase (Praeoxyteuthis pugio zone) is characterized by δ18O values of - 1.2‰ to 0.3‰ (16°C to 10°C) with most data plotting around - 0.2‰ (12°C). This "P. pugio cool phase", which extends into the underlying Hauterivian, is followed by a distinctive warming event in the late early Barremian Aulacoteuthis zone. This "Aulacoteuthis warm pulse", which supplied δ18O data of - 2‰ to - 1‰ (20°C to 16°C), is a relatively short termed peak lasting ~ 500kyrs and went along with widespread anoxic conditions of bottom waters. These resulted in the deposition of TOC rich laminated mudstones. This warm pulse recorded the highest T°C throughout the entire Valanginian-Barremian in the Boreal Realm. A third climatic interval, the "late Barremian cooling phase" marks the Oxyteuthis brunsvicensis, Oxyteuthis germanica and Oxyteuthis depressa zones. The δ18O data steadily increase to values of 0‰ (12°C) in the latest Barremian. The Mg/Ca-proxy data clearly parallel the trend of the δ18O signature. The "P. pugio cool phase" of 13-15°C is followed by the "Aulacoteuthis warm pulse" with temperatures up to 25°C. The overlying Upper Barremian zones show the "late Barremian cooling phase" with temperatures around 15°C. Temperature differences of more than 2°C between the δ18O and the Mg/Ca data have been observed for 48% of the studied belemnite material. These differences may either reflect the natural variation of an unfiltered high resolution record and/or salinity fluctuations, in a palaeoceanographically restricted setting where alternating seasons of raised and lowered salinities were controlled by variations of the run-off. Warm periods (early late Barremian) went along with warmer δ18O temperature values or alternatively a higher salinity, cool periods (late Barremian) with cooler δ18O temperatures or a lowered salinity.

A tale of two timescales: Mixing, mass generation, and phase transitions in the early universe

NASA Astrophysics Data System (ADS)

Dienes, Keith R.; Kost, Jeff; Thomas, Brooks

2016-02-01

Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically—such as during cosmological mass-generating phase transitions—the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this paper, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system—often by many orders of magnitude—but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "reoverdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings.

Identification of Hürthle cell tumor by single-injection, double-phase scintigraphy with technetium-99m-sestamibi.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A

1995-05-01

Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a comparative study of the scintigraphic aspects of Hürthle cell tumors and other thyroid tumors. Single-injection, dual-phase (15-30 min and 3-4 hr) thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular uptake was done to compare thyroidal and background tracer uptake. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured. Cytologic results were obtained for all patients; histopathologic results were obtained for the 20 patients who had surgery. In eight patients (Group A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/- 0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%); histopathology revealed Hürthle cell tumors (two carcinomas and three adenomas) in five surgical patients. In 15 patients (Group B), the nodule displayed intense uptake in the early image with fading activity in the late image (N/T = 1.45 +/- 0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%); histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18 patients (Group C), the nodule was cold and late images were not acquired. Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in five surgical patients. Single-injection, dual-phase MIBI scintigraphy of the thyroid can identify Hürthle cell tumors because these tumors have intense, persistent tracer uptake in contrast to other thyroid tumors.

Discovery of Dihydrobenzoxazepinone (GS-6615) Late Sodium Current Inhibitor (Late INai), a Phase II Agent with Demonstrated Preclinical Anti-Ischemic and Antiarrhythmic Properties.

PubMed

Zablocki, Jeff A; Elzein, Elfatih; Li, Xiaofen; Koltun, Dmitry O; Parkhill, Eric Q; Kobayashi, Tetsuya; Martinez, Ruben; Corkey, Britton; Jiang, Haibo; Perry, Thao; Kalla, Rao; Notte, Gregory T; Saunders, Oliver; Graupe, Michael; Lu, Yafan; Venkataramani, Chandru; Guerrero, Juan; Perry, Jason; Osier, Mark; Strickley, Robert; Liu, Gongxin; Wang, Wei-Qun; Hu, Lufei; Li, Xiao-Jun; El-Bizri, Nesrine; Hirakawa, Ryoko; Kahlig, Kris; Xie, Cheng; Li, Cindy Hong; Dhalla, Arvinder K; Rajamani, Sridharan; Mollova, Nevena; Soohoo, Daniel; Lepist, Eve-Irene; Murray, Bernard; Rhodes, Gerry; Belardinelli, Luiz; Desai, Manoj C

2016-10-03

Late sodium current (late I Na ) is enhanced during ischemia by reactive oxygen species (ROS) modifying the Na v 1.5 channel, resulting in incomplete inactivation. Compound 4 (GS-6615, eleclazine) a novel, potent, and selective inhibitor of late I Na , is currently in clinical development for treatment of long QT-3 syndrome (LQT-3), hypertrophic cardiomyopathy (HCM), and ventricular tachycardia-ventricular fibrillation (VT-VF). We will describe structure-activity relationship (SAR) leading to the discovery of 4 that is vastly improved from the first generation late I Na inhibitor 1 (ranolazine). Compound 4 was 42 times more potent than 1 in reducing ischemic burden in vivo (S-T segment elevation, 15 min left anteriorior descending, LAD, occlusion in rabbits) with EC 50 values of 190 and 8000 nM, respectively. Compound 4 represents a new class of potent late I Na inhibitors that will be useful in delineating the role of inhibitors of this current in the treatment of patients.

Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.

PubMed

Wang, Dian; Zhang, Qiang; Eisenberg, Burton L; Kane, John M; Li, X Allen; Lucas, David; Petersen, Ivy A; DeLaney, Thomas F; Freeman, Carolyn R; Finkelstein, Steven E; Hitchcock, Ying J; Bedi, Manpreet; Singh, Anurag K; Dundas, George; Kirsch, David G

2015-07-10

We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS. © 2015 by American Society of Clinical Oncology.

DNA-Damage Response RNA-Binding Proteins (DDRBPs): Perspectives from a New Class of Proteins and Their RNA Targets.

PubMed

Dutertre, Martin; Vagner, Stéphan

2017-10-27

Upon DNA damage, cells trigger an early DNA-damage response (DDR) involving DNA repair and cell cycle checkpoints, and late responses involving gene expression regulation that determine cell fate. Screens for genes involved in the DDR have found many RNA-binding proteins (RBPs), while screens for novel RBPs have identified DDR proteins. An increasing number of RBPs are involved in early and/or late DDR. We propose to call this new class of actors of the DDR, which contain an RNA-binding activity, DNA-damage response RNA-binding proteins (DDRBPs). We then discuss how DDRBPs contribute not only to gene expression regulation in the late DDR but also to early DDR signaling, DNA repair, and chromatin modifications at DNA-damage sites through interactions with both long and short noncoding RNAs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cell-cycle progress in obligate predatory bacteria is dependent upon sequential sensing of prey recognition and prey quality cues.

PubMed

Rotem, Or; Pasternak, Zohar; Shimoni, Eyal; Belausov, Eduard; Porat, Ziv; Pietrokovski, Shmuel; Jurkevitch, Edouard

2015-11-03

Predators feed on prey to acquire the nutrients necessary to sustain their survival, growth, and replication. In Bdellovibrio bacteriovorus, an obligate predator of Gram-negative bacteria, cell growth and replication are tied to a shift from a motile, free-living phase of search and attack to a sessile, intracellular phase of growth and replication during which a single prey cell is consumed. Engagement and sustenance of growth are achieved through the sensing of two unidentified prey-derived cues. We developed a novel ex vivo cultivation system for B. bacteriovorus composed of prey ghost cells that are recognized and invaded by the predator. By manipulating their content, we demonstrated that an early cue is located in the prey envelope and a late cue is found within the prey soluble fraction. These spatially and temporally separated cues elicit discrete and combinatory regulatory effects on gene transcription. Together, they delimit a poorly characterized transitory phase between the attack phase and the growth phase, during which the bdelloplast (the invaded prey cell) is constructed. This transitory phase constitutes a checkpoint in which the late cue presumably acts as a determinant of the prey's nutritional value before the predator commits. These regulatory adaptations to a unique bacterial lifestyle have not been reported previously.

Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats

PubMed Central

Song, Zhenqiang; Li, Jing; Li, Chunshen

2016-01-01

In the study, type 2 diabetic rat model was established using streptozotocin (STZ) combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD) early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP), protein kinase C (PKC), and protein kinase A (PKA) were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P < 0.05); compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P < 0.05). In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway. PMID:27703477

Effect of glucocorticosteroid treatment on ovalbumin-induced IgE-mediated immediate and late allergic response in guinea pig.

PubMed

Andersson, P; Brange, C; von Kogerer, B; Sonmark, B; Stahre, G

1988-01-01

The effect of glucocorticosteroid (GCS) treatment on ovalbumine-induced IgE-mediated immediate and late allergic response was studied in sensitized guinea pigs. The results show that the GCS budesonide (BUD) inhibits the allergen-induced IgE-mediated immediate and late bronchial obstruction. The effect on the early reaction is correlated to the inhibition of leukotrienes and histamine release. The importance of mediator release inhibition for the antianaphylactic effect of GCS is discussed. In examining the effect on the late reaction, it was found that BUD had to be present during the early reaction but did not inhibit the early reaction. Furthermore, the effect on the late reaction was correlated to the inhibition of vascular leakage but not to the infiltration of inflammatory cells as examined in bronchoalveolar lavage. The results indicate that some triggering factors important for the development of the late reaction are released during the early reaction. Inhibition of the release of that factor or the activation of inflammatory cells by that factor might be the mechanism behind the antiinflammatory activities of GCS.

Guidelines for screening and management of late and long-term consequences of myeloma and its treatment.

PubMed

Snowden, John A; Greenfield, Diana M; Bird, Jennifer M; Boland, Elaine; Bowcock, Stella; Fisher, Abigail; Low, Eric; Morris, Monica; Yong, Kwee; Pratt, Guy

2017-03-01

A growing population of long-term survivors of myeloma is now accumulating the 'late effects' not only of myeloma itself, but also of several lines of treatment given throughout the course of the disease. It is thus important to recognise the cumulative burden of the disease and treatment-related toxicity in both the stable and active phases of myeloma, some of which is unlikely to be detected by routine monitoring. We summarise here the evidence for the key late effects in long-term survivors of myeloma, including physical and psychosocial consequences (in Parts 1 and 2 respectively), and recommend the use of late-effects screening protocols in detection and intervention. The early recognition of late effects and effective management strategies should lead to an improvement in the management of myeloma patients, although evidence in this area is currently limited and further research is warranted. © 2017 John Wiley & Sons Ltd.

Responses to novel odors mediate maternal behavior and concaveation in gerbils.

PubMed

Clark, M M; Spencer, C A; Galef, B G

1986-01-01

In a series of three experiments we examined: (Experiment 1) responses to novel odors by early- and late-maturing not-pregnant, pregnant, nursing and postweaning female Mongolian gerbils, (Experiment 2) the response of the same eight groups of female gerbils to unfamiliar pups, and (Experiment 3) the rate of induction of maternal behavior by concaveation in early- and late-maturing nulliparous gerbils. We found: (1) that those females that responded relatively positively to novel odors in Experiment 1 were more likely to retrieve and less likely to attack unfamiliar pups in Experiment 2 than those females responding relatively negatively to novel odors in Experiment 1, and (2) that early-maturing nulliparous gerbils both responded more positively to novel odors and exhibited more rapid induction of maternal behavior by concaveation than late-maturing nulliparous gerbils. The results both confirm and extend Fleming and Rosenblatt's (1974) hypothesis that differences in response to novel odors mediate individual differences in maternal responsiveness.

Alteration of swing leg work and power during human accelerated sprinting

PubMed Central

Matsubayashi, Takeo; Matsuo, Akifumi; Zushi, Koji

2017-01-01

ABSTRACT This study investigated changes in lower-extremity joint work and power during the swing phase in a maximal accelerated sprinting. Twelve male sprinters performed 60 m maximal sprints while motion data was recorded. Lower-extremity joint work and power during the swing phase of each stride for both legs were calculated. Positive hip and negative knee work (≈4.3 and ≈−2.9 J kg−1) and mean power (≈13.4 and ≈−8.7 W kg−1) during the entire swing phase stabilized or decreased after the 26.2±1.1 (9.69±0.25 m s−1) or 34.3±1.5 m mark (9.97±0.26 m s−1) during the acceleration phase. In contrast, the hip negative work and mean power during the early swing phase (≈7-fold and ≈3.7-fold increase in total), as well as the knee negative work and power during the terminal swing phase (≈1.85-fold and ≈2-fold increase in total), increased until maximal speed. Moreover, only the magnitudes of increases in negative work and mean power at hip and knee joints during the swing phase were positively associated with the increment of running speed from the middle of acceleration phase. These findings indicate that the roles of energy generation and absorption at the hip and knee joints shift around the middle of the acceleration phase as energy generation and absorption at the hip during the late swing phase and at the knee during early swing phase are generally maintained or decreased, and negative work and power at hip during the early swing phase and at knee during the terminal swing phase may be responsible for increasing running speed when approaching maximal speed. PMID:28396485

Recent Progress in Understanding the Shock Response of Ferroelectric Ceramics*

NASA Astrophysics Data System (ADS)

Setchell, Robert E.

2001-06-01

Ferroelectric ceramics exhibit a permanent remanent polarization, and the use of shock depoling of these materials to achieve pulsed sources of electrical power was proposed in the late 1950s. During the following twenty years, extensive studies were conducted to examine the shock response of ferroelectric ceramics primarily based on lead zirconate titanate (PZT). Under limited conditions, relatively simple analytical models were found to adequately describe the observed electrical behavior. In general, however, the studies indicated a complex behavior involving finite-rate depoling kinetics with stress and field dependencies. Dielectric relaxation and shock-induced conductivity were also suggested. Unfortunately, few experimental studies were undertaken over the next twenty years, and the development of more comprehensive models was inhibited. In recent years, a strong interest in advancing numerical simulation capabilities has motivated new experimental studies and corresponding model development. More than seventy gas gun experiments have examined several ferroelectric ceramics, with most experiments on lead zirconate titanate having a Zr:Ti ratio of 95:5 and modified with 2ferroelectric but is near an antiferroelectric phase boundary, and depoling results from a shock-driven phase transition. Experiments have examined unpoled, normally poled, and axially poled PZT 95/5 over broad ranges of shock pressure and peak electric field. The extensive base of new data provides quantitative insights into the stress and field dependencies of depoling kinetics and dielectric properties, and is being actively utilized to develop and refine material response models used in numerical simulations of pulsed power devices.

20th century climate warming and tree-limit rise in the southern Scandes of Sweden.

PubMed

Kullman, L

2001-03-01

Climate warming by ca. 0.8 degree C between the late-19th and late-20th century, although with some fluctuations, has forced multispecies elevational tree-limit advance by > 100 m for the principal tree species in the Swedish part of the Scandinavian mountain range. Predominantly, these processes imply growth in height of old-established individuals and less frequently upslope migration of new individuals. After a slight retardation during some cooler decades after 1940, a new active phase of tree-limit advance has occurred with a series of exceptionally mild winters and some warm summers during the 1990s. The magnitude of total 20th century tree-limit rise varies with topoclimate and is mainly confined to wind-sheltered and snow-rich segments of the landscape. Thickening of birch tree stands in the "advance belt" has profoundly altered the general character of the subalpine/low alpine landscape and provides a positive feedback loop for further progressive change and resilience to short-term cooling episodes. All upslope tree-limit shifts and associated landscape transformations during the 20th century have occurred without appreciable time lags, which constitutes knowledge fundamental to the generation of realistic models concerning vegetation responses to potential future warming. The new and elevated pine tree-limit may be the highest during the past 4000 14C years. Thus, it is tentatively inferred that the 20th century climate is unusually warm in a late-Holocene perspective.

A 27cal ka biomarker-based record of ecosystem changes from lacustrine sediments of the Chihuahua Desert of Mexico

NASA Astrophysics Data System (ADS)

Chávez-Lara, C. M.; Holtvoeth, J.; Roy, P. D.; Pancost, R. D.

2018-07-01

Hydroclimate variation of the northwest Mexico during the late Pleistocene and Holocene is an active area of debate, with uncertainty in the nature and sources of precipitation. Previous research has inferred the influences of winter storms, summer monsoonal rain and autumn tropical cyclones. The impacts on regional and local ecosystems, however, are not well constrained. Here, we investigate the response of lacustrine and terrestrial habitats of the Santiaguillo Basin in the Chihuahua Desert (Mexico) to hydrological changes occurring since the late last glacial. Biomarkers from the sediments reflect variable input of organic matter (OM) from algal and bacterial biomass, aquatic microfauna and surrounding vegetation, revealing distinct stages of ecosystem adaption over the last 27 cal ka. Based on previously published and new data, we show that a perennial productive lake was present during the late glacial and it persisted until 17.5 cal ka BP. Coinciding with Heinrich event 1, OM supply from deteriorating wetland soils may have been caused by early dry conditions. Further phases of increasing aridity and a shrinking water body drove changing OM quality and biomarker composition during the early and mid-Holocene. A pronounced shift in biomarker distributions at 4 cal ka BP suggests that the supply of plant litter from resinous trees and grasses increased, likely reflecting the establishment of modern vegetation. Our results illustrate the potential of biomarker applications in the area, adding to the evidence of hydroclimate variability and enabling reconstructions of local ecosystem dynamics.

Involvement of STI1 protein in the differentiation process of Trypanosoma cruzi.

PubMed

Schmidt, Juliana C; Manhães, Lauro; Fragoso, Stenio P; Pavoni, Daniela P; Krieger, Marco A

2018-04-01

The protozoan Trypanosoma cruzi is a parasite exposed to several environmental stressors inside its invertebrate and vertebrate hosts. Although stress conditions are involved in its differentiation processes, little information is available about the stress response proteins engaged in these activities. This work reports the first known association of the stress-inducible protein 1 (STI1) with the cellular differentiation process in a unicellular eukaryote. Albeit STI1 expression is constitutive in epimastigotes and metacyclic trypomastigotes, higher protein levels were observed in late growth phase epimastigotes subjected to nutritional stress. Analysis by indirect immunofluorescence revealed that T. cruzi STI1 (TcSTI1) is located throughout the cell cytoplasm, with some cytoplasmic granules appearing in greater numbers in late growing epimastigotes and late growing epimastigotes subjected to nutritional stress. We observed that part of the fluorescence signal from both TcSTI1 and TcHSP70 colocalized around the nucleus. Gene silencing of sti1 in Trypanosoma brucei did not affect cell growth. Similarly, the growth of T. cruzi mutant parasites with a single allele sti1 gene knockout was not affected. However, the differentiation of epimastigotes in metacyclic trypomastigotes (metacyclogenesis) was compromised. Lower production rates and numbers of metacyclic trypomastigotes were obtained from the mutant parasites compared with the wild-type parasites. These data indicate that reduced levels of TcSTI1 decrease the rate of in vitro metacyclogenesis, suggesting that this protein may participate in the differentiation process of T. cruzi. Copyright © 2017 Elsevier B.V. All rights reserved.

Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy.

PubMed

Malbrain, Manu L N G; Van Regenmortel, Niels; Saugel, Bernd; De Tavernier, Brecht; Van Gaal, Pieter-Jan; Joannes-Boyau, Olivier; Teboul, Jean-Louis; Rice, Todd W; Mythen, Monty; Monnet, Xavier

2018-05-22

In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.

Toxicity Screening of the ToxCast Phase II Chemical Library Using a Zebrafish Developmental Assay (SOT)

EPA Science Inventory

As part of the chemical screening and prioritization research program of the US EPA, the ToxCast Phase II chemicals were assessed using a vertebrate screen for developmental toxicity. Zebrafish embryos (Danio rerio) were exposed in 96-well plates from late-blastula stage (6hr pos...

Instructional Film Research and the Learner.

ERIC Educational Resources Information Center

Bowie, Melvin McKinney

A brief discussion of three phases in research on instructional films--whether films can teach (approximately 1910-1950), how films teach (1940 through the late 1950s), and who learns from films (1960-1985)--introduces a review of the research literature on the third phase. The experimental studies reviewed focus on three concerns: (1) use of…

Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle.

PubMed

Zhu, Xun; Kelly, Thomas H; Curry, Thomas E; Lal, Chitra; Joseph, Jane E

2015-09-30

Mental rotation is a visuospatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional MRI. Ten premenopausal women were tested on a 3D mental rotation task during the early follicular and late follicular phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the late follicular than the early follicular phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuospatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function.

Hot spine loops and the nature of a late-phase solar flare

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

Sun, Xudong; Todd Hoeksema, J.; Liu, Yang

2013-12-01

The fan-spine magnetic topology is believed to be responsible for many curious features in solar explosive events. A spine field line links distinct flux domains, but direct observation of such a feature has been rare. Here we report a unique event observed by the Solar Dynamic Observatory where a set of hot coronal loops (over 10 MK) connected to a quasi-circular chromospheric ribbon at one end and a remote brightening at the other. Magnetic field extrapolation suggests that these loops are partly tracers of the evolving spine field line. Continuous slipping- and null-point-type reconnections were likely at work, energizing themore » loop plasma and transferring magnetic flux within and across the fan quasi-separatrix layer. We argue that the initial reconnection is of the 'breakout' type, which then transitioned to a more violent flare reconnection with an eruption from the fan dome. Significant magnetic field changes are expected and indeed ensued. This event also features an extreme-ultraviolet (EUV) late phase, i.e., a delayed secondary emission peak in warm EUV lines (about 2-7 MK). We show that this peak comes from the cooling of large post-reconnection loops beside and above the compact fan, a direct product of eruption in such topological settings. The long cooling time of the large arcades contributes to the long delay; additional heating may also be required. Our result demonstrates the critical nature of cross-scale magnetic coupling—topological change in a sub-system may lead to explosions on a much larger scale.« less

Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: A cohort study.

PubMed

Rozen, Laurence; Noubouossie, Denis; Dedeken, Laurence; Huybrechts, Sophie; Lê, Phu Quoc; Ferster, Alina; Demulder, Anne

2017-02-01

Asparaginase (Asp) and corticosteroid (CS) treatment in patients with acute lymphoblastic leukaemia (ALL) is associated with an increased risk of thrombotic events. Characterization of global haemostatic phenotypes of patients with ALL during Asp therapy. Thrombin generation (TG) was monitored in platelet-poor plasma of 56 children treated for a B lineage ALL (36 with native, 20 with PEG Asp) using 1 pM tissue factor and 4 μM phospholipids, with and without thrombomodulin. Protein C activity (PC), free protein S (PS), antithrombin (AT) and fibrinogen levels were also measured. Elevated endogenous thrombin potential (ETP) and peak of TG were noted at diagnosis, throughout the Induction phase and Late Intensification but was significantly less for PEG than for native Asp (P < 0.001), while age, sex, type of corticosteroid during Induction and molecular response had no significant effect. The reduction of ETP after addition of thrombomodulin was significantly lower in ALL children compared with that in controls, suggesting impairment in PS/PC pathway. Three patients experienced thrombosis: two treated with native and one with PEG Asp. The two patients with native Asp had, at the time of thrombosis, a prothrombotic profile. Treatment with Asp, in combination with CS, enhances TG in children with ALL, more significantly with native than PEG Asp, which is present early at diagnosis, persists during Induction and reappears during Late Intensification. This is consistent with the high incidence of thrombotic events described during these phases of therapy. The less pronounced effect of PEG Asp remains to be elucidated. © 2016 Wiley Periodicals, Inc.