Growing evidence indicates that glia pathology and amino-acid neurotransmitter system abnormalities contribute to the pathophysiology and possibly the pathogenesis of major depressive disorder. This ...study investigates changes in glial function occurring in the rat prefrontal cortex (PFC) after chronic unpredictable stress (CUS), a rodent model of depression. Furthermore, we analyzed the effects of riluzole, a Food and Drug Administration-approved drug for the treatment of amyotrophic laterosclerosis, known to modulate glutamate release and facilate glutamate uptake, on CUS-induced glial dysfunction and depressive-like behaviors. We provide the first experimental evidence that chronic stress impairs cortical glial function. Animals exposed to CUS and showing behavioral deficits in sucrose preference and active avoidance exhibited significant decreases in 13C-acetate metabolism reflecting glial cell metabolism, and glial fibrillary associated protein (GFAP) mRNA expression in the PFC. The cellular, metabolic and behavioral alterations induced by CUS were reversed and/or blocked by chronic treatment with the glutamate-modulating drug riluzole. The beneficial effects of riluzole on CUS-induced anhedonia and helplessness demonstrate the antidepressant action of riluzole in rodents. Riluzole treatment also reversed CUS-induced reductions in glial metabolism and GFAP mRNA expression. Our results are consistent with recent open-label clinical trials showing the drug's effect in mood and anxiety disorders. This study provides further validation of hypothesis that glial dysfunction and disrupted amino-acid neurotransmission contribute to the pathophysiology of depression and that modulation of glutamate metabolism, uptake and/or release represent viable targets for antidepressant drug development.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A potential threat to the performance of magnetically confined fusion plasmas is the problem of impurity accumulation, which causes the concentration of highly charged impurity ions to rise ...uncontrollably in the center of the plasma and spoil the energy confinement by excessive radiation. It has long been thought that the collisional transport of impurities in stellarators always leads to such an accumulation (if the electric field points inwards, which is usually the case), whereas tokamaks, being axisymmetric, can benefit from "temperature screening," i.e., an outward flux of impurities driven by the temperature gradient. Here it is shown, using analytical techniques supported by results from a new numerical code, that such screening can arise in stellarator plasmas, too, and indeed does so in one of the most relevant operating regimes, where the impurities are highly collisional while the bulk plasma is at low collisionality.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Summary Background Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against ...CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). Methods Healthy women aged 15–25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov , number NCT00122681. Findings Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5–100) in the TVC-naive and 45·7% (22·9–62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9–98·7) in the TVC-naive and 45·6% (28·8–58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15–17 year age group and progressively decreased in the 18–20 year and 21–25 year age groups. Vaccine efficacy against all AIS was 100% (31·0–100) and 76·9% (16·0–95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination. Interpretation PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. Funding GlaxoSmithKline Biologicals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The present review covers two independent approaches, a neuroanatomical and a pharmacological (focused on serotonergic transmission), which converge in highlighting the critical role of the ...hypothalamus and midbrain periaqueductal gray matter in the generation of panic attacks and in the mechanism of action of current antipanic medication. Accordingly, innate and learned fear responses to different threats (i.e., predator, aggressive members of the same species, interoceptive threats and painful stimuli) are processed by independent circuits involving corticolimbic regions (the amygdala, the hippocampus and the prefrontal and insular cortices) and downstream hypothalamic and brainstem circuits. As for the drug treatment, animal models of panic indicate that the drugs currently used for treating panic disorder should work by enhancing 5-HT inhibition of neural systems that command proximal defense in both the dorsal periaqueductal gray and in the medial hypothalamus. For the anticipatory anxiety, the reviewed evidence points to corticolimbic structures, such as the amygdala, the septo-hippocampus and the prefrontal cortex, as its main neural substrate, modulated by stimulation of 5-HT2C and 5-HT1A receptors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Superior predatory skills led to the evolutionary triumph of jawed vertebrates. However, the mechanisms by which the vertebrate brain controls predation remain largely unknown. Here, we reveal a ...critical role for the central nucleus of the amygdala in predatory hunting. Both optogenetic and chemogenetic stimulation of central amygdala of mice elicited predatory-like attacks upon both insect and artificial prey. Coordinated control of cervical and mandibular musculatures, which is necessary for accurately positioning lethal bites on prey, was mediated by a central amygdala projection to the reticular formation in the brainstem. In contrast, prey pursuit was mediated by projections to the midbrain periaqueductal gray matter. Targeted lesions to these two pathways separately disrupted biting attacks upon prey versus the initiation of prey pursuit. Our findings delineate a neural network that integrates distinct behavioral modules and suggest that central amygdala neurons instruct predatory hunting across jawed vertebrates.
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•Stimulation of central amygdala (CeA) elicited hunting of live and artificial prey•CeA projections to the reticular formation (PCRt) control biting attacks•CeA projections to periaqueductal gray (PAG) control locomotion during pursuit•CeA integrates craniofacial and locomotor modules during goal-directed behavior
Two neuronal pathways originating in the central amygdala coordinate distinct behaviors necessary for efficient predatory hunting: the ability to pursue a prey and deliver fatal bites upon capture.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Carbon particles containing mineral matter promote soil fertility, helping it to overcome the rather unfavorable climate conditions of the humid tropics. Intriguing examples are the Amazonian Dark ...Earths, anthropogenic soils also known as “Terra Preta de Índio’’ (TPI), in which chemical recalcitrance and stable carbon with millenary mean residence times have been observed. Recently, the presence of calcium and oxygen within TPI-carbon nanoparticles at the nano- and mesoscale ranges has been demonstrated. In this work, we combine density functional theory calculations, scanning transmission electron microscopy, energy dispersive X-ray spectroscopy, Fourier transformed infrared spectroscopy, and high resolution X-ray photoelectron spectroscopy of TPI-carbons to elucidate the chemical arrangements of calcium–oxygen–carbon groups at the molecular level in TPI. The molecular models are based on graphene oxide nanostructures in which calcium cations are strongly adsorbed at the oxide sites. The application of material science techniques to the field of soil science facilitates a new level of understanding, providing insights into the structure and functionality of recalcitrant carbon in soil and its implications for food production and climate change.
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IJS, KILJ, NUK, PNG, UL, UM
The dorsal periaqueductal gray (dPAG) contains a tonically GABAergic network controlling defensive responses. Determining how this intrinsic dPAG inhibitory circuit functions might provide critical ...insights into how anti-predatory responses are organized.
The dorsal periaqueductal gray (dPAG) contains a tonically GABAergic network controlling defensive responses. Determining how this intrinsic dPAG inhibitory circuit functions might provide critical insights into how anti-predatory responses are organized.
Anxiety is a complex phenomenon: Its eliciting stimuli and circumstances, component behaviors, and functional consequences are only slowly coming to be understood. Here, we examine defense systems ...from field studies; laboratory studies focusing on experimental analyses of behavior; and, the fear conditioning literature, with a focus on the role of uncertainty in promoting an anxiety pattern that involves high rates of stimulus generalization and resistance to extinction. Respectively, these different areas provide information on evolved elicitors of defense (field studies); outline a defense system focused on obtaining information about uncertain threat (ethoexperimental analyses); and, provide a simple, well-researched, easily measured paradigm for analysis of nonassociative stress-enhanced fear conditioning (the SEFL). Results suggest that all of these—each of which is responsive to uncertainty—play multiple and interactive roles in anxiety. Brain system findings for some relevant models are reviewed, with suggestions that further analyses of current models may be capable of providing a great deal of additional information about these complex interactions and their underlying biology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Spectroscopic techniques including X-ray photoelectron spectroscopy (XPS) can identify particular chemical groups of humic acids (HA) from “Terra Preta de Índios” (TPI) or Amazonian dark earth, the ...highly fertile anthropogenic soil found in the Amazonian region. The high fertility and resilience of these soils cannot be explained by their chemically inert pyrogenic C content alone, but the natural aging of this C generates reactive carboxyl functional groups attached directly to the recalcitrant polycondensed aromatic backbone. Through spectroscopic techniques used in this work, the HA fraction (the alkaline-soluble organic matter that precipitates at low pH) of the TPI soil was compared with humic and fulvic acids, obtained by oxidizing activated charcoal with sodium hypochlorite. The yields recovery of HA-like substances was 12 and 28 wt% by using 10 and 20 cmol L⁻¹ of oxidizing agent, respectively. X-ray photoelectron spectroscopy, energy dispersive X-ray, and solid-state ¹³C nuclear magnetic resonance (¹³C NMR) spectroscopies were used to evaluate the elements and structures present in all samples. XPS C 1 s spectra of HA extracted from TPI soil and from prepared HA showed aromatic structures (C = C and π–π* shake-up satellite peak) bounded to carboxyl groups (COOH). The morphology and polycondensation level of aromatic C were evaluated by scanning electron microscopy (SEM). The similarities of the spectra indicated that the used method was efficient to obtain an organic amendment similar to TPI soil organic matter.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We analyze the dynamics of fast electrons in plasmas containing partially ionized impurity atoms, where the screening effect of bound electrons must be included. We derive analytical expressions for ...the deflection and slowing-down frequencies, and show that they are increased significantly compared to the results obtained with complete screening, already at subrelativistic electron energies. Furthermore, we show that the modifications to the deflection and slowing down frequencies are of equal importance in describing the runaway current evolution. Our results greatly affect fast-electron dynamics and have important implications, e.g., for the efficacy of mitigation strategies for runaway electrons in tokamak devices, and energy loss during relativistic breakdown in atmospheric discharges.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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