Context.
The accretion history of protostars remains widely mysterious, even though it represents one of the best ways to understand the protostellar collapse that leads to the formation of stars.
...Aims.
Molecular outflows, which are easier to detect than the direct accretion onto the prostellar embryo, are here used to characterize the protostellar accretion phase in W43-MM1.
Methods.
The W43-MM1 protocluster hosts a sufficient number of protostars to statistically investigate molecular outflows in a single, homogeneous region. We used the CO(2–1) and SiO(5–4) line datacubes, taken as part of an ALMA mosaic with a 2000 AU resolution, to search for protostellar outflows, evaluate the influence that the environment has on these outflows’ characteristics and put constraints on outflow variability in W43-MM1.
Results.
We discovered a rich cluster of 46 outflow lobes, driven by 27 protostars with masses of 1−100
M
⊙
. The complex environment inside which these outflow lobes develop has a definite influence on their length, limiting the validity of using outflows’ dynamical timescale as a proxy of the ejection timescale in clouds with high dynamics and varying conditions. We performed a detailed study of Position–Velocity diagrams of outflows that revealed clear events of episodic ejection. The time variability of W43-MM1 outflows is a general trend and is more generally observed than in nearby, low- to intermediate-mass star-forming regions. The typical timescale found between two ejecta, ~500 yr, is consistent with that found in nearby protostars.
Conclusions.
If ejection episodicity reflects variability in the accretion process, either protostellar accretion is more variable, or episodicity is easier to detect in high-mass star-forming regions than in nearby clouds. The timescale found between accretion events could result from instabilities associated with bursts of inflowing gas arising from the close dynamical environment of high-mass star-forming cores.
Stressful life events produce a state of vulnerability to depression in some individuals. The mechanisms that contribute to vulnerability to depression remain poorly understood. A rat model of ...intense stress (social defeat (SD), first hit) produced vulnerability to depression in 40% of animals. Only vulnerable animals developed a depression-like phenotype after a second stressful hit (chronic mild stress). We found that this vulnerability to depression resulted from a persistent state of oxidative stress, which was reversed by treatment with antioxidants. This persistent state of oxidative stress was due to low brain-derived neurotrophic factor (BDNF) levels, which characterized the vulnerable animals. We found that BDNF constitutively controlled the nuclear translocation of the master redox-sensitive transcription factor Nrf2, which activates antioxidant defenses. Low BDNF levels in vulnerable animals prevented Nrf2 translocation and consequently prevented the activation of detoxifying/antioxidant enzymes, ultimately resulting in the generation of sustained oxidative stress. Activating Nrf2 translocation restored redox homeostasis and reversed vulnerability to depression. This mechanism was confirmed in Nrf2-null mice. The mice displayed high levels of oxidative stress and were inherently vulnerable to depression, but this phenotype was reversed by treatment with antioxidants. Our data reveal a novel role for BDNF in controlling redox homeostasis and provide a mechanistic explanation for post-stress vulnerability to depression while suggesting ways to reverse it. Because numerous enzymatic reactions produce reactive oxygen species that must then be cleared, the finding that BDNF controls endogenous redox homeostasis opens new avenues for investigation.
The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and ...duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.
Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which ...takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.
Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Across evolution, maternal care ...is a key source of environmental sensory signals to the developing brain, and a vast body of work has linked quantitative and qualitative aspects of maternal care to emotional outcome in children and animals. However, the fundamental properties of maternal signals, that promote advantageous vs pathological outcomes in the offspring, are unknown and have been a topic of intense study. We studied emotional outcomes of adolescent rats reared under routine or impoverished environments, and used mathematical approaches to analyze the nurturing behaviors of the dams. Unexpectedly, whereas the quantity and typical qualities of maternal care behaviors were indistinguishable in the two environments, their patterns and rhythms differed drastically and influenced emotional outcomes. Specifically, unpredictable, fragmented maternal care patterns translated into high-entropy rates of sensory signals to the offspring in the impoverished cages. During adolescence, these offspring had significant reductions in sucrose preference and in peer-play, two independent measures of the ability to experience pleasure. This adolescent anhedonia, often a harbinger of later depression, was not accompanied by measures of anxiety or helplessness. Dopaminergic pleasure circuits underlying anhedonia are engaged by predictable sequences of events, and predictable sensory signals during neonatal periods may be critical for their maturation. Conversely, unpredictability maternal-derived signals may disrupt these developmental processes, provoking anhedonia. In sum, high-entropy and fragmented patterns of maternal-derived sensory input to the developing brain predicts, and might promote, the development of anhedonia in rodents, with potential clinical implications.
Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies ...reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.
Context. High-mass analogues of low-mass prestellar cores are searched for to constrain the models of high-mass star formation. Several high-mass cores, at various evolutionary stages, have been ...recently identified towards the massive star-forming region W43-MM1 and amongst them a high-mass prestellar core candidate. Aims. We aim to characterise the chemistry in this high-mass prestellar core candidate, referred to as W43-MM1 core #6, and its environment. Methods. Using ALMA high-spatial resolution data of W43-MM1, we have studied the molecular content of core #6 and a neighbouring high-mass protostellar core, referred to as #3, which is similar in size and mass to core #6. We first subtracted the continuum emission using a method based on the density distribution of the intensities on each pixel. Then, from the distribution of detected molecules, we identified the molecules centred on the prestellar core candidate (core #6) and those associated to shocks related to outflows and filament formation. Then we constrained the column densities and temperatures of the molecules detected towards the two cores. Results. While core #3 appears to contain a hot core with a temperature of about 190 K, core #6 seems to have a lower temperature in the range from 20 to 90 K from a rotational diagram analysis. We have considered different source sizes for core #6 and the comparison of the abundances of the detected molecules towards the core with various interstellar sources shows that it is compatible with a core of size 1000 au with T = 20−90 K or a core of size 500 au with T ~ 80 K. Conclusions. Core #6 of W43-MM1 remains one of the best high-mass prestellar core candidates even if we cannot exclude that it is at the very beginning of the protostellar phase of high-mass star formation.
Aims. To constrain the physical processes that lead to the birth of high-mass stars it is mandatory to study the very first stages of their formation. We search for high-mass analogs of low-mass ...prestellar cores in W43-MM1. Methods. We conducted a 1.3 mm ALMA mosaic of the complete W43-MM1 cloud, which has revealed numerous cores with ~2000 au FWHM sizes. We investigated the nature of cores located at the tip of the main filament, where the clustering is minimum. We used the continuum emission to measure the core masses and the 13CS(5-4) line emission to estimate their turbulence level. We also investigated the prestellar or protostellar nature of these cores by searching for outflow signatures traced by CO(2-1) and SiO(5-4) line emission, and for molecular complexity typical of embedded hot cores. Results. Two high-mass cores of ~1300 au diameter and ~60 M⊙ mass are observed to be turbulent but gravitationally bound. One drives outflows and is associated with a hot core. The other core, W43-MM1#6, does not yet reveal any star formation activity and thus is an excellent high-mass prestellar core candidate.
•NO mole fraction profiles measured by LIF in high pressure lean CH4/air flames.•Three kinetic mechanisms: GDFkin®3.0_NCN, GRImech2.11 and GRImech3.0 are compared.•Kinetic analysis to better ...understand the differences between the three mechanisms.•Inclusion of the new prompt-NO formation pathway in the GRImech3.0 mechanism.
Nitric oxide (NO) is an atmospheric pollutant responsible for the destruction of the ozone layer and the creation of photochemical smog. As a result, NOx emissions from combustion sources are regulated in most industrialised countries. The need to control NOx emissions while also promoting more efficient use of fossil energy resources requires a better understanding of combustion processes, especially the chemical kinetics of NOx formation. NO formation in high-pressure flames is a research area of great practical interest as high pressure exists in practically all power-generation and propulsion engines and it is known that pressure influences the combustion chemistry. In the present work, NO mole fraction profiles were measured by Laser Induced Fluorescence in laminar high pressure (up to 0.7MPa) counter-flow lean CH4/air (E.R.=0.7) flames. Inherent problems linked to the application of the NO LIF technique in high pressure environment were addressed. The experimental NO profiles were then compared with modelling using the OPPDIF code and the three detailed kinetic mechanisms: the GDFkin®3.0_NCN mechanism developed by Lamoureux et al. and the two mechanisms from the Gas Research Institute: GRImech 2.11 and GRImech 3.0. A kinetic analysis based on rate of production/consumption analyses was performed to better understand the differences between the three mechanisms. Finally, the GRImech3.0 mechanism was modified with three updated prompt-NO submechanisms proposed in the literature and the consequences on the N-containing species mole fractions predictions are discussed.