ABSTRACT
The temporal evolution of weak shocks in radiative media is theoretically investigated in this work. The structure of radiative shocks has traditionally been studied in a stationary framework. Their systematic classification is complex because layers of optically thick and thin regions alternate to form a radiatively driven precursor and a temperature-relaxation layer, between which the hydrodynamic shock is embedded. In this work we analyze the formation of weak shocks when two radiative plasmas with different pressures are put in contact. Applying a reductive perturbative method yields a Burgers-type equation that governs the temporal evolution of the perturbed variables including the radiation field. The conditions upon which optically thick and thin solutions exist have been derived and expressed as a function of the shock strength and Boltzmann number. Below a certain Boltzmann number threshold, weak shocks always become optically thick asymptotically in time, while thin solutions appear as transitory structures. The existence of an optically thin regime is related to the presence of an overdense layer in the compressed material. Scaling laws for the characteristic formation time and shock width are provided for each regime. The theoretical analysis is supported by FLASH simulations, and a comprehensive test case has been designed to benchmark radiative hydrodynamic codes.
ABSTRACT
Isolation of neuron-derived extracellular vesicles (NDEVs) with L1 Cell Adhesion Molecule (L1CAM)-specific antibodies has been widely used to identify blood biomarkers of CNS disorders. However, full methodological validation requires demonstration of L1CAM in individual NDEVs and lower levels or absence of L1CAM in individual EVs from other cells. Here, we used multiple single-EV techniques to establish the neuronal origin and determine the abundance of L1CAM-positive EVs in human blood. L1CAM epitopes of the ectodomain are shown to be co-expressed on single-EVs with the neuronal proteins ß-III-tubulin, GAP43, and VAMP2, the levels of which increase in parallel with the enrichment of L1CAM-positive EVs. Levels of L1CAM-positive EVs carrying the neuronal proteins VAMP2 and ß-III-tubulin range from 30% to 63%, in contrast to 0.8%-3.9% of L1CAM-negative EVs. Plasma fluid-phase L1CAM does not bind to single-EVs. Our findings support the use of L1CAM as a target for isolating plasma NDEVs and leveraging their cargo to identify biomarkers reflecting neuronal function.
Subject(s)
Biomarkers , Extracellular Vesicles , Neural Cell Adhesion Molecule L1 , Neurons , Vesicle-Associated Membrane Protein 2 , Humans , Neural Cell Adhesion Molecule L1/metabolism , Extracellular Vesicles/metabolism , Biomarkers/metabolism , Biomarkers/blood , Neurons/metabolism , Vesicle-Associated Membrane Protein 2/metabolism , Tubulin/metabolismABSTRACT
First theorized by Hebb, neuronal ensembles have provided a framework for understanding how the mammalian brain operates, especially regarding learning and memory. Neuronal ensembles are discrete, sparsely distributed groups of neurons that become activated in response to a specific stimulus and are thought to provide an internal representation of the world. Beyond the study of region-wide or projection-wide activation, the study of ensembles offers increased specificity and resolution to identify and target specific memories or associations. Neuroscientists interested in the neurobiology of learning, memory, and motivated behavior have used electrophysiological-, calcium-, and protein-based proxies of neuronal activity in preclinical models to better understand the neurobiology of learned and motivated behaviors. Although these three approaches may be used to pursue the same general goal of studying neuronal ensembles, technical differences lead to inconsistencies in the output and interpretation of data. This mini-review highlights some of the methodologies used in electrophysiological-, calcium-, and protein-based studies of neuronal ensembles and discusses their strengths and weaknesses.
ABSTRACT
Magnetized target fusion approach to inertial confinement fusion involves the formation of strong shocks that travel along a magnetized plasma. Shocks, which play a dominant role in thermalizing the upstream kinetic energy generated in the implosion stage, are seldom free from perturbations, and they wrinkle in response to upstream or downstream disturbances. In Z-pinch experiments, significant plasma instability mitigation was observed with pre-embedded axial magnetic fields. To isolate effects, in this work we theoretically study the impact of perpendicular magnetic fields on the planar shock dynamics for different equations of state. For fast magnetosonic shocks in ideal gases, it was found that the magnetic field amplifies the intensity of the perturbations when γ>2 or it weakens them when γ<2. Weak shocks have been found to be stable regardless of the magnetic plasma intensity and gas compressibility; however, for sufficiently strong shocks the magnetic fields can promote a neutral stability/SAE at the shock if the adiabatic index is higher than 1+sqrt[2]. Results have been validated with numerical simulations performed with the FLASH code.
ABSTRACT
Learning and behavior activate cue-specific patterns of sparsely distributed cells and synapses called ensembles that undergo memory-encoding engram alterations. While Fos is often used to label selectively activated cell bodies and identify neuronal ensembles, there is no comparable endogenous marker to label activated synapses and identify synaptic ensembles. For the purpose of identifying candidate synaptic activity markers, we optimized a flow cytometry of synaptoneurosome (FCS) procedure for assessing protein alterations in activated synapses from male and female rats. After injecting yellow fluorescent protein (YFP)-expressing adeno-associated virus into medial prefrontal cortex (mPFC) to label terminals in nucleus accumbens (NAc) of rats, we injected 20 mg/kg cocaine in a novel context (cocaine+novelty) to activate synapses, and prepared NAc synaptoneurosomes 0-60 min following injections. For FCS, we used commercially available antibodies to label presynaptic and postsynaptic markers synaptophysin and PSD-95 as well as candidate markers of synaptic activity [activity-regulated cytoskeleton protein (Arc), CaMKII and phospho-CaMKII, ribosomal protein S6 (S6) and phospho-S6, and calcineurin and phospho-calcineurin] in YFP-labeled synaptoneurosomes. Cocaine+novelty increased the percentage of S6-positive synaptoneurosomes at 5-60 min and calcineurin-positive synaptoneurosomes at 5-10 min. Electron microscopy verified that S6 and calcineurin levels in synaptoneurosomes were increased 10 min after cocaine+novelty. Pretreatment with the anesthetic chloral hydrate blocked cocaine+novelty-induced S6 and calcineurin increases in synaptoneurosomes, and novel context exposure alone (without cocaine) increased S6, both of which indicate that these increases were due to neural activity per se. Overall, FCS can be used to study protein alterations in activated synapses coming from specifically labeled mPFC projections to NAc.SIGNIFICANCE STATEMENT Memories are formed during learning and are stored in the brain by long-lasting molecular and cellular alterations called engrams formed within specific patterns of cue-activated neurons called neuronal ensembles. While Fos has been used to identify activated ensemble neurons and the engrams within them, we have not had a similar marker for activated synapses that can be used to identify synaptic engrams. Here we developed a procedure for high-throughput in-line analysis of flow cytometry of synaptoneurosome (FCS) and found that ribosomal S6 protein and calcineurin were increased in activated mPFC-NAc synapses. FCS can be used to study protein alterations in activated synapses within specifically labeled circuits.
Subject(s)
Calcineurin , Cocaine , Female , Rats , Male , Animals , Rats, Sprague-Dawley , Nucleus Accumbens/physiology , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Flow Cytometry , Synapses , Prefrontal Cortex/physiology , Cocaine/pharmacologyABSTRACT
We previously demonstrated a role of piriform cortex (Pir) in relapse to fentanyl seeking after food choice-induced voluntary abstinence. Here, we used this model to further study the role of Pir and its afferent projections in fentanyl relapse. We trained male and female rats to self-administer palatable food pellets for 6 d (6 h/day) and fentanyl (2.5 µg/kg/infusion, i.v.) for 12 d (6 h/day). We assessed relapse to fentanyl seeking after 12 voluntary abstinence sessions, achieved through a discrete choice procedure between fentanyl and palatable food (20 trials/session). We determined projection-specific activation of Pir afferents during fentanyl relapse with Fos plus the retrograde tracer cholera toxin B (injected into Pir). Fentanyl relapse was associated with increased Fos expression in anterior insular cortex (AI) and prelimbic cortex (PL) neurons projecting to Pir. We next used an anatomical disconnection procedure to determine the causal role of these two projections (AIâPir and PLâPir) in fentanyl relapse. Contralateral but not ipsilateral disconnection of AIâPir projections decreased fentanyl relapse but not reacquisition of fentanyl self-administration. In contrast, contralateral but not ipsilateral disconnection of PLâPir projections modestly decreased reacquisition but not relapse. Fluorescence-activated cell sorting and quantitative PCR data showed molecular changes within Pir Fos-expressing neurons associated with fentanyl relapse. Finally, we found minimal or no sex differences in fentanyl self-administration, fentanyl versus food choice, and fentanyl relapse. Our results indicate that AIâPir and PLâPir projections play dissociable roles in nonreinforced relapse to fentanyl seeking versus reacquisition of fentanyl self-administration after food choice-induced voluntary abstinence.SIGNIFICANCE STATEMENT We previously showed a role of Pir in fentanyl relapse after food choice-induced voluntary abstinence in rats, a procedure mimicking human abstinence or a significant reduction in drug self-administration because of the availability of alternative nondrug rewards. Here, we aimed to further characterize the role of Pir in fentanyl relapse by investigating the role of Pir afferent projections and analyzing molecular changes in relapse-activated Pir neurons. We identified dissociable roles of two Pir afferent projections (AIâPir and PLâPir) in relapse to fentanyl seeking versus reacquisition of fentanyl self-administration after voluntary abstinence. We also characterized molecular changes within Pir Fos-expressing neurons associated with fentanyl relapse.
Subject(s)
Fentanyl , Piriform Cortex , Humans , Rats , Male , Female , Animals , Rats, Sprague-Dawley , Food Preferences , Food , Self Administration , Extinction, Psychological , Drug-Seeking Behavior/physiologyABSTRACT
Transposition flaps are some of the most commonly used flaps for reconstructing scalp defects. Limberg first described his rhomboid transposition flap in 1946. Dufourmentel flap was an improved version of the Limberg flap published in 1962 in which the base of the flap is widened to improve vascularisation. Transposition flaps are one of the best known and most widely used transposition flaps in reconstructive surgery. They have proven successful in different types of reconstructive and aesthetic situations as a full-thickness random transposition flap. Combination of three Dufourmentel flaps to reconstruct hexagonal defects has not been reported in the literature. It is a modification of the triple Limberg flap, in which, after removing a hexagonal defect, we reconstruct the primary defect with a triple Dufourmentel flap. This flap is very useful for reconstructing large scalp defects as it provides a large amount of skin tissue with high viability; however, given its versatility, it could be used in other anatomical areas. Ann Med Surg (Lond) 2021 7:102544; Plast Reconstr Surg 2015 136:163-164; Atlas Oral Maxillofac Surg Clin North Am 2020 28:17-22.
Subject(s)
Ectodermal Dysplasia , Plastic Surgery Procedures , Humans , Scalp , Surgical FlapsABSTRACT
High relapse rate is a key feature of opioid addiction. In humans, abstinence is often voluntary due to negative consequences of opioid seeking. To mimic this human condition, we recently introduced a rat model of incubation of oxycodone craving after electric barrier-induced voluntary abstinence. Incubation of drug craving refers to time-dependent increases in drug seeking after cessation of drug self-administration. Here, we used the activity marker Fos, muscimol-baclofen (GABAa + GABAb receptor agonists) global inactivation, Daun02-selective inactivation of putative relapse-associated neuronal ensembles, and fluorescence-activated cell sorting of Fos-positive cells and quantitative polymerase chain reaction to demonstrate a key role of vSub neuronal ensembles in incubation of oxycodone craving after voluntary abstinence, but not homecage forced abstinence. We also used a longitudinal functional magnetic resonance imaging method and showed that functional connectivity changes in vSub-related circuits predict opioid relapse after abstinence induced by adverse consequences of opioid seeking.
ABSTRACT
[This corrects the article DOI: 10.3389/fnsyn.2022.875904.].
ABSTRACT
Neuronal ensembles in ventromedial prefrontal cortex (vmPFC) play a role in both cocaine and palatable food seeking. However, it is unknown whether similar or different vmPFC neuronal ensembles mediate food and cocaine seeking. Here, we used the Daun02 inactivation procedure to assess whether the neuronal ensembles mediating food and cocaine seeking can be functionally distinguished. We trained male and female Fos-LacZ rats to self-administer palatable food pellets and cocaine on alternating days for 18 days. We then exposed the rats to a brief nonreinforced food- or cocaine-seeking test to induce Fos and ß-gal in neuronal ensembles associated with food or cocaine seeking, respectively and infused Daun02 into vmPFC to ablate the ß-gal-expressing ensembles. Two days later, we tested the rats for food or cocaine seeking under extinction conditions. Although inactivation of the food-seeking ensemble did not influence food or cocaine seeking, inactivation of the cocaine-seeking ensemble reduced cocaine seeking but not food seeking. Results indicate that the neuronal ensemble activated by cocaine seeking in vmPFC is functionally separate from the ensemble activated by food seeking.
Subject(s)
Cocaine/administration & dosage , Drug-Seeking Behavior/physiology , Extinction, Psychological/physiology , Neurons/metabolism , Oncogene Proteins v-fos/metabolism , Prefrontal Cortex/physiology , Animals , Conditioning, Operant/drug effects , Conditioning, Operant/physiology , Drug-Seeking Behavior/drug effects , Extinction, Psychological/drug effects , Female , Male , Neurons/drug effects , Prefrontal Cortex/drug effects , Rats , Rats, Sprague-Dawley , Rats, Transgenic , Self Administration , Time FactorsABSTRACT
The COVID pandemic has made telematic consultations a basic tool in daily practice. AIMS: The main objective of the study is to assess the results of the application of telematic consultations to limit the mobility of patients. The operational objectives are; to propose a consultation plan, to know how attendance limits consultations and to define which pathologies benefit the most from this plan. METHODS: A scheme is proposed with the creation of pre-scheduled clinic to assess suitability and the possibility of carrying them out in a single non face-to-face act. RESULTS: Phone call to 5,619 patients were made with a lack of response of 19%. The cases of 74% of the patients that answered were resolved virtually. There is a difference between units, obtaining a higher answering rate from patients appointed to specific clinic units, OR = 0.60, or to general trauma ones, OR = 0.67. The lowest answering rate was obtained from those derived from the emergency department. Twenty per cent of the consultations were not accompanied by complementary tests that would have favored the resolution in a single act. The general trauma consultations, OR = 0.34, postoperative control, OR = 0.49, and specific unit ones, OR = 0.40, were the ones that better met this requirement. Out of the remaining patients, the general trauma consultations, OR = 0.50, and those referred to units, OR = 0.54, were the ones that had a higher resolution rate without in- person consultation. CONCLUSIONS: The cases of 74% of the patients who answered the phone call were resolved virtually. Cases of 20% of the patients cannot be solved in a single act because they are derived without complementary tests. Osteosynthesis and postoperative arthroscopic follow-up consultations are the ones that need to be carried out in person the most.
Subject(s)
COVID-19 , Orthopedic Procedures , Orthopedics/methods , Remote Consultation/organization & administration , Traumatology/methods , Humans , Laparoscopy , SpainABSTRACT
MAIN AIM: To know the result of the Girdlestone resection arthroplasty in the treatment of the infected hip arthroplasty. SECONDARY AIMS: To analyze the effectiveness in the control of pain and infection, the functional outcome and to contrast factors correlated with the final result. PATIENTS AND METHODS: Case series with a total of 17 patients. The control of the infection was assessed according to the presence or absence of sinus, and the clinical status using EuroQol 5D scale, residual pain and limb length discrepancy. OUTCOMES: The most common infecting germ at the time of removal of the arthroplasty was Staphylococcus CN and one patient presented infection by Candida albicans. In 2 patients the draining sinus persisted. The residual dysmetria was 5.24cm. In the EQ-5D scale, the most affected dimensions were mobility, need for help for self-care and ability to carry out activities of daily life. 8 patients maintained, pain levels worse than 4 in the VAS. The variables of dysmetria were correlated inversely with health index (-0,54) and self-perceived general health status (-0,45). CONCLUSIONS: The Girdlestone resection arthroplasty is an alternative in the treatment of the infected hip arthroplasty. Patient perception is inversely corelated to residual dysmetria. The dysmetria is greater in women and in ages over 65 years.
ABSTRACT
This work is focused on optimal control of mechanical compression refrigeration systems. A reduced-order state-space model based on the moving boundary approach is proposed for the canonical cycle, which eases the controller design. The optimal cycle (that satisfying the cooling demand while maximizing efficiency) is defined by three variables, but only two inputs are available, therefore the controllability of the proposed model is studied. It is shown through optimization simulations how optimal cycles for a range of the cooling demand turn out not to be achieved by keeping the degree of superheating to a minimum. The Practical NMPC and a well-known feedback-plus-feedforward strategy from the literature are compared in simulation, both showing trouble in reaching the optimal cycle, which agrees with the controllability study.
ABSTRACT
Vitamin E is considered a powerful biological antioxidant; however, its characteristics such as high hydrophobicity and low stability limit its application. We propose to use nanotechnology as an innovative tool in spermatology, formulating nanoemulsions (NE) that accommodate vitamin E, protecting it from oxidation and promoting its release into the medium. The protective effect of the NE against oxidative stress was assessed in red deer epididymal sperm incubated at 37 °C. Cryopreserved sperm from eleven stags were thawed and extended to 400 × 106 sperm/ml in Bovine Gamete Medium (BGM). Once aliquoted, the samples were supplemented with the NE at different concentrations (0, 6 and 12 mM), with or without induced oxidative stress (100 µM Fe2+/ascorbate). The samples were evaluated after 0, 2 and 4 h of incubation at 37 °C. Motility (CASA), viability, mitochondrial membrane potential, acrosomal status, lipoperoxidation (C11 BODIPY 581/591), intracellular reactive oxygen species (ROS) production and DNA status (SCSA®) were assessed. After 2 and 4 h of incubation, the NE were able to prevent the deleterious effects of oxidative stress, thus improving total and progression motility (P Ë0.05). Moreover, the highest concentration tested (12 mM) improved almost every sperm kinematic variable (P Ë0.05) and preserved sperm viability in samples subjected to oxidative stress. In addition, 12 mM of NE protected the acrosomes integrity, maintained and protected mitochondrial activity, prevented sperm lipoperoxidation and reduced ROS production (P Ë0.05) in samples subjected to oxidative stress. This work indicates for the first time that vitamin E formulated in NE could be a new approach against sperm oxidative damage. This could be highly relevant for sperm physiology preservation in the context of assisted reproduction techniques.
Subject(s)
Deer , Nanotechnology , Oxidative Stress , Sperm Motility , Vitamin E , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Humans , Male , Reactive Oxygen Species/metabolism , Reproduction , Spermatozoa/metabolism , Vitamin E/metabolism , Vitamin E/pharmacologyABSTRACT
Most of the athalassic saline and hypersaline lakes are located in arid and semiarid regions where water availability drives the hydrological dynamics of the lake itself and the associated ecosystems. This is the case of the Salada de Chiprana Lake, in the Ebro River basin (Spain). It is the only athalassic permanent hypersaline lake in Western Europe, and where rare and endangered bacterial mats exist. This work presents a robust hydrogeological conceptual model for the lake system. The model evaluates the contribution of groundwater discharge to the whole water budget and explains the hydrological behaviour of the lake system. The lake behaves as a flow-through system rather than a closed basin. About 40% of total water outflow from the lake occurs as groundwater, whereas evaporation accounts for the remaining 60%. The surface water inflows are variable, but the groundwater contribution seems almost constant, amounting to 13% of the average total water inflow and contributing 1.9% of salt income. The high water salinity of the lake is controlled by evaporation, by saline water inflows from irrigation return flows, and the by groundwater outflows. The role of groundwater should be taken into account when drafting the water and land planning, once the conditions for the conservation of the algal mats are defined. A major contribution of this study is the water balance in the Salada de Chiprana Lake, which is consistent with a robust hydrogeological conceptual model defined upon scarce hydrogeological, hydrochemical and isotopic data in the local context as conditioned by the regional behaviour. The water balance is a key tool to help to correctly manage this unique athalassic saline lake, and the approach used here can be extrapolated to other similar ecosystems around the world.
ABSTRACT
BACKGROUND: Methamphetamine (Meth) seeking progressively increases after withdrawal (incubation of Meth craving). We previously demonstrated a role of anterior intralaminar nucleus of thalamus (AIT) to dorsomedial striatum (DMS) projections in this incubation. Here, we examined molecular alterations in DMS and AIT neurons activated (identified by neuronal activity marker Fos) during "incubated" Meth-seeking relapse test after prolonged withdrawal. METHODS: We trained male rats to self-administer Meth or saline (control condition) for 10 days (6 hr/day). Using fluorescence-activated cell sorting, we examined gene expression in Fos-positive (activated during a 2-hr relapse test) and Fos-negative (nonactivated) DMS and AIT neurons. RESULTS: In DMS, we found increased mRNA expressions of immediate early genes (IEGs) (Arc, Egr1, Npas4, Fosb), Trkb, glutamate receptors subunits (Gria3, Grin1, Grin2b, Grm1), and epigenetic enzymes (Hdac3, Hdac5, Crebbp) in Fos-positive neurons, compared with Fos-negative neurons. In AIT, we found that fewer genes (Egr1, Fosb, TrkB, Grin1, and Hdac5) exhibited increased mRNA expression in Fos-positive neurons. Unexpectedly, in both brain regions, gene alterations described above also occurred in drug-naïve saline self-administration control rats. CONCLUSIONS: These results demonstrated that transcriptional regulations in Fos-positive neurons activated during the relapse tests are brain region-specific but are not uniquely associated with drug exposure during the self-administration training.
Subject(s)
Corpus Striatum/metabolism , Gene Expression Regulation/drug effects , Methamphetamine/administration & dosage , Proto-Oncogene Proteins c-fos/metabolism , Substance Withdrawal Syndrome/genetics , Substance Withdrawal Syndrome/metabolism , Thalamus/metabolism , Animals , Corpus Striatum/drug effects , Craving/physiology , Disease Models, Animal , Male , Neurons/drug effects , Neurons/metabolism , Proto-Oncogene Proteins c-fos/genetics , Rats , Rats, Sprague-Dawley , Self Administration , Thalamus/drug effectsABSTRACT
Recent studies suggest that the ventral medial prefrontal cortex (vmPFC) encodes both operant drug self-administration and extinction memories. Here, we examined whether these opposing memories are encoded by distinct neuronal ensembles within the vmPFC with different outputs to the nucleus accumbens (NAc) in male and female rats. Using cocaine self-administration (3 h/d for 14 d) and extinction procedures, we demonstrated that vmPFC was similarly activated (indexed by Fos) during cocaine-seeking tests after 0 (no-extinction) or 7 extinction sessions. Selective Daun02 lesioning of the self-administration ensemble (no-extinction) decreased cocaine seeking, whereas Daun02 lesioning of the extinction ensemble increased cocaine seeking. Retrograde tracing with fluorescent cholera toxin subunit B injected into NAc combined with Fos colabeling in vmPFC indicated that vmPFC self-administration ensembles project to NAc core while extinction ensembles project to NAc shell. Functional disconnection experiments (Daun02 lesioning of vmPFC and acute dopamine D1-receptor blockade with SCH39166 in NAc core or shell) confirm that vmPFC ensembles interact with NAc core versus shell to play dissociable roles in cocaine self-administration versus extinction, respectively. Our results demonstrate that neuronal ensembles mediating cocaine self-administration and extinction comingle in vmPFC but have distinct outputs to the NAc core and shell that promote or inhibit cocaine seeking.SIGNIFICANCE STATEMENT Neuronal ensembles within the vmPFC have recently been shown to play a role in self-administration and extinction of food seeking. Here, we used the Daun02 chemogenetic inactivation procedure, which allows selective inhibition of neuronal ensembles identified by the activity marker Fos, to demonstrate that different ensembles for cocaine self-administration and extinction memories coexist in the ventral mPFC and interact with distinct subregions of the nucleus accumbens.