Drug self-administration and intracranial self-stimulation (ICSS) are two preclinical behavioral procedures used to predict abuse potential of drugs, and abuse-related drug effects in both procedures ...are thought to depend on increased mesolimbic dopamine (DA) signaling. Drug self-administration and ICSS yield concordant metrics of abuse potential across a diverse range of drug mechanisms of action. The “rate of onset,” defined as the velocity with which a drug produces its effect once administered, has also been implicated as a determinant of abuse-related drug effects in self-administration procedures, but this variable has not been systematically examined in ICSS. Accordingly, this study compared ICSS effects produced in rats by three DA transporter inhibitors that have different rates of onset (fastest to slowest: cocaine, WIN-35428, RTI-31) and that produced progressively weaker metrics of abuse potential in a drug self-administration procedure in rhesus monkeys. Additionally, in vivo photometry using the fluorescent DA sensor dLight1.1 targeted to the nucleus accumbens (NAc) was used to assess the time course of extracellular DA levels as a neurochemical correlate of behavioral effects. All three compounds produced ICSS facilitation and increased DA levels assessed by dLight. In both procedures, the rank order of onset rate was cocaine > WIN-35428 > RTI-31; however, in contrast to monkey drug self-administration results, maximum effects did not differ across compounds. These results provide additional evidence that drug-induced increases in DA drive ICSS facilitation in rats and illustrate the utility of both ICSS and photometry to evaluate the time course and magnitude of abuse-related drug effects in rats.
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DOBA, EMUNI, FIS, FSPLJ, 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, VSZLJ, ZAGLJ
Recently, a comparison between the locations of 6.7-GHz methanol masers and dust continuum emission has renewed speculation that these masers can be associated with evolved stars. The implication of ...such a scenario would be profound, especially for the interpretation of large surveys for 6.7-GHz masers, individual studies where high-mass star formation has been inferred from the presence of 6.7-GHz methanol masers and for the pumping mechanisms of these masers. We have investigated the two instances where 6.7-GHz methanol masers have been explicitly suggested to be associated with evolved stars, and we find the first to be associated with a standard high-mass star formation region, and the second to be a spurious detection. We also find no evidence to suggest that the methanol maser action can be supported in the environments of evolved stars. We thereby confirm their exclusive association with high-mass star formation regions.
Abstract
A critical challenge during volcanic emergencies is responding to rapid changes in eruptive behaviour. Actionable advice, essential in times of rising uncertainty, demands the rapid ...synthesis and communication of multiple datasets with prognoses. The 2020–2021 eruption of La Soufrière volcano exemplifies these challenges: a series of explosions from 9–22 April 2021 was preceded by three months of effusive activity, which commenced with a remarkably low level of detected unrest. Here we show how the development of an evolving conceptual model, and the expression of uncertainties via both elicitation and scenarios associated with this model, were key to anticipating this transition. This not only required input from multiple monitoring datasets but contextualisation via state-of-the-art hazard assessments, and evidence-based knowledge of critical decision-making timescales and community needs. In addition, we share strategies employed as a consequence of constraints on recognising and responding to eruptive transitions in a resource-constrained setting, which may guide similarly challenged volcano observatories worldwide.
Mining environmental liabilities generate environmental pollution. The objective of the present study was to determine the yield of white clover (Trifolium repens) and orchard grass (Dactylis ...glomerata) cultivated in mining environmental passives adding black earth and compost as a substrate in the Buenaventura Julcani Huancavelica Company. The treatments were the combinations: 4: 3.1: 3.1: 3:1.1 kg of RP: RP, TN: RP, C: RP, TN, C respectively. They were distributed in four treatments with twelve experimental units for each species of leguminous and gramineous grass, we worked according to the completely randomized design (DCA) with a 2 x 4 factorial arrangement, the experimental unit being a treatment with twelve repetitions. The variables evaluated were: germination percentage (TG) and stem survival percentage (TST). For the statistical analysis, the SPSS software was used.
The Fermi Gamma-ray Space Telescope (Fermi) is producing the most detailed inventory of the gamma-ray sky to date. Despite tremendous achievements approximately 25 per cent of all Fermi extragalactic ...sources in the Second Fermi Large Area Telescope Catalogue (2FGL) are listed as active galactic nuclei (AGN) of uncertain type. Typically, these are suspected blazar candidates without a conclusive optical spectrum or lacking spectroscopic observations. Here, we explore the use of machine-learning algorithms - random forests and support vector machines - to predict specific AGN subclass based on observed gamma-ray spectral properties. After training and testing on identified/associated AGN from the 2FGL we find that 235 out of 269 AGN of uncertain type have properties compatible with gamma-ray BL Lacertae and flat-spectrum radio quasars with accuracy rates of 85 per cent. Additionally, direct comparison of our results with class predictions made after following the infrared colour-colour space of Massaro et al. shows that the agreement rate is over four-fifths for 54 overlapping sources, providing independent cross-validation. These results can help tailor follow-up spectroscopic programmes and inform future pointed surveys with ground-based Cherenkov telescopes.
An alternative method called pulsed-DC powder-pack boriding process (PDCPB) is presented in this study. The main components of the PDCPB consisted of a metal box containing the specimen embedded in a ...powder mixture, and placed between two electrodes, which were connected to a DC power supply, and a programmable electronic control device producing the polarity changes during the process. A set of boriding conditions were carried out on the surfaces of AISI 316 L stainless steel and Inconel 718 superalloy using a constant current input of 5 A with polarity inversion cycles of 10 s. After the PDCPB, the boride layers were characterized by optical microscopy, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy.
The growth kinetics of the boride layers was established using a diffusion model that considered the mass balance equations at the growth interfaces, in which the boron diffusion coefficients in the layers were expressed as a function of the boriding temperatures to estimate the boron activation energies in the borided materials. The change of polarity in the electrodes allowed a uniform flux of boron during the process, obtaining similar layer thicknesses on the surfaces of the material exposed to the pulsed-DC field. Finally, the results showed that the growth rate of the layers was increased by the effect of the pulsed-DC field, whilst the boron activation energies, in the borided materials, decreased drastically compared to those obtained for the conventional powder-pack boriding process.
•A novel method denominated pulsed-DC powder-pack boriding is presented in this work.•Uniform boron fluxes were produced on the surfaces exposed to pulsed-DC field.•Pulsed-DC field developed similar layer thicknesses at the material surface.•Pulsed-DC field increased the growth kinetics of boride layer in treated materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rationale
Cancer patients receiving the antineoplastic drug paclitaxel report higher incidences and longer duration of treatment-resistant depression than patients receiving other classes of ...chemotherapeutics. Rodents treated with paclitaxel exhibit a suite of changes in affect-like behaviors. Further, paclitaxel causes chemotherapy-induced peripheral neuropathy (CIPN) in humans and rodents. Kappa opioid receptors (KOR) have a well-established role in depression and neuropathy. The contributions of KOR signaling to paclitaxel-induced aversive-like state and CIPN in rodents remain to be explored.
Objectives
We aimed to investigate whether dysregulation of the KOR/dynorphin system is associated with paclitaxel-mediated pain-like behavior and depression-like behavior.
Methods
Cancer-free male C57BL/6J mice were treated with four injections of vehicle or paclitaxel (32 mg/kg cumulative). The effects of the selective KOR antagonist norbinaltorphimine (norBNI) on paclitaxel-induced sucrose preference deficits and mechanical hypersensitivity were measured. Prodynorphin mRNA and receptor-mediated G protein activation were measured at two time points following the last paclitaxel injection using quantitative real-time polymerase chain reaction and agonist-stimulated
35
Sguanosine-5′-O′-(γ-thio)-triphosphate (
35
SGTPγS) binding, respectively, in the nucleus accumbens (NAc), caudate-putamen, amygdala, and spinal cord.
Results
Paclitaxel produced a norBNI-reversible sucrose preference deficit, whereas mechanical hypersensitivity was not reversed by norBNI. Paclitaxel treatment increased the levels of mRNA for prodynorphin, a precursor for endogenous KOR agonists, in the NAc. Paclitaxel also had time-dependent effects on KOR-mediated G protein activation in the NAc.
Conclusions
These results suggest that KOR signaling mediates an initial aversive component of paclitaxel, but not necessarily paclitaxel-induced mechanical hypersensitivity.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Premature ventricular contractions (PVCs) are the most frequent ventricular arrhythmias in the overall population. PVCs are known to acutely enhance contractility by the post-extrasystolic ...potentiation phenomenon, but over time persistent PVCs promote PVC-induced cardiomyopathy (PVC-CM), characterized by a reduction of the left ventricular (LV) ejection fraction. Ca
2+
cycling in myocytes commands muscle contraction and in this process, SERCA2 leads the Ca
2+
reuptake into the sarcoplasmic reticulum (SR) shaping cytosolic Ca
2+
signal decay and muscle relaxation. Altered Ca
2+
reuptake can contribute to the contractile dysfunction observed in PVC-CM. To better understand Ca
2+
handling using our PVC-CM model (canines with 50% PVC burden for 12 weeks), SR-Ca
2+
reuptake was investigated by measuring Ca
2+
dynamics and analyzing protein expression. Kinetic analysis of Ca
2+
reuptake in electrically paced myocytes showed a ~ 21 ms delay in PVC-CM compared to Sham in intact isolated myocytes, along with a ~ 13% reduction in SERCA2 activity assessed in permeabilized myocytes. Although these trends were not statistically significant between groups using hierarchical statistics, relaxation of myocytes following contraction was significantly slower in PVC-CM
vs
Sham myocytes. Western blot analyses indicate a 22% reduction in SERCA2 expression, a 23% increase in phospholamban (PLN) expression, and a 50% reduction in PLN phosphorylation in PVC-CM samples
vs
Sham. Computational analysis simulating a 20% decrease in SR-Ca
2+
reuptake resulted in a ~ 22 ms delay in Ca
2+
signal decay, consistent with the experimental result described above. In conclusion, SERCA2 and PLB alterations described above have a modest contribution to functional adaptations observed in PVC-CM.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Pituitary adenomas (PA) are neoplasms of pituitary adenohypophyseal cell lineage, which are the third most common cause of brain tumors among adults. Due to hormone secretion, PAs are ...closely related to metabolic syndrome (MetS). However, the relationship between these two entities has been scarcely studied to date.
Purpose
This paper aims to evaluate changes in the metabolic status of patients with PA before and after surgical treatment and to look for differences in metabolic outcomes among patients according to the adenoma type and the surgery success rate.
Methods
We assessed patients with PA who went through transsphenoidal surgery for its treatment, documenting metabolic parameters before and after surgery, analyzed whole sample changes, and then stratified them according to adenoma type (nonfunctioning, somatotroph, lactotroph, and corticotroph), and surgery success (total resection, near-total resection, partial resection, subtotal resection).
Results
A total of 214 patients were enrolled for this study. The prevalence of MetS with AACE criteria went from 51.52% before surgery to 28.99% after surgery (
P
< 0.001). Hyperglycemia (HG) was the most beneficial component; it went from 56% pre-surgery to 40.51% post-surgery (
P
= 0.03). The total resection group had the best improvement, with a significant decrease of prevalence in MetS from 83 to 16% (
P
< 0.001), and every component, except hypoalphalipoproteinemia (HA): obesity went from 96 to 67% (
P
< 0.001), arterial hypertension (AH) 59 to 24% (
P
< 0.001), HG 74 to 23% (
P
< 0.001), and hypertriglyceridemia (HTG) from 81 to 54% (
P
< 0.001). According to MetS prevalence, there was no difference in the improvement according to PA type.
Conclusion
Surgical treatment in patients with PA is associated with MetS improvement.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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