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1.
Nature ; 614(7947): 239-243, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36755175

RESUMO

Planetary rings are observed not only around giant planets1, but also around small bodies such as the Centaur Chariklo2 and the dwarf planet Haumea3. Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius4 of 555 km and possesses a roughly 80-km satellite5 (Weywot) that orbits at 24 Quaoar radii6,7. The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar's classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments8, can maintain a ring far away from the body. Moreover, Quaoar's ring orbits close to the 1/3 spin-orbit resonance9 with Quaoar, a property shared by Chariklo's2,10,11 and Haumea's3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies.

3.
Nano Lett ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38604944

RESUMO

The phase-shift, transmittance, and polarization properties of meta-atoms are investigated, motivated by their use as building blocks of metasurfaces used in metalenses, holograms, and beam shaping. We studied dielectric nanorod meta-atoms of several geometries, which included cylinders, triangles, squares, hexagons, octagons, and truncated cones. By analyzing light propagation through these meta-atoms for three different wavelengths (632.8, 545, and 50 nm), we show that the phase-shift introduced is independent of their cross-section shape, contrary to the expected behavior. Additionally, we show that the polarization response is independent of the shape and that the transmittance is partially shape-independent. We identify a novel dependence of phase-shift on the effective cross-sectional area of meta-atoms. These meta-atom optical properties are independent of its shape if its geometry has a C3 or larger rotational symmetry. This optical invariance has significant implications for the topological optimization of flat optics.

4.
Phys Rev Lett ; 132(16): 166601, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38701448

RESUMO

In multivalley systems, the valley pseudospin offers rich physics going from encoding of information by its polarization (valleytronics), to exploring novel phases of matter when its degeneracy is changed. Here, by strain engineering, we reveal fully valley-polarized quantum Hall phases in the Pb_{1-x}Sn_{x}Se Dirac system. Remarkably, when the valley energy splitting exceeds the fundamental band gap, we observe a "bipolar quantum Hall phase," heralded by the coexistence of hole and electron chiral edge states at distinct valleys in the same quantum well. This suggests that spatially overlaid counterpropagating chiral edge states emerging at different valleys do not interfere with each other.

5.
Am J Obstet Gynecol ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38432413

RESUMO

OBJECTIVE: Accurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12-16 weeks' gestation when there is evidence for its effectiveness, as well as guiding appropriate pregnancy care pathways and surveillance. The primary objective of this study was to evaluate the performance of artificial neural network models for the prediction of preterm preeclampsia (<37 weeks' gestation) using patient characteristics available at the first antenatal visit and data from prenatal cell-free DNA (cfDNA) screening. Secondary outcomes were prediction of early onset preeclampsia (<34 weeks' gestation) and term preeclampsia (≥37 weeks' gestation). METHODS: This secondary analysis of a prospective, multicenter, observational prenatal cfDNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and two characteristics of cfDNA, total cfDNA and fetal fraction (FF), were used to develop predictive models for early-onset (<34 weeks), preterm (<37 weeks), and term (≥37 weeks) preeclampsia. For the models, the 'reference' classifier was a shallow logistic regression (LR) model. We also explored several feedforward (non-linear) neural network (NN) architectures with one or more hidden layers and compared their performance with the LR model. We selected a simple NN model built with one hidden layer and made up of 15 units. RESULTS: Of 17,520 participants included in the final analysis, 72 (0.4%) developed early onset, 251 (1.4%) preterm, and 420 (2.4%) term preeclampsia. Median gestational age at cfDNA measurement was 12.6 weeks and 2,155 (12.3%) had their cfDNA measurement at 16 weeks' gestation or greater. Preeclampsia was associated with higher total cfDNA (median 362.3 versus 339.0 copies/ml cfDNA; p<0.001) and lower FF (median 7.5% versus 9.4%; p<0.001). The expected, cross-validated area under the curve (AUC) scores for early onset, preterm, and term preeclampsia were 0.782, 0.801, and 0.712, respectively for the LR model, and 0.797, 0.800, and 0.713, respectively for the NN model. At a screen-positive rate of 15%, sensitivity for preterm preeclampsia was 58.4% (95% CI 0.569, 0.599) for the LR model and 59.3% (95% CI 0.578, 0.608) for the NN model.The contribution of both total cfDNA and FF to the prediction of term and preterm preeclampsia was negligible. For early-onset preeclampsia, removal of the total cfDNA and FF features from the NN model was associated with a 6.9% decrease in sensitivity at a 15% screen positive rate, from 54.9% (95% CI 52.9-56.9) to 48.0% (95% CI 45.0-51.0). CONCLUSION: Routinely available patient characteristics and cfDNA markers can be used to predict preeclampsia with performance comparable to other patient characteristic models for the prediction of preterm preeclampsia. Both LR and NN models showed similar performance.

6.
Phys Chem Chem Phys ; 26(13): 9915-9930, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38482723

RESUMO

Ab initio electron-propagator calculations continue to be useful companions to experimental investigations of electronic structure in molecular anions. A new generation of electron-propagator methods recently has surpassed its antecedents' predictive accuracy and computational efficiency. Interpretive clarity has been conserved, for no adjustable parameters have been introduced in the preparation of molecular orbitals or in the formulation of approximate self-energies. These methods have employed the diagonal self-energy approximation wherein each Dyson orbital equals a canonical Hartree-Fock orbital times the square root of a probability factor. Numerical tests indicate that explicitly renormalized, diagonal self-energies are needed when Dyson orbitals have large valence nitrogen, oxygen or fluorine components. They also demonstrate that even greater accuracy can be realized with generalizations that do not employ the diagonal self-energy approximation in the canonical Hartree-Fock basis. Whereas the diagonal methods have fifth-power arithmetic scaling factors, the non-diagonal generalizations introduce only non-iterative sixth-power contractions. Composite models conserve the accuracy of the most demanding combinations of self-energy approximations and flexible basis sets with drastically reduced computational effort. Composite-model results on anions that resemble the chromophore of the green fluorescent protein illustrate the interpretive capabilities of explicitly renormalized self-energies. Accurate predictions on the lowest vertical electron detachment energy of each anion confirm experimental data and the utility of the diagonal self-energy approximation.

7.
J Phys Chem A ; 128(23): 4730-4749, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38814678

RESUMO

New-generation ab initio electron propagator methods for calculating electron detachment energies of closed-shell molecules and anions have surpassed their predecessors' accuracy and computational efficiency. Derived from an Hermitian, intermediately normalized superoperator metric, these methods contain no adjustable parameters. To assess their versatility, a standard set (NIST-50-EA) of 50 vertical electron affinities of small closed-shell molecules based on NIST reference data has been created. Errors with respect to reference data on 23 large, conjugated organic photovoltaic (OPV23) molecules have also been analyzed. All final states are valence anions that correspond to electron affinities between 0.2 and 4.2 eV. For a given scaling of the arithmetic bottleneck, the new-generation methods obtain the lowest mean absolute errors (MAEs). The best methods with fifth-power arithmetic scaling realize MAEs below 0.1 eV. Composite models comprising cubically and quintically scaling calculations executed with large and small basis sets, respectively, produce OPV23 MAEs near 0.05 eV. The accuracy of quintically scaling methods executed with large basis sets is thereby procured with reduced computational effort. New-generation results obtained with and without the diagonal self-energy approximation in the canonical Hartree-Fock basis have been compared. These results indicate that Dyson orbitals closely resemble canonical Hartree-Fock orbitals multiplied by the square root of a probability factor above 0.85.

8.
J Phys Chem A ; 128(8): 1399-1416, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38377355

RESUMO

A new generation of electron-propagator methods for the calculation of electron binding energies has surpassed its antecedents with respect to accuracy, efficiency, and interpretability. No adjustable parameters are introduced in these fully ab initio procedures. Numerical tests versus several databases of valence, vertical electron binding energies of closed-shell molecules and atoms have been performed. Easily interpreted self-energy approximations with cubic arithmetic scaling produce mean absolute errors (MAEs) of 0.2 and 0.3 eV for electron detachments and attachments, respectively. The most accurate explicitly renormalized methods with fifth-power arithmetic scaling yield MAEs below 0.1 eV for detachments and attachments. Approximate renormalization leads to more efficient fifth-power alternatives for electron detachments that achieve similar accuracy with fewer bottleneck operations. Composite protocols generate excellent predictions versus highly accurate basis-extrapolated standards and experiments. The validity of the diagonal self-energy approximation and the accuracy of the approximate renormalizations are confirmed. The success of these perturbative methods based on canonical Hartree-Fock orbitals rests on a Hermitized, intermediately normalized superoperator metric. The results of all of the new-generation calculations may be analyzed in terms of final-state orbital relaxation and differential correlation effects.

9.
Opt Lett ; 48(21): 5647-5650, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910724

RESUMO

While transmission-mode metalenses have been extensively studied, reflection-mode metalenses remain almost unexplored, presenting advantages in terms of improved efficiency and reduced complexity. In this Letter, we investigate a multilayer dielectric metalens operating in reflection mode at visible wavelengths without a metallic layer. Simulations and analysis demonstrate the performance of the metalens, with an 84% reflectivity the metalens proves its efficacy in reflection mode. At a numerical aperture of 0.15, the metalens achieves a 33% focusing efficiency, which is approximately twice that of similar reflective metalenses, facilitating efficient light manipulation and subwavelength resolution. Additionally, the metalens exhibits a well-defined focal spot with a full width at half maximum of 2.03 µm, approaching the diffraction limit.

10.
J Phys Chem A ; 127(4): 1085-1101, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36656801

RESUMO

A new generation of ab initio electron-propagator self-energy approximations that are free of adjustable parameters is tested on a benchmark set of 55 vertical electron detachment energies of closed-shell anions. Comparisons with older self-energy approximations indicate that several new methods that make the diagonal self-energy approximation in the canonical Hartree-Fock orbital basis provide superior accuracy and computational efficiency. These methods and their acronyms, mean absolute errors (in eV), and arithmetic bottlenecks expressed in terms of occupied (O) and virtual (V) orbitals are the opposite-spin, non-Dyson, diagonal second-order method (os-nD-D2, 0.2, OV2), the approximately renormalized quasiparticle third-order method (Q3+, 0.15, O2V3) and the approximately renormalized, non-Dyson, linear, third-order method (nD-L3+, 0.1, OV4). The Brueckner doubles with triple field operators (BD-T1) nondiagonal electron-propagator method provides such close agreement with coupled-cluster single, double, and perturbative triple replacement total energy differences that it may be used as an alternative means of obtaining standard data. The new methods with diagonal self-energy matrices are the foundation of a composite procedure for estimating basis-set effects. This model produces accurate predictions and clear interpretations based on Dyson orbitals for the photoelectron spectra of the nucleotides found in DNA.

11.
Nature ; 550(7675): 219-223, 2017 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-29022593

RESUMO

Haumea-one of the four known trans-Neptunian dwarf planets-is a very elongated and rapidly rotating body. In contrast to other dwarf planets, its size, shape, albedo and density are not well constrained. The Centaur Chariklo was the first body other than a giant planet known to have a ring system, and the Centaur Chiron was later found to possess something similar to Chariklo's rings. Here we report observations from multiple Earth-based observatories of Haumea passing in front of a distant star (a multi-chord stellar occultation). Secondary events observed around the main body of Haumea are consistent with the presence of a ring with an opacity of 0.5, width of 70 kilometres and radius of about 2,287 kilometres. The ring is coplanar with both Haumea's equator and the orbit of its satellite Hi'iaka. The radius of the ring places it close to the 3:1 mean-motion resonance with Haumea's spin period-that is, Haumea rotates three times on its axis in the time that a ring particle completes one revolution. The occultation by the main body provides an instantaneous elliptical projected shape with axes of about 1,704 kilometres and 1,138 kilometres. Combined with rotational light curves, the occultation constrains the three-dimensional orientation of Haumea and its triaxial shape, which is inconsistent with a homogeneous body in hydrostatic equilibrium. Haumea's largest axis is at least 2,322 kilometres, larger than previously thought, implying an upper limit for its density of 1,885 kilograms per cubic metre and a geometric albedo of 0.51, both smaller than previous estimates. In addition, this estimate of the density of Haumea is closer to that of Pluto than are previous estimates, in line with expectations. No global nitrogen- or methane-dominated atmosphere was detected.

12.
Environ Res ; 228: 115887, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37054836

RESUMO

Coastal ecosystems are particularly vulnerable to terrestrial inputs from human-impacted areas. The prevalence of wastewater treatment plants, unable to remove contaminants such as pharmaceuticals (PhACs), leads to their continuous input into the marine environment. In this paper, the seasonal occurrence of PhACs in a semi-confined coastal lagoon (the Mar Menor, south-eastern Spain) was studied during 2018 and 2019 by evaluating their presence in seawater and sediments, and their bioaccumulation in aquatic organisms. Temporal variation in the contamination levels was evaluated by comparison to a previous study carried out between 2010 and 2011 before the cessation of permanent discharges of treated wastewater into the lagoon. The impact of a flash flood event (September 2019) on PhACs pollution was also assessed. A total of seven compounds (out of 69 PhACs analysed) were found in seawater during 2018-2019, with a limited detection frequency (<33%) and concentrations (up to 11 ng/L of clarithromycin). Only carbamazepine was found in sediments (ND-1.2 ng/g dw), suggesting an improved environmental quality in comparison to 2010-2011 (when 24 and 13 compounds were detected in seawater and sediments, respectively). However, the biomonitoring of fish and molluscs showed a still remarkable accumulation of analgesic/anti-inflammatory drugs, lipid regulators, psychiatric drugs and ß-blocking agents, albeit not higher than in 2010. The flash flood event from 2019 increased the prevalence of PhACs in the lagoon, compared to the 2018-2019 sampling campaigns, especially in the upper water layer. After the flash flood the antibiotics clarithromycin and sulfapyridine yielded the highest concentrations ever reported in the lagoon (297 and 145 ng/L, respectively), alongside azithromycin in 2011 (155 ng/L). Flash flood events associated with sewer overflows and soil mobilisation, which are expected to increase under climate change scenarios, should be considered when assessing the risks posed by pharmaceuticals to vulnerable aquatic ecosystems in the coastal areas.


Assuntos
Ecossistema , Poluentes Químicos da Água , Humanos , Animais , Monitoramento Ambiental , Inundações , Bioacumulação , Claritromicina , Poluentes Químicos da Água/análise , Preparações Farmacêuticas
13.
J Chem Phys ; 159(12)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-38127383

RESUMO

A new generation of diagonal self-energies for the calculation of electron removal energies of molecules and molecular ions that has superseded its predecessors with respect to accuracy, efficiency, and interpretability is extended to include non-diagonal self-energies that permit Dyson orbitals to be expressed as linear combinations of canonical Hartree-Fock orbitals. In addition, an improved algorithm for renormalized methods eliminates the convergence difficulties encountered in the first studies of the new, diagonal self-energies. A dataset of outer-valence, vertical ionization energies with almost full-configuration-interaction quality serves as a standard of comparison in numerical tests. The new non-diagonal, renormalized methods are slightly more accurate than their diagonal counterparts, with mean absolute errors between 0.10 and 0.06 eV for outer-valence final states. This advantage is procured at the cost of an increase in the scaling of arithmetic bottlenecks that accompany the inclusion of non-diagonal self-energy terms. The new, non-diagonal, renormalized self-energies are also more accurate and efficient than their non-diagonal predecessors.

14.
J Assist Reprod Genet ; 40(10): 2317-2324, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37592098

RESUMO

PURPOSE: Evaluate which factors are involved in the increased rate of mosaicism in embryos. METHODS: A systematic review and meta-analysis was performed. After an exhaustive search of the literature, a total of seven papers were included in the analysis. In addition, data collected from IVF cycles performed in our fertility clinic were also analysed. Day of biopsy, embryo quality, maternal and paternal age and seminal quality were the chosen factors to be studied. RESULTS: The results of the meta-analysis show that neither embryo quality nor seminal quality were related to mosaic embryo rate (OR: 1.09; 95% CI: 0.94-1.28 and OR: 1.10; 95% CI: 0.87-1.37, respectively). A positive association was observed for the variable "biopsy day" with embryos biopsied at day 6 or 7 having the highest rate of mosaicism (OR: 1.06; 95% CI: 1.01-1.11). In opposite to what happens with aneuploidy rate, which increases with maternal age, embryo mosaicism is higher in younger women (<34 years) rather than in older ones (≥34 years) (OR: 0.95; 95% CI: 0.92-0.98). However, for the "paternal age" factor, no association with mosaicism was found (OR: 1.04; 95% CI: 0.90-1.21). CONCLUSIONS: With the present study, we can conclude that the factors related to the presence of mosaicism in embryos are the embryo biopsy day and maternal age. The rest of the studied factors showed no significant relationship with mosaicism. These results are of great importance as knowing the possible causes leading to mosaicism helps to improve the clinical results of reproductive treatments.


Assuntos
Aneuploidia , Mosaicismo , Feminino , Humanos , Idoso , Adulto , Fatores Etários , Biópsia , Embrião de Mamíferos
15.
J Assist Reprod Genet ; 40(7): 1755-1763, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37171739

RESUMO

PURPOSE: To identify novel genetic variants responsible for meiotic embryonic aneuploidy. METHODS: A prospective observational cohort study that included 29 couples who underwent trophectoderm biopsies from 127 embryos and performed whole-exome sequencing (WES) between November 2019 and March 2022. Patients were divided into two groups according to the expected embryo aneuploidy rate based on maternal age. RESULTS: After variant filtering in the WES analysis of 58 patients/donors, five heterozygous variants were identified in female partners from the study group that had an impact on embryo aneuploidy. Additionally, a slowdown in embryo development and a decrease in the number of blastocysts available for biopsy were observed in the study group embryos. CONCLUSION: This study has identified new candidate genes and variants not previously associated with meiotic embryo aneuploidy, but which are involved in important biological processes related to cell division and chromosome segregation. WES may be an efficient tool to identify patients with a higher-than-expected risk of embryo aneuploidy based on maternal age and allow for individualized genetic counselling prior to treatment.


Assuntos
Diagnóstico Pré-Implantação , Gravidez , Humanos , Feminino , Estudos Prospectivos , Sequenciamento do Exoma , Aneuploidia , Idade Materna , Blastocisto , Testes Genéticos
16.
Opt Lett ; 47(20): 5333-5336, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36240355

RESUMO

We propose and analyze a metalens whose meta-atoms (nanoscatterers) are integrated by a stack of quarter-wave dielectric layers. Each multilayer meta-atom is a nanopillar, which consists of alternating layers of high- and low-refractive-index materials. We show that the nanopillars of a multilayer metalens may have a smaller aspect ratio than the nanopillars of a standard metalens and have similar optical properties (focusing efficiency and chromaticity).

17.
J Assist Reprod Genet ; 39(11): 2595-2605, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36208357

RESUMO

PURPOSE: To identify candidate variants in genes possibly associated with premature ovarian insufficiency (POI). METHODS: Fourteen women, from 7 families, affected by idiopathic POI were included. Additionally, 98 oocyte donors of the same ethnicity were enrolled as a control group. Whole-exome sequencing (WES) was performed in 14 women with POI to identify possibly pathogenic variants in genes potentially associated with the ovarian function. The candidate genes selected in POI patients were analysed within the exome results of oocyte donors. RESULTS: After the variant filtering in the WES analysis of 7 POI families, 23 possibly damaging genetic variants were identified in 22 genes related to POI or linked to ovarian physiology. All variants were heterozygous and five of the seven families carried two or more variants in different genes. We have described genes that have never been associated to POI pathology; however, they are involved in important biological processes for ovarian function. In the 98 oocyte donors of the control group, we found no potentially pathogenic variants among the 22 candidate genes. CONCLUSION: WES has previously shown as an efficient tool to identify causative genes for ovarian failure. Although some studies have focused on it, and many genes are identified, this study proposes new candidate genes and variants, having potentially moderate/strong functional effects, associated with POI, and argues for a polygenic etiology of POI in some cases.


Assuntos
Doenças Ovarianas , Insuficiência Ovariana Primária , Humanos , Feminino , Sequenciamento do Exoma/métodos , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia , Exoma/genética , Doenças Ovarianas/genética
18.
Clin Invest Ginecol Obstet ; 49(4): 100776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693637

RESUMO

Aim: To assess the impact of the coronavirus SARS-CoV-2 pandemic on the level of anxiety in low-risk pregnant women. Material and method: Epidemiological, descriptive, prevalence study. A total of 74 patients who underwent low risk antenatal controls during the state of alarm because of COVID-19, were included. They filled in the Hamilton Anxiety Rating Scale and a specific document about the pandemic. Clinical histories and different variables of clinical interest were reviewed and compiled, respectively. Results: Mean age was 34.05 years with average amenorrhoea of 28.17 weeks. A total of 77% of the sample presented symptoms and signs compatible with anxiety. Of these, 44.6% and 32.4% presented minor and major anxiety, respectively. Concern over the time of the birth and postpartum and fear of being at greater risk because of possible infection was present in 95.9% and 94.6% of the sample, respectively. A total of 93.2% of the sample was afraid of intrauterine virus transmission; 94.5% admitted fear over the neonatal consequences of infection. Conclusions: The pregnant women assessed had three times more anxiety during the COVID-19 pandemic. This incidence is independent of most study variables.


Objetivo: Evaluar el impacto de la pandemia del coronavirus SARS-CoV-2 en el nivel de ansiedad en mujeres embarazadas de bajo riesgo. Material y método: Estudio epidemiológico, descriptivo, de prevalencia. Se incluyeron un total de 74 pacientes que se sometieron a controles prenatales de bajo riesgo durante el estado de alarma por COVID-19. Completaron la escala de calificación de ansiedad de Hamilton y un documento específico sobre la pandemia. Se revisaron y recopilaron historias clínicas y diferentes variables de interés clínico, respectivamente. Resultados: La edad promedio fue de 34,05 años con amenorrea promedio de 28,17 semanas. El 77% de la muestra presentó síntomas y signos compatibles con la ansiedad. De estos, el 44,6 y el 32,4% presentaron ansiedad menor y mayor, respectivamente. La preocupación por el momento del parto y el puerperio y el temor de presentar mayor riesgo por una posible infección estuvieron presentes en el 95,9 y 94,6% de la muestra, respectivamente. El 93,2% de la muestra temía una posible transmisión del virus intrauterino; el 94,5% admitió tener miedo a las consecuencias neonatales tras una posible infección. Conclusiones: Las embarazadas evaluadas tenían tres veces más ansiedad durante la pandemia de COVID-19. Esta incidencia es independiente de la mayoría de las variables de estudio.

19.
Hippocampus ; 31(2): 221-231, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33241879

RESUMO

Past studies find that chronic stress alters inhibitory, GABAergic circuitry of neurons in distinct hippocampal subregions. Less clear is whether these effects persist weeks after chronic stress ends, and whether these effects involve changes in the total number of hippocampal GABAergic neurons or modulates the function of specific GABAergic subtypes. A transgenic mouse line (VGAT:Cre Ai9) containing an indelible marker for GABAergic neurons (tdTomato) throughout the brain was used to determine whether chronic stress alters total GABAergic neuronal number or the expression of two key GABAergic cell subtypes, calretinin expressing (CR+) and somatostatin expressing (SOM+) neurons, and whether these changes endure weeks later. Male and female mice were chronically stressed in wire mesh restrainers for 6h/d/21d (Str) or not (Con), and then allowed a 3 week rest period (Str-Rest) and compared to those without a rest period (Str-NoRest). Epifluorescent microscope images of immunohistochemistry-processed brains were quantified to estimate the total number of fluorescently-labeled hippocampal GABAergic neurons and the proportion that were CR+ or SOM+. Neither chronic stress nor sex altered the total number of GABAergic cells. In contrast, chronic stress reduced the expression of CR+ in the CA3 region of the hippocampus in both males and females, with robust reductions in the DG region of males, but not females, and these changes reversed following a rest period. Chronic stress also reduced the proportion of hippocampal SOM+ neurons and this reduction persisted even with a rest period. These results show chronic stress dynamically reduced CR expression without changing total inhibitory neuronal number and point to CR as a potential new lead to understand mechanisms by which chronic stress alters hippocampal function.


Assuntos
Hipocampo , Somatostatina , Animais , Calbindina 2/metabolismo , Feminino , Neurônios GABAérgicos/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Somatostatina/metabolismo
20.
Neurochem Res ; 46(12): 3159-3165, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34370167

RESUMO

Glutamate (Glu) is considered the most important excitatory amino acid neurotransmitter in the mammalian Central Nervous System. Zinc (Zn) is co-released with Glu during synaptic transmission and interacts with Glutamate receptors and transporters. We performed binding experiments using [3H]MK-801 (NMDA), and [3H]Fluorowillardine (AMPA) as ligands to study Zn-Glutamate interactions in rat cortical synaptic membranes. We also examined the effects of mercury and lead on NMDA or AMPA receptors. Zinc at 1 nM, significantly potentiates [3H]MK-801 binding. Lead inhibits [3H]MK-801 binding at micromolar concentrations. At millimolar concentrations, Hg also has a significant inhibitory effect. These effects are not reversed by Zn (1 nM). Zinc displaces the [3H]FW binding curve to the right. Lead (nM) and Hg (µM) inhibit [3H]FW binding. At certain concentrations, Zn reverses the effects of these metals on [3H]FW binding. These specific interactions serve to clarify the role of Zn, Hg, and Pb in physiological and pathological conditions.


Assuntos
Alanina/análogos & derivados , Maleato de Dizocilpina/metabolismo , Chumbo/farmacologia , Mercúrio/farmacologia , Pirimidinas/metabolismo , Membranas Sinápticas/metabolismo , Zinco/farmacologia , Alanina/metabolismo , Animais , Fármacos Neuroprotetores/metabolismo , Ratos , Membranas Sinápticas/efeitos dos fármacos
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