Region Of Nucleus Research Articles

Computational approach for counting of SISH amplification signals for HER2 status assessment

The human epidermal growth factor receptor 2 (HER2) gene is a critical biomarker for determining amplification status and targeting clinical therapies in breast cancer treatment. This study introduces a computer-aided method that automatically measures and scores HER2 gene status from invasive tissue regions of breast cancer using whole slide images (WSI) through silver in situ hybridization (SISH) staining. Image processing and deep learning techniques are employed to isolate untruncated and non-overlapping single nuclei from cancer regions. The Stardist deep learning model is fine-tuned on our HER2-SISH data to identify nuclei regions, followed by post-processing based on identified HER2 and CEP17 signals. Conventional thresholding techniques are used to segment HER2 and CEP17 signals. HER2 amplification status is determined by calculating the HER2-to-CEP17 signal ratio, in accordance with ASCO/CAP 2018 standards. The proposed method significantly reduces the effort and time required for quantification. Experimental results demonstrate a 0.91% correlation coefficient between pathologists manual enumeration and the proposed automatic SISH quantification approach. A one-sided paired t-test confirmed that the differences between the outcomes of the proposed method and the reference standard are statistically insignificant, with p-values exceeding 0.05. This study illustrates how deep learning can effectively automate HER2 status determination, demonstrating improvements over current manual methods and offering a robust, reproducible alternative for clinical practice.

IDENTIFYING THE FINE STRUCTURE OF THE EXPERIMENTALLY OBSERVED PEAK FOR 254No AT 2.5 MeV

Thus far, the low-lying dipole response has been observed throughout the deformed nuclear chart, with the exception of the transfermium region. In addition, the spectroscopic energy region of the 254No nucleus has recently been investigated and a broad peak at ≈ 2.5 MeV has been observed. This study, for the first time, explains the fine structure of this experimentally observed broad peak by predicting it through the QRPA framework. More specifically, the calculations revealed the experimentally observed peak comprises at least six dipole excitations.

Evaluation of Protective Efficacy of Recombinant Toxoplasma gondii DDX39 Protein Vaccine against Acute and Chronic T. gondii Infection in Mice

Toxoplasma gondii, a pervasive parasite responsible for toxoplasmosis, poses significant health risks to humans and animals. In this study, we investigated the immunogenicity and protective efficacy of the recombinant T. gondii DDX39 protein formulated with ISA201 adjuvant (rTgDDX39) as a candidate vaccine against toxoplasmosis. The full-length of TgDDX39 gene was successfully amplified, cloned into the pET-30a vector, and expressed in BL21 (DE3) competent cells, which was purified and identified as a 57.1 kDa protein via sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Western blot analysis confirmed that rTgDDX39 was specifically recognized by serum from T. gondii-infected mice. Furthermore, immunization of rats with rTgDDX39 generated antiserum that could specifically recognize the native TgDDX39 protein in T. gondii tachyzoite lysates. Immunofluorescence assay revealed that TgDDX39 was primarily located in the nucleus and perinuclear region of tachyzoites. Our vaccination strategy significantly increased T cell proliferation, with CD4+ T cells rising by 21.9% and CD8+ T cells by 57.8% by the sixth week compared to the adjuvant control group. Additionally, high titers of anti-rTgDDX39 IgG antibodies were detected in vaccinated mice, with a notable induction of IgG1 and IgG2a isotypes, and IgG1/IgG2a > 1 suggests a Th2-biased immune response.Furthermore, in vitro and in vivo assays demonstrated that polyclonal antibodies raised against rTgDDX39 could inhibit the proliferation of T. gondii RH tachyzoites, highlighting the potential of these antibodies to neutralize this parasite effectively. This study provides compelling evidence of the immunogenicity and protective efficacy of rTgDDX39, supporting its potential as a potential candidate vaccine against toxoplasmosis. The protective efficacy of the vaccine was evaluated in mice challenged with acute (RH) and chronic (PRU) strains of T. gondii, showing a survival time extended to 17 days in the acute model, compared to 13.5 and 14 days in the control groups, and a significant 34% reduction in cyst burden in the chronic model. Additionally, the survival rate in the PRU-infected mice increased from 15-20% in the control groups to 45% in the vaccinated group. In vitro and in vivo assays demonstrated that polyclonal antibodies raised against rTgDDX39 could inhibit the proliferation of T. gondii RH tachyzoites, highlighting the potential of these antibodies to neutralize the parasite effectively. This study provides compelling evidence of the immunogenicity and protective efficacy of rTgDDX39, supporting its potential as a candidate vaccine against toxoplasmosis.

Hypothalamic cerebrospinal fluid-contacting neurons project to the rostral agranular insular cortex: An immunofluorescence and ultrastructural analysis in the rat.

Cerebrospinal fluid-contacting neurons (CSF-cNS) are considered mechanoreceptors and chemoreceptors involved in detecting changes in CSF circulation. However, considering that recent data suggest that this type of cell could exert an active response when an external stimulus is sensed, identification of CSF-cNS may be relevant. In this regard, some data suggest that a neuronal connection exists between the ventral region of the hypothalamic paraventricular nucleus (PVN) and rostral agranular insular cortex (RAIC); indeed, a potential CSF-cNS is hypothesized. However, a detailed analysis of this connection has not been conducted. Thus, using neuronal tracers (Fluoro-Gold® (FG) and cholera toxin (ChT)) coupled with transmission electron microscopy and immunofluorescence assays against Fluoro-Gold®, oxytocin (OXT), vasopressin (AVP) and oxytocin receptors (OTR), we describe an oxytocinergic or vasopressinergic CSF-cNS between the PVN and RAIC. Our results showed that CSF-cNS along the PVN labelled with oxytocin and/or AVP were present in dendritic projections near the third ventricle. This CSF-cNS in the PVN seems to project to the RAIC. Inside the RAIC, ultrastructural analysis showed that axons immunopositive for oxytocin from the PVN sustained synaptic connections with neurons that expressed OTR. These findings show that the CSF-cNS from the PVN sends projections to the RAIC. To the best of our knowledge, the relevance of CSF-cNS has not been elucidated; however, we hypothesized that the activation of cells could concomitantly release neuropeptides (i.e., oxytocin and AVP) in the CSF and RAIC. Thus, further analysis of the impact of neuropeptides released into the third ventricle and RAIC is warranted.

The Galaxy Activity, Torus, and Outflow Survey (GATOS) V. Unveiling PAH survival and resilience in the circumnuclear regions of AGNs with JWST

This study analyses JWST MIRI/MRS observations of the infrared (IR) polycyclic aromatic hydrocarbon (PAH) bands in the nuclear (sim 0.4 at 11\,mu m; sim 75\,pc) and circumnuclear regions (inner sim kpc) of local active galactic nuclei (AGNs) from the Galactic Activity, Torus, and Outflow Survey (GATOS). We examine the PAH properties in the circumnuclear regions of AGNs and the projected direction of AGN-outflows and compare them to those in star-forming regions and the innermost regions of AGNs. This study employs 4.9-28.1\,mu m sub-arcsecond angular resolution data to investigate the properties of PAHs in three nearby sources L $ sim 30-40\,Mpc). Our findings are aligned with previous JWST studies, demonstrating that the central regions of AGNs display a larger fraction of neutral PAH molecules (i.e. elevated 11.3/6.2 and 11.3/7.7\,mu m PAH ratios) in comparison to star-forming galaxies. We find that AGNs might affect not only the PAH population in the innermost region, but also in the extended regions up to sim kpc scales. By comparing our observations to PAH diagnostic diagrams, we find that, in general, regions located in the projected direction of the AGN-outflow occupy similar positions on the PAH diagnostic diagrams as those of the innermost regions of AGNs. Star-forming regions that are not affected by the AGNs in these galaxies share the same part of the diagram as star-forming galaxies. We also examined the potential of the PAH-H$_2$ diagram to disentangle AGN-versus-star-forming activity. Our results suggest that in Seyfert-like AGNs, the illumination and feedback from the AGN might affect the PAH population at nuclear and kpc scales, particularly with respect to the ionisation state of the PAH grains. However, PAH molecular sizes are rather similar. The carriers of the ionised PAH bands (6.2 and 7.7\,mu m) are less resilient than those of neutral PAH bands (11.3\,mu m), which might be particularly important for strongly AGN-host coupled systems. Therefore, caution must be applied when using PAH bands as star-formation rate indicators in these systems even at kpc scales, with the effects of the AGN being more important for ionised ones.

Association between ASPECTS region of infarction and clinical outcome in non-acute large vessel occlusion ischaemic stroke after endovascular recanalisation

PurposeThis study retrospectively investigated whether infarction in specific Alberta Stroke Program Early CT Score (ASPECTS) regions is associated with clinical outcome in patients with symptomatic non-acute internal carotid or middle...

Barred active galactic nucleus galaxies in paired systems: Exploring the impact on nuclear activity

To unveil the influence of galaxy-galaxy interactions on the material transport driven by galactic bars toward the central regions of active galactic nucleus (AGN) galaxies, and to assess the efficiency of the combined mechanisms of interactions and bars in fueling massive black holes, we meticulously examine barred active galaxies in paired systems. Our study focuses on barred AGN galaxies in pairs with projected separations of $r_ p \,kpc $ and relative radial velocities of $ V< 500 \,km $ within $z<0.1$, identified by the Sloan Digital Sky Survey (SDSS). To quantify the impact of interactions on material transport by galactic bars, we also constructed a suitable control sample of barred active galaxies without paired companions, matched in redshift, absolute r-band magnitude, stellar mass, color, and stellar age distributions. Additionally, we calculated the structural characteristics of galactic bars through two-dimensional image modeling, considering that bars exhibit a wide range of shapes and sizes, which may influence their ability to channel material. From this study, we clearly found that nuclear activity (derived from the $Lum OIII $) increases as the projected separations between galaxy pair members decrease. Notably, barred AGN galaxies in close pairs ($r_p 25 kpc $) exhibit significantly higher nuclear activity compared to galaxies in the control sample. Additionally, barred galaxies with a close pair companion show enhanced nuclear activity across all ranges of luminosity, stellar mass, and color. We also found that barred AGN galaxies with longer bar structures exhibit more efficient nuclear activity compared to those with shorter bars. This trend is especially pronounced in barred AGN galaxies within close pair systems, which show a significant excess of high $Lum OIII $ values. Furthermore, we examined the central nuclear activity in barred AGNs undergoing major and minor interactions. Our findings show a clear escalation in nuclear activity as the pair projected separations decrease, particularly pronounced in major systems. Additionally, nuclear activity distributions in barred AGN samples within major and minor pairs exhibit similar trends. However, a significant deviation occurs among barred AGN galaxies in close pair systems within major interactions, showing a substantial excess of high $Lum OIII $ values. This result is also reflected in the analysis of the accretion strength onto central black holes. These findings indicate that external perturbations from a nearby galaxy companion can influence gas flows induced by galactic bars, leading to increased nuclear activity in barred AGN galaxies within pair systems. Thus, the coexistence of both — bars and interactions — significantly amplifies central nuclear activity, thereby influencing the accretion processes onto massive black holes.

Feedforward inhibition of stress by brainstem neuropeptide Y neurons

Resistance to stress is a key determinant for mammalian functioning. While many studies have revealed neural circuits and substrates responsible for initiating and mediating stress responses, little is known about how the brain resists to stress and prevents overreactions. Here, we identified a previously uncharacterized neuropeptide Y (NPY) neuronal population in the dorsal raphe nucleus and ventrolateral periaqueductal gray region (DRN/vlPAG) with anxiolytic effects in male mice. NPYDRN/vlPAG neurons are rapidly activated by various stressful stimuli. Inhibiting these neurons exacerbated hypophagic and anxiety responses during stress, while activation significantly ameliorates acute stress-induced hypophagia and anxiety levels and transmits positive valence. Furthermore, NPYDRN/vlPAG neurons exert differential but synergic anxiolytic effects via inhibitory projections to the paraventricular thalamic nucleus (PVT) and the lateral hypothalamic area (LH). Together, our findings reveal a feedforward inhibition neural mechanism underlying stress resistance and suggest NPYDRN/vlPAG neurons as a potential therapeutic target for stress-related disorders.

DB-FCN: An end-to-end dual-branch fully convolutional nucleus detection model

Detecting cells or nuclei in histopathological image analysis is a crucial prerequisite for subsequent cancer diagnosis. By precisely locating cell nuclei, pathologists can quantitatively analyze the morphology of each cell nucleus. This enables accurate cancer grading, allowing for the implementation of tailored treatment plans based on distinct cancer stages. Manual nucleus detection methods are labor-intensive, making the development of automatic cell nucleus detection algorithms highly necessary. However, due to the small size of the nucleus and increased adhesions between cells, tissue staining may be uneven, leading to a higher occurrence of false positives in the results of the current automatic nucleus detection algorithm. This paper introduces an end-to-end dual-branch-based fully convolutional neural network (DB-FCN) that effectively addresses the aforementioned challenges, thereby enhancing the accuracy of automatic nucleus detection. This algorithm introduces for the first time the use of two detection branches, namely the coarse detection branch and the fine detection branch, to accomplish the detection task. The role of the coarse detection branch is to identify all cell regions in the pathological image as comprehensively as possible and then transmit the detection results as prior information to the fine detection branch. The fine detection branch is necessary solely to conduct more precise detection based on the coarse detection results. Given that the coarse detection branch has already eliminated interference from many background regions, the fine detection branch can focus on detecting the nucleus region, thereby significantly enhancing the efficiency and accuracy of model detection. The detection model proposed in this paper was evaluated on three classic datasets and compared with many existing detection algorithms. Compared with other algorithms, the detection algorithm proposed in this paper has made significant progress in detecting cell nuclei in histopathological images.

Deep brain stimulation targeted at lateral hypothalamus-medial forebrain bundle reverses depressive-like symptoms and related cognitive deficits in rat: Role of serotoninergic system

The aim of the study is to understand the rationale behind the application of deep brain stimulation (DBS) in the treatment of depression. Male Wistar rats, rendered depressive with chronic unpredictable mild stress (CUMS) were implanted with electrode in the lateral hypothalamus-medial forebrain bundle (LH-MFB) and subjected to deep brain stimulation (DBS) for 4 h each day for 14 days. DBS rats, as well as controls, were screened for a range of parameters indicative of depressive state. Symptomatic features noticed in CUMS rats like the memory deficit, anhedonia, reduction in body weight and 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in mPFC and elevated plasma corticosterone were reversed in rats subjected to DBS. DBS arrested CUMS induced degeneration of 5-HT cells in interfascicular region of dorsal raphe nucleus (DRif) and fibers in LH-MFB and induced dendritic proliferation in mPFC neurons. MFB is known to serve as a major conduit for the DRif-mPFC serotoninergic pathway. While the density of serotonin fibers in the LH-MFB circuit was reduced in CUMS, it was upregulated in DBS-treated rats. Furthermore, microinjection of 5-HT1A receptor antagonist, WAY100635 into mPFC countered the positive effects of DBS like the antidepressant and memory-enhancing action. In this background, we suggest that DBS at LH-MFB may exercise positive effect in depressive rats via upregulation of the serotoninergic system. While these data drawn from the experiments on rat provide meaningful clues, we suggest that further studies aimed at understanding the usefulness of DBS at LH-MFB in humans may be rewarding.

On the Interpretation of Mid-infrared Absorption Lines of Gas-phase H2O as Observed by JWST/MIRI

Rovibrational absorption lines of H2O in the 5–8 μm wavelength range selectively probe gas against the mid-infrared continuum-emitting background of the inner regions of young stellar objects and active galactic nuclei and deliver important information about these warm, dust-obscured environments. JWST/Mid-Infrared Instrument (MIRI) detects these lines in many lines of sight at a moderate spectral resolving power of R ∼ 3500 (full width at half-maximum of 85 km s−1). Based on our analysis of high-resolution SOFIA/EXES observations, we find that the interpretation of JWST/MIRI absorption spectra can be severely hampered by the blending of individual transitions and the lost information on the intrinsic line width or the partial coverage of the background continuum source. In this paper, we point out problems such as degeneracy that arise in deriving physical properties from an insufficiently resolved spectrum. This can lead to differences in the column density by 2 orders of magnitude. We emphasize the importance of weighting optically thin and weak lines in spectral analyses and provide recipes for breaking down the coupled parameters. We also provide an online tool to generate the H2O absorption line spectra that can be compared to observations.

Mistargeted retinal axons form synaptically segregated subcircuits in the visual thalamus of albino mice.

A Hebbian model of circuit remodeling predicts that two sets of inputs with sufficiently distinct activity patterns will synaptically capture separate sets of target cells. Mice in which a subset of retinal ganglion cells (RGCs) target the wrong region of the dorsal lateral geniculate nucleus (dLGN) provide the conditions for testing this prediction. In albino mice, mistargeted RGC axons form an island of terminals that is distinct from the surrounding neuropil. Blocking retinal activity during development prevents the formation of this island. However, the synaptic connectivity of the island was unknown. Here, we combine light and electron microscopy to determine if this activity-dependent island of axon terminals represent a synaptically segregated subcircuit. We reconstructed the microcircuitry of the boundary between the island and non-island RGCs and found a remarkably strong segregation within retinogeniculate connectivity. We conclude that, when sets of retinal input are established in the wrong part of the dLGN, the developing circuitry responds by forming a synaptically isolated subcircuit from the otherwise fully connected network. The fact that there is a developmental starting condition that can induce a synaptically segregated microcircuit has important implications for our understanding of the organization of visual circuits and for our understanding of the implementation of activity dependent development.

The expression profiles of piRNAs and their interacting Piwi proteins in cellular model of renal development: Focus on Piwil1 in mitosis

Piwi proteins and Piwi interacting RNAs, piRNAs, presented in germline cells play a role in transposon silencing during germline development. In contrast, the role of somatic Piwi proteins and piRNAs still remains obscure. Here, we characterize the expression pattern and distribution of piRNAs in human renal cells in terms of their potential role in kidney development. Further, we show that all PIWI genes are expressed at the RNA level, however, only PIWIL1 gene is detected at the protein level by western blotting in healthy and cancerous renal cells. So far, the expression of human Piwil1 protein has only been shown in testes and cancer cells, but not in healthy somatic cell lines. Since we observe only Piwil1 protein, the regulation of other PIWI genes is probably more intricated, and depends on environmental conditions. Next, we demonstrate that downregulation of Piwil1 protein results in a decrease in the rate of cell proliferation, while no change in the level of apoptotic cells is observed. Confocal microscopy analysis reveals that Piwil1 protein is located in both cellular compartments, cytoplasm and nucleus in renal cells. Interestingly, in nucleus region Piwil1 is observed close to the spindle during all phases of mitosis in all tested cell lines. It strongly indicates that Piwil1 protein plays an essential role in proliferation of somatic cells. Moreover, involvement of Piwil1 in cell division could, at least partly, explain invasion and metastasis of many types of cancer cells with upregulation of PIWIL1 gene expression. It also makes Piwil1 protein as a potential target in the anticancer therapy.

The effect of preterm birth on thalamic development based on shape and structural covariance analysis

Acting as a central hub in regulating brain functions, the thalamus plays a pivotal role in controlling high-order brain functions. Considering the impact of preterm birth on infant brain development, traditional studies focused on the overall development of thalamus other than its subregions. In this study, we compared the volumetric growth and shape development of the thalamic hemispheres between the infants born preterm and full-term (Left volume: P = 0.027, Left normalized volume: P < 0.0001; Right volume: P = 0.070, Right normalized volume: P < 0.0001). The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth. The structural covariance (SC) between the thickness of thalamus and insula in preterm infants (Left: corrected P = 0.0091, Right: corrected P = 0.0119) showed significant increase as compared to full-term controls. Current findings suggest that preterm birth affects the development of the thalamus and has differential effects on its subregions. The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus are more susceptible to the impacts of preterm birth.

STUDY OF fMRI BRAIN ACTIVITY DURING NON-HANDWRITING AND HANDWRITING TASKS ON ESSENTIAL HAND TREMOR

Essential hand tremor (EHT) is a prevalent neurological condition affecting geriatric populations, yet its underlying mechanisms remain poorly understood. This study aims to investigate the neural substrates associated with motor tasks in EHT patients, illuminating the complex neural activity characterizing this condition. Twenty participants underwent a thorough evaluation to ensure eligibility, excluding factors such as mental illness, drug dependency, or Parkinson’s disease (PD). Functional magnetic resonance imaging (fMRI) was utilized to examine brain activation patterns during non-handwriting tasks (NHWT) and handwriting tasks (HWT). Participants received training to standardize hand and forearm movements for effective fMRI assessment. fMRI data preprocessing included motion correction, filtering, removal of linear trends, normalization to Montreal Neurological Institute (MNI) space, and spatial smoothing. Distinctive patterns of brain activation were observed during motor tasks in individuals with EHT compared to controls. During NHWT, the EHT group showed significantly increased activation in the precentral gyrus, supplementary motor area, thalamus, and posterior cerebellar lobe, highlighting their role in mediating motor challenges in EHT. Similarly, during HWT, the EHT group exhibited heightened activation in the precentral gyrus and supplementary motor areas. In contrast, reduced activation was noted in the caudate nucleus, inferior temporal gyrus, and precuneus during HWT in the EHT group compared to controls. These findings align with previous research on involuntary movement disorders, such as early-stage PD, emphasizing the importance of the caudate nucleus and related regions in EHT. In conclusion, this study sheds light on the intricate neural activity underlying motor tasks in EHT patients. The identified neural regions and their functions offer insights into the neurophysiological basis of EHT-related motor impairments. These findings have the potential to enhance the understanding of EHT beyond its surface-level effects. This study has identified the brain regions involved in motor tasks affected by EHT. This sets a foundation for future research to better understand the complexities of this neurological condition. These discoveries may lead to novel therapeutic interventions tailored to address the unique challenges faced by individuals with EHT, representing a significant milestone in understanding and managing EHT.

Quantitative susceptibility mapping in the brain reflects spatial expression of genes involved in iron homeostasis and myelination.

Quantitative susceptibility mapping (QSM) is an MRI modality used to non-invasively measure iron content in the brain. Iron exhibits a specific anatomically varying pattern of accumulation in the brain across individuals. The highest regions of accumulation are the deep grey nuclei, where iron is stored in paramagnetic molecule ferritin. This form of iron is considered to be what largely contributes to the signal measured by QSM in the deep grey nuclei. It is also known that QSM is affected by diamagnetic myelin contents. Here, we investigate spatial gene expression of iron and myelin related genes, as measured by the Allen Human Brain Atlas, in relation to QSM images of age-matched subjects. We performed multiple linear regressions between gene expression and the average QSM signal within 34 distinct deep grey nuclei regions. Our results show a positive correlation (p < .05, corrected) between expression of ferritin and the QSM signal in deep grey nuclei regions. We repeated the analysis for other genes that encode proteins thought to be involved in the transport and storage of iron in the brain, as well as myelination. In addition to ferritin, our findings demonstrate a positive correlation (p < .05, corrected) between the expression of ferroportin, transferrin, divalent metal transporter 1, several gene markers of myelinating oligodendrocytes, and the QSM signal in deep grey nuclei regions. Our results suggest that the QSM signal reflects both the storage and active transport of iron in the deep grey nuclei regions of the brain.

Euclid preparation. XLV. Optical emission-line predictions of intermediate-z galaxy populations in GAEA for the Euclid Deep and Wide Surveys

In anticipation of the upcoming Euclid Wide and Deep Surveys, we present optical emission-line predictions at intermediate redshifts from 0.4 to 2.5. Our approach combines a mock light cone from the Gaea semi-analytic model with advanced photoionisation models to construct emission-line catalogues. This allows us to self-consistently model nebular emission from H ii regions around young stars, and, for the first time with a semi-analytic model, narrow-line regions of active galactic nuclei (AGN) and evolved stellar populations. Gaea Mpc $, marks the largest volume this set of models has been applied to. We validate our methodology against observational and theoretical data at low redshift. Our analysis focuses on seven optical emission lines: Halpha , Hbeta S ii N ii O i O iii 5007$, and O ii 3727, 3729$. In assessing selection bias, we find that it will predominantly observe line-emitting galaxies, which are massive (stellar mass $ solarmass $), star-forming (specific star-formation rate $&gt; 10^ yr^ $), and metal-rich (oxygen-to-hydrogen abundance $ logten(O/H)+12 &gt; 8$). We provide percentages of emission-line populations in our underlying Gaea sample with a mass resolution limit of $10^ solarmass $ and an $H$-band magnitude cut of 25. We compare results with and without an estimate of interstellar dust attenuation, which we model using a Calzetti law with a mass-dependent scaling. According to this estimate, the presence of dust may decrease observable percentages by a further 20-30&lt;!PCT!&gt; with respect to the overall population, which presents challenges for detecting intrinsically fainter lines. We predict to observe around 30--70&lt;!PCT!&gt; of Halpha - N ii S ii -, and O iii -emitting galaxies at redshift below 1. At higher redshift, these percentages decrease below 10&lt;!PCT!&gt;. Hbeta O ii and O i emission are expected to appear relatively faint, thus limiting observability to at most 5&lt;!PCT!&gt; at the lower end of their detectable redshift range, and below 1&lt;!PCT!&gt; at the higher end. This is the case both for these lines individually and in combination with other lines. For galaxies with line emission above the flux threshold in the Euclid Deep Survey, we find that BPT diagrams can effectively distinguish between different galaxy types up to around redshift 1.8, attributed to the bias toward metal-rich systems. Moreover, we show that the relationships of Halpha and O iii +Hbeta to the star-formation rate, as well as the O iii -AGN luminosity relation, exhibit minimal, if any, changes with increasing redshift when compared to local calibrations. Based on the line ratios $ N ii /H N ii O ii $, and $ N ii S ii $, we further propose novel redshift-invariant tracers for the black hole accretion rate-to-star formation rate ratio. Lastly, we find that commonly used metallicity estimators display gradual shifts in normalisations with increasing redshift, while maintaining the overall shape of local calibrations. This is in tentative agreement with recent JWST data.

Optical Spectropolarimetric Variability Properties in Blazars PKS 0637–75 and PKS 1510–089

Spectropolarimetry is a powerful tool to investigate the central regions of active galactic nuclei (AGNs) as polarization signatures are key to probing magnetic field structure, evolution, and the physics of particle acceleration in jets. Optical linear polarization of blazars is typically greater than a few percent, indicating the emission is dominated by nonthermal synchrotron radiation, while polarization less than a few percent is common for other type 1 AGNs. We present a spectropolarimetric study of PKS 0637–75 and PKS 1510–089 to determine how the head-on orientation of a jet and dominant emission processes influence polarimetric variations in the broad lines and continuum. Observations were obtained biweekly from the Robert Stobie Spectrograph on the Southern African Large Telescope. Variability in the continuum polarization is detected for both PKS 0637–75 and PKS 1510–089, with a total average level of 2.5% ± 0.1% and 7.5% ± 0.1%, respectively. There is no clear polarization in the broad Balmer emission lines and weak polarization in Mg ii as the average level across all observations is 0.2% ± 0.1% for Hβ, 0.2% ± 0.3% for Hγ, and 0.6% ± 0.2% for Mg ii. We find that polarization measurements confirm the conclusions drawn from spectral energy distribution modeling of the disk–jet contributions to the emission as optical polarization and time variability for PKS 0637–75 are shown to be dominated by accretion disk emission while those of PKS 1510–089 are due to both disk and jet emission, with greater jet contribution during flaring states.

Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. Esaxerenone has antihypertensive and cardiorenal protective effects without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Medial superior olive in the rat: Anatomy, sources of input and axonal projections

Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential aspect of binaural hearing: the ability of animals to localize the sources of low-frequency sounds by detecting the interaural time difference (ITD), that is the difference in the time at which the sound arrives at each ear. In mammals, ITDs are mostly encoded in the medial superior olive (MSO), one of the main nuclei of the superior olivary complex (SOC). Because of their small heads and high frequency hearing range, rats and mice are often considered unable to use ITDs for sound localization. Moreover, their MSO is frequently viewed as too small or insignificant compared to that of mammals that use ITDs to localize sounds, including cats and gerbils. However, recent research has demonstrated remarkable similarities between most morphological and physiological features of mouse MSO neurons and those of MSO neurons of mammals that use ITDs. In this context, we have analyzed the structure and neural afferent and efferent connections of the rat MSO, which had never been studied by injecting neuroanatomical tracers into the nucleus.The rat MSO spans the SOC longitudinally. It is relatively small caudally, but grows rostrally into a well-developed column of stacked bipolar neurons. By placing small, precise injections of the bidirectional tracer biotinylated dextran amine (BDA) into the MSO, we show that this nucleus is innervated mainly by the most ventral and rostral spherical bushy cells of the anteroventral cochlear nucleus of both sides, and by the most ventrolateral principal neurons of the ipsilateral medial nucleus of the trapezoid body. The same experiments reveal that the MSO densely innervates the most dorsolateral region of the central nucleus of the inferior colliculus, the central region of the dorsal nucleus of the lateral lemniscus, and the most lateral region of the intermediate nucleus of the lateral lemniscus of its own side. Therefore, the MSO is selectively innervated by, and sends projections to, neurons that process low-frequency sounds. The structural and hodological features of the rat MSO are notably similar to those of the MSO of cats and gerbils. While these similarities raise the question of what functions other than ITD coding the MSO performs, they also suggest that the rat MSO is an appropriate model for future MSO-centered research.