Main Nucleus Research Articles

THE DORSAL LATERAL GENICULATE NUCLEUS: ANATOMY, HISTOLOGY, ONTOGENESIS

Review is devoted to the structure and function of the main visual thalamic nucleus – dorsal part of the lateral geniculate nucleus, and its formation during prenatal and postnatal ontogenesis. The structure and ontogeny of the related structures (retinal ganglion cells and visual cortex, and their projections) are also reviewed. Particular attention is paid to the morphological and functional differences between X, Y, and W parallel channels, and to the development of different layers of the dorsal the lateral geniculate nucleus.

The locus coeruleus input to the rostral ventromedial medulla mediates stress-induced colorectal visceral pain

Unlike physiological stress, which carries survival value, pathological stress is widespread in modern society and acts as a main risk factor for visceral pain. As the main stress-responsive nucleus in the brain, the locus coeruleus (LC) has been previously shown to drive pain alleviation through direct descending projections to the spinal cord, but whether and how the LC mediates pathological stress-induced visceral pain remains unclear. Here, we identified a direct circuit projection from LC noradrenergic neurons to the rostral ventromedial medulla (RVM), an integral relay of the central descending pain modulation system. Furthermore, the chemogenetic activation of the LC-RVM circuit was found to significantly induce colorectal visceral hyperalgesia and anxiety-related psychiatric disorders in naïve mice. In a dextran sulfate sodium (DSS)-induced visceral pain model, the mice also presented colorectal visceral hypersensitivity and anxiety-related psychiatric disorders, which were associated with increased activity of the LC-RVM circuit; LC-RVM circuit inhibition markedly alleviated these symptoms. Furthermore, the chronic restraint stress (CRS) model precipitates anxiety-related psychiatric disorders and induces colorectal visceral hyperalgesia, which is referred to as pathological stress-induced hyperalgesia, and inhibiting the LC-RVM circuit attenuates the severity of colorectal visceral pain. Overall, the present study clearly demonstrated that the LC-RVM circuit could be critical for the comorbidity of colorectal visceral pain and stress-related psychiatric disorders. Both visceral inflammation and psychological stress can activate LC noradrenergic neurons, which promote the severity of colorectal visceral hyperalgesia through this LC-RVM circuit.

The Central Noradrenergic System in Neurodevelopmental Disorders: Merging Experimental and Clinical Evidence.

The aim of this article is to highlight the potential role of the locus-coeruleus-noradrenergic (LC-NA) system in neurodevelopmental disorders (NdDs). The LC is the main brain noradrenergic nucleus, key in the regulation of arousal, attention, and stress response, and its early maturation and sensitivity to perinatal damage make it an interesting target for translational research. Clinical data shows the involvement of the LC-NA system in several NdDs, suggesting a pathogenetic role in the development of such disorders. In this context, a new neuroimaging tool, LC Magnetic Resonance Imaging (MRI), has been developed to visualize the LC in vivo and assess its integrity, which could be a valuable tool for exploring morphological alterations in NdD in vivo in humans. New animal models may be used to test the contribution of the LC-NA system to the pathogenic pathways of NdD and to evaluate the efficacy of NA-targeting drugs. In this narrative review, we provide an overview of how the LC-NA system may represent a common pathophysiological and pathogenic mechanism in NdD and a reliable target for symptomatic and disease-modifying drugs. Further research is needed to fully understand the interplay between the LC-NA system and NdD.

Synthesis, Characterization and Biological Evaluation of 6-(5-Chloro-8-Hydroxynapthalene-2-yl)-4(4-Hydroxyphenyl)-4-5-Dihydroxypyrimidin-2(1h)-One

1-(4- Chloro -1-hydroxynaphthalen-2-yl)-ethanone was prepared by refluxing 4-chloronaphthalen-1-ol with glacial acetic acid in presence of fused ZnCl2. From this synthesized compound we prepared 1-(4- Chloro -1- hydroxynaphthalen-2-yl)-3-(4-hydroxy phenyl)-prop-2-en-1-one from condensing 1-(4- Chloro -1-hydroxynaphthalen-2- yl)-ethenone, The final product 6-(5-chloro-8-hydroxynapthalene-2-yl)-4(4-hydroxyphenyl)-4-5-dihydroxypyrimidin-2(1h)-one, by condensation in presence of urea and concentrated HCl in DMF. The compounds thus synthesized have been characterized by physical and spectral data. This titled synthesized compound was screened for antimicrobial study and are found to possess excellent antimicrobial activities due to presence of chlorine as a substituent on main nucleus.

Fate of micronuclei and micronucleated cells after treatment of HeLa cells with different genotoxic agents

Although micronuclei are well-known biomarkers of genotoxic damage, the biological consequences of micronucleus induction are only poorly understood. To further elucidate these consequences, HeLa cells stably expressing histone 2B coupled with green fluorescent protein were used for long-term live cell imaging to investigate the fate of micronuclei and micronucleated cells after treatment of cells with various genotoxic agents (doxorubicin (20, 30 and nM), tert-butyl hydroperoxide (tBHP, 50, 100 and 150 µM), radiation (0.5, 1 and 2 Gy), methyl methanesulfonate (MMS, 20, 25 and 30 µg/ml) and vinblastine (1, 2 and 3 nM)). Most micronuclei persist for multiple cell cycles or reincorporate while micronucleated cells were more prone to cell death, senescence and fatal mitotic errors compared to non-micronucleated cells, which is consistent with previous studies using etoposide. No clear substance-related effects on the fate of micronuclei and micronucleated cells were observed. To further investigate the fate of micronuclei, extrusion of micronuclei was studied with treatments reported as inducing the extrusion of micronuclei. Since extrusion was not observed in HeLa cells, the relevance of extrusion of micronuclei remains unclear. In addition, degradation of micronuclei was analysed via immunostaining of γH2AX, which demonstrated a high level of DNA damage in micronuclei compared to the main nuclei. Furthermore, transduction with two reporter genes (LC3B-dsRed and LaminB1-dsRed) was conducted followed by long-term live cell imaging. While autophagy marker LC3B was not associated with micronuclei, Lamin B1 was found in approximately 50% of all micronuclei. While degradation of micronuclei was not observed to be a frequent fate of micronuclei, the results show impaired stability of DNA and micronuclear envelope indicating rupture of micronuclei as a pre-step to chromothripsis.

Functional connectivity of basal nucleus of Meynert, locus coeruleus and ventral tegmental area in MCI and mild dementia in Alzheimer’s disease

AbstractBackgroundCholinergic, noradrenergic and dopaminergic dysfunction plays an important role in Alzheimer’s disease (AD). Basal nucleus of Meynert (BNM), locus coeruleus (LC) and ventral tegmental area (VTA) are its main producer nuclei, respectively. Neuropathological studies have shown that structural changes are present in these areas from the beginning of the disease. As such, we aim to identify changes in the functional connectivity (FC) from these nuclei in patients with mild cognitive impairment (MCI) and dementia (DA) in AD, compared with healthy controls (HCs).MethodWe analyzed data from 43 subjects with altered beta‐amyloide in the cerebrospinal fluid (23 MCI; 20 mild to moderate dementia) and 16 controls. Participants underwent rs‐fMRI and neuropsychological evaluation. FC maps to the whole brain were generated (UF²C‐toolbox) using the BNM, LC and the VTA as seeds separately. The second level analysis was performed with an ANCOVA test including the individual FC maps, transformed to z‐score (Fischer R‐Z transformation) generated with each seed and group and regressing for age and years of education using SPM12‐toolbox. The significance level was defined as p<0.001 at the voxel level and p<0.05 FDR corrected at the cluster‐level. In addition, only anatomical regions with more than 60 voxels were described.ResultRegarding BNM, compared to HCs, patients with MCI showed significantly decreased FC in the left precentral gyrus and left anterior insula (volume 62.05 and 61.59 voxels, respectively, Figure 1). Similarly, DA patients, when compared to HCs, showed significantly decreased FC in the left and right medial precentral gyrus (volume 104.06 and 82.75 voxels, respectively) and in the right supramarginal gyrus (volume 64.68 voxels, Figure 2). Regarding VTA, unexpectedly, we found that, compared with MCIs, DA patients showed increased FC in the left central operculum (volume 92.29 voxels, Figure 3). There were no other between‐group changes that reached statistical significance for right and LC and VTA.ConclusionAD patients present changes in the NBM‐FC to the precentral gyrus, insula and supramarginal gyrus. These findings may embase new research for cholinergic dysfunction and possible biomarkers.

Functional connectivity of basal nucleus of Meynert, locus coeruleus and ventral tegmental area in MCI and mild dementia in Alzheimer’s disease

AbstractBackgroundCholinergic, noradrenergic and dopaminergic dysfunction plays an important role in Alzheimer’s disease (AD). Basal nucleus of Meynert (BNM), locus coeruleus (LC) and ventral tegmental area (VTA) are its main producer nuclei, respectively. Neuropathological studies have shown that structural changes are present in these areas from the beginning of the disease. As such, we aim to identify changes in the functional connectivity (FC) from these nuclei in patients with mild cognitive impairment (MCI) and dementia (DA) in AD, compared with healthy controls (HCs).MethodWe analyzed data from 43 subjects with altered beta‐amyloide in the cerebrospinal fluid (23 MCI; 20 mild to moderate dementia) and 16 controls. Participants underwent rs‐fMRI and neuropsychological evaluation. FC maps to the whole brain were generated (UF²C‐toolbox) using the BNM, LC and the VTA as seeds separately. The second level analysis was performed with an ANCOVA test including the individual FC maps, transformed to z‐score (Fischer R‐Z transformation) generated with each seed and group and regressing for age and years of education using SPM12‐toolbox. The significance level was defined as p<0.001 at the voxel level and p<0.05 FDR corrected at the cluster‐level. In addition, only anatomical regions with more than 60 voxels were described.ResultRegarding BNM, compared to HCs, patients with MCI showed significantly decreased FC in the left precentral gyrus and left anterior insula (volume 62.05 and 61.59 voxels, respectively, Figure 1). Similarly, DA patients, when compared to HCs, showed significantly decreased FC in the left and right medial precentral gyrus (volume 104.06 and 82.75 voxels, respectively) and in the right supramarginal gyrus (volume 64.68 voxels, Figure 2). Regarding VTA, unexpectedly, we found that, compared with MCIs, DA patients showed increased FC in the left central operculum (volume 92.29 voxels, Figure 3). There were no other between‐group changes that reached statistical significance for right and LC and VTA.ConclusionAD patients present changes in the NBM‐FC to the precentral gyrus, insula and supramarginal gyrus. These findings may embase new research for cholinergic dysfunction and possible biomarkers.

The multifaceted role of micronuclei in tumour progression: A whole organism perspective.

Within most tumour types, cancerous cells exist in a state of aneuploidy, an incorrect chromosome number or structure. Additionally, tumour cells frequently exhibit chromosomal instability; the ongoing loss or gain of whole or parts of chromosomes during cell division. Chromosomal instability results in a high rate of chromosome segregation defects, and a constantly changing genomic landscape. A second consequence of recurrent chromosome segregation defects is the exclusion of mis-segregated chromatin from the newly reforming nucleus. Chromosomes, or chromosome fragments that are not incorporated into the main nucleus are often packaged into extranuclear structures called micronuclei. While the initial impact of micronucleus formation is an imbalance or loss of genetic material in the resulting daughter cells, several other downstream consequences are now known to result from this process. In this review, we discuss the further consequences of micronucleus formation, including how structural changes to the micronuclear envelope, and the rupturing of micronuclear membranes can contribute to metastasis, immune cell activation and overall, tumour progression.

Autopallidotomy: From Colloquial Term to Scientific Theory

Levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD), occurs in ∼30% of patients after five years' treatment with levodopa. In atypical parkinsonism, LID occurs less frequently than in PD. Lower frequency of LID in atypical parkinsonism has traditionally been attributed to lower amounts of levodopa used by these patients; however, recent studies have shown lower frequency of LID in atypical parkinsonism compared with PD when adjusting for levodopa dose. The mechanism of LID is complex but requires pulsatile levodopa stimulation, progressive presynaptic dopaminergic degeneration, and a relatively intact postsynaptic dopaminergic system. The globus pallidus internus (GPi), the main inhibitory nucleus of the basal ganglia, may play a major role in the development and treatment of LID. Surgical lesioning of the posteroventral GPi is directly antidyskinetic; animal models showing GPi-associated striatal neurons are directly responsible for the development of LID. However, other cortical areas, particularly the primary sensory and motor cortices may also play a role in LID. In some cases of atypical parkinsonism, particularly progressive supranuclear palsy and corticobasal degeneration, severe degeneration of the GPi, a so-called "autopallidotomy," may explain the absence of LID in these patients. In other atypical parkinsonisms, such as PD dementia and dementia with Lewy bodies, the lower incidence of LID may partly be attributed to more striatal degeneration but likely also relates to the degeneration of the motor cortex and resultant network dysfunction. Overall, atypical parkinsonism serves as a natural model that may ultimately reveal more effective therapies for LID.

Synthesis, Molecular Docking and Molecular Dynamics Simulation Studies of Some Pyridazinone Derivatives as Lipase Inhibitors

Human health and illness are dependent on lipases, which play a key role in maintaining cell integrity, storing fat for energy and serving as signaling molecules. In this study, 4 compounds that carry 6-phenylpyridazin-3(2H)-one main nucleus, which can be effective as lipase inhibitors, were synthesized and their structures were elucidated. The biological activity of synthesized compounds was evaluated via the porcine pancreatic lipase type II (PLL) inhibitor assay. Orlistat, a lipase inhibitor, was used as a positive control. Compound 8d was found to be the most effective compound, with an IC50 value of 32.66±2.8265 (μg/mL). In addition, molecular docking and molecular dynamics simulations studies were carried out to examine the interactions of the compounds with the target in detail. The results obtained as a result of these in silico studies were found to be compatible with the lipase inhibition effects of the compounds. It was observed that the compounds may have potential lipase inhibitory effects as a result of the substitutions of the 3-(6-oxo-3-phenylpyridazin-1(6H)-yl)propanehydrazide structure.

Micronuclei from misaligned chromosomes that satisfy the spindle assembly checkpoint in cancer cells

SummaryChromosome alignment to the spindle equator is a hallmark of mitosis thought to promote chromosome segregation fidelity in metazoans. Yet chromosome alignment is only indirectly supervised by the spindle assembly checkpoint (SAC) as a byproduct of chromosome bi-orientation, and the consequences of defective chromosome alignment remain unclear. Here, we investigated how human cells respond to chromosome alignment defects of distinct molecular nature by following the fate of live HeLa cells after RNAi-mediated depletion of 125 proteins previously implicated in chromosome alignment. We confirmed chromosome alignment defects upon depletion of 108/125 proteins. Surprisingly, in all confirmed cases, depleted cells frequently entered anaphase after a delay with misaligned chromosomes. Using depletion of prototype proteins resulting in defective chromosome alignment, we show that misaligned chromosomes often satisfy the SAC and directly missegregate without lagging behind in anaphase. In-depth analysis of specific molecular perturbations that prevent proper kinetochore-microtubule attachments revealed that misaligned chromosomes that missegregate frequently result in micronuclei. Higher-resolution live-cell imaging indicated that, contrary to most anaphase lagging chromosomes that correct and reintegrate the main nuclei, misaligned chromosomes are a strong predictor of micronuclei formation in a cancer cell model of chromosomal instability, but not in non-transformed near-diploid cells. We provide evidence supporting that intrinsic differences in kinetochore-microtubule attachment stability on misaligned chromosomes account for this distinct outcome. Thus, misaligned chromosomes that satisfy the SAC may represent a previously overlooked mechanism driving chromosomal/genomic instability during cancer cell division, and we unveil genetic conditions predisposing for these events.

Conselhos econômicos e sociais. Uma revisão da literatura com foco em sua eficácia e avaliação

Abstract Despite its widespread trajectory and global presence, studies on Economic and Social Councils (ESCs) are not frequent. Thus, this study aims to review the existing scientific literature on this institution to identify the main thematic nuclei, agreements, and discrepancies, and detect research gaps and outline future research lines. Based on the application of the PRISMA Protocol, three emerging thematic nuclei on ESCs have been detected: the factors that explain their creation; the factors that influence their effectiveness (and condition their success), and the criteria used to evaluate their effectiveness (related to these institutions’ success or failure). In short, this is the first qualitative synthesis of the international literature on ESCs, focusing on their effectiveness and evaluation. It offers elements for future intervention and studies on these institutions, especially those newly created.

Subthalamic Nucleus Modulation of the Pontine Nuclei and Its Targeting of the Cerebellar Cortex.

The subthalamic nucleus (STN) has been implicated in motor and nonmotor tasks, and is an effective target of deep brain stimulation for the treatment of Parkinson's disease, likely in part because of the STN's projections outside of the basal ganglia to other brain regions. While there is some evidence of a disynaptic connection between the STN and the cerebellum via the pontine nuclei (PN), how the STN modulates the activity of the neurons in the PN remains unknown. Here we addressed this question using a combination of anatomical tracings, optogenetics, and in vivo electrophysiology in both wild-type (WT) and transgenic mice of both sexes. Approximately half of recorded neurons in the PN, which were located primarily in the medial area, responded with short latency to both single pulses and trains of optogenetic stimulation of channelrhodopsin (ChR2)-expressing STN axons in awake, head-restrained mice. Furthermore, the increase in the activity of PN neurons correlated with the strength of activation of STN axons, suggesting that the STN projections to the PN could, in principle, encode information in a graded manner. In addition, transsynaptic retrograde tracing confirmed that the STN sends disynaptic projections to the cerebellar cortex. These results suggest that the STN sends robust functional projections to the PN, which then propagate to the cerebellum, and have important implications for understanding motor control of normal conditions, and Parkinsonian symptoms, where this pathway may have a role in the therapeutic efficacy of STN deep brain stimulation.SIGNIFICANCE STATEMENT The primary excitatory nucleus in the basal ganglia, the subthalamic nucleus, is known to play a role in pathways modulating movement. The pontine nuclei are the main precerebellar nuclei, which transmit signals through their axonal projections to the cerebellum as mossy fibers. The pathway we have functionally characterized in this paper represents an additional cortex-independent pathway capable of relaying information between the basal ganglia and cerebellum. The effectiveness of subthalamic nucleus deep brain stimulation in Parkinson's disease suggests that this pathway could be explored as an avenue of investigation for therapeutic purposes.

A rapid and fully automated in vitro micronucleus assay using imaging flow cytometry and convolutional neural network analysis

Abstract Micronuclei (MN) originate from whole chromosomes or chromosome fragments that lag behind during cell division and fail to be incorporated into one of the two main nuclei. As a result, scoring MN using the well-established in vitro micronucleus assay evaluates the ability of chemicals or other agents to induce DNA damage. This technique is typically performed by manual microscopy, which can be time-consuming and prone to variability. Additionally, automated methods lack cytoplasmic visualization when using slide-scanning microscopy, and conventional flow cytometry doesn’t provide visual confirmation of MN. The ImageStream®X Mk II (ISX) imaging flow cytometer combines the high-resolution imagery of microscopy with conventional flow cytometry’s speed and statistical robustness in a single system. Previously, we developed a rapid and automated MN assay based on high-throughput image capture and feature-based image analysis using IDEAS® Software. However, the feature-based analysis was not readily applicable to multiple cell lines and chemicals, so we developed a deep learning method based on convolutional neural networks to score imaging flow cytometry data in both the cytokinesis-blocked and unblocked versions of the MN assay using Amnis® AI Software. Our current study validates our previously established assay and analyses using three different chemicals (Mitomycin C, Cyclophosphamide, and Eugenol) and three different cell lines (TK6, L5178Y, CHO-K1). Here, we demonstrate how using Amnis AI to score imagery acquired on the ISX provides a rapid and fully automated in vitro MN assay with improved accuracy, reproducibility, and time-to-results in toxicity and biodosimetry applications across multiple cell lines.

Hypothalamic Nesfatin-1 Resistance May Underlie the Development of Type 2 Diabetes Mellitus in Maternally Undernourished Non-obese Rats.

Intrauterine growth retardation (IUGR) poses a high risk for developing late-onset, non-obese type 2 diabetes (T2DM). The exact mechanism underlying this phenomenon is unknown, although the contribution of the central nervous system is recognized. The main hypothalamic nuclei involved in the homeostatic regulation express nesfatin-1, an anorexigenic neuropeptide and identified regulator of blood glucose level. Using intrauterine protein restricted rat model (PR) of IUGR, we investigated, whether IUGR alters the function of nesfatin-1. We show that PR rats develop fat preference and impaired glucose homeostasis by adulthood, while the body composition and caloric intake of normal nourished (NN) and PR rats are similar. Plasma nesfatin-1 levels are unaffected by IUGR in both neonates and adults, but pro-nesfatin-1 mRNA expression is upregulated in the hypothalamus of adult PR animals. We find that centrally injected nesfatin-1 inhibits the fasting induced neuronal activation in the hypothalamic arcuate nucleus in adult NN rats. This effect of nesfatin-1 is not seen in PR rats. The anorexigenic effect of centrally injected nesfatin-1 is also reduced in adult PR rats. Moreover, chronic central nesfatin-1 administration improves the glucose tolerance and insulin sensitivity in NN rats but not in PR animals. Birth dating of nesfatin-1 cells by bromodeoxyuridine (BrDU) reveals that formation of nesfatin-1 cells in the hypothalamus of PR rats is disturbed. Our results suggest that adult PR rats acquire hypothalamic nesfatin-1-resistance, probably due to the altered development of the hypothalamic nesfatin-1 cells. Hypothalamic nesfatin-1-resistance, in turn, may contribute to the development of non-obese type T2DM.

Locus Coeruleus magnetic resonance imaging: a comparison between native-space and template-space approach

Locus Coeruleus (LC) is the main noradrenergic nucleus of the brain, which is involved in many physiological functions including cognition; its impairment may be crucial in the neurobiology of a variety of brain diseases. Locus Coeruleus-Magnetic Resonance Imaging (LC-MRI) allows to identify in vivo LC in humans. Thus, a variety of research teams have been using LC-MRI to estimate LC integrity in normal aging and in patients affected by neurodegenerative disorders, where LC integrity my work as a biomarker. A number of variations between LC-MRI studies exist, concerning post-acquisition analysis and whether this had been performed within MRI native space or in ad hoc-built MRI template space. Moreover, the reproducibility and reliability of this tool is still to be explored. Therefore, in the present study, we analyzed a group of neurologically healthy, cognitively intact elderly subjects, using both a native space- and a template space-based LC-MRI analysis. We found a good inter-method agreement, particularly considering the LC Contrast Ratio. The template space-based approach provided a higher spatial resolution, lower operator-dependency, and allowed the analysis of LC topography. Our ad hoc-developed LC template showed LC morphological data that were in line with templates published very recently. Remarkably, present data significantly overlapped with a recently published LC “metaMask”, that had been obtained by averaging the results of a variety of previous LC-MRI studies. Thus, such a template space-based approach may pave the way to a standardized LC-MRI analysis and to be used in future clinic–anatomical correlations.

Functional connectivity of intercalated nucleus with medial amygdala: A circuit relevant for chemosignal processing.

Medial amygdala processes social/reproductive chemosensory input, and its projections to preoptic and hypothalamic areas evoke appropriate behavioral and physiological responses. We and others have shown that different chemosensory signals elicit differential responses in medial amygdala subregions and in adjacent main intercalated nucleus (mICN). The largely GABAergic mICN receives no direct chemosensory input but, as we show, mICN has functional circuit connections with medial amygdala that could be responsible both for mICN chemosensitivity and for a feedforward inhibitory effect on posterior medial amygdala; which, in turn would affect chemosignal response. mICN is subject to inhibition by dopamine and is probably regulated by neuropeptides and input from frontal cortex. Thus, mICN is in position to modify chemosensory processing in medial amygdala and behavioral responses to social signals, according to internal brain state. Patch-clamp recordings from neurons in each relevant nucleus in horizontal brain-slices, with electrical stimulation in adjacent nuclei, reveal multiple functional connections between medial amygdala subregions and mICN. We highlight a triangular circuit which may underlie mICN chemosensitivity and its potential for modifying chemosensory information transmitted to basal forebrain. Anterior medial amygdala, which receives most of the chemosensory input, connects to posterior medial amygdala directly and both areas send information on to basal forebrain. Anterior medial amygdala can also modulate posterior medial amygdala indirectly via the mICN side-loop, which also provides a pathway for modulation by cortical input or, when inhibited by dopamine, could allow a more automatic response – as proposed for other amygdala circuits with similar ICN side loops.

First direct dynamical detection of a dual supermassive black hole system at sub-kiloparsec separation

We investigated whether the two recently discovered nuclei in NGC 7727 both host a super-massive black hole (SMBH). We used the high spatial resolution mode of the integral-field spectrograph MUSE on the VLT in adaptive optics mode to resolve the stellar kinematics within the sphere of influence of both putative black holes. We combined the kinematic data with an HST-based mass model and used Jeans models to measure their SMBH mass. We report the discovery of a dual SMBH system in NGC 7727. We detect a SMBH in the photometric center of the galaxy in Nucleus 1, with a mass of MSMBH = 1.54−0.15+0.18 × 108 M⊙. In the second nucleus, which is 500 pc offset from the main nucleus, we also find a clear signal for a SMBH with a mass of MBH = 6.33−1.40+3.32 × 106 M⊙. Both SMBHs are detected at high significance. The off-axis nature of Nucleus 2 makes modeling the system challenging; however, a number of robustness tests suggest that a black hole is required to explain the observed kinematics. The SMBH in the offset Nucleus 2 makes up 3.0% of its total mass, which means its SMBH is over-massive compared to the MBH − MBulge scaling relation. This confirms it as the surviving nuclear star cluster of a galaxy that has merged with NGC 7727. This discovery is the first dynamically confirmed dual SMBH system with a projected separation of less than a kiloparsec and the nearest dynamically confirmed dual SMBH at a distance of 27.4 Mpc. The second Nucleus is in an advanced state of inspiral, and it will eventually result in a 1:24 mass ratio SMBH merger. Optical emission lines suggest Nucleus 2 is a Seyfert galaxy, making it a low-luminosity Active Galactic Nuclei. There are likely many more quiescent SMBHs as well as dual SMBH pairs in the local Universe that have been missed by surveys that focus on bright accretion signatures.

Nuclear Fragility in Radiation-Induced Senescence: Blebs and Tubes Visualized by 3D Electron Microscopy.

Irreparable DNA damage following ionizing radiation (IR) triggers prolonged DNA damage response and induces premature senescence. Cellular senescence is a permanent state of cell-cycle arrest characterized by chromatin restructuring, altered nuclear morphology and acquisition of secretory phenotype, which contributes to senescence-related inflammation. However, the mechanistic connections for radiation-induced DNA damage that trigger these senescence-associated hallmarks are poorly understood. In our in vitro model of radiation-induced senescence, mass spectrometry-based proteomics was combined with high-resolution imaging techniques to investigate the interrelations between altered chromatin compaction, nuclear envelope destabilization and nucleo-cytoplasmic chromatin blebbing. Our findings confirm the general pathophysiology of the senescence-response, with disruption of nuclear lamin organization leading to extensive chromatin restructuring and destabilization of the nuclear membrane with release of chromatin fragments into the cytosol, thereby activating cGAS-STING-dependent interferon signaling. By serial block-face scanning electron microscopy (SBF-SEM) whole-cell datasets were acquired to investigate the morphological organization of senescent fibroblasts. High-resolution 3-dimensional (3D) reconstruction of the complex nuclear shape allows us to precisely visualize the segregation of nuclear blebs from the main nucleus and their fusion with lysosomes. By multi-view 3D electron microscopy, we identified nanotubular channels formed in lamin-perturbed nuclei of senescent fibroblasts; the potential role of these nucleo-cytoplasmic nanotubes for expulsion of damaged chromatin has to be examined.

Improvement of drought tolerance in rice using line X tester mating design and biochemical molecular markers

BackgroundWater stress, specifically the limited water resources needed to grow strategic crops, especially rice, poses a great threat to crop productivity. So, it was imperative that scientists all work together to try genetically improving the rice for drought tolerance in light of these environmental challenges. The aim of this study is trying to know the genetic behavior responsible for water-deficit tolerance in rice genotypes but at the molecular level. Moreover, this attempt will be an important leap in the process of genetic improvement in rice for water stress tolerance in Egypt.ResultsTwenty-three rice genotypes including eight parents and their fifteen F1 crosses or (the first hybrid generation) by line X tester analysis were evaluated for water stress tolerance during two experiments (the control and drought experiment) besides some molecular–biochemical studies for eight parents and the highest selected five crosses for water stress tolerance. The research revealed that five rice crosses out of fifteen hybrids were highly tolerant to water stress compared to the normal conditions. Data of biochemical markers indicated the presence of bands that are considered as molecular genetic markers for water-deficit tolerance in some rice genotypes, and this is the scientific progress achieved in this research. This was evident by increasing the density and concentration of SDS-protein electrophoresis besides enhancing the activities of peroxidase (POD) and polyphenol oxidase (PPO) under water-deficit conditions, which confirmed the tolerance of drought stress in the eight rice genotypes and the best five crosses from the first hybrid generation.ConclusionThe five promising and superior rice hybrids showed an unparalleled tolerance to water stress in all evaluated traits under water stress treatment compared to the standard experiment. Also, biochemical and molecular parameters evidence confirmed the existence of unquestionable evidence that it represents the main nucleus for producing rice lines tolerated for drought stress under Egyptian conditions.