scholarly journals Processing of visually evoked innate fear by a non-canonical thalamic pathway

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Pengfei Wei ◽  
Nan Liu ◽  
Zhijian Zhang ◽  
Xuemei Liu ◽  
Yongqiang Tang ◽  
...  
Keyword(s):  
Animal Species ◽  
Full Range ◽  
Visual Stimuli ◽  
Defensive Responses ◽  
Life Threatening ◽  
Lateral Posterior ◽  
Lateral Posterior Nucleus ◽  
Defensive Behaviours ◽  
Innate Fear

Abstract The ability of animals to respond to life-threatening stimuli is essential for survival. Although vision provides one of the major sensory inputs for detecting threats across animal species, the circuitry underlying defensive responses to visual stimuli remains poorly defined. Here, we investigate the circuitry underlying innate defensive behaviours elicited by predator-like visual stimuli in mice. Our results demonstrate that neurons in the superior colliculus (SC) are essential for a variety of acute and persistent defensive responses to overhead looming stimuli. Optogenetic mapping revealed that SC projections to the lateral posterior nucleus (LP) of the thalamus, a non-canonical polymodal sensory relay, are sufficient to mimic visually evoked fear responses. In vivo electrophysiology experiments identified a di-synaptic circuit from SC through LP to the lateral amygdale (Amg), and lesions of the Amg blocked the full range of visually evoked defensive responses. Our results reveal a novel collicular–thalamic–Amg circuit important for innate defensive responses to visual threats.

Mechanisms Underlying the Synchronizing Action of Corticothalamic Feedback Through Inhibition of Thalamic Relay Cells

1998 ◽  
Vol 79 (2) ◽  
pp. 999-1016 ◽  
Author(s):  
Alain Destexhe ◽  
Diego Contreras ◽  
Mircea Steriade
Keyword(s):  
Large Scale ◽  
Computational Models ◽  
Pyramidal Cells ◽  
Cellular Mechanism ◽  
Axonal Projections ◽  
Thalamic Relay ◽  
Lateral Posterior ◽  
Lateral Posterior Nucleus ◽  
Corticothalamic Feedback

Destexhe, Alain, Diego Contreras, and Mircea Steriade. Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells. J. Neurophysiol. 79: 999–1016, 1998. Early studies have shown that spindle oscillations are generated in the thalamus and are synchronized over wide cortical territories. More recent experiments have shown that this large-scale synchrony depends on the integrity of corticothalamic feedback. Previously proposed mechanisms emphasized exclusively intrathalamic mechanisms to generate the synchrony of these oscillations. In the present paper, we propose a cellular mechanism in which the synchrony is dependent of a mutual interaction between cortex and thalamus. This cellular mechanism is tested by computational models consisting of pyramidal cells, interneurons, thalamic reticular (RE) and thalamocortical (TC) relay cells, on the basis of voltage-clamp data on intrinsic currents and synaptic receptors present in the circuitry. The model suggests that corticothalamic feedback must operate on the thalamus mainly through excitation of GABAergic RE neurons, therefore recruiting relay cells essentially through inhibition and rebound. We provide experimental evidence for such dominant inhibition in the lateral posterior nucleus. In these conditions, the model shows that cortical discharges optimally evoked thalamic oscillations. This feature is essential to the present cellular mechanism and is also consistently observed experimentally. The model further shows that, with this type of corticothalamic feedback, cortical discharges recruited large areas of the thalamus because of the divergent cortex-to-RE and RE-to-TC axonal projections. Consequently, the thalamocortical network generated patterns of oscillations and synchrony similar to in vivo recordings. The model also emphasizes the important role of the modulation of the I h current by calcium in TC cells. This property conferred a relative refractoriness to the entire network, a feature also observed experimentally, as we show here. Further, the same property accounted for various spatiotemporal features of oscillations, such as systematic propagation after low-intensity cortical stimulation, local oscillations, and more generally, a high variability in the patterns of spontaneous oscillations, similar to in vivo recordings. We propose that the large-scale synchrony of spindle oscillations in vivo is the result of thalamocortical interactions in which the corticothalamic feedback acts predominantly through the RE nucleus. Several predictions are suggested to test the validity of this model.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases

2020 ◽  
Vol 20 ◽  
Author(s):  
Trinath Chowdhury ◽  
Gourisankar Roymahapatra ◽  
Santi M. Mandal
Keyword(s):  
Rna Polymerase ◽  
Viral Entry ◽  
In Silico ◽  
Rna Dependent Rna Polymerase ◽  
Replication Complex ◽  
In Silico Study ◽  
Life Threatening ◽  
In Vivo Analysis ◽  
3Cl Protease

Background: COVID-19 is a life threatening novel corona viral infection to our civilization and spreading rapidly. Terrific efforts are generous by the researchers to search for a drug to control SARS-CoV-2. Methods: Here, a series of arsenical derivatives were optimized and analyzed with in silico study to search the inhibitor of RNA dependent RNA polymerase (RdRp), the major replication factor of SARS-CoV-2. All the optimized derivatives were blindly docked with RdRp of SARS-CoV-2 using iGEMDOCK v2.1. Results: Based on the lower idock score in the catalytic pocket of RdRp, darinaparsin (-82.52 kcal/mol) revealed most effective among them. Darinaparsin strongly binds with both Nsp9 replicase protein (-8.77 kcal/mol) and Nsp15 endoribonuclease (-8.3 kcal/mol) of SARS-CoV-2 as confirmed from the AutoDock analysis. During infection, the ssRNA of SARS-CoV2 is translated into large polyproteins forming viral replication complex by specific proteases like 3CL protease and papain protease. This is also another target to control the virus infection where darinaparsin also perform the inhibitory role to proteases of 3CL protease (-7.69 kcal/mol) and papain protease (-8.43 kcal/mol). Conclusion: In host cell, the furin protease serves as a gateway to the viral entry and darinaparsin docked with furin protease which revealed a strong binding affinity. Thus, screening of potential arsenic drugs would help in providing the fast invitro to in-vivo analysis towards development of therapeutics against SARS-CoV-2.

scholarly journals Nanoscale Strontium-Substituted Hydroxyapatite Pastes and Gels for Bone Tissue Regeneration

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1611
Author(s):  
Caroline J. Harrison ◽  
Paul V. Hatton ◽  
Piergiorgio Gentile ◽  
Cheryl A. Miller
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Culture Media ◽  
Full Range ◽  
Sol Gel ◽  
Tissue Growth ◽  
Bone Tissue Regeneration ◽  
Tissue Culture Media ◽  
Bone Deposition

Injectable nanoscale hydroxyapatite (nHA) systems are highly promising biomaterials to address clinical needs in bone tissue regeneration, due to their excellent biocompatibility, bioinspired nature, and ability to be delivered in a minimally invasive manner. Bulk strontium-substituted hydroxyapatite (SrHA) is reported to encourage bone tissue growth by stimulating bone deposition and reducing bone resorption, but there are no detailed reports describing the preparation of a systematic substitution up to 100% at the nanoscale. The aim of this work was therefore to fabricate systematic series (0–100 atomic% Sr) of SrHA pastes and gels using two different rapid-mixing methodological approaches, wet precipitation and sol-gel. The full range of nanoscale SrHA materials were successfully prepared using both methods, with a measured substitution very close to the calculated amounts. As anticipated, the SrHA samples showed increased radiopacity, a beneficial property to aid in vivo or clinical monitoring of the material in situ over time. For indirect methods, the greatest cell viabilities were observed for the 100% substituted SrHA paste and gel, while direct viability results were most likely influenced by material disaggregation in the tissue culture media. It was concluded that nanoscale SrHAs were superior biomaterials for applications in bone surgery, due to increased radiopacity and improved biocompatibility.

scholarly journals Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value

2021 ◽  
Vol 9 (1) ◽  
pp. 16
Author(s):  
Renato Francesco Maria Scalise ◽  
Rosalba De Sarro ◽  
Alessandro Caracciolo ◽  
Rita Lauro ◽  
Francesco Squadrito ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathways ◽  
Ventricular Dysfunction ◽  
Healing Process ◽  
Molecular Signaling ◽  
Cellular Processes ◽  
Molecular Signaling Pathways ◽  
Fibrotic Scar ◽  
Life Threatening

The ischemic injury caused by myocardial infarction activates a complex healing process wherein a powerful inflammatory response and a reparative phase follow and balance each other. An intricate network of mediators finely orchestrate a large variety of cellular subtypes throughout molecular signaling pathways that determine the intensity and duration of each phase. At the end of this process, the necrotic tissue is replaced with a fibrotic scar whose quality strictly depends on the delicate balance resulting from the interaction between multiple actors involved in fibrogenesis. An inflammatory or reparative dysregulation, both in term of excess and deficiency, may cause ventricular dysfunction and life-threatening arrhythmias that heavily affect clinical outcome. This review discusses cellular process and molecular signaling pathways that determine fibrosis and the imaging technique that can characterize the clinical impact of this process in-vivo.

scholarly journals Current Status of Putative Animal Sources of SARS-CoV-2 Infection in Humans: Wildlife, Domestic Animals and Pets

2021 ◽  
Vol 9 (4) ◽  
pp. 868
Author(s):  
Max Maurin ◽  
Florence Fenollar ◽  
Oleg Mediannikov ◽  
Bernard Davoust ◽  
Christian Devaux ◽  
...  
Keyword(s):  
Animal Species ◽  
Biological Properties ◽  
Experimental Models ◽  
Current Data ◽  
The Body ◽  
Receptor Expression ◽  
Current Status ◽  
Susceptible Animal

SARS-CoV-2 is currently considered to have emerged from a bat coronavirus reservoir. However, the real natural cycle of this virus remains to be elucidated. Moreover, the COVID-19 pandemic has led to novel opportunities for SARS-CoV-2 transmission between humans and susceptible animal species. In silico and in vitro evaluation of the interactions between the SARS-CoV-2 spike protein and eucaryotic angiotensin-converting enzyme 2 (ACE2) receptor have tentatively predicted susceptibility to SARS-CoV-2 infection of several animal species. Although useful, these data do not always correlate with in vivo data obtained in experimental models or during natural infections. Other host biological properties may intervene such as the body temperature, level of receptor expression, co-receptor, restriction factors, and genetic background. The spread of SARS-CoV-2 also depends on the extent and duration of viral shedding in the infected host as well as population density and behaviour (group living and grooming). Overall, current data indicate that the most at-risk interactions between humans and animals for COVID-19 infection are those involving certain mustelids (such as minks and ferrets), rodents (such as hamsters), lagomorphs (especially rabbits), and felines (including cats). Therefore, special attention should be paid to the risk of SARS-CoV-2 infection associated with pets.

Protein Phosphatase 2A Activation via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome

2021 ◽  
Author(s):  
Haiyan Chu ◽  
Anastasia Sacharidou ◽  
An Nguyen ◽  
Chun Li ◽  
Ken L Chambliss ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Protein Phosphatase ◽  
In Vivo Studies ◽  
Hypertensive Disorder ◽  
Fetal Demise ◽  
Maternal Hypertension ◽  
Life Threatening ◽  
Phosphatase 2A ◽  
And Migration

Rationale: Preeclampsia (PE) is a potentially life-threatening, placenta-based hypertensive disorder during pregnancy, and the antiphospholipid syndrome (APS) frequently leads to PE. APS pregnancies are also complicated by fetal demise and intrauterine growth restriction (IUGR). Objective: Here we determined how the circulating antiphospholipid antibodies (aPL) characteristic of APS alter placental trophoblast function to cause PE and also endanger the fetus. Methods and Results: Experiments were performed in mice, in cultured human trophoblasts, and in human placenta samples. Effects of aPL and IgG from healthy subjects were compared. Based on prior findings in culture, in vivo studies were done in mice deficient in apolipoprotein E receptor 2 (ApoER2) in trophoblasts. Endpoints in tissues and cells were determined by enzymatic assay, Q-PCR, ELISA or immunoblotting. Whereas in wild-type mice aPL caused maternal hypertension and proteinuria, fetal demise and IUGR, mice lacking trophoblast ApoER2 were protected. In culture aPL attenuated trophoblast proliferation and migration via an ApoER2-related protein complex comprised of the protein phosphatase PP2A, Dab2, and JIP4. Via trophoblast ApoER2 in mice and in culture, aPL stimulated PP2A activity, leading to MMP14 and HIF1alpha upregulation and increased soluble endoglin (sEng) production. HIF1alpha and sEng upregulation was related to PP2A desphosphorylation of PHD2. In mice PP2A inhibition prevented aPL-induced maternal hypertension and proteinuria, and fetal demise and IUGR. Placentas from APS patients displayed PP2A hyperactivation, PHD2 dephosphorylation and HIF1α upregulation, and these findings were generalizable to placentas of women with PE from causes other from APS. Conclusions: In APS pregnancies trophoblasts are the critical cell target of aPL, and via ApoER2-dependent PP2A activation, aPL cause PE through MMP14 upregulation and PHD2 dephosphorylation leading to HIF1 and sEng upregulation. Moreover, parallel processes may be operative in PE in non-APS patients. Interventions targeting PP2A may provide novel means to combat APS-related PE and PE unrelated to APS.

In vivo imaging with high-speed full-range complex spectral domain optical coherence tomography

2005 ◽  
Author(s):  
Erich Goetzinger ◽  
Michael Pircher ◽  
Rainer A. Leitgeb ◽  
Adolf F. Fercher ◽  
Christoph K. Hitzenberger
Keyword(s):  
Optical Coherence Tomography ◽  
In Vivo Imaging ◽  
High Speed ◽  
Full Range ◽  
Spectral Domain ◽  
Optical Coherence

scholarly journals Two Populations of Glucocorticoid Receptor-Binding Sites in the Male Rat Hippocampal Genome

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1832-1844 ◽  
Author(s):  
J. Annelies E. Polman ◽  
E. Ronald de Kloet ◽  
Nicole A. Datson
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Glucocorticoid Receptors ◽  
Full Range ◽  
Male Rat ◽  
Motif Analysis ◽  
Wide Range ◽  
Neuronal Processes ◽  
Almost All

Abstract In the present study, genomic binding sites of glucocorticoid receptors (GR) were identified in vivo in the rat hippocampus applying chromatin immunoprecipitation followed by next-generation sequencing. We identified 2470 significant GR-binding sites (GBS) and were able to confirm GR binding to a random selection of these GBS covering a wide range of P values. Analysis of the genomic distribution of the significant GBS revealed a high prevalence of intragenic GBS. Gene ontology clusters involved in neuronal plasticity and other essential neuronal processes were overrepresented among the genes harboring a GBS or located in the vicinity of a GBS. Male adrenalectomized rats were challenged with increasing doses of the GR agonist corticosterone (CORT) ranging from 3 to 3000 μg/kg, resulting in clear differences in the GR-binding profile to individual GBS. Two groups of GBS could be distinguished: a low-CORT group that displayed GR binding across the full range of CORT concentrations, and a second high-CORT group that displayed significant GR binding only after administering the highest concentration of CORT. All validated GBS, in both the low-CORT and high-CORT groups, displayed mineralocorticoid receptor binding, which remained relatively constant from 30 μg/kg CORT upward. Motif analysis revealed that almost all GBS contained a glucocorticoid response element resembling the consensus motif in literature. In addition, motifs corresponding with new potential GR-interacting proteins were identified, such as zinc finger and BTB domain containing 3 (Zbtb3) and CUP (CG11181 gene product from transcript CG11181-RB), which may be involved in GR-dependent transactivation and transrepression, respectively. In conclusion, our results highlight the existence of 2 populations of GBS in the rat hippocampal genome.

scholarly journals Pushing behavior and hemiparesis: which is critical for functional recovery in pusher patients ? Case report

2007 ◽  
Vol 65 (2b) ◽  
pp. 536-539 ◽  
Author(s):  
Taiza E.G. Santos-Pontelli ◽  
Octávio M. Pontes-Neto ◽  
José Fernando Colafêmina ◽  
Dráulio B. de Araújo ◽  
Antônio Carlos Santos ◽  
...  
Keyword(s):  
Case Report ◽  
Barthel Index ◽  
Functional Improvement ◽  
Chronic Hypertension ◽  
Acute Hemorrhage ◽  
Lateral Posterior ◽  
History Of ◽  
Lateral Posterior Nucleus ◽  
Neuroimaging Study ◽  
The Right

We report a sequential neuroimaging study in a 48-years-old man with a history of chronic hypertension and lacunar strokes involving the ventral lateral posterior nucleus of the thalamus. The patient developed mild hemiparesis and severe contraversive pushing behavior after an acute hemorrhage affecting the right thalamus. Following standard motor physiotherapy, the pusher behavior completely resolved 3 months after the onset and, at that time, he had a Barthel Index of 85, although mild left hemiparesis was still present. This case report illustrates that pushing behavior itself may be severely incapacitating, may occur with only mild hemiparesis and affected patients may have dramatic functional improvement (Barthel Index 0 to 85) after resolution pushing behavior without recovery of hemiparesis.

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