scholarly journals Novel Approaches for Detection Fluorescent-Labeled by Cellvizio Lab System on Hippocampal CA1 Region

2019 ◽  
Vol 8 (1) ◽  
pp. 1-6
Author(s):  
Asma Ulhusna Shaimi ◽  
Wan Raihana Wan Aasim ◽  
Hasmah Abdullah ◽  
Tan Soo Choon ◽  
Ang Chee Wei ◽  
...  
Keyword(s):  
De Novo ◽  
Future Research ◽  
Sprague Dawley ◽  
Fluorescence Labelling ◽  
Alexa Fluor ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Novel Approach ◽  
Fluorescence Level ◽  
Cholesterol Precursor

Neurosteroids have been identified in the 1981. Dehydroepiandrosterone sulphate (DHEAS) is one of the vital neurosteroids that de novo synthesized in the nervous system from cholesterol precursor (Baulieu & Robel, 1998). The aim of the study is to develop a method for fluorescence labelling. Alexa Fluor 488 dye with DHEAS antibody can binds the DHEAS antibody in the rat brain monitored by Cellvizio Lab System. DHEAS antibody (IgG isotype antibodies) was fluorescently conjugated by an amine-reactive compound, Alexa Fluor 5-SDP ester 488 dye. The resultant Alexa Fluor 488-conjugated antibodies were collected and analyzed by UV-Vis spectrophotometer instrument. The absorbance of the protein-dye conjugate at 280 nm and 494 nm were measured. Then, the degree of labeling (DOL) was calculated to achieve the desired results. Fluorescence labelling were carried out into the CA1 region of hippocampus Sprague-Dawley rat. We reported that the conjugation was successful. Optimal labeling depending on degree of labeling (DOL) needs some necessity to achieve and effective binding to the target neurosteroid, DHEAS. Cellvizio Lab system connected with Fiber Fluorescence Microscopy (FFM) probe is presented as a new approach in real-time imaging of DHEAS. In conclusion, we have developed a new method of DHEAS-Alexa Fluor fluorescence labelling to visualize and evaluate the changes of DHEAS fluorescence level in the rat hippocampus. This novel approach as a diagnostic tool and can be used to better understand the mechanisms and functions of DHEAS and other neurosteroids in future research.

scholarly journals Dexmedetomidine Improved One-lung Ventilation-induced Cognitive Dysfunction in Rats

2021 ◽  
Author(s):  
Mengyun LI ◽  
Zhe JIN ◽  
Jia ZHAN ◽  
Yanlin WANG ◽  
Kai CHEN
Keyword(s):  
Cognitive Function ◽  
Memory Function ◽  
Lung Ventilation ◽  
Sprague Dawley ◽  
One Lung Ventilation ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Synaptic Structure ◽  
Transmission Electron ◽  
Hippocampal Ca1

Abstract Background: One-lung ventilation (OLV) is widely used in thoracic surgery. However, OLV may also increase CERO2 and aggravate delayed cognitive recovery. Here, we aimed to investigate the effect of dexmedetomidine (DEX) on cognitive function in rats undergoing OLV. Methods: Sprague-Dawley rats were randomly divided into two-lung ventilation (TLV) group, OLV group and OLV treated with DEX group. Group DEX received 25 μg/kg DEX i.p. 30 min before induction. After mechanical ventilation (MV), Morris water maze (MWM) test was carried out to examine spatial memory function. Western blotting was used to detect pERK1/2, pCREB, Bcl-2 and BAX in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the hippocampal CA1 region. Results: Post-MV, compared with group OLV, group DEX showed increases in percentage of target quadrant time (P<0.05), platform crossings (P<0.05), a reduction in CERO2 (P<0.05), and pERK1/2, pCREB, and Bcl-2 significantly increased (P<0.01 or P<0.05), while BAX significantly decreased (P<0.01), besides, a less damaged synaptic structure was observed in group DEX. Conclusions: DEX improved post-MV cognitive function in rats undergoing OLV, reduced cerebral oxygen consumption, protected synaptic structure and upregulated ERK1/2-CREB anti-apoptotic signaling pathway in hippocampal CA1 region.

scholarly journals Dissociating encoding of memory and salience by manipulating long-term synaptic potentiation

2022 ◽  
Author(s):  
Konstantin Kaganovsky ◽  
Mark H Plitt ◽  
Renzhi Yang ◽  
Richard Sando ◽  
Lisa M Giocomo ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Physiological Effect ◽  
Cognitive Representations ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Novel Approach ◽  
Term Potentiation

Neural codes are thought to be reorganized during memory formation by long-term potentiation (LTP) of synapses. Here, using a novel approach for selectively blocking LTP, we found that eliminating LTP in hippocampal or striatal circuits only produces limited effects on learning and memory. To reconcile the discrepancy between the large physiological effect of blocking LTP and the absent effect on learning, we studied how LTP impacts neuronal computations in the hippocampus using in-vivo Ca2+-imaging. Contrary to current conceptual frameworks, we found that hippocampal CA1-region LTP is not required for accurate representations of space in hippocampal neurons, but rather endows these neurons with reward- and novelty-coding properties. Thus, instead of driving formation of cognitive maps and memory engrams, CA1-region LTP incorporates salience information into cognitive representations.

A Plug-and-Play Approach for the De Novo Generation of Dually Functionalised Bispecifics

2019 ◽  
Author(s):  
Antoine Maruani ◽  
Peter A. Szijj ◽  
Calise Bahou ◽  
João C. F. Nogueira ◽  
Stephen Caddick ◽  
...  
Keyword(s):  
De Novo ◽  
Therapeutic Index ◽  
Antibody Fragments ◽  
Bispecific Antibodies ◽  
Full Potential ◽  
Mechanisms Of Resistance ◽  
Large Excess ◽  
Chemical Methods ◽  
New Class ◽  
Novel Approach

<p>Diseases are multifactorial, with redundancies and synergies between various pathways. However, most of the antibody-based therapeutics in clinical trials and on the market interact with only one target thus limiting their efficacy. The targeting of multiple epitopes could improve the therapeutic index of treatment and counteract mechanisms of resistance. To this effect, a new class of therapeutics emerged: bispecific antibodies.</p><p>Bispecific formation using chemical methods is rare and low yielding and/or requires a large excess of one of the two proteins to avoid homodimerisation. In order for chemically prepared bispecifics to deliver their full potential, high-yielding, modular and reliable cross-linking technologies are required. Herein, we describe a novel approach not only for the rapid and high-yielding chemical generation of bispecific antibodies from native antibody fragments, but also for the site-specific dual functionalisation of the resulting bioconjugates. Based on orthogonal clickable functional groups, this strategy enables the assembly of functionalised bispecifics with controlled loading in a modular and convergent manner.</p>

scholarly journals Dissecting the chromosome-level genome of the Asian Clam (Corbicula fluminea)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tongqing Zhang ◽  
Jiawen Yin ◽  
Shengkai Tang ◽  
Daming Li ◽  
Xiankun Gu ◽  
...  
Keyword(s):  
De Novo ◽  
Corbicula Fluminea ◽  
Gene Families ◽  
Ruditapes Philippinarum ◽  
Genomic Sequences ◽  
Future Research ◽  
Asian Clam ◽  
Sequencing Technologies ◽  
East And Southeast Asia ◽  
Clam Corbicula

AbstractThe Asian Clam (Corbicula fluminea) is a valuable commercial and medicinal bivalve, which is widely distributed in East and Southeast Asia. As a natural nutrient source, the clam is rich in protein, amino acids, and microelements. The genome of C. fluminea has not yet been characterized; therefore, genome-assisted breeding and improvements cannot yet be implemented. In this work, we present a de novo chromosome-scale genome assembly of C. fluminea using PacBio and Hi-C sequencing technologies. The assembled genome comprised 4728 contigs, with a contig N50 of 521.06 Kb, and 1,215 scaffolds with a scaffold N50 of 70.62 Mb. More than 1.51 Gb (99.17%) of genomic sequences were anchored to 18 chromosomes, of which 1.40 Gb (92.81%) of genomic sequences were ordered and oriented. The genome contains 38,841 coding genes, 32,591 (83.91%) of which were annotated in at least one functional database. Compared with related species, C. fluminea had 851 expanded gene families and 191 contracted gene families. The phylogenetic tree showed that C. fluminea diverged from Ruditapes philippinarum, ~ 228.89 million years ago (Mya), and the genomes of C. fluminea and R. philippinarum shared 244 syntenic blocks. Additionally, we identified 2 MITF members and 99 NLRP members in C. fluminea genome. The high-quality and chromosomal Asian Clam genome will be a valuable resource for a range of development and breeding studies of C. fluminea in future research.

scholarly journals Orexin receptor antagonists reverse aberrant dopamine neuron activity and related behaviors in a rodent model of stress-induced psychosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hannah B. Elam ◽  
Stephanie M. Perez ◽  
Jennifer J. Donegan ◽  
Daniel J. Lodge
Keyword(s):  
United States ◽  
Sensorimotor Gating ◽  
The United States ◽  
Dopamine Neuron ◽  
Neuron Activity ◽  
Sprague Dawley ◽  
Post Traumatic Stress ◽  
Neuron Population ◽  
Population Activity ◽  
Novel Approach

AbstractPost-traumatic stress disorder (PTSD) is a prevalent condition affecting approximately 8% of the United States population and 20% of United States combat veterans. In addition to core symptoms of the disorder, up to 64% of individuals diagnosed with PTSD experience comorbid psychosis. Previous research has demonstrated a positive correlation between symptoms of psychosis and increases in dopamine transmission. We have recently demonstrated projections from the paraventricular nucleus of the thalamus (PVT) to the nucleus accumbens (NAc) can regulate dopamine neuron activity in the ventral tegmental area (VTA). Specifically, inactivation of the PVT leads to a reversal of aberrant dopamine system function and psychosis-like behavior. The PVT receives dense innervation from orexin containing neurons, therefore, targeting orexin receptors may be a novel approach to restore dopamine neuron activity and alleviate PTSD-associated psychosis. In this study, we induced stress-related pathophysiology in male Sprague Dawley rats using an inescapable foot-shock procedure. We observed a significant increase in VTA dopamine neuron population activity, deficits in sensorimotor gating, and hyperresponsivity to psychomotor stimulants. Administration of selective orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) antagonists (SB334867 and EMPA, respectively) or the FDA-approved, dual-orexin receptor antagonist, Suvorexant, were found to reverse stress-induced increases in dopamine neuron population activity. However, only Suvorexant and SB334867 were able to reverse deficits in behavioral corelates of psychosis. These results suggest that the orexin system may be a novel pharmacological target for the treatment of comorbid psychosis related to PTSD.

scholarly journals Cohort profile of Acutelines: a large data/biobank of acute and emergency medicine

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e047349
Author(s):  
Ewoud ter Avest ◽  
Barbara C van Munster ◽  
Raymond J van Wijk ◽  
Sanne Tent ◽  
Sanne Ter Horst ◽  
...  
Keyword(s):  
Acute Care ◽  
De Novo ◽  
Medical Center ◽  
Large Data ◽  
Future Research ◽  
Imaging Data ◽  
Novel Studies ◽  
Long Term Follow Up ◽  
Registration Number

PurposeResearch in acute care faces many challenges, including enrolment challenges, legal limitations in data sharing, limited funding and lack of singular ownership of the domain of acute care. To overcome these challenges, the Center of Acute Care of the University Medical Center Groningen in the Netherlands, has established a de novo data, image and biobank named ‘Acutelines’.ParticipantsClinical data, imaging data and biomaterials (ie, blood, urine, faeces, hair) are collected from patients presenting to the emergency department (ED) with a broad range of acute disease presentations. A deferred consent procedure (by proxy) is in place to allow collecting data and biomaterials prior to obtaining written consent. The digital infrastructure used ensures automated capturing of all bed-side monitoring data (ie, vital parameters, electrophysiological waveforms) and securely importing data from other sources, such as the electronic health records of the hospital, ambulance and general practitioner, municipal registration and pharmacy. Data are collected from all included participants during the first 72 hours of their hospitalisation, while follow-up data are collected at 3 months, 1 year, 2 years and 5 years after their ED visit.Findings to dateEnrolment of the first participant occurred on 1 September 2020. During the first month, 653 participants were screened for eligibility, of which 180 were approached as potential participants. In total, 151 (84%) provided consent for participation of which 89 participants fulfilled criteria for collection of biomaterials.Future plansThe main aim of Acutelines is to facilitate research in acute medicine by providing the framework for novel studies and issuing data, images and biomaterials for future research. The protocol will be extended by connecting with central registries to obtain long-term follow-up data, for which we already request permission from the participant.Trial registration numberNCT04615065.

scholarly journals High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raul Loera-Valencia ◽  
Erika Vazquez-Juarez ◽  
Alberto Muñoz ◽  
Gorka Gerenu ◽  
Marta Gómez-Galán ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Cholesterol Homeostasis ◽  
Stratum Radiatum ◽  
Actin Binding ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Term Potentiation

AbstractAlterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine long-term potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schaffer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a significantly higher density of synaptopodin-positive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fine-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.

scholarly journals Analysis of High-Friction Surface Texture with Respect to Friction and Wear

Coatings ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 758
Author(s):  
Cibi Pranav ◽  
Minh-Tan Do ◽  
Yi-Chang Tsai
Keyword(s):  
Friction Coefficient ◽  
Surface Texture ◽  
Safety Concern ◽  
Future Research ◽  
Scanning System ◽  
Novel Approach ◽  
Texture Parameters ◽  
Aggregate Loss ◽  
Friction Surfaces ◽  
The Impact

High Friction Surfaces (HFS) are applied to increase friction capacity on critical roadway sections, such as horizontal curves. HFS friction deterioration on these sections is a safety concern. This study deals with characterization of the aggregate loss, one of the main failure mechanisms of HFS, using texture parameters to study its relationship with friction. Tests are conducted on selected HFS spots with different aggregate loss severity levels at the National Center for Asphalt Technology (NCAT) Test Track. Friction tests are performed using a Dynamic Friction Tester (DFT). The surface texture is measured by means of a high-resolution 3D pavement scanning system (0.025 mm vertical resolution). Texture data are processed and analyzed by means of the MountainsMap software. The correlations between the DFT friction coefficient and the texture parameters confirm the impact of change in aggregates’ characteristics (including height, shape, and material volume) on friction. A novel approach to detect the HFS friction coefficient transition based on aggregate loss, inspired by previous works on the tribology of coatings, is proposed. Using the proposed approach, preliminary outcomes show it is possible to observe the rapid friction coefficient transition, similar to observations at NCAT. Perspectives for future research are presented and discussed.

scholarly journals A New Model Averaging Approach in Predicting Credit Risk Default

Risks ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 114
Author(s):  
Paritosh Navinchandra Jha ◽  
Marco Cucculelli
Keyword(s):  
Machine Learning ◽  
Credit Risk ◽  
Model Averaging ◽  
Research Direction ◽  
Future Research ◽  
Classification Problems ◽  
Average Technique ◽  
Model Average ◽  
Novel Approach ◽  
Unbalanced Dataset

The paper introduces a novel approach to ensemble modeling as a weighted model average technique. The proposed idea is prudent, simple to understand, and easy to implement compared to the Bayesian and frequentist approach. The paper provides both theoretical and empirical contributions for assessing credit risk (probability of default) effectively in a new way by creating an ensemble model as a weighted linear combination of machine learning models. The idea can be generalized to any classification problems in other domains where ensemble-type modeling is a subject of interest and is not limited to an unbalanced dataset or credit risk assessment. The results suggest a better forecasting performance compared to the single best well-known machine learning of parametric, non-parametric, and other ensemble models. The scope of our approach can be extended to any further improvement in estimating weights differently that may be beneficial to enhance the performance of the model average as a future research direction.

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