scholarly journals Spaced training enhances memory and prefrontal ensemble stability in mice

2020 ◽  
Author(s):  
Annet Glas ◽  
Mark Hübener ◽  
Tobias Bonhoeffer ◽  
Pieter M. Goltstein
Keyword(s):  
Spacing Effect ◽  
Memory Task ◽  
Memory Storage ◽  
Population Activity ◽  
Neuronal Ensembles ◽  
Trial Spacing ◽  
Spaced Learning ◽  
Place Task ◽  
The Stability

SummaryMemory is substantially improved when learning is distributed over time, an effect called “spacing effect”. So far it has not been studied how spaced learning affects neuronal ensembles presumably underlying memory. In the present study, we investigate whether trial spacing increases the stability or size of neuronal ensembles. Mice were trained in the “everyday memory” task, an appetitive, naturalistic, delayed matching-to-place task. Spacing trials by 60 minutes produced more robust memories than training with shorter or longer intervals. c-Fos labeling and chemogenetic inactivation established the necessity of the dorsomedial prefrontal cortex (dmPFC) for successful memory storage. In vivo calcium imaging of excitatory dmPFC neurons revealed that longer trial spacing increased the similarity of the population activity pattern on subsequent encoding trials and upon retrieval. Conversely, trial spacing did not affect the size of the total neuronal ensemble or the size of subpopulations dedicated to specific task-related behaviors and events. Thus, spaced learning promotes reactivation of prefrontal neuronal ensembles processing episodic-like memories.

Formation and Structure of Casein Micelles in Lactating Mammary Tissue

1970 ◽  
Vol 28 ◽  
pp. 150-151
Author(s):  
Robert J. Carroll ◽  
Marvin P. Thompson ◽  
Harold M. Farrell
Keyword(s):  
Size Distribution ◽  
G Protein ◽  
Milk Proteins ◽  
Mammary Tissue ◽  
Colloidal System ◽  
Casein Micelles ◽  
The Stability

Milk is an unusually stable colloidal system; the stability of this system is due primarily to the formation of micelles by the major milk proteins, the caseins. Numerous models for the structure of casein micelles have been proposed; these models have been formulated on the basis of in vitro studies. Synthetic casein micelles (i.e., those formed by mixing the purified αsl- and k-caseins with Ca2+ in appropriate ratios) are dissimilar to those from freshly-drawn milks in (i) size distribution, (ii) ratio of Ca/P, and (iii) solvation (g. water/g. protein). Evidently, in vivo organization of the caseins into the micellar form occurs in-a manner which is not identical to the in vitro mode of formation.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

Applicability of Instability Index for In vitro Protein Stability Prediction

2019 ◽  
Vol 26 (5) ◽  
pp. 339-347 ◽  
Author(s):  
Dilani G. Gamage ◽  
Ajith Gunaratne ◽  
Gopal R. Periyannan ◽  
Timothy G. Russell
Keyword(s):  
Protein Stability ◽  
Caulobacter Crescentus ◽  
Effect Of Temperature ◽  
Instability Index ◽  
Dipeptide Composition ◽  
Experimental Conditions ◽  
The Stability ◽  
Vitro Protein

Background: The dipeptide composition-based Instability Index (II) is one of the protein primary structure-dependent methods available for in vivo protein stability predictions. As per this method, proteins with II value below 40 are stable proteins. Intracellular protein stability principles guided the original development of the II method. However, the use of the II method for in vitro protein stability predictions raises questions about the validity of applying the II method under experimental conditions that are different from the in vivo setting. Objective: The aim of this study is to experimentally test the validity of the use of II as an in vitro protein stability predictor. Methods: A representative protein CCM (CCM - Caulobacter crescentus metalloprotein) that rapidly degrades under in vitro conditions was used to probe the dipeptide sequence-dependent degradation properties of CCM by generating CCM mutants to represent stable and unstable II values. A comparative degradation analysis was carried out under in vitro conditions using wildtype CCM, CCM mutants and two other candidate proteins: metallo-β-lactamase L1 and α -S1- casein representing stable, borderline stable/unstable, and unstable proteins as per the II predictions. The effect of temperature and a protein stabilizing agent on CCM degradation was also tested. Results: Data support the dipeptide composition-dependent protein stability/instability in wt-CCM and mutants as predicted by the II method under in vitro conditions. However, the II failed to accurately represent the stability of other tested proteins. Data indicate the influence of protein environmental factors on the autoproteolysis of proteins. Conclusion: Broader application of the II method for the prediction of protein stability under in vitro conditions is questionable as the stability of the protein may be dependent not only on the intrinsic nature of the protein but also on the conditions of the protein milieu.

scholarly journals Stability and ocular biodistribution of topically administered PLGA nanoparticles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sean Swetledge ◽  
Renee Carter ◽  
Rhett Stout ◽  
Carlos E. Astete ◽  
Jangwook P. Jung ◽  
...  
Keyword(s):  
Uv Light ◽  
Light Exposure ◽  
Polymeric Nanoparticles ◽  
Plga Nanoparticles ◽  
Eye Disease ◽  
Control Group ◽  
Eye Tissues ◽  
Nanoparticle Morphology ◽  
The Stability

AbstractPolymeric nanoparticles have been investigated as potential delivery systems for therapeutic compounds to address many ailments including eye disease. The stability and spatiotemporal distribution of polymeric nanoparticles in the eye are important regarding the practical applicability and efficacy of the delivery system in treating eye disease. We selected poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with lutein, a carotenoid antioxidant associated with eye health, as our model ophthalmic nanodelivery system and evaluated its stability when suspended in various conditions involving temperature and light exposure. We also assessed the ocular biodistribution of the fluorescently labeled nanoparticle vehicle when administered topically. Lutein-loaded nanoparticles were stable in suspension when stored at 4 °C with only 26% lutein release and no significant lutein decay or changes in nanoparticle morphology. When stored at 25 °C and 37 °C, these NPs showed signs of bulk degradation, had significant lutein decay compared to 4 °C, and released over 40% lutein after 5 weeks in suspension. Lutein-loaded nanoparticles were also more resistant to photodegradation compared to free lutein when exposed to ultraviolet (UV) light, decaying approximately 5 times slower. When applied topically in vivo, Cy5-labled nanoparticles showed high uptake in exterior eye tissues including the cornea, episcleral tissue, and sclera. The choroid was the only inner eye tissue that was significantly higher than the control group. Decreased fluorescence in all exterior eye tissues and the choroid at 1 h compared to 30 min indicated rapid elimination of nanoparticles from the eye.

scholarly journals Effect of food processing on the antioxidant activity of flavones from Polygonatum odoratum (Mill.) Druce

2021 ◽  
Vol 16 (1) ◽  
pp. 92-101
Author(s):  
Guanghui Xia ◽  
Xinhua Li ◽  
Zhen Zhang ◽  
Yuhang Jiang
Keyword(s):  
Antioxidant Activity ◽  
High Pressure ◽  
Food Processing ◽  
Yeast Fermentation ◽  
Pressure Treatment ◽  
Processing Methods ◽  
High Pressure Treatment ◽  
Effect Of Food ◽  
The Stability

Abstract Polygonatum odoratum (Mill.) Druce (POD) is a natural plant widely used for food and medicine, thanks to its rich content of a strong antioxidant agent called homoisoflavones. However, food processing methods could affect the stability of POD flavones, resulting in changes to their antioxidant activity. This study attempts to evaluate the antioxidant activity of POD flavones subject to different processing methods and determines which method could preserve the antioxidant activity of POD flavones. Therefore, flavones were extracted from POD samples, which had been treated separately with one of the four processing methods: extrusion, baking, high-pressure treatment, and yeast fermentation. After that, the antioxidant activity of the flavones was subject to in vivo tests in zebrafish embryos. The results show that yeast fermentation had the least disruption to the antioxidant activity of POD flavones, making it the most suitable food processing method for POD. By contrast, extrusion and high-pressure treatment both slightly weakened the antioxidant activity of the flavones and should be avoided in food processing. The research results provide a reference for the development and utilization of POD and the protection of its biological activity.

scholarly journals Clinical Application and Efficacy of Silver Drug in Ophthalmology: A Literature Review and New Formulation of EYE Drops with Drug Silver (I) Complex of Metronidazole with Improved Dosage Form

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 210
Author(s):  
Arleta Waszczykowska ◽  
Dominik Żyro ◽  
Justyn Ochocki ◽  
Piotr Jurowski
Keyword(s):  
Dosage Form ◽  
Complex Analysis ◽  
Bacterial Resistance ◽  
Eye Drops ◽  
Ophthalmic Diseases ◽  
The Stability ◽  
New Formulation ◽  
Additional Therapy ◽  
Antibacterial Potential

The use of silver preparations in medicine is becoming increasingly popular. The basic aim of this evaluation was to review the literature on the clinical (in vivo) and antibacterial potential of silver preparations in ophthalmic diseases. The second goal was to summarize the results of experimental research on the use of silver preparations in ophthalmology. The third objective was to present a method for stabilizing eye drops containing silver (I) complex. Analysis of the pH stability of the silver (I) complex with metronidazole in the prepared dosage form (eye drops) was carried out. Most silver preparations are clinically used for topical application. Few experimental results indicate the usefulness of intraocular or systemic administration of silver (I) preparations as an alternative or additional therapy in infectious and angiogenic eye diseases. The development of a new formulation increases the stability of the dosage form. New forms of silver (I) products will certainly find application in the treatment of many ophthalmic diseases. One of the most important features of the silver (I) complex is its capacity to break down bacterial resistance. The new eye drops formula can significantly improve comfort of use. Due to their chemical nature, silver (I) compounds are difficult to stabilize, especially in the finished dosage form.

scholarly journals Effect of Mixing Ratio of Oppositely Charged Block Copolymers on Polyion Complex Micelles for In Vivo Application

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 5
Author(s):  
Noriko Nakamura ◽  
Yuki Mochida ◽  
Kazuko Toh ◽  
Shigeto Fukushima ◽  
Horacio Cabral ◽  
...  
Keyword(s):  
Physicochemical Characteristics ◽  
Charge Ratio ◽  
Structural Variations ◽  
Polyion Complex ◽  
Functional Capabilities ◽  
The Stability ◽  
Biological Performance ◽  
Complex Micelles ◽  
Oppositely Charged

Self-assembled supramolecular structures based on polyion complex (PIC) formation between oppositely charged polymers are attracting much attention for developing drug delivery systems able to endure harsh in vivo environments. As controlling polymer complexation provides an opportunity for engineering the assemblies, an improved understanding of the PIC formation will allow constructing assemblies with enhanced structural and functional capabilities. Here, we focused on the influence of the mixing charge ratio between block aniomers and catiomers on the physicochemical characteristics and in vivo biological performance of the resulting PIC micelles (PIC/m). Our results showed that by changing the mixing charge ratio, the structural state of the core was altered despite the sizes of PIC/m remaining almost the same. These structural variations greatly affected the stability of the PIC/m in the bloodstream after intravenous injection and determined their biodistribution.

scholarly journals DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbα

2013 ◽  
Vol 451 (3) ◽  
pp. 453-461 ◽  
Author(s):  
Claudia C. S. Chini ◽  
Carlos Escande ◽  
Veronica Nin ◽  
Eduardo N. Chini
Keyword(s):  
Breast Cancer ◽  
Nuclear Receptor ◽  
Clock Genes ◽  
Mrna Levels ◽  
Protein Levels ◽  
The Stability ◽  
And Function ◽  
Interfering Rna ◽  
In Cells

The nuclear receptor Rev-erbα has been implicated as a major regulator of the circadian clock and integrates circadian rhythm and metabolism. Rev-erbα controls circadian oscillations of several clock genes and Rev-erbα protein degradation is important for maintenance of the circadian oscillations and also for adipocyte differentiation. Elucidating the mechanisms that regulate Rev-erbα stability is essential for our understanding of these processes. In the present paper, we report that the protein DBC1 (Deleted in Breast Cancer 1) is a novel regulator of Rev-erbα. Rev-erbα and DBC1 interact in cells and in vivo, and DBC1 modulates the Rev-erbα repressor function. Depletion of DBC1 by siRNA (small interfering RNA) in cells or in DBC1-KO (knockout) mice produced a marked decrease in Rev-erbα protein levels, but not in mRNA levels. In contrast, DBC1 overexpression significantly enhanced Rev-erbα protein stability by preventing its ubiquitination and degradation. The regulation of Rev-erbα protein levels and function by DBC1 depends on both the N-terminal and C-terminal domains of DBC1. More importantly, in cells depleted of DBC1, there was a dramatic decrease in circadian oscillations of both Rev-erbα and BMAL1. In summary, our data identify DBC1 as an important regulator of the circadian receptor Rev-erbα and proposes that Rev-erbα could be involved in mediating some of the physiological effects of DBC1.

Phenotype–genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p–Pex6p interaction

2001 ◽  
Vol 357 (2) ◽  
pp. 417-426 ◽  
Author(s):  
Shigehiko TAMURA ◽  
Naomi MATSUMOTO ◽  
Atsushi IMAMURA ◽  
Nobuyuki SHIMOZAWA ◽  
Yasuyuki SUZUKI ◽  
...  
Keyword(s):  
Zellweger Syndrome ◽  
Complementation Group ◽  
Temperature Sensitive ◽  
Permissive Temperature ◽  
Peroxisome Biogenesis ◽  
Causative Gene ◽  
Aaa Atpase ◽  
Peroxisome Biogenesis Disorders ◽  
The Stability

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS), neonatal adrenoleucodystrophy (NALD) and infantile Refsum disease (IRD), are fatal autosomal recessive diseases caused by impaired peroxisome biogenesis, of which 12 genotypes have been reported. ZS patients manifest the severest clinical and biochemical abnormalities, whereas those with NALD and IRD show less severity and the mildest features respectively. We have reported previously that temperature-sensitive peroxisome assembly is responsible for the mildness of the clinical features of IRD. PEX1 is the causative gene for PBDs of complementation group E (CG-E, CG1 in the U.S.A. and Europe), the PBDs of highest incidence, encoding the peroxin Pex1p of the AAA ATPase family. It has been also reported that Pex1p and Pex6p interact with each other. In the present study we investigated phenotype–genotype relationships of CG1 PBDs. Pex1p from IRD such as Pex1p with the most frequently identified mutation at G843D was largely degraded in vivo at 37°C, whereas a normal level of Pex1p was detectable at the permissive temperature. In contrast, PEX1 proteins derived from ZS patients, including proteins with a mutation at L664P or the deletion of residues 634–690, were stably present at both temperatures. Pex1p-G843D interacted with Pex6p at approx. 50% of the level of normal Pex1p, whereas Pex1p from ZS patients mostly showing non-temperature-sensitive peroxisome biogenesis hardly bound to Pex6p. Taking these results together, we consider it most likely that the stability of Pex1p reflects temperature-sensitive peroxisome assembly in IRD fibroblasts. Failure in Pex1p–Pex6p interaction gives rise to more severe abnormalities, such as those manifested by patients with ZS.

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