scholarly journals Can Low-Level Exposure to Radiofrequency Fields Effect Cognitive Behaviour in Laboratory Animals? A Systematic Review of the Literature Related to Spatial Learning and Place Memory

2019 ◽  
Vol 16 (9) ◽  
pp. 1607 ◽  
Author(s):  
Zenon Sienkiewicz ◽  
Eric van Rongen
Keyword(s):  
Molecular Mechanisms ◽  
A Priori ◽  
Laboratory Animals ◽  
Experimental Protocol ◽  
Mobile Phone Technology ◽  
Low Level ◽  
Place Memory ◽  
Cognitive Behaviour ◽  
Independent Replication ◽  
Testing Protocols

This review considers whether exposure to low-level radiofrequency (RF) fields, mostly associated with mobile phone technology, can influence cognitive behaviour of laboratory animals. Studies were nominated for inclusion using an a priori defined protocol with preselected criteria, and studies were excluded from analysis if they did not include sufficient details about the exposure, dosimetry or experimental protocol, or if they lacked a sham-exposed group. Overall, 62 studies were identified that have investigated the effects of RF fields on spatial memory and place learning and have been published since 1993. Of these, 17 studies were excluded, 20 studies reported no significant field-related effects, 21 studies reported significant impairments or deficits, and four studies reported beneficial consequences. The data do not suggest whether these outcomes are related to specific differences in exposure or testing conditions, or simply represent chance. However, some studies have suggested possible molecular mechanisms for the observed effects, but none of these has been substantiated through independent replication. Further behavioural studies could prove useful to resolve this situation, and it is suggested that these studies should use a consistent animal model with standardized exposure and testing protocols, and with detailed dosimetry provided by heterogeneous, anatomically-realistic animal models.

scholarly journals Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food

2021 ◽  
Vol 18 (7) ◽  
pp. 3332
Author(s):  
Olga V. Naidenko ◽  
David Q. Andrews ◽  
Alexis M. Temkin ◽  
Tasha Stoiber ◽  
Uloma Igara Uche ◽  
...  
Keyword(s):  
Immune System ◽  
High Throughput ◽  
Environmental Protection Agency ◽  
High Throughput Screening ◽  
Molecular Mechanisms ◽  
Specific Activity ◽  
Laboratory Animals ◽  
In Vitro Assays ◽  
Toxicological Studies

The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

Memory impairment induced by amphetamine derivatives in laboratory animals and in humans: a review

2012 ◽  
Vol 3 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Jordi Camarasa ◽  
Teresa Rodrigo ◽  
David Pubill ◽  
Elena Escubedo
Keyword(s):  
Illicit Drugs ◽  
Molecular Mechanisms ◽  
Memory Performance ◽  
Laboratory Animals ◽  
Club Drugs ◽  
Synthetic Drugs ◽  
History Of ◽  
Amphetamine Derivatives ◽  
Considerable Body

AbstractThe 20th century brought with it the so-called club drugs (the most notorious being amphetamine derivatives), which are used by young adults at all-night dance parties. Methamphet­amine and 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) are synthetic drugs with stimulant and psychoactive properties that belong to the amphetamine family. Here, we have reviewed the literature about the cognitive impairment induced by these two amphetamine derivatives and the preclinical and clinical outcomes. Although there is controversial evidence about the effect of methamphetamine and MDMA on learning and memory in laboratory animals, results from published papers demonstrate that amphetamines cause long-term impairment of cognitive functions. A large number of pharmacological receptors have been studied and screened as targets of amphetamine-induced cognitive dysfunction, and extensive research efforts have been invested to provide evidence about the molecular mechanisms behind these cognitive deficits. In humans, there is a considerable body of evidence indicating that methamphetamine and MDMA seriously disrupt memory and learning processes. Although an association between the impairments of memory performance and a history of recreational amphetamine ingestion has also been corroborated, a number of methodological difficulties continue to hamper research in this field, the most important being the concomitant use of other illicit drugs.

scholarly journals An Associational Examination of the CaptialCube Effect Context for the MPV over the Linguistic Partitions: Testing Sensitivity & Specificity

2017 ◽  
Vol 6 (2) ◽  
pp. 1
Author(s):  
Edward J. Lusk ◽  
Michael Halperin
Keyword(s):  
A Priori ◽  
Market Performance ◽  
Random Processes ◽  
Random Selection ◽  
Testing Model ◽  
Performance Variables ◽  
Market Effects ◽  
Median Split ◽  
Sensitivity Specificity ◽  
Testing Protocols

In this third examination of the CapitalCubeÔ Market Navigation Platform [CCMNP] we have selected the previously vetted set of embedded variables: Market Performance Variables [MPV] for their Linguistic Qualifiers [LQ] considering their directional market effects or MPV[LQ[{Neutral: Unfavorable: Favorable}]]. In the testing, we are interested in the Sensitivity and the Specificity of these vetted variables over the annual S&P500 Panel from 2005 to 2013. The inference framework employed a Median Split: High or Low for each of the 13 MPV tested and a random selection to avoid the FPE-jeopardy that is part of the Chi2 testing model. We used the Tamhane & Dunlop cut-off to identify Chi2 cells effects of interest and used these to develop the Sensitivity and the Specificity tests. Results: We were able to reject the a priori Nulls proffered for the testing protocols indicating that one may reject the supposition that the labeling of the LQ is formed by random processes in the CCMNP.     

Investigation of the Stem Cells Used in Modeling Human Placental Trophoblast

2021 ◽  
Author(s):  
Lulu Ji ◽  
Lin Wang
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Cell Types ◽  
Model Systems ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
Placental Development ◽  
Induced Pluripotent

Human placenta is vital for fetal development, and act as an interface between the fetus and the expecting mother. Abnormal placentati on underpins various pregnancy complications such as miscarriage, pre-eclampsia and intrauterine growth restriction. Despite the important role of placenta, the molecular mechanisms governing placental formation and trophoblast cell lineage specification is poorly understand. It is mostly due to the lack of appropriate model system. The great various in placental types across mammals make it limit for the use of laboratory animals in studying human placental development. However, over the past few years, alternative methods have been employed, including human embryonic stem cells, induced pluripotent stem cells, human trophoblast stem cell, and 3-dimensional organoids. Herein, we summarize the present knowledge about human development, differentiated cell types in the trophoblast epithelium and current human placental trophoblast model systems.

scholarly journals Calretinin expression in molecular subtypes of invasive carcinoma breast

2020 ◽  
Vol 8 (4) ◽  
pp. 1498
Author(s):  
Suryagayathri Venugopal ◽  
Cicy P. J. ◽  
Deepa S. ◽  
Sankar Sundaram
Keyword(s):  
Breast Carcinoma ◽  
Molecular Mechanisms ◽  
Invasive Carcinoma ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Prognostic Significance ◽  
P Value ◽  
Carcinoma Breast ◽  
Low Level ◽  
High Level

Background: Breast cancer is a leading cause of cancer death  in women worldwide. Breast carcinoma is currently managed by assessing clinicopathological features. Elucidation of molecular mechanisms of pathogenesis of breast carcinoma  may lead to the development of new targeted therapies, particularly in triple negative cancers. Literature shows a few studies on the expression of calretinin  in breast carcinoma particularly in basal like type and its prognostic significance.  In this study, authors are trying  to assess the expression of  a new marker calretinin in different molecular subtypes of invasive carcinoma breast.Methods: This study was done in  107 cases of invasive carcinoma breast specimens received in  Department of Pathology, Government Medical college, Kottayam from December  2017 to May 2019.Results: Among the molecular subtypes, Basal like tumours showed 68.4% of cases with high level and 31.6% of cases with low level calretinin expression which is comparable with the study by Farrag et al. All the other molecular subgroups showed predominantly low level of calretinin expression.Conclusions: Different molecular subtypes of invasive carcinoma breast showed varied calretinin expression. High level calretinin expression was significantly associated with grade 3 (p value = 0.002), ER negativity (p = 0.004), PR negativity (p = 0.018)  and Basal like molecular subtype (p : <0.001). This suggests that calretinin might play a role in pathogenesis of basal like breast carcinomas.

scholarly journals Effects of Ketamine on Rodent Fear Memory

2020 ◽  
Vol 21 (19) ◽  
pp. 7173
Author(s):  
Kwang H. Choi ◽  
Rina Y. Berman ◽  
Michael Zhang ◽  
Haley F. Spencer ◽  
Kennett D. Radford
Keyword(s):  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Traumatic Injury ◽  
Psychological Impact ◽  
Fear Memory ◽  
Individual Variability ◽  
Laboratory Animals ◽  
Preclinical Studies ◽  
Post Traumatic Stress ◽  
Biological Sex

Ketamine, a multimodal anesthetic drug, has become increasingly popular in the treatment of pain following traumatic injury as well as treatment-resistant major depressive disorders. However, the psychological impact of this dissociative medication on the development of stress-related disorders such as post-traumatic stress disorder (PTSD) remains controversial. To address these concerns, preclinical studies have investigated the effects of ketamine administration on fear memory and stress-related behaviors in laboratory animals. Despite a well-documented line of research examining the effects of ketamine on fear memory, there is a lack of literature reviews on this important topic. Therefore, this review article summarizes the current preclinical literature on ketamine and fear memory with a particular emphasis on the route, dose, and timing of ketamine administration in rodent fear conditioning studies. Additionally, this review describes the molecular mechanisms by which ketamine may impact fear memory and stress-related behaviors. Overall, findings from previous studies are inconsistent in that fear memory may be increased, decreased, or unaltered following ketamine administration in rodents. These conflicting results can be explained by factors such as the route, dose, and timing of ketamine administration; the interaction between ketamine and stress; and individual variability in the rodent response to ketamine. This review also recommends that future preclinical studies utilize a clinically relevant route of administration and account for biological sex differences to improve translation between preclinical and clinical investigations.

scholarly journals Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

2005 ◽  
Vol 2005 (1) ◽  
pp. 57-61 ◽  
Author(s):  
Mandy Williams ◽  
Allal Ouhtit
Keyword(s):  
Skin Cancer ◽  
Uv Radiation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Uv Light ◽  
Laboratory Animals ◽  
Environmental Carcinogen ◽  
Biological Studies ◽  
Significant Gene ◽  
Recent Developments

Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM) is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV) light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16INK4aand p14ARF. Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16p16INK4a/Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

Neuronal circuits of fear memory and fear extinction

e-Neuroforum ◽  
2013 ◽  
Vol 19 (3) ◽  
Author(s):  
C.T. Wotjak ◽  
H.-C. Pape
Keyword(s):  
Anxiety Disorders ◽  
Molecular Mechanisms ◽  
Fear Extinction ◽  
Intervention Strategies ◽  
Laboratory Animals ◽  
Mammalian Brain ◽  
Synaptic Circuits ◽  
Fear And Anxiety ◽  
High Degree ◽  
Synaptic Circuitry

AbstractThe paradigm“eat or be eaten” has proven to be a critical guiding element during the evolution of both humans and animals. This helps to explain the fact that the ability to de­tect danger or a threat has been highly con­served throughout evolution and thus exhib­its a high degree of homology between spe­cies. Studies in laboratory animals thereby enable the identification of key neurochem­ical, cellular and molecular mechanisms un­derlying fear and anxiety, and important­ly, permit conclusions to be drawn regard­ing the situation in humans. This, in turn, pro­vides a highly valuable basis for further im­provements in prognosis, diagnosis, preven­tion and therapy of anxiety disorders. The present article focuses on one aspect cen­tral to translational anxiety research: the neu­ronal substrates and circuits of fear memo­ry and fear extinction. Following a brief intro­duction into the principles of fear condition­ing, the synaptic circuits that underlie the ac­quisition and extinction of fear memories in the mammalian brain will be described. His­torically established principles will be system­atically compared with novel findings on the detailed synaptic circuitry of the fear matrix. Knowledge of the neuronal substrates and circuitry will significantly improve our under­standing of pathologically transformed states of fear and anxiety and thereby help to derive novel intervention strategies for the treat­ment of anxiety disorders.

scholarly journals Genetic Requirements for Spontaneous and Transcription-Stimulated Mitotic Recombination inSaccharomyces cerevisiae

Genetics ◽  
2002 ◽  
Vol 162 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Jennifer A Freedman ◽  
Sue Jinks-Robertson
Keyword(s):  
Gene Conversion ◽  
Molecular Mechanisms ◽  
Inducible Promoter ◽  
Mitotic Recombination ◽  
Low Level ◽  
Recombination Proteins ◽  
Recombination System ◽  
Gene Conversions

AbstractThe genetic requirements for spontaneous and transcription-stimulated mitotic recombination were determined using a recombination system that employs heterochromosomal lys2 substrates that can recombine only by crossover or only by gene conversion. The substrates were fused either to a constitutive low-level promoter (pLYS) or to a highly inducible promoter (pGAL). In the case of the “conversion-only” substrates the use of heterologous promoters allowed either the donor or the recipient allele to be highly transcribed. Transcription of the donor allele stimulated gene conversions in rad50, rad51, rad54, and rad59 mutants, but not in rad52, rad55, and rad57 mutants. In contrast, transcription of the recipient allele stimulated gene conversions in rad50, rad51, rad54, rad55, rad57, and rad59 mutants, but not in rad52 mutants. Finally, transcription stimulated crossovers in rad50, rad54, and rad59 mutants, but not in rad51, rad52, rad55, and rad57 mutants. These data are considered in relation to previously proposed molecular mechanisms of transcription-stimulated recombination and in relation to the roles of the recombination proteins.

scholarly journals Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Chanika D. Jayasinghe ◽  
Uthpala A. Jayawardena
Keyword(s):  
Herbal Medicine ◽  
Molecular Mechanisms ◽  
Zebrafish Embryo ◽  
Toxicity Testing ◽  
Toxicity Assessment ◽  
Scientific Data ◽  
Herbal Remedies ◽  
Laboratory Animals ◽  
Genetic Redundancy ◽  
Crude Extracts

Herbal remedies have been practiced by humans over centuries and therefore possess time-proven safety. However, it is imperative to evaluate the toxic effects of herbal medicine to confirm their safety, particularly when developing therapeutic leads. Use of laboratory animals such as rats, mice, and rabbits was considered as gold standard in herbal toxicity assessments. However, in the last few decades, the ethical consideration of using higher vertebrates for toxicity testing has become more contentious. Thus, possible alternative models entailing lower vertebrates such as zebrafish were introduced. The zebrafish embryotoxicity model is at the forefront of toxicology assessment due to the transparent nature of embryos, low cost, short cycle, higher fecundity, and genetic redundancy to the humans. Recently, its application has been extended to herbal toxicology. The present review intends to provide a comprehensive assembly of studies that applied the zebrafish embryo model for the assessment of herbal toxicity. A systematic literature survey was carried out in popular scientific databases. The literature search identified a total of 1014 articles in PubMed = 12, Scopus SciVerse® = 623, and Google Scholar = 1000. After screening, 25 articles were included in this review, and they were categorized into three groups in which the zebrafish embryotoxicity assay has been applied to investigate the toxicity of (1) polyherbal formulae/medical prescription (2 full texts), (2) crude extracts (12 full texts), and (3) phytocompounds/isolated constituents (11 full texts). These studies have investigated the toxicity of 6 polyherbal formulae, 16 crude extracts, and more than 30 phytocompounds/isolated constituents using the zebrafish embryotoxicity model. Moreover, this model has explicated the teratogenic effects and specific organ toxicities such as the kidney, heart, and liver. Furthermore, in some studies, the molecular mechanisms underlying the toxicity of herbal medicine have been elucidated. This comprehensive collection of scientific data solidifies the zebrafish embryo model as an effective model system for studying toxicological effects of a broad spectrum of herbal remedies. Henceforth, it provides a novel insight into the toxicity assessment of herbal medicine.

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