Bioinformatic Analysis Reveals the Distinct Role of 5’UTR-specific m6A RNA Modification in Mice Developing Cerebral Cortices

N6-methyladenosine (m6A) abundantly exists in the cerebral cortex, and is emerging as an essential factor in cortical development and function. As the m6A binding site appears to be dynamically methylated in different RNA regions at the temporal-specific developing stage, it is of value to distinguish the unique character of region- and temporal-specific m6A. Herein, we analyzed the status of temporal-specific m6A within RNA 5’ untranslated region (5’UTR) using m6A-methylated sequencing data and transcriptomic sequencing data from 12.5-13-day embryonic cerebral cortices and 14-day postnatal ones. We identified sorts of RNAs that are uniquely m6A-methylated in the 5’UTR region and sorted them into specific neurological processes. Compared with 3’UTR-m6A-methylated RNAs, 5’UTR-m6A-methylated RNAs showed unique functions and mechanisms in regulating cortical development, especially through the pathway of mRNA transport and surveillance. Moreover, the 5’UTR-specific m6A was associated with neurological disorders as well. The FoxO signaling pathway was then focused by these pathogenic 5’UTR-m6A-methylated RNAs, and explored to be involved in the determination of neurological disorders. Additionally, the 5’UTR-m6A-modification patterns and transcriptional patterns play independent but cohesive roles in the developing cortices. Our study emphasizes the importance of 5’UTR-specific m6A in the developing cortex and provides an informative reference for future studies of 5’UTR-specific m6A in normal cortical development and neurological disorders.

Memory and Memories: An Interdisciplinary Approach

Only humans seem to have the ability to project themselves into their past or future. This mental phenomenon, called autonoetic consciousness, proves the interrelation of memory, imagination, emotion, intelligence and consciousness as a way of creating self-images. The current paper constitutes an integrative study on memory from a theoretical perspective. The first part presents the most known neuroscientific viewpoints on the memory process, along with the pathological case of patient HM, who lost his memory following the removal of his hippocampus. The second part provides a humanistic perspective on recollection to demonstrate its compatibility with the neurological processes of storing information and forming memories. The final part conveys the phenomenon of recollection from the perspective of identity crisis in Kazuo Ishiguro’s novels, as a case study in memory literature. According to memory theories to date, identity cannot exist outside the process of recording and recalling past experiences. Despite the fallible nature of recollection, human beings return to their past in order to give a healthy meaning to their present.

Musical perception and teaching-learning of French language-culture: Some acoustic and neuroscientific elements for the French music teacher

The musical nature of the sounds of a modern language emitted in the spoken mode, as well as their rhythmic and melodic combinations, exert a considerable "power" on teaching-learning: they provoke, in the learner, decisive auditory reactions, the variables of which are difficult to control, lead to more or less pleasant sensations, (in) understanding, interpretation, produce meaning. Musical perception is at the heart of successful teaching-learning. A language teacher is first and foremost a language music teacher. A French language-culture teacher is above all and always a French music teacher. Among the multidisciplinary relations of the discipline in which it is located, namely Didactology-didactics of the music of the French language-culture, are acoustics and cognitive neurosciences. Despite the extreme complexity of perceptual and neurological processes, turning to musical acoustics at first and then to musical neurosciences secondly makes it possible to recall and discover essential elements and data likely to be of interest to teaching practices.

Neuroplastin in Neuropsychiatric Diseases

Molecular mechanisms underlying neuropsychiatric and neurodegenerative diseases are insufficiently elucidated. A detailed understanding of these mechanisms may help to further improve medical intervention. Recently, intellectual abilities, creativity, and amnesia have been associated with neuroplastin, a cell recognition glycoprotein of the immunoglobulin superfamily that participates in synapse formation and function and calcium signaling. Data from animal models suggest a role for neuroplastin in pathways affected in neuropsychiatric and neurodegenerative diseases. Neuroplastin loss or disruption of molecular pathways related to neuronal processes has been linked to various neurological diseases, including dementia, schizophrenia, and Alzheimer’s disease. Here, we review the molecular features of the cell recognition molecule neuroplastin, and its binding partners, which are related to neurological processes and involved in learning and memory. The emerging functions of neuroplastin may have implications for the treatment of diseases, particularly those of the nervous system.

3D Models as an Adjunct for Models in Studying Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common causes of dementia. Disease progression is marked by cognitive decline and memory impairment due to neurodegenerative processes in the brain stemming from amyloid-β (Aβ) deposition and formation of neurofibrillary tangles. Pathogenesis in AD is dependent on two main neurological processes: formation of intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein and deposition of extracellular senile Aβ peptides. Given the nature of the disease, the pathology and progression of AD in vivo in humans have been difficult to study in vivo. To this degree, models can help to study the disease pathogenesis, biochemistry, immunological functions, genetics, and potential pharmacotherapy. While animal and two-dimensional (2D) cell culture models have facilitated significant progress in studying the disease, more recent application of novel three-dimensional (3D) culture models has exhibited several advantages. Herein, we describe a brief background of AD, and how current animal, 2D, and 3D models facilitate the study of this disease and associated therapeutics.

The body in the German neurology of the early twentieth century

In the past years, there has been an increasing interest in the experience of the own body in the field of experimental psychology and cognitive neuroscience. However, these questions are not new to neuroscience. Interestingly, the German neurology of the early twentieth century showed an extraordinary interest in the neurological processes underlying the experience of the body. One of the most controversial theoretical frameworks to this day is the distinction between the body schema and the body image. The latter is often referred to Paul Schilder and has caused some considerable discussions not only today, but also during the 1920/1930s. This chapter discusses Paul Schilder’s work in more detail, with a particular focus on his German writings. The chapter will describe the influence of Carl Wernicke and his concept of the somatopsyche. It was an important source of inspiration not only to Schilder, but also to the whole German neurology of that time. As the chapter will show, Schilder and his contemporaries had rather diverse concepts of the body image. By shedding light on some of these discussions, and the persons behind them, it is hoped the chapter will provide a better understanding of the evolution of this concept within the early German-speaking neurology.

Transcriptome signature of miRNA-26b KO mouse model suggests novel targets

Background MicroRNAs (miRNAs) are short (20–24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. One of the miRNAs that has been shown to play a role in various pathologies like cancer, neurological disorders and cardiovascular diseases is miRNA-26b. However, these studies only demonstrated rather ambiguous associations without revealing a causal relationship. Therefore, the aim of this study is to establish and validate a mouse model which enables the elucidation of the exact role of miRNA-26b in various pathologies. Results A miRNA-26b-deficient mouse model was established using homologous recombination and validated using PCR. miRNA-26b-deficient mice did not show any physiological abnormalities and no effects on systemic lipid levels, blood parameters or tissue leukocytes. Using next generation sequencing, the gene expression patterns in miRNA-26b-deficient mice were analyzed and compared to wild type controls. This supported the already suggested role of miRNA-26b in cancer and neurological processes, but also revealed novel associations of miRNA-26b with thermogenesis and allergic reactions. In addition, detailed analysis identified several genes that seem to be highly regulated by miRNA-26b, which are linked to the same pathological conditions, further confirming the role of miRNA-26b in these pathologies and providing a strong validation of our mouse model. Conclusions miRNA-26b plays an important role in various pathologies, although causal relationships still have to be established. The described mouse model of miRNA-26b deficiency is a crucial first step towards the identification of the exact role of miRNA-26b in various diseases that could identify miRNA-26b as a promising novel diagnostic or even therapeutic target in a broad range of pathologies.

B Cells in Neuroinflammation: New Perspectives and Mechanistic Insights

In recent years, the role of B cells in neurological disorders has substantially expanded our perspectives on mechanisms of neuroinflammation. The success of B cell-depleting therapies in patients with CNS diseases such as neuromyelitis optica and multiple sclerosis has highlighted the importance of neuroimmune crosstalk in inflammatory processes. While B cells are essential for the adaptive immune system and antibody production, they are also major contributors of pro- and anti-inflammatory cytokine responses in a number of inflammatory diseases. B cells can contribute to neurological diseases through peripheral immune mechanisms, including production of cytokines and antibodies, or through CNS mechanisms following compartmentalization. Emerging evidence suggests that aberrant pro- or anti-inflammatory B cell populations contribute to neurological processes, including glial activation, which has been implicated in the pathogenesis of several neurodegenerative diseases. In this review, we summarize recent findings on B cell involvement in neuroinflammatory diseases and discuss evidence to support pathogenic immunomodulatory functions of B cells in neurological disorders, highlighting the importance of B cell-directed therapies.

Evaluation of Behavioral Immune System and its Unique Effect on Prejudice and Stigmatization in Patients with Infectious Diseases

Introduction: Behavioral immune systems allow organisms to detect the presence of disease-causing pathogens in their environment more immediately and engage in behaviors that prevent them from coming into contact with objects and individuals. There is extensive research linking behavioral immune systems to a variety of prejudices. These prejudices cause labeling and ultimately social stigma on these people. Therefore, the present study investigated the behavioral safety system and its unique effect on prejudice and stigmatization in people with infectious diseases. In this review study, the research literature was searched through Google Scholar and PubMed with the words "Behavioral Immune System, Prejudice, Stigmatization", and the relevant authorities were included in this study. Research has shown that people tend to associate illness with obesity, the manifestation of facial symptoms, physical disability, and foreign nationality in order to avoid becoming ill by predicting illness and thus overreacting to them. These reactions occur in many groups of people who do not actually have the contagious disease and are called a type of psychological allergy. These prejudicial reactions and labeling can cause social distress for these people and their long-term social isolation. Conclusion: Disgust is triggered in response to pathogen-related stimuli and is associated with unique patterns of autonomic nervous system activity and neural activity, but in functional connections between anatomical structures, chemical neurological processes, and various cognitive and behavioral phenomena, the genetic structure is involved. Demonstrating behavioral immunity, there is not much information and more study is needed.

Altered ribosomal function and protein synthesis caused by tau

The synthesis of new proteins is a fundamental aspect of cellular life and is required for many neurological processes, including the formation, updating and extinction of long-term memories. Protein synthesis is impaired in neurodegenerative diseases including tauopathies, in which pathology is caused by aberrant changes to the microtubule-associated protein tau. We recently showed that both global de novo protein synthesis and the synthesis of select ribosomal proteins (RPs) are decreased in mouse models of frontotemporal dementia (FTD) which express mutant forms of tau. However, a comprehensive analysis of the effect of FTD-mutant tau on ribosomes is lacking. Here we used polysome profiling, de novo protein labelling and mass spectrometry-based proteomics to examine how ribosomes are altered in models of FTD. We identified 10 RPs which were decreased in abundance in primary neurons taken from the K3 mouse model of FTD. We further demonstrate that expression of human tau (hTau) decreases both protein synthesis and biogenesis of the 60S ribosomal subunit, with these effects being exacerbated in the presence of FTD-associated tau mutations. Lastly, we demonstrate that expression of the amino-terminal projection domain of hTau is sufficient to reduce protein synthesis and ribosomal biogenesis. Together, these data reinforce a role for tau in impairing ribosomal function.