Three Good Things

Let us consider some good things that have happened before the year 2021 concludes: 1) On February 1, 2021, researchers at Children's Hospital of Philadelphia (CHOP) announced that the autism spectrum disorders may be caused by defects in the mitochondria of brain cells of the eye. The research continues. 2) In the year 2021, many people have adopted the term “on the spectrum” to refer to the many brain dysfunctions that can and cannot be named and diagnosed yet. 3) Yale University Child Study Center and The Jim Henson Institute have invited many experts from many fields of study together to discover what happens when spectrum and non-spectrum children and adults look at puppets. What are they looking at? What do they see? Why don't we already know what they see? Are we looking at the important things? The chapter will explore these questions and specifically learning and the impact of puppets further.

Identification of potential astrocytes in the teleost brain

Astrocytes are abundant star-shaped glial cells in the mammalian brain, with essential roles in metabolism, development, homeostasis, response to injury, behavior, and learning. Surprisingly, most regions of the teleost brain are thought to lack astrocytes, based primarily on the use of GFAP (glial fibrillary acidic protein) as a marker. Here, drawing on recent evidence that astrocytes are molecularly heterogeneous, we propose that astrocytes exist in the teleost brain, albeit of the olig2 subtype. Highly branched cells are present throughout the zebrafish brain, as shown here in Tg(sox10:EGFP) fish and previously in Tg(olig2:GFP) fish. Transcriptome data indicates the presence of brain cells that are olig2 and sox10 positive, which also express the astrocyte markers sox9b, sparcl1 and slc1a2b but lack gfap and the oligodendrocyte marker mbp. In situ hybridization confirms that stellate sox10:EGFP cells express olig2 and sox9b, while immunofluorescence indicates that they lack HuC/D and GFAP. We suggest that these cells be classified as astrocytes as this may more accurately reflect their functions.

A Mathematical Model for Controlling Exchanged Spinor Waves between Hemoglobin, Tumor and T-Cells

To date, it is known that tumor cells respond to attacks of T-cells by producing some PD-1/PD-L1 and other connections. Unfortunately, medical methods for preventing these connections are expensive and sometimes non-effective. In this study, we suggest a new way for reducing these connections by producing some noise in the exchanged information between tumor cells, T-cells, hemoglobin, and controller cells such as those of the heart or brain. In this model, we assume that human cells use spinor waves for exchanging information because the velocity of exchanged information between two spinors, which are located a large distance apart, exceeds the velocity of light. In fact, two spinors could send and receive information from each other instantaneously. In this hypothesis, the DNAs within heart cells, brain cells or any controller are built from some spinors such as electrons, and by their motion, some waves are generated. These spinor waves are received by iron atoms and multi-gonal molecules within hemoglobin and other spinors within the blood vessels. The hemoglobin molecules are located on some blood cells, move along the blood vessels and pass on their information to cells, proteins and RNAs. The spins of the spinors within the hemoglobin and also the spins of the charges and ions within the blood vessels are entangled and could transmit any information between cells. Thus, when a tumor is formed, its spinor waves change, and are transmitted rapidly into the heart cells, brain cells and other controller cells. The heart, brain or other controller cells diagnose these quantum waves, and by using the entanglement between the spinors within the blood vessels and the hemoglobin, send some messages to the T-cells. These messages are received by tumor cells and they become ready to respond to attacks. To prevent the reception of information by tumor cells, we can make use of some extra cells or hemoglobin, which interact with spinors and hemoglobin around tumor cells and produce some noise. Science quantum spinor waves are minute and have minor power and intensity; we cannot detect them by our present electronic devices and for this reason, we suggest using biological cells. This is a hypothesis; however, if experiments show its validity, some types of cancers could be cured or controlled by this method. We formulate the model by considering quantum entanglement between spinors within biological systems. By changing any spin within this system, all spins change and consequently, information is transmitted immediately. Then, we add new spinors to this system mathematically, and show that this causes the correlations between the initial spinors to reduce. Thus, the spinors of the extra hemoglobin or cells could act like noise, and prevent reception of real information by tumor cells.

Autoimmune Encephalitis and Autism Spectrum Disorder

The concept of “acquired autism” refers to the hypothesis that amongst the massive heterogeneity that encompasses autism spectrum disorder (ASD) there may be several phenotypes that are neither syndromic nor innate. Strong and consistent evidence has linked exposure to various pharmacological and infective agents with an elevated risk of a diagnosis of ASD including maternal valproate use, rubella and herpes encephalitis. Autoimmune encephalitis (AE) describes a group of conditions characterised by the body's immune system mounting an attack on healthy brain cells causing brain inflammation. The resultant cognitive, psychiatric and neurological symptoms that follow AE have also included ASD or autism-like traits and states. We review the current literature on AE and ASD. Drawing also on associated literature on autoimmune psychosis (AP) and preliminary evidence of a psychosis-linked subtype of ASD, we conclude that AE may either act as a potentially causative agent for ASD, and/or produce symptoms that could easily be mistaken for or misdiagnosed as autism. Further studies are required to discern the connection between AE and autism. Where autism is accompanied by regression and atypical onset patterns, it may be prudent to investigate whether a differential diagnosis of AE would be more appropriate.

Insights into neurodegeneration from electron microscopy studies

Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, pose an increasingly severe burden for individuals and society in an ageing population. The causes and mechanisms of the diseases are poorly understood and as yet there are no effective treatments. Some of the molecular complexes involved in degeneration have been identified and electron microscopy has provided an essential tool in the investigations. The focus of this review is to show how electron microscopy has contributed historically to the understanding of disease and to summarize the most striking current advances. It does not seek to cover in detail the recent technical developments in microscopy, involving better microscopes, better electron detectors and more powerful image processing techniques, which have made possible the new insights. In many instances pathological filament assemblies are associated with brain cells that die in the disease, causing the observed symptoms such as dementia or movement disorders. Using electron microscopy it is now possible to go beyond morphological descriptions to produce atomic structures of many of the filaments. This information may help to understand the seeding and assembly of the filaments, with the aim of finding small molecule inhibitors that could potentially provide a form of treatment for the diseases.

Cell-type specialization is encoded by specific chromatin topologies

The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1–3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi4–6. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation7, are invisible with such approaches8. Here we developed immunoGAM, an extension of genome architecture mapping (GAM)2,9, to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation2,10. We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive ‘melting’ of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.