The Three Stage Digital Evolution of Linguistic Humans

2019 ◽  
Author(s):  
Kumon Tokumaru
Keyword(s):  
B Lymphocyte ◽  
Life Support ◽  
Immune Cell ◽  
3D Structure ◽  
Variable Region ◽  
Molecular Structures ◽  
Digital Evolution ◽  
Antibody Molecule ◽  
Reflex Mechanism ◽  
Support Mechanism

Digital Linguistics (DL) is an interdisciplinary study that identifies human language as a digital evolution of mammal analog vocal sign communications, founded on the vertebrate spinal sign reflex mechanism [Tokumaru 2017 a/b, 2018 a/b/c/d]. Analog signs are unique with their physical sound waveforms but limited in number, whilst human digital word signs are infinite by permutation of their logical property, phonemes. The first digital evolution took place 66,000 years ago with South African Neolithic industries, Howiesons Poort, when linguistic humans acquired a hypertrophied mandibular bone to house a descended larynx for vowel accented syllables containing logical properties of phonemes and morae. Morae made each syllable distinctive in the time axis and enabled grammatical modulation by alternately transmitting conceptual and grammatical syllables. The sign reflex mechanism is an unconscious self-protection and life-support mechanism, operated by immune cell networks inside the ventricle system. DL identified cellular and molecular structures for the sign (=concept) device as a B lymphocyte (or, in other words, Mobile Ad-Hoc Networking Neuron), connects to sensory, conceptual and networking memories, which consist of its meanings [Table 1]. Its antibodies can network with antigens of CSF-Contacting Neurons at the brainstem reticular formation and of Microglia cells at the neocortex [Figure 1]. It is plausible that the 3D structure of the antigen molecule takes the shape of word sound waveform multiplexing intensity and pitch, and that specifically pairing the antibody molecule consists of three CDRs (Complementality Defining Regions) in the Antibody Variable Region network with the logic of dichotomy and dualism. As sign reflex deals with survival issues such as food, safety and reproduction, it is stubborn, passive and inflexible: It does not spontaneously look for something new, and it is not designed to revise itself. These characteristics are not desirable for the development of human intelligence, and thus are to be overcome. All the word, sensory and network memories in the brain must be acquired postnatally through individual learning and thought. The reason and intelligence of humans depend on how correctly and efficiently humans learn new words and acquire appropriate meanings for them.

Visualizing 3D Molecular Structures Using an Augmented Reality App

2019 ◽  
Author(s):  
Kristina Eriksen ◽  
Bjarne Nielsen ◽  
Michael Pittelkow
Keyword(s):  
Augmented Reality ◽  
Small Molecules ◽  
Computer Modelling ◽  
Simple Procedure ◽  
3D Structure ◽  
Molecular Structures ◽  
Free Software ◽  
Programming Skills ◽  
2D Space ◽  
Made In

<p>We present a simple procedure to make an augmented reality app to visualize any 3D chemical model. The molecular structure may be based on data from crystallographic data or from computer modelling. This guide is made in such a way, that no programming skills are needed and the procedure uses free software and is a way to visualize 3D structures that are normally difficult to comprehend in the 2D space of paper. The process can be applied to make 3D representation of any 2D object, and we envisage the app to be useful when visualizing simple stereochemical problems, when presenting a complex 3D structure on a poster presentation or even in audio-visual presentations. The method works for all molecules including small molecules, supramolecular structures, MOFs and biomacromolecules.</p>

scholarly journals Immune-Related Circulating miR-125b-5p and miR-99a-5p Reveal a High Recurrence Risk Group of Pancreatic Cancer Patients after Tumor Resection

2019 ◽  
Vol 9 (22) ◽  
pp. 4784
Author(s):  
Vietsch ◽  
Peran ◽  
Suker ◽  
van den Bosch ◽  
Sijde ◽  
...  
Keyword(s):  
Cancer Progression ◽  
B Lymphocyte ◽  
Immune Cell ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Tumor Stroma ◽  
Recurrence Risk ◽  
High Serum ◽  
Ductal Adenocarcinoma ◽  
Before And After

Clinical follow-up aided by changes in the expression of circulating microRNAs (miRs) may improve prognostication of pancreatic ductal adenocarcinoma (PDAC) patients. Changes in 179 circulating miRs due to cancer progression in the transgenic KrasG12D/+; Trp53R172H/+; P48-Cre (KPC) animal model of PDAC were analyzed for serum miRs that are altered in metastatic disease. In addition, expression levels of 250 miRs were profiled before and after pancreaticoduodenectomy in the serum of two patients with resectable PDAC with different progression free survival (PFS) and analyzed for changes indicative of PDAC recurrence after resection. Three miRs that were upregulated ≥3-fold in progressive PDAC in both mice and patients were selected for validation in 26 additional PDAC patients before and after resection. We found that high serum miR-125b-5p and miR-99a-5p levels after resection are significantly associated with shorter PFS (HR 1.34 and HR 1.73 respectively). In situ hybridization for miR detection in the paired resected human PDAC tissues showed that miR-125b-5p and miR-99a-5p are highly expressed in inflammatory cells in the tumor stroma, located in clusters of CD79A expressing cells of the B-lymphocyte lineage. In conclusion, we found that circulating miR-125b-5p and miR-99a-5p are potential immune-cell related prognostic biomarkers in PDAC patients after surgery.

Scope of action of the immunoglobulin mutator system

Genome ◽  
1989 ◽  
Vol 31 (1) ◽  
pp. 118-121 ◽  
Author(s):  
Matthias R. Wabl ◽  
Hans-Martin Jäck ◽  
R. C. von Borstel ◽  
Charles M. Steinberg
Keyword(s):  
B Cell ◽  
Mutation Rate ◽  
Heavy Chain ◽  
B Lymphocyte ◽  
Somatic Hypermutation ◽  
Spontaneous Mutation ◽  
Cell Lineage ◽  
Variable Region ◽  
High Rate ◽  
Spontaneous Mutation Rate

The authors have developed a method to measure the rate of spontaneous mutations taking place in IgH, the gene encoding the immunoglobulin heavy chain. When an amber chain-termination codon mutates to a sense codon, translation of the polypeptide chain will be completed, and mutant cells producing the heavy chain can be detected with a fluorescent labelled antibody. The protocol used is the compartmentalization test which minimizes any effect of selection. In subclones of the pre-B lymphocyte line 18–81, the spontaneous mutation rate in the part of IgH encoding the variable region is somewhat greater than 10−5 mutations per base pair per generation. This supports the hypothesis that hypermutation is not dependent on cell stimulation by an antigen. In a hybrid between a cell of this line and a myeloma (which represents the terminal stage of the B-cell lineage), the mutation rate was too low to be determined by this test, less than 10−9. When the same loss to gain procedure system was used with an opal chain-terminating codon in the part of IgH encoding the constant region (Cμ), a high rate of reversion by deletion was found. Long (more than one exon) and short (less than one exon) deletions occurred at rates of 1.7 × 10−5 and 1.4 × 10−7 per generation, respectively. It is thought that the high rate of deletion is not related to somatic hypermutation but rather to DNA rearrangement during the heavy-chain class switch, which is occurring in these pre-B cell lines. The point mutation rate was too low to be detected above the background of deletion mutants, less than 5 × 10−8. The immunoglobulin mutator system works weakly, if at all, on two other, nonimmunoglobulin, genes tested: B2m (β2 microglobulin) and the gene for ouabain resistance.Key words: pre-B lymphocyte, B lymphocyte, spontaneous mutation rate, compartmentalization test, deletion mutation, hypermutation.

scholarly journals MolAR: Bringing Chemical Structures to Life with Augmented Reality and Machine Learning

2021 ◽  
Author(s):  
Sukolsak Sakshuwong ◽  
Hayley Weir ◽  
Umberto Raucci ◽  
Todd J. Martínez
Keyword(s):  
Machine Learning ◽  
Augmented Reality ◽  
3D Structure ◽  
Three Dimensional ◽  
Real Life ◽  
Data Bank ◽  
Molecular Structures ◽  
Chemical Structures ◽  
Food And Drink ◽  
Research And Education

Visualizing three-dimensional molecular structures is crucial to understanding and predicting their chemical behavior. Existing visualization software, however, can be cumbersome to use, and, for many, hand-drawn skeletal structures remain the preferred method of chemical communication. Although convenient, the static, two-dimensional nature of these drawings can be misleading in conveying the molecule’s 3D structure, not to mention that dynamic movement is completely disregarded. Here, we combine machine learning and augmented reality (AR) to develop MolAR, an immersive mobile application for visualizing molecules in real-world scenes. The application uses deep learning to recognize hand-drawn hydrocarbons structures which it converts into interactive 3D molecules in AR. Users can also “hunt” for chemicals in food and drink to uncover molecules in their real-life environment. A variety of interesting molecules are pre-loaded into the application, and users can visualize molecules in PubChem by providing their name or SMILES string and proteins in the Protein Data Bank by providing their PDB ID. MolAR was designed to be used in both research and education settings, providing an almost barrierless platform to visualize and interact with 3D molecular structures in a uniquely immersive way.

The Lymph Node Niche.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-51-SCI-51
Author(s):  
Thorsten R. Mempel
Keyword(s):  
Lymph Nodes ◽  
B Lymphocyte ◽  
Immune Cell ◽  
Conflicts Of Interest ◽  
Lymphatic Vessels ◽  
Potential Threat ◽  
Peripheral Tissues ◽  
Pathogen Invasion ◽  
Cognate Antigen

Abstract Abstract SCI-51 Lymph nodes provide specialized stromal environments that support the maintenance and homeostasis of T and B lymphocyte populations and are also staging grounds for lymphocyte effector responses against pathogens and transformed cells. They serve as immune information hotspots by collecting lymph fluid from peripheral tissues, especially our external and internal epithelial body surfaces, thus displaying a condensed representation of foreign and self-antigens at these sites in addition to integrating innate alarm signals that report tissue damage or pathogen invasion. Naïve B and T cells constantly traffic through these environments via the blood stream and efferent lymphatic vessels, which allows for efficient matching of their antigen receptor repertoires with the regional antigenic landscape. Depending on the absence or presence of signs of a potential threat to the organism, the result may be either tolerance or immunity towards the origin of these antigens. The architecture of lymph nodes is optimized to facilitate the presentation of lymph-borne antigen in various forms and to guide naïve lymphocytes in their search for 'their' cognate antigen in the form in which they are able to 'see' it. It also facilitates the cellular crosstalk with other immune cell populations that shape and regulate an ensuing adaptive response if cognate antigen is encountered in an immunogenic context. Our conception of how these various tasks are accomplished has recently been enriched through new methodological approaches that include the dynamic in situ or in vivo visualization of cellular and molecular processes using modern microscopy technology. We will review some recent insights into the function of lymph nodes derived from these studies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparative study of Danshen and Siwu decoction based on the molecular structures of the components and predicted targets

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Li ◽  
Li Qiao ◽  
Cong Chen ◽  
Zhenguo Wang ◽  
Xianjun Fu
Keyword(s):  
Comparative Study ◽  
Structural Feature ◽  
3D Structure ◽  
Chemical Properties ◽  
Principal Component ◽  
Molecular Structures ◽  
Physical And Chemical Properties ◽  
Material Basis ◽  
Physical And Chemical ◽  
And Chemical Properties

Abstract Background The sentence of “Danshen (Salvia Miltiorrhizae Radix et Rhizoma) and Siwu decoction are similar in function” was first recorded in an ancient Chinese medical book “Fu Ren Ming Li Lun”. This theory has far-reaching influence on the clinical practice of Chinese medicine and is highly respected by Chinese medical doctors. However, the theory has limitations and controversial part for there is no in-depth and system comparative study. Methods We collected the molecular structures of 129 compounds of Danshen and 81 compounds of Siwu decoction from the literatures. MACCS fingerprints and Tanimoto similarity were calculated based on the molecular structures for comparing the structural feature. Molecular descriptors which represent physical and chemical properties were calculated by Discovery Studio. Principal component analysis (PCA) of was performed based on the descriptors. The ADMET properties were predicted by FAF-Drugs4. The effect targets for the compounds with good ADMET properties were confirmed from experimental data and predicted using the algorithm comprising Bernoulli Naive Bayes profiling. Results Based on the molecular structures, the presented study compared the structural feature, physical and chemical properties, ADMET properties, and effect targets of compounds of Danshen and Siwu decoction. It is found that Danshen and Siwu decoction do not have the same main active components. Moreover, the 2D structure of compounds from Danshen and Siwu decoction is not similar. Some of the compounds of Danshen and Siwu decoction are similar in 3D structure. The compounds with good ADMET properties of Danshen and Siwu decoction have same predicted targets, but some have different targets. Conclusions It can be inferred from the result that Danshen and Siwu decoction have some similarities, but also present differences from each other in the structure of the compounds and predicted targets. This may be the material basis of the similar and different traditional efficacy of Danshen and Siwu decoction. The setence of “ Danshen and Siwu decoction are similar in function. “ which is used in clinical has its material basis and target connotation to some extent. However, the traditional effects of Danshen and Siwu decoction are not exactly the same.

scholarly journals Assessment of changes in autophagic vesicles in human immune cell lines exposed to nano particles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christopher A. W. David ◽  
M. Estela del Castillo Busto ◽  
Susana Cuello-Nuñez ◽  
Heidi Goenaga-Infante ◽  
Michael Barrow ◽  
...  
Keyword(s):  
Cell Lines ◽  
B Lymphocyte ◽  
Immune Cell ◽  
Human Monocyte ◽  
Significant Degree ◽  
Autophagic Vacuole ◽  
Nano Particles ◽  
Rational Development ◽  
Monocyte Cell ◽  
Negative Controls

Abstract Background Safe and rational development of nanomaterials for clinical translation requires the assessment of potential biocompatibility. Autophagy, a critical homeostatic pathway intrinsically linked to cellular health and inflammation, has been shown to be affected by nanomaterials. It is, therefore, important to be able to assess possible interactions of nanomaterials with autophagic processes. Results CEM (T cell), Raji (B lymphocyte), and THP-1 (human monocyte) cell lines were subject to treatment with rapamycin and chloroquine, known to affect the autophagic process, in order to evaluate cell line-specific responses. Flow cytometric quantification of a fluorescent autophagic vacuole stain showed that maximum observable effects (105%, 446%, and 149% of negative controls) were achieved at different exposure durations (8, 6, and 24 h for CEM, Raji, and THP-1, respectively). THP-1 was subsequently utilised as a model to assess the autophagic impact of a small library of nanomaterials. Association was observed between hydrodynamic size and autophagic impact (r2 = 0.11, p = 0.004). An ELISA for p62 confirmed the greatest impact by 10 nm silver nanoparticles, abolishing p62, with 50 nm silica and 180 nm polystyrene also lowering p62 to a significant degree (50%, 74%, and 55%, respectively, p < 0.05). Conclusions This data further supports the potential for a variety of nanomaterials to interfere with autophagic processes which, in turn, may result in altered cellular function and viability. The association of particle size with impact on autophagy now warrants further investigation. Graphic abstract

scholarly journals Predicting Chemical Shifts with Graph Neural Networks

2020 ◽  
Author(s):  
Ziyue Yang ◽  
Maghesree Chakraborty ◽  
Andrew D White
Keyword(s):  
Neural Networks ◽  
Chemical Shifts ◽  
Protein Nmr ◽  
3D Structure ◽  
Gradient Methods ◽  
Molecular Structures ◽  
Feature Engineering ◽  
Chemical Shift Prediction ◽  
Domain Expertise ◽  
Graph Neural Networks

AbstractInferring molecular structure from NMR measurements requires an accurate forward model that can predict chemical shifts from 3D structure. Current forward models are limited to specific molecules like proteins and state of the art models are not differentiable. Thus they cannot be used with gradient methods like biased molecular dynamics. Here we use graph neural networks (GNNs) for NMR chemical shift prediction. Our GNN can model chemical shifts accurately and capture important phenomena like hydrogen bonding induced downfield shift between multiple proteins, secondary structure effects, and predict shifts of organic molecules. Previous empirical NMR models of protein NMR have relied on careful feature engineering with domain expertise. These GNNs are trained from data alone with no feature engineering yet are as accurate and can work on arbitrary molecular structures. The models are also efficient, able to compute one million chemical shifts in about 5 seconds. This work enables a new category of NMR models that have multiple interacting types of macromolecules.

scholarly journals Acetyltransferases GCN5 and PCAF are Required for B Lymphocyte Maturation

2021 ◽  
Author(s):  
Valentyn Oksenych ◽  
Dan Su ◽  
Jeremy A. Daniel
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Lymphocyte ◽  
Cytidine Deaminase ◽  
Dna Recombination ◽  
Variable Region ◽  
Open Chromatin ◽  
Recombination Activating Gene ◽  
Spleen And Lymph Nodes

B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an &ldquo;open chromatin&rdquo; state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacks both GCN5 and PCAF in B cells. We found that double-deficient mice possess low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We conclude that both GCN5 and PCAF are required for B cell development in vivo.

scholarly journals Acetyltransferases GCN5 and PCAF are Required for B Cell Maturation in Mice

2021 ◽  
Author(s):  
Valentyn Oksenych
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Cytidine Deaminase ◽  
Dna Recombination ◽  
Variable Region ◽  
Open Chromatin ◽  
Spleen And Lymph Nodes

B lymphocyte development includes two DNA recombination processes, the V(D)J recombination of immunoglobulin (Igh) gene variable region and class switching when the Igh constant regions are changed from IgM to IgG, IgA, or IgE. The V(D)J recombination is required for successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. The CSR occurs outside the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an &ldquo;open chromatin&rdquo; state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated by complex breeding a mouse model with B cells lacking both GCN5 and PCAF. We found that double-deficient mice possess low levels of mature B cells in the bone marrow and peripheral organs, accumulation of pro-B cells in bone marrow, and reduced CSR levels. We concluded that both GCN5 and PCAF are required for B cell development in vivo.

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