Specific Tissues Research Articles

Enrichment of Spatial eGenes Colocalized with Type 2 Diabetes Mellitus Genome-Wide Association Study Signals in the Lysosomal Pathway

Genome-wide association studies (GWAS) have identified genetic markers associated with type 2 diabetes mellitus (T2DM). Additionally, tissue-specific expression quantitative trait loci (eQTL) studies have revealed regulatory elements influencing gene expression in specific tissues. We performed enrichment analyses using spatial eGenes corresponding to known T2DM GWAS signals to uncover T2DM pathological pathways. T2DM GWAS signals were obtained from the GWAS Catalog, and spatial eQTL data from T2DM-associated tissues, including visceral adipose tissue, liver, skeletal muscle, and pancreas, were sourced from the Genotype-Tissue Expression Consortium. The eGenes were enriched in Kyoto Encyclopedia of Genes and Genomes biological pathways using the Benjamini–Hochberg method. Colocalization analysis of 2857 independent T2DM GWAS signals identified 556 eGenes in visceral adipose tissue, 176 in liver, 715 in skeletal muscle, and 384 in pancreas (PFDR < 0.05 where PFDR is the false discovery rate). These eGenes showed enrichment in various pathways (PBH < 0.05 where PBH is the corrected P for the Benjamini–Hochberg multiple testing), especially the lysosomal pathway in pancreatic tissue. Unlike the mTOR pathway in T2DM autophagy dysregulation, the role of lysosomes remains poorly understood. The enrichment analysis of spatial eGenes associated with T2DM GWAS signals highlights the importance of the lysosomal pathway in autophagic termination. Thus, investigating the processes involving autophagic termination associated with lysosomes is a priority for understanding T2DM pathogenesis.

An Exploration of the Effects of Gene-Editing Technology on Human Identity

An Exploration of the Effects of Gene-Editing Technology on Human Identity

Tissue and subcellular localization of CycD2 and KRPs are dissimilarly distributed by glucose and sucrose during early maize germination

In maize, immunoprecipitation assays have shown that CycD2;2 interacts with KRPs. However, evidence on CycD2;2 or KRPs localization and their possible interaction in specific tissues is lacking and its physiological consequence is still unknown. This work explores the spatiotemporal presence of CyclinD2s and KRPs, cell cycle regulators, during maize seed germination (18 and 36 h) after soaking on glucose or sucrose (120 mM). CyclinD2s are positive actors driving proliferation; KRPs are inhibitors of the main kinase controlling proliferation (a negative signal that slows down the cell cycle). Cell cycle proteins were analyzed by immunolocalization on longitudinal sections of maize embryo axis in seven different tissues or zones (with different proliferation or differentiation potential) and in the nucleus of their cells. Results showed a prevalence of these cell cycle proteins on embryo axes from dry seeds, particularly, their accumulation in nuclei of radicle cells. The absence of sugar caused the accumulation of these regulators in different proliferating zones. CyclinD2 abundance was reduced during germination in the presence of sucrose along the embryo axis, while there was an increase at 36 h on glucose. KRP proteins showed a slight increase at 18 h and a decrease at 36 h on both sugars. There was no correlation between cell cycle regulators/DNA co-localization on both sugars. Results suggest glucose induced a specific accumulation of each cell cycle regulator depending on the proliferation zone as well as nuclear localization which may reflect the differential morphogenetic program regarding the proliferation potential in each zone, while sucrose has a mild influence on both cell cycle proteins accumulation during germination. Whenever CycD2s were present in the nucleus, KRPs were absent after treatment with either sugar and at the two imbibition times analyzed, along the different embryo axe zones.

Parallel Chondrogenesis and Osteogenesis Tissue Morphogenesis in Muscle Tissue via Combinations of TGF-β Supergene Family Members.

This study aimed to decipher the temporal and spatial signaling code for clinical cartilage and bone regeneration. We investigated the effects of continuous equal dosages of a single, dual, or triplicate growth factor combination of bone morphogenetic protein (BMP)-2, transforming growth factor (TGF)-β3, and/or BMP-7 on muscle tissue over a culturing period. The hypothesis was that specific growth factor combinations at specific time points direct tissue transformation toward endochondral bone or cartilage formation. The harvested muscle tissues from F-344 adult male rats were cultured in 96-well plates maintained in a specific medium and cultured at specific conditions. And the multidimensional and multi-time point analyses were performed at both the genetic and protein levels. The results insinuate that the application of growth factor stimulates a chaotic tissue response that does not follow a chronological signaling cascade. Both osteogenic and chondrogenic genes showed upregulation after induction, a similar result was also observed in the semiquantitative analysis after immunohistochemical staining against different antigens. The study showed that multiple TGF-β superfamily proteins applied to tissue stimulate developmental tissue processes that do not follow current tissue formation rules. The findings contribute to the understanding of the chronological order of signals and expression patterns needed to achieve chondrogenesis, articular chondrogenesis, or osteogenesis, which is crucial for the development of treatments that can regrow bone and articular cartilage clinically.

Unclassifiable interstitial lung disease and autoimmunity: Towards IPAF in children?

Interstitial pneumonia with autoimmune features (IPAF) has been defined for adults with interstitial lung disease (ILD) and autoimmunity who do not meet the criteria for a specific connective tissue disease (CTD). We aimed to determine whether IPAF criteria could apply to children. We retrospectively studied patients with ILD and autoimmunity followed at Necker Hospital between 2008 and 2019. Children were classified according to specific CTD and IPAF criteria. The epidemiology and course of the disease were studied according to the final diagnosis. Among 27 patients, 6 fulfilled the criteria for IPAF and represented 4.5% of all patients with ILD during the study period. Other diagnoses included juvenile dermatomyositis (30%), overlap syndromes (19%), systemic lupus erythematosus (15%), systemic sclerosis (7%), mixed CTD (4%), and rheumatoid arthritis (4%). IPAF patients were more frequently boys versus CTD-ILD patients (67% vs. 14%, p = .02). Two patients had severe respiratory distress that led to death for one of them. The course was favorable for the others, with a good response to steroids. The course tended to be more favorable for IPAF patients than for those with CTD-ILD (0% lung fibrosis in the IPAF group vs. 43% in the CTD-ILD group, p = .07). We confirmed the existence of IPAF in children. Its prevalence was lower than in adults but comparable to that found for other pediatric series. Boys were more highly represented than in CTD-ILD. The course was favorable for most cases. Larger and more prospective studies are needed to confirm these results.

Hydrogel-Based Formulations for Drug Delivery to the Posterior Segment of the Eye

Hydrogel-based formulations hold significant promise for treating ocular diseases that impact the posterior segment of the eye. These formulations exhibit the ability to surmount ocular barriers and offer sustained drug release, rendering them efficacious drug delivery systems. This article addresses the challenges linked to treating disorders affecting the posterior eye segment and underscores the imperative for less invasive drug delivery methodologies. We further delve into diverse contemporary ocular dosage forms, encompassing gels, nanostructures, and implants, with a specific emphasis on hydrogels. Hydrogels offer several merits, including precise targeting, sustained release, enhanced bioavailability, and non-invasiveness. Moreover, they curtail the risk of adverse effects and foster patient adherence. An enthralling advancement is the amalgamation of hybrid drug delivery systems, integrating nanoparticles, liposomes, dendrimers, and stimuli-activated nano-systems, with hydrogels for posterior eye ailment treatment. These hybrid nano-systems exhibit promise in enhancing drug stability, prolonging drug release, and pinpointing specific tissues within the posterior segment. We also provide an overview of ongoing clinical trials and approved hydrogel-based drug delivery systems, like Retisert and Ozurdex. These systems have demonstrated efficacy in managing chronic non-infectious uveitis, Age-related Macular Degeneration (AMD), and diabetic macular edema. Nevertheless, challenges persist, including optimizing bioavailability, maintaining drug stability, and implementing personalized treatment approaches. The incessant evolution of gel-based drug delivery systems stands to substantially enhance patients’ quality of life and establish new benchmarks in treating posterior eye diseases. The future of ophthalmology brims with excitement, as gel-based drug delivery systems hold the potential to revolutionize ocular therapies, providing effective remedies for an array of vision-related afflictions.

Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking.

The potential of oligonucleotide therapeutics is undeniable as more than 15 drugs have been approved to treat various diseases in the liver, central nervous system (CNS), and muscles. However, achieving effective delivery of oligonucleotide therapeutics to specific tissues still remains a major challenge, limiting their widespread use. Chemical modifications play a crucial role to overcome biological barriers to enable efficient oligonucleotide delivery to the tissues/cells of interest. They provide oligonucleotide metabolic stability and confer favourable pharmacokinetic/pharmacodynamic properties. This review focuses on the various chemical approaches implicated in mitigating the delivery problem of oligonucleotides and their limitations. It highlights the importance of linkers in designing oligonucleotide conjugates and discusses their potential role in escaping the endosomal barrier, a bottleneck in the development of oligonucleotide therapeutics.

Foliar transcriptomes reveal candidate genes for late blight resistance in cultivars of diploid potato Solanum tuberosum L. Andigenum Group.

Characterization of major resistance (R) genes to late blight (LB) -caused by the oomycete Phytophthora infestans- is very important for potato breeding. The objective of this study was to identify novel genes for resistance to LB from diploid Solanum tuberosum L. Andigenum Group (StAG) cultivar accessions. Using comparative analysis with a edgeR bioconductor package for differential expression analysis of transcriptomes, two of these accessions with contrasting levels of resistance to LB were analyzed using digital gene expression data. As a result, various differentially expressed genes (P ≤ 0.0001, Log2FC ≥ 2, FDR < 0.001) were noted. The combination of transcriptomic analysis provided 303 candidate genes that are overexpressed and underexpressed, thereby giving high resistance to LB. The functional analysis showed differential expression of R genes and their corresponding proteins related to disease resistance, NBS-LRR domain proteins, and specific disease resistance proteins. Comparative analysis of specific tissue transcriptomes in resistant and susceptible genotypes can be used for rapidly identifying candidate R genes, thus adding novel genes from diploid StAG cultivar accessions for host plant resistance to P. infestans in potato.

Mechanisms and pathology of protein misfolding and aggregation.

Despite advances in machine learning-based protein structure prediction, we are still far from fully understanding how proteins fold into their native conformation. The conventional notion that polypeptides fold spontaneously to their biologically active states has gradually been replaced by our understanding that cellular protein folding often requires context-dependent guidance from molecular chaperones in order to avoid misfolding. Misfolded proteins can aggregate into larger structures, such as amyloid fibrils, which perpetuate the misfolding process, creating a self-reinforcing cascade. A surge in amyloid fibril structures has deepened our comprehension of how a single polypeptide sequence can exhibit multiple amyloid conformations, known as polymorphism. The assembly of these polymorphs is not a random process but is influenced by the specific conditions and tissues in which they originate. This observation suggests that, similar to the folding of native proteins, the kinetics of pathological amyloid assembly are modulated by interactions specific to cells and tissues. Here, we review the current understanding of how intrinsic protein conformational propensities are modulated by physiological and pathological interactions in the cell to shape protein misfolding and aggregation pathology.

Green tissue-targeted expression of the Cry1Ab/c gene in transgenic maize using the Cre/loxP system as an alternative strategy against lepidopteran pests.

Genetically modified (GM) proteins in edible tissues of transgenic maize are of intense public concern. We provided a Cre/loxP-based strategy for manipulating the expression of transgenes in green tissues while locking them in nongreen tissues. First, the Cre gene was driven by the green tissue-specific promoter Zm1rbcS to generate transgenic maize KEY. Meanwhile, a gene cassette containing a Nos terminator (NosT) in front of the Cry1Ab/c gene was driven by the strong promoter ZmUbi to generate another transgenic maize LOCK. By crossing KEY and LOCK plants, the expressed Cre recombinase under the control of the Zm1rbcS promoter from KEY maize accurately removed the NosT of LOCK maize. Consequently, the expression of blocked Cry1Ab/c was enabled in specific green tissues in their hybrids. The expression level and concentration of Cry1Ab/c were observed using a strategy with high specific accumulation in green tissues (leaf and stem). Still, only a small or absent amount was observed in root and kernel tissues. Furthermore, we assessed the bioactivity of transgenic maize against 2 common lepidopteran pests, Ostrinia furnacalis and Spodoptera frugiperda, in the laboratory and field. The transgenic plants showed high plant resistance levels against the 2 pests, with mortality rates above 97.2% and damage scales below 2.2 compared with the control group. These findings are significant for exploring novel genetic engineering techniques in GM maize and providing a feasible strategy for transgenes avoiding expression in edible parts. In addition, implementing the Cre/loxP-mediated system could relieve public sentiment toward the biosafety of GM plants.

Generation of Conditional Knockout Zebrafish Using an Invertible Gene-Trap Cassette.

Conditional knockout (cKO) is a genetic technique to inactivate gene expression in specific tissues or cell types in a temporally regulated manner. cKO analysis is essential to investigate gene function while avoiding the confounding effects of global gene deletion. Genetic techniques enabling cKO analysis were developed in mice based on culturable embryonic stem cells that were not generally available in zebrafish, which hampered precise analysis of genetic mechanisms of organ development and regeneration. However, recent advances in genome editing technologies have resolved this limitation, providing a platform for the generation of cKO models in any organism. Here we describe a detailed protocol for the generation of cKO zebrafish using a Cre-dependent genetic switch.

Effective investigation of murine femoral bone development utilizing correlative light and electron microscopy (CLEM)

BackgroundFor effective investigation of the developing structure and chemistry of bone, comprehensive studies including compositional analysis can be achieved through the gradual observation from the micro- to nanometer scale via correlative light and electron microscopy (CLEM). This technique is particularly useful considering the complex hierarchical arrangement of bioapatite and collagen fibrils which may vary according to specific bone tissue types (i.e., lamellar bone and woven bone) and different growth stages. Scanning electron microscopy (SEM) accompanied with the attachment of the scanning transmission electron microscopy (STEM) detector, referred to as the STEM-in-SEM can be utilized to produce high contrast images from materials composed of light elements, and efficiently allows the selection of suitable accelerating voltage for energy-dispersive spectroscopy (EDS). This study aims to emphasize the efficacy of CLEM techniques through applying STEM-in-SEM and EDS analyses, and its application to comparative murine bone investigation in differing ontogenetic stages.FindingsWe have designed a new grid-holder which can be used for both light and electron microscopy, and we presented an imaging technique for TEM specimens via reflective light microscopy (RLM). For performing CLEM, ultra-thin-sections (UTS) prepared from the femoral bones of 1- to 16-week old of Sprague-Dawley (SD) rats provided light and electron micrographs that can be correlated based on the regions of interest (ROIs). STEM-in-SEM micrographs revealed information not attainable by secondary electron (SE) and back-scattered electron (BSE) micrographs. In addition, for analyzing chemical variation according to growth and development of femoral bones from 1- to 16-week-old rats, comparative chemical analysis was performed through STEM-in-SEM EDS with two reference materials.ConclusionHerein, from femoral bones of SD rats, we have confirmed the rapid chemical and structural variations within the first 8 weeks after birth. STEM-in-SEM micrographs revealed the bone development process of the early stage porous bone matrix subsequently being filled with collagen fibrils and bioapatite. In addition, chemical analysis for carbon and oxygen showed the ratios of inorganic to organic phases according to growth and progress in bone mineralization. As a result, we were able to postulate the growth mechanism of murine femoral bone in the neonatal stages of development. We also anticipate that our CLEM techniques can be further utilized for more thorough investigation of bone structure and chemistry in diverse scales.

Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms.

The ongoing battle against the coronavirus disease 2019 (COVID-19) pandemic has encountered a complex aspect with the emergence of long COVID syndrome. There has been a growing prevalence of COVID-19-affected individuals experiencing persistent and diverse symptoms that extend beyond the initial infection phase. The phenomenon known as long COVID syndrome raises significant questions about the underlying mechanisms driving these enduring symptoms. This comprehensive analysis explores the complex domain of long COVID syndrome with a view to shed light on the specific tissue and organ pathologies contributing to its intricate nature. This review aims to analyze the various clinical manifestations of this condition across different bodily systems and explore potential mechanisms such as viral persistence, immune dysregulation, autoimmunity, and molecular mimicry. The goal is to gain a better understanding of the intricate network of pathologies contributing to long COVID syndrome. Understanding these distinct pathological indicators provides valuable insights into comprehending the complexities of long COVID and presents opportunities for developing more accurate diagnostic and therapeutic strategies, thereby improving the quality of patient care by effectively addressing the ever-changing medical challenge in a more focused manner.

Space-Flight- and Microgravity-Dependent Alteration of Mast Cell Population and Protease Expression in Digestive Organs of Mongolian Gerbils.

Mast cell (MC)-specific proteases are of particular interest for space biology and medicine due to their biological activity in regulating targets of a specific tissue microenvironment. MC tryptase and chymase obtain the ability to remodel connective tissue through direct and indirect mechanisms. Yet, MC-specific protease expression under space flight conditions has not been adequately investigated. Using immunohistochemical stainings, we analyzed in this study the protease profile of the jejunal, gastric, and hepatic MC populations in three groups of Mongolian gerbils-vivarium control, synchronous experiment, and 12-day orbital flight on the Foton-M3 spacecraft-and in two groups-vivarium control and anti-orthostatic suspension-included in the experiment simulating effects of weightlessness in the ground-based conditions. After a space flight, there was a decreased number of MCs in the studied organs combined with an increased proportion of chymase-positive MCs and MCs with a simultaneous content of tryptase and chymase; the secretion of specific proteases into the extracellular matrix increased. These changes in the expression of proteases were observed both in the mucosal and connective tissue MC subpopulations of the stomach and jejunum. Notably, the relative content of tryptase-positive MCs in the studied organs of the digestive system decreased. Space flight conditions simulated in the synchronous experiment caused no similar significant changes in the protease profile of MC populations. The space flight conditions resulted in an increased chymase expression combined with a decreased total number of protease-positive MCs, apparently due to participating in the processes of extracellular matrix remodeling and regulating the state of the cardiovascular system.

Revolutionizing Drug Delivery: The Potential of PLGA Nanoparticles in Nanomedicine

Abstract: Nanomedicine is an emerging field that utilizes nanoparticles to deliver drugs and other therapeutic agents to specific cells and tissues in the body. One of the most promising materials for creating these nanoparticles is Poly(Lactic-co-glycolic Acid) (PLGA), which has several unique properties that make it well-suited for biomedical applications. These nanomedicines, made from a combination of lactic acid and glycolic acid, can deliver drugs and other therapeutic agents directly to specific cells or tissues in the body. This allows for more precise and targeted treatment, reducing the potential for side effects and improving the effectiveness of the treatment. Additionally, PLGA nanomedicines are biocompatible and biodegradable, making them an attractive option for use in a wide range of biomedical applications to deliver a wide range of drugs, including proteins, peptides, nucleic acids, and small molecules for various biomedical applications such as neurodegenerative, cardiovascular diseases, inflammatory disorders, and cancer. In summary, research on PLGA nanoparticles for biomedical applications is ongoing and has the potential to lead a new and improved treatments for a wide range of diseases and conditions. Looking ahead, PLGA nanoparticles have the potential to revolutionize the way we treat diseases and improve human health. As research continues to advance, we can expect to see new and innovative uses for PLGA nanoparticles in the biomedical field, leading to the development of more effective and targeted therapeutics. The current review focuses on the synthesis, physicochemical properties, biodegradation properties of PLGA, method to prepare PLGA nanoparticles and biomedical application of PLGA. It examines the current progress and future directions for research on PLGA in drug delivery.

3D Hyperspectral Light-Field Imaging: a first intraoperative implementation

Abstract Hyperspectral imaging is an emerging technology that has gained significant attention in the medical field due to its ability to provide precise and accurate imaging of biological tissues. The current methods of hyperspectral imaging, such as filter-wheel, snapshot, line-scanning, and push-broom cameras have limitations such as low spatial and spectral resolution, slow acquisition time. New developments on the field of light field cameras show the potential to overcome these limitations. In this paper, we use a novel hyperspectral lightfield camera and try to combine the capability of hyperspectral and 3D analysis. For this purpose we calibrate our system and test it during two ENT-surgeries to show its potential for improving surgical outcomes. The micro-lenses of the camera map 66 spectral sub-images onto the sensor allowing to reconstruct the spectral behavior of the captured scene in the spectral range of 350-1000nm. In addition, we use the sensor data to apply a 3D camera calibration pipeline to allow 3D surface reconstruction. We captured 26 calibration images and achieved calibration results in accordance to stated company data. The best calibration showed a re-projection error of 0.55 px. Further, we tested the camera during a parotidectomy and a neck-dissection. The extracted reflectance spectra of the selected venal and arterial regions correspond perfectly to the spectrum of oxygenated and deoxygenated hemoglobin. For the first time, up to our knowledge, a hyperspectral lightfield camera has been used during a surgery. We were able to continuously capture images and analyze the reconstructed spectra of specific tissue types. Further, we are able to use the sensor data of the micro-lens projections to calibrate the multilens camera system for later intraoperative measurement tasks.

Spatiotemporal remodeling of extracellular matrix orients epithelial sheet folding.

Biological systems are inherently noisy; however, they produce highly stereotyped tissue morphology. Drosophila pupal wings show a highly stereotypic folding through uniform expansion and subsequent buckling of wing epithelium within a surrounding cuticle sac. The folding pattern produced by buckling is generally stochastic; it is thus unclear how buckling leads to stereotypic tissue folding of the wings. We found that the extracellular matrix (ECM) protein, Dumpy, guides the position and direction of buckling-induced folds. Dumpy anchors the wing epithelium to the overlying cuticle at specific tissue positions. Tissue-wide alterations of Dumpy deposition and degradation yielded different buckling patterns. In summary, we propose that spatiotemporal ECM remodeling shapes stereotyped tissue folding through dynamic interactions between the epithelium and its external structures.

Tissue-specific stilbene accumulation is an early response to wounding/grafting as revealed by using spatial and temporal metabolomics.

Grafting is widely used in horticulture. Shortly after grafting, callus tissues appear at the graft interface and the vascular tissues of the scion and rootstock connect. The graft interface contains a complex mix of tissues, we hypothesised that each tissue has its own metabolic response to wounding/grafting and accumulates different metabolites at different rates. We made intact and wounded cuttings and grafts of grapevine, and then measured changes in bulk flavonoid, phenolic acid and stilbenoid concentration and used metabolite imaging to study tissue-specific responses. We show that some metabolites rapidly accumulate in specific tissues after grafting, for example, stilbene monomers accumulate in necrotic tissues surrounding mature xylem vessels. Whereas other metabolites, such as complex stilbenes, accumulate in the same tissues at later stages. We also observe that other metabolites accumulate in the newly formed callus tissue and identify genotype-specific responses. In addition, exogenous resveratrol application did not modify grafting success rate, potentially suggesting that the accumulation of resveratrol at the graft interface is not linked to graft union formation. The increasing concentration of complex stilbenes often occurs in response to plant stresses (via unknown mechanisms), and potentially increases antioxidant activity and antifungal capacities.

Artificial Intelligence and Computational Pathology: A comprehensive review of advancements and applications

Abstract Conventional pathology is essential for disease diagnosis, but challenges like inter-observer variability can impact treatment decisions. Immunohistochemistry assays improve patient identification, but advanced quantitative tools are needed for accurate marker quantification and spatial analysis. AI enhances accuracy in pathology by contextualizing spatial data and revolutionizing medicine through advanced data processing and machine learning. Clinical informatics and AI integration advance patient care and open new horizons in pathology. Artificial intelligence (AI) is crucial in pathology, leveraging deep learning techniques to integrate pathological images with radiological, clinical, and genomic data. These pattern recognition methods enhance disease diagnosis and prognosis assessment. This review article provides an overview of AI in pathology, recent advancements, and future prospects. It emphasizes digital pathology, image acquisition, data preprocessing, and feature extraction for AI-driven pathology analysis. A comprehensive analysis of the key findings and outcomes from recent studies incorporating AI in pathology is done. A focus on various applications, including but not limited to cancer diagnosis, grading, and prognosis, as well as the identification of specific tissue patterns and rare diseases. The impact of AI on workflow optimization, quality assurance, and predictive analytics in pathology is also discussed. This section explores the implications and challenges of AI adoption in pathology. We discuss benefits like enhanced accuracy and resource allocation but also cover limitations such as dataset requirements, ethics, interpretability, and regulations. Ongoing research and collaborations aim to address these concerns and ensure responsible AI implementation in pathology.

Gastrulation: The mechanism of the spiritual living body

This novel study would describe a new notion about the spirit, whose eternity should anticipate that it couldn’t be incorporated into our cells, rather a particular cell gene would develop during the embryonic period which could receive and decode the higher informational learning knowledge of the Spiritual energy. Gastrulation is a key developmental process during which embryonic pluripotent stem cells of the blastula reorganize into lineage-committed precursor cells to form the gastrula. Gastrulation takes place after cleavage and the formation of the blastula. The inner cell mass of embryo is pluripotent during this stage, meaning that each cell has the potential to differentiate into any cell type in the human body (organogenesis). When individual organs develop within the newly formed germ layers, then each layer gives rise to specific tissues and organs in the developing embryo. The nodal signaling pathway has a significant role in regional and cellular differentiation during development. The nodal family of proteins, a subset of the transforming growth factor beta (TGFβ) superfamily is responsible for patterning of the nervous system, It is evident that the embryo is formed in the third week post-fertilization and is accompanied by the process of brain formation that requires regulatory signals for the cells by a variety of genes that work like a communication network, during which the pluripotent embryonic stem cells and the signal induction of the homeobox genes are reorganized to plan the development and the future of embryo. Organizational plan does not take place unless a maximum information momentum is available with the highest concentration of information energy. This is the right time to blow the spirit to supply informational energy. Spirit is the eternal energy of universal cosmic information that formulate the higher cognition and consciousness of the human being, specifically, Adam’s sons.