At Longevity Horizon (Online ISSN: 3088-4063), we unite leading researchers and innovators to advance transformative technologies that will shape the future. Bringing together experts from diverse fields, we cultivate an environment where impactful ideas and scientific breakthroughs can emerge. Our mission is to support collaboration and make cutting-edge knowledge accessible to the global community, promoting research that improves lives and contributes to a sustainable, thriving future. Our platform provides high-quality, peer-reviewed articles that drive scientific progress. These contributions help turn such visions as expanded living space, optimal health, food security, and even the pursuit of radical longevity into realistic possibilities. This is an open access journal, meaning all content is freely available to read, download, copy, distribute, print, search, or link, in accordance with the BOAI definition of open access. Immortalitas in Hac Vita
A Murine Model Yielding Functional Sperm and Implications for Human In Vitro Gametogenesis
The reconstitution of complete spermatogenesis in vitro remains a pivotal challenge in reproductive biology, with transformative potential for treating infertility and modeling disease. This study establishes a three-step protocol for synthetic spermatogenesis, enabling the generation of functional spermatozoa from mouse and human pluripotent stem cells (PSCs). Initially, PSCs were efficiently differentiated into primordial germ cell-like cells (PGCLCs) with appropriate epigenetic reprogramming. PGCLCs were then co-cultured with primary testicular somatic cells on a 3D scaffold, where they self-organized into seminiferous tubule-like structures. Sequential hormonal stimulation with retinoic acid, testosterone, and follicle-stimulating hormone (FSH) drove meiotic progression and haploid spermatid formation. In the mouse system, complete spermiogenesis was achieved, yielding sperm capable of fertilizing oocytes via intracytoplasmic sperm injection (ICSI) and producing healthy, fertile offspring. Human PGCLCs entered meiosis and formed haploid cells, but terminal spermiogenesis efficiency remained low. This work provides a foundational model for in vitro gametogenesis, offering new avenues for studying male reproduction and addressing absolute infertility, while highlighting critical technical and ethical considerations.
Copyright (c) 2026 Iason Papadopulo (Author) https://creativecommons.org/licenses/by/4.0/
In vitro gametogenesis (IVG)—the generation of functional gametes from pluripotent or somatic cells in culture—represents a paradigm-shifting frontier in reproductive medicine with the potential to address absolute infertility (Saitou & Hayashi, 2021). This review synthesizes the current state and formidable challenges of human oocyte IVG. We detail the two primary strategies: the stepwise differentiation of induced pluripotent stem cells (iPSCs) through a primordial germ cell-like cell (PGCLC) intermediate, and the direct reprogramming of somatic cells. Both pathways confront significant biological barriers, including the achievement of complete epigenetic reprogramming and correct genomic imprinting, the faithful completion of meiosis I to prevent aneuploidy, and the acquisition of cytoplasmic competence (Seisenberger et al., 2012; Nagaoka, Hassold, & Hunt, 2012). Critically, oocyte development is inseparable from its somatic niche; thus, advances in ovarian organoids and 3D biofabrication are essential to reconstruct the follicular microenvironment (Laronda et al., 2017; Sun, Parikh, & Fuller, 2022). Beyond the laboratory, IVG raises profound ethical and social questions concerning reproductive longevity, embryo selection, the redefinition of parenthood, and equitable access (Greely, 2016; Mathews, Morain, & Finkelstein, 2017). We conclude that while mouse models prove principle, translation to humans requires solving fundamental biological puzzles and concurrently developing rigorous ethical and regulatory frameworks. The clinical application of IVG, likely decades away, must be guided by a paramount commitment to offspring safety and inclusive public discourse.
Copyright (c) 2026 Alexander Taktakidze (Author) https://creativecommons.org/licenses/by/4.0/
Centriole Regulation in Natural and Artificial Gametogenesis
Centriole elimination is an evolutionarily conserved, essential process during gametogenesis that resets centrosome number to prevent aneuploidy in the zygote (Schatten & Sun, 2011). While in vitro gametogenesis (IVG) from pluripotent stem cells offers transformative potential for reproductive medicine, its fidelity in recapitulating key cytoplasmic organelle reprogramming events remains poorly characterized. This study presents a systematic comparative analysis of centriole elimination dynamics between natural mouse gametogenesis and leading IVG protocols. Employing high-resolution imaging, molecular profiling, and functional embryogenesis assays, we demonstrate that IVG-derived gametes exhibit profound defects. Centriole elimination in vitro is asynchronous, frequently incomplete, and driven by a dysregulated molecular cascade, leading to the persistent retention of structurally aberrant centrioles (Clift & Schuh, 2013). These organelles act as ectopic microtubule-organizing centers, causing multipolar spindle formation during meiosis and the first embryonic division. Consequently, embryos from IVG gametes with centriole retention suffer catastrophic failure, characterized by severe chromosome segregation errors and preimplantation arrest (Hendriks, Dancet, van Pelt, Hamer, & Repping, 2015). Our findings establish centriole elimination fidelity as a critical, previously overlooked benchmark for IVG. They reveal that the artificial microenvironment fails to provide the precise niche signaling required for this stringent developmental program, highlighting a major safety consideration and providing a mechanistic roadmap for refining synthetic gametogenesis protocols.
Copyright (c) 2026 Gabro Gakely (Author) https://creativecommons.org/licenses/by/4.0/
Mesenchymal Progenitor Cell Resilience Counteracts Tissue Aging
The age-related functional decline of mesenchymal stromal/progenitor cells (MSCs) is a central driver of skeletal aging, leading to osteoporosis and impaired tissue regeneration (Li, Wu, & Tuan, 2019). Challenging the paradigm of a uniformly aging MSC pool, this study identifies a rare subpopulation of mesenchymal progenitors with innate senescence resistance, termed Senescence-Resistant Committed progenitors (SRCs). Isolated from aged murine and human tissues via a unique immunophenotype (CD45⁻CD31⁻CD34⁻CD73⁺CD90⁺CD105⁺CD200⁺ITGA10⁺), SRCs demonstrated remarkable numerical preservation compared to severely depleted classical MSCs. Functionally, aged SRCs maintained low senescence markers (p16INK4a, SA-β-gal), lacked a pro-inflammatory secretome, and retained high clonogenic, proliferative, and osteogenic potential, countering the age-related adipogenic shift (Moerman, Teng, Lipschitz, & Lecka-Czernik, 2004). Transcriptomic and epigenetic profiling revealed that SRC resilience was underpinned by constitutive activation of DNA repair, antioxidant defense (NRF2), and mitochondrial homeostasis pathways, stabilized by a protective epigenetic landscape featuring *CDKN2A/p16* promoter hypomethylation (Sun, Coppe, & Lam, 2018). In vivo, transplantation of aged SRCs significantly enhanced bone regeneration in critical-sized defects compared to aged bulk MSCs. This discovery reframes mesenchymal aging, revealing a resilient cellular reservoir essential for tissue homeostasis. Targeting the SRC pool or mimicking its molecular signature represents a novel therapeutic frontier for age-related skeletal disorders.
Copyright (c) 2026 Laura Gegelia (Author) https://creativecommons.org/licenses/by/4.0/
The Strength of Clay, The Weakness of Gods
The Standard Babylonian Epic of Gilgamesh is traditionally interpreted through the archetype of the heroic king and his wild companion. This article challenges that reading by arguing that the epic systematically inverts these roles to conduct a profound philosophical investigation into the nature of strength. Through close textual analysis framed by contemporary psychological and ecological theory, it demonstrates that Gilgamesh, despite his divine lineage and royal power, is characterized by profound existential, cognitive, and emotional weaknesses. His rule begins in tyrannical hybris, he depends entirely on others to interpret his own subconscious (dreams), and his response to mortality is a pathological flight into denial. In contrast, Enkidu, created from primal clay, embodies an integrated strength rooted in ecological harmony, hermeneutic wisdom, and, ultimately, stoic acceptance of his fate. The analysis further explores the tragic irony of their bond: Gilgamesh’s civilizing process actively weakens Enkidu, severing his connection to his natural strength and rendering him vulnerable to divine retribution. The epic’s resolution is found not in the victory of one archetype but in their synthesis. Gilgamesh’s journey evolves from a quest for personal immortality to an embrace of symbolic immortality through his cultural legacy—the walls of Uruk. This represents a hard-won integration of Enkidu’s lesson of acceptance with his own rebellious drive to transcend limits. The article concludes that the epic redefines true strength not as an innate attribute of divinity or nature, but as a dynamic, earned wisdom forged through relationship, loss, and the creative confrontation with human finitude.
Copyright (c) 2026 Jaba Tkemaladze (Author) https://creativecommons.org/licenses/by/4.0/
This paper posits that the most significant long-term existential risk to human civilization is not an acute technological or environmental catastrophe, but a chronic, systemic decay driven by the psychological and demographic consequences of a biologically capped lifespan. The entrenched expectation of mortality before 120 years fosters a condition of "temporal myopia," which cultivates cultural short-termism, consumerist nihilism, and demographic apathy. A critical and compounding aspect of this risk is the observed strong negative correlation between high cognitive ability and reproductive rates, leading to a systematic, dysgenic drain on humanity's problem-solving capacity. This creates a recursive threat far greater than any single hazard, as it erodes the intellectual capital necessary to navigate all other complex challenges. To counter this civilizational trajectory, we propose a novel biomedical paradigm: a strategy of continuous personal rejuvenation. This approach is based on utilizing in-vitro gametogenesis to generate autologous gametes, followed by auto-fertilization to create a new embryonic lineage. This protocol enables a comprehensive reset of cellular age, including the critical de novo formation of young centrioles, addressing the Centriolar Theory of Organismal Aging. The resulting young, perfectly matched adult stem cells are proposed for periodic autologous transplantation to maintain the body's regenerative potential indefinitely. We argue that this intervention transcends its medical purpose. By enabling the indefinite maintenance of cognitive and physical vitality, it allows the most capable individuals to remain active contributors for centuries, provides time for wisdom to accumulate, and transforms detrimental demographic structures. Therefore, rejuvenation biotechnology should be framed not as a mere luxury, but as a necessary civilizational safeguard—a strategic imperative to prevent a slow-motion intellectual and demographic collapse and to secure a flourishing long-term future for humanity.
Sequential data prediction represents a fundamental challenge across multiple domains, from genomic analysis to clinical monitoring, requiring sophisticated approaches that balance predictive accuracy with computational efficiency. This paper introduces Ze, a novel hybrid system that integrates frequency-based counting with hierarchical Bayesian modeling to address the complex demands of sequential pattern recognition. The system's architecture employs dual-processor analysis with complementary beginning (forward) and inverse (backward) processing strategies, enabling comprehensive pattern discovery that captures both progressive sequences and symmetrical structures. At its core, Ze implements a three-layer hierarchical Bayesian framework that operates at individual, group, and context levels, facilitating multi-scale pattern recognition while naturally quantifying prediction uncertainty. The individual layer employs Beta-Binomial conjugate priors for sequential Bayesian updating, while the group layer enables knowledge transfer across related patterns through shared hyperparameters. The context layer incorporates temporal dependencies through configurable sequence memory, capturing crucial short-term patterns that significantly influence prediction accuracy. Implementation results demonstrate that the hierarchical Bayesian approach achieves an 8.3% accuracy improvement over standard Bayesian methods and 2.3× faster convergence through efficient knowledge sharing. The system maintains practical computational efficiency through sophisticated memory management, including automatic counter reset mechanisms and compact binary representations that reduce storage requirements by 45%. Ze's modular design and open-source availability ensure broad applicability across diverse domains including genomic sequence annotation, clinical time series forecasting, and real-time anomaly detection. The system represents a significant advancement in sequential data prediction methodology, combining statistical rigor with computational practicality to address complex pattern recognition challenges in scientific and clinical applications.
This article proposes the "Heroic Self-Myth Hypothesis," a transdisciplinary framework explaining a specific pathology of modern identity construction. Through a detailed analysis of Dostoevsky’s Smerdyakov (The Brothers Karamazov) as a conceptual prototype for Joyce’s characters in Ulysses, the article argues that a pervasive psychological mechanism involves transforming banality into pseudo-heroism to compensate for a profound internal vacuum. The hypothesis posits a sequence of neurocognitive and clinical processes: a dysregulated Default Mode Network fails to generate a coherent self-narrative, creating an existential void. This void is managed through performative substitution, where a hyper-vigilant Salience Network directs attention to external appearances as a substitute for internal substance. This process is catalyzed by developmental traumas, including paternal conflict rooted in envy and a traumatic maternal relationship leading to a fixation on physicality as a threat. The resulting moral disengagement and annihilation of a stable ethical core, often justified by a vulgarized "death of God" liberal philosophy, create a psychic vacuum. This vacuum is subsequently colonized by an "epic self-deception," a grandiose cognitive narrative that reframes a mundane life as a mythic journey. Synthesizing literary analysis, neurobiology, and clinical psychology, the article concludes that Smerdyakov represents not merely a literary character but an archetype of moral disintegration. The modernist hero is thus revealed not as an artistic innovation but as the aesthetic realization of a pre-existing psychological type—the individual who, having lost their moral center, elevates their own insignificance to cosmic significance through a self-authored, illusory heroism.
The paradigm of set , developed by the Georgian psychologist D. Uznadze, represents a foundational yet often overlooked contribution to the science of non-conscious behavioral regulation. This article provides a comprehensive theoretical and experimental analysis of the set phenomenon, revisiting its core premise as a holistic, pre-conscious state that arises from the interaction of a subject's need and the objective situation, thereby determining the direction of subsequent mental activity. We systematically examine the classical haptic methodology—a two-phase experiment involving set-inducing and critical trials—and its modern modifications, including visual, computerized, and cross-modal paradigms that enhance its precision and scope. The analysis confirms the diagnostic power of set parameters, linking individual differences in set strength and lability to cognitive rigidity or flexibility, with significant implications for developmental, clinical, and neuropsychology. Furthermore, we integrate classical theory with contemporary neuroscience, framing set within the predictive coding framework and identifying its neurophysiological substrates in a distributed network including the basal ganglia for habit formation, the prefrontal cortex for cognitive control, and sensory association areas for perceptual integration. The article concludes by highlighting the paradigm's significant potential as a quantitative diagnostic tool and proposes future research directions, including the exploration of its neurochemical bases, its role in social cognition and implicit bias, and the development of cognitive training interventions to enhance behavioral flexibility.
Lake Aquaculture for Catastrophic Food Security
The intensifying frequency of climate disasters, geopolitical conflicts, and pandemics exposes critical vulnerabilities in globalized, input-intensive food systems. Traditional protein sources—terrestrial livestock, crops, and marine fisheries—are highly susceptible to collapse under such catastrophic scenarios due to their dependencies on complex supply chains, external inputs, and stable climatic conditions. This article posits that lake-based aquaculture represents a strategically undervalued yet indispensable component of a resilient food security framework. We argue that the inherent characteristics of lacustrine systems—including superior feed conversion ratios, the utilization of natural trophic pathways, and a static "live storage" production model—confer a unique capacity to function autonomously during prolonged infrastructural and logistical breakdowns. The analysis delineates criteria for selecting resilient fish species, advocates for extensive polyculture management models, and outlines strategies for mitigating risks related to disease, genetic resource security, and ecological degradation. Furthermore, a strategic roadmap is proposed for integrating this approach into national policy, emphasizing legislative action, targeted research, economic incentives, and specialized education. The conclusion asserts that proactive investment in developing lake aquaculture as a decentralized protein reserve is a critical imperative for enhancing national food sovereignty and long-term survivability in an era of escalating systemic risks.
This article presents the Ze artificial life system, a novel bio-inspired architecture for predictive processing in infinite data streams under severe memory constraints. The system implements Bayesian probability updating through a mechanism of dynamic chronotropic frequency analysis, demonstrating remarkable computational efficiency and biological plausibility. Unlike traditional approaches such as LSTM networks and Markov models, Ze processes information through parallel beginning and inverse processors, enabling complementary pattern discovery while maintaining sublinear memory complexity. The core algorithm exhibits distinctive probability dynamics characterized by an initial match probability of 0.5 with exponential decay to 0.00001 as counter diversity increases, achieving 78-92% prediction accuracy for stable data flows. Experimental results using synthetic datasets (1,048,576 binary sequences) confirm 37-42% operational savings compared to conventional methods, rapid adaptation to changing stream characteristics within 2-3 seconds, and robust noise tolerance up to 15% input distortion. The Go implementation processes 1.2 million operations per second with 850 nanosecond latency while maintaining memory usage of 12.8 bytes per counter. The system's architecture shows strong neurobiological correlations with predictive coding principles and synaptic plasticity mechanisms, providing both a practical solution for resource-constrained environments and a computational model of Bayesian inference in neural systems. Future development pathways include extension to non-binary data streams, integration with hierarchical Bayesian models, and hardware acceleration through memristor-based implementations.
Concept of Death Awareness as an Existential Regulator in the Age of Biological Immortality
The rapid advancement of biogerontology, particularly through interventions like senolytic therapies and stem cell rejuvenation, is transforming the prospect of radical life extension and even biological immortality from science fiction into a plausible future scenario. This impending paradigm shift necessitates a profound re-examination of existential psychology, which has traditionally posited awareness of mortality as the fundamental source of life's meaning, motivation, and authenticity. This article argues that the psychological phenomenon of death awareness would not simply vanish with the elimination of biological finitude. Instead, it would undergo a critical functional transformation. It proposes the concept of an "existential alarm clock," a reconstituted internal mechanism that shifts from serving as a chronological limit to acting as a qualitative regulator of existence. In a state of immortality, this alarm would awaken the individual from the unique perils of an endless lifespan: existential apathy, identity stagnation, and the "bad infinity" of undifferentiated time. The article analyzes the mechanisms of this alarm—triggering identity crises, combating profound boredom, and stimulating self-transcendence—and explores its vast social, cultural, and ethical implications. It concludes that, paradoxically, a continued dialogue with the concept of death remains a crucial condition for a meaningful and authentic life, even in the context of biological immortality.
Induction of de novo centriole biogenesis in planarian stem cells
The centriole is a fundamental organelle templating cilia formation and ensuring genomic stability. While most cells assemble centrioles using a pre-existing mother as a template, the de novo pathway allows for assembly in their absence. However, the physiological role and regulation of de novo biogenesis in vivo remain poorly understood. The planarian Schmidtea mediterranea, with its abundant somatic stem cells (neoblasts) and dependence on a massive ciliated epithelium for locomotion, presents a unique model to address this gap. We demonstrate that quiescent neoblasts are acentriolar, lacking the templates for canonical duplication. Upon tissue injury, neoblasts are activated and initiate a programmed de novo centriole biogenesis pathway. Super-resolution microscopy and transmission electron microscopy reveal the formation of cytoplasmic procentriolar foci and mature centrioles, independent of any parental structure. Crucially, genetic ablation of Sas-6 or pharmacological inhibition of PLK4—interventions that effectively block the canonical pathway—fail to prevent the formation of new centrioles and functional basal bodies in the regenerating ciliated epithelium. This work provides the first in vivo evidence in a whole organism for an induced de novo centriole biogenesis pathway in adult somatic stem cells. We propose this pathway is a key evolutionary adaptation, enabling rapid, large-scale ciliogenesis essential for planarian regeneration, and represents a distinct, genetically regulated program separable from canonical duplication.
Exploring the Chemical Composition, Therapeutic Properties, and Innovative Delivery Methods of Melissa officinalis
Melissa officinalis L., colloquially termed lemon balm, stands as a preeminent medicinal herb lauded for its intricate phytochemical matrix and diverse therapeutic applications. This comprehensive review synthesizes contemporary research on its chemical constituents, pharmacological efficacy, and advancements in nanotechnology-driven delivery platforms. The plant’s bioactive arsenal—encompassing flavonoids, terpenoids, phenolic acids, and volatile oils—exerts antioxidant, antimicrobial, anti-inflammatory, and neuroprotective effects. Innovations in drug delivery, such as nanoemulsions, lipid nanoparticles, and polymeric films, aim to enhance bioavailability and therapeutic precision. By integrating multidisciplinary insights, this article underscores the imperative for continued exploration of Melissa officinalis in modern pharmacotherapy.
Different Molecular Pathways of Cardiovascular Aging
Aging is an inevitable process that affects every living organism. It is a bodys response to a variety of stressors and is connected to many chronic diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cardiovascular disease… The aim of this review was to further comprehend the mechanisms of aging process and its effect on cardiovascular system. For collecting sufficient data, different scientific databases were used. In the end, there is no exact conclusion of exactly what causes aging, instead we have different theories of its molecular origins such as: oxidative stress, general wear-and-tear and genetic instability, mitochondrial genome damage, telomere shortening, genetic aging programs… Aging process, especially oxidative stress plays a major role in the pathophysiology of cardiomyocyte senescence. Biological compounds like MicroRNAs, SIR1 gene, NF-κB and IL-4, P66Shc, AMP-activated kinase (AMPK) has also been shown to participate or conduct molecular pathways that take part in aging process as well.
The Tkemaladze Method maps cell lineage with mutant mitochondrial transfer
The comprehensive mapping of cellular lineages from the zygote to a fully formed organism remains a fundamental and unresolved challenge in developmental biology. While modern single-cell technologies offer snapshots of cellular heterogeneity, they lack the inherent, permanent markers required to trace progeny through the complex events of asymmetric division and migration over time. This work introduces the Tkemaladze Method, a novel lineage-tracing approach that utilizes mutant mitochondrial DNA (mtDNA) as a stable, inheritable genetic label. The method involves the isolation of mitochondria from cytoplasts harboring known pathogenic mtDNA mutations and their microinjection into murine embryonic stem cells (mESCs). We confirmed successful transfer and functional integration via fluorescence microscopy and quantitative PCR. These labeled progenitor cells were used to generate chimeric embryos, where we demonstrated stable heteroplasmy and faithful inheritance of the mutant mtDNA in clonal progeny throughout development. Using fluorescent reporters, we visualized the fate of individual progenitors, enabling the quantitative construction of a detailed cytogenealogical map across tissues like the central nervous system, liver, and myocardium. A key finding was the tissue-specific segregation of mitochondrial tags, revealing selective pressure in high-energy-demand tissues. The Tkemaladze Method thus provides an unprecedented, powerful tool for fundamental developmental biology, disease modeling, and tracking the fate of transplanted cells in regenerative medicine.
The dramatic decline in human lifespan described in the biblical genealogies of Genesis 5 and 11 presents a unique intersection of theological narrative and biological inquiry. This paper proposes a multidisciplinary theory to explain this phenomenon, integrating textual analysis with principles from biogerontology and population genetics. We argue that the Genesis Flood narrative represents a catastrophic event that triggered a fundamental shift in human life-history strategy. Statistical analysis of the biblical data reveals a synchronized decline in total lifespan, age at sexual maturity, and reproductive window—a triad consistent with an adaptive transition from a slow to a fast life-history strategy in response to postdiluvian environmental harshness and a genetic bottleneck. This model explains the decline as a trade-off favoring rapid reproduction over somatic maintenance. The case of Job’s divinely granted 140 years is analyzed not as a reversion to antediluvian norms, but as a supernatural blessing within the new biological paradigm, affirming divine sovereignty over natural law. The study concludes that the biblical account, while theological in purpose, exhibits an internal consistency with modern biological principles, offering a coherent framework for understanding this ancient mystery.
Production of Functional Gametes from Somatic Cells of the Planarian Schmidtea Mediterranea Via in Vitro Gametogenesis
This study establishes a novel and robust protocol for the direct reprogramming of differentiated somatic cells into functional gamete precursors in the planarian Schmidtea mediterranea, bypassing the need for a pluripotent intermediate state. Through an optimized two-phase in vitro gametogenesis (IVG) protocol involving transient low-dose Yamanaka factor exposure followed by a defined germline-commitment cocktail, we successfully redirected cell fate. Molecular analyses confirmed a stepwise transcriptional and epigenetic reprogramming towards a germline identity, marked by the activation of conserved markers (vasa, nanos, sycp1/3) and global DNA demethylation. While in vitro-derived cells (gametocytes) displayed characteristic oocyte-like and spermatid-like morphologies and ultrastructures, full terminal maturation required in vivo transplantation. Crucially, these IVG-derived gametocytes demonstrated full functionality: upon injection into sterilized recipients, they migrated to gonads, completed maturation, and produced viable, genetically donor-derived offspring. This work provides a powerful platform for studying germ cell development and represents a significant proof-of-concept for somatic cell-to-gamete conversion.
Unlocking the Voynich Cipher via the New Algorithmic Coding Hypothesis
The Voynich Manuscript (VM) remains one of history's most perplexing cryptographic and linguistic puzzles (Landini & Foti, 2020). This paper introduces a novel hypothesis: that the VM's text is not a direct encoding of a natural language but represents a compressed data stream utilizing principles analogous to modern LZ77 compression and Huffman coding (Huffman, 1952; Ziv & Lempel, 1977). We propose that the manuscript's unusual statistical properties, including its low redundancy and specific word structure, are artifacts of a sophisticated encoding process rather than features of an unknown language (Montemurro & Zanette, 2013; Reddy & Knight, 2011). To evaluate this, we developed a computational framework that treats VM transliterations as a encoded bitstream. This framework systematically tests decompression parameters, using Shannon entropy as a primary fitness metric to identify outputs resembling natural language (Shannon, 1948; Cover & Thomas, 2006). While a complete decipherment is not yet achieved, this methodology provides a new, rigorous, and reproducible computational approach to VM analysis, moving beyond traditional linguistic correlation (Hauer & Kondrak, 2011). The framework's architecture and initial proof-of-concept results are presented, outlining a clear pathway for future research with a fully digitized VM corpus.
Why do planarian cells without centrioles divide and cells with centrioles do not divide?
Planarians present a unique cellular paradox: their proliferative stem cells (neoblasts) completely lack centrioles, while their post-mitotic, differentiated cells possess them. This review investigates the mechanisms and biological significance of this inverse correlation. We synthesize evidence demonstrating that neoblasts employ a robust, evolutionarily conserved acentrosomal pathway for spindle assembly, reliant on chromatin-mediated nucleation via RanGTP and motor protein-driven self-organization. This adaptation potentially confers advantages including enforced asymmetric division, metabolic economy, and a significantly reduced risk of centrosome amplification-driven genomic instability, which may underpin the planarians' extensive regenerative capabilities and resistance to tumors. Conversely, the quiescence of centriole-bearing somatic cells is not caused by the organelles themselves but is a consequence of terminal differentiation. These cells epigenetically silence the cell cycle machinery and repurpose centrioles as basal bodies for ciliogenesis. The presence of centrioles is thus a marker, not a driver, of the differentiated state. This system represents a profound uncoupling of the mitotic apparatus from the centriole, offering novel insights into stem cell biology, alternative modes of cell division, and providing conceptual frameworks for regenerative medicine and cancer research.
A Novel Integrated Bioprocessing Strategy for the Manufacturing of Shelf-Stable, Nutritionally Upgraded Activated Wheat: Development of a Comprehensive Protocol, In-Depth Nutritional Characterization, and Evaluation of Biofunctional Properties
Wheat, a cornerstone of global nutrition, possesses inherent nutritional constraints primarily due to the presence of phytic acid, which significantly impedes mineral bioavailability. The process of sprouting has been identified as a promising biological strategy to mitigate these limitations and enhance the nutrient profile. However, a major industrial challenge remains: the pronounced perishability and microbial instability of sprouted grains, which limits their practical application in food systems. The principal aim of this investigation was to conceive, engineer, and rigorously validate an innovative and scalable biotechnological procedure for the generation of shelf-stable activated wheat. This protocol adheres to stringent technical criteria, including the avoidance of aerial agitation, the implementation of in-vessel dehydration, and the exclusion of convective heat transfer mechanisms. The methodology centered on the design and operational characterization of a Multi-Function Bioreactor (MFB) system. A comparative examination was executed, pitting the novel protocol against two control processes: traditional laboratory-scale sprouting techniques and historical Georgian artisanal practices. A exhaustive analytical framework was employed, encompassing detailed nutritional assessment (targeting phytic acid, essential vitamins, and macro- and micro-minerals) and comprehensive biochemical evaluation (focusing on antioxidant potential and protein profile modifications). The implemented protocol yielded a highly successful reduction of phytic acid content, exceeding 60%. Furthermore, it facilitated a substantial augmentation in the concentrations of B-complex vitamins, notably a 30% increase in Thiamine (B1), a 25% rise in Riboflavin (B2), and a 50% enhancement in Folate levels. The antioxidant capacity, as quantified by DPPH radical scavenging assays, reached an impressive 89%. Critically, the final product achieved a shelf-stable format, demonstrating no significant nutritional degradation over a period exceeding 12 months. The innovative methodology described herein effectively translates a traditional food processing concept into a sophisticated, reproducible, and industrially viable biotechnological operation. The resultant product is a premium-grade, shelf-stable functional food ingredient, whose enhanced nutritional credentials have been thoroughly validated through empirical analysis.
The Tkemaladze Method: A Modernized Caucasian Technology for the Production of Shelf-Stable Activated Wheat with Enhanced Nutritional Properties
This paper describes an advanced technological protocol for the production of activated wheat, developed by Tkemaladze et al. and based on traditional Caucasian sprouting practices. The method addresses the critical limitation of traditional sprouted wheat—its high perishability—through the introduction of precise control over activation parameters and a novel low-temperature drying stage. The resulting product is a shelf-stable ingredient (6-12 month stability) with a guaranteed low phytic acid content and preserved high bioactivity. Analytical comparisons confirm that the wheat produced by this method exhibits superior nutritional properties, including higher mineral bioavailability and enhanced antioxidant capacity, compared to samples prepared using standard laboratory sprouting protocols. The Tkemaladze method represents a significant step towards the standardization and commercial scalability of activated wheat for the functional food and nutraceutical industries.
The Stage of Differentiation Into Mature Gametes During Gametogenesis in Vitro
In vitro gametogenesis (IVG) stands as a revolutionary breakthrough in reproductive biology, offering the unprecedented capability to generate functional gametes from pluripotent stem cells (PSCs). This comprehensive review systematically consolidates contemporary advancements in the differentiation of PSCs into mature germ cells, with a particular emphasis on the pivotal stages governing this intricate process: the formation of primordial germ cells (PGCs), the execution of meiotic division, and the final maturation of gametes. Special attention is devoted to the molecular mechanisms orchestrating each differentiation phase, including the critical roles of BMP and WNT signaling pathways, as well as transcription factors such as PRDM1 and SOX17. In murine models, IVG technology has yielded remarkable outcomes—functional oocytes and spermatozoa capable of successful fertilization and the production of healthy offspring have been reliably generated. However, when applied to human cells, researchers encounter substantial challenges, including suboptimal differentiation efficiency (ranging from 20-40% for PGCs and plummeting to less than 1% for meiotic entry), epigenetic aberrations, and the inadequacy of current in vitro culture systems. This review meticulously examines these limitations and proposes potential strategies to overcome them, such as the integration of organoid technologies, CRISPR-based screening, and epigenetic modulators. The clinical prospects of IVG encompass the treatment of diverse infertility disorders, preimplantation genetic diagnostics, and the conservation of genetic diversity in endangered species. Particular emphasis is placed on the ethical dimensions of this technology and the urgent necessity for establishing international regulatory standards to govern its clinical application. The review underscores the importance of a multidisciplinary approach, merging insights from cell biology, genetic engineering, and reproductive medicine to propel this promising field forward.
Induction of germline-like cells (PGCLCs)
Investigations into primordial germ cell-like cells (PGCLCs) constitute a rapidly evolving frontier in reproductive biology and regenerative medicine, offering transformative potential for both basic research and clinical applications. These in vitro-derived PGCLCs, generated either from pluripotent stem cells (including embryonic and induced pluripotent stem cells) or through direct somatic cell reprogramming, serve as indispensable models for elucidating the intricate molecular mechanisms governing gametogenesis, large-scale epigenetic reprogramming events, and the pathophysiology underlying various forms of infertility. Seminal advancements in this domain include the establishment of robust differentiation protocols employing critical signaling molecules such as bone morphogenetic proteins (BMPs), WNT pathway agonists, and retinoic acid derivatives, alongside innovative approaches involving direct lineage conversion of somatic cell types. Nevertheless, persistent challenges remain, particularly concerning the incomplete recapitulation of epigenetic reprogramming fidelity and suboptimal differentiation efficiencies observed in human cellular systems compared to murine models. The potential applications of PGCLC technology span diverse areas including but not limited to: novel infertility interventions, precise genetic correction of heritable disorders through advanced gene editing techniques, and groundbreaking conservation strategies for endangered species preservation. Importantly, the ethical and regulatory landscapes surrounding artificial gamete derivation, including ontological status considerations and longitudinal safety assessments for potential offspring, necessitate ongoing multidisciplinary discourse and policy development.
Through In Vitro Gametogenesis — Young Stem Cells
In vitro gametogenesis (IVG) represents a groundbreaking technology that opens new horizons in reproductive and regenerative medicine. Recent advancements enable the direct reprogramming of somatic cells into germline cells, bypassing the pluripotency stage, which reduces the risk of genetic abnormalities and accelerates the process. The key stages of IVG include the induction of primordial germ cell-like cells (PGCLCs), differentiation into mature gametes, and the formation of functional germ cells under controlled conditions. The primary signaling pathways involved in this process are BMP, WNT, and retinoic acid, which regulate initiation, proliferation, and meiotic entry. To accurately replicate the gonadal microenvironment, researchers employ 3D cultures, organoid systems, and microfluidic devices. Despite significant progress, the efficiency and quality of in vitro-derived gametes still fall short of their natural counterparts. Future developments in this technology hinge on optimizing differentiation protocols, leveraging single-cell technologies, integrating genome editing, and establishing international standards. Additionally, IVG holds promise for systemic rejuvenation by replacing aged stem cells with young ones derived from reprogrammed cells. Ethical and regulatory concerns remain pressing, particularly regarding artificial embryo creation and potential social inequalities. IVG has the potential to become a cornerstone technology in treating aging, extending healthy lifespan, addressing age-related diseases, and overcoming infertility.
This article presents an innovative predictive model of the world based on dynamic updating and adaptive filtering of predicates. The system processes elementary units of information - "crumbs" - to build a probabilistic picture of the environment, demonstrating an initial probability of matches of 0.5 and exponential decay to 0.00001 as the number of counters increases. Key mechanisms include: (1) updating significant patterns with PredictIncrement=2, (2) filtering rarely used predicates while maintaining plasticity balance (γ≥0.95), and (3) resource-efficient architecture providing 37-42% computational savings. Experimental results show prediction accuracy of 78-92% for stable flows, adaptation speed of 2-3 seconds, and robustness to 15% noise. A comparative analysis revealed advantages over LSTM networks (3 times less training data) and Markov models (40% higher adaptability). The model exhibits biologically plausible properties, including nonlinear attention distribution and energy efficiency similar to that of the neocortex (40-45%). Application prospects include IoT, cybersecurity and power system management, and further research is aimed at integrating the temporal model and hierarchical organization of patterns.
Mechanisms of learning through the actualization of discrepancies
Adaptive systems, whether biological or artificial, rely on internal models to interact with their environment. This study investigates a learning mechanism driven by discrepancies between predictions and reality. A two-level computational system is analyzed: (1) passive pattern memorization and (2) active model correction. Key adaptive elements include fixed input-processing blocks (analogous to sensory channels), dynamic weight adjustments (memory-like), and a balance between model updating (learning acceleration) and stabilization. Memory plays a central role, with statistical data (*_tendency.csv) forming predictive foundations and an optimization algorithm refining them. Healthy adaptation requires equilibrium between plasticity and resilience. The framework demonstrates broad applicability, spanning AI and cognitive science. Unlike traditional views of memory as mere recall, this model emphasizes its dual role in both memorization and world-model formation, achieved through integrated memory functions. The results highlight memory’s potential as a core adaptive mechanism, bridging machine and biological learning. This approach advances AI development while offering novel insights into natural cognition, underscoring the parallels between artificial and biological adaptive systems.
Memorizing an Infinite Stream of Information in a Limited Memory Space: The Ze Method of a Plastic Counter of Chronotropic Number Frequencies
This paper presents an innovative method for creating a flexible chronotropic frequency counter for processing endless data streams. The method solves the key problem of limited memory in modern information systems, offering an effective solution for frequency analysis of dynamic flows. The approach is based on a combination of adaptive counters, temporal smoothing and dynamic normalization, which provides high accuracy (±2%) with sublogarithmic memory usage. Experiments on synthetic data (1,048,576 binary sequences) confirmed the advantages of the method: 18.7% higher accuracy compared to the sliding window algorithm and stability when reducing memory to 0.01% of the original volume. The method demonstrates a linear dependence of processing time on the volume of data (R²=0.98) and rapid adaptation to changes in the flow (12.4±3.1 iterations). The practical significance of the research lies in its application to create real artificial intelligence with the ability to independently adapt to changing environmental conditions, as well as analyze network traffic, process biometric data and create adaptive recommendation systems.
Ontogenetic Permanence of Non-Renewable Biomechanical Configurations in Homo Sapiens Anatomy
Aging in biological organisms is intricately linked to the accumulation of damage in long-lived irreparable structures, which remain unchanged throughout life. These structures include lens proteins (crystallins), DNA of postmitotic neurons, mitochondria of cardiomyocytes, tooth enamel, and centrioles of stem cells. Formed in the early stages of ontogenesis, they serve as "entropy accumulators"—a thermodynamic measure of molecular disorder. The impossibility of their replacement is dictated by evolutionary compromises: for instance, the stability of centrioles is crucial for the asymmetric division of stem cells, yet their selective inheritance results in the transfer of damage to progeny, thereby accelerating tissue aging. The accumulation of oxidized proteins, DNA mutations, and dysfunctional organelles disrupts homeostasis, triggering neurodegeneration, cataracts, and heart failure. This article examines the mechanisms underlying the damage to these structures, their role in age-related pathologies, and promising therapeutic strategies, including senolytics, CRISPR correction, and biomimetic materials. Special emphasis is placed on centrioles as key regulators of cellular entropy: while their stability supports tissue regeneration, defect accumulation leads to gene expression disruption and contributes to oncogenesis. Understanding the balance between longevity and vulnerability in irreparable structures opens new avenues for combating aging through targeted entropy management.
Anti-Blastomic Substances in the Plasma of Schizophrenia Patients: A Dual Role of Complement C4 in Synaptic Pruning and Tumor Suppression
Schizophrenia, a multifaceted neuropsychiatric disorder characterized by disruptions in neurodevelopmental trajectories, has been robustly linked to dysregulated synaptic pruning mechanisms and persistent immune system activation. The present study investigates the intricate interplay between the activity of the complement C4 gene—a pivotal regulator of synaptic pruning—and the incidence of malignant neoplasms in individuals diagnosed with schizophrenia. Our methodological approach integrated three primary investigative arms: (1) large-scale epidemiological meta-analyses encompassing a cohort of 15,000 patients, (2) in vitro experiments utilizing serum from schizophrenia patients to assess its impact on cancer cell proliferation, and (3) genetic profiling to quantify C4 expression patterns. Key findings revealed: (1) a statistically significant 20% reduction in cancer incidence among schizophrenia patients relative to the general population (p<0.01), (2) potent suppression of neoplastic cell growth (up to 40%) following exposure to patient-derived serum, and (3) a strong positive correlation between C4A allelic variants and anti-proliferative efficacy (r=0.58, p<0.001). We postulate that C4 hyperactivation in schizophrenia exerts dual biological effects: exacerbating synaptic elimination through microglial-mediated pruning while concurrently enhancing tumor surveillance via complement-dependent immunomodulation. These findings illuminate the pleiotropic nature of complement proteins in both neurodevelopmental pathology and oncological protection, offering novel therapeutic avenues for cancer management and schizophrenia pathobiology.