RNA m6A dynamic modification mediated by nucleuslocalized FTO is involved in follicular reserve

In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers.The fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO expression.Application of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative splicing.Overexpression of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial follicles.Conversely,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle assembly.These findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle assembly.These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.

‘Prediabetes’ as a practical distinctive window for workable fruitful wonders: Prevention and progression alert as advanced professionalism

Diabetes is a devastating public health problem.Prediabetes is an intermediate stage in the disease processes leading to diabetes,including types 1 and 2 diabetes.In the article“Prediabetes in children and adolescents:An updated review,”the authors presented current evidence.We simplify and systematically clearly present the evidence and rationale for a conceptual framework we term the‘3ASs’:(1)Awareness Sensible;(2)Algorithm Simple;and(3)Appealing Strategies.Policy makers and the public need to be alerted.The prevalence of prediabetes should send alarm bells ringing for parents,individuals,clinicians,and policy makers.Prediabetes is defined by the following criteria:impaired fasting glucose(100-125 mg/dL);impaired glucose tolerance(2 h postprandial glucose 140-199 mg/dL);or hemoglobin A1c values of 5.7%–6.4%.Any of the above positive test alerts for intervention.Clinical guidelines do not recommend prioritizing one test over the others for evaluation.Decisions should be made on the strengths and shortfalls of each test.Patient preferences and test accessibility should be taken into consideration.An algorithm based on age,physiological stage,health status,and risk factors is provided.Primordial prevention targeting populations aims to eliminate risk factors through public education and encouraging practices through environmental modifications.Access to healthy foods is provided.Primary prevention is for individuals with a prediabetes diagnosis and involves a structured program to reduce body weight and increase physical activity along with a healthy diet.An overall methodical move to a healthy lifestyle for lifelong health is urgently needed.Early energetic prediabetes action is necessary.

The Origin of Electric Charge in Quantum Gravity

A model fermion has been produced in a theory of quantum gravity that establishes the existence of a mass gap and half-integral spin. The third requirement for the fermion is electric charge. We herein develop a dualism-based analysis that explains the origin of charge at the fermion scale in a primordial field theory of quantum gravity.

The Origin of Quarks in Quantum Gravity

A theory of quantum gravity has recently been developed by the author based on the concept that all forces converge to one at the moment of Creation. This primordial field can only interact with itself, as no other field exists, contrasting with the Standard Model of Particle Physics in which each elementary particle is an excitation in its own quantum field. The primordial field theory of quantum gravity has produced a model of a fermion with a mass gap, ½-integral spin, discrete charge, and magnetic moment. The mass gap is based on an existence theorem that is anchored in Yang-Mills, while Calabi-Yau anchors ½-integral spin, with charge and magnetic moment based on duality. Based on N-windings, this work is here extended to encompass fractional charge, with the result applied to quarks, yielding fermion mass and charge in agreement with experiment and novel size correlations and a unique quantum gravity-based ontological understanding of quarks.

Calabi-Yau Topology of Primordial Fermions

Quantum field theory creates fermions via abstract operators exciting abstract fields, with a specific field for each type of specific particle. This operator algebra lends itself well to quantum statistics, nevertheless, our physical understanding of this process is nonintuitive at best. In this paper we analyze the creation of fermions from primordial gauge field quantum gravity loops in the context of Calabi-Yau manifold theory. I extend a prior mass-gap treatment based on Yang-Mills gauge theory of higher order self-interaction to include the half-integral spin of fermions.

ARCADE 2 Spatial Roar, What Theory of Relation Reveals

The theory of Relation provides an explanation for the Arcade 2 excess. It assumes that the isotropic radio emission measured by the Arcade 2 Collaboration, which is 5 - 6 times brighter than the expected contributions from known extra-galactic sources, is the residue of an immense primitive energy of ordinary matter released by a relativistic bang almost 100 million years after the big bang, which gave the mass-energy the missing gravity to activate contraction. This relativistic bang, via a Lorentz energy transformation, would have released enormous energy held to be the source of the powerful radio noise detected by the NASA researchers. This transformation would have simultaneously triggered the formation of the first stars from dense gas and the reionization of less dense neutral gas. This departs from the idea that continuous reionization began after the formation of the first stars. We emphasize the importance of primordial magnetic fields, which would have generated significant density fluctuations during recombination and acted as a direct seed for cosmic structures. The first stars and galaxies were bathed in strong magnetic fields that gave rise to the radio microwave din (boom) discovered by Arcade 2. These intense magnetic fields alter the trajectory of charged particles zooming near the speed of light, triggering the space roar and emitting radiation that forms a synchrotron radio background. The theory of Relation offers an alternative to the Lambda-CDM cosmological model, which has become the standard model of the big bang, which leads straight to the vacuum catastrophe.

Research progress of in vitro activation mechanism and clinical application of female ovarian tissue

The activation and development of primordial follicles is the key to the maturation of female gametes.Premature ovarian insufficiency(POI)patients are unable to complete the primordial follicle activation and development due to follicular dormancy and unbalanced developmental regulation in the body,leading to female infertility.Ovarian tissue in vitro activation(IVA)technology has become a new way to solve the problem of patients who cannot auto-activate primordial follicles to obtain their own mature oocytes.In IVA research,signaling pathways such as PI3K/PTEN/Akt and Hippo have become the focus of current research.This review will describe the relevant research progress and clinical application of the IVA mechanism,and provide a reference for clinical research on ovarian tissue culture and activation in vitro.

The Ontology of Velocity

Special relativity formulates a world partitioned into frames in relative motion;absolute motion is prohibited by axiom: no preferred frame, with consequences for the ontology of velocity. The best guide to physical reality is experiment, so ontology of velocity is investigated in the context of primordial field theory in terms of three experiments: Michelson-Morley, Michelson-Gale and Hafele-Keating experiments.

Computational Physics of Mathematica and Geometric Calculus

The latter half of the twentieth century yielded two tools of unprecedented power, both of which took decades to mature to their current states. The purpose of this research is to apply these to a theory of gravity and develop the consequences of the model based on these tools. This paper presents such results without mathematical details, which are presented elsewhere. The tools are: Geometric Calculus, developed by David Hestenes, circa 1965 and Mathematica, released in 1988 by Steven Wolfram. Both tools have steep learning curves, requiring several years to acquire expertise in their use. This paper explains in what sense they are optimal.

Ontology of Quantum Gravity

A theory of Quantum Gravity based on Primordial Field Theory is applied to a fundamental particle, the neutron. The result is compared to the current quantum description of the neutron bouncing in a gravitational field. Our quantum gravity theory yields results in agreement with the Q-bounce experimental data, but ontologically different from quantum mechanics. The differences are summarized and imply that this experiment on a fundamental particle has the potential to radically alter the ontology of field theory.

Initiation of plate tectonics in the Hadean: Eclogitization triggered by the ABEL Bombardment

When plate tectonics began on the Earth has been long debated and here we argue this topic based on the records of Earth-Moon geology and asteroid belt to conclude that the onset of plate tectonics was during the middle Hadean（4.37-4.20 Ga）. The trigger of the initiation of plate tectonics is the ABEL Bombardment, which delivered oceanic and atmospheric components on a completely dry reductive Earth, originally comprised of enstatite chondrite-like materials. Through the accretion of volatiles, shock metamorphism processed with vaporization of both CI chondrite and supracrustal rocks at the bombarded location, and significant recrystallization went through under wet conditions, caused considerable eclogitization in the primordial continents composed of felsic upper crust of 21 km thick anorthosite, and 50 km or even thicker KREEP lower crust. Eclogitization must have yielded a powerful slab-pull force to initiate plate tectonics in the middle Hadean. Another important factor is the size of the bombardment. By creating Pacific Ocean class crater by 1000 km across impactor, rigid plate operating stagnant lid tectonics since the early Hadean was severely destroyed, and oceanic lithosphere was generated to have bi-modal lithosphere on the Earth to enable the operation of plate tectonics.Considering the importance of the ABEL Bombardment event which initiated plate tectonics including the appearance of ocean and atmosphere, we propose that the Hadean Eon can be subdivided into three periods：（1） early Hadean（4.57-4.37 Ga）,（2） middle Hadean（4.37-4.20 Ga）, and（3） late Hadean（4.20-4.00 Ga）.

Targeting lentiviral vectors to primordial germ cells(PGCs):An efficient strategy for generating transgenic chickens

Recent advances in avian transgenic studies highlight the possibility of utilizing lentiviral vectors as tools to generate transgenic chickens. However, low rates of gonadal chimerism and germ line transmission efficiency still limit the broad usage of this method in creating transgenic chickens. In this study, we implemented a simple strategy using modified lentiviral vectors targeted to chicken primordial germ cells(PGCs) to generate transgenic chickens. The lentiviral vectors were pseudotyped with a modified Sindbis virus envelope protein(termed M168) and conjugated with an antibody specific to PGC membrane proteins. We demonstrated that these optimized M168-pseudotyped lentiviral vectors conjugated with SSEA4 antibodies successfully targeted transduction of PGCs in vitro and in vivo. Compared with the control, 50.0%–66.7% of chicken embryos expressed green fluorescent protein(GFP) in gonads transduced by the M168-pseudotyped lentivirus. This improved the targeted transduction efficiency by 30.0%–46.7%. Efficient chimerism of exogenous genes was also observed. This targeting technology could improve the efficiency of germ line transmission and provide greater opportunities for transgenic poultry studies.

Primordial germ cell-mediated transgenesis and genome editing in birds

Transgenesis and genome editing in birds are based on a unique germline transmission system using primordial germ cells(PGCs), which is quite different from the mammalian transgenic and genome editing system. PGCs are progenitor cells of gametes that can deliver genetic information to the next generation. Since avian PGCs were first discovered in nineteenth century, there have been numerous efforts to reveal their origin, specification, and unique migration pattern, and to improve germline transmission efficiency. Recent advances in the isolation and in vitro culture of avian PGCs with genetic manipulation and genome editing tools enable the development of valuable avian models that were unavailable before. However, many challenges remain in the production of transgenic and genome-edited birds,including the precise control of germline transmission, introduction of exogenous genes, and genome editing in PGCs.Therefore, establishing reliable germline-competent PGCs and applying precise genome editing systems are critical current issues in the production of avian models. Here, we introduce a historical overview of avian PGCs and their application, including improved techniques and methodologies in the production of transgenic and genome-edited birds, and we discuss the future potential applications of transgenic and genome-edited birds to provide opportunities and benefits for humans.

Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem （ES） cells and induced pluripotent stem （iPS） cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem （AFS） ceils as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.

High-reliability zircon separation for hunting the oldest material on Earth： An automatic zircon separator with image-processing/microtweezers-manipulating system and double-step dating

Despite the recent development in radiometric dating of numerous zircons by LA-ICPMS, mineral separation still remains a major obstacle, particularly in the search for the oldest material on Earth. To improve the efficiency in zircon separation by an order of magnitude, we have designed/developed a new machine-an automatic zircon separator（AZS）. This is designed particularly for automatic pick-up of100 μm-sized zircon grains out of a heavy mineral fraction after conventional separation procedures. The AZS operates in three modes：（1） image processing to choose targeted individual zircon grains out of all heavy minerals spread on a tray,（2） automatic capturing of the individual zircon grains with microtweezers, and（3） placing them one-by-one in a coordinated alignment on a receiving tray. The automatic capturing was designed/created for continuous mineral selecting without human presence for many hours. This software also enables the registration of each separated zircon grain for dating, by recording digital photo-image, optical（color） indices, and coordinates on a receiving tray. We developed two new approaches for the dating; i.e.（1） direct dating of zircons selected by LA-ICPMS without conventional resin-mounting/polishing,（2） high speed U-Pb dating, combined with conventional sample preparation procedures using the new equipment with multiple-ion counting detectors（LA-MIC-ICPMS）.With the first approach, Pb-Pb ages obtained from the surface of a mineral were crosschecked with the interior of the same grain after resin-mounting/polishing. With the second approach, the amount of time required for dating one zircon grain is ca. 20 s, and a sample throughput of 〉150 grains per hour can be achieved with sufficient precision（ca. 0.5%）.We tested the practical efficiency of the AZS, by analyzing an Archean Jack Hills conglomerate in Western Australia with the known oldest（〉4.3 Ga） zircon on Earth. Preliminary results are positive; we were able to obtain more than 194 zircons that are over 4.0 Ga out of ca. 3800 checked grains, and 9 grains were over 4300 Ma with the oldest at 4371 ± 7 Ma. This separation system by AZS, combined with the new approaches, guarantees much higher yield in the hunt for old zircons.

Effects of 17beta-estradiol on cell migration in male chicks distribution of primordial germ

Aim： To assess whether exogenous estradiol has any effect on migration of primordial germ cells （PGCs） in the chick. Methods： Fertilized eggs were treated with 17beta-estradiol （E2） （80 lag/egg） at stage X （day 0 of incubation）, stages 8-10 （incubation 30 h） and 13-15 （incubation 55 h）. Controls received vehicle （emulsion） only. Changes in PGC number were measured on different days according to developmental stages. Results： In male right gonads, but not in female left gonads, at stages 28-30 （incubation 132 h） significant decreases in the mean number of PGCs aggregating were observed compared with the controls （P 〈 0.05） while the total PGC number in the right and left gonads at each stage did not change （P 〉 0.05）. Conclusion： The present study provides evidence that E2 has significant effects on the localization of PGCs in male right, but not female left, gonads of chicken embryos at stages 28-30, compared with controls. （Asian J Andro12008 Mar; 10： 243-248）

Subduction of the primordial crust into the deep mantle

The primordial crust on the Earth formed from the crystallization of the surface magma ocean during the Hadean.However,geological surveys have found no evidence of rocks dating back to more than 4 Ga on the Earth＇s surface,suggesting the Hadean crust was lost due to some processes.We investigated the subduction of one of the possible candidates for the primordial crust,anorthosite and KREEP crust similar to the Moon,which is also considered to have formed from the crystallization of the magma ocean.Similar to the present Earth,the subduction of primordial crust by subduction erosion is expected to be an effective way of eliminating primordial crust from the surface.In this study,the subduction rate of the primordial crust via subduction channels is evaluated by numerical simulations.The subduction channels are located between the subducting slab and the mantle wedge and are comprised of primordial crust materials supplied mainly by subduction erosion.We have found that primordial anorthosite and KREEP crust of up to - 50 km thick at the Earth＇s surface was able to be conveyed to the deep mantle within 0.1-2 Gy by that mechanism.

A New Theoretical Technique for the Measurement of High-Frequency Relic Gravitational Waves

Under most models of the early universe evolution, high-frequency gravitational waves (HFGWs) were produced. They are referred to as “relic” high-frequency gravitational waves or HFRGWs and their detection and measurement could provide important information on the origin and development of our Universe – information that could not otherwise be obtained. So far three instruments have been built to detect and measure HFRGWs, but so far none of them has achieved the required sensitivity. This paper concerns another detector, originally proposed by Baker in 2000 and patented, which is based upon a recently discovered physical effect (the Li effect);this detector has accordingly been named the “Li-Baker detector.” The detector has been a joint development effort by the P. R. China and the United States HFGW research teams. A rigorous examination of the detector’s performance is important in the ongoing debate over the value of attempting to construct a Li-Baker detector and, in particular, an accurate prediction of its sensitivity in the presence of significant noise will decide whether the Li-Baker detector will be capable of detecting and measuring HFRGWs. The potential for useful HFRGW measurement is theoretically confirmed.

Frontiers in early Earth history and primordial life--PartⅠ

The history of the early Earth is shrouded in mystery, and one of the major outcomes of the Apollo Program, lunar sampling, and the data acquired by subsequent orbiting missions, is that the Moon is an important analogue for the Hadean Earth, which includes primordial planet-forming materials. We assemble two special issues of ＂Geoscience Frontiers＂ with state-of-the-art contributions that provide insights into planetary formation, Earth＇s early history and primordial life. New theories show why the Earth began as a dry planetary system and was later seeded by an ocean-atmosphere system through the bombardment of carbonaceous chondrites. A combination of the information concerning the evolution of Earth, Mars, and the other terrestrial planets is important in understanding the fate of the primordial continental crustal materials and the making of habitable planets.

The Primordial Principle of Self-Interaction

The Standard Model of Particle Physics treats four fields—the gravitational, electromagnetic, weak and strong fields. These fields are assumed to converge to a single field at the big bang, but the theory has failed to produce this convergence. Our theory proposes one primordial field and analyzes the evolution of this field. The key assumption is that only the primordial field exists—if any change is to occur, it must be based upon self-interaction, as there is nothing other than the field itself to interact with. This can be formalized as the Principle of Self-interaction and the consequences explored. I show that this leads to the linearized Einstein field equations and discuss the key ontological implications of the theory.