Rapid Division Research Articles

Glutathione accelerates the cell cycle and cellular reprogramming in plant regeneration.

The plasticity of plant cells underlies their wide capacity to regenerate, with increasing evidence in plants and animals implicating cell cycle dynamics in cellular reprogramming. To investigate the cell cycle during cellular reprogramming, we developed a comprehensive set of cell cycle phase markers in the Arabidopsis root. Using single-cell RNA-seq profiles and live imaging during regeneration, we found that a subset of cells near an ablation injury dramatically increases division rate by truncating G1. Cells in G1 undergo a transient nuclear peak of glutathione (GSH) prior to coordinated entry into S phase followed by rapid divisions and cellular reprogramming. A symplastic block of the ground tissue impairs regeneration, which is rescued by exogenous GSH. We propose a model in which GSH from the outer tissues is released upon injury licensing an exit from G1 near the wound to induce rapid cell division and reprogramming.

Newton's cradle: Cell cycle regulation by two mutually inhibitory oscillators

The cell division cycle is a fundamental physiological process displaying a great degree of plasticity during the course of multicellular development. This plasticity is evident in the transition from rapid and stringently-timed divisions of the early embryo to subsequent size-controlled mitotic cycles. Later in development, cells may pause and restart proliferation in response to myriads of internal or external signals, or permanently exit the cell cycle following terminal differentiation or senescence. Beyond this, cells can undergo modified cell division variants, such as endoreplication, which increases their ploidy, or meiosis, which reduces their ploidy. This wealth of behaviours has led to numerous conceptual analogies intended as frameworks for understanding the proliferative program. Here, we aim to unify these mechanisms under one dynamical paradigm. To this end, we take a control theoretical approach to frame the cell cycle as a pair of arrestable and mutually-inhibiting, doubly amplified, negative feedback oscillators controlling chromosome replication and segregation events, respectively. Under appropriate conditions, this framework can reproduce fixed-period oscillations, checkpoint arrests of variable duration, and endocycles. Subsequently, we use phase plane and bifurcation analysis to explain the dynamical basis of these properties. Then, using a physiologically realistic, biochemical model, we show that the very same regulatory structure underpins the diverse functions of the cell cycle control network. We conclude that Newton's cradle may be a suitable mechanical analogy of how the cell cycle is regulated.

Unraveling the Mystery of Energy-Sensing Enzymes and Signaling Pathways in Tumorigenesis and Their Potential as Therapeutic Targets for Cancer.

Cancer research has advanced tremendously with the identification of causative genes, proteins, and signaling pathways. Numerous antitumor drugs have been designed and screened for cancer therapeutics; however, designing target-specific drugs for malignant cells with minimal side effects is challenging. Recently, energy-sensing- and homeostasis-associated molecules and signaling pathways playing a role in proliferation, apoptosis, autophagy, and angiogenesis have received increasing attention. Energy-metabolism-based studies have shown the contribution of energetics to cancer development, where tumor cells show increased glycolytic activity and decreased oxidative phosphorylation (the Warburg effect) in order to obtain the required additional energy for rapid division. The role of energy homeostasis in the survival of normal as well as malignant cells is critical; therefore, fuel intake and expenditure must be balanced within acceptable limits. Thus, energy-sensing enzymes detecting the disruption of glycolysis, AMP, ATP, or GTP levels are promising anticancer therapeutic targets. Here, we review the common energy mediators and energy sensors and their metabolic properties, mechanisms, and associated signaling pathways involved in carcinogenesis, and explore the possibility of identifying drugs for inhibiting the energy metabolism of tumor cells. Furthermore, to corroborate our hypothesis, we performed meta-analysis based on transcriptomic profiling to search for energy-associated biomarkers and canonical pathways.

An ultrasensitive and specific fluorescence split-aptasensor for VEGF165 detection based on nicking enzyme-assisted 3D DNA walker coupling with CRISPR-Cas12a

The overexpression of vascular endothelial growth factor 165 (VEGF165) in cancer cells plays a pivotal role in promoting tumor metastasis by facilitating their excessively rapid proliferation and division. Hence, the development of analytical methods possessing high sensitivity and resistance to interference is imperative for the detection of VEGF165. Various types of aptasensors have been devised for VEGF165 detection; however, the performance of these biosensors can be influenced by non-target signals caused by conformational changes in unbound aptamers. The paper shows the creation of a precise and sensitive fluorescence biosensor designed to detect VEGF165 by using a VEGF165-specific split aptamer. Additionally, this biosensor employs nicking enzyme-assisted DNA walker coupling with CRISPR-Cas12a to achieve dual-signal amplification. The VEGF165 calibration curve shows a detection limit of 268 fM and has a broad linear range from 5 to 4000 nM. The fluorometric biosensor was utilized to detect VEGF165 in human serum and cellular homogenate samples, yielding good outcomes. The innovative design serves as proof of concept and demonstrates significant potential in detecting various targets.

Mitigating the Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Gastrointestinal Acute Radiation Syndrome after Total-Body Irradiation in Mice.

Total-body irradiation (TBI) with gamma rays can damage organisms in various unexpected ways and trigger several organ dysfunction syndromes, such as acute radiation syndrome (ARS). Hematopoietic cells and enterocytes are particularly sensitive to radiation due to their self-renewal ability and rapid division, which leads to hematopoietic ARS (H-ARS) and gastrointestinal ARS (GI-ARS). We previously showed that a lipid-based small molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), improved 30-day survival and alleviated H-ARS symptoms in BALB/c mice after a lethal dose (LD70/30) of gamma-ray TBI. In this study, we investigated the mitigating effects of PLAG on radiation-induced GI damage that occurs under the same conditions as H-ARS in BALB/c mice. Our study showed that PLAG facilitated the structural restoration of intestinal tissues by increasing villus height, crypt depth, crypt number, mucin-producing goblet cells, and proliferating cell nuclear antigen (PCNA)-positive crypt cells. PLAG significantly improved intestinal absorptive capacity and reduced intestinal injury-induced bacterial translocation. In addition, PLAG effectively inhibited radiation-induced necroptosis signaling activation in the intestinal crypt cells, which was responsible for sustained tissue damage and the release of high mobility group box 1 (HMGB1), a typical damage-associated molecular pattern. Overall, our findings support the radiation-mitigating potential of PLAG against GI-ARS after accidental radiation exposure.

A PLATZ transcription factor PhePLATZ8 from Moso bamboo (Phyllostachys edulis) plays a positive role in regulating growth and abiotic stress tolerance

Moso bamboo is recognized as a rapid-growing plant with abundant lignocellulosic content, making it a crucial non-timber forest resource on a global scale. The growth of Moso bamboo is influenced by the rapid division and elongation of its internode meristem cells, but the molecular mechanism behind this process is still unclear. Here, by combining RNA-seq data from Moso bamboo internode samples with gene co-expression network and gene functional annotation enrichment analysis, a key candidate gene named PhePLATZ8, which regulates cell division in the internodes of Moso bamboo, has been screened out. PhePLATZ8 is localized to the nucleus and cytoplasm. The phenotype of transgenic Arabidopsis thaliana plants showed that PhePLATZ8 positively regulated the organ development of transgenic plants, including hypocotyl length, plant height, petiole length, blade shape, and seed size. Overexpression of PhePLATZ8 also significantly improved cell proliferation activities in the hypocotyl calluses of transgenic plants. qRT-PCR and luciferase assays showed that PhePLATZ8 was involved in the regulation of cell proliferation by activating the expression of several GRFs in A. thaliana and Moso bamboo. Futhermore, PhePLATZ8 was significantly induced by abiotic stress, and overexpression of PhePLATZ8 increased the tolerance of transgenic A. thaliana plants to drought and salt stress. Overall, our current study initially explored the role of PhePLATZ8 in the process of rapid growth and stress response of Moso bamboo, providing genetic resources for future molecular breeding of Moso bamboo.

The maternal-to-zygotic transition

Rapid cleavage divisions and the transition from maternal to zygotic control of gene expression are the hallmarks of early embryonic development in most species. Early development in insects, fish and amphibians is characterized by several short cell cycles with no gap phases, necessary for the rapid production of cells prior to patterning and morphogenesis. Maternal mRNAs and proteins loaded into the egg during oogenesis are essential to drive these rapid early divisions. Once the function of these maternal inputs is complete, the maternal-to-zygotic transition (MZT) marks the handover of developmental control to the gene products synthesized from the zygotic genome. The MZT requires three major events: the removal of a subset of maternal mRNAs, the initiation of zygotic transcription, and the remodeling of the cell cycle. In each species, the MZT occurs at a highly reproducible time during development due to a series of feedback mechanisms that tightly couple these three processes. Dissecting these feedback mechanisms and their spatiotemporal control will be essential to understanding the control of the MZT. In this primer, we outline the mechanisms that govern the major events of the MZT across species and highlight the role of feedback mechanisms that ensure the MZT is precisely timed and orchestrated.

Evolution and disappearance of the paleo-West Pacific Anomaly: Implications to the future of South Atlantic Anomaly

Palaeomagnetic and modern geomagnetic measurements indicate that the South Atlantic Anomaly (SAA) has undergone rapid changes over the past few hundred years. Its minimum intensity decreased at an average rate of 26 not yr−1, accompanied by a continuous westward drift and spatial expansion. Recently, a secondary minimum of SAA emerged near southern Africa, leading to speculation that expansion of the SAA could indicate an impending geomagnetic reversal. Here, we focus on the evolution and disappearance of the paleo-West Pacific Anomaly (WPA), as another SAA-like structure, which may have implications for the future of SAA evolution. We regard the WPA as SAA-like due to its feature and its association with a reversal flux patch on the core-mantle boundary. Consequently, we suggest that the observed evolutionary pattern in the WPA can serve as a reference for other negative anomalies, such as the SAA. By analysing models that combine datasets of archaeomagnetic and historical records, such as gufm1 and HistKalmag, it is found that the WPA occurred between 1600 and 1820 CE. Over its duration, the WPA experienced phases of rapid expansion, drift, and division. Eventually, its primary component faded away, giving rise to a new segment that continued to expand. The initial two evolutionary phases of the WPA are similar to the evolution of the SAA over the past century. According to the WPA's evolution, it suggests that the current state of the SAA may correspond to an early stage of splitting. Forecasts based on the evolution of the WPA indicate a rapid expansion of the anomalous region in the short term, followed by a gradual reduction in its primary component and continued expansion of a new local minimum. This study provides valuable insight into the evolution of the SAA and highlights the potential utility of the WPA as an evolutionary reference for such geomagnetic phenomena.

Paradoxical imbalance between activated lymphocyte protein synthesis capacity and rapid division rate.

Rapid lymphocyte cell division places enormous demands on the protein synthesis machinery. Flow cytometric measurement of puromycylated ribosome-associated nascent chains after treating cells or mice with translation initiation inhibitors reveals that ribosomes in resting lymphocytes in vitro and in vivo elongate at typical rates for mammalian cells. Intriguingly, elongation rates can be increased up to 30% by activation in vivo or fever temperature in vitro. Resting and activated lymphocytes possess abundant monosome populations, most of which actively translate in vivo, while in vitro, nearly all can be stalled prior to activation. Quantitating lymphocyte protein mass and ribosome count reveals a paradoxically high ratio of cellular protein to ribosomes insufficient to support their rapid in vivo division, suggesting that the activated lymphocyte proteome in vivo may be generated in an unusual manner. Our findings demonstrate the importance of a global understanding of protein synthesis in lymphocytes and other rapidly dividing immune cells.

Paradoxical imbalance between activated lymphocyte protein synthesis capacity and rapid division rate

Rapid lymphocyte cell division places enormous demands on the protein synthesis machinery. Flow cytometric measurement of puromycylated ribosome-associated nascent chains after treating cells or mice with translation initiation inhibitors reveals that ribosomes in resting lymphocytes in vitro and in vivo elongate at typical rates for mammalian cells. Intriguingly, elongation rates can be increased up to 30% by activation in vivo or fever temperature in vitro. Resting and activated lymphocytes possess abundant monosome populations, most of which actively translate in vivo, while in vitro, nearly all can be stalled prior to activation. Quantitating lymphocyte protein mass and ribosome count reveals a paradoxically high ratio of cellular protein to ribosomes insufficient to support their rapid in vivo division, suggesting that the activated lymphocyte proteome in vivo may be generated in an unusual manner. Our findings demonstrate the importance of a global understanding of protein synthesis in lymphocytes and other rapidly dividing immune cells.

Morphokinetic Profiling Suggests That Rapid First Cleavage Division Accurately Predicts the Chances of Blastulation in Pig In Vitro Produced Embryos.

The study of pig preimplantation embryo development has several potential uses: from agriculture to the production of medically relevant genetically modified organisms and from rare breed conservation to acting as a physiologically relevant model for progressing human and other (e.g., endangered) species' in vitro fertilisation technology. Despite this, barriers to the widespread adoption of pig embryo in vitro production include lipid-laden cells that are hard to visualise, slow adoption of contemporary technologies such as the use of time-lapse incubators or artificial intelligence, poor blastulation and high polyspermy rates. Here, we employ a commercially available time-lapse incubator to provide a comprehensive overview of the morphokinetics of pig preimplantation development for the first time. We tested the hypotheses that (a) there are differences in developmental timings between blastulating and non-blastulating embryos and (b) embryo developmental morphokinetic features can be used to predict the likelihood of blastulation. The abattoir-derived oocytes fertilised by commercial extended semen produced presumptive zygotes were split into two groups: cavitating/blastulating 144 h post gamete co-incubation and those that were not. The blastulating group reached the 2-cell and morula stages significantly earlier, and the time taken to reach the 2-cell stage was identified to be a predictive marker for blastocyst formation. Reverse cleavage was also associated with poor blastulation. These data demonstrate the potential of morphokinetic analysis in automating and upscaling pig in vitro production through effective embryo selection.

Modifying the electrical, optical, and magnetic properties of cancer cells: A comprehensive approach for cancer management

AbstractDespite the recent successes of cancer therapy, numerous obstacles remain. The medical community of the 16th century believed that magnets might be used to cure or prevent illness. However, this concept has only recently been put into practice in the treatment of cancer. Cancers vary greatly not only at the patient, tissue, and cellular levels but also at the molecular level. Because of this multiscale heterogeneity, effective treatments that not only differentiate between cancerous and healthy tissues but also target a wide variety of tumor subclones are difficult to develop. Most treatments either take advantage of a specific biological characteristic shared by cancer cells (e.g., their propensity for rapid division) or indiscriminately eradicate every cell in an area of interest. In this article, we review the physical, chemical, electrical, optical, and magnetic properties of cancer cells, before discussing how these properties may be modulated by current and future cancer therapies.

Regulation of centrosome size by the cell-cycle oscillator in Drosophila embryos

Mitotic centrosomes assemble when centrioles recruit large amounts of pericentriolar material (PCM) around themselves. In early C. elegans embryos, mitotic centrosome size appears to be set by the limiting amount of a key component. In Drosophila syncytial embryos, thousands of mitotic centrosomes are assembled as the embryo proceeds through 13 rounds of rapid nuclear division, driven by a core cell cycle oscillator. These divisions slow during nuclear cycles 11–13, and we find that centrosomes respond by reciprocally decreasing their growth rate, but increasing their growth period—so that they grow to a relatively consistent size at each cycle. At the start of each cycle, moderate CCO activity initially promotes centrosome growth, in part by stimulating Polo/PLK1 recruitment to centrosomes. Later in each cycle, high CCO activity inhibits centrosome growth by suppressing the centrosomal recruitment and/or maintenance of centrosome proteins. Thus, in fly embryos, mitotic centrosome size appears to be regulated predominantly by the core cell cycle oscillator, rather than by the depletion of a limiting component.

Histomorphometric study of seminiferous tubules and epididymis in adult ram

This research set out to examine the epididymis and seminiferous tubules of adult male Rams, use both histological and histomorphometric methods. For this purpose, ten paired of testis of healthy adult local rams were taken from local abattoir in Fallujah. Tissue was removed and cut into tiny pieces from different parts of the testicles before being put in Bouin's solution. The tissue samples were processed by common paraffin technique then stained with routine H & E stain as well as Masson's trichrome stain. According to the results of the present histological analysis, the ram's testis is enclosed by a capsule of thick irregular connective tissue, and its lobules are separated by trabecular and interlobular septa, with seminiferous tubules and interstitial tissue making up each lobule. Spermatogenic cells and Sertoli cells border the seminiferous tubules. Spermatozoa develop from spermatogenic cells. Spermatogonia are the earliest stages of spermatogenic cells; they are tiny, spherical cells with black, spherical nuclei that sit on the basement membrane. Primary spermatocytes, which are bigger cells with often-distinct chromatin, are generated during mitosis in the spermotogonia. Because of their rapid second meiotic division and subsequent formation of haploid spermatids, secondary spermatocytes are seldom seen. Clustered near the seminiferous tubule's lumen, the spermatids are spherical cells with pale nuclei. There are less Sertoli cells (sustentacular cells) than spermatogenic cells. The nucleus is oval or triangular in shape and pale in colour, with a large nucleolus. Leydig cells are found in the connective tissue between neighbouring tubules. Epithelium that is pseudostratified lines the epididymis. The stereocilia are long cytoplasmic structures that extend into the lumen. Circular smooth muscle is present in varying amounts, and the epithelium is supported by a connective tissue lamina propria.In conclusion, the current study concluded that the thickness of the epithelium of epididymis was decrease toward the tail while the thickness of the smooth muscle layer was increase toward the tail.

Numerical simulation of biaxial undrained shear test based on fluid–solid coupling DEM method

The undrained shear test plays a crucial role in comprehending the deformation and failure mechanisms inherent in rock and soil. While the test offers a macroscopic perspective, numerical simulations can delve into the microscopic aspects of sample behavior, thereby compensating for this limitation. Drawing inspiration from the measurement sphere fluid–solid coupling method and the discrete element method, this paper proposes a tailored numerical simulation approach for the biaxial undrained shear test. This approach is implemented in the high-performance discrete element software MatDEM. In this study, a rapid division method for the fluid network is presented, along with a detailed explanation of the control equation governing excess pore water pressure and fluid–solid interaction during shear. Subsequently, A custom flexible boundary with a relatively smooth surface is introduced to simulate the constraint of the rubber membrane, which helps reduce simulation errors. Furthermore, the specific process of the numerical simulation is introduced, and an effective method for generating samples with high void ratios is proposed. Finally, three different cases are presented, involving varying confining pressures, different void ratios, and specific shear paths, respectively. The results indicate that the proposed method can effectively simulate the process of undrained shear tests and accurately capture the excess pore water pressure responses, and lateral deformation of the samples during shearing.

Pemekaran Daerah dan Otonomi Daerah Kerangka Hubungan Pusat Daerah

Regional autonomy as the government's choice in the administration of regional government to assist efficient and effective regional governments in managing governance. The desantralization pattern distributes authority to the regions within territorial limits. The fundamental organization enables the governing policies of a system. A policy itself in the whole system of government. The pattern of power and financial relations between the central government and regional governments is largely determined by the national political configuration at a given time. This article was written using the method of conceptual thinking with critical legal studies as the type of research. The result of this article is that the formation of new regions must be aimed at improving public services, accelerating the realization of community welfare, and also channeling political education at the local level. There is also a need for an evaluation of regional expansion with indicators of the objectives of the expansion. The urgency of evaluation is so that the desire and rapid division of regions does not make local governments paradoxical with goals. it is necessary to implement it as a corrective action so that the positive implications of corrective action can be felt more properly, it must have a legal basis by the provider of regional autonomy, namely the central government.

The Impossibility of Party Unity in Peru: Party Affiliation, Subnational Electoral Competition and Party Discipline (2011–2019)

Party division in Peru is a constant event and has become an expected feature of Peruvian parliamentary politics. For instance, in 2016, the elected Congress was composed of six parliamentary groups, and at the moment of its dissolution, that number doubled. This article explores the factors that produce such rapid division in the Peruvian Congress during two parliamentary periods (2011–2016, 2016–2019). It argues, through quantitative analysis, that there is a direct and negative relationship between the fragmentation of parliamentary groups and party discipline due to party affiliation and the dynamics of subnational party competition.

Orchestral role of lipid metabolic reprogramming in T-cell malignancy.

The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.

Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids.

Essential aromatic amino acids (AAAs) are building blocks for synthesizing new biomasses in cells and sustaining normal biological functions. For example, an abundant supply of AAAs is important for cancer cells to maintain their rapid growth and division. With this, there is a rising demand for a highly specific, noninvasive imaging approach with minimal sample preparation to directly visualize how cells harness AAAs for their metabolism in situ. Here, we develop an optical imaging platform that combines deuterium oxide (D2O) probing with stimulated Raman scattering (DO-SRS) and integrates DO-SRS with two-photon excitation fluorescence (2PEF) into a single microscope to directly visualize the metabolic activities of HeLa cells under AAA regulation. Collectively, the DO-SRS platform provides high spatial resolution and specificity of newly synthesized proteins and lipids in single HeLa cell units. In addition, the 2PEF modality can detect autofluorescence signals of nicotinamide adenine dinucleotide (NADH) and Flavin in a label-free manner. The imaging system described here is compatible with both in vitro and in vivo models, which is flexible for various experiments. The general workflow of this protocol includes cell culture, culture media preparation, cell synchronization, cell fixation, and sample imaging with DO-SRS and 2PEF modalities.

Mitotic chromosomes scale to nuclear-cytoplasmic ratio and cell size in Xenopus.

During the rapid and reductive cleavage divisions of early embryogenesis, subcellular structures such as the nucleus and mitotic spindle scale to decreasing cell size. Mitotic chromosomes also decrease in size during development, presumably to scale coordinately with mitotic spindles, but the underlying mechanisms are unclear. Here we combine in vivo and in vitro approaches using eggs and embryos from the frog Xenopus laevis to show that mitotic chromosome scaling is mechanistically distinct from other forms of subcellular scaling. We found that mitotic chromosomes scale continuously with cell, spindle, and nuclear size in vivo. However, unlike for spindles and nuclei, mitotic chromosome size cannot be reset by cytoplasmic factors from earlier developmental stages. In vitro, increasing nuclear-cytoplasmic (N/C) ratio is sufficient to recapitulate mitotic chromosome scaling, but not nuclear or spindle scaling, through differential loading of maternal factors during interphase. An additional pathway involving importin α scales mitotic chromosomes to cell surface area/volume ratio (SA/V) during metaphase. Finally, single-chromosome immunofluorescence and Hi-C data suggest that mitotic chromosomes shrink during embryogenesis through decreased recruitment of condensin I, resulting in major rearrangements of DNA loop architecture to accommodate the same amount of DNA on a shorter chromosome axis. Together, our findings demonstrate how mitotic chromosome size is set by spatially and temporally distinct developmental cues in the early embryo.