Separation Of Poly Research Articles

The central spindle drives anaphase chromosome segregation.

Anaphase chromosome segregation depends on forces exerted by spindle microtubules. In the current model, forces on chromosomes are mediated through the spindle poles: sliding of antiparallel microtubules in the central spindle pushes poles apart, while kinetochore microtubule (kMT) depolymerization pulls chromosomes towards the poles. Here we show that the central spindle is directly linked to the chromosomes rather than the poles in anaphase, based on three lines of evidence. Chromosomes in monopolar spindles can move away from the pole, consistent with forces exerted by antiparallel microtubule sliding. In bipolar spindles, kMT depolymerization is constrained by suppressing central spindle sliding, indicating kinetochore linkage to the central spindle. Finally, increasing the rate of kMT depolymerization slows pole separation without increasing chromosome separation velocity. We conclude that central spindle sliding drives anaphase chromosome separation, while kMT depolymerization limits spindle elongation.

Plasticity of the mitotic spindle in response to karyotype variation

Karyotypes, composed of chromosomes, must be accurately partitioned by the mitotic spindle for optimal cell health. However, it is unknown how underlying characteristics of karyotypes, such as chromosome number and size, govern the scaling of the mitotic spindle to ensure accurate chromosome segregation and cell proliferation. We utilize budding yeast strains engineered with fewer chromosomes, including just two "mega chromosomes," to study how spindle size and function are responsive to, and scaled by, karyotype. We determined that deletion and overexpression of spindle-related genes are detrimental to the growth of strains with two chromosomes, suggesting that mega chromosomes exert altered demands on the spindle. Using confocal microscopy, we demonstrate that cells with fewer but longer chromosomes have smaller spindle pole bodies, fewer microtubules, and longer spindles. Moreover, using electron tomography and confocal imaging, we observe elongated, bent anaphase spindles with fewer core microtubules in strains with mega chromosomes. Cells harboring mega chromosomes grow more slowly, are delayed in mitosis, and a subset struggle to complete chromosome segregation. We propose that the karyotype of the cell dictates the microtubule number, type, spindle pole body size, and spindle length, subsequently influencing the dynamics of mitosis, such as the rate of spindle elongation and the velocity of pole separation. Taken together, our results suggest that mitotic spindles are highly plastic ultrastructures that can accommodate and adjust to a variety of karyotypes, even within a species.

Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing.

Many proteins regulating mitosis have emerged as targets for cancer therapy, including the kinesin spindle protein (KSP) and Aurora kinase B (AurB). KSP is crucial for proper spindle pole separation during mitosis, while AurB plays roles in chromosome segregation and cytokinesis. Agents targeting KSP and AurB selectively affect dividing cells and have shown significant activity in vitro. However, these drugs, despite advancing to clinical trials, often yield unsatisfactory outcomes as monotherapy, likely due to variable responses driven by cyclin B degradation and apoptosis signal accumulation networks. Accumulated data suggest that combining emerging antimitotics with various cytostatic drugs can enhance tumor-killing effects compared to monotherapy. Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. The combination of BH3-mimetics with both KSP and AurB inhibitors synergistically induced substantial cell death, primarily through apoptosis. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness.

The electroweak monopole–antimonopole pair in the standard model

We present the first numerical solution that corresponds to a pair of Cho–Maison monopoles and antimonopoles (MAPs) in the SU(2) × U(1) Weinberg–Salam (WS) theory. The monopoles are finitely separated, while each pole carries a magnetic charge ±4π/e. The positive pole is situated in the upper hemisphere, whereas the negative pole is in the lower hemisphere. The Cho–Maison MAP is investigated for a range of Weinberg angles, 0.4675≤tanθW≤10 , and Higgs self-coupling, 0 ≤ β ≤ 1.7704. The magnetic dipole moment (μ m) and pole separation (d z ) of the numerical solutions are calculated and analyzed. The total energy of the system, however, is infinite due to point singularities at the locations of monopoles.

Elucidation of the trapping characteristics of magnetic disk-like particles in a Hagen-Poiseuille flow via Brownian dynamics simulations (usage of multi-magnetic poles)

In the present study, we elucidate the behaviour of a suspension composed of magnetic disk-like particles that flow in a Hagen-Poiseuille flow in a gradient magnetic field and the trapping characteristics of the magnetic particles. To this end, we utilise multiple pairs of magnetic poles located outside the cylindrical system. Brownian dynamics simulations were performed in order to clarify the dependence of these characteristics on a variety of factors. It is seen that an increase in the magnetic field strength improves the trapping characteristics of disk-like particles if the influence of an applied magnetic field is sufficiently more dominant than that of a flow field and that of the magnetic particle-particle interaction. In the case of a strong magnetic particle-particle interaction, thin chain-like clusters are formed from an anchored particle trapped around a magnetic pole. If the two poles are sufficiently close to each other, an arch-type cluster is formed between them. We expect that this arch-type cluster may give rise to good trapping performance even in the presence of a strong flow field if the formation arises at a sufficiently large separation distance between the pair of magnetic poles. Highlights We have performed Brownian dynamics simulations for a magnetic disk-like particle suspension in a Hagen-Poiseuille flow. If the magnetic particle-particle interaction is sufficiently more dominant than the flow field, thin chain-like clusters are formed from an anchored particle. As the pole separation distance decreases, an arch-type configuration tends to be formed along the surface of the wall. This arch-type cluster that is formed between the pair of magnetic poles may be expected to improve the trapping characteristics depending on the pole separation distance.

Second-generation Fragments of a Comet Split in the Making: The Liller Family Comets

Kreutz sungrazers and Kracht, Marsden, and Meyer sunskirters are regarded as second- or third-generation fragments of split comets. First-generation fragments have been observed to form, for example, in the cases of comets 73P/Schwassmann–Wachmann 3, D/1993 F2 (Shoemaker–Levy 9), and 332P/Ikeya–Murakami. Here, we compare relevant orbital correlation properties (the distributions of mutual nodal distances, and the angular separation of perihelia and poles) of the Liller family comets—C/1988 A1 (Liller), C/1996 Q1 (Tabur), C/2015 F3 (SWAN), C/2019 Y1 (ATLAS), and C/2023 V5 (Leonard)—with those of fragments of 332P and some Kreutz sungrazers to show that they are first-generation cometary fragments in the process of producing the second-generation.

Pole decomposition of BFKL eigenvalue at zero conformal spin and the real part of digamma function

We consider the powers of leading order eigenvalue of the Balitsky-Fadin-Kuraev-Lipatov (BFKL) equation at zero conformal spin. Using reflection identities of harmonic sums we demonstrate how involved generalized polygamma functions are introduced by pole separation of a rather simple digamma function. This generates higher weight generalized polygamma functions at any given order of perturbative expansion. As a byproduct of our analysis we develop a general technique for calculating powers of the real part of digamma function in a pole separated form.

Kinesin-5 Eg5 is essential for spindle assembly, chromosome stability and organogenesis in development

Chromosome stability relies on bipolar spindle assembly and faithful chromosome segregation during cell division. Kinesin-5 Eg5 is a plus-end-directed kinesin motor protein, which is essential for spindle pole separation and chromosome alignment in mitosis. Heterozygous Eg5 mutations cause autosomal-dominant microcephaly, primary lymphedema, and chorioretinal dysplasia syndrome in humans. However, the developmental roles and cellular mechanisms of Eg5 in organogenesis remain largely unknown. In this study, we have shown that Eg5 inhibition leads to the formation of the monopolar spindle, chromosome misalignment, polyploidy, and subsequent apoptosis. Strikingly, long-term inhibition of Eg5 stimulates the immune responses and the accumulation of lymphocytes in the mouse spleen through the innate and specific immunity pathways. Eg5 inhibition results in metaphase arrest and cell growth inhibition, and suppresses the formation of somite and retinal development in zebrafish embryos. Our data have revealed the essential roles of kinesin-5 Eg5 involved in cell proliferation, chromosome stability, and organogenesis during development. Our findings shed a light on the cellular basis and pathogenesis in microcephaly, primary lymphedema, and chorioretinal dysplasia syndrome of Eg5-mutation-positive patients.

Highly Selective Frequency Selective Surface With Ultrawideband Rejection

Frequency selective surface (FSS) with ultrawide out-of-band rejection is proposed in this article. For achieving an ultrawide and high-intensity stopband, a common second-order bandpass FSS is designed and then improved by an equivalent circuit model (ECM) design. The hybrid resonator pole separation (HRPS) decoupling method is proposed and applied during the design process. The modified ECM could realize the suppress effect on the unexcepted out-of-band transmission pole caused by coupling between layers and achieve the desired ultrawideband rejection. Furthermore, the corresponding FSS structure is established from the modified ECM through the mapping method. In addition, we conducted a detailed analysis of equivalent circuit design and the required frequency response achieve method. The measured results show that a second-order passband from 3.12 to 4.64 GHz with 0.3 dB insertion loss (IL) in the band is obtained by the proposed FSS. Meanwhile, transition bands from the passband to the stopband are narrow, and the transmission coefficients out of the passband could be suppressed under −20 dB from 5.5 to over 40 GHz. All the results demonstrate that the proposed FSS can realize an excellent out-of-band rejection while maintaining a well passband.

Improvement of trapping performance of magnetic particles by magnetic multi-poles via Brownian dynamics simulations of magnetic rod-like particles in a Hagen-Poiseuille flow

In the present study we have implemented a Brownian dynamics simulation of a Hagen-Poiseuille flow in a cylindrical vessel and have investigated the feasibility of multi-pairs of magnetic poles for exhibiting a good particle trapping performance. We have focused on two representative types of configuration consisting of two pairs of magnetic poles. The first is a vertical configuration of two pairs of poles arranged perpendicular to the direction of the flow field. The second is a parallel configuration, where each pair of magnetic poles is arranged along the surface of the vessel wall. In the case of the vertical pole arrangement, although densely-packed aggregates were formed between the poles, their location was unstable in the flow field and they tended to be carried away downstream. In contrast, a densely-packed cluster formed in the parallel arrangement tended locate in a more stable manner along the surface of the wall where the flow field is weaker. We conclude that under appropriate conditions of the magnetic particle-particle interaction strength, the applied magnetic field strength and the pole separation distance, the parallel arrangement of magnetic poles is the configuration of choice for giving rise to a superior trapping performance.

Sister chromatids separate during anaphase in a three-stage program as directed by interaxis bridges

During mitosis, from late prophase onward, sister chromatids are connected along their entire lengths by axis-linking chromatin/structure bridges. During prometaphase/metaphase, these bridges ensure that sister chromatids retain a parallel, paranemic relationship, without helical coiling, as they undergo compaction. Bridges must then be removed during anaphase. Motivated by these findings, the present study has further investigated the process of anaphase sister separation. Morphological and functional analyses of mammalian mitoses reveal a three-stage pathway in which interaxis bridges play a prominent role. First, sister chromatid axes globally separate in parallel along their lengths, with concomitant bridge elongation, due to intersister chromatin pushing forces. Sister chromatids then peel apart progressively from a centromere to telomere region(s), step-by-step. During this stage, poleward spindle forces dramatically elongate centromere-proximal bridges, which are then removed by a topoisomerase IIα–dependent step. Finally, in telomere regions, widely separated chromatids remain invisibly linked, presumably by catenation, with final separation during anaphase B. During this stage increased separation of poles and/or chromatin compaction appear to be the driving force(s). Cohesin cleavage licenses these events, likely by allowing bridges to respond to imposed forces. We propose that bridges are not simply removed during anaphase but, in addition, play an active role in ensuring smooth and synchronous microtubule-mediated sister separation. Bridges would thereby be the topological gatekeepers of sister chromatid relationships throughout all stages of mitosis.

Breakage of CRISPR/Cas9-Induced Chromosome Bridges in Mitotic Cells.

Chromosomal instability, the most frequent form of plasticity in cancer cells, often proceeds through the formation of chromosome bridges. Despite the importance of these bridges in tumor initiation and progression, debate remains over how and when they are resolved. In this study, we investigated the behavior and properties of chromosome bridges to gain insight into the potential mechanisms underlying bridge-induced genome instability. We report that bridges may break during mitosis or may remain unbroken until the next interphase. During mitosis, we frequently observed discontinuities in the bridging chromatin, and our results strongly suggest that a substantial fraction of chromosome bridges are broken during this stage of the cell cycle. This notion is supported by the observation that the chromatin flanking mitotic bridge discontinuities is often decorated with the phosphorylated form of the histone H2AX, a marker of DNA breaks, and by MDC1, an early mediator of the cell response to DNA breaks. Also, free 3′OH DNA ends were detected in more than half of the bridges during the final stages of cell division. However, even if detected, the DNA ends of broken bridges are not repaired in mitosis. To investigate whether mitotic bridge breakage depends on mechanical stress, we used experimental models in which chromosome bridges with defined geometry are formed. Although there was no association between spindle pole separation or the distance among non-bridge kinetochores and bridge breakage, we found a direct correlation between the distance between bridge kinetochores and bridge breakage. Altogether, we conclude that the discontinuities observed in bridges during mitosis frequently reflect a real breakage of the chromatin and that the mechanisms responsible for chromosome bridge breakage during mitosis may depend on the separation between the bridge kinetochores. Considering that previous studies identified mechanical stress or biochemical digestion as possible causes of bridge breakage in interphase cells, a multifactorial model emerges for the breakage of chromosome bridges that, according to our results, can occur at different stages of the cell cycle and can obey different mechanisms.

Naked emergence of an anti-Hale active region

Aims. In order to understand the emergence of the active region, we investigate the emerging process and magnetic properties of a naked anti-Hale active region during the period between August 24 to 25, 2018. Methods. Using the data from Helioseismic and Magnetic Imager on board the Soar Dynamic Observatory and the New Vacuum Solar Telescope, we calculated different evolving parameters (such as pole separation, tilt angle) and magnetic parameters (such as vertical electric current, force-free parameter, relative magnetic helicity) during the emergence of the active region. With these calculated parameters and some reasonable assumptions, we use two different methods to estimate the twist of the active region. Results. The magnetic flux and pole separation continue increasing while the tilt angle exhibits a decreasing pattern during the emergence of the active region. The increase of the pole separation is mainly contributed as a result of the enhancement in the longitude direction. A power-law relationship between pole separation and total flux is found during the emergence of the active region. On the other hand, it is found that both the positive and negative electric currents increased equivalently and the average flux-weighted force-free parameter α̃ remains almost consistently positive, on the order of ∼10−8 m−1. The relative magnetic helicity is mainly contributed by the shear term, while the relative magnetic helicity injection flux of the shear term changes its sign at the latter stage of the emergence. The twist number of the whole active region remains on the order of 10−1 turns during the emergence of the active region. Conclusions. We find that the magnetic flux tube with low twist also could emerge into the solar atmosphere.

Microtubule pivoting enables mitotic spindle assembly in S. cerevisiae.

To assemble a bipolar spindle, microtubules emanating from two poles must bundle into an antiparallel midzone, where plus end-directed motors generate outward pushing forces to drive pole separation. Midzone cross-linkers and motors display only modest preferences for antiparallel filaments, and duplicated poles are initially tethered together, an arrangement that instead favors parallel interactions. Pivoting of microtubules around spindle poles might help overcome this geometric bias, but the intrinsic pivoting flexibility of the microtubule-pole interface has not been directly measured, nor has its importance during early spindle assembly been tested. By measuring the pivoting of microtubules around isolated yeast spindle poles, we show that pivoting flexibility can be modified by mutating a microtubule-anchoring pole component, Spc110. By engineering mutants with different flexibilities, we establish the importance of pivoting in vivo for timely pole separation. Our results suggest that passive thermal pivoting can bring microtubules from side-by-side poles into initial contact, but active minus end-directed force generation will be needed to achieve antiparallel alignment.

Optimal Design of Double-Pole Magnetization BLDC Motor and Comparison with Single-Pole Magnetization BLDC Motor in Terms of Electromagnetic Performance

This study presents an optimal double-pole magnetization brushless DC (BLDC) motor design, compared to a single-pole magnetization BLDC motor in terms of electromagnetic performance. Initially, a double-pole model is selected based on the permanent magnet (PM) of the single-pole model. The pole separation space, which is generated in the magnetization process of the double-pole PM, is selected based on the pole space of the single-pole model. Moreover, the PM offset is selected considering the PM volume of the single-pole model. Further, an optimal model is selected using the multiple response optimal method, which is a type of response surface methodology (RSM). The objective of the optimal design is to maintain the back EMF and decrease the cogging torque; the design variables include the pole separation space and PM offset. The experimental points of the initial model are designed using the central composite method (CCD). Finally, the optimization is verified by comparing the experimental and analysis results of the single-pole model with the analysis results of the optimal model.

Multiblock Analysis to Relate Polyphenol Targeted Mass Spectrometry and Sensory Properties of Chocolates and Cocoa Beans.

Chocolate quality is largely due to the presence of polyphenols and especially of flavan-3-ols and their derivatives that contribute to bitterness and astringency. The aim of the present work was to assess the potential of a quantitative polyphenol targeted metabolomics analysis based on mass spectrometry for relating cocoa bean polyphenol composition corresponding chocolate polyphenol composition and sensory properties. One-hundred cocoa bean samples were transformed to chocolates using a standard process, and the latter were attributed to four different groups by sensory analysis. Polyphenols were analyzed by an ultra-high-performance liquid chromatography (UPLC) system hyphenated to a triple quadrupole mass spectrometer. A multiblock method called a Common Component and Specific Weights Analysis (CCSWA) was used to study relationships between the three datasets, i.e., cocoa polyphenols, chocolate polyphenols and sensory profiles. The CCSWA multiblock method coupling sensory and chocolate polyphenols differentiated the four sensory poles. It showed that polyphenolic and sensory data both contained information enabling the sensory poles’ separation, even if they can be also complementary. A large amount of variance in the cocoa bean and corresponding chocolate polyphenols has been linked. The cocoa bean phenolic composition turned out to be a major factor in explaining the sensory pole separation.

Continuous Interfacial Centrifugal Separation and Recovery of Silver Nanoparticles

AbstractContinuous‐flow separation and recovery of silver nanoparticles (AgNPs) using an annular centrifugal extractor (ACE) is demonstrated. Separation was achieved at the liquid‐liquid interface based on the balance between centrifugal force and the solubility of the capping agent. A mathematical model is presented to understand the mechanism in greater detail. The separation of poly(vinylpyrrolidone) (PVP)‐coated AgNPs in an ACE using a strong immiscible solvent was performed. The material accumulated at the interface was separated periodically without discontinuing the operation. The method is also suitable for separation of large particles or 1D/2D nanostructures even employing a single annular centrifugal extractor. Stable AgNPs were selected for a detailed antimicrobial activity study.

Filanesib for the treatment of multiple myeloma

ABSTRACTIntroduction: Kinesin spindle protein (KSP) is indispensable for the proper separation of spindle poles during mitosis. Importantly, this protein is expressed only in cells undergoing cell division and hence represents an appealing target for the treatment of cancer. Many KSP inhibitors have demonstrated a strong antitumoral effect in vitro, however, they have exhibited only limited activity in clinical trials. By contrast, the KSP inhibitor filanesib has demonstrated clinical efficacy in patients with multiple myeloma (MM).Areas covered: This article provides a comprehensive overview about the progress to date in the preclinical and clinical development of filanesib for the treatment of cancer, and particularly, MM.Expert opinion: Responses observed with filanesib alone or in combination with dexamethasone were encouraging in MM. However, the subsequent appearance of highly effective novel agents such as monoclonal antibodies, has hindered the development of agents such as filanesib that exhibit a more limited activity. Nevertheless, filanesib has shown interesting results for some patients when combined with carfilzomib and pomalidomide. Most importantly, the availability of a biomarker of response such as alpha 1-acid glycoprotein (AAG), could be key to the identification of patients that could benefit most from these combinations.

Successive Kinesin-5 Microtubule Crosslinking and Sliding Promote Fast, Irreversible Formation of a Stereotyped Bipolar Spindle

Separation of duplicated spindle poles is the first step in forming the mitotic spindle. Kinesin-5 crosslinks and slides anti-parallel microtubules (MTs), but it is unclear how these two activities contribute to the first steps in spindle formation. In this study, we report that in monopolar spindles, the duplicated spindle poles snap apart in a fast and irreversible step that produces a nascent bipolar spindle. Using mutations in Kinesin-5 that inhibit microtubule sliding, we show that the fast, irreversible pole separation is primarily driven by microtubule crosslinking. Electron tomography revealed microtubule pairs in monopolar spindles have short overlaps that intersect at high angles and are unsuited for ensemble Kinesin-5 sliding. However, maximal extension of a subset of anti-parallel microtubule pairs approaches the length of nascent bipolar spindles and is consistent with a Kinesin-5 crosslinking-driven transition. Nonetheless, microtubule sliding by Kinesin-5 contributes to stabilizing the nascent spindle and setting its stereotyped equilibrium length.

Kinetochore-mediated outward force promotes spindle pole separation in fission yeast.

Bipolar spindles are organized by motor proteins that generate microtubule-­dependent forces to separate the two spindle poles. The fission yeast Cut7 (kinesin-5) is a plus-end-directed motor that generates the outward force to separate the two spindle poles, whereas the minus-end-directed motor Pkl1 (kinesin-14) generates the inward force. Balanced forces by these antagonizing kinesins are essential for bipolar spindle organization in mitosis. Here, we demonstrate that chromosomes generate another outward force that contributes to the bipolar spindle assembly. First, it was noted that the cut7 pkl1 double knockout failed to separate spindle poles in meiosis I, although the mutant is known to succeed it in mitosis. It was assumed that this might be because meiotic kinetochores of bivalent chromosomes joined by cross-overs generate weaker tensions in meiosis I than the strong tensions in mitosis generated by tightly tethered sister kinetochores. In line with this idea, when meiotic mono-oriented kinetochores were artificially converted to a mitotic bioriented layout, the cut7 pkl1 mutant successfully separated spindle poles in meiosis I. Therefore, we propose that spindle pole separation is promoted by outward forces transmitted from kinetochores to spindle poles through microtubules.