Nuclear Size Research Articles

False positivity in break apart fluorescence in-situ hybridization due to polyploidy.

In-situ hybridization (ISH) is a diagnostic tool in the detection of chromosomal anomalies, which has important implications for diagnosis, classification and prediction of cancer therapy in various diseases. Certain thresholds of number of cells showing an aberrant pattern are commonly used to declare a sample as positive for genomic rearrangements. The phenomenon of polyploidy can be misleading in the interpretation of break apart fluorescence in-situ hybridization (FISH). The aim of this study is to investigate the impact of cell size and ploidy on FISH results. In sections of varying thickness of control liver tissue and non-small cell lung cancer cases, nuclear size was measured and the number of MET chromogenic ISH and ALK FISH (liver) or ALK and ROS1 FISH (lung cancer) signals was manually counted and quantified. In liver cell nuclei the number of FISH/chromogenic ISH signals increases with nuclear size related to physiological polyploidy and is related to section thickness. In non-small cell lung cancer cases tumour cells with higher ploidy levels and nuclear size have an increased chance of single signals. Furthermore, additional lung cancer samples with borderline ALK FISH results were examined with a commercial kit for rearrangements. No rearrangements could be demonstrated, proving a false positive ALK FISH result. In case of polyploidy there is an increased likelihood of false positivity when using break apart FISH probes. Therefore, we state that prescribing one single cut-off in FISH is inappropriate. In polyploidy, the currently proposed cut-off should only be used with caution and the result should be confirmed by an additional technique.

Research on Effect of Initiation Detonation Method on Fragment Velocity Distribution

To enhance the damage effect of focusing warhead, the investigation about the scattering behavior of focusing warhead is conducted. Based on the momentum method and the detonation wave theory, the influence of initiation detonation methods and curvature radius of the charge on fragment velocity is analyzed. The fragments velocity distribution models of the end-initiated, the center-initiated and the two ends-initiated are obtained. Numerical simulation shows that fragments velocity distribution and the propagation of the detonation wave of numerical simulation results have a good fit with the theoretical model. It is shown that fragments velocity is higher in the middle and low on both sides. When it was end-initiated, the location where the fragment velocity reaches the maximum was 18.6cm from the initiation end. When it was center-initiated, the maximum fragment velocity appeared at the center of the projectile axis. When it was two ends-initiated, the maximum fragment velocity appeared symmetric about the center line of the projectile axis. With increasing of the curvature radius of the circular charge, the maximum velocity of the fragments increased.

High-Resolution Ultrasound Characterization of Local Scattering in Cancer Tissue.

Ultrasound (US) has afforded an approach to tissue characterization for more than a decade. The challenge is to reveal hidden patterns in the US data that describe tissue function and pathology that cannot be seen in conventional US images. Our group has developed a high-resolution analysis technique for tissue characterization termed H-scan US, an imaging method used to interpret the relative size of acoustic scatterers. In the present study, the objective was to compare local H-scan US image intensity with registered histologic measurements made directly at the cellular level. Human breast cancer cells (MDA-MB 231, American Type Culture Collection, Manassas, VA, USA) were orthotopically implanted into female mice (N=5). Tumors were allowed to grow for approximately 4 wk before the study started. In vivo imaging of tumor tissue was performed using a US system (Vantage 256, Verasonics Inc., Kirkland, WA, USA) equipped with a broadband capacitive micromachined ultrasonic linear array transducer (Kolo Medical, San Jose, CA, USA). A 15-MHz center frequency was used for plane wave imaging with five angles for spatial compounding. H-scan US image reconstruction involved use of parallel convolution filters to measure the relative strength of backscattered US signals. Color codes were applied to filter outputs to form the final H-scan US image display. For histologic processing, US imaging cross-sections were carefully marked on the tumor surface, and tumors were excised and sliced along the same plane. By use of optical microscopy, whole tumor tissue sections were scanned and digitized after nuclear staining. US images were interpolated to have the same number of pixels as the histology images and then spatially aligned. Each nucleus from the histologic sections was automatically segmented using custom MATLAB software (The MathWorks Inc., Natick, MA, USA). Nuclear size and spacing from the histology images were then compared with local H-scan US image features. Overall, local H-scan US image intensity exhibited a significant correlation with both cancer cell nuclear size (R2 > 0.27, p < 0.001) and the inverse relationship with nuclear spacing (R2 > 0.17, p < 0.001).

Cluster model for calculation binding energy of 222,224Ra

The nucleus can be considered a relativistic system, In particular, we focus on heavy nuclei with zero spin and utilize the relativistic core-cluster model to investigate their structure properties. A zero-spin nucleus is assumed to consist of a core and a cluster, core and cluster spins are zero. We will solve the Klein–Gordon equation, which is a relativistic equation optimized for studying zero-spin systems, with the new phenomenological potential. Then, we will calculate the binding energy and charge radius of the zero-spin heavy nuclei by employing the wave function obtained from the Klein–Gordon equation.

MP50-12 CLINICOPATHOLOGIC ANALYSIS AND DIGITAL EVALUATION OF ORCHIECTOMY SPECIMENS IN PATIENTS WITH GENDER DYSPHORIA

You have accessJournal of UrologyCME1 Apr 2023MP50-12 CLINICOPATHOLOGIC ANALYSIS AND DIGITAL EVALUATION OF ORCHIECTOMY SPECIMENS IN PATIENTS WITH GENDER DYSPHORIA Ivan De La Riva, Ruoji Zhou, Alcino Gama, Bonnie Choy, Bogdan Isaila, Diana Bowen, Robert Brannigan, and Ximing Yang Ivan De La RivaIvan De La Riva More articles by this author , Ruoji ZhouRuoji Zhou More articles by this author , Alcino GamaAlcino Gama More articles by this author , Bonnie ChoyBonnie Choy More articles by this author , Bogdan IsailaBogdan Isaila More articles by this author , Diana BowenDiana Bowen More articles by this author , Robert BranniganRobert Brannigan More articles by this author , and Ximing YangXiming Yang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Gender-affirmation therapy for transgender individuals is an area of increasing importance in genitourinary pathology. These patients undergo various forms of hormonal replacement therapy (HRT) followed by bilateral orchiectomy. To date, there are very limited studies on the histological and biochemical alterations in these testes. METHODS: We conducted a retrospective search of the database for gender-affirming orchiectomies performed at our institution from 2018 to 2022. Clinical features, including age, length and types of hormonal treatment, and pathologic features, were reviewed and summarized. 19 cases were subjected to whole slide imaging scanning for digital analysis using the Leica system. Immunohistochemistry for OCT4 and CD117 was performed on selected cases. RESULTS: Atrophic changes and decreased spermatogenesis were found in all the gender-affirming orchiectomy specimens examined, with decreased mean tubule diameter (102.9 μm, 202 tubules examined) compared to the tubular size of germ cell neoplasia in situ (GCNIS) and normal testis (139.3 μm and 143.7 μm, 326 and 185 tubules examined, respectively). All cases showed significant maturation arrest, with 55 testes showing aspermatogenesis and the remaining 14 testes showing hypospermatogenesis. Various degrees of basement membrane thickening were observed in all testes, and 55.1% of the testes were found to have focal tubule hyalinization/obliteration. The number of Leydig cells was reduced, with marked cytoplasmic vacuolization and degenerative changes. In a subset of specimens, scattered germ cells displayed prominent nucleomegaly. Using digital analysis, the average nuclear size of these abnormal germ cells was 14.4 μm in diameter (35 cells counted), approaching or exceeding the size of the neoplastic nucleus in GCNIS (mean diameter=12.1 μm, 33 cells counted). However, the enlarged nuclei of these germ cells demonstrated a smooth nuclear membrane, small nucleoli, and fine granular and smudged chromatin, significantly different from the nuclei in GCNIS. Furthermore, immunohistochemistry staining of the germ cells with nucleomegaly in tested cases demonstrated negative staining for both OCT4 and CD117, militating again the possibility of GCNIS. CONCLUSIONS: All the testes from gender-affirming orchiectomies in our study exhibit significantly reduced spermatogenesis, including maturation arrest and atrophic changes. In addition, the presence of scattered germ cells with nucleomegaly in these specimens can mimic GCNIS. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e689 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ivan De La Riva More articles by this author Ruoji Zhou More articles by this author Alcino Gama More articles by this author Bonnie Choy More articles by this author Bogdan Isaila More articles by this author Diana Bowen More articles by this author Robert Brannigan More articles by this author Ximing Yang More articles by this author Expand All Advertisement PDF downloadLoading ...

Urothelial carcinoma in situ with “overriding” features can evade detection by mimicking umbrella cells

Urothelial carcinoma in situ (uCIS) is typically recognized by overtly malignant cells with characteristic nuclear features; multiple histologic patterns have been described. A rare "overriding" pattern, in which uCIS tumor cells extend on top of normal urothelium, has previously been mentioned in the literature, but not well described. Herein, we report 3 cases of uCIS with "overriding" features. Detailed morphologic evaluation revealed somewhat subtle cytologic atypia: variably enlarged hyperchromatic nuclei and scattered mitotic figures but with abundant cytoplasmand limited to superficial urothelium. Immunohistochemical (IHC) analysis showed a distinctive diffuse positive aberrant p53 pattern, limited to the atypical surface urothelial cells; these cells also showed CK20+, CD44-, and increased Ki-67. In 2 cases, there was a history of urothelial carcinoma and adjacent conventional uCIS. In the third case, the "overriding" pattern was the first presentation of urothelial carcinoma; therefore, next-generation sequencing molecular testing was also performed, revealing pathogenic mutations in TERTp, TP53, and CDKN1a to further support neoplasia. Notably, the "overriding" pattern mimicked umbrella cells, which normally line surface urothelium, can have abundant cytoplasm and more variation in nuclear and cell size and shape, and show CK20+ IHC. We therefore also evaluated umbrella cell IHC patterns in adjacent benign/reactive urothelium, which showed CK20+, CD44-, p53 wild-type, and very low Ki-67 (3/3). We also reviewed 32 cases of normal/reactive urothelium: all showed p53 wild-type IHC in the umbrella cell layer (32/32). In conclusion, caution is warranted to avoid overdiagnosis of usual umbrella cells as CIS; however, "overriding" uCIS should be recognized, may have morphologic features that fall short of the diagnostic threshold of conventional CIS, and requires further study.

Determining the gluonic gravitational form factors of the proton.

The proton is one of the main building blocks of all visible matter in the Universe1. Among its intrinsic properties are its electric charge, mass and spin2. These properties emerge from the complex dynamics of its fundamental constituents-quarks and gluons-described by the theory of quantum chromodynamics3-5. The electric charge and spin of protons, which are shared among the quarks, have been investigated previously using electron scattering2. An example is the highly precise measurement of the electric charge radius of the proton6. By contrast, little is known about the inner mass density of the proton, which is dominated by the energy carried by gluons. Gluons are hard to access using electron scattering because they do not carry an electromagnetic charge. Here we investigated the gravitational density of gluons using a small colour dipole, through the threshold photoproduction of the J/ψ particle. We determined the gluonic gravitational form factors of the proton7,8from our measurement. We used a variety of models9-11 and determined, in all cases, a mass radius that is notably smaller than the electric charge radius. In some, but not all cases, depending on the model, the determined radius agrees well with first-principle predictions from lattice quantum chromodynamics12. This work paves the way for a deeper understanding of the salient role of gluons in providing gravitational mass to visible matter.

A Kohn-Sham scheme based neural network for nuclear systems

A Kohn-Sham scheme based multi-task neural network is elaborated for the supervised learning of nuclear shell evolution. The training set is composed of the single-particle wave functions and occupation probabilities of 320 nuclei, calculated by the Skyrme density functional theory. It is found that the deduced density distributions, momentum distributions, and charge radii are in good agreements with the benchmarking results for the untrained nuclei. In particular, accomplishing shell evolution leads to a remarkable improvement in the extrapolation of nuclear density. After a further charge-radius-based calibration, the network evolves a stronger predictive capability. This opens the possibility to infer correlations among observables by combining experimental data for nuclear complex systems.

The α-particle clustering and half-lives of the newly discovered 207,208Th decay chains within relativistic-Hartree-Bogoliubov approach

The structural and decay properties of the ground state of recently discovered neutron-deficient 207Th and remeasured 208Th isotopes Yang et al. (2022) [26] is examined using the Relativistic-Hartree-Bogoliubov (RHB) formalism using the DD-ME2 parameter set within the preformed cluster-decay model (PCM). The relativistic medium-dependant R3Y so-called DD-R3Y NN potentials are for the first time used to obtain the nucleus-nucleus potential as input into the PCM. The penetration probability is calculated using the WKB approximation, and the preformation probability (Pα) is estimated using our newly derived formula, which is based on parameters well known to influence the α -particle radioactivity. A close correlation is observed between the α-preformation factor and the crucial role of the pairing correlation in the α-decay process. Furthermore, the Pα values for the even-even nuclei are generally found to be of higher magnitude than those for the odd-A nuclei. Our results further affirm that the odd-even staggering effect on the Qα values and its accompanying effects on other observables such as the charge radii and the decay half-lives, which can be largely attributed to the pairing correlation and Pauli blocking of the unpaired valence nucleons.

Ground state baryons in the flux-tube three-body confinement model using diffusion Monte Carlo

We make a systematical diffusion Monte Carlo (DMC) calculation for all ground state baryons in two confinement scenarios, the pairwise confinement and the three-body flux-tube confinement. With the baryons as an example, we illustrate a feasible procedure to investigate the few-quark states with possible few-body confinement mechanisms, which can be extended to the multiquark states easily. For each baryon, we extract the mass, mean-square radius, charge radius, and the quark distributions. We use the Jackknife resampling method to estimate the statistical uncertainties of masses to be less than 1 MeV. To determine the baryon charge radii, we include the constituent quark size effect, which is fixed by the experimental and lattice QCD results. Our results show that both two-body and three-body confinement mechanisms can give a good description of the experimental data if the parameters are chosen properly. In the flux-tube confinement, introducing different tension parameters for the baryons and mesons are necessary, specifically, $\sigma_Y= 0.9204 \sigma_{Q\bar{Q}}$. The lesson from the calculation of the nucleon mass with the DMC method is that the improper pre-assignment of the channels may prevent us from obtaining the real ground state. With this experience, we obtain the real ground state (the $\eta_c \eta_c$ threshold with the di-meson configuration) of the $cc\bar{c}\bar{c}$ system with $J^{PC}=0^{++}$ starting from the diquark-antidiquark spin-color channels alone, which is hard to achieve in the variational method and was not obtained in the previous DMC calculations.

Nuclear-level effective theory of μ→e conversion: Formalism and applications

New mu-to-e conversion searches aim to advance limits on charged lepton flavor violation (CLFV) by four orders of magnitude. By considering P and CP selection rules and the structure of possible charge and current densities, we show that rates are governed by six nuclear responses. To generate a microscopic formulation of these responses, we construct in non-relativistic effective theory (NRET) the CLFV nucleon-level interaction, then embed it in a nucleus. We discuss previous work, noting the lack of a systematic treatment of the various small parameters. Because the momentum transfer is comparable to the inverse nuclear size, a full multipole expansion of the response functions is necessary, a daunting task with Coulomb-distorted electron partial waves. We perform such an expansion to high precision by introducing a simplifying local electron momentum, treating the full set of 16 NRET operators. Previous work has been limited to the simplest charge/spin operators, ignored Coulomb distortion (or alternatively truncated the partial wave expansion) and the nucleon velocity operator, which is responsible for three of the response functions. This generates inconsistencies in the treatment of small parameters. We obtain a "master formula" for mu-to-e conversion that properly treats all such effects and those of the muon velocity. We compute muon-to-electron conversion rates for a series of experimental targets, deriving bounds on the coefficients of the CLFV operators. We discuss the nuclear physics: two types of coherence enhance certain CLFV operators and selection rules blind elastic mu-to-e conversion to others. We discuss the matching of the NRET onto higher level EFTs, and the relation to mu-to-e conversion to other CLFV tests. Finally we describe a publicly available script that can be used to compute mu-to-e conversion rates in nuclear targets.

Contribution of Neutralino and Chargino to Diagonal Form Factor of Majorana Neutrino in the Minimal Supersymmetric Standard Model

In this study, we have calculated the diagonal form factor and charge radius of Majorana neutrinos in the Minimal Supersymmetry Standard Model (MSSM) using Feynman-'t Hooft gauge and dimensional regularization. From the obtained result of calculations, we have seen that the main contribution come from chargino particles in MSSM and its contribution is very small than SM contribution. It is found that 〈r_ν^2 〉=1,66 .〖10〗^(-32) cm^2 for the charge radius of electron neutrinos which is in good agreement with results obtained from the scattering experiments.

Self-Consistent Extraction of Spectroscopic Bounds on Light New Physics

Fundamental physical constants are determined from a collection of precision measurements of elementary particles, atoms, and molecules. This is usually done under the assumption of the standard model (SM) of particle physics. Allowing for light new physics (NP) beyond the SM modifies the extraction of fundamental physical constants. Consequently, setting NP bounds using these data, and at the same time assuming the Committee on Data of the International Science Council recommended values for the fundamental physical constants, is not reliable. As we show in this Letter, both SM and NP parameters can be simultaneously determined in a consistent way from a global fit. For light vectors with QED-like couplings, such as the dark photon, we provide a prescription that recovers the degeneracy with the photon in the massless limit and requires calculations only at leading order in the small new physics couplings. At present, the data show tensions partially related to the proton charge radius determination. We show that these can be alleviated by including contributions from a light scalar with flavor nonuniversal couplings.

Low-energy nuclear physics and global neutron star properties

We address the question of the role of low-energy nuclear physics data in constraining neutron star global properties, e.g., masses, radii, angular momentum, and tidal deformability, in the absence of a phase transition in dense matter. To do so, we assess the capacity of 415 relativistic mean field and nonrelativistic Skyrme-type interactions to reproduce the ground state binding energies, the charge radii, and the giant monopole resonances of a set of spherical nuclei. The interactions are classified according to their ability to describe these characteristics, and we show that a tight correlation between the symmetry energy and its slope is obtained provided that $N=Z$ and $N\ensuremath{\ne}Z$ nuclei are described with the same accuracy (mainly driven by the charge radius data). By additionally imposing the constraints from isobaric analog states and neutron skin radius in $^{208}\mathrm{Pb}$, we obtain the following estimates: ${E}_{\mathrm{sym},2}=31.8\ifmmode\pm\else\textpm\fi{}0.7$ MeV and ${L}_{\mathrm{sym},2}=58.1\ifmmode\pm\else\textpm\fi{}9.0$ MeV. We then analyze predictions of neutron star properties and we find that the $1.4{M}_{\ensuremath{\bigodot}}$ neutron star (NS) radius lies between 12 and 14 km for the ``better'' nuclear interactions. We show that (i) the better reproduction of low-energy nuclear physics data by the nuclear models only weakly impacts the global properties of canonical mass neutron stars and (ii) the experimental constraint on the symmetry energy is the most effective one for reducing the uncertainties in NS matter. However, since the density region where constraints are required are well above densities in finite nuclei, the largest uncertainty originates from the density dependence of the energy density functional (EDF), which remains largely unknown.

Revisiting the second law and weak cosmic censorship conjecture in high-dimensional charged-AdS black hole: an additional assumption

The verification of the second law of black hole mechanics and the WCCC in the context of enthalpy as mass of the black hole and its related thermodynamic properties has not been tested through a vast number of literature in the recent past. Such studies are of great physical importance as they provide us with a large number of information regarding the thermodynamics and the dynamics of AdS black hole systems. We invest the prior limited surveys of such analysis to investigate the WCCC for the D- dimensional asymptotically AdS-charged black holes characterized by its mass (M), electric charge (Q), and AdS radius (l) under the absorption of scalar particles of charge q. We examine the WCCC by analyzing the energy-momentum condition of the electrically charged particles as absorbed by the black holes. We prove that the conjecture is well verified irrespective of whether the initial black hole configurations are extremal or non-extremal by changing its charge, the AdS radius, and their variations. We show that the first law and the WCCC are valid for all spacetime dimensions (D) independent of the choice of the parameters characterizing the black holes. But to verify the second law in the extremal and non- extremal configurations one has to be very cautious as it gets strongly affected by the choices of the values of the black hole parameters and their variations. In other words, we use charged particle dynamics as described by the Hamilton-Jacobi equation to obtain the energy-momentum relation as the charged particle dropped into the higher dimensional charged AdS black hole and verify the thermodynamic laws when the scalar charged particle gets absorbed by the black holes and correspondingly the black hole neutralization in different manners. Additionally, we further probe the validity of WCCC in such a black hole background. In the context of the extended phase space, taking the grand canonical potential into account allow us to obtain the missing information about the variation of the cosmological constant necessary to construct the extended phase space, namely the notion of the black hole pressure, and which is absent in the previous literature so far.

Refined theoretical values of field and mass isotope shifts in thallium to extract charge radii of Tl isotopes.

Electronic factors for the field and mass isotope shifts in the 6p 2P3/2 → 7s 2S1/2 (535nm), 6p 2P1/2 → 6d 2D3/2 (277nm), and 6p 2P1/2 → 7s 2S1/2 (378nm) transitions in neutral thallium were calculated within the high-order relativistic coupled cluster approach. These factors were used to reinterpret previous experimental isotope shift measurements in terms of charge radii of a wide range of Tl isotopes. Good agreement between theoretical and experimental King-plot parameters was found for the 6p 2P3/2 → 7s 2S1/2 and 6p 2P1/2 → 6d 2D3/2 transitions. It was shown that the value of the specific mass shift factor for the 6p 2P3/2 → 7s 2S1/2 transition is not negligible compared with the value of normal mass shift in contrast to what had been suggested previously. Theoretical uncertainties in the mean square charge radii were estimated. They were substantially reduced compared with the previously ascribed ones and amounted to less than 2.6%. The achieved accuracy paves the way for a more reliable comparison of the charge radii trends in the lead region.

Dark states with electromagnetic form factors at electron colliders

Electromagnetically neutral dark sector particles may feebly interact with photons through higher dimensional effective operators, such as mass-dimension 5 magnetic and electric dipole moment, and a mass-dimension 6 anapole moment and charge radius operators. In this work, we use hypercharge gauge field form factors to treat dark states, which will induce not only electromagnetic form factors but also the corresponding $Z$ boson operators. Taking a Dirac fermion $\chi$ as an example, we investigate the probes of searching for such dark states at current and future $e^+e^-$ collider experiments including BESIII, STCF, Belle II and CEPC via monophoton searches. Comparing to current experiments, we find that electron colliders including BESIII, STCF, Belle II, which operate with the center-of-mass at several GeV, have leading sensitivity on the corresponding electromagnetic form factors for the mass-dimension 5 operators with dark states lighter than several GeV, while they can not provide competitive upper limits for the mass-dimension 6 operators. Future CEPC operated with the center-of-mass on and beyond the mass of $Z$-boson with competitive luminosity can probe the unexplored parameter space for dark states with mass-dimension 5 (6) operators in the mass region of $m\lesssim 100 $ GeV (10 MeV $\lesssim m\lesssim 100 $ GeV).

Tp53 haploinsufficiency is involved in hotspot mutations and cytoskeletal remodeling in gefitinib-induced drug-resistant EGFRL858R-lung cancer mice

Tumor heterogeneity is the major factor for inducing drug resistance. p53 is the major defender to maintain genomic stability, which is a high proportion mutated in most of the cancer types. In this study, we established in vivo animal models of gefitinib-induced drug-resistant lung cancer containing EGFRL858R and EGFRL858R*Tp53+/− mice to explore the molecular mechanisms of drug resistance by studying the genomic integrity and global gene expression. The cellular morphology of the lung tumors between gefitinib-induced drug-resistant mice and drug-sensitive mice were very different. In addition, in drug-resistant mice, the expression of many cytoskeleton-related genes were changed, accompanied by decreased amounts of actin filaments and increased amounts of microtubule, indicating that significant cytoskeletal remodeling is induced in gefitinib-induced drug-resistant EGFRL858R and EGFRL858R*Tp53+/− lung cancer mice. The gene expression profiles and involved pathways were different in gefitinib-sensitive, gefitinib-resistant and Tp53+/−-mice. Increases in drug resistance and nuclear size (N/C ratio) were found in EGFRL858R*Tp53+/− drug-resistant mice. Mutational hotspot regions for drug resistance via Tp53+/+- and Tp53+/−-mediated pathways are located on chromosome 1 and chromosome 11, respectively, and are related to prognosis of lung cancer cohorts. This study not only builds up a gefitinib-induced drug-resistant EGFRL858R lung cancer animal model, but also provides a novel mutation profile in a Tp53+/+- or Tp53+/−-mediated manner and induced cytoskeleton remodeling during drug resistance, which could contribute to the prevention of drug resistance during cancer therapy.

Dodecaploid Xenopus longipes provides insight into the emergence of size scaling relationships during development

Genome and cell size are strongly correlated across species1,2,3,4,5,6 and influence physiological traits like developmental rate.7,8,9,10,11,12 Although size scaling features such as the nuclear-cytoplasmic (N/C) ratio are precisely maintained in adult tissues,13 it is unclear when during embryonic development size scaling relationships are established. Frogs of the genus Xenopus provide a model to investigate this question, since 29 extant Xenopus species vary in ploidy from 2 to 12 copies (N)of the ancestral frog genome, ranging from 20 to 108 chromosomes.14,15 The most widely studied species, X.laevis (4N= 36) and X.tropicalis (2N= 20), scale at all levels, from body size to cellular and subcellular levels.16 Paradoxically, the rare, critically endangered dodecaploid (12N= 108) Xenopus longipes (X.longipes) is a small frog.15,17 We observed that despite some morphological differences, X.longipes and X.laevis embryogenesis occurred with similar timing, with genome to cell size scaling emerging at the swimming tadpole stage. Across the three species, cell size was determined primarily by egg size, whereas nuclear size correlated with genome size during embryogenesis, resulting in different N/C ratios in blastulae prior to gastrulation. At the subcellular level, nuclear size correlated more strongly with genome size, whereas mitotic spindle size scaled with cell size. Our cross-species study indicates that scaling of cell size to ploidy is not due to abrupt changes in cell division timing, that different size scaling regimes occur during embryogenesis, and that the developmental program of Xenopus is remarkably consistent across a wide range of genome and egg sizes.

Moonlight Is Perceived as a Signal Promoting Genome Reorganization, Changes in Protein and Metabolite Profiles and Plant Growth

Rhythmic exposure to moonlight has been shown to affect animal behavior, but its effects on plants, often observed in lunar agriculture, have been doubted and often regarded as myth. Consequently, lunar farming practices are not well scientifically supported, and the influence of this conspicuous environmental factor, the moon, on plant cell biology has hardly been investigated. We studied the effect of full moonlight (FML) on plant cell biology and examined changes in genome organization, protein and primary metabolite profiles in tobacco and mustard plants and the effect of FML on the post-germination growth of mustard seedlings. Exposure to FML was accompanied by a significant increase in nuclear size, changes in DNA methylation and cleavage of the histone H3 C-terminal region. Primary metabolites associated with stress were significantly increased along with the expression of stress-associated proteins and the photoreceptors phytochrome B and phototropin 2; new moon experiments disproved the light pollution effect. Exposure of mustard seedlings to FML enhanced growth. Thus, our data show that despite the low-intensity light emitted by the moon, it is an important environmental factor perceived by plants as a signal, leading to alteration in cellular activities and enhancement of plant growth.