Non-uniform liquid in external field

To calculate the density profile of a liquid in an external field, it is necessary to consider the density as a functional of the system\u27s chemical potential, i.e. the correlation effects must be investigated. On the basis of a statistical-mechanical calculation, the authors obtained an expansion of the liquid density into a series of moments of correlation functions of different orders. The expression for the liquid density profile was obtained as a sum of local and correlation terms. The correlation term has been calculated within the Ornstein-Zernike approximation in the vicinity of the critical point. It is shown that this term decreases the total variation of density by about 10%

Дослідження структурних особливостей взаємодії S-протеїну SARS-CoV-2 з ліпідними мембранами методом малокутового розсіяння нейтронів

The effect of SARS-CoV-2 coronavirus S-protein on the structural parameters of the model lipid membrane on dimyristoylphosphatidylcholine (DMPC) systems with cholesterol and melatonin impurities was studied by the method of small angle neutron scattering. It is shown that an increase in the concentration of melatonin in the lipid membrane leads to a decrease in the thickness of the lipid bilayer, and an increase in the concentration of cholesterol leads to an increase in it. It has been suggested that increasing the concentration of melatonin in the membrane prevents the interaction of coronaviral S-protein with the lipid membrane of the cell. In the presence of cholesterol impurities in the system, the interaction of the lipid membrane with the active part of the S-protein occurs depending on the phase state of the lipid. Thus, when the lipid is in the gel phase (at 10 ° C), the active part of the S-protein does not change the structural parameters of the lipid bilayer, i.e. the interaction between the lipid membrane and the active part of the S-protein does not occur. At 37 ° C, when the lipid is in the liquid crystalline phase, the addition of RBD SARS-CoV-2 in the system DMPC / 30% Cholesterol / D2O leads to a decrease in membrane thickness, indicating the interaction of S-protein with the membrane. Pages of the article in the issue: 127 - 130 Language of the article: UkrainianМетодом малокутового розсіяння нейтронів проведено дослідження впливу S-протеїну коронавірусу SARS-CoV-2 на структурні параметри модельної ліпідної мембрани на системах диміристоїлфосфатидилхоліну (ДМФХ) з домішками холестерину та мелатоніну. Висунуто припущення, що збільшення концентрації мелатоніну в мембрані запобігає взаємодії коронавірусного S-протеїну з ліпідною мембраною клітини. За присутності домішок холестерину в системі взаємодія ліпідної мембрани з активною частиною S-протеїну відбувається залежно від фазового стану ліпіду: у випадку гель-фази взаємодія не відбувається, а у рідкокристалічній фазі додавання RBD SARS-CoV-2 в систему призводить до зменшення товщини мембрани

The type 2C phosphatase Wip1: An oncogenic regulator of tumor suppressor and DNA damage response pathways

The Wild-type p53-induced phosphatase 1, Wip1 (or PPM1D), is unusual in that it is a serine/threonine phosphatase with oncogenic activity. A member of the type 2C phosphatases (PP2Cδ), Wip1 has been shown to be amplified and overexpressed in multiple human cancer types, including breast and ovarian carcinomas. In rodent primary fibroblast transformation assays, Wip1 cooperates with known oncogenes to induce transformed foci. The recent identification of target proteins that are dephosphorylated by Wip1 has provided mechanistic insights into its oncogenic functions. Wip1 acts as a homeostatic regulator of the DNA damage response by dephosphorylating proteins that are substrates of both ATM and ATR, important DNA damage sensor kinases. Wip1 also suppresses the activity of multiple tumor suppressors, including p53, ATM, p16INK4a and ARF. We present evidence that the suppression of p53, p38 MAP kinase, and ATM/ATR signaling pathways by Wip1 are important components of its oncogenicity when it is amplified and overexpressed in human cancers

The decatenation checkpoint

The decatenation checkpoint delays entry into mitosis until the chromosomes have been disentangled. Deficiency in or bypass of the decatenation checkpoint can cause chromosome breakage and nondisjunction during mitosis, which results in aneuploidy and chromosome rearrangements in the daughter cells. A deficiency in the decatenation checkpoint has been reported in lung and bladder cancer cell lines and may contribute to the accumulation of chromosome aberrations that commonly occur during tumour progression. A checkpoint deficiency has also been documented in cultured stem and progenitor cells, and cancer stem cells are likely to be derived from stem and progenitor cells that lack an effective decatenation checkpoint. An inefficient decatenation checkpoint is likely to be a source of the chromosome aberrations that are common features of most tumours, but an inefficient decatenation checkpoint in cancer stem cells could also provide a potential target for chemotherapy

Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium

10.1186/bcr3381Breast Cancer Research15

HPV16 E7-Dependent Transformation Activates NHE1 through a PKA-RhoA-Iinduced Inhibition of p38alpha

Background: Neoplastic transformation originates from a large number of different genetic alterations. Despite this genetic variability, a common phenotype to transformed cells is cellular alkalinization. We have previously shown in human keratinocytes and a cell line in which transformation can be turned on and followed by the inducible expression of the E7 oncogene of human papillomavirus type 16 (HPV16), that intracellular alkalinization is an early and essential physiological event driven by the up-regulation of the Na/H-+(+) exchanger isoform 1 (NHE1) and is necessary for the development of other transformed phenotypes and the in vivo tumor formation in nude mice.Methodology: Here, we utilize these model systems to elucidate the dynamic sequence of alterations of the upstream signal transduction systems leading to the transformation-dependent activation of NHE1.Principal Findings: We observe that a down-regulation of p38 MAPK activity is a fundamental step in the ability of the oncogene to transform the cell. Further, using pharmacological agents and transient transfections with dominant interfering, constitutively active, phosphorylation negative mutants and siRNA strategy to modify specific upstream signal transduction components that link HPV16 E7 oncogenic signals to up-regulation of the NHE1, we demonstrate that the stimulation of NHE1 activity is driven by an early rise in cellular cAMP resulting in the down-stream inhibition of p38 MAPK via the PKA-dependent phosphorylation of the small G-protein, RhoA, and its subsequent inhibition.Conclusions: All together these data significantly improve our knowledge concerning the basic cellular alterations involved in oncogene-driven neoplastic transformation

MAPK-Activated Protein Kinase 2 Is Required for Mouse Meiotic Spindle Assembly and Kinetochore-Microtubule Attachment

MAPK-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple physiological functions in mitosis. Here, we show for the first time the unique distribution pattern of MK2 in meiosis. Phospho-MK2 was localized on bipolar spindle minus ends and along the interstitial axes of homologous chromosomes extending over centromere regions and arm regions at metaphase of first meiosis (MI stage) in mouse oocytes. At metaphase of second meiosis (MII stage), p-MK2 was localized on the bipolar spindle minus ends and at the inner centromere region of sister chromatids as dots. Knockdown or inhibition of MK2 resulted in spindle defects. Spindles were surrounded by irregular nondisjunction chromosomes, which were arranged in an amphitelic or syntelic/monotelic manner, or chromosomes detached from the spindles. Kinetochore–microtubule attachments were impaired in MK2-deficient oocytes because spindle microtubules became unstable in response to cold treatment. In addition, homologous chromosome segregation and meiosis progression were inhibited in these oocytes. Our data suggest that MK2 may be essential for functional meiotic bipolar spindle formation, chromosome segregation and proper kinetochore–microtubule attachments