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

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

10.1186/bcr3381Breast Cancer Research15

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

Medulloblastomas overexpress the p53-inactivating oncogene WIP1/PPM1D

Medulloblastoma is the most common malignant brain tumor of childhood. Despite numerous advances, clinical challenges range from recurrent and progressive disease to long-term toxicities in survivors. The lack of more effective, less toxic therapies results from our limited understanding of medulloblastoma growth. Although TP53 is the most commonly altered gene in cancers, it is rarely mutated in medulloblastoma. Accumulating evidence, however, indicates that TP53 pathways are disrupted in medulloblastoma. Wild-typep53-induced phosphatase 1 (WIP1 or PPM1D) encodes a negative regulator of p53. WIP1 amplification (17q22-q23) and its overexpression have been reported in diverse cancer types. We examined primary medulloblastoma specimens and cell lines, and detected WIP1 copy gain and amplification prevalent among but not exclusively in the tumors with 17q gain and isochromosome 17q (i17q), which are among the most common cytogenetic lesions in medulloblastoma. WIP1 RNA levels were significantly higher in the tumors with 17q gain or i17q. Immunoblots confirmed significant WIP1 protein in primary tumors, generally higher in those with 17q gain or i17q. Under basal growth conditions and in response to the chemotherapeutic agent, etoposide, WIP1 antagonized p53-mediated apoptosis in medulloblastoma cell lines. These results indicate that medulloblastoma express significant levels of WIP1 that modulate genotoxic responsiveness by negatively regulating p53

A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine

Background: p53 is an important tumour suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated. Methods: We have conditionally deleted the Adenomatous Polyposis coli gene (Apc) from the adult murine intestine in wild type and p53 deficient environments and subsequently compared the phenotype and transcriptome profiles in both genotypes. Results: Expression of p53 was shown to be elevated following the conditional deletion of Apc in the adult small intestine. Furthermore, p53 status was shown to impact on the transcription profile observed following Apc loss. A number of key Wnt pathway components and targets were altered in the p53 deficient environment. However, the aberrant phenotype observed following loss of Apc (rapid nuclear localisation of β-catenin, increased levels of DNA damage, nuclear atypia, perturbed cell death, proliferation, differentiation and migration) was not significantly altered by the absence of p53. Conclusion: p53 related feedback mechanisms regulating Wnt signalling activity are present in the intestine, and become activated following loss of Apc. However, the physiological Wnt pathway regulation by p53 appears to be overwhelmed by Apc loss and consequently the activity of these regulatory mechanisms is not sufficient to modulate the immediate phenotypes seen following Apc loss. Thus we are able to provide an explanation to the apparent contradiction that, despite having a Wnt regulatory capacity, p53 loss is not associated with early lesion development