The EGFR phosphatase RPTPγ is a redox-regulated suppressor of promigratory signaling.

Spatially organized reaction dynamics between proto-oncogenic epidermal growth factor receptor (EGFR) and protein tyrosine phosphatases determine EGFR phosphorylation dynamics in response to growth factors and thereby cellular behavior within developing tissues. We show that the reaction dynamics of mutual inhibition between RPTPγ phosphatase and autocatalytic ligandless EGFR phosphorylation enable highly sensitive promigratory EGFR signaling responses to subnanomolar EGF levels, when < 5% receptors are occupied by EGF. EGF thereby triggers an autocatalytic phospho-EGFR reaction by the initial production of small amounts of phospho-EGFR through transient, asymmetric EGF-EGFR2 dimers. Single cell RPTPγ oxidation imaging revealed that phospho-EGFR induces activation of NADPH oxidase, which in turn inhibits RPTPγ-mediated dephosphorylation of EGFR, tilting the autocatalytic RPTPγ/EGFR toggle switch reaction towards ligandless phosphorylated EGFR. Reversibility of this reaction to EGF is maintained by the constitutive phosphatase activity of endoplasmic reticulum-associated TCPTP. This RPTPγ/EGFR reaction at the plasma membrane causes promigratory signaling that is separated from proliferative signaling induced by accumulated, liganded, phosphorylated EGF-EGFR in endosomes. Accordingly, loss of RPTPγ results in constitutive promigratory signaling from phosphorylated EGFR monomers. RPTPγ is thus a suppressor of promigratory oncogenic but not of proliferative EGFR signaling.

Comparative Analysis of the Measles Antibody Levels in Healthy Medical Personnel of Maternity Ward and Women in Labor.

It has been proven that post-vaccination immunity to measles virus after two doses of vaccine is not able to persistently protect against infection throughout life. The goal of this research was to determine the immune layer to the measles virus among women in labor and maternity ward personnel in the same medical institution. The levels of IgG antibodies to measles virus in the umbilical cord blood of 594 women in labor and 88 workers of the maternity ward were studied by ELISA. It was revealed that 22.7% of umbilical cord blood serum samples from parturient women and 21.4% of blood serum samples from maternity ward personnel were seronegative (<0.18 IU/ml). Levels of IgG antibodies to measles virus in low values (<1.0 IU/ml) were detected in 67% of blood serum samples among women in labor and 68.9% among employees of the maternity ward. Among women in labor, women under 35 years of age are at the highest risk of contracting measles; the proportion of women with low levels of protective antibodies in this age group was almost 70%, and the proportion of women without protective levels of antibodies was 23%. Compared with the age group 36-43, the age of women in labor under 35 was associated with a higher chance of not having immune protection against infection with measles virus OR [95% CI] = 2.2 [1.1-4.5] (p = 0.02) or had a low level of protection OR [95% CI] = 1.9 [1.2-3.0] (p = 0.001). It was also found that among women over 35 years of age, the proportion of persons with a high level of antibodies in women in labor was statistically significantly higher than among members of the maternity ward staff (13 and 0%, respectively, p = 0.007). Thus, maternity ward employees and women in labor constitute a risk group for measles due to the presence of a high proportion of seronegative persons among women of childbearing age (both maternity ward employees and women in labor). These conditions create the need to revise current approaches to present vaccination procedures, especially in the current epidemiological situation with COVID-19.

Relativistic slingshot: A source for single circularly polarized attosecond x-ray pulses.

We propose a mechanism to generate a single intense circularly polarized attosecond x-ray pulse from the interaction of a circularly polarized relativistic few-cycle laser pulse with an ultrathin foil at normal incidence. Analytical modeling and particle-in-cell simulation demonstrate that a huge charge-separation field can be produced when all the electrons are displaced from the target by the incident laser, resulting in a high-quality relativistic electron mirror that propagates against the tail of the laser pulse. The latter is efficiently reflected as well as compressed into an attosecond pulse that is also circularly polarized.

Pregnancy-Associated Plasma Protein-A, Alpha-2-Macroglobulin, Pregnancy Zone Protein and Their Complexes with IgG in Sera of Healthy Non-Pregnant and Pregnant Woman, and Patients with Breast Cancer.

The purpose of this study was to measure alpha-2-macroglobulin-IgG (alpha(2)-MG-IgG), pregnancy zone protein-IgG (PZP-IgG) and pregnancy-associated plasma protein-A-IgG (PAPP-A-IgG) complex concentrations in serum in comparison with total alpha(2)-MG, PZP and PAPP-A concentration, and to determine the possible role of such complexes. Serum samples were obtained from 20 healthy women, 30 patients with verified metastatic breast cancer (stage III-IV) before the treatment and 40 healthy women with normal pregnancy (I-III trimester in dynamics). The serum concentrations of alpha(2)-MG-IgG, PZP-IgG and PAPP-A-IgG complexes were measured by ELISA. It has been shown that the immune complexes of the major proteinase inhibitors such as alpha(2)-MG, PZP and PAPP-A with IgG may be found at minor concentration in blood of both the healthy women and patients with breast cancer. On the other hand, their physiological functions in organism are absolutely different. We suggest that alpha(2)-MG-IgG and PZP-IgG complexes can serve as immunoregulatory signal molecules. Thus, after calculation of a molar ratio, less than 1% of alpha(2)-MG and PZP were marked by IgG. On the contrary, one PAPP-A molecule can bind to 10-15 IgG molecules in samples of control non-pregnant women and breast cancer patients. Such a kind of binding gives an evidence in favor of alternative way of utilization and degradation of PAPP-A by monocyte-macrophages through a Fc-receptor.