Tumour suppressor function of MDA-7/IL-24 in human breast cancer

Introduction Melanoma differentiation associated gene-7 (MDA-7), also known as interleukin (IL)-24, is a tumour suppressor gene associated with differentiation, growth and apoptosis. However, the mechanisms underlying its anti-neoplastic activity, tumour-specificity and efficacy across a spectrum of human cancers have yet to be fully elucidated. In this study, the biological impact of MDA-7 on the behavior of breast cancer (BC) cells is evaluated. Furthermore, mRNA expression of MDA-7 is assessed in a cohort of women with BC and correlated with established pathological parameters and clinical outcome. Methods The human BC cell line MDA MB-231 was used to evaluate the in-vitro impact of recombinant human (rh)-MDA-7 on cell growth and motility, using a growth assay, wounding assay and electric cell impedance sensing (ECIS). Localisation of MDA-7 in mammary tissues was assessed with standard immuno-histochemical methodology. BC tissues (n = 127) and normal tissues (n = 33) underwent RNA extraction and reverse transcription, MDA-7 transcript levels were determined using real-time quantitative PCR. Transcript levels were analyzed against tumour size, grade, oestrogen receptor (ER) status, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI) and clinical outcome over a 10 year follow-up period. Results Exposure to rh-MDA-7 significantly reduced wound closure rates for human BC cells in-vitro. The ECIS model demonstrated a significantly reduced motility and migration following rh-MDA-7 treatment (p = 0.024). Exposure to rh-MDA-7 was only found to exert a marginal effect on growth. Immuno-histochemical staining of human breast tissues revealed substantially greater MDA-7 positivity in normal compared to cancer cells. Significantly lower MDA-7 transcript levels were identified in those predicted to have a poorer prognosis by the NPI (p = 0.049) and those with node positive tumours. Significantly lower expression was also noted in tumours from patients who died of BC compared to those who remained disease free (p = 0.035). Low levels of MDA-7 were significantly correlated with a shorter disease free survival (mean = 121.7 vs. 140.4 months, p = 0.0287) on Kaplan-Meier survival analysis. Conclusion MDA-7 significantly inhibits the motility and migration of human BC cells in-vitro. MDA-7 expression is substantially reduced in malignant breast tissue and low transcript levels are significantly associated with unfavourable pathological parameters, including nodal positivity; and adverse clinical outcomes including poor prognosis and shorter disease free survival. MDA-7 offers utility as a prognostic marker and potential for future therapeutic strategies

Thermal Degradation of Adsorbed Bottle-Brush Macromolecules: Molecular Dynamics Simulation

The scission kinetics of bottle-brush molecules in solution and on an adhesive substrate is modeled by means of Molecular Dynamics simulation with Langevin thermostat. Our macromolecules comprise a long flexible polymer backbone with $L$ segments, consisting of breakable bonds, along with two side chains of length $N$, tethered to each segment of the backbone. In agreement with recent experiments and theoretical predictions, we find that bond cleavage is significantly enhanced on a strongly attractive substrate even though the chemical nature of the bonds remains thereby unchanged. We find that the mean bond life time decreases upon adsorption by more than an order of magnitude even for brush molecules with comparatively short side chains $N=1 \div 4$. The distribution of scission probability along the bonds of the backbone is found to be rather sensitive regarding the interplay between length and grafting density of side chains. The life time declines with growing contour length $L$ as $\propto L^{-0.17}$, and with side chain length as $\propto N^{-0.53}$. The probability distribution of fragment lengths at different times agrees well with experimental observations. The variation of the mean length $L(t)$ of the fragments with elapsed time confirms the notion of the thermal degradation process as a first order reaction.Comment: 15 pages, 7 figure

Nomenclatural standards and genetic passports of potato cultivars bred at the Leningrad Research Institute for Agriculture “Belogorka”

In the present paper, the potato cultivars bred at the Leningrad Research Institute for Agriculture “Belogorka”, were taken as an example for demonstrating the results of elaboration of methodological approaches that are currently developed at the N.I. Vavilov Institute of Plant Genetic Resources (VIR) for the preparing of nomenclatural standards and their genotyping. In 2018, joint research of VIR scientists and breeders from the Leningrad Research Institute for Agriculture “Belogorka” began in the field of preparing nomenclatural standards for potato cultivars bred at this institute. Nomenclatural standards were prepared according to the ‘International Code of Nomenclature for Cultivated Plants’. Plant material for herbarium specimens was collected in the experimental field of the “Belogorka” Institute in 2018 by cultivar authors and handed over to the VIR Herbarium of cultivated plants, their wild relatives and weeds (WIR). The plant material included stems with inflorescences and later - tubers of 21 cultivars which were bred at the “Belogorka” Institute. Two precultivars undergoing State variety testing and three breeding clones were also included in this study. Just before herbarium preparation, the obtained plant material was photographed, plant morphological characters described, and the results compared with the description given in such official documents as the “Cultivar Questionnaireˮ and “Description of selection achievementˮ. The nomenclatural standards of 21 cultivars registered in the VIR Herbarium Database and transferred for conservation to the VIR herbarium, are published in this paper. Before herbarium preparation, the plant material was sampled for DNA extraction and subsequent genotyping and molecular screening. The genetic passports include information about the polymorphism of 10 chromosome-specific microsatellite loci, as well as the data on the presence/absence of diagnostic fragments of 12 markers of the 11 R-genes conferring resistance to diseases and pests, and for some cultivars – the information about their cytoplasm type. These genetic passports are valuable not only because different types of DNA markers were used in their preparing (SSR, SCAR and CAPS markers of the R genes; markers specific to different loci of the nuclear and organelle genomes), but first of all because of the material itself, as the DNA samples were isolated from the plants with the assigned status of nomenclatural standard for each particular cultivar. Based on the genetic passports data, trueness to type of the “Belogorka” cultivar samples obtained from various sources was verified

Effect of Peierls transition in armchair carbon nanotube on dynamical behaviour of encapsulated fullerene

The changes of dynamical behaviour of a single fullerene molecule inside an armchair carbon nanotube caused by the structural Peierls transition in the nanotube are considered. The structures of the smallest C20 and Fe@C20 fullerenes are computed using the spin-polarized density functional theory. Significant changes of the barriers for motion along the nanotube axis and rotation of these fullerenes inside the (8,8) nanotube are found at the Peierls transition. It is shown that the coefficients of translational and rotational diffusions of these fullerenes inside the nanotube change by several orders of magnitude. The possibility of inverse orientational melting, i.e. with a decrease of temperature, for the systems under consideration is predicted.Comment: 9 pages, 6 figures, 1 tabl

Contradiction and change in state socialism

No abstract available

MOLECULAR SCREENING OF POTATO VARIETIES BRED IN THE NORTHWESTERN ZONE OF THE RUSSIAN FEDERАTION

Increasing the resistance of varieties to diseases and pests is a priority in potato breeding. Many potato varieties created in the Leningrad Scientific Research Institute of Agriculture “Belogorka” are multi-species hybrids possessing complex resistance to the most spread pathogens in combination with a high plasticity, which determined their zoning in many regions of the Russian Federation. Potato varieties and hybrids created in different periods of time in this institute and in the Ltd Breeding company “LiGa” were included in marker-assisted selection with 22 markers of 14 R genes conferring extreme resistance to viruses PVY and PVX, resistance to cyst nematodes Globodera pallida (patotypes Pa2, Pa3) and G. rostochiensis (pathotype Ro1) and resistance to late blight. The data of molecular screening were compared with the results of the State Test of Varieties for Disease Resistance, as well as with other published sources. Markers of sterile and fertile cytoplasm types were also used in the study. Based on the results of molecular screening, varieties and hybrids with different combinations of markers of R genes conferring resistance to the most harmful pathogens (Rysto, Ry-fsto, Rx1, Rx2, Gro1-4, H1, Gpa2, R1, R3a, Rpi-blb1, Rpi-sto1) were detected. Among them, genotypes with sterile D-, T-, W/gamma cytoplasmic types were selected. Analysis of their pollen fertility, crossability and pedigree data showed that breeders succeed in obtaining fertile forms with the D- and T-types of cytoplasm carrying genetic material of Mexican polyploid species Solanum stoloniferum and S. demissum. The information about the presence of markers of R genes and about cytoplasm types of hybrids and varieties will allow an effective implementation of further breeding programs for resistance to a complex of pathogens, including pyramiding of R genes. The data of molecular screening made it possible to specify the pedigrees of several varieties and hybrids that have been created over several decades

Эффект интрамиокардиального введения аллогенного биоматериала на уровень ангиогенеза и ремоделирования постишемического рубца у крыс

Scar smoothing out, angiogenesis stimulation and cardiomyogenesis in myocardial infarction still remain pressing issues despite the variety of existing methods. One of the ways to correct them is intramyocardial implantation of an alloplant biomaterial (ABM) suspension. ABM serves as an inhibitor of fibroneogenesis in various tissues with chronic inflammatory processes. No studies have been carried out with regards to acute myocardial infarction. Objective: to assess the dynamics of the number of bFGF-1 + cells and CD68 macrophages, the degree of angiogenesis amidst the use of ABM in the formation of postinfarction scar in the experiment. Materials and methods. Experimental studies were performed on 100 male Wistar rats weighing 0.18–0.25 kg. Coronary artery ligation was performed on all animals. In the experimental group, the ABM suspension (12 mg) was injected intramyocardially. We used histological, electron microscopic, immunohistochemical (CD68, bFGF-1), morphometric and statistical research methods. Hearts were procured at day 3, 7, 14, 30, and 45. Results. The use of an allogeneic biomaterial immediately after coronary artery stenosis could reduce the area of cicatricial myocardial degeneration by two fold by accelerating inflammatory response and the onset of early proliferative phase. In the reactive zone after ABM implantation, macrophage myocardial infiltration significantly decreased in comparison to the control group. The use of ABM ensures significant predominance of bFGF-1+ cells in the initial period of inflammation (3–14 days). Subsequently (14–45 days), inflammatory cytokine expression became several times less, which corresponded to biodegradation and resorption of the biomaterial. In the control group, during the acute phase of inflammation (3–14 days), bFGF-1+ cells were low in number. Subsequently (14–45 days), cytokine expression increased significantly, causing rapid accumulation of collagen fibers and scarring. In myocardial regeneration after a heart attack in the experiment, ABM stimulated angiogenesis, whose level was three times higher than in the control group. It was noted that ABM serves as a regulator of the neofibrillogenesis-fibroclasia balance in tissue. Conclusion. Macrophage migration inhibition and suppression of pro-inflammatory orientation of macrophages should be indicated as one of the directions of therapeutic correction strategy for ischemic myocardial injuries. Alloplant biomaterial used in the acute phase of myocardial inflammation can serve as such alternative.Проблемы нивелирования рубца, стимуляция ангиогенеза и кардиомиогенеза при инфаркте миокарда не теряют своей актуальности, несмотря на многообразие существующих методов. Одним из способов их коррекции предлагается интрамиокардиальная имплантация суспензии децеллюляризированного биоматериала (ДЦБМ), изготовленного из волокнистых соединительно-тканных образований аллогенного происхождения. ДЦБМ служит ингибитором фибронеогенеза в различных тканях с хроническими воспалительными процессами. В отношении острого инфаркта миокарда исследования не проводились. Цель. Оценка динамики численности bFGF-1 позитивных клеток, макрофагов CD 68, степени ангиогенеза в условиях применения ДЦБМ при формировании постинфарктного рубца в эксперименте. Материалы и методы. Экспериментальные исследования были проведены на 100 крысах-самцах породы Вистар массой 0,18–0,25 кг. Всем животным проведено лигирование коронарной артерии. В опытной группе интрамиокардиально вводили суспензию ДЦБМ (12 мг). В работе использовали гистологические, электронно-микроскопические, иммуногистохимические (CD 68, bFGF-1), морфометрические и статистические методы исследования. Забор сердец проводили через 3, 7, 14, 30, 45 суток. Результаты. Использование аллогенного биоматериала сразу после стенозирования коронарной артерии позволяет более чем в 2 раза уменьшить площадь рубцового перерождения миокарда за счет ускорения течения воспалительного ответа и наступления ранней пролиферативной фазы. В реактивной зоне после имплантации ДЦБМ значительно снижалась инфильтрация миокарда макрофагами по сравнению с контрольной группой. Использование ДЦБМ обеспечивало значительное преобладание bFGF-1+-клеток в начальный период воспаления (3–14 суток). В последующем (14–45 суток) экспрессия фиброкина становилась в разы меньше, что соответствовало биодеградации и резорбции биоматериала. В контрольной же группе в период острой фазы воспаления (3–14 суток) уровень bFGF-1+-клеток был низким, а в последующем (14–45 суток) экспрессия цитокина значительно увеличивалась, что вызывало стремительное накопление коллагеновых волокон и рубцевание. В процессе формирования постинфарктного регенерата в эксперименте ДЦБМ стимулировал ангиогенез, уровень которого превышал показатели контрольной группы в три раза. Отмечено, что биоматериал служил регулятором баланса неофибриллогенеза-фиброклазии в ткани. Заключение. Одним из направлений стратегии терапевтической коррекции при ишемических повреждениях миокарда следует указать ингибирование миграции макрофагов и подавление их провоспалительной направленности. В качестве такой альтернативы может являться аллогенный децеллюляризированный биоматериал, изготовленный из экстраклеточного матрикса, примененный в острой фазе воспаления миокарда

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

KIAA0101 Is Overexpressed, and Promotes Growth and Invasion in Adrenal Cancer

Background: KIAA0101 is a proliferating cell nuclear antigen-associated factor that is overexpressed in some human malignancies. Adrenocortical neoplasm is one of the most common human neoplasms for which the molecular causes are poorly understood. Moreover, it is difficult to distinguish between localized benign and malignant adrenocortical tumors. For these reasons, we studied the expression, function and possible mechanism of dysregulation of KIAA0101 in human adrenocortical neoplasm. Methodology/Principal Findings: KIAA0101 mRNA and protein expression levels were determined in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 adrenocortical carcinoma (ACC). SiRNA knockdown was used to determine the functional role of KIAA0101 on cell proliferation, cell cycle, apoptosis, soft agar anchorage independent growth and invasion in the ACC cell line, NCI-H295R. In addition, we explored the mechanism of KIAA0101 dysregulation by examining the mutational status. KIAA0101 mRNA (9.7 fold) and protein expression were significantly higher in ACC (p,0.0001). KIAA0101 had sparse protein expression in only a few normal adrenal cortex samples, which was confined to adrenocortical progenitor cells. KIAA0101 expression levels were 84 % accurate for distinguishing between ACC and normal and benign adrenocortical tumor samples. Knockdown of KIAA0101 gene expression significantly decreased anchorage independent growth by 80 % and invasion by 60 % (p = 0.001; p = 0.006). W

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal