P130Cas Src-Binding and Substrate Domains Have Distinct Roles in Sustaining Focal Adhesion Disassembly and Promoting Cell Migration

The docking protein p130Cas is a prominent Src substrate found in focal adhesions (FAs) and is implicated in regulating critical aspects of cell motility including FA disassembly and protrusion of the leading edge plasma membrane. To better understand how p130Cas acts to promote these events we examined requirements for established p130Cas signaling motifs including the SH3-binding site of the Src binding domain (SBD) and the tyrosine phosphorylation sites within the substrate domain (SD). Expression of wild type p130Cas in Cas −/− mouse embryo fibroblasts resulted in enhanced cell migration associated with increased leading-edge actin flux, increased rates of FA assembly/disassembly, and uninterrupted FA turnover. Variants lacking either the SD phosphorylation sites or the SBD SH3-binding motif were able to partially restore the migration response, while only a variant lacking both signaling functions was fully defective. Notably, the migration defects associated with p130Cas signaling-deficient variants correlated with longer FA lifetimes resulting from aborted FA disassembly attempts. However the SD mutational variant was fully defective in increasing actin assembly at the protruding leading edge and FA assembly/disassembly rates, indicating that SD phosphorylation is the sole p130Cas signaling function in regulating these processes. Our results provide the first quantitative evidence supporting roles for p130Cas SD tyrosine phosphorylation in promoting both leading edge actin flux and FA turnover during cell migration, while further revealing that the p130Cas SBD has a function in cell migration and sustained FA disassembly that is distinct from its known role of promoting SD tyrosine phosphorylation

Cerebellar anaplastic astrocytoma in adult patients: 15 consecutive cases from a single institution and literature review

Adult cerebellar anaplastic astrocytomas (cAA) are rare entities and their clinical and genetic appearances are still ill defined. Previously, malignant gliomas of the cerebellum were combined and reviewed together (cAA and cerebellar glioblastomas (cGB), that could have possibly affected overall survival (OS) and progression-free survival (PFS). We present characteristics of 15 adult patients with cAA and compared them to a series of 45 patients with a supratentorial AA (sAA) in order to elicit the effect of tumor location on OS and PFS. The mean age at cAA diagnosis was 39.3 years (range 19–72). A history of neurofibromatosis type I was noted in 1 patient (6.7%). An IDH-1 mutation was identified in 6/15 cases and a methylated MGMT promoter in 5/15 cases. Patients in study and control groups were matched in age, sex and IDH-1 mutation status. Patients in a study group tended to present with longer overall survival (50 vs. 36.5 months), but the difference did not reach statistical significance. In both cAA and supratentorial AA groups presence of the IDH-1 mutation remains a positive predictor for the prolonged survival. The present study suggests that adult cAA constitute a group of gliomas with relatively higher rate of IDH-1 mutations and prognosis similar to supratentorial AA. The present study is the first to systematically compare cAA and supratentorial AA with respect to their genetic characteristics and suggests that both groups show a similar survival prognosis

The results of orthodontic treatment using computer design of structures

The article deals with the use of mathematical background and computer modeling in the process of treatment dental apparatus engineering. Drawing on mathematical calculations, veracity of which is validated by the results of experimental research, there in the clinic it has been used treatment appliance made of elastic polymer with set-up parameter

Effect of plant communities on aggregate composition and organic matter stabilisation in young soils

© 2014, Springer International Publishing Switzerland. Results: Deciduous forest soil accumulated the highest C content in the 0–5 cm layer (43 g C kg−1), whereas values in coniferous forest and arable soils were lower (30 and 12 g C kg−1, respectively). The highest portion of C in arable soil was accumulated in the mineral fraction (80 %), whereas 50–60 % of the C in forest soils were in POM. More C was associated with minerals in deciduous forest soil (16 g C kg−1 soil) than under coniferous forest and arable land (8–10 g C kg−1 soil). Conclusions: Particulate organic matter explains most of the differences in organic C accumulation in soils developed during 45 years under the three vegetation types on identical parent material. The C content of the mineral soil fraction was controlled by plant cover and contributed the most to differences in C accumulation in soils developed under similar vegetation type (forest). Objectives: Carbon (C) content in pools of very young soils that developed during 45 years from loess was analysed in relation to vegetation: deciduous and coniferous forests and cropland. We hypothesised that variations in the amount of particulate organic matter (POM) can explain the C accumulation and also affects the C bound to mineral surfaces in soil under various vegetation. Methods: Soil samples were collected under three vegetation types of a 45-year-old experiment focused on initial soil development. Aggregate and density fractionations were combined to analyse C accumulation in large and small macro- and microaggregates as well as in free and occluded POM and mineral factions

5-HT2B antagonism arrests non-canonical TGF-β1-induced valvular myofibroblast differentiation

Transforming growth factor-β1 (TGF-β1) induces myofibroblast activation of quiescent aortic valve interstitial cells (AVICs), a differentiation process implicated in calcific aortic valve disease (CAVD). The ubiquity of TGF-β1 signaling makes it difficult to target in a tissue specific manner; however, the serotonin 2B receptor (5-HT2B) is highly localized to cardiopulmonary tissues and agonism of this receptor displays pro-fibrotic effects in a TGF-β1-dependent manner. Therefore, we hypothesized that antagonism of 5-HT2B opposes TGF-β1-induced pathologic differentiation of AVICs and may offer a druggable target to prevent CAVD. To test this hypothesis, we assessed the interaction of 5-HT2B antagonism with canonical and non-canonical TGF-β1 pathways to inhibit TGF-β1-induced activation of isolated porcine AVICs in vitro. Here we show that AVIC activation and subsequent calcific nodule formation is completely mitigated by 5-HT2B antagonism. Interestingly, 5-HT2B antagonism does not inhibit canonical TGF-β1 signaling as identified by Smad3 phosphorylation and activation of a partial plasminogen activator inhibitor-1 promoter (PAI-1, a transcriptional target of Smad3), but prevents non-canonical p38 MAPK phosphorylation. It was initially suspected that 5-HT2B antagonism prevents Src tyrosine kinase phosphorylation; however, we found that this is not the case and time-lapse microscopy indicates that 5-HT2B antagonism prevents non-canonical TGF-β1 signaling by physically arresting Src tyrosine kinase. This study demonstrates the necessity of non-canonical TGF-β1 signaling in leading to pathologic AVIC differentiation. Moreover, we believe that the results of this study suggest 5-HT2B antagonism as a novel therapeutic approach for CAVD that merits further investigation

On the elastic constants of the zeolite chlorosodalite

The use of force-field based molecular modeling to predict the elastic constants of the zeolite chlorosodalite is described. Theoretical predictions of the on-axis and off-axis elastic constants strongly suggest that an error exists in the published elastic constants of the material. When the previous experimental data are corrected by transposing the published directional ultrasound velocities, excellent agreement is observed between the off-axis plots of sodalite produced by experiment and modeling. Further confirmation of the prediction is supplied by considering the Zener ratios of other inorganic materials that possess cubic symmetry. ©2006 American Institute of Physics

Comparative evaluation of the effectiveness of methods of alveolar bone preservation before dental implantation

This article presents comparative results of the developed concept with the use of a direct immediate prosthetics and a group where the postoperative period was managed without it. The concept of bone preservation before implantation allows not only to preserve the volume of its own tissues, but also prevents the development of complications characteristic of traditional methods of bone augmentatio

Efficiency of antinocyceptive support of patients with endodontic interventions for acute periodontitis

It is known that periodontitis is an inflammatory disease ofthe connective tissue anatomical formation located in the space between the compact plate of the dental alveoli and the cement of the tooth root. It has been proven that endodontic treatment for complicated forms of carious lesions is based on invasive interventio

Моделирование процессов возникновения и роста фрактальных структур и дефектов камер теплоэнергетических установок. Часть 1

The paper considers modeling the emergence and growth of possible fractal structures and defects on the inner surface of the chambers of thermal power units, which allow control and regulation of the development of such stochastic dynamic processes. We are talking about the use of modeling procedures for the given analysis, which are quite universal in the framework of certain approaches. A general qualitative consideration of the modeling of processes such as the deposition of materials on a solid surface of various complex configurations, and the occurrence of its fracturing and defects of fractal types, is given. In the first part, we consider an analogy between the processes of the emergence and growth of fractal structures and chamber defects with laser processes of controlled deposition of substances on the surface of a solid body and the growth of its fracturing. A number of models have been developed for the emergence and growth of fractal inhomogeneities of various types and configurations on a solid surface with identification of the possibility of their preliminary monitoring at the initial stage of their appearance. At the same time, both various surfaces in the form of coatings and the formation of fracturing and cluster zones of inhomogeneities and defects have been analyzed. The emphasis in the course of research has been made both on the analysis of their regulated structure, and also on the dynamics of the growth of fracturing and cluster zones of heterogeneities and defects in a certain direction. At the initial stage, the indicated process of formation of fractures and cluster zones of inhomogeneities and defects in space was monitored with different scaling: nano- and microscales. This study has been carried out within the framework of an analogy under the following conditions: firstly, given control over the cha-racteristics of similar objects in the corresponding laser experiment; secondly, the presence of a real possibility of ensuring their formation on the inner surfaces of the chambers in contact with the working substance; thirdly, the possibility of such structures influencing on the efficiency of various types of thermal power units in the context of achieving the desired direction and/or undesirability of changing the indicators and characteristics of units taking into account the laws of technical thermodynamics.Рассматривается моделирование возникновения и роста возможных фрактальных структур и дефектов на внутренней поверхности камер тепловых энергетических установок, допускающих контролирование и регулирование развития таких стохастических динамических процессов. Речь идет об использовании процедур моделирования для приводимого анализа, имеющих достаточно универсальный характер в рамках определенных подходов. Приведено общее качественное рассмотрение моделирования процессов как осаждения материалов на твердую поверхность различных сложных конфигураций, так и возникновения ее трещиноватости и дефектов фрактальных типов. В первой части проводится аналогия процессов возникновения и роста фрактальных структур и дефектов камер с лазерными процессами управляемого осаждения веществ на поверхность твердого тела и роста ее трещиноватости. Развит ряд моделей возникновения и роста фрактальных неоднородностей разного типа и конфигураций на твердой поверхности с выявлением возможности их предварительного мониторинга на начальном этапе появления. При этом проанализированы как различные поверхности в виде покрытий, так и образование трещиноватости и кластерных зон неоднородностей и дефектов. Акцент в ходе исследований сделан на анализе регулируемой их структуры, а также на динамике роста трещиноватости и кластерных зон неоднородностей и дефектов в определенном направлении. На начальном этапе осуществлялся мониторинг указанного процесса образования в пространстве трещиноватости и кластерных зон неоднородностей и дефектов с различным масштабированием: нано- и микромасштабами. Данное исследование проведено в рамках аналогии в условиях: во-первых, заданного управления характеристиками подобных объектов в соответствующем лазерном эксперименте; во-вторых, наличия реальной возможности обеспечения их образования на внутренних поверхностях камер при контакте с рабочим веществом; в-третьих, возможности влияния таких структур  на эффективность работы тепловых энергетических установок разного типа в контексте достижения нужной направленности и/или нежелательности изменения показателей и характеристик установок с учетом закономерностей технической термодинамики

Моделирование процессов возникновения и роста фрактальных структур и дефектов камер теплоэнергетических установок. Часть 2

The paper describes further development of model studies with the purpose to draw analogies of the occurrence  of possible inhomogeneities and defects of the fractal type on the surface of various objects under the action of laser radiation for different conditions and schemes of a laser simulation experiment in comparison with real processes in the chambers of thermal machines due to the contacts of the working substances with their surface. The subject of this consideration is related to the fact that in laser schemes one can relatively easily and in a controlled manner to study their topology in various modifications (in the range of 0D–3D structures formed on surfaces of various geometric shapes of the fractal type). This provides great opportunities for studying various frequently occurring undesirable random defects and inhomogeneities of  complex configuration with the development of unexpected processes in the dynamic modes of operation of various types of power units in their actual operation. This is determined by geometric analysis within the framework of the correspondding non-linear models with different  non-linear fractal images. In this aspect, we have used two models to consider the development of emerging fractal fractured structures: first, diffusion propagation/growth of cracks of different geometry with a set of local segments and fragments in different directions; secondly, with diffusely limited aggregation of their distribution (Diffusion-Limited Aggregation – DLA) using the formalism of cellular automata in percolation approximation for different algorithms for the formation of fractal structures. We present only the final results of calculations without details of their procedure, which is sufficient for a visual and qualitative determination of the process of growth of fracturing and defects. In this case, the final goal of consideration is to study the emergence of possible and controllable local areas / collectors, starting from surface structures, and their association with real objects on the surface of chambers with a working substance in power systems. The possible practical significance of such modeling and analysis is discussed to forecast their working conditions.В данной статье находят дальнейшее развитие модельные исследования по проведению аналогий возникновения возможных неоднородностей и дефектов фрактального типа на поверхности различных объектов под действием лазерного излучения в разных условиях и схемах лазерного имитационного эксперимента в сравнении с реальными процессами в камерах тепловых машин из-за контактов рабочего вещества с их поверхностью. Предмет такого рассмотрения связан с тем, что в лазерных схемах можно относительно легко и регулируемым образом управлять их топологией в разных модификациях (в диапазоне 1D–3D структур, образующихся на поверхностях разной геометрической формы фрактального типа). Это дает большие возможности для изучения различных часто возникающих нежелательных случайных дефектов и неоднородностей сложной конфигурации с развитием неожидаемых процессов при динамических режимах работы энергетических установок разного типа в условиях их реальной эксплуатации и определяется с помощью геометрического анализа в рамках соответствующих нелинейных моделей с различными нелинейными фрактальными образами. Нами использовались в данном аспекте две модели для рассмотрения развития возникающих фрактальных трещиноватых структур: во-первых, диффузионное распространение/рост трещин разной геометрии с совокупностью локальных отрезков и фрагментов в различных направлениях; во-вторых, с диффузно-ограниченной агрегацией их распространения (Diffusion-Limited Aggregation – DLA) с использованием формализма клеточных автоматов в перколяционном приближении для разных алгоритмов образования фрактальных структур. Приведем только итоговые результаты расчетов без деталей их процедуры, что достаточно для наглядного и качественного определения процесса роста трещиноватости и дефектов. При этом конечной целью рассмотрения является изучение возникновения возможных и контролируемых локальных областей/коллекторов, начиная с поверхностных структур, и их ассоциация с реальными объектами на поверхности камер с рабочим веществом в энергосистемах. Обсуждается возможная практическая значимость подобного моделирования и анализа