Paxillin-Y118 phosphorylation contributes to the control of Src-induced anchorage-independent growth by FAK and adhesion

<p>Abstract</p> <p>Background</p> <p>Focal adhesion kinase (FAK) and Src are protein tyrosine kinases that physically and functionally interact to facilitate cancer progression by regulating oncogenic processes such as cell motility, survival, proliferation, invasiveness, and angiogenesis.</p> <p>Method</p> <p>To understand how FAK affects oncogenesis through the phosphorylation of cellular substrates of Src, we analyzed the phosphorylation profile of a panel of Src substrates in parental and v-Src-expressing FAK+/+ and FAK-/- mouse embryo fibroblasts, under conditions of anchorage-dependent (adherent) and -independent (suspension) growth.</p> <p>Results</p> <p>Total Src-induced cellular tyrosine phosphorylation as well as the number of phosphotyrosyl substrates was higher in suspension versus adherent cultures. Although the total level of Src-induced cellular phosphorylation was similar in FAK+/+ and FAK-/- backgrounds, the phosphorylation of some substrates was influenced by FAK depending on adherence state. Specifically, in the absence of FAK, Src induced higher phosphorylation of p190RhoGAP, paxillin (poY118) and Crk irrespective of adhesion state, PKC-δ (poY311), connexin-43 (poY265) and Sam68 only under adherent conditions, and p56Dok-2 (poY351) and p120catenin (poY228) only under suspension conditions. In contrast, FAK enhanced the Src-induced phosphorylation of vinculin (poY100 and poY1065) and p130CAS (poY410) irrespective of adherence state, p56Dok-2 (poY351) and p120catenin (poY228) only under adherent conditions, and connexin-43 (poY265), cortactin (poY421) and paxillin (poY31) only under suspension conditions. The Src-induced phosphorylation of Eps8, PLC-γ1 and Shc (poY239/poY240) were not affected by either FAK or adherence status. The enhanced anchorage-independent growth of FAK-/-[v-Src] cells was selectively decreased by expression of paxillin^Y118F, but not by WT-paxillin, p120catenin^Y228For Shc^Y239/240F, identifying for the first time a role for paxillin^poY118in Src-induced anchorage-independent growth. Knockdown of FAK by siRNA in the human colon cancer lines HT-25 and RKO, resulted in increased paxillin^poY118levels under suspension conditions as well as increased anchorage-independent growth, supporting the notion that FAK attenuates anchorage-independent growth by suppressing adhesion-dependent phosphorylation of paxillin^Y118.</p> <p>Conclusion</p> <p>These data suggest that phosphorylation of Src substrates is a dynamic process, influenced temporally and spatially by factors such as FAK and adhesion.</p

The Design and Construction of Public Service Building in Developing Rural Regions During the Post COVID-19 Period: Cased on a Chinese Village Centre

The spread of COVID-19 has caused an increasing demand for public medical room. Cases of Chinese Huoshenshan Hospital and mobile cabin hospitals proved the effectiveness of constructing emergent medical buildings. However, these cases, usually with strict requirements on technology and infrastructure, are hard to implement in developing rural regions. Therefore, there is an urgent need for adapting industrial construction to the rural situation. This research introduced an adaptive approach for rural projects delivery during COVID-19. It is based on a longitudinal case study, recording and analysing the construction process of a village centre in Jiangsu, China, from 2019 to 2020. By comparing the construction process of actual operation and traditional method, the advantages in a shorter building period and lower labour density were verified. This research pointed out neglected risks in developing countries and provided a practical construction approach in these areas. It supported the prevention of COVID-19 global wide

Prevalence of dentine hypersensitivity among university students in Turkey

Background and Objective: Dentine hypersensitivity (DH) is a common clinical finding with a wide variation in prevalence values. There is lack of data on the prevalence of dentinal sensitivity in Turkish population. The aim of this study was to establish the prevalence of DH and to examine some associated factors such as initiating stimuli among university students in Kýrýkkale, Turkey.Materials and Methods: A cross-sectional survey was conducted among undergraduates of University of Kýrýkkale, Turkey. An electronic questionnaire was developed and distributed via e-mail to undergraduate students in Kýrýkkale University. Self-administered questionnaire elicited information on demography, self-reported dentinal sensitivity, thetrigger factor, professional treatment taken, and duration time. Test of significance was done with Chi square statistics. P&lt;0.05 was considered as significant.Results: A total of 1463 responses were evaluated in this study. One hundred and twenty-four students were diagnosed as having DH, giving a prevalence figure of 8.4%. The prevalence of DH in females was significantly higher than that in males. The most common initiating factor was cold drinks. Tooth sensitivity was found to be common among hardtoothbrush users. About 46% of patients reported that they had not undergone any treatment for the discomfort and 35% reported having had some sort of treatment. Among the participants with dentinal sensitivity, 58.8% of the respondents reported that they use soft drinks occasionally. Approximately 64.2% of the patients claimed that DH was present for1–6 days and the majority (87%) of the patients with hypersensitive teeth experienced pain occasionally.Conclusion: The prevalence of DH among university students was 8.4%. DH is not a common problem in undergraduate university students

Influence of amendments on soil structure and soil loss under simulated rainfall China’s loess plateau

Macromolecule polymers are significant types of chemical amendments because of their special structure, useful functions and low cost. Macromolecule polymers as soil amendment provide new territory for studying China’s agricultural practices and for soil and water conservation, because polymers have the ability to improve soil structure, increase rainfall penetration and control slope runoff. Through indoor laboratory experiments and outdoor artificial rainfall simulations, this study applied different consistencies of three amendments; polypropylene acid (PPA), polythene alcoholic (PTA) and urea-formaldehyde poly-condensate (UR) to China’s Loess and determined their effects on soil physical properties and on runoff-sediment yield. The results indicate that as a result of applying the amendments, (1) the water-stable soil aggregates content increases by 17.3%, the soil permeability increases by 41.8%, the soil density decreases by 11.2% and the soil water content increases by 28.0% compared to the control; (2) three amendment applied on sloping land can delay runoff and decrease runoff velocity; decrease erosive forces of raindrop impact and flowing water, reduce surface crusting and improve water infiltration, delay runoff engenderation and decrease runnoff velocity and soil erosion yield. Finally, this study also ascertained optimal application quantities and the most effective sort in three amendments, which PPA is most effective at lowering surface runoff, reducing soil loss and increasing soil penetration. These three amendments have broad potential for soil and water conservation; however, the duration of their effect and the optimal application quantities need to be researched further.Key words: Amendment, Runoff-Sediment Yield, Soil Physical Properties, Soil erosio

Effect of Addition of Different Levels of Commercial Inoculant of Lactic Acid Bacteria And Soluble Sugars on Fermentation of Wheat Straw Silage

اجريت الدراسة للتحري عن تأثير اضافة مستويات مختلفة من اللقاح التجاري لبكتيريا حامض اللاكتيك ((Ecosyl، 0 و 510 ×1 و610 ×1 وحدة مكونة للسبورات/غم مادة رطبة واربعة مستويات من الدبس كمصدر للسكريات الذائبة، 4 و 6 و 8 و 10% على اساس المادة الجافة على خصائص تخمرات سايلج تبن الحنطة. اضيفت اليوريا الى جميع نماذج السايلج بمعدل 1%. اظهرت النتائج ان اضافة اللقاح ادت الى تحسين (P&lt;0.01) تخمرات السايلج, اذ سجل اوطأ اس هيدروجيني (3.97) وتركيز نتروجين الامونيا (0.89% من النتروجين الكلي) واعلى تركيز لحامض اللاكتيك والأحماض&nbsp;الدهنية الطيارة الكلية (7.86 و1.74ملي مكافئ من المادة الجافة على التوالي) في نماذج سايلج تبن الحنطة المصنعة بإضافة المستوى المرتفع من اللقاح، الا انها ادت ايضا الى تراجع المتبقي من السكريات الذائبة. اظهرت النتائج ايضا حصول انخفاض معنوي (P&lt;0.01) في الأس الهيدروجيني بزيادة مستوى الدبس من 4 و6 الى 8 و10%، اذ بلغت القيم 4.86 و4.90 و4.70 و4.51 على التوالي. كما لوحظ حصول انخفاض معنوي (P&lt;0.01) في المتبقي من السكريات الذائبة في الماء وتركيز نتروجين الأمونيا بزيادة مستوى الدبس المضاف عند تصنيع نماذج السايلج. فيما ادى ذلك الى حصول زيادة معنوية (P&lt;0.01) تدريجية في تركيز حامض اللاكتيك، اذ بلغت القيم 2.69 و2.82 و2.23 &nbsp;و 4% من المادة الجافة في نماذج سايلج تبن الحنطة المصنعة بإضافة الدبس بمعدل 4 و 6 و8 و 10% على التوالي. كما لوحظ تأثير معنوي مماثل لزيادة مستوى الدبس على تركيز الاحماض الدهنية الطيارة الكلية. وبينت نتائج الدراسة ايضا ان جميع معايير التخمرات باستثناء تركيز الأحماض الدهنية الطيارة قد تأثرت معنويا (P&lt;0.01) بالتداخل بين تركيز لقاح بكتيريا حامض اللاكتيك ومصدر السكريات الذائبة.This study was conducted to investigate the effect of addition of different levels of commercial inoculant of lactic acid Bacteria (Ecosyl), 0, 1×105 and&nbsp; 1×106 &nbsp;cfu/g wet material and 4 levels of debis as a source of soluble sugars, 4, 6, 8 and 10% on dry matter (DM) basis on fermentation of wheat straw silage. Urea was added to all samples at rate of 1%. Results revealed that addition of inoculant improved (P&lt;0.01) silage fermentation, where, lower pH (3.97) and ammonia nitrogen (NH3-N) concentration (0.89% of total N) and higher lactic acid (LA) and total volatile fatty acids (VFA) concentrations (7.86 and 1.74% of DM, respectively) were recorded in samples of wheat straw silages prepared with addition of high level of inoculant. However, it also reduced the residual of water soluble carbohydrates (WSC) in these samples. Results also revealed that there was a significant (P&lt;0.01) reduction in pH with increasing level of debis from 4 to 6, 8 and 10%, values were 4.86, 4.90, 4.70 and 4.51, respectively. A significant (P&lt;0.01) reduction was also shown in the residual of WSC, values were, 2.69, 2.82, 2.23 and 4% of DM in samples of wheat straw silage prepared with addition of debis at rate of 4, 6, 8 and 10% respectively. Similar significant effect due to increasing level of debis was also observed in VFA concentrations. Results of this study showed that all parameters of silage fermentation except that of&nbsp; total VFA were significantly (P&lt;0.01) affected by interaction between levels of inoculant and source of soluble sugars.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp