Very ‘sticky’ proteins – not too sticky after all?

Abstract A considerable number of soluble proteins in cells that biochemists try to analyze are difficult to handle because they seem to behave like sponges that ‘suck up’ many other proteins. We argue here that this behavior is commonly an artifact introduced by the experimenting scientist and that we need to study proteins like animals in the wild: they will only reveal many of their secrets when carefully observed in their largely undisturbed, natural environment. Computational studies that attempt to realistically model cellular protein networks must also factor in the diverse protein habitats to be found in cells.</p

Derrida’s Earth: A Topography of World, Earth, and Khôra

In this paper, I develop a topography of Derrida’s concepts of earth, world, and khôra in order to better map out, triangulate, and ultimately understand Derrida’s thought of the earth both as a response to Heidegger’s earth and on his own terms. In Heidegger, earth is what presents itself as concealed in the disclosure of Being, it is what resists intelligible analysis. Derrida argues that there is a more anterior earth than this one that presents itself in the disclosure of Being. Derrida’s earth can only be recognized in the trace of passive alterity left behind and re-inherited when the world and earth are continuously deferred and re-differentiated from one another. This anterior earth is pointed to only in the ways Being is vulnerable to this context of alterity in the differentiation into world and earth, shaping this differentiation without becoming present in itself. For Derrida, the disclosure of Being can only happen in the repetition of its sense through the deferral to and differentiation of its elements. This anterior earth can only be disclosed through differentiation, and thus cannot become present in itself, not because any particular part of it cannot ever be uncovered, but because the very way it comes to be disclosed as Being is through this repetition of differentiation that changes Being even as it is gathered. The “site” which receives this world anew in each deferral and differentiation is khôra

The Src family kinase inhibitor drug Dasatinib and glucocorticoids display synergistic activity against tongue squamous cell carcinoma and reduce MET kinase activity

Background: Tongue squamous cell carcinoma (TSCC) is an aggressive cancer associated with a poor prognosis and limited treatment options, necessitating new drug targets to improve therapeutic outcomes. Our current work studies protein tyrosine kinases as well-known targets for successful cancer therapies. It focuses on Src family kinases (SFK), which are known to play a critical role in some head and neck tumors. Methods: Western blot analyses of phospho-tyrosine protein patterns in 34 TSCC lines facilitated the investigation of SFK as contributors to these phosphorylations. The SFK inhibitors PP2 and Dasatinib were utilized to determine SFK contributions to cell motility and survival. A high-throughput screen with 1600 FDA-approved drugs was performed with three TSCC lines to discover drugs that act synergistically with Dasatinib against TSCC cell viability. Glucocorticoids emerged as potential candidates and were further investigated in 2D culture and by 3D soft agar colony formation. Dexamethasone was chosen as the major tool for our analyses of synergistic effects of Dasatinib and glucocorticoids on TSCC lines. Effects on the cell cycle were investigated by flow cytometry and expression levels of cell cycle regulators. Senescence was analyzed by senescence-associated β galactosidase detection and p27Kip1 protein expression. Autophagy was measured by Acridine Orange staining. Results: A panel of 34 TSCC lines showed a surprisingly homogenous pTyr-protein pattern and a prominent 130 kDa pTyr-protein. Inhibition of SFK activity greatly reduced overall pTyr-protein levels and p130Cas tyrosine phosphorylation. It also impaired TSCC viability in 2D cell culture and 3D soft agar colony formation. A high-throughput drug combination screen with Dasatinib identified glucocorticoids as promising candidates for synergistic activity. Dasatinib and Dexamethasone combination treatment showed strong synergistic effects on Src and p130Cas phosphorylation and led to reduced p130Cas expression. Dexamethasone also suppressed phosphorylation of the MET kinase and its key substrate Gab1. On the cellular level, Dasatinib combination with glucocorticoids led to G1 cell cycle arrest, appeared to increase senescence and enhanced autophagy. This was also reflected by effects on cell cycle regulatory proteins, including CDKs and cyclins. Conclusion: This work is the first to show a strong synergistic activity of Dasatinib in combination with clinically used glucocorticoids in solid tumors. Furthermore, the tyrosine kinase MET and its effector protein Gab1 are newly identified glucocorticoid targets. Given the extensive research on MET as a drug target in various cancers, our findings have the potential to advance future cancer treatments

Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells

Background. The p38 mitogen-activated protein kinase (p38 MAPK) is an important intracellular signal transduction pathway involved in TGF-β1-induced epithelial–mesenchymal transition (EMT). Sema4C, a member of the semaphorin family, was found to be essential for the activation of p38 MAPK. However, the role of Sema4C in promoting TGF-β1-induced EMT is unclear

The Vehicle, Spring 2013

Vol. 54, Issue 1 Table of Contents About Face!: A Confederacy of ClichesKaren Neuberg page 8 HopeJames Coxpage 9 IN or OUTTaryn DeVriespage 12 The Imagination of a ChildMaxwell Collinspage 16 How Free to be a TreeLeann Kirchnerpage 18 CrowsValentina Canopage 19 Old West PhotosFred Pollackpage 20 Lava LampFred Pollackpage 21 Mort MotGerry Mark Nortonpage 23 If ILaura Adrianpage 24 Finding my MonkeyDavid Lewitzkypage 25 Slow DragDavid Lewitzkypage 26 Political ScienceElizabeth Marlowpage 27 ...Were Punctuated By...Elizabeth Marlowpage 28 St. E Pt 1Elizabeth Marlowpage 29 The Steamboat CaptainElizabeth Marlowpage 30 Pretty EyesRyan Sheapage 31 The World is RoundRyan Sheapage 32 End SongsJason Graffpage 33 The Sensitive Youth Grows UpRichard King Perkins IIpage 41 Colors and LightKyle Owenspage 42 RE-TARDKarlyn Thayerpage 44 Where Is Waldo?Riley Parishpage 57 Beneath Shifting SoundsHolly Daypage 58 Talking Shop with Mike Kardospage 60 Winnie Davis Neely Award winner: Paper CutsGregory Robert Petersonpage 68 Paper-Mache PoetryGregory Robert Petersonpage 69 James K. Johnson Award winners: ValveChristopher Robinsonpage 72 Dear MotherEliot Thompsonpage 76 Why Are There Bars on the WindowsEliot Thompsonpage 77 To Be a ScholarEliot Thompsonpage 79 OccidentalEliot Thompsonpage 80 Falling is for the ClumsyEliot Thompsonpage 81 Scary MonstersC. David Banyaipage 83 I Called My Grandmother DollyRashelle Spearpage 90 Tender FleshH R Greenpage 92 Faking ItShelby Koehnepage 95 Contributor\u27s notespage 101https://thekeep.eiu.edu/vehicle/1095/thumbnail.jp

The Vehicle, Spring 2013

Vol. 54, Issue 1 Table of Contents About Face!: A Confederacy of ClichesKaren Neuberg page 8 HopeJames Coxpage 9 IN or OUTTaryn DeVriespage 12 The Imagination of a ChildMaxwell Collinspage 16 How Free to be a TreeLeann Kirchnerpage 18 CrowsValentina Canopage 19 Old West PhotosFred Pollackpage 20 Lava LampFred Pollackpage 21 Mort MotGerry Mark Nortonpage 23 If ILaura Adrianpage 24 Finding my MonkeyDavid Lewitzkypage 25 Slow DragDavid Lewitzkypage 26 Political ScienceElizabeth Marlowpage 27 ...Were Punctuated By...Elizabeth Marlowpage 28 St. E Pt 1Elizabeth Marlowpage 29 The Steamboat CaptainElizabeth Marlowpage 30 Pretty EyesRyan Sheapage 31 The World is RoundRyan Sheapage 32 End SongsJason Graffpage 33 The Sensitive Youth Grows UpRichard King Perkins IIpage 41 Colors and LightKyle Owenspage 42 RE-TARDKarlyn Thayerpage 44 Where Is Waldo?Riley Parishpage 57 Beneath Shifting SoundsHolly Daypage 58 Talking Shop with Mike Kardospage 60 Winnie Davis Neely Award winner: Paper CutsGregory Robert Petersonpage 68 Paper-Mache PoetryGregory Robert Petersonpage 69 James K. Johnson Award winners: ValveChristopher Robinsonpage 72 Dear MotherEliot Thompsonpage 76 Why Are There Bars on the WindowsEliot Thompsonpage 77 To Be a ScholarEliot Thompsonpage 79 OccidentalEliot Thompsonpage 80 Falling is for the ClumsyEliot Thompsonpage 81 Scary MonstersC. David Banyaipage 83 I Called My Grandmother DollyRashelle Spearpage 90 Tender FleshH R Greenpage 92 Faking ItShelby Koehnepage 95 Contributor\u27s notespage 101https://thekeep.eiu.edu/vehicle/1095/thumbnail.jp

Two Factor Reprogramming of Human Neural Stem Cells into Pluripotency

BACKGROUND:Reprogramming human somatic cells to pluripotency represents a valuable resource for the development of in vitro based models for human disease and holds tremendous potential for deriving patient-specific pluripotent stem cells. Recently, mouse neural stem cells (NSCs) have been shown capable of reprogramming into a pluripotent state by forced expression of Oct3/4 and Klf4; however it has been unknown whether this same strategy could apply to human NSCs, which would result in more relevant pluripotent stem cells for modeling human disease. METHODOLOGY AND PRINCIPAL FINDINGS:Here, we show that OCT3/4 and KLF4 are indeed sufficient to induce pluripotency from human NSCs within a two week time frame and are molecularly indistinguishable from human ES cells. Furthermore, human NSC-derived pluripotent stem cells can differentiate into all three germ lineages both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE:We propose that human NSCs represent an attractive source of cells for producing human iPS cells since they only require two factors, obviating the need for c-MYC, for induction into pluripotency. Thus, in vitro human disease models could be generated from iPS cells derived from human NSCs

Voices from the field: How did you come to engage in students-as-partners work?

The language of students as partners was cemented into higher education (HE) practice and scholarship 10 years ago. While it had been circulating in higher education policy, practices, and publications before that, two key 2014 publications on engaging students as partners, or SaP, inspired a myriad of practices and publications brought together by the relational, values-based ethos of partnership (Cook-Sather et al., 2014; Healey et al., 2014). A seductively simple idea— that students can collaborate with staff as partners on matters of teaching and learning—landed at the right time. The higher education sector was increasingly fixated on student involvement and engagement, particularly on how university changes students (Klemenčič, 2024). SaP offered a related but direction-shifting proposition: what if students could shape higher education