40 research outputs found
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
Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76.
SH3 domains are protein recognition modules within many adaptors and enzymes. With more than 500 SH3 domains in the human genome, binding selectivity is a key issue in understanding the molecular basis of SH3 domain interactions. The Grb2-like adaptor protein Mona/Gads associates stably with the T-cell receptor signal transducer SLP-76. The crystal structure of a complex between the C-terminal SH3 domain (SH3C) of Mona/Gads and a SLP-76 peptide has now been solved to 1.7 A. The peptide lacks the canonical SH3 domain binding motif P-x-x-P and does not form a frequently observed poly-proline type II helix. Instead, it adopts a clamp-like shape around the circumfence of the SH3C beta-barrel. The central R-x-x-K motif of the peptide forms a 3(10) helix and inserts into a negatively charged double pocket on the SH3C while several other residues complement binding through hydrophobic interactions, creating a short linear SH3C binding epitope of uniquely high affinity. Interestingly, the SH3C displays ion-dependent dimerization in the crystal and in solution, suggesting a novel mechanism for the regulation of SH3 domain functions
Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76
SH3 domains are protein recognition modules within many adaptors and enzymes. With more than 500 SH3 domains in the human genome, binding selectivity is a key issue in understanding the molecular basis of SH3 domain interactions. The Grb2-like adaptor protein Mona/Gads associates stably with the T-cell receptor signal transducer SLP-76. The crystal structure of a complex between the C-terminal SH3 domain (SH3C) of Mona/Gads and a SLP-76 peptide has now been solved to 1.7 A. The peptide lacks the canonical SH3 domain binding motif P-x-x-P and does not form a frequently observed poly-proline type II helix. Instead, it adopts a clamp-like shape around the circumfence of the SH3C beta-barrel. The central R-x-x-K motif of the peptide forms a 3(10) helix and inserts into a negatively charged double pocket on the SH3C while several other residues complement binding through hydrophobic interactions, creating a short linear SH3C binding epitope of uniquely high affinity. Interestingly, the SH3C displays ion-dependent dimerization in the crystal and in solution, suggesting a novel mechanism for the regulation of SH3 domain functions
Association of HLA-DRB1
OBJECTIVE: To assess whether preliminary findings of associations between the HLA-DRB1*04 and HLA-DRB1* shared epitope (SE) allelic groups and response to the anti-IL-17A mAb secukinumab in RA were reproducible in an independent RA cohort.
METHODS: Biologic-naïve subjects (n = 100) with RA by 2010 criteria with tender/swollen joint counts (each ≥6) and high-sensitivity CRP (hsCRP) >10 mg/l were randomized 2:1 to secukinumab 10 mg/kg i.v. or placebo every 2 weeks until week 10. Potential associations with treatment response to secukinumab at week 12 (DAS28-CRP change from baseline by analysis of covariance, ACR20 response rate by logistic regression) were assessed for HLA-DRB1*04 (primary end point), HLA-DRB1*SE and HLA-DRB1 position 11 V/L (HLA-DRB1*pos11 V/L) allelic groups, and baseline levels of hsCRP, RF and anti-CCP.
RESULTS: Secukinumab was significantly more effective than placebo in reducing DAS28-CRP (-2.41 vs -0.71; P < 0.0001) and producing ACR20 responses (87.1% vs 25.0%; P < 0.0001) at week 12. The HLA-DRB1*04 allelic group was not significantly related to secukinumab response vs placebo. For change from baseline in DAS28-CRP, HLA-DRB1*SE (P = 0.003) and HLA-DRB1*pos11 V/L (P = 0.002) allelic groups were associated with positive treatment response. Higher RF levels, but not anti-CCP positivity, were significantly associated with DAS28-CRP reductions (P = 0.015) and ACR20 (P = 0.008) responses. Secukinumab was well tolerated.
CONCLUSION: Secukinumab significantly reduced signs and symptoms of RA vs placebo. As the HLA-DRB1*SE and HLA-DRB1*pos11 V/L results were driven by lack of placebo response in carriers, the hypothesis of clinical utility for HLA-DRB1* allelic groups in RA anti-IL-17A short-term response prediction could not be corroborated.
TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/; NCT01426789