4 research outputs found
Neutrophils promote venular thrombosis by shaping the rheological environment for platelet aggregation
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2019
- Field of study
In advanced inflammatory disease, microvascular thrombosis leads to the interruption of blood supply and provokes ischemic tissue injury. Recently, intravascularly adherent leukocytes have been reported to shape the blood flow in their immediate vascular environment. Whether these rheological effects are relevant for microvascular thrombogenesis remains elusive. Employing multi-channel in vivo microscopy, analyses in microfluidic devices, and computational modeling, we identified a previously unanticipated role of leukocytes for microvascular clot formation in inflamed tissue. For this purpose, neutrophils adhere at distinct sites in the microvasculature where these immune cells effectively promote thrombosis by shaping the rheological environment for platelet aggregation. In contrast to larger (lower-shear) vessels, this process in high-shear microvessels does not require fibrin generation or extracellular trap formation, but involves GPIb alpha-vWF and CD40-CD40L-dependent platelet interactions. Conversely, interference with these cellular interactions substantially compromises microvascular clotting. Thus, leukocytes shape the rheological environment in the inflamed venular microvasculature for platelet aggregation thereby effectively promoting the formation of blood clots. Targeting this specific crosstalk between the immune system and the hemostatic system might be instrumental for the prevention and treatment of microvascular thromboembolic pathologies, which are inaccessible to invasive revascularization strategies
A global resource allocation strategy governs growth transition kinetics of Escherichia coli
- Publication venue
- eScholarship, University of California
- Publication date
- 25/10/2017
- Field of study
A grand challenge of systems biology is to predict the kinetic responses of living systems to perturbations starting from the underlying molecular interactions. Changes in the nutrient environment have long been used to study regulation and adaptation phenomena in microorganisms and they remain a topic of active investigation. Although much is known about the molecular interactions that govern the regulation of key metabolic processes in response to applied perturbations, they are insufficiently quantified for predictive bottom-up modelling. Here we develop a top-down approach, expanding the recently established coarse-grained proteome allocation models from steady-state growth into the kinetic regime. Using only qualitative knowledge of the underlying regulatory processes and imposing the condition of flux balance, we derive a quantitative model of bacterial growth transitions that is independent of inaccessible kinetic parameters. The resulting flux-controlled regulation model accurately predicts the time course of gene expression and biomass accumulation in response to carbon upshifts and downshifts (for example, diauxic shifts) without adjustable parameters. As predicted by the model and validated by quantitative proteomics, cells exhibit suboptimal recovery kinetics in response to nutrient shifts owing to a rigid strategy of protein synthesis allocation, which is not directed towards alleviating specific metabolic bottlenecks. Our approach does not rely on kinetic parameters, and therefore points to a theoretical framework for describing a broad range of such kinetic processes without detailed knowledge of the underlying biochemical reactions
The lipid products of phosphoinositide 3-kinase isoforms in cancer and thrombosis
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- A Kihara
- A Naguib
- A Ragab
- AC Nascimbeni
- AL Marat
- AM Battram
- AM Scharenberg
- AP Sagona
- B Catimel
- B Catimel
- B Furie
- B Pasquier
- B Pasquier
- B Vanhaesebroeck
- BD Manning
- Bernard Payrastre
- C Ellson
- C Sultan
- C Trumel
- C Valet
- D Wang
- D Woulfe
- DA Fruman
- DC Rubinsztein
- DS Woulfe
- E Boucrot
- EK Paterson
- F Campa
- F Janku
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- VP Sharma
- WE Dowdle
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- Y Liu
- Y Mosesson
- Y Posor
- Y Samuels
- Y Sugimoto
- Y Wang
- YS Bae
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
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- T Tachiki
- T Tachiki
- T Takahashi
- T Tanaka
- T Taniguchi
- T Taniguchi
- T Taniguchi
- T Taniguchi
- T Ueda
- T Ueda
- T Uozumi
- T Uozumi
- T Uwajima
- T Vant-Riet
- T Walsh
- T Wieland
- T Yagi
- T Yamamoto
- T Yamanaka
- T Yamanaka
- T Yamanaka
- T Yamanaka
- T Yamanaka
- T Yonetani
- T Yonetani
- T Yonetani
- T Yonetani
- T Yonetani
- T Yoshida
- T Yoshida
- T Yoshida
- T Yoshinaga
- T Yubisui
- T Yuzuriha
- TA Abalikhina
- TA Hoeven Der
- TA Hoeven Der
- TA Oshino
- TB Eronina
- TC Strekas
- TE Hardingham
- TE King
- TE King
- TE Meyer
- TG Ebrey
- TH Cromartie
- TH Cromartie
- TH Cromatrie
- TH Fife
- TH Finlay
- TH Grove
- TH Ji
- TL Glass
- TL Trosper
- TN Akopyan
- TN Bruzhinina
- TS Chang
- TS Srivasta
- TT Lee
- TW Bresters
- TW Brewster
- TW Kwon
- TW Kwon
- TW Seale
- TW Szezepkowski
- TY Shih
- TY Yang
- U Branzoli
- U Branzoli
- U Fischer
- U Fischer
- U Menge
- U Shimada
- U Weser
- U Weser
- U Weser
- U Weser
- U Weser
- U Weser
- U Weser
- UE Handschin
- V Gonzales-Prevatt
- V Harisdangkul
- V Krasnobajeu
- V Larraga
- V Massey
- V Massey
- V Redkar
- V Scardi
- VA Eterovic
- VA Leonenko
- VA Rasskazov
- VB Yanushauskaite
- VF Kalb
- VG Neef
- VG Tumanyan
- VI Ivanov
- VK Shah
- VM Kochkina
- VP Miroshnichenko
- VP Pigiet
- VP Piriet
- VR Naik
- VS Sharma
- VS Zolotova
- VT Aikazyan
- VT Aikazyan
- VT Aikazyan
- VV Mesyanzhinov
- VV Moslov
- W Ardelt
- W Birchmeier
- W Birchmeier
- W Byers
- W Duntze
- W Junge
- W Kufer
- W Kunzer
- W Leicht
- W Levin
- W Levin
- W Levin
- W Mori
- W Scheler
- W Sebald
- W Strider
- W Tischer
- WA Bulen
- WA Robison
- WB Im
- WB Southerland
- WB Whitman
- WB Whitten
- WC Mccubbin
- WC Merrick
- WD Behnske
- WD Hewson
- WD Hewson
- WD Horrocks
- WF Cleere
- WF Line
- WF Swain
- WFHM Mommaerts
- WG Zumft
- WG Zumft
- WG Zumft
- WH Bannister
- WH Bannister
- WH Bishop
- WH Wu
- WJ Chang
- WJ Grip
- WJ Haas
- WJ Haas
- WJ Ray
- WJ Wallace
- WJ Wallace
- WJ Wallace
- WK Liu
- WL Hughes
- WL Muth
- WM Awad
- WM Moore
- WR Browett
- WR Carper
- WR Fisher
- WR Heineman
- WR Holmquist
- WR Melander
- WR Richards
- WR Richards
- WR Veatch
- WR Waud
- WR Waud
- WS Hancock
- WS Pierpoint
- WS Pierpoint
- WT Butler
- WT Morgan
- WT Morgan
- WT Perrie
- WV Sweeney
- WV Sweeney
- WV Sweeney
- WW Fish
- WW Ward
- WY Huang
- Y
- Y Atsuta
- Y Atsuta
- Y Beaux
- Y Beuzard
- Y Degani
- Y Fukumori
- Y Furusawa
- Y Hatefi
- Y Hayashi
- Y Hayashi
- Y Hayashi
- Y Henry
- Y Henry
- Y Ichikawa
- Y Igarashi
- Y Imai
- Y Imai
- Y Imai
- Y Imai
- Y Imai
- Y Ishida
- Y Itoh
- Y Kanai
- Y Kato
- Y Kurono
- Y Matsushita
- Y Miyake
- Y Morikawa
- Y Morino
- Y Morino
- Y Morino
- Y Morita
- Y Morita
- Y Motokawa
- Y Muto
- Y Nagi
- Y Nakagawa
- Y Nakagawa
- Y Nakamura
- Y Nisimoto
- Y Nisimoto
- Y Ohta
- Y Ohta
- Y Ohta
- Y Ohta
- Y Orii
- Y Orii
- Y Orii
- Y Ota
- Y Peled
- Y Sakagami
- Y Sakaki
- Y Sanada
- Y Sawada
- Y Schechter
- Y Schechter
- Y Seki
- Y Shichida
- Y Shioi
- Y Shioi
- Y Shioi
- Y Stefanovsky
- Y Sugimura
- Y Sugimura
- Y Sugita
- Y Takahara
- Y Tamura
- Y Tanagida
- Y Tani
- Y Tani
- Y Tominaga
- Y Tominatsu
- Y Tominatsu
- Y Watanabe
- Y Yamasai
- Y Yasukochi
- Y Yasukochi
- Y Yoshida
- Y Yoshida
- Y Yoshida
- Y. Miyake T. Abe, and T. Yamano, in International Symposium on Oxidases and Related Redox Systems
- YA Sharonov
- YA Sharonov
- YA Sharonov
- YE Erokhin
- YJ Kang
- YK Turakulov
- YK Turakulov
- YK Yip
- YP Lin
- YP Meyer
- YP Meyer
- YP Meyer
- YP Myer
- YS Choong
- YS Choong
- YV Peive
- YV Peive
- YV Pieve
- YV Shtamm
- YY Vasilev
- YYH Chao
- Z Bradic
- Z Gasyna
- Z Vogel
- Z Zak
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/1984
- Field of study