Search results for "target"

TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin-CDK-Cks1

2017

Eukaryotic cell cycle progression through G(1)-S is driven by hormonal and growth-related signals that are transmitted by the target of rapamycin complex 1 (TORC1) pathway. In yeast, inactivation of TORC1 restricts G(1)-S transition due to the rapid clearance of G(1) cyclins (Cln) and the stabilization of the B-type cyclin (Clb) cyclin-dependent kinase (CDK) inhibitor Sic1. The latter mechanism remains mysterious but requires the phosphorylation of Sic1-Thr(173) by Mpk1 and inactivation of the Sic1-pThr(173)-targeting phosphatase (PP2A(Cdc55)) through greatwall kinase-activated endosulfines. Here we show that the Sic1-pThr(173) residue serves as a specific docking site for the CDK phospho-a…

TORC1 controls G1–S cell cycle transition in yeast via Mpk1 and the greatwall kinase pathway

2015

The target of rapamycin complex 1 (TORC1) pathway couples nutrient, energy and hormonal signals with eukaryotic cell growth and division. In yeast, TORC1 coordinates growth with G1–S cell cycle progression, also coined as START, by favouring the expression of G1 cyclins that activate cyclin-dependent protein kinases (CDKs) and by destabilizing the CDK inhibitor Sic1. Following TORC1 downregulation by rapamycin treatment or nutrient limitation, clearance of G1 cyclins and C-terminal phosphorylation of Sic1 by unknown protein kinases are both required for Sic1 to escape ubiquitin-dependent proteolysis prompted by its flagging via the SCFCdc4 (Skp1/Cul1/F-box protein) ubiquitin ligase complex.…

Filling the gap between Guidelines and Real World in the cardiovascular approach to the diabetic patients: the need for a call to action

2020

Average real variability of 24-h systolic blood pressure is associated with microalbuminuria in patients with primary hypertension.

2015

Limited and conflicting data are available about the association between short-term blood pressure (BP) variability and urinary albumin excretion rate (uAER). The objective of our study was to analyze the relationships between microalbuminuria (MAU), defined as an uAER between 20 and 200 μg min(-1), and short-term BP variability (BPV), assessed as average real variability (ARV), weighted s.d. of 24-h BP and as s.d. of daytime and night-time BP. The study population consisted of 315 untreated essential hypertensives with normal estimated glomerular filtration rate (>60 ml min(-1) per 1.73 m(2)), who underwent 24-h ambulatory BP monitoring and 24-h uAER determination. MAU was detected in 82 (…

Should reduction of increased short‐term blood pressure variability be a target of antihypertensive therapy?

2021

Abstract It has long been known that blood pressure (BP) is characterized by marked short‐term fluctuations occurring within a 24‐h period and also by long‐term oscillations occurring over more prolonged periods of time. An increased short‐term blood pressure variability (BPV) appears to importantly contribute to target organ damage and to the enhanced cardiovascular risk of hypertensive patients, over and above the effect of an increase in mean BP levels. Reducing 24‐h mean BP is the main aim of antihypertensive therapy, but initial data are available that additional cardiovascular protection can be achieved by reducing BPV. However, to definitively prove the prognostic role of short‐term …

New Measurements of the Beam Normal Spin Asymmetries at Large Backward Angles with Hydrogen and Deuterium Targets

2017

International audience; New measurements of the beam normal single spin asymmetry in the electron elastic and quasielastic scattering on the proton and deuteron, respectively, at large backward angles and at ⟨Q2⟩=0.22  (GeV/c)2 and ⟨Q2⟩=0.35  ( GeV/c)2 are reported. The experimentally observed asymmetries are compared with the theoretical calculation of Pasquini and Vanderhaeghen [Phys. Rev. C 70, 045206 (2004).PRVCAN0556-281310.1103/PhysRevC.70.045206]. The agreement of the measurements with the theoretical calculations shows a dominance of the inelastic intermediate excited states of the nucleon, πN and the Δ resonance. The measurements explore a new, important parameter region of the exc…

ProcessWiki: A Contribution for Bridging the Last Mile Problem in Automotive Retail

2012

In many real-world business process management (BPM) installments, the benefit of BPM is diminished by an insufficient implementation of the to-be business processes. One of the key reasons for this problem is the complexity of classical process modeling representations that exceed the BPM knowledge of many target groups.

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Thera…

2022

Simple Summary We present the long-term results of patients receiving allogeneic stem cell transplantation (allo-SCT) for relapsed/refractory mantle cell lymphoma (R/R MCL) in the last 25 years in Spain. We conclude that allo-SCT may be a curative option in R/R MCL with a low cumulative incidence (CI) of relapse, although non-relapse mortality (NRM) is still high, which is mainly secondary to acute graft-versus-host disease (aGVHD). Results are better for fit patients, using HLA-identical (related or unrelated) or haploidentical related donors and without previous ASCT. However, the arrival of new highly effective and low toxic immunotherapeutic or targeted therapies inevitably will relegat…

Gene Expression Analyses during Spontaneous Reversal of Cardiomyopathy in Mice with Repressed Nuclear CUG-BP, Elav-Like Family (CELF) Activity in Hea…

2015

CUG-BP, Elav-like family (CELF) proteins regulate cell type- and developmental stage-specific alternative splicing in the heart. Repression of CELF-mediated splicing activity via expression of a nuclear dominant negative CELF protein in heart muscle was previously shown to induce dysregulation of alternative splicing, cardiac dysfunction, cardiac hypertrophy, and dilated cardiomyopathy in MHC-CELFΔ transgenic mice. A “mild” line of MHC-CELFΔ mice that expresses a lower level of the dominant negative protein exhibits cardiac dysfunction and myopathy at a young age, but spontaneously recovers normal cardiac function and heart size with age despite the persistence of splicing defects. To the b…

The Cytokine GM-CSF Drives the Inflammatory Signature of CCR2+ Monocytes and Licenses Autoimmunity.

2015

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as a crucial cytokine produced by auto-reactive T helper (Th) cells that initiate tissue inflammation. Multiple cell types can sense GM-CSF, but the identity of the pathogenic GM-CSF-responsive cells is unclear. By using conditional gene targeting, we systematically deleted the GM-CSF receptor (Csf2rb) in specific subpopulations throughout the myeloid lineages. Experimental autoimmune encephalomyelitis (EAE) progressed normally when either classical dendritic cells (cDCs) or neutrophils lacked GM-CSF responsiveness. The development of tissue-invading monocyte-derived dendritic cells (moDCs) was also unperturbed upon Csf2r…