Search results for "response"

African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system

2019

Significance Many parasites escape the host immune system by undergoing antigenic variation, a process in which surface antigens are regularly shed and replaced by new ones. Trypanosoma brucei employs multiple sophisticated molecular mechanisms to ensure the expression of a homogeneous VSG coat. We generated a mutant parasite that expresses multiple distinct VSGs and studied the consequences of having a multi-VSG coat during an infection. We showed that expression of multiple VSGs makes the parasites more vulnerable to the immune response, which can now control the trypanosomes from the onset of the infection, allowing most mice to survive. In the future, trypanosome infections may be treat…

Development of Novel Benzodiazepine-Based Peptidomimetics as Inhibitors of Rhodesain from Trypanosoma brucei rhodesiense.

2020

Starting from the reversible rhodesain inhibitors 1 a-c, which have Ki values towards the target protease in the low-micromolar range, we have designed a series of peptidomimetics, 2 a-g, that contain a benzodiazepine scaffold as a β-turn mimetic; they are characterized by a specific peptide sequence for the inhibition of rhodesain. Considering that irreversible inhibition is strongly desirable in the case of a parasitic target, a vinyl ester moiety acting as Michael-acceptor was introduced as the warhead; this portion was functionalized in order to evaluate the size of corresponding enzyme pocket that could accommodate this substituent. With this investigation, we identified an irreversibl…

On the Moving Least Squares (MLS) approximation effectiveness in a T-Shaped tube hydroforming design

2009

Plasmacytoid dendritic cells are inefficient in activation of human regulatory T cells

2011

BACKGROUND: Dendritic cells (DC) play a key role in initiation and regulation of immune responses. Plasmacytoid DC (pDC), a small subset of DC, characterized as type-I interferon producing cells, are critically involved in anti-viral immune responses, but also mediate tolerance by induction of regulatory T cells (Treg). In this study, we compared the capacity of human pDC and conventional DC (cDC) to modulate T cell activity in presence of Foxp3(+) Treg. PRINCIPAL FINDINGS: In coculture of T effector cells (Teff) and Treg, activated cDC overcome Treg anergy, abrogate their suppressive function and induce Teff proliferation. In contrast, pDC do not break Treg anergy but induce Teff prolifera…

Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells

2011

Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…

Clinico-Pathological Features Influencing the Prognostic Role of Body Mass Index in Patients With Advanced Renal Cell Carcinoma Treated by Immuno-Onc…

2023

Background: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC). Patients and methods: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the r…

Extended Environmental Contour Methods for Long-Term Extreme Response Analysis of Offshore Wind Turbines1

2020

Abstract Environmental contour method is an efficient method for predicting the long-term extreme response of offshore structures. The traditional environmental contour is obtained using the joint distribution of mean wind speed, significant wave height, and spectral peak period. To improve the accuracy of traditional environmental contour method, a modified method was proposed considering the non-monotonic aerodynamic behavior of offshore wind turbines. Still, the modified method assumes constant wind turbulence intensity. In this paper, we extend the existing environmental contour methods by considering the wind turbulence intensity as a stochastic variable. The 50-year extreme responses …

The Foreign Body Response to an Implantable Therapeutic Reservoir in a Diabetic Rodent Model

2021

Advancements in type 1 diabetes mellitus treatments have vastly improved in recent years. The move toward a bioartificial pancreas and other fully implantable systems could help restore patient's glycemic control. However, the long-term success of implantable medical devices is often hindered by the foreign body response. Fibrous encapsulation "walls off" the implant to the surrounding tissue, impairing its functionality. In this study we aim to examine how streptozotocin-induced diabetes affects fibrous capsule formation and composition surrounding implantable drug delivery devices following subcutaneous implantation in a rodent model. After 2 weeks of implantation, the fibrous capsule sur…

FACIT collagen (1alpha-chain) is expressed by hemocytes and epidermis during the inflammatory response of the ascidian Ciona intestinalis

2008

Based on previous cloning and sequencing study, real-time PCR and in situ hybridization assays of the inflamed body wall of LPS-injected Ciona intestinalis showed the enhanced gene expression of a collagen with FACIT structural features (Ci-type IX-Col 1a-chain). By using specific antibodies raised against an opportunely chosen Ci-type IX-Col synthetic peptide, the fibroblast property of hemocytes challenged in vitro with LPS (at 4 h) was displayed by flow cytometry, while immunocytochemistry identified hemocytes with large granules (morula cells) as collagen-producing cells. Hemocyte lysate supernatant analyzed in immunoblotting contained a 60 kDa band identifiable as 1a-chain-Ci-type IX-C…

Unraveling the complex trait of low temperature adaptation in the wine yeast Saccharomyces cerevisiae

2016

1. Introducción Se cree que las uvas fueron domesticadas entre el Mar Negro e Irán durante el periodo del 7000-4000 aC. Las primeras evidencias de elaboración de vino provienen de la presencia de ácido tartárico en un tarro antiguo que data de 5400 - 5000 aC en el yacimiento neolítico de Tepe en Mesopotamia y de los restos de la extracción del zumo de uva en el yacimiento neolítico de Dikili Tash en Grecia (5000 aC). La colonización de los romanos extendió la elaboración del vino por todo el Mediterráneo; en el 500 aC el vino ya se producía en Italia, Francia, España, Portugal y el norte de África. Posteriormente también fue extendido a los Balcanes, Alemania y otras partes del norte de Eur…