Search results for " Effector"

2017

Despite rapid progress, many problems and limitations persist and limit the applicability of gene-editing techniques. Making use of meganucleases, TALENs, or CRISPR/Cas9-based tools requires an initial step of pre-screening to determine the efficiency and specificity of the designed tools. This step remains time consuming and material consuming. Here we propose a simple, cheap, reliable, time-saving, and highly sensitive method to evaluate a given gene-editing tool based on its capacity to induce chromosomal translocations when combined with a reference engineered nuclease. In the proposed technique, designated engineered nuclease-induced translocations (ENIT), a plasmid coding for the DNA-…

NKG2D stimulation of CD8(+) T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice

2017

NKG2D is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ and CD8+ T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8+ T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here we studied the impact of NKG2D on effector CD8+ T-cell formation. NKG2D-deficiency that is restricted to murine CD8+ T cells did not impair antigen-specific T-cell expansion following mCMV and LCMV infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8+ T cells via the Da…

A Rough-Terrain Casting Robot for the ESA Lunar Robotics Challenge

2009

This paper describes the design and implementation of DAVID, a lunar vehicle developed for the European Space Agency (ESA) Lunar Robotics Challenge, presenting severe terrain negotiation and sample acquisition challenges. We discuss in some detail two of the main innovative aspects of our entry to the challenge, i.e. the locomotion system and the sample acquisition system. Motivated by the challenge specifications, a range of different locomotion systems were considered, among which we chose a simple, rugged and effective wheeled system. We provide an account of the choice of five different types of wheels, which were designed, analyzed and experimentally tested in conditions similar to the…

Salmonella bongori Provides Insights into the Evolution of the Salmonellae

2011

The genus Salmonella contains two species, S. bongori and S. enterica. Compared to the well-studied S. enterica there is a marked lack of information regarding the genetic makeup and diversity of S. bongori. S. bongori has been found predominantly associated with cold-blooded animals, but it can infect humans. To define the phylogeny of this species, and compare it to S. enterica, we have sequenced 28 isolates representing most of the known diversity of S. bongori. This cross-species analysis allowed us to confidently differentiate ancestral functions from those acquired following speciation, which include both metabolic and virulence-associated capacities. We show that, although S. bongori…

Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study

2020

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, and they have been described as being associated with tumor prognosis. Here, miRNA profiling was planned to explore new molecular prognostic biomarkers in localized intestinal high-risk GIST. Paraffin tumor blocks of 14 and 86 patients were used in the discovery and expansion sets, respectively. GeneChip miRNA v3.0 was employed to identify the miRNAs differentially expressed between relapsed and non-relapsed patient samples, which were validated in the expansion set, by qRT-PCR. RT2 Profiler PCR Array was used for the screening of let-7e targets. Expression levels were co…

Adaptive neuro-fuzzy inference system for kinematics solutions of redundant robots

2016

This written paper presents aspects concerning the implementation of the Adaptive Neuro-Fuzzy Inference System (ANFIS) in the resolution of a redundant serial robot kinematics. The kinematics solutions are divided into two categories: direct kinematics solutions and inverse kinematics solutions. To be able to control a robot the most important solutions are the ones for the inverse kinematics since one knows the position and the final orientation of the end effector and needs to determine the relative displacement or movements into the robot couplings. To obtain the optimal solutions for the inverse kinematics of a redundant robot the mathematical equations were based onto the redundancy ci…

Design and control of a novel 3D casting manipulator

2010

This paper focuses on casting manipulation and presents an innovative mechanism that allows objects placed in a three-dimensional space to be reached with a relatively small robot. Casting manipulation is a technique by which a robotic end-effector is thrown and its ballistic flight is controlled through a tether cable so as to reach a target object. Previous work presented a solution that is viable only when the position of the target object is perfectly known or aligned with the throwing plane. Our work extends the technique by use of a novel mechanical design of the arm, and a suitable control scheme for the flight of the end-effector, which makes it applicable for objects placed at gene…

Structural and functional diversity of the lectin repertoire in teleost fish: Relevance to innate and adaptive immunity

2011

Protein–carbohydrate interactions mediated by lectins have been recognized as key components of innate immunity in vertebrates and invertebrates, not only for recognition of potential pathogens, but also for participating in downstream effector functions, such as their agglutination, immobilization, and complement-mediated opsonization and killing. More recently, lectins have been identified as critical regulators of mammalian adaptive immune responses. Fish are endowed with virtually all components of the mammalian adaptive immunity, and are equipped with a complex lectin repertoire. In this review, we discuss evidence suggesting that: (a) lectin repertoires in teleost fish are highly dive…

Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?

2020

Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical tria…

Immunological Markers for PML Prediction in MS Patients Treated with Natalizumab

2015

International audience; Natalizumab (NTZ), a monoclonal antibody recognizing the alpha4 integrin chain, has been approved for the treatment of active multiple sclerosis, but expose to the onset of a rare side effect, progressive multifocal leukoencephalopathy (PML). Estimating the individual risk of PML in NTZ-treated patients is a major challenge, and therapeutic strategies are mainly guided by the overall PML risk assessed by identified risk factors: JC virus (JCV) seropositivity, treatment duration (with peak incidence after 24 months), and the previous use of immunosuppressive therapies. Given that this stratification does not yet allow a precise individual prediction of PML, other pred…