scholarly journals The Level of Friend Retrovirus Replication Determines the Cytolytic Pathway of CD8+ T-Cell-Mediated Pathogen Control

2007 ◽  
Vol 81 (21) ◽  
pp. 11881-11890 ◽  
Author(s):  
Gennadiy Zelinskyy ◽  
Sandra Balkow ◽  
Simone Schimmer ◽  
Tanja Werner ◽  
Markus M. Simon ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Replication ◽  
Effector T Cells ◽  
The Other ◽  
Mouse Strains ◽  
Granule Exocytosis ◽  
Low Level ◽  
Pathogen Control ◽  
Cytotoxic Molecules ◽  
High Level

ABSTRACT Cytotoxic T cells (CTL) play a central role in the control of viral infections. Their antiviral activity can be mediated by at least two cytotoxic pathways, namely, the granule exocytosis pathway, involving perforin and granzymes, and the Fas-FasL pathway. However, the viral factor(s) that influences the selection of one or the other pathway for pathogen control is elusive. Here we investigate the role of viral replication levels in the induction and activation of CTL, including their effector potential, during acute Friend murine leukemia virus (F-MuLV) infection. F-MuLV inoculation results in a low-level infection of adult C57BL/6 mice that is enhanced about 500-fold upon coinfection with the spleen focus-forming virus (SFFV). Both the low- and high-level F-MuLV infections generated CD8+ effector T cells that were essential for the control of viral replication. However, the low-level infection induced CD8+ T cells expressing solely FasL but not the cytotoxic molecules granzymes A and B, whereas the high-level infection resulted in induction of CD8+ effector T cells secreting molecules of the granule exocytosis pathway. By using knockout mouse strains deficient in one or the other cytotoxic pathway, we found that low-level viral replication was controlled by CTL that expressed FasL but control of high-level viral replication required perforin and granzymes. Additional studies, in which F-MuLV replication was enhanced experimentally in the absence of SFFV coinfection, supported the notion that only the replication level of F-MuLV was the critical factor that determined the differential expression of cytotoxic molecules by CD8+ T cells and the pathway of CTL cytotoxicity.

scholarly journals Evaluation of Resistance Development in Bemisia tabaci Genn. (Homoptera: Aleyrodidae) in Cotton against Different Insecticides

Insects ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 996
Author(s):  
Muhammad Zaryab Khalid ◽  
Sohail Ahmed ◽  
Ibrahim Al-ashkar ◽  
Ayman EL Sabagh ◽  
Liyun Liu ◽  
...  
Keyword(s):  
Bemisia Tabaci ◽  
The Other ◽  
Resistance Development ◽  
Susceptible Population ◽  
Low Level ◽  
Development Of Resistance ◽  
Major Pest ◽  
Selection For ◽  
High Level ◽  
Very High

Cotton is a major crop of Pakistan, and Bemisia tabaci (Homoptera: Aleyrodidae) is a major pest of cotton. Due to the unwise and indiscriminate use of insecticides, resistance develops more readily in the whitefly. The present study was conducted to evaluate the resistance development in the whitefly against the different insecticides that are still in use. For this purpose, the whitefly population was selected with five concentrations of each insecticide, for five generations. At G1, compared with the laboratory susceptible population, a very low level of resistance was observed against bifenthrin, cypermethrin, acetamiprid, imidacloprid, thiamethoxam, nitenpyram, chlorfenapyr, and buprofezin with a resistance ratio of 3-fold, 2-fold, 1-fold, 4-fold, 3-fold, 3-fold, 3-fold, and 3-fold, respectively. However, the selection for five generations increased the resistance to a very high level against buprofezin (127-fold), and to a high level against imidacloprid (86-fold) compared with the laboratory susceptible population. While, a moderate level of resistance was observed against cypermethrin (34-fold), thiamethoxam (34-fold), nitenpyram (30-fold), chlorfenapyr (29-fold), and acetamiprid (21-fold). On the other hand, the resistance was low against bifenthrin (18-fold) after selection for five generations. A very low level of resistance against the field population of B. tabaci, at G1, showed that these insecticides are still effective, and thus can be used under the field conditions for the management of B. tabaci. However, the proper rotation of insecticides among different groups can help to reduce the development of resistance against insecticides.

Efficacy of a ciprofloxacin/amikacin combination against planktonic and biofilm cultures of susceptible and low-level resistant Pseudomonas aeruginosa

2019 ◽  
Vol 74 (11) ◽  
pp. 3252-3259 ◽  
Author(s):  
Anaïs Soares ◽  
Kévin Alexandre ◽  
Fabien Lamoureux ◽  
Ludovic Lemée ◽  
François Caron ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Biofilm ◽  
The Other ◽  
Clinical Strain ◽  
Bacterial Reduction ◽  
Low Level ◽  
Mechanical Dispersion ◽  
Resistant Mutants ◽  
High Level

Abstract Background Eradicating bacterial biofilm without mechanical dispersion remains a challenge. Combination therapy has been suggested as a suitable strategy to eradicate biofilm. Objectives To evaluate the efficacy of a ciprofloxacin/amikacin combination in a model of in vitro Pseudomonas aeruginosa biofilm. Methods The antibacterial activity of ciprofloxacin and amikacin (alone, in combination and successively) was evaluated by planktonic and biofilm time–kill assays against five P. aeruginosa strains: PAO1, a WT clinical strain and three clinical strains overexpressing the efflux pumps MexAB-OprM (AB), MexXY-OprM (XY) and MexCD-OprJ (CD), respectively. Amikacin MIC was 16 mg/L for XY and ciprofloxacin MIC was 0.5 mg/L for CD. The other strains were fully susceptible to ciprofloxacin and amikacin. The numbers of total and resistant cells were determined. Results In planktonic cultures, regrowth of high-level resistant mutants was observed when CD was exposed to ciprofloxacin alone and XY to amikacin alone. Eradication was obtained with ciprofloxacin or amikacin in the other strains, or with the combination in XY and CD strains. In biofilm, bactericidal reduction after 8 h followed by a mean 4 log10 cfu/mL plateau in all strains and for all regimens was noticed. No regrowth of resistant mutants was observed whatever the antibiotic regimen. The bacterial reduction obtained with a second antibiotic used simultaneously or consecutively was not significant. Conclusions The ciprofloxacin/amikacin combination prevented the emergence of resistant mutants in low-level resistant strains in planktonic cultures. Biofilm persister cells were not eradicated, either with monotherapy or with the combination.

CMV Specific T Cells Prevent Progression From Low to High Level Viremia In D+R+ but Not D-R+ Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4532-4532
Author(s):  
Mette Hoegh-Petersen ◽  
Lina Roa ◽  
Yiping Liu ◽  
Feng Zhou ◽  
Alejandra Ugarte-Torres ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Conflicts Of Interest ◽  
Spontaneous Resolution ◽  
Cell Transplant ◽  
Low Level ◽  
Peak Viremia ◽  
Cell Counts ◽  
High Level ◽  
Ifnγ And Tnfα

Abstract Abstract 4532 Background. Cytomegalovirus (CMV) reactivates (becomes detectable in blood) in most seropositive hematopoietic cell transplant (HCT) recipients. In some reactivating patients, low level viremia (<50,000 DNA copies/ml plasma, ie, less than our institutional threshold for preemtive therapy) progresses to high level viremia or CMV disease, which is potentially fatal. We hypothesized that low level viremia progresses in patients with low specific T cell counts and spontaneously resolves in patients with high specific T cell counts. Methods. In 30 CMV seropositive HCT recipients monitored weekly for reactivation by real-time PCR, blood was drawn for specific T cell counts within 4 days from the first episode of low level viremia. Fourteen patients received grafts from seropositive donors (D+R+), and 16 patients from seronegative donors (D-R+). Mononuclear cells were stimulated overnight with CMV lysate, pp65 overlapping peptides, no stimulus (negative control) or staphylococcal enterotoxin B (positive control). T cells producing IFNγ, TNFα and/or IL2 were enumerated by flow cytometry. Results. Among D+R+ patients, counts of CMV lysate and pp65 specific CD4 T cells producing IFNγ and TNFα (and not IL2) were higher in patients with spontaneous resolution than patients with progression (p=0.02 for CMV lysate, p=0.004 for pp65). Also, there was an inverse correlation between pp65 specific CD8 T cells producing IFNγ and TNFα and peak viremia (r=-0.94, p=0.005) in D+R+ patients who progressed to high level viremia/disease. In contrast, among D-R+ patients, CMV lysate and pp65 specific T cell counts were similar in patients with spontaneous resolution and patients with progression, and there was no correlation between specific T cell counts and peak viremia. Conclusion. CMV specific T cells play a role in preventing progression from low to high level CMV reactivation/disease in D+R+ patients. Other immune mechanisms (eg, NK cells?) play the role in D-R+ patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Decrease of Clone Diversity in IgM Repertoires of HBV Chronically Infected Individuals With High Level of Viral Replication

2021 ◽  
Vol 11 ◽  
Author(s):  
Binbin Hong ◽  
Lizhi Wang ◽  
Chunlan Huang ◽  
Xiaoju Hong ◽  
Alan Liu ◽  
...  
Keyword(s):  
Viral Replication ◽  
Healthy Adults ◽  
Human Antibody ◽  
Low Level ◽  
Hbv Replication ◽  
Cdr3 Length ◽  
Chronic Hbv ◽  
Antibody Repertoires ◽  
High Level ◽  
The Comparative Study

High-throughput antibody sequencing allows in-depth insights into human antibody repertoires. To investigate the characteristics of antibody repertoires in patients with chronic HBV infection, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of B lymphocytes from healthy adults and the HBV carriers with high or low level of viral replication. The comparative study revealed high levels of similarity between the IgM and IgG repertoires of the HBV carriers and the healthy adults, including the somatic mutations in V regions, the average CDR3 length, and the occurrence of junctional modifications. Nevertheless, the diversity of the unique clones decreased and some clusters of unique clones expanded in the IgM repertoire of chronic HBV carriers (CHB) compared with healthy adults (HH) and inactive HBV carriers (IHB). Such difference in clone diversity and expansion was not observed in the IgG repertoires of the three populations. More shared antibody clones were found between the IgM repertoires of IHB and HH than that found between CHB and HH (7079 clones vs. 2304 clones). Besides, the biased used IGHD genes were IGHD2-2 and IGHD3-3 in CHB library but were IGHD3-10 and IGHD3-22 in IHB and HH library. In contrast, for IgG repertories, the preferred used VDJ genes were similar in all the three populations. These results indicated that low level of serum HBV might not induce significant changes in BCR repertoires, and high level of HBV replication could have more impacts on IgM repertories than IgG repertoires. Taken together, our findings provide a better understanding of the antibody repertoires of HBV chronically infected individuals.

scholarly journals JSOX: A Justly Simple Objectization for XML

2014 ◽  
Author(s):  
Steven J. DeRose
Keyword(s):  
The Other ◽  
Low Level ◽  
Other Hand ◽  
High Level ◽  
Cross Language

XML can be as easy to work with as JSON. However, this has not been obvious until now. JSON is easy because it supports only datatypes that are already native to Javascript and uses the same syntax to access them (such as [1:10], ["x"], and “.” notation). XML, on the other hand, supports additional datatypes, and is most commonly handled via SAX or DOM, both of which are low-level and meant to be cross-language. Typical developers want high-level access that feels “native” in the language they are using. These shortcomings have little or nothing to do with XML, and can be remedied by a different API. Software that demonstrates this is presented and described. It uses Python's richer set of abstract datatypes (such as tuples and sets), and provides native Python style syntax with richer semantics than JSON or Javascript.

scholarly journals Enabling Gene-Edited, Regulatory-like, T Cells (edTreg) for Treatment of IPEX and Other Autoimmune Disorders

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2071-2071 ◽  
Author(s):  
Yuchi Honaker ◽  
Karen Sommer ◽  
Noelle Dahl ◽  
Yufei Xiang ◽  
Christina Lopez ◽  
...  
Keyword(s):  
T Cells ◽  
Safety Data ◽  
Autoimmune Disorder ◽  
Foxp3 Expression ◽  
Effector T Cells ◽  
Therapy Strategy ◽  
Equity Ownership ◽  
High Level ◽  
And Function

IPEX (immunedysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is a severe congenital autoimmune disorder in males resulting from hemizygous inheritance of a mutant FOXP3 allele. FOXP3 encodes a transcription factor that governs the development, maintenance, and function of regulatory T cells (Treg). We have developed a cell therapy strategy for treatment of IPEX using a gene-editing approach in which CRISPR/Cas9 RNPs are co-delivered with an AAV6 donor template designed to integrate into the FOXP3 locus an expression cassette containing the MND promoter driving expression of a functional FOXP3 cDNA and a surface LNGFR tag linked by a 2A ribosomal skip peptide. This approach enforces heterologous FOXP3 expression in IPEX CD4 effector T cells (Teff), while simultaneously eliminating expression of the endogenous FOXP3 allele. The resultant high level and stable expression of functional FOXP3 converts Teff to Treg-like cells with immunosuppressive activity. Using an optimized protocol, we obtained efficient HDR rates across multiple healthy donors. Edited cells were consistently enriched to >95% purity by a magnetic LNGFR antibody selection and expanded 50-fold in a week. Expression of FOXP3 cDNA in edited cells was sufficient to enforce Treg-like phenotypes including the up-regulation of Treg-associated markers (CD25, CTLA-4, and ICOS), and down-regulation of CD127 and inflammatory cytokines (IL2, IFNgamma, TNFalpha). Importantly, we demonstrate sustained in vivo suppressive activity of these edited Treg-like cells (edTreg) in a xeno-GvHD mouse model. edTreg (as well as expanded natural Treg) limited effector T cell expansion and tissue infiltration and significantly protected mice from xeno-GvHD induced by co-transferred autologous effector T cells. Along with preliminary data showing successful editing in CD4 T cells from IPEX patients, our data provide key pre-clinical proof-of-concept and safety data supporting use of edTreg in a clinical trial for IPEX and, potentially, for use in other autoimmune diseases. Disclosures Torgerson: Shire: Consultancy; CSL Behring: Consultancy; ADMA Biosciences: Consultancy; UCB: Consultancy. Scharenberg:Casebia Therapeutics LLc: Employment, Equity Ownership; Alpine Biosciences: Consultancy, Equity Ownership; Generation Bio: Equity Ownership.

Categorization

2020 ◽  
pp. 27-37
Author(s):  
Stephen K. Reed
Keyword(s):  
Baby Boomers ◽  
The Other ◽  
Social Categories ◽  
Elbow Angle ◽  
Low Level ◽  
High Level ◽  
Selection Of

Categories reduce the complexity of the environment, are the means by which objects are identified, reduce the need for constant learning, allow for the selection of an appropriate action, and support the organization of objects and events. The most typical members of categories share attributes with the other members of the category. Prototypes are the central members. Hierarchies are composed of subordinate (desk lamp), basic (lamp), and superordinate (furniture) categories. Social categories such as “ baby boomers” classify people but may be associated with misleading stereotypes. Action categories include event boundaries that mark the transition between actions. They are organized into low-level (elbow angle) and high-level (pouring milk) actions.

Tingkat Kepemilikan Manajerial dan Nilai Perusahaan: Bukti Empiris pada Perusahaan Publik di Indonesia

2006 ◽  
Vol 1 (2) ◽  
pp. 135
Author(s):  
Henry Henry ◽  
Hamin Hamin
Keyword(s):  
Panel Data ◽  
Firm Value ◽  
Fixed Effects ◽  
Firm Heterogeneity ◽  
The Other ◽  
Managerial Ownership ◽  
Fixed Effects Model ◽  
Low Level ◽  
Other Hand ◽  
High Level

Initial analyses using panel data for none intercept model show a positive and significant effect of low level of managerial ownership on firm value ond negative and significant effect of high level of managerial ownership on firm value. This conclusion is dffirent when unobserved firm heterogeneity controlled using firm fixed effects model. Thefixed effects analyses suggest that managerial ownership doesn't have significant effect on firm value. The 2SLS analyses show that both managerial ownership and firm value are jointly endogenous. Managerial ownership has positively impacts on firm value, on higher firm value, on the other hand, inspires larger managerial ownershipKeywords: Managerial Ownership, Firm Yalue, Tobin's Q

Representations reclaimed

2010 ◽  
Vol 18 (2) ◽  
pp. 273-312 ◽  
Author(s):  
Joel Parthemore ◽  
Anthony F. Morse
Keyword(s):  
Mental Content ◽  
The Other ◽  
Conceptual Spaces ◽  
Low Level ◽  
Context Sensitive ◽  
High Level ◽  
The Relationship ◽  
Context Free ◽  
Content Of Experience

Understanding the relationship between concepts and experience seems necessary to specifying the content of experience, yet current theories of concepts do not seem up to the job. With Peter Gärdenfors’s conceptual spaces theory as a foundation and with enactivist philosophy as inspiration, we present a proposed extension to conceptual spaces theory and use it to outline a model of the emergence of concepts and experience. We conclude that neither is ultimately primary but each gives rise to the other: i.e., that they co-emerge. Such a model can then serve as the anchor to a theory of concepts more generally. Concepts are most naturally understood in symbolic and representational terms, while much of experience, in contrast, is non-symbolic and non-representational; yet the conflict between the two will, herein, be shown to be more apparent than real. The main contribution of this paper is to argue for, by means of this account of co-emergence, a continuum between “low-level” mental content that is more appropriately understood in highly context-sensitive and directly sensorimotor-based terms, and “high-level” mental content that is more appropriately understood in context-free and representational or symbolic terms. In doing so we conclude that the extreme positions of representationalism and anti-representationalism are fatally flawed.

scholarly journals Interferon–inducible T Cell Alpha Chemoattractant (I-TAC): A Novel Non-ELR CXC Chemokine with Potent Activity on Activated T Cells through Selective High Affinity Binding to CXCR3

1998 ◽  
Vol 187 (12) ◽  
pp. 2009-2021 ◽  
Author(s):  
Katherine E. Cole ◽  
Christine A. Strick ◽  
Timothy J. Paradis ◽  
Kevin T. Ogborne ◽  
Marcel Loetscher ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Fold Increase ◽  
Effector T Cells ◽  
Chemotactic Migration ◽  
Activated T Cells ◽  
Cxc Chemokine ◽  
Ifn Γ ◽  
High Level ◽  
Normal Leukocyte

Chemokines are essential mediators of normal leukocyte trafficking as well as of leukocyte recruitment during inflammation. We describe here a novel non-ELR CXC chemokine identified through sequence analysis of cDNAs derived from cytokine-activated primary human astrocytes. This novel chemokine, referred to as I-TAC (interferon-inducible T cell alpha chemoattractant), is regulated by interferon (IFN) and has potent chemoattractant activity for interleukin (IL)-2–activated T cells, but not for freshly isolated unstimulated T cells, neutrophils, or monocytes. I-TAC interacts selectively with CXCR3, which is the receptor for two other IFN-inducible chemokines, the IFN-γ–inducible 10-kD protein (IP-10) and IFN-γ– induced human monokine (HuMig), but with a significantly higher affinity. In addition, higher potency and efficacy of I-TAC over IP-10 and HuMig is demonstrated by transient mobilization of intracellular calcium as well as chemotactic migration in both activated T cells and transfected cell lines expressing CXCR3. Stimulation of astrocytes with IFN-γ and IL-1 together results in an ∼400,000-fold increase in I-TAC mRNA expression, whereas stimulating monocytes with either of the cytokines alone or in combination results in only a 100-fold increase in the level of I-TAC transcript. Moderate expression is also observed in pancreas, lung, thymus, and spleen. The high level of expression in IFN- and IL-1–stimulated astrocytes suggests that I-TAC could be a major chemoattractant for effector T cells involved in the pathophysiology of neuroinflammatory disorders, although I-TAC may also play a role in the migration of activated T cells during IFN-dominated immune responses.

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