scholarly journals Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and children

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Rasmus Mortensen ◽  
Thomas Nørrelykke Nissen ◽  
Sine Fredslund ◽  
Ida Rosenkrands ◽  
Jan Pravsgaard Christensen ◽  
...  
2021 ◽  
Vol 8 (4) ◽  
pp. 507-520
Author(s):  
Ashley N. Edes ◽  
Eli Baskir ◽  
Karen L. Bauman ◽  
Nathasha Chandrasekharan ◽  
Michael Macek ◽  
...  

Studies on how visitors affect penguins in human care report a mixture of negative, neutral, and positive impacts on behavior and physiology. Swimming is a highly motivated behavior that may promote positive welfare in penguins. We investigated how visitor crowd size, composition, and noise levels impact pool use in a mixed-species colony housing king (Aptenodytes patagonicus; n = 20), gentoo (Pygoscelis papua; n = 14), and southern rockhopper (Eudyptes chrysocome; n = 24) penguins. We used video and sound loggers to record if penguins were on land or in water, the number of human adults and children present, and noise levels using 5-minute scan samples from 09:00-15:00 over 36 continuous days. Data were analyzed using linear mixed models with proportion of penguins in the water as the dependent variable and crowd size, composition, and noise levels in A-weighted (dBA) and C-weighted (dBC) scales as independent variables. Crowd size was positively associated with pool use in gentoo penguins. Crowd composition did not predict pool use in any species. Noise levels in dBA, which is adjusted to the higher frequencies of human hearing, positively predicted pool use in southern rockhopper penguins. Noise levels in dBC, which captures lower frequencies, did not predict pool use in any species. No evidence of negative visitor effects was observed. Instead, these results suggest visitors are a neutral stimulus to king penguins and may be enriching to gentoo and southern rockhopper penguins.


2014 ◽  
Vol 3 (2) ◽  
Author(s):  
Bhupander Kumar ◽  
Virendra Kumar Verma ◽  
Satish Kumar Singh ◽  
Sanjay Kumar ◽  
Chandra Shekhar Sharma ◽  
...  

<em>Background</em>. Polychlorinated biphenyls (PCBs) have never been produced in India, but were used in industrial applications. PCBs have been detected in environmental samples since 1966, and their sources in soils come from depositions of industrial applications, incinerators and biomass combustions. PCBs adsorb to soil particles and persist for long time due to their properties. Their close proximity may also lead to human exposure through ingestion, inhalation, dermal contact, and may exert neurotoxic, mutagenic and carcinogenic health effects. <br /><em>Design and Methods</em>. Residential soil from Korba, India, was extracted using pressurized liquid extraction procedure, cleaned on modified silica and quantified for PCBs. Soil ingestion was considered as the main exposure pathways of life-long intake of PCBs. Human health risk in terms of life time average daily dose, incremental lifetime cancer risk (ILCR) and non-cancer hazard quotient (HQ) were estimated using established guidelines. <br /><em>Results</em>. The estimated average ILCR from non dioxin like PCBs for human adults and children was 3.1×10−8 and 1.1×10−7, respectively. ILCR from dioxin like PCBs for human adults and children was 3.1×10−6 and 1.1×10−5, respectively. The HQ for PCBs was 6.3×10−4 and 2.2×10−3, respectively for human adults and children. Study observed that ILCR from non dioxin like PCBs was lower than acceptable guideline range of 10−6-10−4, and ILCR from dioxin like PCBs was within the limit. HQ was lower than safe limit of 1. <br /><em>Conclusions</em>. Study concluded that human population residing in Korba had low health risk due to PCBs in residential soils.


1995 ◽  
Vol 182 (6) ◽  
pp. 1727-1737 ◽  
Author(s):  
S I Staprans ◽  
B L Hamilton ◽  
S E Follansbee ◽  
T Elbeik ◽  
P Barbosa ◽  
...  

Little is known about the factors that govern the level of HIV-1 replication in infected individuals. Recent studies (using potent antiviral drugs) of the kinetics of HIV-1 replication in vivo have demonstrated that steady-state levels of viremia are sustained by continuous rounds of de novo infection and the associated rapid turnover of CD4+ T lymphocytes. However, no information is available concerning the biologic variables that determine the size of the pool of T cells that are susceptible to virus infection or the amount of virus produced from infected cells. Furthermore, it is not known whether all CD4+ T lymphocytes are equally susceptible to HIV-1 infection at a given time or whether the infection is focused on cells of a particular state of activation or antigenic specificity. Although HIV-1 replication in culture is known to be greatly facilitated by T cell activation, the ability of specific antigenic stimulation to augment HIV-1 replication in vivo has not been studied. We sought to determine whether vaccination of HIV-1-infected adults leads to activation of virus replication and the targeting of vaccine antigen-responsive T cells for virus infection and destruction. Should T cell activation resulting from exposure to environmental antigens prove to be an important determinant of the steady-state levels of HIV-1 replication in vivo and lead to the preferential loss of specific populations of CD4+ T lymphocytes, it would have significant implications for our understanding of and therapeutic strategies for HIV-1 disease. To begin to address these issues, HIV-1-infected individuals and uninfected controls were studied by measurement of immune responses to influenza antigens and quantitation of virion-associated plasma HIV-1 RNA levels at baseline and at intervals after immunization with the trivalent influenza vaccine. Influenza vaccination resulted in readily demonstrable but transient increases in plasma HIV-1 RNA levels, indicative of activation of viral replication, in HIV-1-infected individuals with preserved ability to immunologically respond to vaccine antigens. Activation of HIV-1 replication by vaccination was more often seen and of greater magnitude in individuals who displayed a T cell proliferative response to vaccine antigens at baseline and in those who mounted a significant serologic response after vaccination. The fold increase in viremia, as well as the rates of increase of HIV-1 in plasma after vaccination and rates of viral decline after peak viremia, were higher in individuals with higher CD4+ T cell counts.(ABSTRACT TRUNCATED AT 400 WORDS)


2015 ◽  
Vol 45 (7) ◽  
pp. 1926-1933 ◽  
Author(s):  
Florence Jacomet ◽  
Emilie Cayssials ◽  
Sara Basbous ◽  
Anaïs Levescot ◽  
Nathalie Piccirilli ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tristan Scott ◽  
Ryan Urak ◽  
Citradewi Soemardy ◽  
Kevin V. Morris

Abstract CRISPR/Cas is a transformative gene editing tool, that offers a simple and effective way to target a catalytic Cas9, the most widely used is derived from Streptococcus pyogenes (SpCas9), with a complementary small guide RNA (sgRNA) to inactivate endogenous genes resulting from insertions and deletions (indels). CRISPR/Cas9 has been rapidly applied to basic research as well as expanded for potential clinical applications. Utilization of spCas9 as an ribonuclearprotein complex (RNP) is considered the most safe and effective method to apply Cas9 technology, and the efficacy of this system is critically dependent on the ability of Cas9 to generate high levels of indels. We find here that novel sequence changes to the tracrRNA significantly improves Cas9 activity when delivered as an RNP. We demonstrate that a dual-guide RNA (dgRNA) with a modified tracrRNA can improve reporter knockdown and indel formation at several targets within the long terminal repeat (LTR) of HIV. Furthermore, the sequence-modified tracrRNAs improved Cas9-mediated reduction of CCR5 surface receptor expression in cell lines, which correlated with higher levels of indel formation. It was demonstrated that a Cas9 RNP with a sequence modified tracrRNA enhanced indel formation at the CCR5 target site in primary CD4+ T-cells. Finally, we show improved activity at two additional targets within the HBB locus and the BCL11A GATA site. Overall, the data presented here suggests that novel facile tracrRNA sequence changes could potentially be integrated with current dgRNA technology, and open up the possibility for the development of sequence modified tracrRNAs to improve Cas9 RNP activity.


2005 ◽  
Vol 35 (6) ◽  
pp. 1987-1994 ◽  
Author(s):  
Siegfried Kohler ◽  
Ulf Wagner ◽  
Matthias Pierer ◽  
Sonja Kimmig ◽  
Birgit Oppmann ◽  
...  

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii421-iii421
Author(s):  
Perla Moukhaiber ◽  
Anna Samolej ◽  
Palita Somsri ◽  
Geoffrey McCowage

Abstract BACKGROUND Trametinib (Tr) has been applied in the treatment of children with various tumor types, often for prolonged periods. Little is known regarding immune function (IF) following prolonged Tr in this age group. OBJECTIVE Describe laboratory measures of IF in children on Tr. METHOD Patients receiving Tr had low grade glioma with BRAF anomalies (6), or neurofibromatosis-1 (16) with glioma or plexiform neurofibroma. IF was evaluated using leukocyte/lymphocyte counts, immunoglobulin levels, and antibody titres. RESULTS 22 patients received Tr. 2 also received Dabrafenib. Median age at Tr initiation of Tr was 7.75 years. As of June 2020, 7 patients have had IFT; results are pending on 15. Median duration of Tr therapy at time of IF was 3.5 years (0.8 – 4). In these 7 patients, median white cell count was 6.9 x 10^9/L (4.1 – 12.6), neutrophils 4.2 x 10^9/L (1.8 – 6.8) and lymphocytes 3.2 x 10^9/L (1.4 – 7). IgG levels, B cells and CD8 cytotoxic T cells were normal across 7/7 patients:medians 9.47 g/L (8.62 – 17), 0.51 x 10^9/L (0.2 – 1.26) and 0.58 x 10^9/L (0.25 – 2.03) respectively. CD3 and CD4 T cells: median 2.08 x 10^9/L (0.67 – 4.62) and 1.34 x 10^9/L (0.35 – 2.31), borderline low in 1 heavily pre-treated patient. An adequate immune response was present in all 4 vaccine antigens tested in 5/5 patients. CONCLUSION IF appears relatively intact, relevant for immunisation and infection precautions in children on Tr. Data on the complete cohort will be presented.


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