scholarly journals Discrete SARS-CoV-2 antibody titers track with functional humoral stability

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yannic C. Bartsch ◽  
Stephanie Fischinger ◽  
Sameed M. Siddiqui ◽  
Zhilin Chen ◽  
Jingyou Yu ◽  
...  

AbstractAntibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity—defined by the level of antibodies—is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses.

2020 ◽  
Vol 28 (1) ◽  
pp. 230949901989061
Author(s):  
Suroosh Madanipour ◽  
Aditya Prinja ◽  
Marcus Lee ◽  
Abbas Rashid

There is limited literature to guide shoulder surgeons in the management of juvenile idiopathic arthritis (JIA). We aim to help clinicians to formulate an approach to the surgical management of the condition through a review of the available literature on arthroplasty in JIA, general considerations when operating on patients with inflammatory arthropathy and recommendations based on the authors’ experience. Four articles report formal data on arthroplasty in JIA with favourable improvements in post-operative pain and function scores after the long-term follow-up. Significant heterogeneity in treatment and a lack of standardisation in quantitative outcomes highlights the need for further larger scale and higher quality research. The aim of this study is to review the evidence and provide information on preoperative evaluation of surgical candidates, operative techniques, choice of implant design and to evaluate functional outcomes in patients who undergo shoulder arthroplasty.


Author(s):  
Lia Almeida Mapurunga ◽  
Elcyana Bezerra Elcyana Bezerra Carvalho

A neurociência é uma ciência natural que estuda a função e a estrutura, que compõem o cérebro. A educação, embora tenha outra natureza, tem tido muitos benefícios com as contribuições que a neurociência tem para oferecer. Como o cérebro aprende e por que aprende traz para o ensino o objetivo e a função de criar condições (entre estratégias, recursos e adequação do meio), para que ocorra a aprendizagem. E, para que essa ocorra, é necessário que as funções mentais superiores, como a memória, estejam envolvidas. O objetivo deste estudo consiste em fazer uma revisão de literatura para conhecer a função da memória de longo prazo na aprendizagem, analisar os mecanismos neurobiológicos, que ocorrem durante esse processo e algumas estratégias de aprendizagem, que se utilizam da memória como recurso. Para isso, foi realizado no período de agosto a outubro de 2016, um levantamento bibliográfico nas bases de dados Scielo, Capes, Bireme e Google Acadêmico, buscando artigos científicos, que poderiam trazer alguma contribuição na construção dessa pesquisa. Foram selecionados, preferencialmente, os que continham enfoque na relação entre aprendizagem e memória, tanto na perspectiva da neurociência, quanto da psicologia cognitiva, trazendo argumentos que pudessem  comprovar o entendimento das estratégias de aprendizagem, a partir da memória de longo prazo. Também foram selecionados livros que apresentavam apoio às temáticas discorridas para esse trabalho, possibilitando essa relação. Os resultados apontam que estratégias de aprendizagens, que utilizam a memória, produzem efeitos positivos para a retenção de longo prazo.Palavras-chave: Aprendizagem. Neurociências. Estratégias de Aprendizagem.AbstractNeuroscience is a natural science that studies the function and structure that forms the brain. Although education has another nature, it has had many benefits from the contributions that neuroscience has to offer. How the brain learns and why it learns brings to teaching the intent and function to create conditions (among strategies, resources and suitability to the environment) so that learning can happen. And, for it to occur, it is  necessary that higher mental functions, such as memory, beinvolved. The purpose of this study is to do a literature review to get to know the function of long-term memory on the learning process, to analyze the neurobiological mechanisms that happen during that process, and some learning strategies that use memory as a resource. Therefore a bibliographical survey was conducted at the databases Scielo, Capes, Bireme and Academic Google, from August to October 2016, searching for scientific articles that could contribute somehow on the construction of this research. The articles that used the neuroscience perspective or the cognitive psychology to focus on the relationship  between learning and memory were chosen, preferentially those whose arguments could prove the  learning strategies understanding about he long-term memory. Books supporting the themes discussed for this work were also selected, creating, therefore, a relationship. The results show that learning strategies that use memory have positive effects for long-term retention.Keywords: Learning. Neuroscience. Learning Strategies.


Author(s):  
Ryan Insolera ◽  
Péter Lőrincz ◽  
Alec J Wishnie ◽  
Gábor Juhász ◽  
Catherine A Collins

AbstractA healthy population of mitochondria, maintained by proper fission, fusion, and degradation, is critical for the long-term survival and function of neurons. Here, our discovery of mitophagy intermediates in fission-impaired Drosophila neurons brings new perspective into the relationship between mitochondrial fission and mitophagy. Neurons lacking either the ataxia disease gene Vps13D or the dynamin related protein Drp1 contain enlarged mitochondria that are engaged with autophagy machinery and also lack matrix components due to rupture. Reporter assays combined with genetic studies imply that mitophagy both initiates and is completed in Drp1 impaired neurons, but fails to complete in Vps13D impaired neurons, which accumulate compromised mitochondria within stalled mito-phagophores. Our findings imply that in fission-defective neurons, mitophagy becomes induced, and that the lipid channel containing protein Vps13D has separable functions in mitochondrial fission and phagophore elongation.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243967
Author(s):  
Viola Hähnel ◽  
David Peterhoff ◽  
Veronika Bäuerlein ◽  
Andreas-Michael Brosig ◽  
Irene Pamler ◽  
...  

The ongoing coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019. Convalescent plasma represents a promising COVID-19 treatment. Here, we report on the manufacturing of a plasma-based product containing antibodies specific to SARS-CoV-2 obtained from recently recovered COVID-19 patients. Convalescent plasma donors were screened as follows: 1) previously confirmed SARS-CoV-2 infection (by real-time PCR (RT-PCR)); 2) a subsequent negative PCR test followed by a 2-week waiting period; 3) an additional negative PCR test prior to plasmapheresis; and 4) confirmation of the presence of SARS-CoV-2 specific antibodies. Convalescent plasma was stored fresh (2–6°C) for up to 5 days or frozen (-30°C) for long-term storage. Donor peripheral blood and final plasma product were assayed for binding antibodies targeting the SARS-CoV-2 S-protein receptor-binding domain (RBD) and their titers measured by an enzyme-linked immunosorbent assay (ELISA). We performed 72 plasmaphereses resulting in 248 final products. Convalescent plasma contained an RBD-specific antibody titer (IgG) ranging from 1:100 to 1:3200 (median 1:800). The titer was congruent to the titer of the blood (n = 34) before collection (1:100–1:6400, median 1:800). Levels of IL-8 and LBP of donors were slightly increased. Therapeutic products derived from a human origin must undergo rigorous testing to ensure uniform quality and patient safety. Whilst previous publications recommended RBD-specific binding antibody titers of ≥ 1:320, we selected a minimum titer of 1:800 in order to maximize antibody delivery. Production of highly standardized convalescent plasma was safe, feasible and was readily implemented in the treatment of severely ill COVID-19 patients.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009731
Author(s):  
Ryan Insolera ◽  
Péter Lőrincz ◽  
Alec J. Wishnie ◽  
Gábor Juhász ◽  
Catherine A. Collins

A healthy population of mitochondria, maintained by proper fission, fusion, and degradation, is critical for the long-term survival and function of neurons. Here, our discovery of mitophagy intermediates in fission-impaired Drosophila neurons brings new perspective into the relationship between mitochondrial fission and mitophagy. Neurons lacking either the ataxia disease gene Vps13D or the dynamin related protein Drp1 contain enlarged mitochondria that are engaged with autophagy machinery and also lack matrix components. Reporter assays combined with genetic studies imply that mitophagy both initiates and is completed in Drp1 impaired neurons, but fails to complete in Vps13D impaired neurons, which accumulate compromised mitochondria within stalled mito-phagophores. Our findings imply that in fission-defective neurons, mitophagy becomes induced, and that the lipid channel containing protein Vps13D has separable functions in mitochondrial fission and phagophore elongation.


2021 ◽  
Author(s):  
Kristen A Earle ◽  
Donna M Ambrosino ◽  
Andrew Fiore-Gartland ◽  
David Goldblatt ◽  
Peter B Gilbert ◽  
...  

Though eleven novel COVID-19 vaccines have demonstrated efficacy, additional affordable, scalable, and deliverable vaccines are needed to meet unprecedented global demand. With placebo-controlled efficacy trials becoming infeasible due to the roll out of licensed vaccines, a correlate of protection is urgently needed to provide a path for regulatory approval of novel vaccines. To assess whether antibody titers may reasonably predict efficacy, we evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccines for which sufficient data have been generated. Once calibrated to titers of human convalescent sera reported in each study, a robust correlation was seen between neutralizing titer and efficacy (ρ= 0.79) and binding antibody titer and efficacy (ρ = 0.93), despite geographically diverse study populations subject to different forces of infection and circulating variants, and use of different endpoints, assays, convalescent sera panels and manufacturing platforms. This correlation is strengthened by substituting post-hoc analyses for efficacy against the ancestral strain (D614G), where available. Together with an accumulating body of evidence from natural history studies and animal models, these results support the use of post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccines.


2022 ◽  
Author(s):  
Tingting Qiao ◽  
Ganghua Lu ◽  
Zhongwei Lv ◽  
Dan Li ◽  
Chengyou Jia ◽  
...  

Abstract BackgroundThe practices of monks mainly include long-term vegetarianism and meditation, which are likely to fundamentally influence the gut microbiota and fecal metabolites. We aim to study the relationship between the practices of Chinese monks and gut microbiotas and metabolites.MethodsTwenty-four monks and forty-eight omnivorous controls (never meditated) were included. The microbiotas of all samples were profiled by 16S rRNA gene sequencing, and the metabolomes were examined by nontargeted LC–MS metabolomics. Twenty-four monks were divided into the H group and the L group according to the median time of practice, and microbiota and metabolite analyses were carried out in the two groups.ResultsMicrobial communities and metabolites were decreased in monks. Bacteroidetes was increased in monks, while the Firmicutes, Actinobacteria, and Firmicutes/Bacteroidetes ratios were decreased. At the genus level, Faecalibacterium, Lachnospira, Roseburia, norank_f__Lachnospiraceae, etc. were higher in monks, while Blautia, Eubacterium__hallii_group, Bifidobacteria, etc. were lower (all p < 0.05). Most identical KEGG categories in both Tax4Fun and PICRUSt2 were related to metabolism (6/8, 75.0%). Most higher abundance genera were positively correlated with higher abundance metabolites in monks, indicating that intestinal flora significantly affects intestinal metabolic function. Lipids and lipid-like molecules were the major differential metabolites (VIP >2, p < 0.05) in the two groups. L-dopa plays an important role in many metabolic pathways in monks. Prevotella_9 was enriched in the L group, while norank_f__Lachnospiraceae was enriched in the H group. DG (16:0/18:0/0:0) was highly expressed in the H group and participated in sixteen KEGG functional pathways as well as many immune-related KEGG enrichment pathways.ConclusionThe monks' lifestyle practices of vegetarianism and meditation have the potential to modulate human metabolism and function by affecting the gut microbial composition and metabolites. The appropriate practice of monks makes the intestine younger and increases immunity, but long-term practice may cause adverse physical and mental events.


2020 ◽  
Vol 22 (4) ◽  
pp. 536-543
Author(s):  
Sen-Te Wang ◽  
Yen-Kuang Lin ◽  
Shuen-Fu Weng ◽  
Chen-Ling Huang ◽  
Hui-Chuan Huang ◽  
...  

Background: An increase in the physical activity level reduces body weight, decreases body fat, increases skeletal muscle mass, and improves serum glucose; however, the influence of body composition parameters on the relationship between physical activity and serum glucose remains unclear. Objective: This study investigated whether skeletal muscle and visceral fat affect the relationship between high physical activity and long-term serum glucose goals. Method: This cross-sectional study recruited patients with type 2 diabetes. The Chinese version of the International Physical Activity Questionnaire was used for estimating the physical activity level, and a bioimpedance device was used to measure the skeletal muscle ratio (skeletal muscle mass/total body weight, %) and visceral fat area (cm2). Hierarchical logistic regression models and mediation tests were conducted according to Hayes’ procedures. Results: Of the total 543 Chinese individuals with type 2 diabetes enrolled, HbA1C levels of fewer than half (n = 243, 44.8%) met the target of ≤7.0%. The skeletal muscle ratio was found to be a complete mediator (OR = 0.920, 95% CI: 0.848 to 0.998; indirect effect: −0.238, 95% CI: −0.525 to −0.020) of the relationship between high physical activity and the target HbA1C level after controlling for visceral fat area (indirect effect: −0.013, 95% CI: −0.183 to 0.156), age, time since diabetes diagnosis, and rice intake. Conclusion: Nurses should include an increase in the skeletal muscle ratio as an objective in physical activity interventions for patients with type 2 diabetes to help them achieve their long-term serum glucose goals.


Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).


1991 ◽  
Vol 65 (03) ◽  
pp. 263-267 ◽  
Author(s):  
A M H P van den Besselaar ◽  
R M Bertina

SummaryIn a collaborative trial of eleven laboratories which was performed mainly within the framework of the European Community Bureau of Reference (BCR), a second reference material for thromboplastin, rabbit, plain, was calibrated against its predecessor RBT/79. This second reference material (coded CRM 149R) has a mean International Sensitivity Index (ISI) of 1.343 with a standard error of the mean of 0.035. The standard error of the ISI was determined by combination of the standard errors of the ISI of RBT/79 and the slope of the calibration line in this trial.The BCR reference material for thromboplastin, human, plain (coded BCT/099) was also included in this trial for assessment of the long-term stability of the relationship with RBT/79. The results indicated that this relationship has not changed over a period of 8 years. The interlaboratory variation of the slope of the relationship between CRM 149R and RBT/79 was significantly lower than the variation of the slope of the relationship between BCT/099 and RBT/79. In addition to the manual technique, a semi-automatic coagulometer according to Schnitger & Gross was used to determine prothrombin times with CRM 149R. The mean ISI of CRM 149R was not affected by replacement of the manual technique by this particular coagulometer.Two lyophilized plasmas were included in this trial. The mean slope of relationship between RBT/79 and CRM 149R based on the two lyophilized plasmas was the same as the corresponding slope based on fresh plasmas. Tlowever, the mean slope of relationship between RBT/79 and BCT/099 based on the two lyophilized plasmas was 4.9% higher than the mean slope based on fresh plasmas. Thus, the use of these lyophilized plasmas induced a small but significant bias in the slope of relationship between these thromboplastins of different species.


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