scholarly journals Antibody heavy chain CDR3 length-dependent usage of human IGHJ4 and IGHJ6 germline genes

2021 ◽  
Author(s):  
Huimin Wang ◽  
Kai Yan ◽  
Ruixue Wang ◽  
Yi Yang ◽  
Yuelei Shen ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Immune Repertoire ◽  
Model Framework ◽  
Synthetic Antibody ◽  
Cdr3 Length ◽  
Germline Genes ◽  
Antibody Discovery ◽  
Human Immune ◽  
Antibody Heavy Chain

Abstract Background Therapeutic antibody discovery using synthetic diversity has been proved productive, especially for target proteins not suitable for traditional animal immunization-based antibody discovery approaches. In recent years, many lines of evidences suggest that the quality of synthetic diversity design limits the development success of synthetic antibody hits. The aim of our study is to understand the quality limitation and to properly address the challenges with a better design. Methods Using VH3–23 as a model framework, we analyzed the naturally and productively rearranged CDR-H3 diversity in human immune repertoire. With homology modeling, we further built VH3–23-based structural models to understand the spatial paratope and its influencing parameters. Results We observed and quantitatively mapped CDR-H3 loop length-dependent usage of human IGHJ4 and IGHJ6 germline genes in the natural human immune repertoire. Skewed usage of DH2-JH6 and DH3-JH6 rearrangements was quantitatively determined in a CDR-H3 length-dependent manner in natural human antibodies with long CDR-H3 loops. Such CDR-H3 length dependent usage of human germline genes was not impacted by the choices of VH in the V(D)J recombination, ethnic background and health conditions. Structural modeling suggests choices of JH help to stabilize antibody CDR-H3 loop and JH only partially contributes to the paratope. Conclusions We quantitatively determined the CDR-H3 length-dependent usage of human germline genes, which makes it possible to design synthetic diversity fully mimicking that of natural immune repertoire. Our observations shed light on the design of next generation synthetic diversity with improved probability of success.

scholarly journals Testing the applicability of a model of oral health-related quality of life

2015 ◽  
Vol 31 (9) ◽  
pp. 1871-1880 ◽  
Author(s):  
Camila Mello dos Santos ◽  
Roger Keller Celeste ◽  
Juliana Balbinot Hilgert ◽  
Fernando Neves Hugo
Keyword(s):  
Quality Of Life ◽  
Oral Health ◽  
Functional Status ◽  
Conceptual Model ◽  
Direct Effect ◽  
Health Related Quality ◽  
Model Framework ◽  
Related Quality ◽  
Health Related

The aim of this study was to test Wilson & Cleary’s conceptual model of the direct and mediated pathways between clinical and non-clinical variables in relation to oral health-related quality of life. A random sample of 578 older people was evaluated. Wilson & Cleary’s conceptual model was tested using structural equations modeling including: biological variables, symptom status, functional health, oral health perceptions, oral health-related quality of life. Oral health-related quality of life was assessed with the Oral Health Impact Profile-14 (OHIP-14). In the final model, edentulism was negatively correlated to dissatisfaction of appearance of their dental prostheses (r = -0.25). Worse functional status was correlated with poor oral health perception (r = 0.24). Being aged over 68 (r = 0.25), being a female (r = 0.39) and living in rural areas (r = 0.15) had a direct effect on the edentulism. Age had a direct effect on OHIP-14 (r = -0.15). There was an indirect effect of sex on OHIP-14 via functional status (r = 0.12). The present findings partially support Wilson & Cleary’s model framework.

scholarly journals Survival Augmented Patient Preference Incorporated Reinforcement Learning to Evaluate Tailoring Variables for Personalized Healthcare

Stats ◽  
2021 ◽  
Vol 4 (4) ◽  
pp. 776-792
Author(s):  
Yingchao Zhong ◽  
Chang Wang ◽  
Lu Wang
Keyword(s):  
Quality Of Life ◽  
Patient Preference ◽  
Treatment Strategies ◽  
Treatment Decision ◽  
Personalized Treatment ◽  
Model Framework ◽  
Q Learning ◽  
Treatment Decision Making ◽  
Weighted Utility

In this paper, we consider personalized treatment decision strategies in the management of chronic diseases, such as chronic kidney disease, which typically consists of sequential and adaptive treatment decision making. We investigate a two-stage treatment setting with a survival outcome that could be right censored. This can be formulated through a dynamic treatment regime (DTR) framework, where the goal is to tailor treatment to each individual based on their own medical history in order to maximize a desirable health outcome. We develop a new method, Survival Augmented Patient Preference incorporated reinforcement Q-Learning (SAPP-Q-Learning) to decide between quality of life and survival restricted at maximal follow-up. Our method incorporates the latent patient preference into a weighted utility function that balances between quality of life and survival time, in a Q-learning model framework. We further propose a corresponding m-out-of-n Bootstrap procedure to accurately make statistical inferences and construct confidence intervals on the effects of tailoring variables, whose values can guide personalized treatment strategies.

Promotion of the Growth and Quality of Chinese Cabbage by Application of Biogas Slurry of Water Hyacinth

2012 ◽  
Vol 195-196 ◽  
pp. 1200-1206 ◽  
Author(s):  
Yan Feng Xue ◽  
Zhi Qi Shi ◽  
Jian Chen ◽  
Shao Hua Yan ◽  
Jian Chu Zheng
Keyword(s):  
Chinese Cabbage ◽  
Water Hyacinth ◽  
Quality Index ◽  
Soluble Sugar ◽  
Dependent Manner ◽  
Biogas Slurry ◽  
Fresh Weight ◽  
Shoot Height ◽  
Nitrite Content

Biomass and quality index of Chinese cabbage were investigated under the following treatment, control (CK), 25% biogas slurry + 75% fertilizer (Z-25%), 50% biogas slurry + 50% fertilizer (Z-50%), 75% biogas slurry + 25% fertilizer (Z-75%), and 100% biogas slurry (Z-100%). The results indicated that Z-25% significantly increased shoot height and fresh weight. But shoot height and fresh weight significantly decreased in a time-dependent manner when the concentration of the biogas slurry was greater than 50%. Vitamin C, soluble sugar, protein, and nitrite were measured to evaluate the effect of biogas slurry on the quality of Chinese cabbage. Z-25% treatment could remarkably increased the content of dehydroascorbate (DHA) and total Vc, whereas did not significantly affect reduced ascorbate (AsA) content compared to the CK for 60 d. The content soluble sugar and protein were significantly enhanced under Z-25% treatment. In addition, Z-25% effectively reduced nitrite content in Chinese cabbage. Biogas slurry with concentration more than 50% could not promote quality index of Chinese cabbage. To sum up, biogas slurry of water hyacinth could improve the growth and quality of Chinese cabbage under the optimal applied concentration.

scholarly journals Plasma glutathione status as indicator of pre-analytical centrifugation delay

2020 ◽  
Author(s):  
Tomin Tamara ◽  
Natalie Bordag ◽  
Elmar Zuegner ◽  
Abdullah Al-Baghdadi ◽  
Maximilian Schinagl ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Time Dependent ◽  
Dependent Manner ◽  
Prolonged Incubation ◽  
Glutathione Status ◽  
Potential Marker ◽  
Analytical Centrifugation ◽  
Plasma Glutathione ◽  
Downstream Analysis

Prolonged incubation of blood prior to plasma preparation can significantly influence the quality of the resulting data. Different markers for this pre-clinical variability have been proposed over the years but with limited success. In this study we explored the usefulness of glutathione (GSH) status, namely ratio of reduced to oxidized glutathione (GSH/GSSG), as potential marker of plasma preparation delay. For that purpose, blood from 20 healthy volunteers was collected into tubes with a cysteine quencher (N-ethylmaleimide; NEM) for GSH stabilization. Plasma preparation was delayed at room temperature for up to 3 hours and every hour, a plasma sample was prepared and the GSH/GSSG ratio measured. We report that over the course of the investigation, plasma concentrations of both GSH and GSSG increased linearly (R2 = 0.99 and 0.98, respectively). Since GSH increased at a much faster rate compared to GSSG, the GSH/GSSG ratio also increased linearly in a time dependent manner (R2 = 0.99). As GSH is an intracellular antioxidant, we speculated that this might stem from ongoing blood hemolysis, which was confirmed by the time dependent rise in lactate dehydrogenase (LDH) activity in the plasma samples. Moreover, we demonstrate that the addition of the thiol alkylating reagent NEM directly to the blood tubes does not seem to influence downstream analysis of clinical parameters. In conclusion we propose that the glutathione status could be used as an indicator of the centrifugation delay prior to plasma preparation.

Effect of Diglyceryl Dicaprylate on Candida albicans growth and pathogenicity

2021 ◽  
Author(s):  
Tomojiro Koide ◽  
Muneaki Tamura
Keyword(s):  
Candida Albicans ◽  
Proteolytic Enzymes ◽  
Pathogenic Fungus ◽  
Oral Care ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Highly Pathogenic ◽  
Antifungal Effect ◽  
Pathogenic Factors

Abstract The antifungal effect of diglyceryl dicaprylate (DGDC), one of the emulsifiers used as a food additive, on Candida albicans which is a pathogenic fungus that is predominant in the oral cavity was investigated. This component did not affect C. albicans growth, however, it suppressed some virulence factors in a concentration-dependent manner. Furthermore, the suppression of pathogenic factors, such as biofilm formation, adhesion, highly pathogenic dimorphism, and ability to produce proteolytic enzymes was due to reduction in mRNA expression levels of genes involved in fungal pathogenicities. From these results, this emulsifier could potentially prevent the development of intraoral and extraoral diseases involving C. albicans and could potentially use in oral care and improvement of quality of life.

scholarly journals Recent Advancements and Applications of Human Immune System Mice in Preclinical Immuno-Oncology

2019 ◽  
Vol 48 (2) ◽  
pp. 302-316 ◽  
Author(s):  
Michelle Curran ◽  
Maelle Mairesse ◽  
Alba Matas-Céspedes ◽  
Bethany Bareham ◽  
Giovanni Pellegrini ◽  
...  
Keyword(s):  
Immune System ◽  
New Technologies ◽  
Immune Cell ◽  
Human Immune System ◽  
Immunodeficient Mice ◽  
Graft Versus Host ◽  
Human Immune ◽  
And Function ◽  
Human Cytokines

Significant advances in immunotherapies have resulted in the increasing need of predictive preclinical models to improve immunotherapeutic drug development, treatment combination, and to prevent or minimize toxicity in clinical trials. Immunodeficient mice reconstituted with human immune system (HIS), termed humanized mice or HIS mice, permit detailed analysis of human immune biology, development, and function. Although this model constitutes a great translational model, some aspects need to be improved as the incomplete engraftment of immune cells, graft versus host disease and the lack of human cytokines and growth factors. In this review, we discuss current HIS platforms, their pathology, and recent advances in their development to improve the quality of human immune cell reconstitution. We also highlight new technologies that can be used to better understand these models and how improved characterization is needed for their application in immuno-oncology safety, efficacy, and new modalities therapy development.

scholarly journals Imaging of Cell Structures Using Optimized Soft X-ray Contact Microscopy

2020 ◽  
Vol 10 (19) ◽  
pp. 6895 ◽  
Author(s):  
Paulina Natalia Osuchowska ◽  
Przemysław Wachulak ◽  
Agata Nowak-Stępniowska ◽  
Andrzej Bartnik ◽  
Kajangi Gnanachandran ◽  
...  
Keyword(s):  
Breast Cancer Cells ◽  
Carcinoma Cells ◽  
Dependent Manner ◽  
X Ray ◽  
Cell Structures ◽  
A Cell ◽  
The Relationship ◽  
Cell Thickness ◽  
Exposure Conditions

This work is to study the relationship between the exposure conditions and the quality of cell imaging with soft X-ray contact microscopy (SXCM). It is a crucial step in the efficient visualization of cell structures. Three different human cell lines: DU145 prostate carcinoma cells, HCC38 breast cancer cells, and Poietics mesenchymal stem cells were used to establish the optimal exposure conditions in SXCM. The image quality depended on the soft X-ray (SXR) absorbed energy and photoresist development conditions. At lower SXR energy (200 or 400 SXR pulses), sharp cell edges, membrane projections, and cell–cell connections were visible. In contrast, higher energy (600 or 800 SXR pulses) allowed observation of the cytoskeleton and the nucleus in a cell type-dependent manner (the influence of cell thickness and internal complexity was noted).

Synthetic antibody discovery against native antigens by CRISPR/Cas9-library generation and endoplasmic reticulum screening

2020 ◽  
Vol 104 (6) ◽  
pp. 2501-2512
Author(s):  
Joana H. Ministro ◽  
Soraia S. Oliveira ◽  
Joana G. Oliveira ◽  
Miguel Cardoso ◽  
Frederico Aires-da-Silva ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Synthetic Antibody ◽  
Antibody Discovery

scholarly journals The Role of Estrogens in Rheumatoid Arthritis Physiopathology

2020 ◽  
Author(s):  
Maria Fernanda Romo-García ◽  
Martín Zapata-Zuñiga ◽  
José Antonio Enciso-Moreno ◽  
Julio Enrique Castañeda-Delgado
Keyword(s):  
Rheumatoid Arthritis ◽  
Direct Action ◽  
Hormone Replacement ◽  
Joint Disease ◽  
Dependent Manner ◽  
Sexual Hormones ◽  
Dose Dependent ◽  
Estrogen Administration

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease that can lead to irreversible disability. It affects women in a higher proportion than men (3:1 cases). Several reports suggest a link between female sexual hormones (estrogens) and RA features. It’s been described that biological processes where basal estrogen levels are altered like in menstruation, pregnancy, and menopause modifies RA onset, flare, disease severity, and inflammation. Estrogens have a direct action upon the immune system though ERα and ERβ receptors, which have distinct affinity to estrogen concentrations and modifications and have effects upon RA in a dose and receptor dependent manner. The studies focused on dose dependent response at experimental settings reveal a wide (from 25 pg/L to several μg/L) and even contradictory spectrum of effects in patients and cells. This chapter summarizes the contributions and effects of estrogens in RA physiopathology, clinical features, and discusses the possible contributions of estrogen administration and concentration of hormone replacement therapy (HRT) to improve the quality of life and reduce the symptoms of RA patients based on the knowledge of the biology of these hormones.

scholarly journals 0790 The Clinical Significance of Hepcidin as a Predictive Value for Treatment Responses in Restless Legs Syndrome

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A300-A301
Author(s):  
H Im
Keyword(s):  
Restless Legs Syndrome ◽  
Iron Homeostasis ◽  
Dependent Manner ◽  
Healthy Controls ◽  
Restless Legs ◽  
Inflammatory Processes ◽  
Drug Naïve ◽  
Therapeutic Responses

Abstract Introduction Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is related to iron-dopamine dysregulation and immune system alteration. Hepcidin is the key regulatory hormone of systemic iron homeostasis and is related to inflammatory processes. We aimed to evaluate the clinical utility of hepcidin as a diagnostic biomarker and index of therapeutic responses in RLS patients after dopaminergic treatment. Methods Non-anemic and drug-naive RLS patients (n=18) and healthy controls (n=15) were enrolled. Hepcidin (pre-prohepcidin) and iron-related values in serum were measured upon the first visit in both groups and 12 weeks later after dopaminergic treatment in 12 RLS patients. Information about sociodemographic characteristics, sleep-related profiles, mood, and anxiety was obtained upon the first visit in all participants as well as after treatment in RLS patients. Results Hepcidin levels exhibited no significant differences between patients with drug-naïve RLS and healthy controls at a diagnosis (7.1 ± 2.4 vs. 7.0 ± 3.2 ng/ml, p = 0.978). Decreased hepcidin levels were significantly associated with decreased RLS severity (β = 0.002, 95% CI = 0.00−0.00, p = 0.005) and improved quality of life (β = 0.002, 95% CI = 0.00−7.01, p = 0.044) in a dose-dependent manner after 12 weeks of treatment with a dopamine agonist. This association was independent of age, sex, inflammatory markers, sleep quality, insomnia, daytime sleepiness, depression, and anxiety. Conclusion This study demonstrates a role of hepcidin as a predictor of therapeutic responses in RLS patients. Support This work was supported by the Korea Health technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, South Korea [grant number HI17C2072].

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