class i
Recently Published Documents


TOTAL DOCUMENTS

17961
(FIVE YEARS 2476)

H-INDEX

228
(FIVE YEARS 16)

2022 ◽  
Vol 12 ◽  
Author(s):  
Chongming Jiang ◽  
Evelien Schaafsma ◽  
Wei Hong ◽  
Yanding Zhao ◽  
Ken Zhu ◽  
...  

BackgroundNeoantigens are presented on the cancer cell surface by peptide-restricted human leukocyte antigen (HLA) proteins and can subsequently activate cognate T cells. It has been hypothesized that the observed somatic mutations in tumors are shaped by immunosurveillance.MethodsWe investigated all somatic mutations identified in The Cancer Genome Atlas (TCGA) Skin Cutaneous Melanoma (SKCM) samples. By applying a computational algorithm, we calculated the binding affinity of the resulting neo-peptides and their corresponding wild-type peptides with the major histocompatibility complex (MHC) Class I complex. We then examined the relationship between binding affinity alterations and mutation frequency.ResultsOur results show that neoantigens derived from recurrent mutations tend to have lower binding affinities with the MHC Class I complex compared to peptides from non-recurrent mutations. Tumor samples harboring recurrent SKCM mutations exhibited lower immune infiltration levels, indicating a relatively colder immune microenvironment.ConclusionsThese results suggested that the occurrences of somatic mutations in melanoma have been shaped by immunosurveillance. Mutations that lead to neoantigens with high MHC class I binding affinity are more likely to be eliminated and thus are less likely to be present in tumors.


Author(s):  
Abhishek Jain ◽  
Garima Jain ◽  
Madhuli Bhide ◽  
Pratibha Sharma ◽  
Janhavi Sapre ◽  
...  

A 12 years 6 months old Indian male presented with a chief complaint of irregular upper and lower front teeth. Patient exhibited a mild convex profile on Class l skeletal base with slightly decreased vertical proportions. This was complicated by severe upper and lower labial segment crowding. Also the molar relationship was half unit class ll bilaterally. Since the patient did not want to go for extraction of premolars, treatment involved use of Pendulum appliance along with upper and lower pre-adjusted edgewise appliance (0.022x0.028” slot) with MBT prescription. Various elastics and overlay wires were used along with proximal stripping for the correction of severe crowding in upper and lower anterior teeth.: Clinically Angle’s Class I occlusion was achieved bilaterally with good intercuspal relationship. Vertical growth continued throughout the treatment.


2022 ◽  
Vol 12 ◽  
Author(s):  
Valentina Ceglia ◽  
Sandra Zurawski ◽  
Monica Montes ◽  
Mitchell Kroll ◽  
Aurélie Bouteau ◽  
...  

CD40 is a potent activating receptor expressed on antigen-presenting cells (APCs) of the immune system. CD40 regulates many aspects of B and T cell immunity via interaction with CD40L expressed on activated T cells. Targeting antigens to CD40 via agonistic anti-CD40 antibody fusions promotes both humoral and cellular immunity, but current anti-CD40 antibody-antigen vaccine prototypes require co-adjuvant administration for significant in vivo efficacy. This may be a consequence of dulling of anti-CD40 agonist activity via antigen fusion. We previously demonstrated that direct fusion of CD40L to anti-CD40 antibodies confers superagonist properties. Here we show that anti-CD40-CD40L-antigen fusion constructs retain strong agonist activity, particularly for activation of dendritic cells (DCs). Therefore, we tested anti-CD40-CD40L antibody fused to antigens for eliciting immune responses in vitro and in vivo. In PBMC cultures from HIV-1-infected donors, anti-CD40-CD40L fused to HIV-1 antigens preferentially expanded HIV-1-specific CD8+ T cells versus CD4+ T cells compared to analogous anti-CD40-antigen constructs. In normal donors, anti-CD40-CD40L-mediated delivery of Influenza M1 protein elicited M1-specific T cell expansion at lower doses compared to anti-CD40-mediated delivery. Also, on human myeloid-derived dendritic cells, anti-CD40-CD40L-melanoma gp100 peptide induced more sustained Class I antigen presentation compared to anti-CD40-gp100 peptide. In human CD40 transgenic mice, anti-CD40-CD40L-HIV-1 gp140 administered without adjuvant elicited superior antibody responses compared to anti-CD40-gp140 antigen without fused CD40L. In human CD40 mice, compared to the anti-CD40 vehicle, anti-CD40-CD40L delivery of Eα 52-68 peptide elicited proliferating of TCR I-Eα 52-68 CD4+ T cells producing cytokine IFNγ. Also, compared to controls, only anti-CD40-CD40L-Cyclin D1 vaccination of human CD40 mice reduced implanted EO771.LMB breast tumor cell growth. These data demonstrate that human CD40-CD40L antibody fused to antigens maintains highly agonistic activity and generates immune responses distinct from existing low agonist anti-CD40 targeting formats. These advantages were in vitro skewing responses towards CD8+ T cells, increased efficacy at low doses, and longevity of MHC Class I peptide display; and in mouse models, a more robust humoral response, more activated CD4+ T cells, and control of tumor growth. Thus, the anti-CD40-CD40L format offers an alternate DC-targeting platform with unique properties, including intrinsic adjuvant activity.


2022 ◽  
Vol 12 ◽  
Author(s):  
Richèl J. C. Bilderbeek ◽  
Maksim V. Baranov ◽  
Geert van den Bogaart ◽  
Frans Bianchi

Cytolytic T cell responses are predicted to be biased towards membrane proteins. The peptide-binding grooves of most alleles of histocompatibility complex class I (MHC-I) are relatively hydrophobic, therefore peptide fragments derived from human transmembrane helices (TMHs) are predicted to be presented more often as would be expected based on their abundance in the proteome. However, the physiological reason of why membrane proteins might be over-presented is unclear. In this study, we show that the predicted over-presentation of TMH-derived peptides is general, as it is predicted for bacteria and viruses and for both MHC-I and MHC-II, and confirmed by re-analysis of epitope databases. Moreover, we show that TMHs are evolutionarily more conserved, because single nucleotide polymorphisms (SNPs) are present relatively less frequently in TMH-coding chromosomal regions compared to regions coding for extracellular and cytoplasmic protein regions. Thus, our findings suggest that both cytolytic and helper T cells are more tuned to respond to membrane proteins, because these are evolutionary more conserved. We speculate that TMHs are less prone to mutations that enable pathogens to evade T cell responses.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Anne Julie Tybjerg ◽  
Søren Friis ◽  
Katrina Brown ◽  
Mef Christina Nilbert ◽  
Lina Morch ◽  
...  

AbstractEnvironmental exposures and avoidable risk factors account for a large proportion of cancer burden. Exposures and lifestyle vary over time and between populations, which calls for updated and population-specific quantification of how various avoidable risk factors influence cancer risk to plan and design rational and targeted prevention initiatives. The study considered 12 risk-factor groups categorized as class I carcinogens by IARC/WCRF. Exposure data was derived from national studies and surveys and were linked to cancer incidence in 2018 based on the nationwide Danish Cancer Registry. In 2018, 23,078 men and 21,196 women were diagnosed with cancer excluding non-melanoma skin cancer, in Denmark. Of these, 14,235 (32.2%) were estimated to be attributable to avoidable class I carcinogens. Tobacco smoking accounted for 14.6% of total cancers, followed by UV-radiation that accounted for 5.8%. Based on exposure data from 2008, one-third of the cancers in Denmark in 2018 are estimated to be caused by class I carcinogens with tobacco use being the main contributor followed by UV-radiation. Our results should be integrated with public health policies to effectively increase awareness and promote strategies to decrease risk factor exposures at population level.


2022 ◽  
pp. canimm.CIR-21-1083-E.2021
Author(s):  
Maryam Pourmaleki ◽  
Caitlin J Jones ◽  
Charlotte E Ariyan ◽  
Zheng Zeng ◽  
Mono Pirun ◽  
...  
Keyword(s):  

Author(s):  
Xiaohui QI ◽  
Bin CUI ◽  
Min CAO

Abstract Context Cortisol, an important hormone regulated by the hypothalamic-pituitary-adrenal (HPA) axis, is associated with obesity. However, it is unclear whether the relationship between cortisol and obesity is causal or could be explained by reverse causality. Objective This work aims to assess the role of morning plasma cortisol in clinical classes of obesity. Methods In this bi-directional two-sample Mendelian Randomization (MR) study, cortisol-associated genetic variants were obtained from the CORtisol NETwork consortium (n = 12,597). The primary outcomes were obesity class I (BMI ≥ 30 kg/m 2), class II (BMI ≥ 35 kg/m 2), and class III (BMI ≥ 40kg/m 2). Inverse variance weighting (IVW) method was used as the main analysis, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Conversely, genetic variants predicting clinical classes of obesity were applied to the cortisol GWAS. Results Genetically predicted cortisol was associated with reduced risk of obesity class I (OR = 0.905; 95% CI, 0.865-0.946; p < 0.001). Evidence from bi-directional MR showed that obesity class II and class III were associated with lower cortisol levels ((class II-cortisol OR = 0.953; 95% CI, 0.923-0.983; p = 0.002); (class III-cortisol OR = 0.955; 95% CI, 0.942-0.967; p < 0.001)), indicating reverse causality between cortisol and obesity. Conclusions This study demonstrates that cortisol is negatively associated with obesity and vice versa. Together, these findings suggest that blunted morning plasma cortisol secretion may be responsible for severe obesity. Regulating morning plasma secretion might be a prevention measure for obese people.


2022 ◽  
Vol 6 (1) ◽  
Author(s):  
Riyadi Idham ◽  
Anindito Rizki Wiraputra

In preventing the Covid-19 pandemic, immigration has a security function which is carried out by selecting the intentions and objectives of foreign nationals to Indonesian territory by examining visa applications, including in handling detainees in the detention room. The problem in this study is whether the arrangements for handling detainees in the detention room of the Class 1 Immigration Office for Non TPI, South Jakarta can be implemented during the covid-19 pandemic. How to optimize the handling of detainees during the covid-19 pandemic in the detention room of the Class 1 Immigration Office for Non TPI, South Jakarta. This research method is empirical normative using primary data and secondary data. The results of the study stated that the arrangements for handling detainees in the detention room of the Class 1 Immigration Office for Non TPI, South Jakarta, could not be fully implemented during the Covid-19 pandemic. This is because until now there is no regulation specifically for the Class I Immigration Office for Non TPI related to the handling of detainees in the detention room, thus causing the absence of standard operating procedures for officers. Optimization of the handling of detainees during a pandemic in the detention room of the Class 1 Immigration Office for Non TPI Special South Jakarta is through the issuance of the Regulation of the Director General of Immigration regarding the handling of detainees during a pandemic in the detention room at the Immigration Office Class 1 Special for Non TPI South Jakarta.


2022 ◽  
Author(s):  
Jiro Miyamae ◽  
Masaharu Okano ◽  
Kohei Nishiya ◽  
Fumihiko Katakura ◽  
Jerzy K. Kulski ◽  
...  
Keyword(s):  
Class I ◽  

Sign in / Sign up

Export Citation Format

Share Document