Search

The novel MICA*112:02 allele was detected by next generation sequencing. [ABSTRACT FROM AUTHOR]

Two novel MICB alleles with coding polymorphisms in exon 3 were detected by next generation sequencing. [ABSTRACT FROM AUTHOR]

This study provides the first immunogenetic preliminary evidence that specific human leucocyte antigen (HLA) class I and class II alleles and haplotypes may be relevant for BRCA1 c.5263_5264insC driven oncogenesis. Observed HLA associations might have practical implications for establishment of predictive markers for the response to immunotherapies in malignancies driven by this germ‐line mutation. [ABSTRACT FROM AUTHOR]

JAK2 V617F‐driven myeloproliferative neoplasms (MPNs) can escape immune surveillance through PD‐L1 up‐regulation and HLA class I pathway down‐regulation. To complement these data we assessed the role of major histocompatibility complex class I—related genes (MICA and MICB) in JAK2 V617F+ MPNs. Using high resolution genotyping we identified two protective alleles, MICA*008:01 and MICA*016. MPN patients had significantly higher levels of soluble sMICA molecules. Peripheral blood JAK2 V617F+ granulocytes had higher surface expression of MICB but did not differ in the amount of MICA and MICB transcripts from normal granulocytes. MICA and MICB genes were significantly down‐regulated in JAK2 V617F+ CD34+ cells from primary myelofibrosis patients in comparison to normal CD34+ hematopoietic stem cells. These data suggest minor but significant role of MICA and MICB genes in the pathogenesis of MPNs. It is also possible that MICA targeting approaches could be of clinical benefit for some of those patients. [ABSTRACT FROM AUTHOR]

Background: Oral Squamous Cell Carcinoma (OSCC) is a malignancy characterized by an aggressive tumor growth and significant mortality. Clarifying mechanisms responsible for immunomodulation are among the main challenges for the development of personalized approaches for the management of patients with Oral Squamous Cell Carcinoma. The aim of the present study was to analyze the relevance of MICA and MICB to Oral Squamous Cell Carcinoma pathogenesis focusing on allele polymorphisms and the levels of soluble MICA and MICB molecules.Materials and Methods: 73 patients diagnosed with Oral Squamous Cell Carcinoma and 149 healthy controls from the Bulgarian population were included in the study. MICA and MICB polymorphism was analyzed at high-resolution level using Next-Generation Sequencing. Serum levels of soluble MICA and MICB molecules were measured by ELISA.Results: Our results show significant protective association with MICB*002:01, while relatively rare alleles MICB*018, *019, and *020 were observed with statistically significant increased frequency in Oral Squamous Cell Carcinoma patients compared to controls. Additionally, a predisposing association was observed for MICA*008:01-MICB*019 haplotype. A correlation analysis between functionally relevant MICA polymorphisms and sMICA showed that homozygosity for MICA-A5.1 or 129Val in OSCC patients was associated with significantly higher serum levels of sMICA.Conclusion: This is the first study showing significant associations between MICB alleles and Oral Squamous Cell Carcinoma and suggesting the possible role of MICB in immunosurveillance in Oral Squamous Cell Carcinoma development. Observed correlations between the levels of soluble MICA molecules and functionally relevant polymorphisms might represent a further step toward a better understanding of molecular mechanisms of Oral Squamous Cell Carcinoma and developing strategies for therapeutic targeting harnessing effective immunosurveillance. [ABSTRACT FROM AUTHOR]

The implementation of the immune checkpoint blockade as a therapeutic option in contemporary oncology is one of the significant immunological achievements in the last century. Constantly accumulating evidence suggests that the response to immune checkpoint inhibitors (ICIs) is not universal. Therefore, it is critical to identify determinants for response, resistance and adverse effects of immune checkpoint therapy that could be developed as prognostic and predictive markers. Recent large scale analyses of cancer genome data revealed the key role of HLA class I and class II molecules in cancer immunoediting, and it appears that HLA diversity can predict response to ICIs. In the present review, we summarize the emerging data on the role of HLA germline variations as a marker for response to ICIs. [ABSTRACT FROM AUTHOR]

This article explores the aesthetic dimensions of scientific experimentation, addressing specifically how aesthetic features enter the construction, evaluation and reception of an experiment. I highlight the relationship between experiments and artistic acts in the early years of the Royal Society where experiments do not serve only epistemic aims but also aim to generate feelings of awe and pleasure. I turn to analysing which aspects of experiments are appreciated aesthetically, identifying several contenders, from the ability of an experiment to uncover nature's beauty, to encapsulating original designs and human creativity. Following this analysis, I focus on the notion of beauty: what makes an experiment beautiful? Several common qualities are explored, from the simplicity and economy of the experiment, to the significance of the experimental results. [ABSTRACT FROM AUTHOR]

We provide evidence for a linear correlation between the frequency of clonal haematopoiesis and COVID‐19 mortality rate. We discuss the mechanistic explanations for this association mediated by a pathological inflammatory response. Our hypothesis can be tested in COVID‐19‐infected patients and eventually lead to new approaches to risk stratification and therapy. [ABSTRACT FROM AUTHOR]

Scientists often use aesthetic values in the evaluation and choice of theories. Aesthetic values are not only regarded as leading to practically more useful theories but are often taken to stand in a special epistemic relation to the truth of a theory such that the aesthetic merit of a theory is evidence of its truth. This paper explores what aesthetic considerations influence scientists' reasoning, how such aesthetic values relate to the utility of a scientific theory, and how one can justify the epistemic role for such values. The paper examines ways in which the link between beauty and truth can be defended, the challenges facing such accounts, and explores alternative epistemic roles for aesthetic values in scientific practice. [ABSTRACT FROM AUTHOR]