Shared Pathogenicity Features and Sequences between EBV, SARS-CoV-2, and HLA Class I Molecule-binding Motifs with a Potential Role in Autoimmunity.

Epstein-Barr virus (EBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are extraordinary in their ability to activate autoimmunity as well as to induce diverse autoimmune diseases. Here we reviewed the current knowledge on their relation. Further, we suggested that molecular mimicry could be a possible common mechanism of autoimmunity induction in the susceptible individuals infected with SARS-CoV-2. Molecular mimicry between SARS-CoV-2 and human proteins, and EBV and human proteins, are present. Besides, relation of the pathogenicity associated with both coronavirus diseases and EBV supports the notion. As a proof-of-the-concept, we investigated 8mer sequences with shared 5mers of SARS-CoV-2, EBV, and human proteins, which were predicted as epitopes binding to the same human leukocyte antigen (HLA) supertype representatives. We identified significant number of human peptide sequences with predicted-affinities to the HLA-A*02:01 allele. Rest of the peptide sequences had predicted-affinities to the HLA-A*02:01, HLA-B*40:01, HLA-B*27:05, HLA-A*01:01, and HLA-B*39:01 alleles. Carriers of these serotypes can be under a higher risk of autoimmune response induction upon getting infected, through molecular mimicry-based mechanisms common to SARS-CoV-2 and EBV infections. We additionally reviewed established associations of the identified proteins with the EBV-related pathogenicity and with the autoimmune diseases.

Shared 6mer Peptides of Human and Omicron (21K and 21L) at SARS-CoV-2 Mutation Sites.

We investigated the short sequences involving Omicron 21K and Omicron 21L variants to reveal any possible molecular mimicry-associated autoimmunity risks and changes in those. We first identified common 6mers of the viral and human protein sequences present for both the mutant (Omicron) and nonmutant (SARS-CoV-2) versions of the same viral sequence and then predicted the binding affinities of those sequences to the HLA supertype representatives. We evaluated change in the potential autoimmunity risk, through comparative assessment of the nonmutant and mutant viral sequences and their similar human peptides with common 6mers and affinities to the same HLA allele. This change is the lost and the new, or de novo, autoimmunity risk, associated with the mutations in the Omicron 21K and Omicron 21L variants. Accordingly, e.g., the affinity of virus-similar sequences of the Ig heavy chain junction regions shifted from the HLA-B*15:01 to the HLA-A*01:01 allele at the mutant sequences. Additionally, peptides of different human proteins sharing 6mers with SARS-CoV-2 proteins at the mutation sites of interest and with affinities to the HLA-B*07:02 allele, such as the respective SARS-CoV-2 sequences, were lost. Among all, any possible molecular mimicry-associated novel risk appeared to be prominent in HLA-A*24:02 and HLA-B*27:05 serotypes upon infection with Omicron 21L. Associated disease, pathway, and tissue expression data supported possible new risks for the HLA-B*27:05 and HLA-A*01:01 serotypes, while the risks for the HLA-B*07:02 serotypes could have been lost or diminished, and those for the HLA-A*03:01 serotypes could have been retained, for the individuals infected with Omicron variants under study. These are likely to affect the complications related to cross-reactions influencing the relevant HLA serotypes upon infection with Omicron 21K and Omicron 21L.

Information-theoretic approach in allometric scaling relations of DNA and proteins.

Allometric scaling relations can be observed in between molecular parameters. Hence, we looked for presence of such relation among sizes (i.e., lengths) of proteins and genes. Protein lengths exist in the literature as the number of amino acids. They can also be derived from the mRNA lengths. Here, we looked for allometric scaling relation by using such data and simultaneously, the data was compared with the sizes of genes and proteins that were obtained from our modified information-theoretic approach. Results implied presence of scaling relation in the calculated results. This was expected due to the implemented modification in the information-theoretic calculation. Relation in the literature-based data was lacking high goodness of fit value. It could be due to physical factors and selective pressures, which ended up in deviations of the literature-sourced values from those in the model. Genome size is correlated with cell size. Intracellular volume, which is related to the DNA size, would require certain number of proteins, the sizes of which can therefore be correlated with the protein sizes. Cell sizes, genome sizes, and average protein and gene sizes, along with the number of proteins, namely the expression levels of the genes, are the physical factors, and the molecular factors influence those physical factors. The selective pressures on those can act through the connection between those physical factors and limit the dynamic ranges. Biological measures could be prone to such forces and are likely to deviate from expected models, regardless of the validity of assumptions, unless those are also implemented in the models. Yet, present discrepancies could be pointing at the need for model improvement, data imperfection, invalid assumptions, etc. Still, current work highlights possible use of information-theoretic approach in allometric scaling relations' studies.

Peptides of H. sapiens and P. falciparum that are predicted to bind strongly to HLA-A*24:02 and homologous to a SARS-CoV-2 peptide.

AIM: This study is looking for a common pathogenicity between SARS-CoV-2 and Plasmodium species, in individuals with certain HLA serotypes. METHODS: 1. Tblastx searches of SARS-CoV-2 are performed by limiting searches to five Plasmodium species that infect humans. 2. Aligned sequences in the respective organisms' proteomes are searched with blastp. 3. Binding predictions of the identified SARS-CoV-2 peptide to HLA supertype representatives are performed. 4. Blastp searches of predicted epitopes that bind strongly to the identified HLA allele are performed by limiting searches to H. sapiens and Plasmodium species, separately. 5. Peptides with minimum 60% identity to the predicted epitopes are found in results. 6. Peptides among those, which bind strongly to the same HLA allele, are predicted. 7. Step-4 is repeated by limiting searches to H. sapiens, followed by the remaining steps until step-7, for peptides sourced by Plasmodium species after step-6. RESULTS: SARS-CoV-2 peptide with single letter amino acid code CFLGYFCTCYFGLFC has the highest identity to P. vivax. Its YFCTCYFGLF part is predicted to bind strongly to HLA-A*24:02. Peptides in the human proteome both homologous to YFCTCYFGLF and with a strong binding affinity to HLA-A*24:02 are YYCARRFGLF, YYCHCPFGVF, and YYCQQYFFLF. Such peptides in the Plasmodium species' proteomes are FFYTFYFELF, YFVACLFILF, and YFPTITFHLF. The first one belonging to P. falciparum has a homologous peptide (YFYLFSLELF) in the human proteome, which also has a strong binding affinity to the same HLA allele. CONCLUSION: Immune responses to the identified-peptides with similar sequences and strong binding affinities to HLA-A*24:02 can be related to autoimmune response risk in individuals with HLA-A*24:02 serotypes, upon getting infected with SARS-CoV-2 or P. falciparum.

Biophysical and biological perspective in biosemiotics.

The cell and its basic constituents are introduced here through a biophysical and information communication theoretic approach in biology and biosemiotics. With this purpose, the requirements of primordial cellular structures, single binding events, and signalling cascades are first mentioned stepwise, in relation to the model of the cellular sensing mechanism. This is followed by the concepts of cross reactions in sensing and pattern recognitions, wherein an information theoretic approach is addressed and the features of multicellularity are discussed along. Multicellularity is introduced as the path that leads to the loss of the direct causal relations. The loss of true causal relation is considered as a form of translation that enables meaning-encoded communication over the informative processes. In this sense, semiosis may not be exclusive. Synthetic biology is exemplified as a form of artificial selection mechanisms for the generation of 'self-reproducing' systems with information coding and processing machineries. These discussions are summarised at the end.

Breath sensors for lung cancer diagnosis.

The scope of the applications of breath sensors is abundant in disease diagnosis. Lung cancer diagnosis is a well-fitting health-related application of this technology, which is of utmost importance in the health sector, because lung cancer has the highest death rate among all cancer types, and it brings a high yearly global burden. The aim of this review is first to provide a rational basis for the development of breath sensors for lung cancer diagnostics from a historical perspective, which will facilitate the transfer of the idea into the rapidly evolving sensors field. Following examples with diagnostic applications include colorimetric, composite, carbon nanotube, gold nanoparticle-based, and surface acoustic wave sensor arrays. These select sensor applications are widened by the state-of-the-art developments in the sensors field. Coping with sampling sourced artifacts and cancer staging are among the debated topics, along with the other concerns like proteomics approaches and biomimetic media utilization, feature selection for data classification, and commercialization.

Studies on visual detection and surface modification testing of glass microfiber filter paper based biosensor.

Glass microfibers are commonly used as biomolecule adsorption media, as structural or disposable components of the optical biosensors. While any improvement in these components are appreciated, utilizing basic tools of traditional approaches may lead to original sensor opportunities as simple, functional designs that can be easily disseminated. Following this pursuit, surface modification of glass microfiber paper surface was performed by 3-aminopropyltriethoxysilane (APTES) and resulting improvement in the cell entrapment capacity could be observed visually, only after Gram staining. Gram staining offered rapid validation of enhanced binding on the glass surface. The same APTES-modified samples were also tested for binding of complementary DNA sequences and the results were less straightforward due to the necessity of DNA visualization by using a fluorescent stain, YOYO-1. Accordingly, when there were no surface modification, DNA and YOYO-1 adsorbed readily on the glass microfiber filter paper, and prolonged the interaction between DNA and YOYO-1. YOYO-1 adsorption on glass could be recognized from the color profile of YOYO-1 emission. This phenomenon can be used to examine suitability of APTES coverage on glass surfaces since YOYO-1 emission can be distinguished by its glass adsorbed versus DNA-bound forms. Aptness of surface coverage is vital to biosensor studies in the sense that it is preceding the forthcoming surface modifications and its precision is imperative for attaining the anticipated interaction kinetics of the surface-immobilized species. The proposed testing scheme offered in this study secures the work, which is aimed to be carried out utilizing such sensing systems and device components.

CMOS cell sensors for point-of-care diagnostics.

The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions. From this perspective, point-of-care diagnostics is a demanded field in clinics. It is also necessary both for prompt diagnosis and for providing health services evenly throughout the population, including the rural districts. The requirements can only be fulfilled by technologies whose productivity has already been proven, such as complementary metal-oxide-semiconductors (CMOS). CMOS-based products can enable clinical tests in a fast, simple, safe, and reliable manner, with improved sensitivities. Portability due to diminished sensor dimensions and compactness of the test set-ups, along with low sample and power consumption, is another vital feature. CMOS-based sensors for cell studies have the potential to become essential counterparts of point-of-care diagnostics technologies. Hence, this review attempts to inform on the sensors fabricated with CMOS technology for point-of-care diagnostic studies, with a focus on CMOS image sensors and capacitance sensors for cell studies.

Relationship between functional promoter polymorphism in the XBP1 gene (-116C/G) and atherosclerosis, ischemic stroke and hyperhomocysteinemia.

ER stress is associated with a range of pathological conditions, among which, the ischemia/reperfusion injury is also found. The mechanistic array of links among the ER stress and thrombovascular diseases is poorly understood. The XBP1 gene is a transcription factor which modulates the ER stress response; and the XBP1 (-116 C/G) gene polymorphism causes an impairment of its positive feedback system. In the present study we investigated the prevalence of XBP1 gene (-116 C/G) polymorphism, separately among the patients with atherosclerosis, ischemic stroke and hyperhomocysteinemia. The G allele and the (-116 G/G) genotype of the XBP1 (-116 C/G) gene polymorphism were found to be a significant risk factor for the patients with Ischemic Stroke. Yet, this allele was seemingly less significant in case of patients with atherosclerosis and hyperhomocysteinemia. Hence, the XBP1 (-116 C/G) gene polymorphism and especially its involvement in a homozygous state are suggested to take active role in the ER stress related ischemia/reperfusion injury.

Effect of eNOS and ET-1 polymorphisms in thromboangiitis obliterans.

Thromboangiitis obliterans (TAO), or Buerger disease, is a segmental occlusive inflammatory disorder of the arteries and veins, and etiopathogenesis is still obscure. It is strongly connected to the use of tobacco products, especially smoking. Smoking cessation is obligatory for success of the medical treatment. In the current study, we investigated the prevalence of endothelial nitric oxide synthase (eNOS) 894 G-->T and endothelin-1 (ET-1) 8000 T-->C polymorphisms in association with TAO to reveal any possible involvement in the TAO pathophysiology. The T allele of the eNOS 894 G-->T polymorphism was found to be associated with the prevention of TAO.

Secondary structure of lipidated Ras bound to a lipid bilayer.

Ras proteins are small guanine nucleotide binding proteins that regulate many cellular processes, including growth control. They undergo distinct post-translational lipid modifications that are required for appropriate targeting to membranes. This, in turn, is critical for Ras biological function. However, most in vitro studies have been conducted on nonlipidated truncated forms of Ras proteins. Here, for the first time, attenuated total reflectance-FTIR studies of lipid-modified membrane-bound N-Ras are performed, and compared with nonlipidated truncated Ras in solution. For these studies, lipidated N-Ras was prepared by linking a farnesylated and hexadecylated N-Ras lipopeptide to a truncated N-Ras protein (residues 1-181). It was then bound to a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer tethered on an attenuated total reflectance crystal. The structurally sensitive amide I absorbance band in the IR was detected and analysed to determine the secondary structure of the protein. The NMR three-dimensional structure of truncated Ras was used to calibrate the contributions of the different secondary structural elements to the amide I absorbance band of truncated Ras. Using this novel approach, the correct decomposition was selected from several possible solutions. The same parameter set was then used for the membrane-bound lipidated Ras, and provided a reliable decomposition for the membrane-bound form in comparison with truncated Ras. This comparison indicates that the secondary structure of membrane-bound Ras is similar to that determined for the nonlipidated truncated Ras protein for the highly conserved G-domain. This result validates the multitude of investigations of truncated Ras without anchor in vitro. The novel attenuated total reflectance approach opens the way for detailed studies of the interaction network of the membrane-bound Ras protein.