KIR2DL2/2DL3-E(35) alleles are functionally stronger than -Q(35) alleles.

KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E(35)) are functionally stronger than those with glutamine at the same position (Q(35)). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E(35) could kill more target cells lacking their ligands than NK cells with the weaker -Q(35) alleles, indicating better licensing of KIR2DL2/L3(+) NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation

Senescence, NK cells, and cancer: navigating the crossroads of aging and disease

Cellular senescence, a state of stable cell cycle arrest, acts as a double-edged sword in cancer biology. In young organisms, it acts as a barrier against tumorigenesis, but in the aging population, it may facilitate tumor growth and metastasis through the senescence-associated secretory phenotype (SASP). Natural killer (NK) cells play a critical role in the immune system, particularly in the surveillance, targeting, and elimination of malignant and senescent cells. However, age-related immunosenescence is characterized by declining NK cell function resulting in diminished ability to fight infection, eliminate senescent cells and suppress tumor development. This implies that preserving or augmenting NK cell function may be central to defense against age-related degenerative and malignant diseases. This review explores the underlying mechanisms behind these interactions, focusing on how aging influences the battle between the immune system and cancer, the implications of senescent NK cells in disease progression, and the potential of adoptive NK cell therapy as a countermeasure to these age-related immunological challenges

Определение эффективности способов борьбы с асфальтеносмолопарафиновыми отложениями при эксплуатации нефтяных месторождений

В качестве объекта исследования – рассматривается нефтяные месторождения, а именно Талаканского месторождения, а предметом является технологии предупреждение асфальтеносмолопарафиновых отложений (АСПО) на нефтепромысловых оборудованиях. Цель работы – определение наиболее эффективного метода борьбы с асфальтеносмолопарафиновыми отложениями, и применение технологий удаления отложений на различных нефтяных месторождениях. В процессе исследования были раскрыты причины образования парафиновых отложений и эффективность применения некоторых методов борьбы с АСПО на месторождениях. Область применения: месторождения нефти и газа, имеющие осложнения в виде асфальтосмолопарафиновых отложений.The object of the study is the oil fields, namely the Talakan field, and the subject is the technologies for the prevention of asphaltene-tar-paraffin deposits (ASPO) on oilfield equipment. The purpose of the work is to determine the most effective method of controlling asphaltene-tar-paraffin deposits, and to apply technologies for removing deposits in various oil fields. In the course of the study, the reasons for the formation of paraffin deposits and the effectiveness of the use of some methods of combating ASPO in the fields were revealed. Field of application: oil and gas fields with complications in the form of asphalt-resin-paraffin deposits

A novel approach for the suppression of photorespiration in C 3 plants by gene transfer

In the present study, a novel principle is proposed to increase the CO2 concentration in the vicinity of Rubisco thereby suppressing photorespiration in C3 plants. The pathway is derived from E. coli and converts the glycolate formed during photorespiration into glycerate. Three enzymatic activities are required: Glycolate dehydrogenase (GDH), Glyoxylate carboligase (GCL), and Tratronic semialdehyde reductase (TSR). In order to establish the pathway in the chloroplast of tobacco (Nicotiana tabacum), all necessary genes were cloned in both prokaryotic and plant expression vectors in N-terminal translational fusion to a His-tag. The genes were first expressed in bacteria and the enzymatic activity of the constructs was shown. Transgenic tobacco plants were created containing all genes necessary for the proposed pathway by plastdial as well as nuclear transformation. Plastidial transformation was done by constructing a single polycistronic operon with five open reading frames. Nuclear transformation was performed by Agrobacterium-mediated transformation of single or double constructs. Plastid transformants were checked by southern blot analysis. Many transgenic plants with a variable size of shortened transgenic sequences were detected. Moreover, many of the transgenic plants also displayed drastic chlorosis and stunted growth. However, few plants showed integration of the complete operon and the next generation of those plants is currently analysed. Initially, transgenic plants containing TSR and GCL were created by nuclear transformation due to the lack of a suitable glycolate oxidising enzyme. Variable amounts of foreign proteins were detected in Western blots. Enzymatic assays showed that the proteins are active in planta. However transgenic plants containing GCL protein again showed a chlorotic phenotype. A putative open reading frame was identified in the Arabidopsis genome sequence with homology to glycolate-oxidizing enzymes. The open reading frame was cloned and expressed in bacteria. Enzymatic assays and complementation tests showed that the protein is indeed a glycolate dehydrogenase. The gene is preferentially expressed in illuminated leaves and the enzyme is located inside the mitochondria. This protein forms an optimised starting point for the completion of the proposed pathway

A novel approach for the suppression of photorespiration in C 3 plants by gene transfer

In the present study, a novel principle is proposed to increase the CO2 concentration in the vicinity of Rubisco thereby suppressing photorespiration in C3 plants. The pathway is derived from E. coli and converts the glycolate formed during photorespiration into glycerate. Three enzymatic activities are required: Glycolate dehydrogenase (GDH), Glyoxylate carboligase (GCL), and Tratronic semialdehyde reductase (TSR). In order to establish the pathway in the chloroplast of tobacco (Nicotiana tabacum), all necessary genes were cloned in both prokaryotic and plant expression vectors in N-terminal translational fusion to a His-tag. The genes were first expressed in bacteria and the enzymatic activity of the constructs was shown. Transgenic tobacco plants were created containing all genes necessary for the proposed pathway by plastdial as well as nuclear transformation. Plastidial transformation was done by constructing a single polycistronic operon with five open reading frames. Nuclear transformation was performed by Agrobacterium-mediated transformation of single or double constructs. Plastid transformants were checked by southern blot analysis. Many transgenic plants with a variable size of shortened transgenic sequences were detected. Moreover, many of the transgenic plants also displayed drastic chlorosis and stunted growth. However, few plants showed integration of the complete operon and the next generation of those plants is currently analysed. Initially, transgenic plants containing TSR and GCL were created by nuclear transformation due to the lack of a suitable glycolate oxidising enzyme. Variable amounts of foreign proteins were detected in Western blots. Enzymatic assays showed that the proteins are active in planta. However transgenic plants containing GCL protein again showed a chlorotic phenotype. A putative open reading frame was identified in the Arabidopsis genome sequence with homology to glycolate-oxidizing enzymes. The open reading frame was cloned and expressed in bacteria. Enzymatic assays and complementation tests showed that the protein is indeed a glycolate dehydrogenase. The gene is preferentially expressed in illuminated leaves and the enzyme is located inside the mitochondria. This protein forms an optimised starting point for the completion of the proposed pathway