Machine learning-enhanced noninvasive prenatal testing of monogenic disorders.

Objective: Single-nucleotide variants (SNVs) are of great significance in prenatal diagnosis as they are the leading cause of inherited single-gene disorders (SGDs). Identifying SNVs in a non-invasive prenatal screening (NIPS) scenario is particularly challenging for maternally inherited SNVs. We present an improved method to predict inherited SNVs from maternal or paternal origin in a genome-wide manner.

Revealing the tumor suppressive sequence within KL1 domain of the hormone Klotho.

Klotho, a 1012 amino acid transmembrane protein, is a potent tumor suppressor in different cancer types. Klotho is composed of two internal repeats KL1 and KL2, and the tumor suppressor activity is primarily attributed to the KL1 domain. Despite its significant role in regulating various cancer-related pathways, the precise mechanism underlying its tumor suppressor activity remains unresolved.

Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients.

Human cytomegalovirus (CMV) is a major pathogen after solid organ transplantation, leading to high morbidity and mortality. Transplantation from a CMV-seropositive donor to a CMV-seronegative recipient (D+/R-) is associated with high risk of CMV disease. However, that risk is not uniform, suggesting a role for host factors in immune control of CMV.

Pathogenic variant-based preconception carrier screening in the Israeli Jewish population.

Preconception carrier screening allows identification of couples at risk to have offspring with autosomal recessive and X-linked disorders. In a current multiethnic world, screening based on self-reported ancestry has limitations. Here we describe the findings of a comprehensive pan-ethnic variant-based carrier screening, using the Israeli Jewish population as a model.

Photon-by-Photon Hidden Markov Model Analysis for Microsecond Single-Molecule FRET Kinetics.

The function of biological macromolecules involves large-scale conformational dynamics spanning multiple time scales, from microseconds to seconds. Such conformational motions, which may involve whole domains or subunits of a protein, play a key role in allosteric regulation. There is an urgent need for experimental methods to probe the fastest of these motions.

[Process of platelets activation by streptokinase].

This study concerns the influence of streptokinase and antistreptokinase antibodies on rabbits platelets in blood plasma depleted of plasminogen. The immune complex streptokinase-antibody causes platelets activation, whereas other investigated immune complexes didnot express such activity. Platelets aggregation wasnot detected in any case.

[Effect of proteins from the Agkistrodon blomhoffii ussuriensis snake venom on platelets in the hemostasis system].

Influence of proteins from the Agkistrodon blomhoffii ussuriensis snake venom on platelet activation and aggregation was developed on different model systems in vitro. It was shown that novel disintegrin (Blomus-B) and phospholipase A2 (Blopholipase) from the venom, activated platelets and inhibited their aggregation. Fibrino(geno)lityc enzyme (Blomulyse) does not activate platelets and has no effect on their aggregation stimulated by collagen, but inhibit ADP and adrenalin-stimulated platelet aggregation.

[Plasminogen activator from Agkistrodon halys halys venom].

Plasminogen activator "Ahh-32" from Agkistrodon halys halys venom has been isolated and purified using affinity and ion-exchange chromatography. The purified enzyme consists of the single peptide-chain with molecular weigth of 32 kDa. It can convert free plasminogen into active form--plasmin.

[Characterization of platelets aggregation inhibitor from Agkistrodon blomhoffii ussuriensis snake venom].

Platelet aggregation inhibitor--"Blomus-B" from Agkistrodon blomhoffii ussuriensis venom has been isolated by affinity and ion-exchange chromatography. The purified inhibitor is a novel non-enzymatic single-chain protein with molecular weigth of 13 kDa. "Blomus-B" causes a change of platelets shape and takes effect on ADP- and adrenalin-induced platelet aggregation.

[Effect of soluble fibrin on the blood coagulation process and platelets aggregation].

The accumulation of soluble fibrin (SF) in the blood plasma causes acceleration of the final stage of blood coagulation. It increases functional activity of a hemostasis system platelet link, that is the precondition of thrombotic complication. Accumulation of SF in the blood plasma is accompanied by proportional reduction of coagulation time in ancistron and thrombin time tests, and also the intensification of platelets aggregation process.

[Effect of streptokinase on the content of plasminogen activator inhibitor of type 1].

The influence of streptokinase on plasminogen activators inhibitor of type I (PAI-1) was investigated with the use of model systems in vitro and in vivo. It was defined, that intravenous streptokinase injection causes an increase in PAI-1 content in mammals' blood plasma. Experiments in vitro have shown that the increase in PAI-1 concentration takes place as a result of streptokinase action.

[Inhibition of the process of Glu-plasminogen activation by tissue activator with fibrin, DDE-complex, and D-dimer using alpha-2-antiplasmin].

The alpha-2-antiplasmin influence on the Glu-plasminogen activation by tissue activator both on fibrin and fibrin(ogen) fragments was investigated. The kinetics of activation was studied and velocity of this process in the absence and presence of the inhibitor was calculated. It was established that alpha-2-antiplasmin decreased the velocity of Glu-plasminogen activation on desAABBfibrin, DDE-complex and DD-dimer and did no influence upon proenzyme activation on fibrinogen fragment--Ho1-DSK.

[Effect of tissue-type plasminogen activator and its inhibitor in haemostasis system function in norm and pathology].

The paper is dedicated to the study of structure and physiological functions of tissue type plasminogen activator and its inhibitor PAI-1, changes of these parametres in normal and pathology conditions. The interrelation of the coagulation and the fibrinolytic system during the range of pathologies was studied. It was demonstrated that simultaneous analysis of the coagulation and fibrinolytic systems analysis allow to diagnose the thrombotic complications.

[Binding of alpha-2-antiplasmin with fibrinogen/fibrin and their fragments independent of factor XIII].

Possible interaction of alpha-2-antiplasmin with fibrinogen, fibrin and their fragments independent of factor XIII as well as the inhibitor effect on the Glu-plasminogen activation by tissue activator were studied. It was shown that alpha-2-antiplasmin is adsorbed on desAA- and desAABBfibrin films (Kd 69.0 +/- 1.

[Structure-functional analysis of peptide P3 identical to gamma370-383 binding sites with integrin alphaIIbbeta3 in gammaC-domain of fibrinogen].

The interactions between platelet integrin alpha IIb beta 3 and fibrinogen (Fg) mediate a range of adhesive reactions, which are necessary for platelet aggregation and fibrin clot retraction. The binding site for alpha IIb beta 3 resides in the gamma C domain of Fg. In our previous work we have identified a novel binding site in the gamma C domain, gamma 370-383 (P3), for integrin alpha IIb beta 3 and have demonstrated that the P3 sequence together with the C-terminal gamma C sequence 408AGDV411 accounts for the full binding of alpha IIb beta 3.

[Investigations of fibrin clots formation under the effect of thrombin and ancystron].

It was shown that heterogeneous surfaces of two phases influence on fibrin films structures. The clot formed between two phases have the surface layer which is different from fibrin clot surface structure. Transmission electron microscopy revealed to determine the thickness of the surface layer for desAA- and desAABB-fibrin.

[Effect of streptokinase on the parameters of haemostasis in model systems in vivo].

The changes of the haemostasis system parameters were studied under treatment by streptokinase (Sk, thrombolytic agent of bacterial origin) with the use of model systems in vivo. We were especially interested in the study of the changing fibrinolytic system parameters such as tissue type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), plasminogen, alpha2-antiplasmin activities. After treatment by Sk the activity and quantity of t-PA were significantly increased while the activity of PAI-1 was decreased.

[Effect of phospholipids containing omega-3 fatty acids on structural changes of microsomal lipids in cell membranes of functionally different cells].

As a result of the experimental researches conducted it has been shown that administration of some normal animal marine phospholipids (PL) including in their structure omega-3 polyunsaturated fatty acids (PUFA) provides for quantitative changes of individual PL, fatty acids (FA) content and quantity in general and individual PL of liver, heart, brain and gonads microsomes. While estimating general microsomal PL fraction FA content under the action of PL omega-3 PUFA FA concentration change, unsaturation index (omega 6/omega 3) and relation of arachidonic acid to docosahexenic (AA/DHA) decrease have been identified. The decrease of AA/DHA relationship occurs due to AA and DHA quantitative changes.

[Specificity of endometrium phospholipids and their fatty acids changes in the development of hyperplasia].

Quantitative changes in phospholipids (PL) and fatty acids content (FA) in patients with endometrium hyperplasia have been revealed. During observing endomentrium hyperplasia process we found out on the one hand reliable decrease in phosphatidylethanolamine (PEA), phosphatidylcholine (PC) content and on the other hand increase of its lysoforms. Changes in unsaturated fatty acids (PA n-6)--arachidonic (AA) content and docosahaenoic (DHA) acids content were also shown.

[Pilot plant and experimental laboratory production. The role in biotechnology industry development].

A stage-phase approach can contribute to unnecessarily long product development time. A simultaneous approach that integrates all development resources through an effectively managed pilot plant can significantly shorten the product development cycle. An intensive development of the domestic biotechnology manufacturing is impossible without creation of the real pilot plant market in Ukraine.

[Phospholipids of human seminal plasma and their role in ensuring fertility].

The phospholipid composition of seminal plasma from health (n = 13) and infertile men (n = 49) was studied. A significant decrease of lyso-phosphatidyl choline and lyso-phosphatidyl serine levels in seminal plasma of men with relative infertility was shown. Two-fold enhancement of phosphatidyl serine in seminal plasma of men with excretory infertility was found.

[Phospholipids of human spermatozoa and their role in ensuring fertility].

The phospholipid composition of spermatozoa in healthy subjects (n = 13) and infertile men (n = 38) was studied. The level of inorganic phosphorus of total phospholipids decreased in spermatozoa of infertile men (relative and excretory infertility). It was found that the phosphatidyl ethanolamine amount in spermatozoa of infertile men fell.

[Lipid composition and fertility of human ejaculate].

The morpho-functional indexes of ejaculates from 35 healthy and 145 infertile men were studied. The depression of functional sperm activity was found in the majority of infertile men. Phospholipid analysis of whole ejaculates from 12 healthy and 35 infertile subjects was performed.