A Rare Belt Plaque in Zoomorphic Style from the Inner Tien Shan

The article publishes a very rare for Saka culture of the Tien Shan region belt plaque, made with the Scythian-Siberian animal motif. It was accidentally found at an altitude of 2300 m. in the northern part of the Inner Tien Shan, and, most likely, it was lost there in antique time. The plaque has a butterfly-shaped shape, and a relief paired heads of a snow leopard was depicted on its outer surface in a realistic manner. On its reverse side there are two small loops indicating the construction of the combat belt on which it was fixed. Apart from the main belt there were additional leather straps which also were used as laces in the front. Belts of a similar construction with plaques of similar shape were previously found only in an elite burial of the Issyk kurgan in Tien Shan region. Nevertheless, outside this region, this belt plaque has close analogies in the synchronous cultures of the Scythian type in the Forest-steppe Altay, Tuva, Ordos and Northern China, as well as in the forest-steppe part of the Urals region. Based on stylistics and analogies, this belt plaque can be dated back to the turn of the 5th and 4th centuries BC. But in these regions, with the exception of the Urals, all similar plaques have one central loop on the back side. This indicates an independent line of development of these belt garment items on the territory of Saka culture of the Tien Shan region, although the origins of this line, undoubtedly, were initially outside its distribution area.

Galvanic Phase Coupling of Superconducting Flux Qubits

We investigate the galvanic coupling schemes of superconducting flux qubits. From the fundamental boundary conditions, we obtain the effective potential of the coupled system of two or three flux qubits to provide the exact Lagrangian of the system. While usually the two-qubit gate has been investigated approximately, in this study we derive the exact inductive coupling strength between two flux qubits coupled directly and coupled through a connecting central loop. We observe that the inductive coupling strength needs to be included exactly to satisfy the criteria of fault-tolerant quantum computing.

Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABAA and Nicotinic Acetylcholine Receptors

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

Spatial Structure and Activity of Synthetic Fragments of Lynx1 and of Nicotinic Receptor Loop C Models

Lynx1, membrane-bound protein co-localized with the nicotinic acetylcholine receptors (nAChRs) and regulates their function, is a three-finger protein (TFP) made of three β-structural loops, similarly to snake venom α-neurotoxin TFPs. Since the central loop II of α-neurotoxins is involved in binding to nAChRs, we have recently synthesized the fragments of Lynx1 central loop, including those with the disulfide between Cys residues introduced at N- and C-termini, some of them inhibiting muscle-type nAChR similarly to the whole-size water-soluble Lynx1 (ws-Lynx1). Literature shows that the main fragment interacting with TFPs is the C-loop of both nAChRs and acetylcholine binding proteins (AChBPs) while some ligand-binding capacity is preserved by analogs of this loop, for example, by high-affinity peptide HAP. Here we analyzed the structural organization of these peptide models of ligands and receptors and its role in binding. Thus, fragments of Lynx1 loop II, loop C from the Lymnaea stagnalis AChBP and HAP were synthesized in linear and Cys-cyclized forms and structurally (CD and NMR) and functionally (radioligand assay on Torpedo nAChR) characterized. Connecting the C- and N-termini by disulfide in the ws-Lynx1 fragment stabilized its conformation which became similar to the loop II within the 1H-NMR structure of ws-Lynx1, the activity being higher than for starting linear fragment but lower than for peptide with free cysteines. Introduced disulfides did not considerably change the structure of HAP and of loop C fragments, the former preserving high affinity for α-bungarotoxin, while, surprisingly, no binding was detected with loop C and its analogs.

PSYCHOEMOTIONAL STATUS AND HEART RATE VARIABILITY IN ADOLESCENTS IN THE NORTH

Specific extreme climatic conditions of the North can cause long-term psychoemotional stress, causing violations of the state of adaptive mechanisms of the body and the formation of psychosomatic diseases. Adolescence, due to specific changes in the body, is most susceptible to various stressful factors. The purpose of this work was to study the psychoemotional state and features of the regulatory mechanisms of the body of adolescents living in the North, depending on gender. A study of the level of neuroticism (H) according to G. Eysenck, situational (ST) and personal anxiety (LT) according to Spielberger, analysis of heart rate variability (HRV) using the hardware and software complex "VNS-Spectrum" (LLC "Neuro-Soft", Russia, Ivanovo) in adolescents (n = 58; 30 girls, 28 boys), permanently residing in the city of Yakutsk. Statistical data processing was performed using the program Statistica 13 for Windows. The differences were considered statistically significant at p<0.05. The results show that more than 40% of adolescents (40% - girls, 43% - boys) permanently residing in Yakutsk have a high level of neuroticism, which is significantly higher than in adolescents in Central Russia. Gender differences were revealed in the study of CT and LT. In girls, a high level of CT is detected in 31% of individuals, and a high level of LT is detected in 44%. The values of CT and LT in girls correspond to the average values (40.31±1.85 and 44.06±1.37 points, respectively). Boys have a higher number of individuals with high levels of CT (43%) and LT (54%) than girls. The average CT values are 41.42±1.95 points. Average LT values in boys (45.42±1.56 points), which corresponds to a high level of anxiety. The high level of LT in boys strongly correlates (r = 0.81) with the tension of the mechanisms of regulation of heart activity with the involvement of the suprasegmental Central loop of regulation, which indicates a high level of psychoemotional tension in more than 50% of adolescent boys living in Yakutia.

Hereditary angioedema caused by a premature stop codon mutation in the SERPING1 gene

Background Hereditary angioedema with deficient and dysfunctional C1 inhibitor (C1-INH-HAE) is a rare genetic disorder. The majority of the cases with this disease are caused by mutations in the C1-inbitor gene SERPING1 and are classified as type 1 and type 2. We aimed to detect mutations in the SERPING1 gene and evaluate its expression in nine probands with hereditary angioedema from nine different families. Methods Nine probands with hereditary angioedema from nine different families and 53 healthy controls were recruited in this study. All eight exons and intron–exon boundaries in the SERPING1 gene were amplified by PCR and then sequenced. Mutations were identified by alignment with reference sequences. mRNA expression was measured by real-time PCR. Results All probands were diagnosed with HAE type 1. Nine mutations were found in nine patients: c.44delT, c.289C<T, c.296_303delCCATCCAA, c.538C<T, c.786_787insT, c.794 G < A, c.939delT, c.1214_1223delCCAGCCAGGA, and c.1279delC. All mutations formed a premature stop codon that might lead to the impaired synthesis of C1 inhibitor and result in the deficiency of this protein. None of the detected mutations were observed in the controls. In the C1-INH-HAE group, SERPING1 mRNA expression was significantly reduced (20% of the normal average level) compared to controls. Conclusions Three known and six novel mutations in the SERPING1 gene were identified, and they produced a truncated nonfunctional C1 inhibitor without a reactive central loop. All the mutations led to reduced expression of SERPING1 mRNA in peripheral blood and low antigenic C1 inhibitor levels.

Structural analysis of the PATZ1 BTB domain homodimer

PATZ1 is a ubiquitously expressed transcriptional repressor belonging to the ZBTB family that is functionally expressed in T lymphocytes. PATZ1 targets the CD8 gene in lymphocyte development and interacts with the p53 protein to control genes that are important in proliferation and in the DNA-damage response. PATZ1 exerts its activity through an N-terminal BTB domain that mediates dimerization and co-repressor interactions and a C-terminal zinc-finger motif-containing domain that mediates DNA binding. Here, the crystal structures of the murine and zebrafish PATZ1 BTB domains are reported at 2.3 and 1.8 Å resolution, respectively. The structures revealed that the PATZ1 BTB domain forms a stable homodimer with a lateral surface groove, as in other ZBTB structures. Analysis of the lateral groove revealed a large acidic patch in this region, which contrasts with the previously resolved basic co-repressor binding interface of BCL6. A large 30-amino-acid glycine- and alanine-rich central loop, which is unique to mammalian PATZ1 amongst all ZBTB proteins, could not be resolved, probably owing to its flexibility. Molecular-dynamics simulations suggest a contribution of this loop to modulation of the mammalian BTB dimerization interface.