X-ray diffraction and in vivo studies reveal the quinary structure of Trypanosoma cruzi nucleoside diphosphate kinase 1: a novel helical oligomer structure

Trypanosoma cruzi is a flagellated protozoan parasite that causes Chagas disease, which represents a serious health problem in the Americas. Nucleoside diphosphate kinases (NDPKs) are key enzymes that are implicated in cellular energy management. TcNDPK1 is the canonical isoform in the T. cruzi parasite. TcNDPK1 has a cytosolic, perinuclear and nuclear distribution. It is also found in non-membrane-bound filaments adjacent to the nucleus. In the present work, X-ray diffraction and in vivo studies of TcNDPK1 are described. The structure reveals a novel, multi-hexameric, left-handed helical oligomer structure. The results of directed mutagenesis studies led to the conclusion that the microscopic TcNDPK1 granules observed in vivo in T. cruzi parasites are made up by the association of TcNDPK1 oligomers. In the absence of experimental data, analysis of the interactions in the X-ray structure of the TcNDPK1 oligomer suggests the probable assembly and disassembly steps: dimerization, assembly of the hexamer as a trimer of dimers, hexamer association to generate the left-handed helical oligomer structure and finally oligomer association in a parallel manner to form the microscopic TcNDPK1 filaments that are observed in vivo in T. cruzi parasites. Oligomer disassembly takes place on the binding of substrate in the active site of TcNDPK1, leading to dissociation of the hexamers. This study constitutes the first report of such a protein arrangement, which has never previously been seen for any protein or NDPK. Further studies are needed to determine its physiological role. However, it may suggest a paradigm for protein storage reflecting the complex mechanism of action of TcNDPK1.

Digital Audio Scene Recognition Method Based on Machine Learning Technology

Audio scene recognition is a task that enables devices to understand their environment through digital audio analysis. It belongs to a branch of the field of computer auditory scene. At present, this technology has been widely used in intelligent wearable devices, robot sensing services, and other application scenarios. In order to explore the applicability of machine learning technology in the field of digital audio scene recognition, an audio scene recognition method based on optimized audio processing and convolutional neural network is proposed. Firstly, different from the traditional audio feature extraction method using mel-frequency cepstrum coefficient, the proposed method uses binaural representation and harmonic percussive source separation method to optimize the original audio and extract the corresponding features, so that the system can make use of the spatial features of the scene and then improve the recognition accuracy. Then, an audio scene recognition system with two-layer convolution module is designed and implemented. In terms of network structure, we try to learn from the VGGNet structure in the field of image recognition to increase the network depth and improve the system flexibility. Experimental data analysis shows that compared with traditional machine learning methods, the proposed method can greatly improve the recognition accuracy of each scene and achieve better generalization effect on different data.

study of older preschool children’s sensitivity formation state

The purpose of the study is to diagnose the state of older preschool children’s sensitivity formation. The object is the process of older preschool children’s moral education. The study used a set of the following research methods: an analysis, a synthesis, a comparison, a generalization of scientific sources in order to formulate basic concepts and study the level of the issue concern; an observation of children’s play activities; a conversation; a plot role-playing games ‘Hospital’ and ‘Veterinary Clinic,’ a didactic game ‘Who is sensitive?’; methods of mathematical statistics for processing the obtained experimental data. Analysis of the experimental study results allowed us to state the lack of older preschool children’s awareness with the category ‘sensitivity’ and its emotional and activity display. The vast majority of preschoolers understand the theoretical meaning of this category, however, they do not realize the need to be sensitive, can not explain the motives of their sensitive behavior, and are not able to name the sensitive actions of other people. Only a small number of children associate sensitive actions with care, protection, and help. We have noted the highest rate of the emotional and value component development because children tend to show moral feelings.

It’s Time to Talk About HPC Storage: Perspectives on the Past and Future

High-performance computing (HPC) storage systems are a key component of the success of HPC to date. Recently, we have seen major developments in storage-related technologies, as well as changes to how HPC platforms are used, especially in relation to artificial intelligence and experimental data analysis workloads. These developments merit a revisit of HPC storage system architectural designs. In this paper we discuss the drivers, identify key challenges to status quo posed by these developments, and discuss directions future research might take to unlock the potential of new technologies for the breadth of HPC applications.

ORGAN WEIGHT INDICES AS INDICATORS FOR ESTIMATING THE EXPERIMENTAL EFFECT OF METAL NITRIDE COATED IMPLANTS ON ANIMAL ORGANISMS

The obtained results confirm the safety of steel 12ХI8Н9Т implants and titanium plus hafnium nitride TiN+NHf coated steel 12ХI8Н9Т implants. Experimental data analysis shows the toxic properties of copper supported by the earlier research on blood morphology of lab rats.

The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells

SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide—a well-tolerated drug widely used in advanced prostate cancer—reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.

Sialoglyco-Conjugate Abnormalities, IL-6 Trans-Signaling and Anti-Ganglioside Immune Response—Potential Interferences in Lupus Nephritis Pathogenesis

We have investigated glycoconjugates sialization profile, endogen synthesis rate of antiganglioside antibodies (AGA), IL-6 signaling pathways correlated with activity disease in systemic lupus erythematous (SLE) and lupus nephritis (LN). Material and methods. A case-control study was developed and included 109 patients with SLE with or without renal impairment, 32 patients with IgA nephropathy and 60 healthy volunteers, clinically and paraclinically monitored. The following parameters were evaluated in volunteers serum: total sialic acid (TSA), orosomucoids, lipid bound sialic acid (LSA), interleukin-6 (IL-6), soluble factors IL-6R, gp130, anti –GM1, -GM2, -GM3, -GD1a, -GD1b, -GT1b, -GQ1b antigangliosides antibodies of IgG and IgM type. Results. Experimental data analysis showed: increase in synthesis rhythm of sialoglyco-conjugated in SLE (TSA increased in SLE and LN compared to control), accelerated catabolism of LSA in LN (LSA/TSA ratio was higher in SLE and LN than in control group), overexpression of IL-6 mediated trans-signaling (sIL-6R/sgp 130 ratio was subunit in SLE and IgA nephropathy and superunit in LN), large AGA profile synthesis of IgM isotype (over 45.1% in SLE and over 20.7% in LN). Conclusions. Hypersialization, accelerated glycosphingolipids degradation, IL-6 trans-signaling amplify and AGA pattern could represent essential mechanisms in LN pathogenesis.