Search

Helicobacter pyloriis closely connected to upper gastrointestinal tract diseases including gastric cancer. Transgenic plants are found to be successful in expressing the bacterial antigens, which could elicit an immune response when consumed. The Cytotoxicity-associated immunodominant antigen protein (cagA) ofH. pyloriis kindred with pathogenicity and cancer risk. We expressed thecagAtransgenically in the brinjal. We amplified thecagAgene fromH. pyloristrain 26695 chromosomal DNA and transformed it into brinjal callus derived from leaf explants using the pBI121 expression vector. The stable expression and accumulation of the recombinantcagAgene were confirmed by using quantitative real-time PCR, western blot analysis and ELISA. The RT-PCR, western blot and ELISA showed stable expression ofcagAgene in the transgenic lines B3, B5, B11, B17 and B21. Among them, B11 and B17 samples showed higher expression of thecagAcompared to the other samples. Besides, the immunohistochemistry assay showed the abundant expression ofcagAprotein in the parenchymal regions of the transgenic plants. Out of the 52 plants, a set five plants were found to be positive forcagAexpression. Our experimental outcomes can be used further to design the vaccines againstH. pylorifrom the transgenic brinjal plants.

The arrestin domain containing proteins (ARRDCs) are crucial adaptor proteins assist in signal transduction and regulation of sensory physiology. The molecular localization of the ARRDC gene has been confined mainly to the mammalian system while in invertebrates the expression pattern was not addressed significantly. The present study reports the identification, tissue specific expression and functional characterization of an ARRDC transcript in earthworm, Eudrilus eugeniae.The coding region of earthworm ARRDC transcript was 1146 bp in length and encoded a protein of 381 amino acid residues. The worm ARRDC protein consists of conserved N-terminal and C-terminal regions and showed significant homology with the ARRDC3 sequence of other species. The tissue specific expression analysis through whole mount in-situ hybridization denoted the expression of ARRDC transcript in the central nervous system of the worm which includes cerebral ganglion and ventral nerve cord. Besides, the expression of ARRDC gene was observed in the epidermal region of earthworm skin. The functional characterization of ARRDC gene was assessed through siRNA silencing and the gene was found to play key role in the light sensing ability and photophobic movement of the worm.The neuronal and dermal expression patterns of ARRDC gene and its functional characterization hypothesized the role of the gene in assisting the photosensory cells to regulate the process of photoreception and phototransduction in the worm.

BackgroundHypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM.Methods and resultsHere, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 (RPS6KB1 or S6K1) gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect.ConclusionsOur study demonstrates for the first time that the variants in the S6K1 gene are associated with HCM, and early detection of the S6K1 variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of S6K1 gene variants.

Dinitrogen fixation through the Nitrogen Reduction Reaction (NRR) under mild conditions without the use of sacrificial agents has its share of formidable hurdles. It has been shown recently that Ru-doped Au nanoclusters can reduce N2 molecule to NH3 only in the presence of UV-Vis light in aqueous medium. Herein, using theoretical techniques we shed light on the mechanistic avenues traversed for achieving this prodigious chemical feat. Our findings suggest that the bimetallic Au22Ru6 cluster successfully accomplishes the NRR process under ambient pressure and temperature conditions by the very virtue of its bifunctional nature. Contrary to the existing views, we find that NRR propagates through an unconventional associative pathway, where the Ru dopant assists in N2 adsorption while the Au-H bonds formed from Au assisted water splitting is implicated for facilitating NRR.

Background: Plant biotechnology revolutionized the branch of plant sciences contributing to improving crop production. Helicobacter pylori was predominantly seen among all the sectors of the human population, closely stuck to stomach ulcers and cancer. Even though traditional vaccines are effective in preventing H. pylori, edible and non-edible parts of special transgenic plants were also being generated to express its antigens which could elicit an immune response after consuming. The induce by contact with epithelium (iceA1) protein of H. pylori is associated with virulence and stated as predisposing factor to stomach cancer. Objectives: This study intends to study the expression levels of iceA1 gene in the brinjal plant. Materials and Methods: The present study, magnified the iceA1 gene from H. pylori strain 26695 and transformed it into callus of brinjal (from leaf explants) through Agrobacterium tumefacians (EHA105). pBI121 vector was used to construct the plant expression vector, and the transgenic plants generated were further validated through gene amplification and protein expression studies. Results: Out of the 46 plants obtained from this study, five of them were found to be positive for the iceA1 expression as seen on validation assays like gene amplification and protein expression studies. Conclusion: The study could beneficially produce a vaccine candidate against H. pylori from transgenic brinjal. In Addition, it could provide, valid scientific data which can further be used by researchers.

Amid the surge of computational studies of gold thiolate clusters in the recent past, we present a comparison of popular density functionals (DFAs) and three-part corrected methods (3c-methods) on their performance by taking a dataset consisting 18 isomers of Aun(SCH3)m (m ≤ n =1-3) stoichiometry. We have compared the efficiency and accuracy of the DFAs and 3c-methods in geometry optimization with RI-SCS-MP2 and energies with DLPNO-CCSD(T) as reference methods. The lowest energy structure out of the largest stoichiometry from our dataset i.e., Au3(SCH3)3 is considered to evaluate the computational time for SCF and gradient. Alongside, the number of optimization steps to locate the most stable minima of Au3(SCH3)3 are compared to assess the efficiency of the methods. A comparison of relevant bond lengths with the reference geometry was made to estimate the accuracy in geometry optimization. Some methods such as LC-BLYP, ⍵B97M-D3BJ, M06-2X, and PBEh-3c are unable to locate many of the minima that are found by most of the other methods; thus, the versatility in locating various minima is also an important criterion in choosing a method for the given project. We have compared the relative energies among the isomers along every stoichiometric series and the interaction energy of the gold core with the ligands to estimate the accuracy of the methods. The dependence of basis set size and relativistic effects on energies are also compared. Some of the highlights are the following. TPSS shows accuracy, whereas mPWPW is fast with comparable accuracy. The range separated hybrid DFAs are the best choice for the relative energies of the clusters. CAM-B3LYP excels, whereas B3LYP shows poor performance. Overall, LC-BLYP is a balanced performer considering both the geometry and relative stability of the structures, but it lacks diversity. The 3c-methods, although fast, are less impressive in relative stability.

Overmodulation techniques of asymmetrical six-phase machine achieve higher dc-bus utilization by applying voltage in the nonenergy transfer plane. This results into unwanted current and associated copper loss. Existing overmodulation technique minimizes this voltage from space-vector perspective with predefined set of four active vectors. To find the best technique, one needs to perform the above minimization problem with all possible sets of active vectors with which higher voltage gain can be attained. Therefore, this requires evaluation of large number of cases. This article formulates the above minimization problem in terms of average voltage vectors of two three-phase inverters, where active vectors need not to be specified beforehand and, thus, the analysis is more general. Sixteen possible techniques with different set of active vectors are derived following the above analysis, which attain minimum voltage injection in the nonenergy transfer plane. This article also identifies one of these 16 techniques, which can be implemented without involving complex six-dimensional transformation. The above technique is validated through experiments on six-phase induction motor and simulations in MATLAB at 3.5-kW power level.

Overmodulation (OVM) techniques of asymmetrical six-phase induction machine (ASIM) achieve higher dc-bus utilization by applying nonzero average voltage in nonenergy transfer plane. This results into unwanted current and associated copper loss. Existing OVM techniques reduce this loss with pulsewidth modulation (PWM) techniques from six-dimensional space vector perspective, which is both conceptually difficult and computationally challenging. The computational complexity of space vector based techniques is reduced by few existing PWM techniques in linear region by splitting the six-phase inverter as two three-phase inverters and modulate these inverters with linear PWM techniques in 30 $^\circ$ phase shifted. This is referred as three-phase inverter based technique in the title. But, three-phase inverter based OVM technique does not exist in the literature due to lack of knowledge of the relationship between six-dimensional space vectors and space vectors of two three-phase inverters. This article first establishes this relation. Based on this relation, an OVM technique is proposed where the reference voltage vectors of two inverters are phase shifted by 30 $^\circ$ but of different magnitudes. The proposed technique achieves THD and WTHD performances similar to space vector based best technique of ASIM with reduced computational complexity, as shown in details. The proposed strategy is validated through experiments and simulations on six-phase induction machine at 4.2 kW.

Systemic sclerosis (SSc) is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as SSc has been aided by various animal models that recapitulate certain aspects of the human pathology. We found that the transcription factor Snail is overexpressed in the epidermis of SSc patients and a transgenic mouse recapitulating this expression pattern is sufficient to induce many clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin (Spondin-2) in fibrogenesis. Mindin is produced by Snail transgenic skin keratinocytes and aids fibrogenesis by inducing early inflammatory cytokine production and collagen secretion in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.

Bin packing using a robotic arm is an important problem in the context of Industry 4.0. In this work, we present a reliable and efficient bin packing system, called Jampacker . We propose a new offline 3D bin packing algorithm, called Jampack that achieves higher packing efficiency in comparison to the state-of-the-art algorithms. Jampack computes placement points, called internal corner points that tries to maximize the utilization of free spaces in-between objects, which are generally ignored by existing algorithms. Additionally, we introduce a fault recovery module (FRM) for the robotic manipulator that helps to achieve a more reliable and efficient packing in a physical container. The FRM module monitors the object placement by the robotic arm, calculates a fault score for the placement, adjusts the placement if required, and also learns & adjusts the offset for the placement procedure on-the-go. We show that this system achieves faster completion of the overall packing process.

We present a performance study on popular density functionals (DFAs) and three-part corrected methods (3c-methods) for their efficiency and accuracy in the geometry and relative stability of gold-thiolate nanoclusters taking Au 3(SCH3)3 isomers. Normalized mean absolute error (NMAE) is analysed to compare the results with the reference methods DLPNO-CCSD(T) and RI-SCS-MP2. The dependence of basis set size and relativistic effects on energies are also compared. TPSS shows accuracy, whereas PBE is fast for geometry optimization. On the other hand, range separation in hybrid DFAs stands out as the proper choice for the relative energies of the clusters. LC-BLYP excels, but 3c-methods are less impressive in relative stability comparison. Counterpoise corrected thiolate interaction energy and bonding analyses delineate the higher stability of bridging sulfur coordination (RS-Au-SR; R = − methyl) than singly-bonded and capping sulfur bonds in Au3(SCH3)3 . With the selected DFAs, we have analyzed the gold-sulfur interaction in Au3(SCH3)3 , and a comparison is made with AuSCH3 . The bonding analysis has revealed a partial covalency between gold and sul- fur atoms. On going from AuSCH3 to Au3 (SCH3)3 , a substantial flow of charge from gold atoms to thiolate ligands stems from the increase in gold s-d hybridization. As the s-d mixing in Au increases, the main character of Au-S interaction shifts from covalent to ionic. Hence, a covalent-charge-transfer interaction dominates in gold-sulfur bonding and gives rise to a charge-shift bonding.

The oligochaete earthworm, Eudrilus eugeniae is capable of regenerating both anterior and posterior segments. The present study focuses on the transcriptome analysis of earthworm E. eugeniae to identify and functionally annotate the key genes supporting the anterior blastema formation and regulating the anterior regeneration of the worm. The Illumina sequencing generated a total of 91,593,182 raw reads which were assembled into 105,193 contigs using CLC genomics workbench. In total, 40,946 contigs were annotated against the NCBI nr and SwissProt database and among them, 15,702 contigs were assigned to 14,575 GO terms. Besides a total of 9389 contigs were mapped to 416 KEGG biological pathways. The RNA-Seq comparison study identified 10,868 differentially expressed genes (DEGs) and of them, 3986 genes were significantly upregulated in the anterior regenerated blastema tissue samples of the worm. The GO enrichment analysis showed angiogenesis and unfolded protein binding as the top enriched functions and the pathway enrichment analysis denoted TCA cycle as the most significantly enriched pathway associated with the upregulated gene dataset of the worm. The identified DEGs and their function and pathway information can be effectively utilized further to interpret the key cellular, genetic and molecular events associated with the regeneration of the worm.

Fibrosis is a result of chronically activated fibroblasts leading to the overproduction of extracellular matrix (ECM), causing tissue hardening and loss of organ function. Systemic sclerosis (SSc) is a fibrotic skin disease marked by inflammation, autoimmunity and vasculopathy along with progressive fibrosis of the skin and internal organs. A major bottleneck in understanding the etiology of SSc has been the lack of a holistic animal model that can mimic the human SSc disease. We found that the transcription factor Snail is overexpressed in the epidermis of SSc patients and a transgenic mouse recapitulating this expression pattern is sufficient to induce hallmark clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin in fibrogenesis. Mindin is produced by Snail transgenic skin keratinocytes and aids fibrogenesis by inducing inflammatory cytokine and collagen production in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.

We present a benchmark study on popular density functionals for their efficiency and accuracy in the geometry and relative stability of gold-thiolate nanoclusters taking Au3(SMe)3 isomers. We have used normalized mean absolute error (NMAE) analysis as a parameter to compare the results with the reference methods - DLPNO-CCSD(T) and RI-SCS-MP2. We have also compared the performance on the thiolate interaction energy of the stable geometries using the results from our benchmark study. One of the promising functional is PBE that shows robust performance for geometry optimization. On the other hand, M06-2X stands out as the proper choice for the relative energies of the clusters. With the selected methods, we have analyzed the gold-sulfur interaction in Au3(SMe)3 and a comparison is made with AuSMe. The bonding analysis has revealed a partial covalency between gold and sulfur atoms in general. On going from AuSMe to Au3(SMe)3, a substantial flow of charge from gold atoms to thiolate ligands as a result of the increase in gold s-d hybridization. As the s-d mixing in Au increases, the main character of Au-S interaction shifts from covalent to ionic. Hence, a covalent-charge-transfer interaction dominates in gold-sulfur bonding and gives rise to a charge-shift bonding.

Supplemental material, sj-pdf-1-pim-10.1177_14750902221078426 for Safety analysis of a high-pressure fuel gas supply system for LNG fuelled vessels by Konstantinos Milioulis, Victor Bolbot, Gerasimos Theotokatos, Evangelos Boulougouris, Paul Sayan, Kelvin Wen Yong Chio and Wei Siang Lim in Proceedings of the Institution of Mechanical Engineers, Part M: Journal of Engineering for the Maritime Environment