Fusarium circinatum is an important global pathogen of pine trees. Genome plasticity has been observed in different isolates of the fungus, but no genome comparisons are available. To address this gap, we sequenced and assembled to chromosome level five isolates of F. circinatum. These genomes were analysed together with previously published genomes of F. circinatum isolates FSP34 and KS17. Multi-sample variant calling identified a total of 461683 micro variants (SNPs and small indels) and a total of 1828 macro structural variants of which 1717 were copy number variants and 111 were inversions. Variant density was higher on sub-telomeric regions of chromosomes. Variant annotation revealed that genes involved in transcription, transport, metabolism and transmembrane proteins were overrepresented in gene sets affected by high impact variants. A core genome representing genomic elements conserved in all the isolates and a non-redundant pangenome representing all genomic elements is presented. Whole genome alignments showed that an average of 93% of the genomic elements are present in all isolates. The results of this study reveal that some genomic elements are not conserved within the isolates and some variants are high impact. The described genome-scale variations will help inform novel disease management strategies against the pathogen.

The effect of the negative effective mass emerging in the gravitating core-spring-shell system is considered. The effect appears when the entire system is exerted to the external harmonic force and the frequency of external force approaches to the critical frequency from above. The critical frequency depends on the density of the self-gravitating system only. The scaling law predicting the value of for condensed phases is derived. The generalization of the effect for the Coulomb-like forces is reported

The upregulated expression of thyrosine kinase AXL has been reported in several hematologic and solid human tumors including gastric, breast, colorectal, prostate, and ovarian cancers. Thus, AXL can potentially serve as a diagnostic and prognostic biomarker for various cancers. This paper reports the first-ever use of loop-mediated isothermal amplification (LAMP) of the AXL gene as a diagnostic method for ovarian cancer. We demonstrated simple instrumentation toward a point-of-care device to perform LAMP. This paper also reports the first-ever use of core-shell beads as a microreactor to perform LAMP as an attempt to promote environmentally friendly laboratory practices.

In this research, users’ perception towards Universal Mobility in old core cities of India has been critically analyzed. Despite Universal Design guidelines from the United Nations and Union Government of India, old cities in India are seldom having Universal Mobility, in effect endangering the lifestyle of senior citizens and differently-abled people. The core of Kolkata Municipal Corporation in Kolkata, India has been considered as a case example for this research. This research has considered three types of data sets for analysis. First, the authors interviewed 310 respondents from the Indian design fraternity, with the objective of understanding their opinion on the concept of Universal Design. In the next investigative study of 125 respondents from different wards of Kolkata Municipal Corporation, the purpose was to comprehend people’s perception about walkability and mobility in an old Indian city. In the last visual survey of a stretch in Central Kolkata, the focus was identifying the hindrance in Universal Mobility in an old city core of Indian origin. Significant dissatisfaction was found in walkability amongst all user groups; which is linked to poor infrastructural conditions. Furthermore, accessing public transportation is difficult due to improper waiting facilities. However, the design fraternity in India suggests the need of separate accessibility guidelines for old and new cities in India. The design fraternity also recommends a customized rating system for accessing Universal Design. The result of this study indicates a need of recognizing the difficulty in imparting Universal Mobility in old core cities in India. This information can be used for preparing an Access Audit Checklist through Architectural Planning, which is the first step in proposing a framework for Universal Mobility in old core cities in India.

Due to the accuracy of numerical calculation of fluid flow inside a hydrocyclone can be obtained using Computational Fluid Dynamics (CFD), highly modified super computers are used to simulate the fluid flow and track particle motion inside a hydrocyclone. This paper deals with the numerical study using three multiphase models viz. Volume of fluid, Mixture and Eulerian model. The dimensions of the hydrocyclone taken into consideration for numerical analysis is same as considered by Rajamani. Validation of axial and tangential velocities at different strategically decided axial stations, RMS axial and tangential velocity profiles of the hydrocyclone is done using Reynolds Stress Model (RSM). The hydrocyclone model has been designed in Creo 3.0 using the same dimensions which later was imported to CFD for meshing. Fine hexagonal mesh numbering up to 5 lacs were constructed to obtain optimum results. Fluid flow was allowed to be developed in ANSYS FLUENT 16.2. Entire simulation took 96 hours to generate results and track particle movements inside the hydrocyclone. The particle tracking has been done using three multiphase model. The first being the volume of fluid was used for validation purposes and the comparison of the Mixture and Eulerian model are the basic focus of this research work. Conclusive results indicate that usage of different multiphase model does not result in variation in particle motion. The slight variation in grade efficiency values are hardly noticeable. The Mixture model and Eulerian model predict lower separation efficiency as compared with Volume of fluid multiphase model.

The development of sensors for monitoring Carbon Monoxide (CO) in a large range of temperature is of crucial importance in areas as monitoring of industrial processes or personal tracking using smart objects. Devices integrating GaN/Ga₂O₃ core/shell nanowires (NWs) is a promising solution allowing combining the high sensitivity of the electronic properties to the states of GaN-core surface; and the high sensitivity to CO of Ga₂O₃-shell. Because the performances of sensors primarily depend on the material properties composing the active layer of the device, it is essential to control these properties and in first time its synthesis. In this work, we investigate the synthesis of GaN/Ga₂O₃ core-shell NWs with a special focus on the formation of the shell. The GaN NWs grown by Plasma-assisted molecular beam epitaxy, are post-treated following thermal oxidation to form Ga₂O₃-shell surrounding the GaN-core. We establish that the Ga₂O₃-shell thickness can be modulated from 1 up to 14 nm by changing the oxidation conditions, and follows the diffuse-controlled reaction. By combining XRD-STEM and EDX analysis, we also demonstrate that the oxide shell formed by thermal oxidation is crystalline and presents the β-Ga₂O₃ crystalline phase, and is synthesized in epitaxial relationship with the GaN-core.

In this work, numerical simulations for the absorption and scattering efficiencies of spheroid core–shell nanoparticles (CSNs) were conducted and studied using the discrete-dipole approximation method. The characteristics of surface plasmon resonances (SPR) depend upon shell thickness, the compositions of the core and shell materials, and the aspect ratio of the constructed CSNs. We used different core@shell compositions, specifically Au@SiO₂, Ag@SiO₂, Au@TiO₂, Ag@TiO₂, Au@Ag, and Ag@Au, for extinction spectra analysis. We also investigated coupled resonance mode wavelengths by adjusting the composition’s layer thickness and aspect ratio. In this study, we show that the extinction efficiency of the Ag@TiO₂ core–shell nanoparticles (CSNPs) was higher than that of the others, and we examined the impact of TiO₂ shell thickness and Ag core radius on SPR peak positions. From the extinction spectra we found that the Ag@TiO₂ nanoparticle had better refractive index sensitivity and figure of merit when the aspect ratio was set to 0.3. All of the experimental results proved that the tunability of these plasmonic resonances was highly dependent on the material used, the layer thickness, and the aspect ratio of the core@shell CSNPs.

A theoretical analysis of haemoglobin (Hb) concentration detection is presented in this work with the objective of achieving more sensitive detection and monitoring low concentrations. Surface-enhanced SPR spectroscopy on silver nanoparticles was employed for recording Hb concentrations less than 10 g/L. In this paper, Fe₃O₄@Au core-shell, nanocomposite spherical nanoparticle consisting of a spherical Fe₃O₄ core covered by Au shell, was used as an active material for biomolecules detection in the Surface Plasmon Resonance (SPR)-based biosensor in the wavelength 632.8 nm. We present the simulation of detection amplification technique through Attenuated Total Reflection (ATR) spectrum in the Kretschmann configuration. The system consists of a four-layer material i.e prism/Ag/Fe₃O₄@Au+Hb/air. Dielectric function determination of the core-shell nanoparticle (Fe₃O₄@Au) and the composite (Fe₃O₄@Au+Hb) was done by applying the Effective Medium Theory approximation and the calculation of the reflectivity is carried out by varying the size of core-shell (r₀). In this simulation, the refractive index of the BK7 prism is 1.51; the refractive index of Ag thin film is 0.13455+3.98651i with the thickness of 40 nm, and the refractive index of the composite is varied depending on the size of nanoparticle core-shell. Our results show that by varying the radius of the core and the shell thickness, the dip of the reflectivity (ATR) spectrum is shifted to the larger angle of incident light and the addition of core-shell in the conventional SPR-based biosensor leads to enhancement of the SPR biosensor sensitivity, for the core-shell radius 10 nm, the sensitivity increased by 1.35% for F = 0.1, and by 4.89% for F =0.8 compared to the sensitivity of the conventional SPR-based biosensor without core-shell addition.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico, ex vivo, and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) receptors are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. Acute pre-treatment with L-17 robustly increased c-Fos immunoreactivity in the amygdala (central nucleus), suggesting increased neuronal excitability in this brain area after L-17 administration. Acute L-17 also dose-dependently inhibited of 5-HT neurons of the dorsal raphe nucleus (DRN). This inhibition was partially reversed by subsequent administration of WAY100135, suggesting the involvement of extracellular 5-HT. Based on in silico predictions, c-Fos immunohistochemistry, and in vivo electrophysiology, we suggest that L-17 is a potent 5-HT reuptake inhibitor and/or partial 5-HT1A receptor antagonist. Thus, L-17 might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardio-protective properties, it can be useful in post-stroke and post-myocardial infarction (MI) depression. In general, combined in silico predictions and ex vivo neurochemical and in vivo electrophysiological assessment might be a useful strategy for early preclinical assessment of the affectivity and neural mechanism in action of the novel CNS drugs.

Dicarbonyls are electrophiles able to generate the so-called advanced glycation end-products (AGEs). Human exposure occurs via ingestion (e.g., food), inhalation (e.g., electronic cigarettes) and dysregulation of endogenous metabolic pathways (e.g., glycolysis). Biological systems can prevent AGEs formation via enzymatic and nonenzymatic reactions. However, the continuous exposure to dicarbonyls may cause the depletion of endogenous substrates and the beginning of AGEs accumulation (i.e., carbonylation). Since this process has been associated with multiple disorders, several studies advocated the use of dicarbonyl binders as food preservatives or as drugs aimed at mitigating carbonylation damages. As reported for other toxicants (e.g., HNE, acrolein), the screening of selective and potent binders can be performed by measuring the residual amount of a selected dicarbonyl substrate, upon its incubation with candidate binders. Unfortunately, naturally occurring dicarbonyls are poorly responsive to many detectors (e.g., UV or MS). For this reason, most of the screening methods that have been reported to date relies on indirect quantification upon derivatization. However, this strategy can potentially lead to inaccurate results since the tested compounds can affect the derivatization yield. Therefore, we herein reported the use of benzylglyoxal (BGO) as a convenient, UV responsive, dicarboyl surrogate. By using BGO as a substrate, we setup an easy and cheap chromatographic assay for the direct measurement of the binding activity towards dicarbonyls, without derivatization. The method was qualified by assessing the binding ability of some known dicarbonyl binders, obtaining results consistent with literature.

Arrestin-1, or visual arrestin, exhibits an exquisite selectivity for light-activated phosphorylated rhodopsin (P-Rh*) over its other functional forms. That selectivity is believed to be mediated by two well-established structural elements in the arrestin-1 molecule, the activation sensor detecting the active conformation of rhodopsin and the phosphorylation sensor responsive to the rhodopsin phosphorylation, which only active phosphorylated rhodopsin can engage simultaneously. However, in the crystal structure of the arrestin-1-rhodopsin complex there are arrestin-1 residues located close to rhodopsin, which do not belong to either sensor. Here we tested by site-directed mutagenesis the functional role of these residues in wild type arrestin-1 using direct binding assay to P-Rh* and light-activated unphosphorylated rhodopsin (Rh*). We found that many mutations either enhanced the binding only to Rh* or increased the binding to Rh* much more than to P-Rh*. The data suggest that the native residues in these positions act as binding suppressors, specifically inhibiting the arrestin-1 binding to Rh* and thereby increasing arrestin-1 selectivity for P-Rh*. This calls for the modification of a widely accepted model of the arrestin-receptor interactions.

Mucilage from Coccinia grandis was extracted, isolated by maceration technique and precipitated, accordingly. The mucilage was evaluated for its physicochemical, binding, and disintegrant properties in tablets using paracetamol as a model drug. The crucial physicochemical properties such as flow properties, solubility, swelling index, loss on drying, viscosity, pH, microbial load, cytotoxicity were evaluated and the compatibility was analysed using sophisticated instrumental methods (TGA, DTA, DSC, and FTIR). The binding properties of the mucilage were used at three different concentrations and compared with starch and PVP as standard binders. The disintegrant properties of mucilage were used at two different concentrations and compared with standard disintegrants MCCP, SSG, and CCS. The wet granulation technique was used for the preparation of granules and was evaluated for the flow properties. The tablets were punched and evaluated for their hardness, friability, assay, disintegration time, in vitro dissolution profiles. In vitro cytotoxicity study of the mucilage was performed in human embryonic kidney (HEK) cell line using cytotoxic assay by MTT method. The outcome of the study indicated that the mucilage had good performance when compared with starch and PVP. Further, the mucilage acts as a good disintegrant than MCCP, SSG and CCS to paracetamol tablets. Moreover, the in vitro cytotoxicity evaluation results demonstrated that the mucilage is non-cytotoxic to human cells and is safe.

The multi-material design and the adaptability of a modern process chain require joining connections with specifically adjustable mechanical, thermal, chemical or electrical properties, whereby previous considerations have focused primarily on the mechanical properties. With clinching, the multitude of possible combinations of requirements, materials and component or joint geometry makes it impossible to determine these joint properties empirically. As a result of the established and empirically based procedure, no model exists to date that considers all questions of joinability, i.e. the materials (suitability for joining), the design (joining safety) and the production (joining possibility) and allows a calculation of the achievable properties. It is therefore necessary to describe the physical properties of the joint as a function of the three bonding mechanisms force closure, form closure and material closure in relation to the application. This approach enables the illustration of the relationships along the causal chain "joint requirement - binding mechanism - joining parameters". In this way the adaptability of the mechanical joining technology can be improved. A geometric comparison is made using metallographic cross sections, of clinched joints of the combination of aluminum and steel. The torsional testing of the rotationally symmetric clinching points for detection of the mechanical stress state are qualified as examination method and technological test. By measuring the electrical resistance in the base material, in the clinch joint and during the production cycle (after clinching, before precipitation hardening and after precipitation hardening), this change in the stress state can also be detected.

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. In this respect the identification of single agents with multitarget potential might represent the ideal solution. Accordingly, a small library of biphenylhydrazo 4-arylthiazoles derivatives has been synthesised and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity.

In silico analysis is a promising approach for understanding biological events in complex diseases. Herein, we report an in silico analysis of the entire genome of virus ZikaSPH2015 strain, which was performed in order to identify the occurrence of specific motifs on genomic sequence of Zika Virus that is able to bind and therefore, sequester host’s Transcription Factors (TFs) as well as subsequently predict a possible interactions within host genome. Accordingly to obtained results of this original computational work-flow it is possible to hypothesize that these TFs Binding Motifs might be able to explain the complex and heterogeneous phenotype presentation in Zika Virus affected fe-tus/newborns, as well as the less severe condition in adults. Moreover, the proposed in silico protocol identified thirty three different TFs same as the distribution of TFBSs (Transcription Factor Binding Sites) on ZikaSPH2015 strain, potentially able to influence genes and pathways with biological functions confirming that this approach could find potential answers on disease pathogenesis.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Tumor invasion, metastasis, and recrudesce remain a considerable challenge in the treatment of gastric cancer (GC). Herein, we first identified that RBFOX3 (RNA binding protein fox-1 homolog 3) was significantly up-regulated in GC tissues and negatively linked to the survival rate of GC patients. RBFOX3 promoted cell division and cell cycle progression in vitro as well as in vivo. Furthermore, RBFOX3 increased cell invasion and migration ability. Interestingly, both the suppression of GC cell multiplication and invasion moderated by the silencing of RBFOX3 was rescued by HTERT up-regulation. Additionally, RBFOX3 augmented the resistance of GC cells to 5-fluorouracil (5-Fu) by repressing RBFOX3. Mechanistically, exogenous up-regulation of RBFOX3 triggered promoter activity and HTERT expression thereby enhancing the division and development of GC cells. Importantly, our findings revealed that RBFOX3 interacted with AP-2β to modulate the HTERT expression as demonstrated by co-immunoprecipitation analysis. In conclusion, our study indicates that high expression of RBFOX3 promotes GC progression and development but predicts worse prognosis by stimulating HTERT signaling. Moreover, the results suggest that the RBFOX3/AP-2β/HTERT pathway is a novel target for the development of therapeutic agents for the prevention and treatment of GC reappearance and metastasis.

I have recently reiterated that the cross-bridge is a calcium ATPase that is inhibited by magnesium and this arises because in normal hearts Myosin binding Protein-C prevents the use of MgATP as rate limiting substrate ensuring that Ca²⁺ replaces Mg²⁺ in the excitation pathway. Here I revisit the studies on [Ca²⁺] dependency of ATPase and tension under diastolic stretch with a different conclusion on Hill coefficients. This reveals the underlying mechanisms of the Frank-Starling Law and Hypertrophic myopathy are not the same, the former being kinase controlled.

In an attempt to correct misunderstandings this article brings together the observations on Calcium, Myosin Binding Protein-C and Hypertrophic Cardiomyopathy in the basic function of cardiac muscle. A finding of many years ago is reiterated in a novel enzyme kinetic format with defined rate limiting step which makes CaATP the apparent substrate of the actomyosin cross-bridge. The relationship of these kinetics to recent observations on disruption of myosin binding protein-C is described along with how this bears on the understanding of the related cardiomyopathies.

Little is known about the association between equol and bioavailable testosterone (BT) in adults. We examined the associations of urinary equol concentrations with serum total, bioavailable and free testosterone (FT), dehydroepiandrosterone sulfide (DHEAS), free androgen index (FAI) and sex hormone-binding globulin (SHBG) concentrations. This cross-sectional study included 1904 women aged 59.7 years. Urinary equol and serum sex hormone concentrations were measured. Overall, urinary equol tended to be inversely associated with bioactive forms of androgenic indices (BT, FT or FAI) but not with total testosterone (TT) or DHEAS. Urinary equol was also positively associated with SHBG. In multi-covariate-adjusted analyses stratified by menopausal status, graded and inverse associations between urinary equol and bioactive forms of androgenic indices (BT, FT and FAI) were observed in postmenopausal women (all p-trends <0.05), but not in premenopausal women. A significant positive association between urinary equol and SHBG was observed only in postmenopausal women. No significant associations were observed between urinary equol and TT or DHEAS in either group. A path analysis indicated that these associations of equol with androgens in postmenopausal women might be mediated by SHBG. Our findings indicated urinary equol exhibited graded and inverse associations with BT or FT but not TT in women.

Ubiquitin binding domains (UBDs) are modular elements that bind non-covalently to ubiquitin and act as downstream effectors and amplifiers of the ubiquitination signal. With few exceptions, UBDs recognize the hydrophobic path centered on Ile44 (Leu-8, Ile-44, Val-70). Nevertheless, a variety of different orientations, which can be attributed to specific contacts between each UBD and surface residues surrounding the hydrophobic patch, specify how each class of UBD recognizes ubiquitin. Here, we describe the structure of a novel ubiquitin-binding domain that we identified in NEDD4 binding protein 1 (N4BP1). By performing protein sequence analysis, mutagenesis and NMR spectroscopy of the ¹⁵N isotopically labelled protein, we demonstrate that a Phe-Pro motif in N4BP1 recognizes the canonical hydrophobic patch of ubiquitin. This recognition mode resembles the molecular mechanism evolved in the CUE (Coupling of ubiquitin conjugation to ER degradation) domain family, where an invariant proline, usually following a phenylalanine, is required for binding to ubiquitin. Interestingly, the UBD of N4BP1 is evolutionary related to CUBAN (Cullin binding domain associating with NEDD8) (40% identity and 47% similarity), a protein module that also recognizes the ubiquitin-like NEDD8, which is the closest relative of ubiquitin (58% identity and 80% similarity). By performing circular dichroism and ¹⁵N NMR chemical shift perturbation of N4BP1 in complex with ubiquitin, we demonstrate that the UBD of N4BP1 lacks the NEDD8 binding properties observed in CUBAN and it recognizes the Ile44-centered patch of ubiquitin through a dedicated binding site, which share some of the features observed in the CUE domain family. Moreover, we show that, in addition to mediating the interaction with ubiquitin and ubiquitinated substrates, both the CUBAN and the UBD of N4BP1 are poly-ubiquitinated in cells. This modification is dependent on the presence of a functional domain. We believe that the structural and functional characterization of this novel UBD will allow a deeper understanding of the molecular mechanisms governing N4BP1 function, while at the same time providing a valuable tool for clarifying how the discrimination between ubiquitin and the highly related NEDD8 is achieved.

FRAP technique have been used for decades to measure movements of molecules in 2D. Data obtained by FRAP experiments in cell plasma membranes are assumed to be described through means of two parameters, a diffusion coefficient D (as defined in a pure Brownian model) and a mobile fraction M. Nevertheless, it has also been shown that recoveries can be nicely fit using anomalous sub-diffusion. FRAP at variable radii has been developed using the Brownian diffusion model to access geometrical characteristics of the surrounding landscape of the molecule. Here we performed numerical simulations of continuous time random walk (CTRW) anomalous subdiffusion and interpreted them in the context of variable radii FRAP. These simulations were compared to experimental data obtained at variable radii on living cells using the PH domain of the membrane binding protein EFA6 (exchange factor for ARF6, a small G protein). This protein domain is an excellent candidate to explore the structure of the interface between cytosol and plasma membrane in cells. By direct comparison of our numerical simulations to the experiments, we show that this protein does not exhibit anomalous diffusion in BHK cells. The non Brownian PH-EFA6 dynamics observed here is more related to spatial heterogeneities such as cytoskeleton fences effects.

We review the basics of nuclear binding energy scheme assumed to be associated with the existence of a new strong elementary charge associated with square root of reciprocal of the strong coupling constant.

Coffee processing generates a huge amount of waste which contains many natural products. Here, we report the discovery of a panel novel cell-penetrating and metal-ion binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and database search, we showed that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif but without a chitin-binding domain. NMR determination of cC1a revealed a compact structure that confers it resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis revealed that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement like ginsentide precursors. Molecular modeling together with experimental validation revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, and which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have potential to target intracellular proteins.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

A large core size and bending resistance are very important properties of mid-infrared energy transfer fibers, but large core sizes usually lead to a deterioration of bending properties. A negative-curvature nested node-free anti-resonant hollow-core fiber (AR-HCF) based on quartz is proposed. It was made by adding a nested layer to a previous AR-HCF design to provide an additional anti-resonance region while keeping the gap between adjacent tubes strictly correlated to the core diameter to produce a node-free structure. These features improve the fiber’s bending resistance while achieving a larger core diameter. The simulation results show that the radial air-glass anti-resonant layer is increased by the introduction of the nested anti-resonant tube, and the weak interference overlap between the fiber core and the cladding mode is reduced, so the fiber core’s limiting loss and the sensitivity to bending are effectively reduced. When the capillary wall thickness t of the fiber is 0.71 μm, the core diameter D is 70 μm, the ratio of the inner diameter of the cladding capillary to the core diameter d/D is 0.62, and the diameter of the nested tube is d0=29 μm, the fiber has a lower limiting loss at the wavelength of 2.79 μm, and the limiting loss is 3.28×10-4 dB/m. At the same time, the optimized structure also has good bending resistance. When the bending radius is 30 mm, the bending loss is only 4.72×10-2 dB/m. To our knowledge, this is the first research to achieve an anti-bending low-loss micro-structure hollow fiber with a bending radius of less than 30 mm in the 2.79 μm band. An anti-bending low-loss anti-resonant hollow-core fiber with this structure constitutes a reliable choice for the light guiding system of a 2.79 μm band erbium laser therapy instrument.

This study investigates the vertical structure of the dynamical properties of a warm-core ring in the Gulf of Mexico (Loop Current ring) using glider observations. We introduce a new method to correct the glider’s along-track coordinate which is, in general, biased by the unsteady relative movements of the glider and the eddy, yielding large errors on horizontal derivatives. Here, we take advantage of the synopticity of satellite along-track altimetry to apply corrections on the glider’s position, by matching in situ steric height with satellite-measured sea surface height. This relocation method allows to recover the eddy’s azimuthal symmetry, to precisely estimate the rotation axis position, and to compute reliable horizontal derivatives. It is shown to be particularly appropriate to compute the eddy’s cyclo-geostrophic velocity, relative vorticity, and shear strain, which are otherwise out of reach when using the glider’s raw traveled distance as an horizontal coordinate. The Ertel potential vorticity (PV) structure of the warm core ring is studied in details, and we show that the PV anomaly is entirely controlled by vortex stretching. Sign reversal of the PV gradient across the water column suggests that the ring might be baroclinically unstable. The PV gradient is also largely controlled by gradients of the vortex stretching term. We also show that the ring’s total energy partition is strongly skewed, with available potential energy being 3 times larger than kinetic energy. The possible impact of this energy distribution on the Loop Current rings longevity is also discussed.

Composite materials are widely used in the dental field in clinics as biomaterials. For example, it has been used as a biomaterial to repair caries and restore masticatory function, and as a cement to adhere the restoration to the tooth substrate. In order to demonstrate its function, dental biomaterials are measured their mechanical strength. From such basic research, we explained the potential of dental biomaterials, especially flexural strength and modulus of elasticity. Mechanical properties of dental biomaterials similar to those of the tooth, thermal stimulation, and aesthetic elements in the oral cavity. In this part, we will introduce the commercialized products of composites suitable for the characteristics and tooth quality, and provide the reader with the characteristics from the flexural characteristics of the composite materials used in clinical dentistry. In clinical performance, it might be advisable to delay polishing when composite biomaterials are used for luting materials, filling materials and core build-up materials since improved the flexural strength and the flexural modulus of elasticity were displayed after 1-day storage. And it is thought that flexural strength or characteristics is a significant important mechanical property of oral biomaterials.

The implementation of gold-hydrogel core-shell nanomaterials in novel light-driven technologies requires the development of well-controlled and scalable synthesis protocols with precisely tunable properties. Herein, new insights are presented concerning the importance of using the concentration of gold cores as a control parameter in the seeded precipitation polymerization process to modulate – regardless of core size – relevant fabrication parameters such as encapsulation yield, particle size and shrinkage capacity. Controlling the number of nucleation points results in the facile tuning of the encapsulation process, with yields reaching 99% of gold cores even when using different core sizes at a given particle concentration. This demonstration is extended to the encapsulation of bimodal gold core mixtures with equally precise control on the encapsulation yield, suggesting that this principle could be extended to encapsulating cores composed of other materials. These findings could have significant impact on the development of stimuli-responsive smart materials.

This study's objective was to propose the use of textile braiding manufacturing methods, thus facilitating the application of the high precision and accurate measurability of optical fiber Bragg grating sensors to various structures. The purpose of this study was to Combine 3d braid processing with the optical Bragg grating sensor's accurate metrology. Out of limits of the sensor's epoxy attachment methods, the textile braiding method can make applicable scope diversify. The braiding processing is capable of designing a 3D fabric module processing, multiple objective mechanical fiber arrangement, and material characteristics. Optical stress-strain response conditions were explored through the optimization of design elements between the Bragg grating sensor and braiding. For this study, Bragg grating sensors were located 75% apart from the fiber center. The sensor core structure is helical of 1.54 pitch. A polyurethane synthetic yarn was braided together with the sensor on the Weaving machine core part in a braiding. Prototyping results, a negative Poisson's ratio makes curled the braided Bragg grating sensor. The number of polyurethane string yarns has been conducted the role of wrap angle in braiding. The 12 strands condition showed an increase in double stress-strain response rate at a Poisson ratio of 1.3%, and 16 strands condition was found to affect the sensor with noise at a Poisson ratio of 1.5%. This study can suggest applying braid processing of the Bragg grating sensor, which is expected to create and develop a new monitoring sensor.

This study's objective was to propose the use of textile braiding manufacturing methods, thus facilitating the application of the high precision and accurate measurability of optical fiber Bragg grating sensors to various structures.The purpose of this study was to Combine 3d braid processing with the optical Bragg grating sensor's accurate metrology. Out of limits of the sensor's epoxy attachment methods, the textile braiding method can make applicable scope diversify. The braiding processing is capable of designing a 3D fabric module processing, multiple objective mechanical fiber arrangement, and material characteristics. Optical stress-strain response conditions were explored through the optimization of design elements between the Bragg grating sensor and braiding. For this study, Bragg grating sensors were located 75% apart from the fiber center. The sensor core structure is helical of 1.54 pitch. A polyurethane synthetic yarn was braided together with the sensor on the Weaving machine core part in a braiding.Prototyping results, a negative Poisson's ratio makes curled the braided Bragg grating sensor. The number of polyurethan string yarns has been conducted the role of wrap angle in braiding. The 12 strands condition showed an increase in double stress-strain response rate at a Poisson ratio of 1.3%, and 16 strands condition was found to affect the sensor with noise at a Poisson ratio of 1.5%. This study can suggest applying braid processing of the Bragg grating sensor, which is expected to create and develop a new monitoring sensor.

In this paper we show how to efficiently implement parallel discrete simulations on Multi-Core and GPU architectures through a real example of application: a cellular automata model of laser dynamics. We describe the techniques employed to build and optimize the implementations using OpenMP and CUDA frameworks. We have evaluated the performance on two different hardware platforms that represent different target market segments: high-end platforms for scientific computing, using an Intel Xeon Platinum 8259CL server with48cores and also an NVIDIA Tesla6V100 GPU, both running on Amazon Web Server (AWS) Cloud, and on a consumer-oriented platform, using an Intel Core i9 9900k CPU and an NVIDIA GeForce GTX 1050 TI GPU. Performance results are compared and analysed in detail. We show that excellent performance and scalability can be obtained in both platforms, and we extract some important issues that imply a performance degradation for them. We also found that current Multi-Core CPUs with large core numbers can bring a performance very near to that of GPUs, even similar in some cases.

Though the energy density of lithium-ion batteries continues to increase, safety issues related with the internal short-circuit and the resulting combustion of highly flammable electrolyte impede the further development of lithium-ion batteries. It has been well-accepted that a thermal stable separator is important to postpone the entire battery short-circuit and thermal-runaway. Traditional methods to improve the thermal stability of separators includes surface modification and/or developing alternate material systems for separators which may always affect the battery performance negatively. Herein, a thermostable and shrink-free separator with little compromise in battery performance is prepared by coaxial electrospinning and tested. The separator consists of core-shell fiber networks where poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) layer serves as shell and polyacrylonitrile (PAN) as the core. This core-shell fiber network exhibits little or even no shrinking/melting at elevated temperature over 250 °C. Meanwhile, it shows excellent electrolyte wettability and can take large amount of liquid electrolyte three times more than that of conventional Celgard 2400 separator. In addition, the half-cell using LiNi1/3Co1/3Mn1/3O2 as cathode and the aforementioned electrospun core-shell fiber network as separator demonstrates superior electrochemical behavior, stably cycling for 200 cycles at 1 C with a reversible capacity of 130 mAh g-1 and little capacity decay.

The temporo-spatial theory of consciousness postulates that the brain implements its own inner time and space for conscious processing of outside world. In line with this hypothesis, I present a mechanistic model of mutually connected processes that encode the inner space and time. The model is used to elaborate the binding mechanism between two sets of processes representing the inner space and time, respectively. Further, a stochastic version of the model is developed to investigate the interplay between the binding strength and noise. The spectral entropy is used to characterize the noise effects on the systems of processes when the binding strength is varied. The stochastic modeling results reveal that the spectral entropy values for strongly bound systems have similar entropy values for weakly bound or even decoupled systems. Thus, the analysis performed in this study allows to conclude that the binding mechanism is noise-resilient.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

Carbon supported nanoparticles of monometallic Ni catalyst and binary Ni-Transition Metal (Ni-TM/C) electrocatalytic composites were synthesized via chemical reduction method, where TM stands for the doping elements Fe, Co, and Cu. The chemical composition, structure and morphology of the Ni-TM/C materials were characterized by X-ray photoelectron spectroscopy (XPS), X-ray diffractometry (XRD), transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM) and energy-dispersive X-ray spectroscopy (EDS). The electrochemical properties towards hydrogen oxidation reaction in alkaline medium were studied using the rotating disc electrode and cycling voltammetry methods. A significant role of the TM dopant in the promotion of the hydrogen electrooxidation kinetics of the binary Ni-TM/C materials were revealed. A record-high in exchange current density value of 0.060 mA cm²_Ni was measured for Ni₃Fe₁/C, whereas the monometallic Ni/C counterpart has only shown 0.039 mA cm²_Ni. In order to predict the feasibility of the electrocatalysts for hydrogen chemisorption, density functional theory was applied to calculate the hydrogen binding energy and hydroxide binding energy values for bare Ni and Ni₃TM₁.

Semaglutide is a potent GLP-1 receptor agonist used in the treatment of type 2 diabetes mellitus due to its ability to regulate blood glucose levels and promote weight loss. On July 26, 2021, with a manually defined set of computational structural and biophysical analysis, a simple Val27-Arg28 exchange was for the first time introduced in the backbone of semaglutide to strengthen the semaglutide-GLP-1R binding affinity. In this article, a comprehensive structural and biophysical analysis approach is for the first time proposed towards an exhaustive exploration of the semaglutide-GLP-1R sequence space for the design of semaglutide analogues with elevated binding affinity to GLP-1R, thereby potentially enhancing therapeutic efficacy of structurally conceivable semaglutide analogues. Through structure biophysics-based rational design and computational modeling, this article puts forward a set of semaglutide analogues and calculated their binding affinities to GLP-1R, with one particular semaglutide analogue-GLP-1R structural model reaching a K_d of 3.0 × 10^-8 M, while the K_d is 3.4 × 10^-6 M for the binding of native semaglutide to GLP-1. Overall, the computationally designed semaglutide analogues here constitute a hopeful approach for developing GLP-1 receptor agonists with improved efficacy for the treatment of diabetes and weight management in future.

Insulin therapy is a cornerstone in the management of diabetes, yet the pursuit of optimizing its pharmacokinetic profile remains a focal point in diabetes research. For instance, insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising once-weekly treatment option for diabetic patients. However, designing insulin analogues with lower receptor affinity than that of insulin icodec could still produce a further extended duration of action than that of insulin icodec through the suppression of receptor-mediated internalization of insulin analogues. In this study, therefore, I present the design of a novel series of insulin analogues engineered towards lower binding affinity to the insulin receptor compared to that of insulin icodec. Through computational structural biophysics-based rational design strategies, this article aims to further extend the duration of action while maintaining therapeutic efficacy of insulin analogues. Utilizing homology molecular modeling and structural biophysics-based binding affinity calculations, this article puts forward a set of insulin analogues with lower binding affinity to insulin receptor than that of insulin icodec from a structural and biophysical point of view. Overall, this article calls for subsequent in vitro and in vivo evaluations of the efficacy and prolonged action of the engineered insulin analogues to pharmacokinetically test whether these analogues acutally surpass that of insulin icodec as hopeful candidates for next-generation insulin analogue therapies with improved duration of action and enhanced control of blood glucose levels for diabetic patients in future.

The ribosome is a macromolecular complex composed of RNA and proteins that interact through an integrated and interconnected network to preserve its ancient core activities. In this review, we emphasize the pivotal role played by RNA-binding proteins as a driving force in the evolution of the current form of the ribosome, underscoring their importance in ensuring accurate protein synthesis. This category of proteins includes both ribosomal proteins and ribosome biogenesis factors. Impairment of their RNA-binding activity can also lead to ribosomopathies, a group of disorders characterized by defects in ribosome biogenesis that are detrimental to protein synthesis and cellular homeostasis. A comprehensive understanding of these intricate processes is essential for elucidating the mechanisms underlying the resulting diseases and advancing potential therapeutic interventions.

The complexity of RNA cannot be fully expressed with the canonical A, C, G, and U alphabet. To date, over 140 distinct chemical modifications to RNA have been discovered. RNA modifications can profoundly impact the cellular outcomes of messenger RNAs (mRNAs), transfer and ribosomal RNAs, and noncoding RNAs. Additionally, aberrant RNA modifications are associated with human disease. RNA modifications are a rising topic within the fields of biochemistry and molecular biology. This review aims to provide budding scientists with an appreciation for the significance of RNA modifications, alongside the skills required to identify and fluently discuss fundamental RNA-protein interactions. The Pumilio RNA-binding protein and YT521-B homology (YTH) family of modified RNA-binding proteins serve as examples to highlight the fundamental biochemical interactions that underlie the specific recognition of both unmodified and modified ribonucleotides, respectively.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in-silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physiological conditions. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in-silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared to the pertuzumab-HER2 complex.

Production of silkworm silk is the most economically important traits in the silk industry. Silk protein synthesis is regulated by juvenile hormone (JH) and 20-Hydroxyecdysone (20E). Therefore, it is important to understand the genetic regulation of silk production is thus a priority. JH binding protein (JHBP) transports JH from the hemolymph to target organs and cells and protects JH. In a previous study, we identified 41 genes containing a JHBP domain in the Bombyx mori genome. Only one JHBP gene, that is, BmJHBPd2, is highly expressed in the posterior silk gland (PSG) and its function remains unknown. In the present study, we investigated the expression levels of BmJHBPd2 and the major silk protein genes in the high silk-producing practical strain 872 (S872) and the low silk-producing local strain Dazao. Our results have shown that BmJHBPd2 was more highly expressed in S872, than in the Dazao strain, which is consistent with the expression pattern of fibroin genes. A subcellular localization assay indicated that BmJHBPd2 is located in the cytoplasm. In vitro hormone induction experiments showed that BmJHBPd2 was upregulated by treatment with juvenile hormone analogue (JHA). BmKr-h1 upregulation was significantly inhibited by overexpression of BmJHBPd2 at the cell level when induced by JHA. However, overexpression of BmJHBPd2 in the posterior silk gland by transgenic methods led to the inhibition of the expression of the silk fibroin gene, resulting in a reduction in silk yield. Further investigation has shown that in the BmJHBPd2OE individual, the key transcription factor Krüppel homolog 1 (Kr-h1) of the JH signaling pathway was inhibited, and 20E signaling pathway genes, such as broad complex (Brc), E74A, and ultraspiracle protein(USP), were upregulated. Our results have indicated that BmJHBPd2 plays an important role in the JH signaling pathway and was important for silk protein synthesis. Furthermore, our findings have helped to elucidate the mechanisms by which JH regulates silk protein synthesis.

Naltrexone (NTX) is a potent opioid antagonist with good blood-brain barrier permeability, targeting different endogenous opioid receptors, particularly the mu-opioid receptor (MOR). Therefore, it represents a promising candidate for drug development against drug addiction. However, the details of the molecular interactions of NTX and its derivatives with MOR are not fully understood, hindering ligand-based drug discovery. In the present study, taking advantage of the high-resolution X-ray crystal structure of the murine MOR (mMOR), we constructed a homology model of the human MOR (hMOR). A solvated phospholipid bilayer was built around the hMOR and submitted to microsecond (µs) molecular dynamics (MD) simulations to obtain an optimized hMOR model. NTX and its derivatives were docked into the optimized hMOR model and submitted to µs MD simulations in an aqueous membrane system. The MD simulation results were submitted to Molecular Mechanics Generalized-Born surface area (MMGBSA) binding free energy calculations and principal component analysis. Our results revealed that NTX and its derivatives showed differences in protein-ligand interactions; however, they shared contact with residues at TM2, TM3, H6, and TM7. The binding free energy and principal component analysis revealed the structural and energetic effects responsible for the higher potency of NTX compared to its derivatives.

Titanium and its alloys are used biomaterials for medical and dental applications, due to their mechanical and physical properties. The surface modifications of titanium with bioactive molecules can increase the osseointegration by improving the interface between the bone and implant. Titanium dioxide nanotubes (TiO₂NTs) have excellent bioactivity inducing cell adhesion, spreading, growth and differentiation. In this work, TiO₂NTs were functionalized with a lectin from the plasma of the fish Oreochromis niloticus aiming to favour the adhesion and proliferation of osteoblast-like cells, improving its biocompatibility. The TiO₂NTs were obtained by anodization of titanium and annealed at 400 °C for 3 h. The resulting TiO₂NTs were characterized by high-resolution scanning electron microscopy. The successfully incorporation of OniL on the surface of TiO₂NTs by spin coating was demonstrated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIE) and attenuated total reflection-Fourier transform infrared spectrum (ATR-FTIR). Our results showed that TiO₂-NTs were successfully synthesized in a regular and well-distributed way. The functionalization of TiO₂-NTs with OniL favoured adhesion, proliferation, and the osteogenic activity of osteoblast-like cells, suggesting its use to improve the quality and biocompatibility of titanium-based biomaterials.

The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is activated by the small G-protein, RHEB-GTPase. On lysosome, RHEB activates mTORC1 by binding the domains of N-heat, M-heat, and FAT, which allosterically regulates ATP binding in the active site for further phosphorylation. The crucial role of RHEB in regulating growth and survival through mTORC1, makes it a targetable site for anti-cancer therapeutics. However, the binding kinetics of RHEB to mTORC1 is still unknown at the molecular level. Therefore, we studied the kinetics by in vitro and in-cell protein-protein interaction (PPI) assays. For this, we used the split-luciferase system (NanoBiT®) for in-cell studies, and prepared proteins for the in vitro measurements. Consequently, it was shown that RHEB binds to the whole mTOR both in the presence or absence of GTPɣS, with five-fold weaker affinity in the presence of GTPɣS. Also, RHEB bound to the truncated mTOR fragments of N-heat domain (60-167) and M-heat domain (967-1023) in a GTP independent manner. Furthermore, RHEB bound to the truncated kinase domain (2148-2300) with higher affinity also in GTP independently. In conclusion, RHEB binds two different binding sites of mTOR, which probably regulates the kinase activity of mTOR through multiple different molecular mechanisms.

The effects of mixing orders of tannic acid (TA), starch and α-amylase on the enzyme inhibition of TA were studied, including mixing TA with α-amylase before starch addition (order 1), mixing TA with pre-gelatinized starch before α-amylase addition (order 2) and co-gelatinizing TA with starch before α-amylase addition (order 3). It was found that the enzyme inhibition was always highest for order 1 because TA could bind with the enzyme active site thoroughly before digestion occurred. Both order 2 and 3 reduced α-amylase inhibition through decreasing binding of TA with the enzyme, which resulted from the non-covalent physical adsorption of TA with gelatinized starch. Interestingly, at low TA concentration, α-amylase inhibition for order 2 was higher than order 3, while at high TA concentration, the inhibition was shown with opposite trend, which arose from the difference in the adsorption property between the pre-gelatinized and co-gelatinized starch at the corresponding TA concentrations. Besides, both the crystalline structures and apparent morphology of starch were not significantly altered by TA addition for order 2 and 3. Conclusively, although a polyphenol may have an acceptable inhibitory activity in vitro, the actual effect may not reach the expected one when taking processing procedures into account.

Following the concept of strong interaction, theoretically, fusion of proton seems to increase the binding energy of final atom by 8.8 MeV. Due to Coulombic repulsion, asymmetry effect, pairing effect and other nuclear effects, final atom is forced to choose a little bit of binding energy less than 8.8 MeV and thus it is able to release left over binding energy in the form of internal kinetic energy or external thermal energy. Thus, in cold fusion, heat release to occur, binding energy difference of final atom and base atom seems to be less than 8.8 MeV. Qualitatively, energy released during cold fusion seems to be approximately equal to 8.8 MeV minus the difference of binding energy of final and base atoms. Based on this idea, under normal conditions, for the case of ₂He⁴, fusion of four protons can liberate (35.2-28.3)=6.9 MeV and it is 3.5 times less than the current estimates. Point to be understood is that, lesser the binding energy of final atom, higher the liberated thermal energy and vice versa. With a suitable catalyst and sufficient hydrogen under suitable pressure, if reactor’s temperature is maintained at (1000 to 1500) ⁰C, there seems a lot of scope for a chain reaction of cold fusion in which light isotopes transform to their next stage with increased proton number or mass number and liberate safe and clean heat energy continuously. By arranging 4 to 6 reactors and charging them periodically in tandem, required thermal energy can be produced continuously. In this new direction, by carefully selecting the base isotope and its corresponding catalyst, experiments can be conducted and ground reality of cold fusion can be understood at various temperature and pressure conditions.

HspA1A, a molecular chaperone, translocates to the plasma membrane (PM) of stressed and cancer cells. This translocation results in HspA1A’s cell-surface presentation, which renders tumors radiation insensitive. To specifically inhibit the lipid-driven HspA1A’s PM translocation and devise new therapeutics it is imperative to characterize the unknown HspA1A’s lipid-binding regions and determine the relationship between the chaperone and lipid-binding functions. To elucidate this relationship, we determined the effect of phosphatidylserine (PS)-binding on the secondary structure and chaperone functions of HspA1A. Circular dichroism revealed that binding to PS resulted in minimal modification on HspA1A’s secondary structure. Measuring the release of inorganic phosphate revealed that PS-binding had no effect on HspA1A’s ATPase activity. In contrast, PS-binding showed subtle but consistent increases in HspA1A’s refolding activities. Furthermore, using a Lysine-71-Arginine mutation (K71A; a null-ATPase mutant) of HspA1A we show that although K71A binds to PS with affinities similar to the WT, the kinetics of the binding are significantly different, probably because of the mutant’s inability to achieve specific conformations. These observations suggest a two-step binding model that includes conformational changes and strongly support the notion that the chaperone and lipid-binding activities of HspA1A are dependent but the regions mediating these functions do not overlap. These findings provide the basis for future interventions to inhibit HspA1A’s PM-translocation in tumor cells, making them sensitive to radiation therapy.

We analyzed the affinity-proteomics data of saliva absorbed to plate-bound Spike protein of SARS-CoV-2, and identified major virus-binding proteins as MUC7, MUC5B, DMBT1, and neutrophil defensins. Furthermore, we found that saliva from healthy donors inhibited the binding of Spike-protein-specific polyclonal antibodies to Spike antigen. These data suggest that the Spike protein’s glycoprotein-binding domains (GBD) may be targeted to block virus adherence or entry of SARS-CoV-2.

Gold clusters protected by 3-MBA ligands (MBA = mercaptobenzoic acid, -SPhCO2H) have attracted recent interest for their unusual structures and advantageous ligand-exchange and bioconjugation properties. Azubel et al. first determined the core structure of an Au68-complex, which was estimated to have 32 ligands (3-MBA groups). To explain the exceptional structure-composition and reaction properties of this complex, and its larger homologs, Tero et al. proposed a “dynamic stabilization” via carboxyl O-H--Au interactions. Herein, we report the first results of an integrated LC/MS analysis of unfractionated samples of gold / 3-MBA clusters, spanning the narrow size range 13.4 to 18.1 kDa. Using high-throughput procedures adapted from bio-macromolecule analyses, we show that integrated capillary HPLC-ESI-MS, based upon aqueous-methanol mobile phases and ion-pairing reverse-phase chromatography, can separate several major components from the nanoclusters mixture that may be difficult to resolve by standard native gel electrophoresis due to their similar size and charge. For each component, one obtains a well-resolved mass spectrum, nearly free of adducts or signs of fragmentation. A consistent set of molecular mass determinations is calculated from detected charge-states tunable from 3- (or lower), to 2+ (or higher). One thus arrives at a series of new compositions (n, p) specific to the Au/3-MBA system. The smallest major component is assigned to the previously unknown (48, 26); the largest one is evidently (67, 30), vs. the anticipated (68, 32). Various explanations for this discrepancy are considered. A prospective is given for the several members of this novel series, along with a summary of the advantages and present limitations of the micro-scale integrated LC/MS approach to characterize such metallic-core macro-molecules, and their derivatives.

The recognition of (1→3)-β-D-glucans (BGs) by β-1,3-D-glucan recognition protein (BGRP) found in invertebrates plays a significant role in the activation of toll pathway and pro-phenol oxidase system in insect host defense against fungal invasion. To examine the structural diversity of BGs in BGRP interaction, the binding specificity of BGRPs cloned from four different insectswas characterized using ELISA. Recombinant BGRPs expressed as Fc-fusion proteins of human IgG1 bound to solid phase BGs. Because of the binding specificities, the BGRPs were categorized into two different ultrastructure- binding characters. The BGRPs from Silkworm and Indian meal moth bound to BGs containing triple-helical structure. Other BGRPs from red flour beetle and yellow mealworm beetle showed no binding to triple-helical BGs, but to alkaline-treated BGs, which have partially opened helical conformation. These evidences suggest that the innate immune system distinguishes different BG conformations and it is equipped for the diversity of BG structures.

Bacterial pathogens have been attributed to poultry housing structure, financial strength, and incessant use of antibiotics, variable seasons and management systems practiced. Variant forms of bacterial pathogens can be detected by recognizing the molecular pattern of the pathogens through an innate immune mechanism such as mannose-binding lectin. Mannose-binding lectin (MBL) possesses an innate pattern recognition molecule that easily sequestered to region of infections and inflammations. This works by attaching itself to antigen surface thus hinders proliferation and disease activity in the host organism. Baker’s method, nephelometric assays technique, Enzyme-Linked Immunosurbent Assay technique, Polymerase Chain Reaction, Deoxyribonucleic Acid typing and other biotechnology related methods are techniques used in detecting and quantifying MBL. Mannose-binding lectin levels in serum can be influenced by age, management systems, feed formulation strategies and seasons. Therefore, knowledge of MBL should be encouraged in all aspect of poultry production, in order to discourage incessant use of drugs at a slight exposure to prevailing bacterial which can help in maximizing cost.

Aflatoxins in feeds cause great health hazards to animals and in advance, to human. Potential of crude clays designated AC, KC, CC and MC and ashes VA and RA were evaluated for their capacity to adsorb aflatoxins B₁ (AFB₁), B₂ (AFB₂), G₁ (AFG₁) and G₂ (AFG₂) relative to a commercial binder Mycobinder^R (Evonik Industries AG) using in-vitro technique. On average, CC, VA, KC, MC, AC, RA and Mycobind^R adsorbed 39.9%, 51.3%, 61.5%, 62.0%, 72.6%, 84.7% and 98.1% of the total aflatoxins in buffered solution, respectively. The capacity of AC and RA was statistically (p<0.05) better in binding aflatoxins next to Mycobind^R. Capacity of the TBM and Mycobind^R to bind aflatoxins, seemed to follow the trend of their cation exchange capacity (CEC). The CEC (meq/100g) of CC, MC, KC, VA, AC, RA and Mycobind^R were 7.0, 15.4, 18.8, 25.4, 27.2, 27.2 and 38.9, respectively. On average 96.3%, 42.7%, 80.8% and 32.1% of AFB1, AFB2, AFG1 and AFG2 were adsorbed, respectively. Binding capacity of the clays and ashes relative to Mycobind^R was about 100% for AC and RA, 50% for KC, MC and VA and 33.3% for CC. The AC and RA seem to be promising resources in binding aflatoxins in solution.

Ice-binding proteins (IBPs) have several functions that permit their hosts to thrive in the presence of ice. The ability of IBPs to control ice growth makes them potential additives in various industries ranging from food storage and cryopreservation to anti-icing systems. For IBPs to be used in commercial applications, however, methods are needed to produce sufficient quantities of high-quality proteins. Here, we describe a new method for IBP purification, termed falling water ice purification (FWIP). The method is based on the affinity of IBPs for ice. A crude IBP solution is allowed to flow continuously over the large chilled vertical surface of a commercial ice machine. The temperature of the surface is lowered gradually until ice crystals are produced, to which the IBPs bind but other solutes do not. As in other ice affinity methods, FWIP does not require molecular tags and is suitable for purifying recombinant IBPs as well as IBPs from natural sources. The advantage of FWIP over other ice affinity methods is that it exploits an ice machine designed to produce large volumes of clear ice daily. This system can be easily scaled up and suits the purification of industrial quantities of IBPs. The FWIP method significantly advances the use of IBPs in research and industry.

In view of the problem that the output thrust of solenoid actuator is affected by various factors and is difficult to calculate in actual working conditions, this paper proposes a semi-analytical model constructed by magnetic field subdomain method with internal and external boundary conditions in cylindrical coordinate system for calculation, and the general solution equations of magnetic vector potential for each subdomain are derived and solved by MATLAB. Taking a push-pull electromagnet as an example, the finite element simulation and experimental comparative analysis are carried out. The correctness and applicable conditions of the subdomain method are illustrated by comparing the gradient plot of magnetic vector potential, inductance curve and electromagnetic force. By calculating the output thrust after considering the core gravity, spring force and electromagnetic force, it is shown that this method has the advantage of computational flexibility compared with the finite element method, and it is easier to write special algorithms according to various working conditions to calculate the important parameters in engineering applications.

Because data on the fungal gut community structure of African children are scarce, we aimed to describe by reanalysing rRNA ITS1 and ITS2metabarcoding data from a study designed to assess the influence of microbiota in malaria susceptibility in Malian children from the Dogon country. More specifically, we aimed to establish the core gut mycobiome and compare the gut fungal community structure of breastfed children, aged 0-2 years, with other age groups. Briefly, DNA was extracted from 296 children’s stool samples. Both rRNA ITS1 and ITS2 genomic barcodes were amplified and subjected to Illumina MiSeq sequencing. The ITS2 barcode generated 1,975,320 reads and 532 operational taxonomic units (OTUs), while the ITS1 barcode generated 647,816 reads and 532 OTUs. The alpha diversity was significantly higher by using the ITS1 compared to the ITS2 barcode (p

To win a taekwondo competition, more points must be scored, and the key to scoring points is to improve the motor performance of the kick. The wing kick is an offensive and defensive maneuver. Core stability appears to be important for improving athletic performance, but the specific relationship and effect of core stability on athletic performance in the aerial phase of taekwondo is unclear. The aim of this study was to investigate the relationship between core stability and athletic performance in taekwondo in order to provide appropriate theoretical support for training and to help coaches and athletes to improve athletic performance. A total of 16 subjects (height: 167.34±9.2 cm; weight: 61±8.96 kg; age: 24.7±3.25 years) were studied. Data were captured using 13 infrared cameras at 120Hz, kinematic and kinetic data were captured using a motivated motion capture system, and the data were exported to Visual3D in order to calculate the execution time of the aerial phase, the angular momentum of the left lower extremity, and MVC analysis of the EMG using EMG works. The core stability level of the subjects were measured using the Sahrmann Core Stability Test (SCST) to correlate with the other data, and then the subjects were grouped according to their core stability levels and the data from both groups were analyzed with t-tests. Results During the double fly lifting of aerial segments, SCST levels showed a very strong negative correlation with execution time (r= -0.739) and there was a statistically significant difference in execution time between high and low SCST levels (p &lt; 0.001), and the desired negative correlation was also seen in lower limb angular momentum X-axis (thigh r= -0.6294, shank r= -0.536, foot r= -0.6175), especially in the X-axis. The left rectus femoris (LRF) data had greater activation in the low SCST group(p=0.0019*). Through this experiment, we found that athletes with high core stability had faster execution times, lower angular momentum, and higher core muscle activation. Therefore, we conclude that incorporating core stability training into taekwondo training has the potential to improve kicking performance.

The issue of optimising the initial stand density (ISD) of tree plantations has high practical importance. The objective of this study was to nondestructively evaluate the influence of the initial stand density of Scots pine plantations located in the European part of the Russian Federation on wood basic density (BD), moisture content (MC), ultrasound velocity (UV), latewood content, and drilling resistance (DR). 45-year-old trees with stand densities of 500, 1000, 3000, 5000, and 10000 trees/ha were tested by a 5-cm-long core sample for gravimetric MCGM and BD, by PULSAR-2.2 for UV along the height (UVH) and through the tree trunk diameter (UVD), by the IML-RESI PD-400 tool for DR, and by GANN HT 85T for MC based on the electrical resistance method (MCERM). A significant influence of ISD was found on DBH, UVD, MCGM, and MCERM. ISD had no significant impact on BD, UVH, and DR. The wood BD ranged from 356 to 578 kg/m-3, with a mean value of 434±3.3 kg/m-3, and was restricted by the soil and environmental factors. DBH and 70% MCERM were good indicators of tree vitality. Linear correlations between DBH and MCERM (R2=0.67), DBH and MCGM (R2=0.74), DR and BD (R2=0.71), and the two-factor model MCGM=f(DBH, BD), (R2=0.76) were found.

The thermal conductivity of the products of the interaction of molten core with concrete was derived using number theory. A formula has been found that describes the thermal conductivity of ZrO₂, ZrSiO₄, (U,Zr)SiO₄ and UO₂ over a wide temperature range. Formula is expressed in terms of the atomic numbers of elements, their valencies, the crystal structure of substances, and the thermal conductivities of individual chemical elements of the corium.

The Sun is a huge gaseous body. However, we cannot observe events in the inner Sun due to the convection zone opacity according to previous models. Therefore, the flares originate from the front surface of the Sun. But the current study relied on the distance distribution of X-Ray solar flares, which concluded that the inner layers have much lower opacity than expected. It is even less than what was expected by the latest models based on helioseismology. This means that the flares may originate from the solar interior or solar core, and perhaps from the backside surface, and even appear to us from the frontside surface. Which the re-estimate and correct the currently listed solar flare’s location is needed. Additionally, the flare’s distance illustrations the solar interior layers and appears their boundaries from the core to the photosphere. This method allows us to monitor the variation of the core’s radius with time. The model of the flare’s distance has been developed in current study. But this needs to redevelopment after re-estimating the solar flares locations.

One of the potential sources of rare-earth elements (REEs) is the solid waste from alumina industry - bauxite residue, known as “red mud” (RM). The main REEs from the raw bauxite are concentrated in RM after the Bayer leaching process. The earlier worldwide studies were focused on the scandium (Sc) extraction from RM by concentrated acids to enhance the extraction degree. This leads to the dissolution of major oxides (Fe2O3 and Al2O3) from RM. This article studies the possibility of selective Sc extraction from alkali fusion red mud (RMF) by diluted nitric acid (HNO3) leaching at pH ≥ 2 to prevent co-dissolution of Fe2O3. RMF samples have been analyzed by X-ray fluorescence spectrometry (XRF), X-ray diffraction (XRD), electron probe microanalysis (EPMA), and inductively coupled plasma mass spectrometry (ICP-MS). Sc extraction has been found to be 71.2 % at RMF leaching by HNO3 at pH=2 and at 80 °C during 90 min. The kinetic analysis of experimental data by the shrinking core model has shown that Sc leaching process is limited by the interfacial diffusion and the diffusion through the product layer. The apparent activation energy (Ea) was 19.5 kJ/mol. We have established that according to EPMA of RMF, Sc is associated with iron minerals; it could act as the product layer. The linear dependence of Sc extraction of magnesium (Mg) extraction has been revealed. This fact indicates that Mg can act as a leaching agent of Sc presented in RMF by ion-exchangeable phase.

New series of compounds containing both heterocycle moieties and pseudo-symmetric hydroxyethylamine core were obtained using a simple synthetic path that can provide a library of compounds in few steps and high yields. Furthermore, diversity-oriented synthesis was studied to change different functionalities according to needs. The in vitro inhibition activity against recombinant HIV-1 protease was evaluated. A beneficial effect of this class of compounds can be obtained either for the presence of a bis-benzyl group into the core and for the heterocyclic moiety in P1, specifically the indole ring. Docking analysis was also reported.

This paper discusses the basic concepts of phase dislocations and vortex formation in the electric fields of fundamental air core mode of hollow core waveguides with specific types of rotational symmetry of the core – cladding boundary. Analysis of the behavior of the electric field phase in the transmission bands shows that the mechanism of light localization in the hollow core waveguides with discrete rotational symmetry of the core – cladding boundary cannot be completely described by the ARROW model. For an accurate description of the phase behavior, it is necessary to account for phase jumps of the magnitude of π when passing through the phase dislocations.

We prepared poly(3,4-ethylenedioxythiophene) (PEDOT)-coated sulfonated polystyrene copolymer particles as efficient heat-shielding agents, which showed strong near-infrared (NIR) absorption, with high solid contents and good solution stability. The poly(styrene sulfonate -co-styrene) (P(SS-co-St)) copolymers were successfully synthesized via radical solution polymerization, and PEDOT-coated P(SS-co-St) (PEDOT:P(SS-co-St)) was synthesized via Fe⁺-catalyzed oxidative polymerization. PEDOT:P(SS-co-St) was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopies. The particle size and morphology of PEDOT:P(SS-co-St) were examined using transmission electron microscopy, dynamic light scattering, and zeta potential measurements. The maximum NIR-shielding efficiency of the film was 92.0% with 40% transmittance. The high solution stability of PEDOT:P(SS-co-St) make it an ideal candidate for heat-insulating materials that find application in semi-transparent heat-insulator-coated windows.

In this paper, a novel pendulum-type accelerometer based on hetero-core fiber optics has been proposed for structural health monitoring targeting large-scale civil infrastructures. Vibration measurement is a non-destructive method for diagnosing the failure of structures by assessing natural frequencies and other vibration patterns. The hetero-core fiber optic sensor utilized in the proposed accelerometer can serve as a displacement sensor with robustness to temperature changes in addition to immunity to electromagnetic interference and chemical corrosions. Thus the hetero-core sensor inside the accelerometer measures applied acceleration by detecting the rotation of an internal pendulum. A series of experiments showed that the hetero-core fiber sensor linearly responded to the rotation angle of the pendulum ranging within ±5°, and furthermore the proposed accelerometer could reproduce the waveform of input vibration in a frequency band of several Hz order.

Clay ball is a pavement surface defect which refers to a clump in which clay or dirt is mixed with hot asphalt mixture. Clay ball is typically caused by a combination of aggregate contamination of clay or soil, high aggregate moisture, and low production temperature at the asphalt plant. It usually appears a few weeks or months after paving under traffic load, after being liquefied and knocked from the pavement surface. Clay balls can be the source of potholing, raveling, and other issues such as moisture infiltration and reduced ride quality. This paper presents an investigation of the clay balls on US-31 one winter after construction in Hamilton County, Indiana. In order to understand the pavement condition, their severity was measured using both visual observation and infrared image collection system. In addition, a clay ball distribution pattern, its density, and cores condition were evaluated. A precipitation effect on clay ball formation was investigated for finding a cause of the clay balls. The investigation found that infrared image collection system was appropriate in detecting the clay balls. The clay balls were elliptic in shape with 1 inch to 4 inches in diameter, and the maximum clay ball depth is almost penetrating the entire surface course. It was also found that the asphalt paving on the raining days or right after raining could increase the potential of clay balls. Monitoring of aggregate moisture during construction on or after raining days should be able to reduce the risk of clay balls.

China’s leading development of a complete battery value chain for Electric Vehicles (EV) is restructuring the global automotive sector. The competitive advantage of China's EV battery industry lies on its firms’ core competency and political economic geography. Based on first-hand empirical material and data obtained from years of fieldwork in an EV battery cluster in South China, this paper identifies what the Chinese EV battery industry’s core competency is and details how it is built up from below. The current core competency of Chinese battery firms is their mass manufacturing capability to supply lithium-ion batteries vehicle manufacturers (OEMs) with stable and consistent quality as well as competitive prices. This competency is acquired by firms through technological learning at workshop level while taking use of their experiences accumulated in mass production of batteries for consumer electronics sectors. Furthermore, the rapid learning and accumulation of knowledge on battery manufacturing at large scale is also facilitated by the industrial cluster environment where firms are embedded. Supported and promoted by local government policies, Chinese EV battery clusters are composed of firms from different segments of a complete battery value chain. The findings illuminate the likely strategic strengths, weaknesses, and futures of the Chinese EV battery industry in global competition.

To enhance the overall reliability of the power system, engineers have redirected their focus toward health monitoring and early detection of faults in transformers. Among these faults, transformer core defects demand particular attention. While fault simulation using software has traditionally been the preferred approach, these methods suffer from data inaccuracies in real-world conditions. Consequently, conducting actual experimental setups with induced faults is imperative to investigate core issues. This study uses Hilbert Transform (HT) as a signal processing technique to extract crucial data characteristics, thereby enhancing the performance of the classifier model. The research involves analyzing electric current signals from a single-phase 1kVA transformer. A comparative assessment of our proposed model was conducted using raw data and Fast Fourier Transform (FFT), evaluating accuracy, precision, recall, F1-score, and computational time. The results demonstrate a significant improvement in all metrics for the classifier models, particularly the k-nearest neighbor (KNN) algorithm, which exhibited values of 83.89%, 84.39%, 83.89%, 83.79%, and 0.0156 seconds, respectively. Future work aims to extend this analysis under different loading conditions.

In this work, we demonstrate the preparation of easy-to-fabricate nanogranular, strontium ferromolybdate/strontium molybdate core-shell ceramics and examine their properties including tunnel magnetoresistance, magnetic field sensitivity and temperature coefficient of the tunnel magnetoresistance. The tunnel magnetoresistance of nanogranular, strontium ferromolybdate/strontium molybdate core-shell ceramics was modeled yielding values suitable for magnetoresistive sensor application. Such structures possess a narrow peak of magnetic flux sensibility located at about 125 mT. For magnetic flux measurement, single domain granules with superparamagnetic behavior should be applied. The predicted TMR magnetic flux sensitivities for granules with superparamagnetic behavior amount to about 7.7 % per T and 1.5 % per T for granules sizes of 6.8 nm and 4 nm, respectively. A drawback of the tunnel magnetoresistance of such nanogranular core-shell ceramics is the unacceptable large value of the temperature coefficient. Acceptable values, lower than 2 % per K, are obtained only at low temperatures (less than 100 K) or large magnetic flux densities (exceeding 6 T). Therefore, a Wheatstone bridge configuration should be adopted for magnetoresistive sensors design to compensate the effect of temperature.

Complex-structured polymeric microparticles hold significant promise as advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or have limited control over particle size distribution and cargo release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters. The concept behind this method involves the deposition of a specific number of polymer layers on a substrate with low surface energy. Each layer can serve as either the carrier for cargo or a programmable shell-former with predefined permeability. Subsequently, this layered structure is precisely cut into desired-sized blanks using a laser. The manufacturing process is completed by applying of heat to the substrate what results on sealing the edges of the blanks. The combination of the high surface tension of the molten polymer and the low surface energy of the substrate enables the formation of discrete particles, each possessing semi-spherical or other designed geometries determined by their internal composition. Such anisotropic microparticles are envisaged versatile applications.

Water pollution with dyes is a critical environmental issue because off the huge amount of dyes disbarred annually which cause severe damage for the ecosystem and human life. On the other hand, the core-shell based magnetic materials have showed amazing character for controlling the material synthesis with targeted structure to enhance the adsorptive-removal of pollutants. Herein, Fe3O4 core-TiO2/mesoSiO2 and Fe3O4 core-mesoSiO2/TiO2 double shell nanoparticles were prepared by first (R1) and second (R2) routes. The preparation procedure is controlled to prepare the magnetic core with further coating layers from silica and titania for the uptake of methylene blue from aqueous solutions. The reported adsorption capacities for R1-0.2, R1-0.4 and R2 samples were 46, 38 and 50 mg/g respectively at pH 6 after 80 min contact time form 50 ppm methylene blue solution. The adsorption process of methylene blue onto Fe3O4core-meso SiO2/TiO2 double shell was well fitted with the pseudo-second-order kinetic model and Freundlish isotherm which suggested the quick and multilayer adsorption mechanism. In addition, results of thermodynamic investigation indicated that the surfaces of Fe3O4 core-mesoSiO2/TiO2 and Fe3O4 core-TiO2/mesoSiO2 double shell exhibit spontaneous tendency to adsorb methylene blue from the aqueous solutions. These results will encourage the further application of Fe3O4 core-meso SiO2/TiO2 and Fe3O4 core-TiO2/meso SiO2 double shell for removal of other dyes and pollutants from wastewater.

We investigated experimentally, analytically and numerically the formation process of double emulsion formations under dripping regime in a tri-axial co-flow capillary device. The results show that mismatches of core and shell droplets under a given flow condition can be captured both experimentally and numerically. We propose a semi-analytical model using the match ratio between the pinch-off length of the shell droplet and the product of the core growth rate and its pinch-off time. The mismatch issue can be avoided if the match ratio is lower than unity. We considered a model with the wall effect to predict the size of the matched double emulsion. The model shows slight deviations with experimental data if the Reynolds number of continuous phase is lower than 0.06, but asymptotically approaches to good agreement if the Reynolds number increases from 0.06 to 0.14. The numerical simulation generally agrees with the experiments under various flow conditions.

The construction of random fillings from the excavation of medium hardness rocks, with high particle sizes, presents limitations in compaction control. This research applies new control techniques with revised test procedures in the construction of the random fillings core, which constitutes the main part of the embankment, with the bigger volume and provides the geotechnical stability to the infrastructure. The maximum layer thickness researched was 800mm. As there are many types of rocks, this research is applied to metamorphic slates. Quality control has been carried out by applying new research associated with the revision of wheel impression test, topographic settlements and plate bearing test (PBT). A statistical analysis of the core of 16 slate random fillings has been carried out, with a total of 2250 in situ determination of density and moisture content, 75 wheel impression tests, 75 topographic settlement control and 75 PBT. The strong associations found between different tests have allowed to simplify the quality control.

We report the effect of doping Cd1-xZnxS/ZnS core/shell quantum dot (CSQDs) in nematic liquid crystal p-methoxybenzylidene p-decylaniline (MBDA) at 0.05 wt/wt%, 0.1 wt/wt%, 0.15 wt/wt%, 0.2 wt/wt%, 0.25 wt/wt% and 0.3 wt/wt% concentrations of CSQDs in MBDA. Dielectric parameters with and without bias with respect to frequency has been investigated. The change in electro - optical parameters with temperature has also been demonstrated. The increase in the mean dielectric permittivity has been found due to large dipole moment of CSQDs which impose stronger interactions with the liquid crystal molecules. The dielectric anisotropy changes sign on doping CSQDs in MBDA liquid crystal. It was concluded that the CSQDs doping noticeably increases the dielectric permittivity of nematic MBDA in the presence of electric field. The doping of CSQDs in nematic MBDA liquid crystal reduces the ion screening effect effectively. This phenomenon is attributed to the competition between the generated ionic impurities during assembling process and the ion trapping effect of the CSQDs. The rotational viscosity of nematic liquid crystal decreases with increasing concentration of the CSQDs with faster response time observed for 0.05 wt/wt% concentration. The birefringence of the doped system increases with the inclusion of CSQDs in MBDA. These results find application in the field of display devices, phase shifters, industries and projectors.

Bacteria currently included in Rhizobium leguminosarum are too diverse to be considered a single species, so we can refer to this as a species complex (the Rlc). We have found 429 publicly available genome sequences that fall within the Rlc and these show that the Rlc is a distinct entity, well separated from other species in the genus. Its sister taxon is R. anhuiense. We constructed a phylogeny based on concatenated sequences of 120 universal (core) genes, and calculated pairwise average nucleotide identity (ANI) between all genomes. From these analyses, we concluded that the Rlc includes 18 distinct genospecies, plus 7 unique strains that are not placed in these genospecies. Each genospecies is separated by a distinct gap in ANI values, usually at around 96% ANI, implying that it is a 'natural' unit. Five of the genospecies include the type strains of named species: R. laguerreae, R. sophorae, R. ruizarguesonis, "R. indicum" and R. leguminosarum itself. The 16S ribosomal RNA sequence is remarkably diverse within the Rlc, but does not distinguish the genospecies. Partial sequences of housekeeping genes, which have frequently been used to characterise isolate collections, can mostly be assigned unambiguously to a genospecies, but alleles within a genospecies do not always form a clade, so single genes are not a reliable guide to the true phylogeny of the strains. We conclude that access to a large number of genome sequences is a powerful tool for characterising the diversity of bacteria, and that taxonomic conclusions should be based on all available genome sequences, not just those of type strains.

High-resolution laboratory-based thermal infrared spectroscopy is an up-and-coming tool in the field of geological remote sensing. Its spatial resolution allows for detailed analyses at centimeter to sub-millimeter scale. However, this increase in resolution creates challenges with sample characteristics such as grain size, surface roughness and porosity that can influence the spectral signature. This research explores the effect of rock sample surface preparation on the TIR spectral signatures. We applied three surface preparation methods (split, saw and polish) to determine how the resulting differences in surface roughness affects both the spectral shape as well as the spectral contrast. The selected samples are a pure quartz sandstone, a quartz sandstone containing a small percentage of kaolinite, and an intermediate-grained gabbro. To avoid instrument or measurement type biases we conducted measurements on three TIR instruments, resulting in directional hemispherical reflectance spectra, emissivity spectra and bi-directional reflectance images. Surface imaging and analyses were performed with scanning electron microscopy and profilometer measurements. We demonstrate that surface preparation affects the TIR spectral signatures influencing both the spectral contrast as well as the spectral shape. The results show that polished surfaces predominantly display a high spectral contrast while the sawed and split surfaces display up to 25% lower reflectance values. Furthermore, the sawed and split surfaces display spectral signature shape differences at specific wavelengths, which we link to mineral transmission features, surface orientation effects and multiple reflections in fine-grained minerals. Hence, the influence of rock surface preparation should be taken in consideration to avoid an inaccurate geological interpretation.

Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.e., different faces of the same coin) it seems rational to consider targeting of Pol I or, more generally, rRNA synthesis for treatment of disorders associated with the death of terminally differentiated neurons. Principally, ribosomes synthesize proteins and, accordingly, Pol I can be considered the starting point for protein synthesis. Given that cellular accumulation of abnormal proteins such as α-synuclein and tau is an essential feature of neurodegenerative disorders such as Parkinson disease and fronto-temporal dementia, reduction of protein production is now considered as a viable target for treatment of these and closely related neurodegenerative disorders. Abnormalities in polymerase I activity and rRNA production may also be associated with nuclear and nucleolar stress, DNA damage, and childhood onset neuronal death as is the case for the UBTF E210K neuroregression syndrome. Moreover, restraining the activity of Pol I may be a viable strategy to slow aging. Before starting down the road of Pol I inhibition for treating non-cancerous disorders of the nervous system, many questions must be answered. First, how much Pol I inhibition can neurons tolerate and for how long? Should inhibition of Pol I be continuous or pulsed? Will cells compensate for Pol I inhibition by upregulating the number of active rDNAs? At present, we have no effective and safe disease modulatory treatments for Alzheimer disease, α-synucleinopathies, or tauopathies, and novel therapeutic targets and approaches must be explored.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

A defining feature of a productive infection is the co-opting of host cell resources for viral replication. Despite their repertoire of molecular functions, viruses subvert host defenses to take control of cellular factors such as RNA binding proteins (RBPs). RBPs are involved in virtually all steps of mRNA life forming ribonucleoprotein complexes (mRNPs) in a highly ordered and regulated process to control RNA fate and stability in the cell. Thus, the hallmark of this viral takeover is to reshape RNA fate in the cell to modulate host gene expression and evade immune responses. Here we provide an extensive review of work in this area, particularly how the host-viral interplay influences RBP functions to modulate the host cell. Overall, in this review, we highlight the myriad of ways RBPs can regulate RNA stability in either a pro-viral or antiviral manner by gathering novel insights gained from research studies in this field.

(1) Background: To fight for COVID-19 pandemic, immunity against SARS-CoV-2 should be achieved not only through natural infection but also vaccination. Controversies exist about the effect of COVID-19 vaccination on previously infected persons; (2) Methods: A prospective cohort was undergone to collect sera from unvaccinated survivors and vaccinated persons--with and without COVID-19 pre-infection. The sera were analyzed for the anti-Receptor Binding Domain (RBD) titers by ELISA and for the capacity to neutralize the pseudovirus of the Wuhan-Hu-1 strain by luciferase assays; (3) Results; Neither the antibody titers nor the neutralization capacity was significantly different between the three groups. However, the correlation between the antibody titers and the percentage of viral neutralization derived from sera of unvaccinated survivors was higher than that from vaccinated persons with pre-infection (Spearman correlation coefficient (r) = -0.8558; 95% CI, -0.9259 to -0.7288), p &lt;0.0001 vs -0. 581; 95% CI, -0.7679 to -0.3028; p = 0.0002, respectively), indicating the capacity to neutralize the virus is better among the unvaccinated individuals. (4) Conclusions: Vaccines induced anti-RBD titers as high as the natural infection with lower neutralization capacity, and it did not boost the immunity in pre-infected persons.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

Climate change and globalization have raised the risk of vector-borne disease (VBD) introduction and spread in various European nations in recent years. In Italy, viruses carried by tropical vectors have been shown to cause viral encephalitis, one of the symptoms of arbovirosis, a spectrum of viral disorders spread by arthropods such as mosquitoes and ticks. Arbovirosis are currently causing alarm and attention, and the World Health Organization (WHO) has released recommendations to adopt essential measures, particularly during the hot season, to restrict the spreading of the infectious agents among breeding stocks. In this scenario, rapid analysis systems are required, because they can quickly provide information on potential virus-host interactions, the evolution of the infection, and the onset of disabling clinical symptoms, or serious illnesses. Such systems include bioinformatics approaches integrated with molecular evaluation. Viruses have co-evolved different strategies to transcribe their own genetic material, by changing the host's transcriptional machinery, even in short periods of time. The introduction of genetic alterations, particularly in RNA viruses, results in a continuous adaptive fight against the host's immune system. We suggest an in silico pipeline method to unravel viral sequences that may interact with host RNA binding proteins (RBPs), which play important roles in RNA metabolism and its several related biological processes. Indeed, viral RNA sequences, able to bind host RBPs may compete with cellular RNAs, altering important metabolic processes. Our findings suggest that the proposed in silico approach, could be a useful and promising tool to investigate the complex and multiform clinical manifestations of viral encephalitis, and possibly identify altered metabolic pathways as targets of pharmacological treatments and innovative therapeutic protocols.

All living organisms require some metal ions for their energy production as well as metabolic and biosynthetic processes. Within cells, metal ions are involved in the formation of adducts interact with metabolites and macromolecules (proteins and nucleic acids). The proteins that require binding to one or more metal ions to be able to carry out their physiological function are called metalloproteins. About one third of all protein structures in the Protein Data Bank involve metalloproteins. Over the past few years there has been a tremendous progress in the number of computational tools and techniques making use of 3D structural information to support the investigation of metalloproteins. This trend has been boosted also by the successful applications of neural networks and deep learning approaches in molecular and structural biology at large. In this review, we discuss recent advances in the development and availability of resources dealing with metalloproteins from a structure-based perspective. We start by addressing tools for the prediction of metal-binding sites (MBSs) using structural information on apo-proteins. Then, we provide an overview of methods for and lessons learned from the structural comparison of MBSs in a fold-independent manner. We then move to describing databases of metalloprotein/MBS structures. Finally, we summarize recent DL applications enhancing the functional interpretation of metalloprotein structures.

Prediction of protein-ligand binding affinities is crucial for computational drug discovery. A number of deep learning approaches have been developed in recent years to improve the accuracy of such affinity prediction. While the predicting power of these systems have advanced to some degrees depending on the dataset used for model training and testing, the effects of the quality and quantity of the underlying data have not been thoroughly examined. In this study, we employed erroneous datasets and data subsets of different sizes, created from one of the largest databases of experimental binding affinities, to train and evaluate a deep learning system based on convolutional neural networks. Our results show that data quality and quantity do have significant impacts on the prediction performance of trained models. Depending on the variations in data quality and quantity, the performance discrepancies could be comparable to or even larger than those observed among different deep learning approaches. In particular, the presence of proteins during model training leads to a dramatic increase in prediction accuracy. This implies that continued accumulation of high-quality affinity data, especially for new protein targets, is indispensable for improving deep learning models to better predict protein-ligand binding affinities.

Thyroid hormones regulate tissue metabolism establishing an energy balance in the cell, in particular by affecting oxidative phosphorylation. Their long-term impact is mainly associated with changes in gene expression, while the short-term effects may differ in mechanism. Our work is devoted to short-term effects of hormones T2, T3, and T4 on mitochondrial cytochrome c oxidase (CcO) mediated by a direct contact with the enzyme. The data obtained indicate the existence of two separate sites of CcO interaction with thyroid hormones differing in location, affinity and specificity to hormone binding. It is shown that T3 and T4 but not T2 inhibit oxidase activity of CcO in solution and on membrane preparations with Кi≈100–200 M. In solution, T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside for binding to the enzyme. Peroxidase and catalase partial activities of CcO are not sensitive to hormones while electron transfer from heme a to the oxidized binuclear center is affected. We believe that T3 and T4 are ligands of the Bile Acid Binding Site found in the 3D structure of CсO by Ferguson-Miller’s group, and hormone induced inhibition is associated with dysfunction of the K- proton channel. Similar conclusion we made recently with regard to steroid-like compounds. It is found that T2, T3, and T4 inhibit superoxide generation by oxidized CcO in the presence of excess Н2О2. Inhibition is characterized by Ki values of 0.3 – 5 M and apparently affects the formation of О2• at the protein surface. The second binding site for thyroid hormones presumably coincides with the point of tight T2 binding on the Va subunit described in the literature.

The proper regulation of RNA processing is critical for muscle development and the fine-tuning of contractile ability between muscle fiber-types. RNA binding proteins (RBPs) regulate the diverse steps in RNA processing including alternative splicing, which generates fiber-type specific isoforms of structural proteins that confer contractile sarcomeres with distinct biomechanical properties. Alternative splicing is disrupted in muscle diseases such as myotonic dystrophy and dilated cardiomyopathy, and is altered after intense exercise as well as with aging. It is therefore important to understand splicing and RBP function, but currently only a small fraction of the hundreds of annotated RBPs expressed in muscle have been characterized. Here we demonstrate the utility of Drosophila as a genetic model system to investigate basic developmental mechanisms of RBP function in myogenesis. We find that RBPs exhibit dynamic temporal and fiber-type specific expression patterns in mRNA-Seq data and display muscle-specific phenotypes. We performed knockdown with 105 RNAi hairpins targeting 35 RBPs and report associated lethality, flight, myofiber and sarcomere defects, including flight muscle phenotypes for Doa, Rm62, mub, mbl, sbr, and clu. Interestingly, knockdown phenotypes of spliceosome components, as highlighted by phenotypes for A-complex components SF1 and Hrb87F (hnRNPA1), revealed level- and temporal-dependent myofibril defects. We further show that splicing mediated by SF1 and Hrb87F is necessary for Z-disc stability and proper myofibril development, and strong knockdown of either gene results in impaired localization of Kettin to the Z-disc. Our results expand the number of RBPs with a described phenotype in muscle and underscore the diversity in myofibril and transcriptomic phenotypes associated with splicing defects. Drosophila is thus a useful model to gain disease-relevant insight into cellular and molecular phenotypes observed when expression levels of splicing factors, spliceosome components and splicing dynamics are altered.

Bacteria a Microscopic organisms are the most inexhaustible and flexible of microorganisms and constitute a huge division of the whole living earthly biomass, certain microorganisms were found to amass metallic components at a high limit Was Known as Bacterial Bio-sorption Due to their little size, capacity to become under controlled conditions, and their Accommodation to an extensive variety of ecological situations; Potent metal bio-sorbents among microorganisms, at low pH esteems, cell divider ligands are protonated and contend essentially with metals for official. With expanding pH, more ligands, such as amino and carboxyl groups, could be exposed, leading to attraction between these negative charges and the metals, and consequently increment bio-sorption onto the cell surface. Starting with Isolation and identification of heavy metal-resistant bacteria from rock Ore. Studying Factors Affecting Uranium Bio-sorption, Optimization of bacterial growth conditions and optimum for metal uptake by free and immobilized bacterial cells and Desorption ratio of uranium ions adsorbed by Coli. /alginate, All this evidence suggest that functions groups Represented in our study are responsible for metal uptake in our bacterial biomass beside change in peaks position which assigned for it's groups confirm bio-sorption of metal ions from waste due to ions charge interaction comparing with immobilized we found increase in no of binding sites indicate that immobilized bacterial have high efficiency for metal up take which also change in peaks position which assigned for its groups confirm bio-sorption of metal ions from waste due to ions charge interaction, Where the high bio-sorption yield obtained by bacteria, the Uranium & heavy metal bioremediation process expects microorganisms to be joined to a strong surface.

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper spindle architecture is established by a set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 motors are essential for this process, and genetic or chemical inhibition of their activity leads to the emergence of monopolar spindles and cell death. However, these deficiencies can be rescued by simultaneous inactivation of kinesin-14 motors, as they counteract kinesin-5. We conducted detailed genetic analyses in fission yeast to understand the mechanisms driving spindle assembly in the absence of kinesin-5. Here we show that deletion of the nrp1 gene, which encodes a putative RNA-binding protein with unknown function, can rescue temperature sensitivity caused by cut7-22, a fission yeast kinesin-5 mutant. Interestingly, kinesin-14/Klp2 levels on the spindles in the cut7 mutants were significantly reduced by the nrp1 deletion, although the total levels of Klp2 and the stability of spindle microtubules remained unaffected. Moreover, RNA-binding motifs of Nrp1 are essential for its cytoplasmic localization and function. We have also found that a portion of Nrp1 is spatially and functionally sequestered by chaperone-based protein aggregates upon mild heat stress and limits cell division at high temperatures. We propose that Nrp1 might be involved in post-transcriptional regulation through its RNA-binding ability to promote the loading of Klp2 on the spindle microtubules.

Zinc finger proteins (ZFP) play important roles in cellular processes. The DNA binding region of ZFP consists of 3 zinc finger DNA binding domains connected by amino acid linkers, the sequence TGQKP connects ZF1 and ZF2, and TGEKP connects ZF2 with ZF3. Linkers act to tune the zinc finger protein in the right position to bind its DNA target, the type of amino acid residues and length of linkers reflect on ZF1-ZF2-ZF3 interactions and contribute to the search and recognition process of ZF protein to its DNA target. Linker mutations and the affinity of the resulting mutants to specific and nonspecific DNA targets were studied by MD simulations and MM_GB(PB)SA. The affinity of mutants to DNA varied with type and position of amino acid residue. Mutation of K in TGQKP resulted in loss in affinity due to the loss of positive K interaction with phosphates, mutation of G showed loss in affinity to DNA, WT protein and all linker mutants showed loss in affinity to a nonspecific DNA target, this finding confirms previous reports which interpreted this loss in affinity as due to ZF1 having an anchoring role, and ZF3 playing an explorer role in the binding mechanism. The change in ZFP-DNA affinity with linker mutations is discussed in view of protein structure and role of linker residues in binding.

Several animal food allergens assembly into amyloids under gastric-like environments. These aggregated structures provide Gad m 1 with an enhanced IgE interaction due to the amyloid assembly of the epitope regions. However, whether these properties are unique of Gad m 1 or common to other food allergens has not yet been addressed. Using Bos d 5, Bos d 12 and Gal d 2 as food allergen models and Gad m 1 as control, aggregation reactions and the sera of milk, egg and fish allergic patients we have analyzed the IgE interaction of the distinct amyloids. We found that amyloids formed by Bos d 12 and Gal d 2 full-length and truncated chains are recognized by the IgEs of milk and egg allergic patient sera. As with Gad m 1, in most cases amyloid recognition is higher than that of the precursor structure. Bos d 5 was not recognized under any fold by the IgE of the sera studied. These results support that formation of IgE-binding amyloids might be a common feature to animal food allergen.

Emerging paradigms in interferon (IFN) biology suggest a dynamic INF induced interactome that extends through broader Interferon Stimulated Gene (ISG)- induction, which implicates interferon- ISG coordinated cross-talk with mRNA processing, post-translational modification and metabolic processes that underlie pathological (viral, autoimmune and tumor biology) and physiological (stem cell regenerative pathways) processes. INF immune responses can also be triggered by endogenous host-derived molecules that are generated in response to cellular stress or hemostasis imbalance to establish tissue repair and regeneration in first place, however, overactivation or lack of countermeasures can result in host tissue damage. The proteases are integral to viral and tumor pathology, and importantly serine proteases TMPRSS2 and trypsin have been identified as important molecular determinants underlying COVID-19 pathology, and emergence of coronaviruses cultured in vitro, respectively. We propose that pathogen associated proteases can act as novel stress-inducers to facilitate viral- competent immunomodulation. We term it as Protease Induced Transcriptomic/ epi-Transcriptomic Reshaping (PITTR) of host cells to counter cellular stress. We present a novel experimental model and our preliminary findings of trypsin- primed Caco-2 cells (CPT) that result in translational halt comparable to cells grown under serum-starvation conditions (CSS). CPT at escalating trypsin concentration (CPT- EC) induce upregulation of selective proteins that majorly map to ribosomal, RNA transport, and spliceosome ribonucleoproteins (RNPs). The inclusion of proinflammatory IL1-b to CPT (CPT- IL) resulted in global overexpression of proteins comparable to Caco-2 cells cultured in growth-factor rich serum conditions (CFBS), indicating a likely de-repression of trypsin- induced translational halt. Caco-2 cells display abortive interferon proteome under differential trypsin conditions (CPT, CPT-EC and CPT-IL), which is marked by complete lack of INF generation despite induction of intermediate ISGs, suggestive of protease (trypsin)- dependent regulation of INF response. Viruses regulate the proteome of stress granules (SGs) that are induced to cope transient translational halt as a central adaptive response to pathogen induced cellular stress. The integral components of SGs include non-translating mRNA, ribonucleoproteins (RNPs) and RNA binding proteins (RBPs), which together form biological condensates through a biophysical process involving weak electrostatic interactions through intrinsically disordered regions in RBPs resulting in liquid- liquid phase separation. We compared the CPT- EC proteome to the Mammalian Stress Granules Proteome (MSGP) database to explore potential RBPs that could possibly regulate INF response (and could act as potential anti-viral targets). Notably, differentially upregulated RNPs and potential RBPs from ISG family including ADAR and PRKRA, and RNA helicases implicated in viral pathogenesis were found to be upregulated in the CPT- EC proteome further strengthening the role of proteases (trypsin) in regulating INF pathways independent of the pathogen. We propose that the supplementation of viable SARS-CoV-2 viral loads to trypsin- primed host cells could recapitulate an infectious disease model, which may closely phenocopy pathogen- driven inflammation and signaling events. Based on the global downregulation of seven SERPINS (serine protease inhibitors) linked to thromboinflammation in our LCMS profiling data, we support the candidature of serine protease inhibitors for protease mediated viral pathologies. COVID-19 is increasingly linked to coagulopathy and resemblance to Neutrophil Extracellular Trap (NET) related thromboinflammatory features; SERPIN A1AT (alpha 1 antitrypsin) being a potent neutrophil- elastase inhibitor and a negative regulator of coagulation complement pathway may be a promising candidate for establishing hemostasis rebalancing in COVID-19 pathology.

Androgen insensitivity syndrome (AIS) is the most common disorder of sex development in people with karyotype 46,XY. Mutations in AR (androgen receptor) gene are found in most individuals with AIS. Exons 4-8, which encode LBD, were shown to be a mutation hotspot. The aim of this study was the search of mutations in the sequence of exons 6-8 which encode LBD of AR gene in patients with different clinical AIS phenotypes from Ukraine. The investigated patients were 4 women with 46,XY karyotype, SRY-positive and clinical features of AIS (2 – CAIS, 2 – PAIS). Serum levels of T, LH, and FSH were quantified by electrochemiluminescence immunoassay (ECLIA) technology. Cytogenetic studies were performed on peripheral blood lymphocytes with further use of standard protocols of chromosomal analysis (GTG-banding). The presence of SRY sequence was confirmed by FISH with LSI SRY probe. Direct Sanger sequencing of 6-8 exons was performed in patients and family members on the PCR products on the matrix of DNA samples isolated from peripheral blood lymphocytes. Detected SNPs were analysed using gnomAD, VEP, MutationTaster, Human Splicing Finder, NetPhorest 2.1, Group-based Prediction System 5.0, and PhosphoPICK bioinformatical resources. Modelling of mutant proteins based on available 3D models was conducted using the open source software UCSF Chimera 1.14rc. We have detected 3 previously described mutations (missense mutation X:67722905 Т>С (rs9332970) in PAIS patient, missense mutation X:67722943 C>T (rs886041132) in CAIS patient and, samesense mutation X:67723745 C>T (rs137852594) in PAIS patient). We determined these mutations as pathogenic using SIFT, PolyPhen, MutationTaster, Human Splicing Finder. Moreover the synonymous mutation X:67723745 C>T (rs137852594) detected in patient with PAIS was determined as mutation affecting processes of splicing. In our study we have identified novel mutation X:67722884 T>G in CAIS patient and family members. This mutation was predicted as a pathogenic using aforementioned bioinformatical tools. STRUM calculations of the protein stability change caused by single-point mutation showed a destabilization effect of the Ile836Ser substitution ΔΔG=-2.6. Possible aberrant phosphorylation analysis revealed the ability of MAPK family, Akt family, CDK1, CDK7, CDK9, PKC kinases to phosphorylate Ser836. Results concerning the pathogenicity of X:67722905 Т>С (rs9332970), X:67722943 C>T (rs886041132), X:67723745 C>T (rs137852594) mutations detected in patients with AIS from Ukraine obtained using bioinformatical resources SIFT, PolyPhen, MutationTaster, Human Splicing Finder correlate with previously published data concerning weaker binding of androgens in patients with the same mutations. This approves informativity of using such resources for mutation pathogenicity analysis. Analysis of the ortholog proteins, subdomain structure, and aberrant phosphorylation of AR-LBD suggests novel X:67722884 T>G mutation to be pathogenic. Based on analysis of mutant protein modelling followed by assessment of free energy change using STRUM it was predicted that mutant protein binds androgens 460 times worse than wild type.

We remind about the dogma initially established with the nucleic acid double helix, i.e. the DNA structure as the primary source of life. However, we bring into the discussion those additional processes that were crucial to enable life and cell evolution. Studying chemosensory proteins (CSPs) and odor binding proteins (OBPs) of insects, we have found a high level of pinpoint mutations on the RNA and peptide sequences. Many of these mutations are found to be tissue-specific and induce subtle changes in the protein structure, leading to a new theory of cell multifunction and life evolution. Here, attention is given to RNA and peptide mutations in small soluble protein families known for carrying lipids and fatty acids as fuel for moth cells. A new phylogenetic analysis of mutations is presented and provides even more support to the pioneer work, i.e. the finding that mutations in binding proteins have spread through moths and various groups of insects. Then, focus is given to specific mechanisms of mutations that are not random, change α-helical profilings and bring new functions at the protein level. In conclusion, RNA and peptide mutations are not seen as representative of a multitude of diseases, but rather as an alternative way by which protocells developed to acquire multifunction and totipotency. This provides a basis for the theory of RNA/peptide mutations for birth and evolution of life on earth’s crust proposed here.

Human NAD(P)H:quinone oxidoreductase 1 (NQO1) is a multi-functional protein whose alteration is associated with cancer, Parkinson´s and Alzheimer´s diseases. NQO1 displays a remarkable functional chemistry, capable of binding different functional ligands that modulate its activity, stability and interaction with proteins and nucleic acids. Our understanding on this functional chemistry is limited by the difficulty of obtaining structural and dynamic information on many of these states. Herein, we have used hydrogen/deuterium exchange monitored by mass-spectrometry (HDXMS) to investigate the structural dynamics of NQO1 in three ligation states: without ligands (NQO1apo), with FAD (NQO1holo) and with FAD and the inhibitor dicoumarol (NQO1dic). We show that NQO1apo has a minimally stable folded core holding the protein dimer and with FAD and dicoumarol ligand binding sites populating binding non-competent conformations. Binding of FAD significantly decreases protein dynamics and stabilizes the FAD and dicoumarol binding sites as well as the monomer:monomer interface. Dicoumarol binding further stabilizes all three functional sites, a result not previously anticipated by available crystallographic models. Our work provides an experimental perspective into the communication of stability effects through the NQO1 dimer, valuable to understand at the molecular level the effects of disease-associated variants, post-translation modifications and ligand binding cooperativity in NQO1.

Substrate binding proteins (SBP) bind to specific ligands in the periplasmic region and bind to membrane proteins to participate in transport or signal transduction. Typical SBPs consist of two α/β domains and recognize the substrate by hinge motion between two domains. Conversely, short length Rhodothermus marinus SBP (named as RmSBP) exists around the methyl-accepting chemotaxis protein. We previously determined the crystal structure of RmSBP consisting of a single α/β domain, but the substrate recognition mechanism is still unclear. To better understand the short length RmSBP, we performed comparative structure analysis, computational substrate docking, and X-ray crystallographic study. RmSBP shares a high level of similarity in α/β domain with other SBP proteins, but it has a distinct topology in the C-term region. The substrate binding model suggested that conformational change in the peripheral region of RmSBP was required to recognize the substrate. We determined the crystal structures of RmSBP at pH 5.5, 6.0, and 7.5. RmSBP showed structural flexibility of the β1-α2 loop, β5-β6 loop, and extended C-term domain based on the electron density map and temperature B-factor analysis. These results provide information that will further the understanding of the function of the short length SBP.

We present simple relations for nuclear stability and nuclear binding energy with respect to three gravitational constants associated with electroweak, strong and electromagnetic interactions.

Echinococcus granulosus is a harmful cestode parasite which could cause Cystic Echinococcosis in humans, various livestock species and wild animals. Calmodulin (CaM), a Ca²⁺ sensor protein, is widely expressed in eukaryotes and mediates a variety of cellular signaling activities. In our study, the CaM in Echinococcus granulosus (rEgCaM) was successfully cloned and the molecular and biochemical characterizations of rEgCaM were identified. The results showed that rEgCaM was a highly conserved calcium-binding protein, consisting of 149 amino acids. Immunoblot analysis revealed that rEgCaM could be identified using E. granulosus infected sheep serum. The usage of rEgCaM as antigen was evaluated by indirect ELISA which exhibited a high sensitivity of 90.3% but low specificity (47.1%). rEgCaM was mainly located in the tegument tissues and parenchymal region of protoscoleces, the tegument and inner body of adult worm and predominantly expressed in the germinal layer. The mRNA expression of rEgCaM in PSCs were gradually decreased with the increase death of PSCs. In electrophoretic mobility tests and ANS assays, rEgCaM showed a typical calcium-binding protein characteristics. This is the first report on CaM from E. granulosus and rEgCaM is considered to be involved in some important biological function of E. granulosus as a calcium-binding protein.

The R23Cu7Mg4 (R = Ca, Eu) intermetallics, studied by single crystal X-ray diffraction, were found to be isostructural with the Yb23Cu7Mg4 prototype (hP68, k4h2fca, space group P63/mmc), forming a small group inside the bigger 23:7:4 family, otherwise adopting the hP68-Pr23Ir7Mg4 crystal structure. The observed structural peculiarity is connected with the divalent character of the R component and with a noticeable volume contraction, resulting in a clear clustering of title compounds inside the whole 23:7:4 family. The occurrence of fragments typical of similar compounds, particularly Cu-centered trigonal prisms and Mg-centered core-shell polyicosahedral clusters with R at vertices, induced the search of significant structural relationships. In this work, a description of the hexagonal crystal structure of the studied compounds is proposed as a linear intergrowth along the c-direction of the two types of slabs R10CuMg3 (parent type: hP28-kh2ca, SG 194) and R13Cu6Mg (parent type: hR60-b6a2, SG 160). The ratio of these slabs in the studied structure is 2:2 per unit cell, corresponding to the simple equation 2XR10CuMg3 + 2XR13Cu6Mg = 2XR23Cu7Mg4. This description assimilates the studied compounds to the (Ca,Eu,Yb)4CuMg ones, where the same slabs (of p3m1 layer symmetry) are stacked in a different way/ratio, and constitutes a further step towards a structural generalization of R-rich ternary intermetallics.

As the control brain of the petrochemical plant, blast resistant performance requirements of the petrochemical control room should be guaranteed when the vapor cloud explosion occurs in the petrochemical production process. 3D-Kagome truss core sandwich structure is a kind of blast resistant material with high energy absorption. Considering the influence factors of the radius of the truss core rod and thickness of the upper and lower panels, in this paper, blast resistant performance of a real steel petrochemical control room with 3D-Kagome truss core sandwich wall is analyzed. With the optimization goal of plastic deformation energy and panel displacement, the optimal wall thickness and radius of the truss core rode are obtained. The optimized blast resistant wall is assembled, and the dynamic response of the steel petrochemical control room with the 3D-Kagome truss core sandwich blast resistant wall is analyzed. The simulation results show that the truss core layer does not dissipate the blast energy effectively when the radius ratio of the truss core rod is larger than 2.7% of the total thickness of the wall; with the increase of the thickness of the upper and lower panels, the proportion of plastic deformation energy of the truss core layer increases gradually and then tends to be a stable proportion value, that is about 90%; When the thickness ratio of the panel is 6.7% of the total one of the wall and the radius ratio of the truss core rod is 2.7% of the total thickness of the wall, the optimal blast resistant 3D-Kagome sandwich wall is determined.