Search Results (27)

In this contribution, we address quantum transport in long periodic arrays whose basic cells, localized potentials $U\left(x\right)$, display certain particular features. We investigate under which conditions these “local” special characteristics can influence the tunneling behavior through the full structure. As the building blocks, we consider two types of $U\left(x\right)$s: combinations of either Pöschl–Teller, $U_0/{cosh}^2\left[\alpha x\right]$, potentials (for which the reflection and transmission coefficients are known analytically) or Gaussian-shaped potentials. For the latter, we employ an improved potential slicing procedure using basic barriers, like rectangular, triangular and trapezoidal, to approximate $U\left(x\right)$ and thus obtain its scattering amplitudes. By means of a recently derived method, we discuss scattering along lattices composed of a number, N, of these $U\left(x\right)$s. We find that near-resonance energies of an isolated $U\left(x\right)$ do impact the corresponding energy bands in the limit of very large Ns, but only when the cell is spatially asymmetric. Then, there is a very narrow opening (defect or rip) in the system conduction quasi-band, corresponding to the energy of the $U\left(x\right)$ quasi-state. Also, for specific $U_0$’s of a single Pöschl–Teller well, one has 100% transmission for any incident $E>0$. For the $U\left(x\right)$ parameters rather close to such a condition, the associated array leads to a kind of “reflection comb” for large Ns; $|T_N{\left(k\right)|}^2$ is not close to one only at very specific values of k, when $|T_N{|}^2\approx 0$. Finally, the examples here—illustrating how the anomalous transport comportment in finite but long lattices can be inherited from certain singular aspects of the $U\left(x\right)$s—are briefly discussed in the context of known effects in the literature, notably for lattices with asymmetric cells. Full article

The plant-derived toxin ricin is classified as a type 2 ribosome-inactivating protein (RIP) and currently lacks effective clinical antidotes. The toxicity of ricin is mainly due to its ricin toxin A chain (RTA), which has become an important target for drug development. Previous studies have identified two essential binding pockets in the active site of RTA, but most existing inhibitors only target one of these pockets. In this study, we used computer-aided virtual screening to identify a compound called RSMI-29, which potentially interacts with both active pockets of RTA. We found that RSMI-29 can directly bind to RTA and effectively attenuate protein synthesis inhibition and rRNA depurination induced by RTA or ricin, thereby inhibiting their cytotoxic effects on cells in vitro. Moreover, RSMI-29 significantly reduced ricin-mediated damage to the liver, spleen, intestine, and lungs in mice, demonstrating its detoxification effect against ricin in vivo. RSMI-29 also exhibited excellent drug-like properties, featuring a typical structural moiety of known sulfonamides and barbiturates. These findings suggest that RSMI-29 is a novel small-molecule inhibitor that specifically targets ricin toxin A chain, providing a potential therapeutic option for ricin intoxication. Full article

Ribosome inactivating proteins (RIPs) are specific N-β-glycosylases that are well-characterized in plants. Their enzymatic action is to damage ribosomes, thereby blocking protein translation. Recently, several research groups have been working on the screening for these toxins in edible plants to facilitate the use of RIPs as biotechnological tools and biopesticides and to overcome public prejudice. Here, four novel monomeric (type 1) RIPs have been isolated from the seeds of Atriplex hortensis L. var. rubra, which is commonly known as edible red mountain spinach. These enzymes, named hortensins 1, 2, 4, and 5, are able to release the β-fragment and, like many other RIPs, adenines from salmon sperm DNA, thus, acting as polynucleotide:adenosine glycosidases. Structurally, hortensins have a different molecular weight and are purified with different yields (hortensin 1, ~29.5 kDa, 0.28 mg per 100 g; hortensin 2, ~29 kDa, 0.29 mg per 100 g; hortensin 4, ~28.5 kDa, 0.71 mg per 100 g; and hortensin 5, ~30 kDa, 0.65 mg per 100 g); only hortensins 2 and 4 are glycosylated. Furthermore, the major isoforms (hortensins 4 and 5) are cytotoxic toward human continuous glioblastoma U87MG cell line. In addition, the morphological change in U87MG cells in the presence of these toxins is indicative of cell death triggered by the apoptotic pathway, as revealed by nuclear DNA fragmentation (TUNEL assay). Full article

Ribosome-inactivating proteins (RIPs) are plant toxins that were identified for their ability to irreversibly damage ribosomes, thereby causing arrest of protein synthesis and induction of cell death. The RIPs purified from Adenia plants are the most potent ones. Here, we describe a novel toxic lectin from Adenia heterophylla caudex, which has been named heterophyllin. Heterophyllin shows the enzymatic and lectin properties of type 2 RIPs. Interestingly, in immunoreactivity experiments, heterophyllin poorly cross-reacts with sera against all other tested RIPs. The cytotoxic effects and death pathways triggered by heterophyllin were investigated in three human-derived cell lines: NB100, T24, and MCF7, and compared to ricin, the most known and studied type 2 RIP. Heterophyllin was able to completely abolish cell viability at nM concentration. A strong induction of apoptosis, but not necrosis, and the involvement of oxidative stress and necroptosis were observed in all the tested cell lines. Therefore, the enzymatic, immunological, and biological activities of heterophyllin make it an interesting molecule, worthy of further in-depth analysis to verify its possible pharmacological application. Full article

The Type 2 Fuzzy Logic System (T2FLS) is an enhanced form of the classical Fuzzy Logic System (FLS). The T2FLS based control technics demonstrated a lot of improvements for the past few decades. This is based on the advantage of its membership function (MF). Many experimental studies indicated the superiority of Type 2 Fuzzy Logic Controller (T2FLC) over the ordinary Type 1 Fuzzy Logic Controller (T1FLC), particularly in the event of non-linearities and complex uncertainties. However, the organized design method of T2FLCs is still an interesting problem in the control engineering community. This is due to the difficulties in computing the parameters associated it. A novel application of the Modified Flower Pollination (MFP) optimization algorithm in the design of T2FL is presented. The optimized Cascade Interval Type 2 Fuzzy PID Controller (IT2FPIDC) structure is proposed in this study. The best values of the parameters of the antecedent MFs and the PID gains of IT2FPIDC are found using the MFP algorithm. The MFP optimization technique was used because of its lower computational effort and high convergence speed, in view of the higher number of variables to be optimized in cascaded IT2FPIDC. The MFP-based Type-1 Fuzzy Proportional Integral Derivative Controller (T1FPIDC) is compared with the proposed MFP-based cascade-optimized IT2FPIDC. The rotary inverted pendulum (RIP) which is a non-minimum phase, non-linear, and unstable system is employed as a benchmark for testing the proposed controller. Balance and trajectory-tracking controls of the RIP are considered. Furthermore, the disturbance rejection ability of the proposed controller is analysed. The presented control methos is evaluated on the RIP manufactured by Quanser over many simulations and real-world experiments. The performance characteristics considered are steady state error ${(E}_{ss})$, settling time $\left(t_s\right)$, maximum overshoot $\left(M_p\right)$ and rise time $\left(t_r\right)$. The improvement of the effectiveness and robustness proposed controller in the presence of load disturbance, noise effects and parameter variation is shown. Full article

Background and Objectives. Acute aortic syndromes (AASs) are emergencies burdened by high morbidity and mortality. Guideline-recommended diagnostic workup is based on pre-test probability assessment (PPA) and d-dimer testing. However, the performance of PPA and d-dimer has never been studied in individuals with previous AAS (pAAS), which represent a challenging population. Materials and Methods. We analyzed a registry of patients with pAAS evaluated in two Emergency Departments (EDs) for suspected novel AAS (nAAS). Enrolment criteria were history of pAAS and the presence of truncal pain, syncope or perfusion deficit. All patients underwent advanced imaging. Clinical data were registered prospectively and PPA was performed by applying the aortic dissection detection (ADD) and an aorta simplified (AORTAs) score. Results. A total of 128 patients were enrolled, including 77 patients with previous Stanford type A aortic dissection and 45 patients with previous Stanford type B aortic dissection. The final diagnosis was nAAS in 40 (31%) patients. Clinical variables associated with nAAS were: aortic valve disease, thoracic aortic aneurysm, severe pain, sudden pain, ripping/tearing pain and hypotension/shock. ADD score ≥ 2 had a sensitivity of 65% and a specificity of 83% for nAAS; AORTAs score ≥ 2 had a sensitivity of 48% and a specificity of 88%. d-dimer (cutoff ≥ 500 ng/mL or age-adjusted cutoff) had a sensitivity of 97% and a specificity of 13%/14.7%, for diagnosis of nAAS. Patients that were candidates for guideline-compliant PPA/d-dimer integrated rule-out were: 5 (4.9%) with ADD ≤ 1/d-dimer and 8 (7.8%) with AORTAs ≤ 1/d-dimer < age-adjusted cutoff. None of them had a nAAS. Conclusions. Patients with pAAS evaluated in the ED for red-flag symptoms showed intermediate-to-high pre-test probability of nAAS. The ADD score had lower sensitivity and specificity than in unselected patients. d-dimer, alone and integrated with PPA, was highly sensitive for nAAS, but very unspecific. PPA/d-dimer integrated strategies are unlikely to significantly reduce the number of patients with pAAS undergoing advanced imaging. Full article

Pulchellin is a plant biotoxin categorized as a type 2 ribosome-inactivating protein (RIPs) which potentially kills cells at very low concentrations. Biotoxins serve as targeting immunotoxins (IT), consisting of antibodies conjugated to toxins. ITs have two independent protein components, a human antibody and a toxin with a bacterial or plant source; therefore, they pose unique setbacks in immunogenicity. To overcome this issue, the engineering of epitopes is one of the beneficial methods to elicit an immunological response. Here, we predicted the tertiary structure of the pulchellin A-chain (PAC) using five common powerful servers and adopted the best model after refining. Then, predicted structure using four distinct computational approaches identified conformational B-cell epitopes. This approach identified some amino acids as a potential for lowering immunogenicity by point mutation. All mutations were then applied to generate a model of pulchellin containing all mutations (so-called PAM). Mutants’ immunogenicity was assessed and compared to the wild type as well as other mutant characteristics, including stability and compactness, were computationally examined in addition to immunogenicity. The findings revealed a reduction in immunogenicity in all mutants and significantly in N146V and R149A. Furthermore, all mutants demonstrated remarkable stability and validity in Molecular Dynamic (MD) simulations. During docking and simulations, the most homologous toxin to pulchellin, Abrin-A was applied as a control. In addition, the toxin candidate containing all mutations (PAM) disclosed a high level of stability, making it a potential model for experimental deployment. In conclusion, by eliminating B-cell epitopes, our computational approach provides a potential less immunogenic IT based on PAC. Full article

Stressors cause activation of the hypothalamic-pituitary-adrenal (HPA) axis and a systemic inflammatory response. As a newly proposed cell death manner in recent years, necroptosis occurs in a variety of tissue damage and inflammation. However, the role of necroptosis in HPA axis activation remains to be elucidated. The aim of this study was to investigate the occurrence of necroptosis and its role in HPA activation in a porcine stress model induced by Escherichia coli lipopolysaccharide (LPS). Several typical stress behaviors like fever, anorexia, shivering and vomiting were observed in piglets after LPS injection. HPA axis was activated as shown by increased plasma cortisol concentration and mRNA expression of pituitary corticotropin-releasing hormone receptor 1 (CRHR1) and adrenal steroidogenic acute regulatory protein (StAR). The mRNA expression of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 in the hypothalamus, pituitary gland and adrenal gland was elevated by LPS, accompanied by the activation of necroptosis indicated by higher mRNA expression of necroptosis signals including receptor-interacting protein kinase (RIP) 1, RIP3, and phosphorylated mixed-lineage kinase domain-like protein (MLKL). Furthermore, necrostatin-1 (Nec-1), an inhibitor of necroptosis, inhibited necroptosis indicated by decreased mRNA levels of RIP1, RIP3, MLKL, and phosphoglycerate mutase family member 5 (PGAM5) in the hypothalamus, pituitary gland and adrenal gland. Nec-1 also decreased the mRNA expression of TNF-α and IL-β and inhibited the activation of the HPA axis indicated by lower plasma cortisol concentration and mRNA expression of adrenal type 2 melanocortin receptor (MC2R) and StAR. These findings suggest that necroptosis is present and contributes to HPA axis activation induced by LPS. These findings provide a potential possibility for necroptosis as an intervention target for alleviating HPA axis activation and stress responses. Full article

The lengths of leaves, leaf sheaths, and internodes are the main factors affecting individual plant types. An ideotype is a basis for developing a high-yielding population structure. Water and nitrogen (N) fertilizer can directly affect the growth of a plant’s organs. To evaluate the effects of irrigation and nitrogen application on the length and growth of wheat leaves, leaf sheaths, and internodes, we carried out a 5 year field experiment in the high yield wheat fields of the North China Plain. Five treatments (T₂–T₆) were applied, and irrigation was carried out in springtime at the appearance of the second leaf (T₂), the third leaf (T₃), the fourth leaf (T₄), the fifth leaf (T₅) and the sixth leaf (T₆). The results showed that the irrigation and N topdressing periods had different effects on the leaves, leaf sheaths, and internodes. The lengths of the upper three leaves gradually increased with the progression of the irrigation and N topdressing. The increases in the lengths of the leaf sheath were similar and followed the irrigation and N topdressing pattern at four stages of leaves in the spring: n-1, n-2, n-3 and n-4. The most effective growth of the internodes was achieved by irrigation and N topdressing at the n + 2 and n + 3 stages. The vertical spacing among the upper three leaves increased with irrigation and N topdressing at the appearance of the top second (or flag) leaf. Differences in temperature and precipitation over the years either weakened or enhanced the differences in the plants’ organ lengths with the different treatments. However, the orders of treatments did not alter organ length in different years. Earlier irrigation and N topdressing treatments (T₂, T₃, and T₄) showed an inhibitory effect on the leaves and leaf sheaths during the early growth stage. The inhibitory effect was more evident in the later-emerged leaves and leaf sheaths than in those that emerged earlier. However, irrigation and N fertilization increased the final length of the organs by improving the growth rate during the rapid incremental phase (RIP) and the slow incremental phase (SIP). Although the most significant extensions of the lengths of leaves, leaf sheaths, and internodes were achieved by irrigation and N topdressing before the organs entered the RIP, the specific growth stages were different among the three organs. These results can provide a reference for directly regulating the development of wheat organs and constructing an ideotype. Full article

Ribosome-inactivating proteins (RIPs) are a group of proteins with rRNA N-glycosylase activity that catalyze the removal of a specific adenine located in the sarcin–ricin loop of the large ribosomal RNA, which leads to the irreversible inhibition of protein synthesis and, consequently, cell death. The case of elderberry (Sambucus nigra L.) is unique, since more than 20 RIPs and related lectins have been isolated and characterized from the flowers, seeds, fruits, and bark of this plant. However, these kinds of proteins have never been isolated from elderberry leaves. In this work, we have purified RIPs and lectins from the leaves of this shrub, studying their main physicochemical characteristics, sequences, and biological properties. In elderberry leaves, we found one type 2 RIP and two related lectins that are specific for galactose, four type 2 RIPs that fail to agglutinate erythrocytes, and one type 1 RIP. Several of these proteins are homologous to others found elsewhere in the plant. The diversity of RIPs and lectins in the different elderberry tissues, and the different biological activities of these proteins, which have a high degree of homology with each other, constitute an excellent source of proteins that are of great interest in diagnostics, experimental therapy, and agriculture. Full article

Retrotransposon is an important component of the mammalian genome. Previous studies have shown that the expression of protein-coding genes was affected by the insertion of retrotransposon into the proximal genes, and the phenotype variations would be related to the retrotransposon insertion polymorphisms (RIPs). In this study, leptin (LEP), leptin receptor (LEPR), and leptin receptor overlapping transcript (LEPROT), which play important roles in the regulation of fat synthesis and body weight, were screened to search for the RIPs and their effect on phenotype and gene expression, as well as to further study the function of the insertion. The results showed that three RIPs located in intron 1 of LEPROT and intron 2 and 21 of LEPR were identified, and they were all SINEA1, which was one type of retrotransposon. The SINE insertion at the LEPROT was the dominant allele in native pig breeds. The age of 100 kg body weight of SINE+/+ Large White individuals was significantly higher than those of SINE+/− and SINE−/− individuals (p < 0.05). The LEPROT gene expression in the liver and suet of 30-day-old SINE−/− Sujiang piglets were significantly higher than those of SINE+/+ and SINE+/− piglets (p < 0.01). The dual-luciferase reporter gene assay showed that SINE insertion in PK15 and 3T3-L1 cells significantly reduced the promoter activity of the LEPROT gene (p < 0.01). Therefore, SINE insertion can be a repressor to reduce the expression of LEPROT and could be a useful molecular marker for assisted selection of growth traits in pig breeding. Full article

This study aimed to explore how Dab1 gene functional silencing influences the spatial and temporal expression patterns of fibroblast growth factor receptor 1 (FGFR1), fibroblast growth factor receptor 2 (FGFR2), receptor-interacting protein kinase 5 (RIP5), and huntingtin-interacting protein 2 (HIP2) in the developing and postnatal kidneys of the yotari mice as potential determinants of normal kidney formation and function. Dab1^−/− animal kidneys exhibit diminished FGFR1/FGFR2 expression in all examined developmental stages, whereas RIP5 cell immunoreactivity demonstrated negligible variation. The HIP2 expression revealed a discernible difference during the postnatal period, where we noted a significant decrease in almost all the observed kidney structures of yotari animals. An extracellular signal-regulated kinase (Erk1/2) and mammalian target of rapamycin (mTOR) expression in yotari kidneys decreased in embryonic and postnatal developmental phases for which we can hypothesize that the Erk1/2 signaling pathway in the yotari mice kidneys is dependent on Reelin with Dab1 only partially implicated in Reelin-mediated MEK/Erk1/2 activation. The impairment of FGFR1 and FGFR2 expression suggests the involvement of the observed markers in generating the CAKUT phenotype resulting in renal hypoplasia. Our study demonstrates the critical role of HIP2 in reducing cell death throughout nephrogenesis and maturation in wild-type mice and indicates a possible connection between decreased HIP2 expression in postnatal kidney structures and observed podocyte injury in yotari. Our results emphasize the crucial function of the examined markers throughout normal kidney development and their potential participation in kidney pathology and diagnostics, where they might serve as biomarkers and therapeutic targets. Full article

Kirkiin is a new type 2 ribosome-inactivating protein (RIP) purified from the caudex of Adenia kirkii with a cytotoxicity compared to that of stenodactylin. The high toxicity of RIPs from Adenia genus plants makes them interesting tools for biotechnology and therapeutic applications, particularly in cancer therapy. The complete amino acid sequence and 3D structure prediction of kirkiin are here reported. Gene sequence analysis revealed that kirkiin is encoded by a 1572 bp open reading frame, corresponding to 524 amino acid residues, without introns. The amino acid sequence analysis showed a high degree of identity with other Adenia RIPs. The 3D structure of kirkiin preserves the overall folding of type 2 RIPs. The key amino acids of the active site, described for ricin and other RIPs, are also conserved in the kirkiin A chain. Sugar affinity studies and docking experiments revealed that both the 1α and 2γ sites of the kirkiin B chain exhibit binding activity toward lactose and D-galactose, being lower than ricin. The replacement of His246 in the kirkiin 2γ site instead of Tyr248 in ricin causes a different structure arrangement that could explain the lower sugar affinity of kirkiin with respect to ricin. Full article

Type 2 diabetes mellitus is a complex multifactorial disease characterized by insulin resistance and dysfunction of pancreatic β-cells. Rice husk silica liquid (RHSL) is derived from rice husks and has not been explored in diabetes mellitus until now. Previous studies showed that rice husk is enriched with silica, and its silica nanoparticles are higher more biocompatible. To investigate the potential protective role of RHSL on pancreatic β cells, we utilized RIN-m5F pancreatic β cells and explored RHSL effect after streptozotocin (STZ)-stimulation. The recovery effects of RHSL were evaluated using flow cytometry, Western blotting, and immunofluorescence analysis. Results of our study showed that RHSL reversed the cell viability, insulin secretion, reactive oxygen species (ROS) production, and the change of mitochondria membrane potential (ΔΨm) in STZ-treated RIN-m5F cells. Moreover, the expression of phospho-receptor-interacting protein 3 (p-RIP3) and cleaved-poly (ADP-ribose) polymerase (PARP), phospho-mammalian target of rapamycin (p-mTOR), and sequestosome-1 (p62/SQSTM1) were significantly decreased, while the transition of light chain (LC)3-I to LC3-II was markedly increased after RHSL treatment in STZ-induced RIN-m5F cells. Interestingly, using autophagy inhibitors such as 3-methyladenine (3-MA) and chloroquine (CQ) both showed an increase in cleaved-PARP protein level, indicating apoptosis induction. Taken together, this study demonstrated that RHSL induced autophagy and alleviated STZ-induced ROS-mediated apoptosis in RIN-m5F cells. Full article

The initiation stage of protein biosynthesis is a sophisticated process tightly regulated by numerous initiation factors and their associated components. However, the mechanism underlying translation initiation has not been completely understood in rice. Here, we showed knock-out mutation of the rice eukaryotic translation initiation factor 3 subunit h (OseIF3h) resulted in plant growth retardation and seed-setting rate reduction as compared to the wild type. Further investigation demonstrated an interaction between OseIF3h and OsMTA2 (mRNA adenosine methylase 2), a rice homolog of METTL3 (methyltransferase-like 3) in mammals, which provided new insight into how N6-methyladenosine (m6A) modification of messenger RNA (mRNA) is engaged in the translation initiation process in monocot species. Moreover, the RIP-seq (RNA immunoprecipitation sequencing) data suggested that OseIF3h was involved in multiple biological processes, including photosynthesis, cellular metabolic process, precursor metabolites, and energy generation. Therefore, we infer that OseIF3h interacts with OsMTA2 to target a particular subset of genes at translational level, regulating plant growth and pollen development. Full article