Mcmillanmoreno8919

Nerve injury-induced protein 1 (Ninjurin 1, Ninj1) is a cell adhesion molecule responsible for cell-to-cell interactions between immune cells and endothelial cells. In our previous paper, we have shown that Ninj1 plays an important role in the infiltration of neutrophils in the postischemic brain and that the dodecamer peptide harboring the Ninj1 N-terminal adhesion motif (N-NAM, Pro26-Asn37) inhibits infiltration of neutrophils in the postischemic brain and confers robust neuroprotective and anti-inflammatory effects. In the present study, we examinedt the pro-angiogenic effect of N-NAM using human umbilical vein endothelial cells (HUVECs) and rat MCAO (middle cerebral artery occlusion) model of stroke. We found that N-NAM promotes proliferation, migration, and tube formation of HUVECs and demonstrate that the suppression of endogenous Ninj1 is responsible for the N-NAM-mediated pro-angiogenic effects. Importantly, a pull-down assay revealed a direct binding between exogenously delivered N-NAM and endogenous Ninj1 and it is N-terminal adhesion motif dependent. #link# In addition, N-NAM activated the Ang1-Tie2 and AKT signaling pathways in HUVECs, and blocking those signaling pathways with specific inhibitors suppressed N-NAM-induced tube formation, indicating critical roles of those signaling pathways in N-NAM-induced angiogenesis. Moreover, in a rat MCAO model, intranasal administration of N-NAM beginning 4 days post-MCAO (1.5 µg daily for 3 days) augmented angiogenesis in the penumbra of the ipsilateral hemisphere of the brain and significantly enhanced total vessel lengths, vessel densities, and pro-angiogenic marker expression. These results demonstrate that the 12-amino acid Ninj1 peptide, which contains the N-terminal adhesion motif of Ninj1, confers pro-angiogenic effects and suggest that those effects might contribute to its neuroprotective effects in the postischemic brain.The effect of inhomogeneous quantum dot (QD) size distribution on the electronic transport of one-dimensional (1D) QD chains (QDCs) is theoretically investigated. The non-equilibrium Green function method is employed to compute the electron transmission probabilities of QDCs. The ensemble averaged transmission probability shows a close agreement with the conductivity equation predicted by Anderson et al. for a disordered electronic system. The fidelity of quantum transport is defined as the transmission performance of an ensemble of QDCs of length N (N-QDCs) to assess the robustness of QDCs as a practical electronic device. We found that the fidelity of inhomogeneous N-QDCs with the standard deviation of energy level distribution σε is a Lorentzian function of variable Nσε2. With these analytical expressions, we can predict the conductance and fidelity of any QDC characterized by (N, σε). Our results can provide a guideline for combining the chain length and QD size distributions for high-mobility electron transport in 1D QDCs.Every year, about four percent of the plastic waste generated worldwide ends up in the ocean. What happens to the plastic there is poorly understood, though a growing body of evidence suggests it is rapidly spreading throughout the global ocean. The mechanisms of this spread are straightforward for buoyant larger plastics that can be accurately modelled using Lagrangian particle models. But the fate of the smallest size fractions (the microplastics) are less straightforward, in part because they can aggregate in sinking marine snow and faecal pellets. This biologically-mediated pathway is suspected to be a primary surface microplastic removal mechanism, but exactly how it might work in the real ocean is unknown. We search the parameter space of a new microplastic model embedded in an earth system model to show that biological uptake can significantly shape global microplastic inventory and distributions and even account for the budgetary "missing" fraction of surface microplastic, despite being an inefficient removal mechanism. While a lack of observational data hampers our ability to choose a set of "best" model parameters, our effort represents a first tool for quantitatively assessing hypotheses for microplastic interaction with ocean biology at the global scale.Coordinate transformation (CT) theory has shown great potentials in manipulating both time-varying and static fields for different physics ranging from electromagnetism and acoustics to electrostatic and thermal science. Nevertheless, as inhomogeneous and anisotropic materials are required to be realized for the implementation of CT-based devices, the applicability of this method is restricted due to difficulties in the fabrication process. In this paper, based on transformation electrostatic (TE) methodology, the design principle of an arbitrary shape dc electric concentrator is established which yields the enhancement of static electric fields in a predefined region with only one homogeneous conductivity, named as dc null medium (DNM). It is shown that one constant DNM is sufficient for localizing steady electric current in any arbitrary shape region, which in turn obviates the tedious mathematical calculations that conventional methods suffer from. In other words, the same DNM can be used for different concentrators regardless of their cross-section geometries, which makes the presented approach suitable for scenarios where reconfigurability is of utmost importance. Several numerical simulations are performed in order to demonstrate the capability of the proposed dc electric concentrator in localizing steady electric fields into the desired region. Moreover, by utilizing the analogy between electrically conducting materials and resistor networks, the attained DNM is realized with low-cost resistors and then exploited for fabricating a square shape dc electric concentrator on a printed circuit board (PCB). Galicaftor order is demonstrated that the measurement results agree well with the theoretical predictions and numerical simulations, which corroborate the effectiveness of the propounded method. The presented idea of this paper could find applications in scenarios where highly confined electric fields/currents are of critical importance such as electronic skin devices and electrical impedance tomography.Galectin-3 is a biomarker of fibrosis, inflammation and oxidative stress, and its role in heart remodelling and exercise intolerance has not been conclusively proven in heart failure (HF) patients with reduced ejection fraction (rEF). We prospectively assessed 67 consecutive patients with symptomatic HF and left ventricular (LV) EF ≤ 35% during optimal medical therapy, with a mean serum galectin-3 concentration of 15.3 ± 6.4 and a median of 13.5 ng/mL. The group with galectin-3 concentrations greater than or equal to the median had significantly worse right ventricular (RV) systolic function parameters (s', TAPSE), higher pulmonary artery systolic pressure, more advanced tricuspid regurgitation and lower RV-to-pulmonary circulation coupling index, while no significant differences were found in LV parameters. Moreover, this group achieved significantly lower parameters in cardiopulmonary exercise testing. Significant negative correlations were found between galectin-3 concentration and RV parameters and exercise capacity parameters and have persisted after adjustment for glomerular filtration rate, but not all of them have persisted after adjustment for NT-proBNP. Multivariate regression analysis revealed that TAPSE (β coefficient - 0.605; p  less then  0.001) and heart rate at peak exercise (β coefficient - 0.98; p = 0.009) were independently related to galectin-3 concentration. link2 Elevated galectin-3 concentration in patients with HFrEF might indicate concomitant RV dysfunction and exercise intolerance.ACO2 is a mitochondrial protein, which is critically involved in the function of the tricarboxylic acid cycle (TCA), the maintenance of iron homeostasis, oxidative stress defense and the integrity of mitochondrial DNA (mtDNA). Mutations in the ACO2 gene were identified in patients suffering from a broad range of symptoms, including optic nerve atrophy, cortical atrophy, cerebellar atrophy, hypotonia, seizures and intellectual disabilities. In the present study, we identified a heterozygous 51 bp deletion (c.1699_1749del51) in ACO2 in a family with autosomal dominant inherited isolated optic atrophy. link3 A complementation assay using aco1-deficient yeast revealed a growth defect for the mutant ACO2 variant substantiating a pathogenic effect of the deletion. We used patient-derived fibroblasts to characterize cellular phenotypes and found a decrease of ACO2 protein levels, while ACO2 enzyme activity was not affected compared to two age- and gender-matched control lines. Several parameters of mitochondrial function, including mitochondrial morphology, mitochondrial membrane potential or mitochondrial superoxide production, were not changed under baseline conditions. However, basal respiration, maximal respiration, and spare respiratory capacity were reduced in mutant cells. Furthermore, we observed a reduction of mtDNA copy number and reduced mtDNA transcription levels in ACO2-mutant fibroblasts. Inducing oxidative stress led to an increased susceptibility for cell death in ACO2-mutant fibroblasts compared to controls. Our study reveals that a monoallelic mutation in ACO2 is sufficient to promote mitochondrial dysfunction and increased vulnerability to oxidative stress as main drivers of cell death related to optic nerve atrophy.The spotted hyena (Crocuta crocuta) is the only extant species of the genus Crocuta, which once occupied a much wider range during the Pliocene and Pleistocene. However, its origin and evolutionary history is somewhat contentious due to discordances between morphological, nuclear, and mitochondrial data. Due to the limited molecular data from east Asian Crocuta, also known as cave hyena, and the difficulty of extracting ancient DNA from this area, here we present proteomic analysis of cave hyenas from three locations in northern China. This marks the first proteomic data generated from cave hyenas, adding new molecular data to the east Asian populations. Phylogenetic analysis based on these protein sequences reveals two different groups of cave hyenas in east Asia, one of which could not be distinguished from modern spotted hyenas from northern Africa, tentatively the result of previously suggested gene flow between these lineages. With developments of instrumentation and analytical methods, proteomics holds promising potential for molecular phylogenetic reconstructions of ancient fauna previously thought to be unreachable using ancient DNA.In the present study we have evaluated the performance of several immunological biomarkers for early diagnosis and prognosis of congenital toxoplasmosis. Our results showed that ex vivo serum levels of CXCL9, and the frequencies of circulating CD4+CD25+ T-cells and T. gondii-specific IFN-γ+CD4+ T-cells measured 30-45 days after birth presented high accuracy to distinguish T. gondii-infected infants from healthy age-matched controls (Global Accuracy/AUC = 0.9; 0.9 and 0.8, respectively). Of note was the enhanced performance (Accuracy = 96%) achieved by using a combined stepwise analysis of CD4+CD25+ T-cells and CXCL9. In addition, high global accuracy (AUC = 0.9) with elevated sensitivity (Se = 98%) was also reached by using the total frequency of in vitro IFN-γ-producing T. gondii-specific T-cells (∑ IFN-γ+ CD4+ & CD8+) as a biomarker of congenital toxoplasmosis. Furthermore, the analysis of in vitro T. gondii-specific IL5+CD4+ T-cells and IFN-γ+NK-cells displayed a high accuracy for early prognosis of ocular lesion in infant with congenital toxoplasmosis (Global Accuracy/AUC = 0.