Nitric oxide overcomes Cd and Cu toxicity in in vitro-grown tobacco plants through increasing contents and activities of rubisco and rubisco activase

AbstractToxic heavy metals such as cadmium (Cd) and copper (Cu) are global problems that are a growing threat to the environment. Despite some heavy metals are required for plant growth and development, others are considered toxic elements and do not play any known physiological role in plant cells. Elevated doses of Cd or Cu cause toxicity in plants and generate damages due to the stress condition and eventually cause a significant reduction in quantity and quality of crop plants. The nitric oxide (NO) donor sodium nitroprusside (SNP) is reported to alleviate the toxicity of some heavy metals like Cd and Cu. In the current study, the role of NO in alleviating stresses of Cd and Cu was investigated in in vitro-grown tobacco (Nicotiana tabacum) Based on plant growth, total chlorophyll contents, contents and activities of rubisco and rubisco activase. According to the results of this study, the growth and total chlorophyll contents of Cd/Cu stressed plants were hugely decreased in the absence of SNP, while the supplementation of SNP resulted in a significant increase of both fresh weight and total chlorophyll contents. Remarkable reductions of Rubisco and rubisco activase contents and activities were observed in Cd and Cu-induced plants. SNP supplementation showed the highest contents and activities of rubisco and rubisco activase compared to the control and Cu/Cd-stressed plants. Taken together, our findings suggest that SNP could play a protective role in regulation of plant responses to abiotic stresses such as Cd and Cu by enhancing Rubisco and Rubisco activase

Non-invasive flow mapping of parasagittal meningeal lymphatics using 2D interslice flow saturation MRI

The clearance pathways of brain waste products in humans are still under debate in part due to the lack of noninvasive imaging techniques for meningeal lymphatic vessels (mLVs). In this study, we propose a new noninvasive mLVs imaging technique based on an inter-slice blood perfusion MRI called alternate ascending/descending directional navigation (ALADDIN). ALADDIN with inversion recovery (IR) at single inversion time of 2300 ms (single-TI IR-ALADDIN) clearly demonstrated parasagittal mLVs around the human superior sagittal sinus (SSS) with better detectability and specificity than the previously suggested noninvasive imaging techniques. While in many studies it has been difficult to detect mLVs and confirm their signal source noninvasively, the detection of mLVs in this study was confirmed by their posterior to anterior flow direction and their velocities and morphological features, which were consistent with those from the literature. In addition, IR-ALADDIN was compared with contrast-enhanced black blood imaging to confirm the detection of mLVs and its similarity. For the quantification of flow velocity of mLVs, IR-ALADDIN was performed at three inversion times of 2000, 2300, and 2600 ms (three-TI IR-ALADDIN) for both a flow phantom and humans. For this preliminary result, the flow velocity of the dorsal mLVs in humans ranged between 2.2 and 2.7mm/s. Overall, (i) the single-TI IR-ALADDIN can be used as a novel non-invasive method to visualize mLVs in the whole brain with scan time of ~ 17min and (ii) the multi-TI IR-ALADDIN can be used as a way to quantify the flow velocity of mLVs with a scan time of ~ 10min (or shorter) in a limited coverage. Accordingly, the suggested approach can be applied to noninvasively studying meningeal lymphatic flows in general and also understanding the clearance pathways of waste production through mLVs in humans, which warrants further investigation

A Comparative Study on the Ferroelectric Performances in Atomic Layer Deposited Hf0.5Zr0.5O2 Thin Films Using Tetrakis(ethylmethylamino) and Tetrakis(dimethylamino) Precursors

Abstract The chemical, physical, and electrical properties of the atomic layer deposited Hf0.5Zr0.5O2 thin films using tetrakis(ethylmethylamino) (TEMA) and tetrakis(dimethylamino) (TDMA) precursors are compared. The ligand of the metal-organic precursors strongly affects the residual C concentration, grain size, and the resulting ferroelectric properties. Depositing Hf0.5Zr0.5O2 films with the TDMA precursors results in lower C concentration and slightly larger grain size. These findings are beneficial to grow more ferroelectric-phase-dominant film, which mitigates its wake-up effect. From the wake-up test of the TDMA-Hf0.5Zr0.5O2 film with a 2.8 MV/cm cycling field, the adverse wake-up effect was well suppressed up to 105 cycles, with a reasonably high double remanent polarization value of ~40 μC/cm2. The film also showed reliable switching up to 109 cycles with the 2.5MV/cm cycling field without involving the wake-up effect but with the typical fatigue behavior

Resistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22

Transforming growth factor β (TGFβ) is important in maintaining self-tolerance and inhibits T cell reactivity. We show that CD8⁺ T cells that lack the tyrosine phosphatase Ptpn22, a major predisposing gene for autoimmune disease, are resistant to the suppressive effects of TGFβ. Resistance to TGFβ suppression, while disadvantageous in autoimmunity, helps Ptpn22‾/‾ T cells to be intrinsically superior at clearing established tumors that secrete TGFβ. Mechanistically, loss of Ptpn22 increases the capacity of T cells to produce IL-2, which overcomes TGFβ-mediated suppression. These data suggest that a viable strategy to improve anti-tumor adoptive cell therapy may be to engineer tumor-restricted T cells with mutations identified as risk factors for autoimmunity

Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the most common tumor in the adult liver, with high relapse and mortality rates despite diverse treatment modalities. In this study, nicotinamide N-methyltransferase (NNMT), a key enzyme in drug metabolism, was investigated as a potential prognostic factor.</p> <p>Methods</p> <p>Frozen tumors and non-cancerous surrounding tissues from 120 patients with primary HCC were studied. Expressions of NNMT and internal control genes were measured by real-time reverse-transcription PCR (RT-PCR). The relationship of NNMT mRNA level with clinicopathologic parameters and clinical outcome was evaluated.</p> <p>Results</p> <p>NNMT mRNA level is markedly reduced in HCCs compared to non-cancerous surrounding tissues (P < 0.0001), and NNMT expression in tumors was significantly correlated with tumor stage (P = 0.010). Moreover, stratification of patients based on tumor NNMT mRNA levels revealed that the patients who expressed higher NNMT mRNA levels tended to have a shorter overall survival (OS) time (P = 0.053) and a significantly shorter disease-free survival (DFS) time (P = 0.016). Both NNMT expression (P = 0.0096) and tumor stage (P = 0.0017) were found to be significant prognostic factors for DFS in a multivariate analysis.</p> <p>Conclusion</p> <p>The results of this study indicated that NNMT gene expression is associated with tumor stage and DFS time in HCC cases. Because of the broad substrate specificity of NNMT, which could alter the efficacy and adverse effects of chemotherapy, NNMT merits further investigation regarding its role as a prognostic factor with a larger cohort of HCC patients.</p

Prediction of major depressive disorder following beta-blocker therapy in patients with cardiovascular diseases

Incident depression has been reported to be associated with poor prognosis in patients with cardiovascular disease (CVD), which might be associated with beta-blocker therapy. Because early detection and intervention can alleviate the severity of depression, we aimed to develop a machine learning (ML) model predicting the onset of major depressive disorder (MDD). A model based on L1 regularized logistic regression was trained against the South Korean nationwide administrative claims database to identify risk factors for the incident MDD after beta-blocker therapy in patients with CVD. We identified 50,397 patients initiating beta-blockers for CVD, with 774 patients developing MDD within 365 days after initiating beta-blocker therapy. An area under the receiver operating characteristic curve (AUC) of 0.74 was achieved. A history of non-selective beta-blockers and factors related to anxiety disorder, sleeping problems, and other chronic diseases were the most strong predictors. AUCs of 0.62–0.71 were achieved in the external validation conducted on six independent electronic health records and claims databases in the USA and South Korea. In conclusion, an ML model that identifies patients at high-risk for incident MDD was developed. Application of ML to identify susceptible patients for adverse events of treatment may serve as an important approach for personalized medicine

Data from: Genome-wide linkage disequilibrium and past effective population size in three Korean cattle breeds

The routine collection and use of genomic data are useful for effectively managing breeding programs for endangered populations. Linkage disequilibrium (LD) using high-density DNA markers has been widely used to determine population structures and predict the genomic regions that are associated with economic traits in beef cattle. The extent of LD also provides information about historical events, including past effective population size (Ne), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and Ne in three Korean cattle breeds that are genetically similar but have different coat colors (Brown, Brindle and Jeju Black Hanwoo). Brindle and Jeju Black are endangered breeds with small populations, whereas Brown Hanwoo is the main breeding population in Korea. DNA samples from these cattle breeds were genotyped using the Illumina BovineSNP50 Bead Chip. We examined 13 cattle breeds, including European taurines, African taurines and indicines, and hybrids to compare their LD values. Brown Hanwoo consistently had the lowest mean LD compared to Jeju Black, Brindle and the other 13 cattle breeds (0.13, 0.19, 0.21 and 0.15–0.22 respectively). The high LD values of Brindle and Jeju Black contributed to small Ne values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and Ne for each breed reflect the breeding strategy applied. The Ne for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract

Korean cattle 50K SNP data

This compressed data contains our original 50K SNP data of three Korean cattle breeds and 13 cattle breeds compiled from Bovine Hapmap data (Gautier et al., 2010)