Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiotensin II-induced NADPH Oxidase Activation Impairs Insulin Signaling in Skeletal Muscle Cells*

The renin-angiotensin system (RAS) and reactive oxygen species (ROS) have been implicated in the development of insulin resistance and its related complications. There is also evidence that angiotensin II (Ang II)-induced generation of ROS contributes to the development of insulin resistance in skeletal muscle, although the precise mechanisms remain unknown. In the present study, we found that Ang II markedly enhanced NADPH oxidase activity and consequent ROS generation in L6 myotubes. These effects were blocked by the angiotensin II type 1 receptor blocker losartan, and by the NADPH oxidase inhibitor apocynin. Ang II also promoted the translocation of NADPH oxidase cytosolic subunits p47phox and p67phox to the plasma membrane within 15 min. Furthermore, Ang II abolished insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1), activation of protein kinase B (Akt), and glucose transporter-4 (GLUT4) translocation to the plasma membrane, which was reversed by pretreating myotubes with losartan or apocynin. Finally, small interfering RNA (siRNA)-specific gene silencing targeted specifically against p47phox (p47siRNA), in both L6 and primary myotubes, reduced the cognate protein expression, decreased NADPH oxidase activity, restored Ang II-impaired IRS1 and Akt activation as well as GLUT4 translocation by insulin. These results suggest a pivotal role for NADPH oxidase activation and ROS generation in Ang II-induced inhibition of insulin signaling in skeletal muscle cells.
Identification and Characterization of miRNA Transcriptome in Potato by High-Throughput Sequencing

Micro RNAs (miRNAs) represent a class of short, non-coding, endogenous RNAs which play important roles in post-transcriptional regulation of gene expression. While the diverse functions of miRNAs in model plants have been well studied, the impact of miRNAs in crop plant biology is poorly understood. Here we used high-throughput sequencing and bioinformatics analysis to analyze miRNAs in the tuber bearing crop potato (Solanum tuberosum). Small RNAs were analysed from leaf and stolon tissues. 28 conserved miRNA families were found and potato-specific miRNAs were identified and validated by RNA gel blot hybridization. The size, origin and predicted targets of conserved and potato specific miRNAs are described. The large number of miRNAs and complex population of small RNAs in potato suggest important roles for these non-coding RNAs in diverse physiological and metabolic pathways.
Computational Rationalization: The Inverse Equilibrium Problem

Modeling the purposeful behavior of imperfect agents from a small number of observations is a challenging task. When restricted to the single-agent decision-theoretic setting, inverse optimal control techniques assume that observed behavior is an approximately optimal solution to an unknown decision problem. These techniques learn a utility function that explains the example behavior and can then be used to accurately predict or imitate future behavior in similar observed or unobserved situations. In this work, we consider similar tasks in competitive and cooperative multi-agent domains. Here, unlike single-agent settings, a player cannot myopically maximize its reward; it must speculate on how the other agents may act to influence the game's outcome. Employing the game-theoretic notion of regret and the principle of maximum entropy, we introduce a technique for predicting and generalizing behavior.
Calpain-generated natural protein fragments as short-lived substrates of the N-end rule pathway

Significance Calpains are a family of intracellular proteases that have in common their dependence on Ca2+ and their ability to make a small number of specific cuts in their natural protein substrates. Although many calpain-generated protein fragments have been identified, understanding their functions is just beginning. This study shows that natural C-terminal fragments of a variety of proteins, including transmembrane ion channels, transcriptional regulators, apoptosis controllers, kinases, and phosphatases, are short-lived substrates of the N-end rule pathway, a ubiquitin-dependent processive proteolytic system that recognizes destabilizing N-terminal residues of protein substrates. This advance illuminates functional aspects of specific calpain fragments and suggests a specific molecular basis for many of the previously identified, mechanistically unclear roles of the N-end rule pathway. Calpains are Ca2+-dependent intracellular proteases. We show here that calpain-generated natural C-terminal fragments of proteins that include G protein–coupled receptors, transmembrane ion channels, transcriptional regulators, apoptosis controllers, kinases, and phosphatases (Phe-GluN2a, Lys-Ica512, Arg-Ankrd2, Tyr-Grm1, Arg-Atp2b2, Glu-Bak, Arg-Igfbp2, Glu-IκBα, and Arg-c-Fos), are short-lived substrates of the Arg/N-end rule pathway, which targets destabilizing N-terminal residues. We also found that the identity of a fragment’s N-terminal residue can change during evolution, but the residue’s destabilizing activity is virtually always retained, suggesting selection pressures that favor a short half-life of the calpain-generated fragment. It is also shown that a self-cleavage of a calpain can result in an N-end rule substrate. Thus, the autoprocessing of calpains can control them by making active calpains short-lived. These and related results indicate that the Arg/N-end rule pathway mediates the remodeling of oligomeric complexes by eliminating protein fragments that are produced in these complexes through cleavages by calpains or other nonprocessive proteases. We suggest that this capability of the Arg/N-end rule pathway underlies a multitude of its previously known but mechanistically unclear functions.
Transcriptome analysis in primary colorectal cancer tissues from patients with and without liver metastases using next‐generation sequencing

Colorectal cancer (CRC) is the third most common cancer worldwide and liver metastases are the leading cause of death in patients with CRC. In this study, we performed next‐generation sequencing profiling on primary colorectal tumor tissues obtained from three CRC patients with liver metastases and three CRC patients without liver metastases to identify differentially expressed genes (DEGs) that might be responsible for the metastases process. After filtering 2690 DEGs, comprising 996 upregulated and 1694 downregulated RNAs, 22 upregulated and 73 downregulated DEGs were identified. Gene ontology (GO) and pathway analyses were performed to determine the underlying mechanisms. Single‐organism process (biological process), cell (cellular component), and binding (molecular function) were the most related terms in the GO analysis. We selected the top 13 upregulated and top 12 downregulated genes by fold change to verify their differential expression using quantitative real‐time reverse transcription PCR (qRT‐PCR) and immunohistochemistry (IHC). The validation showed that three most significantly upregulated DEGs were HOXD10, UGT2A3, and SLC13A2, whereas the five most significantly downregulated DEGs were SPP1, CXCL8, MMP3, OSM, and CXCL6, respectively. These aberrantly expressed genes may play pivotal roles in promoting or inhibiting metastases. Further studies are required to determine the functions of DEGs to promote the diagnosis of metastases and provide novel chemotherapy targets.
Generic Lossless Visible Watermarking—A New Approach

A novel method for generic visible watermarking with a capability of lossless image recovery is proposed. The method is based on the use of deterministic one-to-one compound mappings of image pixel values for overlaying a variety of visible watermarks of arbitrary sizes on cover images. The compound mappings are proved to be reversible, which allows for lossless recovery of original images from watermarked images. The mappings may be adjusted to yield pixel values close to those of desired visible watermarks. Different types of visible watermarks, including opaque monochrome and translucent full color ones, are embedded as applications of the proposed generic approach. A two-fold monotonically increasing compound mapping is created and proved to yield more distinctive visible watermarks in the watermarked image. Security protection measures by parameter and mapping randomizations have also been proposed to deter attackers from illicit image recoveries. Experimental results demonstrating the effectiveness of the proposed approach are also included.
Biological properties of different extracts of two Senecio species

This study reports on the antioxidant, anti-diabetic and cytotoxic properties of different extracts of two Senecio species, Senecio vulgaris and Senecio inaequidens. Leaves of the latter are used as food in specific populations of Southern of Africa. Both investigated species of Senecio were found to possess different biological activities. S. inaequidens extracts possess a greater antioxidant activity in comparison with S. vulgaris. Highly significant and dose-dependent performance was obtained with the methanolic and dichloromethane extracts of S. vulgaris and the n-hexane extract of S. inaequidens regarding cytotoxic activity on cancer cell lines, while none of the extracts demonstrated activity on normal cell line MRC-5. Both Senecio species also show appreciable α-amylase inhibition, particularly the methanolic and dichloromethane extracts, and this may confer anti-diabetic properties on the extract.
Glutamate Receptor-Mediated Oligodendrocyte Toxicity in Periventricular Leukomalacia: A Protective Role for Topiramate

Periventricular leukomalacia is a form of hypoxic–ischemic cerebral white matter injury seen most commonly in premature infants and is the major antecedent of cerebral palsy. Glutamate receptor-mediated excitotoxicity is a predominant mechanism of hypoxic–ischemic injury to developing cerebral white matter. We have demonstrated previously the protective effect of AMPA–kainate-type glutamate receptor blockade in a rodent model of periventricular leukomalacia. The present study explores the therapeutic potential of glutamate receptor blockade for hypoxic–ischemic white matter injury. We demonstrate that AMPA receptors are expressed on developing human oligodendrocytes that populate fetal white matter at 23–32 weeks gestation, the period of highest risk for periventricular leukomalacia. We show that the clinically available anticonvulsant topiramate, when administered post-insult in vivo, is protective against selective hypoxic–ischemic white matter injury and decreases the subsequent neuromotor deficits. We further demonstrate that topiramate attenuates AMPA–kainate receptor-mediated cell death and calcium influx, as well as kainate-evoked currents in developing oligodendrocytes, similar to the AMPA–kainate receptor antagonist 6-nitro-7-sulfamoylbenzo-(f)quinoxaline-2,3-dione (NBQX). Notably, protective doses of NBQX and topiramate do not affect normal maturation and proliferation of oligodendrocytes either in vivo or in vitro. Taken together, these results suggest that AMPA–kainate receptor blockade may have potential for translation as a therapeutic strategy for periventricular leukomalacia and that the mechanism of protective efficacy of topiramate is caused at least in part by attenuation of excitotoxic injury to premyelinating oligodendrocytes in developing white matter.
Externally Pressurizing Salvaged Blood Reinfusion Bags : Predictable , Preventable Cause of Fatal Air Embolism

To the Editor:—We read with interest the investigation by Dr. Wan et al. of postoperative impairment of cognitive function in rats. We would like to ask whether the investigators believe there was an adequate control group with which to compare the results of their surgical intervention. In addition to the neuroleptic analgesia group alone, it may have been advantageous to include a sham surgical group that received a similar skin incision to the splenectomized group of rats with postoperative treatment of bupivacaine infiltration. This may have permitted an assessment of the contribution of a surgical incision alone with wound infiltration of 0.25% bupivacaine, because, contrary to the suggestion by the authors, the two groups of rats may not have received identical anesthetic regimens, i.e., there was no assessment of the contribution of the local anesthetic infiltration. Bupivacaine has been shown on its own to suppress systemic cytokine activation when given locally or systemically. The investigators suggest the neuroinflammatory changes are related solely to the splenectomy surgical injury and not to other factors, such as the development of postoperative infection, which may or may not have been recognized in these rats. Splenectomized animals would more likely develop postoperative infections, and that by itself may alter neurocytokine levels. In addition, surgical healing and its potential impairment of full ambulation in the rats after splenectomy may have also contributed to their difficulty in completing the learning maze, which may or may not have been related to neurocognitive impairment. A few animals with postoperative infection or impairment in their ambulation may have skewed the results on days 1 and 3 after surgery and may explain the large range of learning abilities seen in the Y-maze testing on those days. It would be interesting to note whether there were individual animal correlates of increased neuroinflammation with increased learning times in the maze. We appreciate the work presented by Dr. Wan et al. because they raise important issues with regard to postoperative cognitive impairment and the role of inflammatory changes in the central nervous system.
Management of iron deficiency anemia in inflammatory bowel disease – a practical approach

Although anemia is the most common systemic manifestation of inflammatory bowel disease (IBD), among the broad spectrum of extraintestinal disease complications encountered in IBD, including arthritis and osteopathy, it has generally received little consideration. However, not only in terms of frequency, but also with regard to its potential effect on hospitalization rates and on the quality of life and work, anemia is indeed a significant and costly complication of IBD. Anemia is multifactorial in nature, the most prevalent etiological forms being iron deficiency anemia (IDA) and anemia of chronic disease. In a condition associated with inflammation, such as IBD, the determination of iron status using common biochemical parameters alone is inadequate. A more accurate assessment may be attained using new iron indices including reticulocyte hemoglobin content, percentage of hypochromic red cells or zinc protoporphyrin. While oral iron supplementation has traditionally been a mainstay of IDA treatment, it has also been linked to extensive gastrointestinal side effects and possible disease exacerbation. However, many physicians are still reluctant to administer iron intravenously, despite the wide availability of a variety of new IV preparations with improved safety profiles, and despite the recommendations of international expert guidelines. This article discusses improved diagnostic and therapeutic strategies based on new clinical insights into the regulation of iron homeostasis.
WHERE DO PHONEMES COME FROM? A VIEW FROM THE BOTTOM

Infants have a remarkable ability to perceive all manner of phonetic contrasts. The phonological categories of a language, however, have to be learned from experience. Two learning paradigms are contrasted – supervised learning (where learners receive feedback on their categorization attempts) and unsupervised learning (where learners rely only on properties of the input). It is argued that unsupervised learning may be the appropriate paradigm, at least for the initial stages of acquisition. Thereafter, the emergence of phoneme categories draws on various kinds of knowledge available to the learner, including knowledge of articulation, and of literacy conventions. A concluding section emphasizes the taxonomic nature of the phoneme, and suggests that the special salience of a phonemic representation reflects the status of the phoneme as a basic level category.
Designing Traceability into Big Data Systems

Providing an appropriate level of accessibility and traceability to data or process elements (so-called Items) in large volumes of data, often Cloud-resident, is an essential requirement in the Big Data era. Enterprise-wide data systems need to be designed from the outset to support usage of such Items across the spectrum of business use rather than from any specific application view. The design philosophy advocated in this paper is to drive the design process using a so-called description-driven approach which enriches models with meta-data and description and focuses the design process on Item re-use, thereby promoting traceability. Details are given of the description-driven design of big data systems at CERN, in health informatics and in business process management. Evidence is presented that the approach leads to design simplicity and consequent ease of management thanks to loose typing and the adoption of a unified approach to Item management and usage.
Communication transmitter individual feature extraction method based on stacked denoising autoencoders under small sample prerequisite

For the goal of improving the effectiveness and robustness of identifying communicatioin radio individual under small sample prerequisite, we proposed a communication radio individual identification method based on stacked denoising auto-encoder, which can learn fingerprint feature from input unlabeled communication radio signal samples and then extract low-dimension feature of raio signals facing to high-dimension sample space. Finally, the accurate individual identification phase will be accomplished in classifier. Experiments showed the effectiveness and reliability of method proposed on three different communication radio data set.
Reviving Inert Knowledge: Analogical Abstraction Supports Relational Retrieval of Past Events

We present five experiments and simulation studies to establish late analogical abstraction as a new psychological phenomenon: Schema abstraction from analogical examples can revive otherwise inert knowledge. We find that comparing two analogous examples of negotiations at recall time promotes retrieving analogical matches stored in memory-a notoriously elusive effect. Another innovation in this research is that we show parallel effects for real-life autobiographical memory (Experiments 1-3) and for a controlled memory set (Experiments 4 and 5). Simulation studies show that a unified model based on schema abstraction can capture backward (retrieval) effects as well as forward (transfer) effects.
Activities of Oseltamivir and Ribavirin Used Alone and in Combination against Infections in Mice with Recent Isolates of Influenza a (H1N1) and B Viruses

Mouse models have been widely used for evaluating potential influenza virus inhibitors. However, the viral strains traditionally used in these models are fairly old and do not represent currently circulating viruses in nature. We developed two new lethal infection models in mice using mouse-adapted influenza A/New Caledonia/20/99 (H1N1) and influenza B/Sichuan/379/99 viruses. Both virus infections were used to study oral treatment with oseltamivir and ribavirin, both alone and in combination. Oral treatments were given twice daily for 5 days starting 4 h before infection in initial studies. Against influenza A, oseltamivir was active at 10, 20, and 40 mg/kg/day, protected 80–100% of mice from death and reduced lung consolidation — ribavirin was similarly effective at 20, 40, and 80 mg/kg/day. When treatments were initiated after virus challenge, delaying treatment with oseltamivir even 1 day caused it to be ineffective. Ribavirin prevented mortality by 50–80% when treatments were delayed 1–4 days after infection. The combination of the two drugs (oseltamivir at 20 mg/kg/day and ribavirin at 40 mg/kg/day) was no better than ribavirin alone. In contrast to what we observed with influenza A virus infections, oseltamivir and ribavirin showed similar dose-related antiviral activities against influenza B virus infections. The compounds both significantly increased survival when treatments started up to 4 days after infection, but ribavirin was more active than oseltamivir (50–80% survival compared to 30–40% survival, respectively, when starting treatments on days 2–4 after infection). By varying the doses of each drug that were used in combination (oseltamivir at 1.25, 2.5 and 5 mg/kg/day; ribavirin at 5, 10 and 20 mg/kg/day) certain dosage combinations were superior to either compound used alone as assessed by decreased mortality, lung virus titre, lung score and lung weight parameters. These activities differed from published results with older, more established virus strains as oseltamivir was less effective and ribavirin was more active than previously reported.
The homologous and heterologous regions within the iap gene allow genus- and species-specific identification of Listeria spp. by polymerase chain reaction

The iap gene of Listeria species encodes protein p60. The comparison of iap-related genes from different Listeria species indicated common and variable regions within these genes which appeared to be specific for each Listeria species. On the basis of the iap gene sequences, pairs of polymerase chain reaction (PCR) primers which allowed the unambiguous identification of all members of the genus Listeria, of groups of related Listeria species, and of L. monocytogenes, exclusively, were selected. The PCR primers specific for L. monocytogenes yielded PCR products which represented essentially the repeat region of the iap gene. The size of these PCR products allowed an estimate of the number of the TN repeat units within the repeat region of the p60 protein of an L. monocytogenes strain. The data indicated that the number of repeat units differed among L. monocytogenes isolates.
Angiotensin II and Angiotensin-(1-7) in Paraventricular Nucleus Modulate Cardiac Sympathetic Afferent Reflex in Renovascular Hypertensive Rats

Background The enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation that contributes to the pathogenesis and progression of hypertension. Activation of AT1 receptors by angiotension (Ang) II in the paraventricular nucleus (PVN) augments the enhanced CSAR and sympathetic outflow in hypertension. The present study is designed to determine whether Ang-(1-7) in PVN plays the similar roles as Ang II and the interaction between Ang-(1-7) and Ang II on CSAR in renovascular hypertension. Methodology/Principal Findings The two-kidney, one-clip (2K1C) method was used to induce renovascular hypertension. The CSAR was evaluated by the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to epicardial application of capsaicin in sinoaortic-denervated and cervical-vagotomized rats with urethane and α-chloralose anesthesia. Either Ang II or Ang-(1-7) in PVN caused greater increases in RSNA and MAP, and enhancement in CSAR in 2K1C rats than in sham-operated (Sham) rats. Mas receptor antagonist A-779 and AT1 receptor antagonist losartan induced opposite effects to Ang-(1-7) or Ang II respectively in 2K1C rats, but losartan had no effects in Sham rats. Losartan but not the A-779 abolished the effects of Ang II, while A-779 but not the losartan blocked the effects of Ang-(1-7). PVN pretreatment with Ang-(1-7) dose-dependently augmented the RSNA, MAP, and CSAR responses to the Ang II in 2K1C rats. Ang II level, AT1 receptor and Mas receptor protein expression in PVN increased in 2K1C rats compared with Sham rats but Ang-(1-7) level did not. Conclusions Ang-(1-7) in PVN is as effective as Ang II in enhancing the CSAR and increasing sympathetic outflow and both endogenous Ang-(1-7) and Ang II in PVN contribute to the enhanced CSAR and sympathetic outflow in renovascular hypertension. Ang-(1-7) in PVN potentiates the effects of Ang II in renovascular hypertension.