THE EFFECTS OF ORAL ARGININE ON ITS METABOLIC PATHWAYS IN SPRAGUE-DAWLEY RATS

Oral arginine supplements are commonly used by the public for their presumed nitric oxide potentiating and vasodilatory role. However, there is a lack of clarity on the physiological impact of oral arginine on its metabolic pathways in the human body. As a versatile molecule, arginine is metabolized by multiple enzymes including arginase, nitric oxide synthase, arginine decarboxylase, and arginine:glycine amidinotransferase. Our lab has recently published a study on the physiological impact of oral arginine at a dose of 500 mg/kg/day administered for 4 weeks in male Sprague-Dawley rats. The present study examined the effects of oral L-arginine and D-arginine in 9-week-old male Sprague-Dawley rats, administered at a higher dose of 1000 mg/kg/day in drinking water for a longer duration of 16 weeks. We measured enzyme expression and activity for different enzymes, and levels of metabolites of the arginine enzymatic pathways in the urine, plasma and various organs of Sprague-Dawley rats. We also measured the expression of the primary arginine transporter, cationic amino acid transporter 1. Oral L-arginine did not alter the expression of cationic amino acid transporter 1 or the levels of arginine and lysine, which use the same transporter, in the plasma and various organs. Oral L-arginine decreased arginase expression in the ileum, and arginase activity in the plasma. It also decreased arginine:glycine amidinotransferase expression in the liver, and creatinine levels in the urine. Similarly, L-arginine supplementation decreased arginine decarboxylase expression in the ileum but increased the expression in the liver with increased plasma total polyamine levels. Interestingly, endothelial nitric oxide synthase expression was significantly increased with oral D-arginine, whereas L-arginine did not cause any significant effects in this pathway, in comparison to control. D-arginine is known to be inactive in the metabolic pathways, but surprisingly, D-arginine supplementation altered the expression of several enzymes and metabolite levels in the treated rats. In conclusion, long term oral supplementation of both L- and D-arginine significantly affected various enzymes and metabolites in the arginine metabolic pathways, as observed with a dose of 500 mg/kg/day for 4 weeks in the previous study from our lab, even though the changes differed in both studies. Determining the physiological impact of oral arginine supplements on the various metabolic pathways of arginine would allow for a better understanding of oral arginine uses, optimum dose and duration, and its safety and efficacy

Test Time Embedding Normalization for Popularity Bias Mitigation

Popularity bias is a widespread problem in the field of recommender systems, where popular items tend to dominate recommendation results. In this work, we propose 'Test Time Embedding Normalization' as a simple yet effective strategy for mitigating popularity bias, which surpasses the performance of the previous mitigation approaches by a significant margin. Our approach utilizes the normalized item embedding during the inference stage to control the influence of embedding magnitude, which is highly correlated with item popularity. Through extensive experiments, we show that our method combined with the sampled softmax loss effectively reduces popularity bias compare to previous approaches for bias mitigation. We further investigate the relationship between user and item embeddings and find that the angular similarity between embeddings distinguishes preferable and non-preferable items regardless of their popularity. The analysis explains the mechanism behind the success of our approach in eliminating the impact of popularity bias. Our code is available at https://github.com/ml-postech/TTEN.Comment: 5 pages, CIKM 202

Item-based Variational Auto-encoder for Fair Music Recommendation

We present our solution for the EvalRS DataChallenge. The EvalRS DataChallenge aims to build a more realistic recommender system considering accuracy, fairness, and diversity in evaluation. Our proposed system is based on an ensemble between an item-based variational auto-encoder (VAE) and a Bayesian personalized ranking matrix factorization (BPRMF). To mitigate the bias in popularity, we use an item-based VAE for each popularity group with an additional fairness regularization. To make a reasonable recommendation even the predictions are inaccurate, we combine the recommended list of BPRMF and that of item-based VAE. Through the experiments, we demonstrate that the item-based VAE with fairness regularization significantly reduces popularity bias compared to the user-based VAE. The ensemble between the item-based VAE and BPRMF makes the top-1 item similar to the ground truth even the predictions are inaccurate. Finally, we propose a `Coefficient Variance based Fairness' as a novel evaluation metric based on our reflections from the extensive experiments.Comment: 6pages, CIKM 2022 Data challeng

A hermaphrodite dog with bilateral ovotestes and pyometra

Hermaphroditism was identified in a 3-year-old American Cocker spaniel with an enlarged os clitoridis that was shown as reddish finger-like structure protruding from the vulva. The urethral orifice was located cranially to the base of the os clitoridis. The gonads were situated caudal to the kidneys at the cranial tips of the uterine horns, and were composed mainly of seminiferous tubules and interstitial cells and had ovarian follicles in the cortices. The uterus was enlarged and revealed pyometra. Gross and histopathological findings of the dog suggested hermaphroditism with bilateral ovotestes and pyometra

Orthotopic transplantation of retinoblastoma cells into vitreous cavity of zebrafish for screening of anticancer drugs

BACKGROUND: With high throughput screening, novel therapeutic agents can be efficiently identified. Unfortunately, researchers only resort to in vitro cell viability assays for screening of anticancer drugs for retinoblastoma, the most common intraocular cancer in the childhood. Current available animal models of retinoblastoma require more than 2 weeks for tumour formation and the investigation of the efficacy of therapeutic agents. In this study, we established a novel orthotopic transplantation model of retinoblastoma in zebrafish as an in vivo animal model for screening of anticancer drugs. METHODS: We injected retinoblastoma cells into the vitreous cavity of zebrafish at 48 hours after fertilization. Eyeballs of zebrafish were scanned daily under the confocal laser microscope, and the tumor population was quantitatively analyzed by measuring the mean intensity of green fluorescent protein (GFP). Transplanted retinoblastoma cells were isolated to perform further analyses including Western blotting and reverse transcriptase-polymerase chain reaction to confirm that retinoblastoma cells maintained their characteristics as tumor cells even after transplantation and further isolation. To figure out the potential of this model for screening of anticancer drugs, zebrafish were cultured in Ringer’s solution containing carboplatin and melphalan after the injection of retinoblastoma cells. RESULTS: The degree of the tumor population was dependent on the number of retinoblastoma cells injected and maintained stably for at least 4 days. Transplanted retinoblastoma cells maintain their proliferative potential and characteristics as retinoblastoma cells after isolation. Interestingly, systemic application of carboplatin and melphalan demonstrated significant reduction in the tumor population, which could be quantitatively analyzed by the estimation of the mean intensity of GFP. CONCLUSIONS: This orthotopic retinoblastoma model in zebrafish is expected to be utilized for the screening of anticancer drugs for the treatment of retinoblastoma

Enzyme replacement therapy for mucopolysaccharidosis type I among patients followed within the MPS Brazil network

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Fewclinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, n3712329CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçã

A recoiling supermassive black hole in the quasar SDSSJ092712.65+294344.0?

We present SDSSJ092712.65+294344.0 as the best candidate to date for a recoiling supermassive black hole (SMBH). SDSSJ0927+2943 shows an exceptional optical emission-line spectrum with two sets of emission lines: one set of very narrow emission lines, and a second set of broad Balmer and broad high-ionization forbidden lines which are blueshifted by 2650 km\s relative to the set of narrow emission lines. This observation is most naturally explained if the SMBH was ejected from the core of the galaxy, carrying with it the broad-line gas while leaving behind the bulk of the narrow-line gas. We show that the observed properties of SDSSJ0927+2943 are consistent with predictions and expectations from recent numerical relativity simulations which demonstrate that SMBHs can receive kicks up to several thousand km\s due to anisotropic emission of gravitational waves during the coalescence of a binary. Our detection of a strong candidate for a rapidly recoiling SMBH implies that kicks large enough to remove SMBHs completely from their host galaxies do occur, with important implications for models of black hole and galaxy assembly at the epoch of structure formation, and for recoil models.Comment: To appear in ApJ Letters, 678, L81, 2008 (May 10 issue); includes 1 colour figure. Version with higher-resolution figure and related papers at http://www.xray.mpe.mpg.de/~skomossa

Original Article Morusin induces cell death through inactivating STAT3 signaling in prostate cancer cells

Abstract: STAT3 has been recognized as an efficacious drug target for prostate cancer because of its constitutive activation in this fatal disease. We recently identified the root bark of Morus alba Linn. as a potential STAT3 inhibitor among 33 phytomedicines traditionally used in Korea. Morusin, an active compound isolated from the root bark of Morus alba, has shown anti-oxidant and anti-inflammatory effects. In the present study, we examined whether morusin has a potential as an anti-cancer agent in prostate cancer. We found that morusin suppressed viability of prostate cancer cells, but little effect in normal human prostate epithelial cells. Morusin also reduced STAT3 activity by inhibiting its phosphorylation, nuclear accumulation, and DNA binding activity. In addition, morusin down-regulated expression of STAT3 target genes encoding Bcl-xL, Bcl-2, Survivin, c-Myc and Cyclin D1, which are involved in regulation of apoptosis and cell cycle. Furthermore, morusin induced apoptosis in human prostate cancer cells by reducing STAT3 activity. Taken together, these results suggest that morusin could be a potentially therapeutic agent for prostate cancer by reducing STAT3 activity and inducing apoptosis

On the nature of the red, 2MASS-selected AGN in the local Universe I: an optical spectroscopic study

We present optical spectra for a representative sample of 27 nearby (z < 0.2) Two Micron All Sky Survey (2MASS)-selected active galactic nuclei (AGN) with red near-infrared colours (J − KS ≳ 2.0). The spectra were taken with the ISIS spectrograph on the William Herschel Telescope with the aim of determining the nature of the red 2MASS AGN, in particular whether they are young quasars obscured by their natal cocoons of gas and dust. We compare our findings with those obtained for comparison samples of PG quasars and unobscured type 1 AGN. The spectra show a remarkable variety, including moderately reddened type 1 objects (45 per cent), type 1 objects that appear similar to traditional ultraviolet (UV)-/optical-selected AGN (11 per cent), narrow-line type 1 Seyfert AGN (15 per cent), type 2 AGN (22 per cent) and H II/composite objects (7 per cent). The high Balmer decrements that we measure in many of the type 1 objects are consistent with their red J − KS colours being due to moderate levels of dust extinction (0.2 < E(B − V) < 1.2). However, we measure only modest velocity shifts and widths for the broader [O III]λ5007 emission-line components that are similar to those measured in the comparison samples. This suggests that the outflows in the red 2MASS objects are not unusual compared with those of optical-/UV-selected AGN of similar luminosity. In addition, the Eddington ratios for the 2MASS sample are relatively modest. Overall, based on their optical spectra, we find no clear evidence that the population of red, 2MASS-selected AGN at low redshifts represents young quasars. Most plausibly, these objects are normal type 1 AGN that are moderately obscured by material in the outer layers of the circumnuclear tori or in the discs of the host galaxies

Laboratory information management system for COVID-19 non-clinical efficacy trial data

Background : As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results : In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions : This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.This research was supported by the National research foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2020M3A9I2109027 and 2021M3H9A1030260)