Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of Dietary Protein on Gulonolactone Hydrolase, Gulonate NADP Oxidoreductase, and Tissue Ascorbate in Male and Female Rats

Conditions interfering with the translational facility of liver ribosomes to synthesize protein have been associated with decreased ability of rats to synthesize, store and excrete L-ascorbic acid. Hypophysectomized rats whose hepatic ribosomes fail to incorporate amino acids into protein at a normal rate (1, 2), also show a substantial diminution in rate of biosynthesis, body pool size and urinary excretion of L-ascorbic acid (3). Growth hormone administration, which has been shown to restore the amino acid incorporating function of ribosomes from hypophysectomized animals (4), has been found to enhance the biosynthesis, storage and excretion of ascorbate (3). This enhancing effect on ascorbate production appears to depend primarily on an induced increase in the activity of gulonolactone hydrolase (EC3.1.1.18) (5), an enzyme in the biosynthetic pathway between D-glucuronic acid and L-ascorbic acid specifically diminished by hypophysectomy and apparently the rate-limiting enzyme in ascorbate synthesis in hypophysectomized rats (6). The specific induction of gulonolactone hydrolase by growth hormone in hypophysectomized rats has been shown to be inhibited by administration of the metabolic inhibitor of protein synthesis, puromycin (7). The decreased ribosomal function after hypophysectomy bears resemblance to decreased translational function of liver ribosomes in conditions of starvation and protein deficiency (8–11), conditions like hypophysectomy associated with decreased biosynthesis, tissue accumulation and excretion of L-ascorbic acid (12). Since hepatic enzymes are dependent on ribosomal protein synthesis, as are other proteins of liver, it is possible that the changes in ascorbate metabolism in these conditions are the result of decreased production of an enzyme or enzymes acting within the biosynthetic pathway to L-ascorbic acid. Unfortunately, the effects of starvation or protein deficiency on specific enzymes in the biosynthesis of L-ascorbic acid from D-glucuconic acid have not been clear.
Chemotactic signaling via carbohydrate phosphotransferase systems in Escherichia coli

Chemotaxis allows bacteria to follow gradients of nutrients, environmental stimuli, and signaling molecules, optimizing bacterial growth and survival. Escherichia coli has long served as a model of bacterial chemotaxis, and the signal processing by the core of its chemotaxis pathway is well understood. However, most of the research so far has focused on one branch of chemotactic signaling, in which ligands bind to periplasmic sensory domains of transmembrane chemoreceptors and induce a conformational change that is transduced across the membrane to regulate activity of the receptor-associated kinase CheA. Here we quantitatively characterize another, receptor-independent branch of chemotactic signaling that is linked to the sugar uptake through a large family of phosphotransferase systems (PTSs). Using in vivo characterization of intracellular signaling and protein interactions, we demonstrate that signals from cytoplasmic PTS components are transmitted directly to the sensory complexes formed by chemoreceptors, CheA and an adapter protein CheW. We further conclude that despite different modes of sensing, the PTS- and receptor-mediated signals have similar regulatory effects on the conformation of the sensory complexes. As a consequence, both types of signals become integrated and undergo common downstream processing including methylation-dependent adaptation. We propose that such mode of signaling is essential for efficient chemotaxis to PTS substrates and may be common to most bacteria.
Long-term efficacy and safety of intra-articular sodium hyaluronate (Hyalgan) in patients with osteoarthritis of the knee.

OBJECTIVE This prospective cohort study evaluated the long-term efficacy and safety of 5 weekly intra-articular (i.a.) injections of sodium hyaluronate (Hyalgan) in 76 patients (92 knees) with moderate to severe osteoarthritis (OA) of the knee whose pain was not controlled by conventional measures. RESULTS Thirteen patients had a repeat treatment course. A total of 72% of patients achieved > 50% improvement (defined by physical examination and assessment of pain using a visual analog scale [VAS]) for 1 year or longer; 9% of patients failed to achieve > 50% improvement for any period of time. The duration of response exceeded 2 years in some patients. Total knee replacement surgery was avoided or significantly delayed in 15 of 19 patients who were considering surgery prior to the injections. Ten of 15 (67%) knees improved after a repeat treatment course. Local adverse events were minor and infrequent. CONCLUSION Intra-articular sodium hyaluronate was an effective and safe treatment for pain in difficult-to-treat patients with moderate to severe OA of the knee.
Development of a Convenient In Vivo Hepatotoxin Assay Using a Transgenic Zebrafish Line with Liver-Specific DsRed Expression

Previously we have developed a transgenic zebrafish line (LiPan) with liver-specific red fluorescent protein (DsRed) expression under the fabp10a promoter. Since red fluorescence in the liver greatly facilitates the observation of liver in live LiPan fry, we envision that the LiPan zebrafish may provide a useful tool in analyses of hepatotoxicity based on changes of liver red fluorescence intensity and size. In this study, we first tested four well-established hepatotoxins (acetaminophen, aspirin, isoniazid and phenylbutazone) in LiPan fry and demonstrated that these hepatotoxins could significantly reduce both liver red fluorescence and liver size in a dosage-dependent manner, thus the two measurable parameters could be used as indicators of hepatotoxicity. We then tested the LiPan fry with nine other chemicals including environmental toxicants and human drugs. Three (mefenamic acid, lindane, and arsenate) behave like hepatotoxins in reduction of liver red fluorescence, while three others (17β-estradiol, TCDD [2,3,7,8-tetrachlorodibenzo-p-dioxin] and NDMA [N-nitrosodimethylamine]) caused increase of liver red fluorescence and the liver size. Ethanol and two other chemicals, amoxicillin (antibiotics) and chlorphenamine (pain killer) did not resulted in significant changes of liver red fluorescence and liver size. By quantitative RT-PCR analysis, we found that the changes of red fluorescence intensity caused by different chemicals correlated to the changes of endogenous fabp10a RNA expression, indicating that the measured hepatotoxicity was related to fatty acid transportation and metabolism. Finally we tested a mixture of four hepatotoxins and observed a significant reduction of red fluorescence in the liver at concentrations below the lowest effective concentrations of individual hepatotoxins, suggesting that the transgenic zebrafish assay is capable of reporting compound hepatotoxicity effect from chemical mixtures. Thus, the LiPan transgenic fry provide a rapid and convenient in vivo hepatotoxicity assay that should be applicable to high-throughput hepatotoxicity test in drug screening as well as in biomonitoring environmental toxicants.
Exogenous FABP4 increases breast cancer cell proliferation and activates the expression of fatty acid transport proteins

Adipose tissue plays an important role in tumor progression, because it provides nutrients and adipokines to proliferating cells. Fatty acid binding protein 4 (FABP4) is a key adipokine for fatty acid transport. In metabolic pathologies, plasma levels of FABP4 are increased. However, the role of this circulating protein is unknown. Recent studies have demonstrated that FABP4 might have a role in tumor progression, but the molecular mechanisms involved are still unclear. In this study, we analysed the role of eFABP4 (exogenous FABP4) in breast cancer progression. MCF‐7 and MDA‐MB‐231 breast cancer cells did not express substantial levels of FABP4 protein, but intracellular FABP4 levels increased after eFABP4 incubation. Moreover, eFABP4 enhanced the proliferation of these breast cancer cells but did not have any effect on MCF‐7 and MDA‐MB‐231 cell migration. Additionally, eFABP4 induced the AKT and MAPK signaling cascades in breast cancer cells, and the inhibition of these pathways reduced the eFBAP4‐mediated cell proliferation. Interestingly, eFABP4 treatment in MCF‐7 cells increased levels of the transcription factor FoxM1 and the fatty acid transport proteins CD36 and FABP5. In summary, we showed that eFABP4 plays a key role in tumor proliferation and activates the expression of fatty acid transport proteins in MCF‐7 breast cancer cells. © 2016 Wiley Periodicals, Inc.
Sydowia polyspora Dominates Fungal Communities Carried by Two Tomicus Species in Pine Plantations Threatened by Fusarium circinatum

Bark beetles (Coleoptera, Scolytinae) carry a diverse filamentous fungal community sometimes acting as vectors or carriers of phytopathogens. In this study, mycobiota carried by two Tomicus species (Tomicus piniperda and Tomicus destruens) were investigated through (i) morphological and molecular identification of taxa; (ii) taxonomic richness, diversity, evenness, dominance and phoresy indices; (iii) ecological network analysis and (iv) statistical co-occurrence analysis. The studied mycobiota were formed by eleven taxa and showed a moderate fungal diversity with low evenness. The fungus Sydowia polyspora was significantly abundant and dominated the community. All the fungal taxa were randomly associated. Both insect species (T. piniperda and T. destruens) were collected from plantations of Pinus radiata infected by Fusarium circinatum. The ecological factors that could drive community ecology and phoretic links between fungi and bark beetles are discussed.
Recognition of Tactile Relief by Children and Adults

This study was designed to compare tactile sensitivity of children and adults on printed target stimuli covering a wide range of elevations and requiring different resolutions. A recognition-relief task using 9 digits at 6 levels of elevation from a surface (0.5, 0.4, 0.3, 0.2, 0.1, and 0.05 mm) was presented to 24 young adults and 24 children. As predicted, relief elevations as low as 0.05 mm were recognized above chance. As predicted, children performed significantly more poorly than the adults on recognition at all elevations, although the difference increased as elevation increased. Adults performed significantly better than children on high-resolution digit 8, but there was no reliable age difference on low-resolution digit 1. Recognition difference between the high- and low-resolution digits decreased nonlinearly as elevation increased, irrespective of age. Overall, the findings support previous research indicating greater tactile sensitivity in adults than in children, but the superiority was moderated by the elevation and resolution requirements of the stimuli.
Rapid and Sustained Response to Tocilizumab in Patients with Polymyalgia Rheumatica Resistant or Intolerant to Glucocorticoids: A Multicenter Open-label Study

To the Editor: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease affecting people aged 50 years or older. PMR usually improves with glucocorticoids (GC), with rapid resolution of symptoms in response to 15–20 mg/day prednisone1. However, around half of the patients with PMR experience a flare of disease when GC are tapered or stopped, and these patients may require longterm GC treatment because of repeated relapses, leading to undesirable side effects. In addition, some patients with PMR have a partial response or do not respond to initial GC treatment1. In this setting, alternative treatments, namely GC-sparing agents, are required. Methotrexate gave conflicting results in PMR while tumor necrosis factor-α inhibitors failed to prevent relapses in randomized controlled studies. Data suggest that interleukin 6 (IL-6) contributes to the inflammatory process of PMR2: Increased serum levels of IL-6 have been described in PMR and correlate with disease activity3; the risk of recurrence/relapse of PMR is associated with persistent elevated IL-6 serum levels as well as with a genetic polymorphism of the IL-6 promoter gene3; and reports described the efficacy of tocilizumab (TCZ), an anti-IL-6 receptor agent, in the treatment of giant cell arteritis (GCA)4,5. The clinical value of TCZ in isolated PMR is less well described. … Address correspondence to Dr. Eric Toussirot, University Hospital, Clinical Investigation Center-Biotherapy, CHU Hopital St Jacques, Bat St Joseph, Besancon, 25000, France. E-mail: etoussirot{at}chu-besancon.fr
First and second dose antibody responses to pneumococcal polysaccharide vaccine in infants

Total (radioimmunoassay) and immunoglobulin class-specific (enzyme-linked immunosorbent assay) antibody responses to pneumococcal capsular polysaccharides were measured in children who received the first dose of 14-valent pneumococcal or control (saline) vaccine at the age of 7 months and the second dose at the age of 13 months. Types 3 and 18C elicited strong antibody responses and types 14 and 19F elicited intermediate responses in all immunoglobulin classes after both doses of the vaccine. The generally poor immunogen types 6A and 23F elicited a weak antibody response mainly in the immunoglobulin M class. The antibody levels to most pneumococcal types also decreased rapidly after both injections of the vaccine.
Antifeedant Activity of Fatty Acid Esters and Phytosterols from Echium wildpretii

Crude extracts and fractions from Echium wildpretii H. Pearson ex Hook. f. subsp. wildpretii (Boraginaceae) have been tested against insect species Spodoptera littoralis, Leptinotarsa decemlineata, and the aphids Myzus persicae, Diuraphis noxia, Metopolophium dirhodum, Rhopalosiphum maidis, and Rhopalosiphum padi. The EtOH extract and the lipid and steroidal fractions of E. wildpretii exhibited significant antifeedant activities against the aphids and L. decemlineata. Two bioactive mixtures composed of fatty acid esters and n‐alkanes were obtained from the lipid fraction. The bioguided fractionation of the steroidal fraction resulted in the isolation of glutinol, β‐sitosterol, (3β,7α)‐stigmast‐5‐ene‐3,7‐diol, and (3β,7α)‐7‐methoxystigmast‐5‐en‐3‐ol. The latter two compounds exhibited potent antifeedant activities against L. decemlineata indicating that the presence of an O‐bearing C(7) was responsible for the activities of these molecules.
Validation of the Clinical, Radiological, Biochemical Parameters of Osteomalacia

Background: Osteomalacia, a metabolic bone disorder characterized by softening of the bones caused by defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium, or because of overactive resorption of calcium from the bone as a result of hyperparathyroidism. The diagnosis of Osteomalacia is dependent on clinical, radiographic and biochemical parameters still, none of these are pathognomonic of the disorder, and histologic examination of a bone biopsy, an invasive procedure is usually necessary to confirm the diagnosis. We used diagnostic criteria based on clinical, biochemical and radiological parameters to diagnose Osteomalacia with adequate accuracy. Methodology: This was Cross sectional and observational study. A total of 100 patients age between 18-65 years attending OPD with complaints of persistent, non-specific and generalized musculoskeletal pain were included in the study. Thorough history was taken and examination was done. They were subjected to biochemical investigation including haemogram, serum vitamin D, serum calcium, serum phosphorus, serum alkaline phosphates, serum PTH and radiological investigation including X-ray: Pelvis with both hips, x-ray lumbosacral spine. We used scoring criteria including pain score and Diet criteria and diagnostic index of [1] for diagnosing Osteomalacia. Data received from biochemical test was analyzed and correlated with the clinical findings. Results: We observed that only generalized pain at presentation and vitamin D level of <19.23ng/ml was significantly associated with outcome. On evaluating the combination of presence of these criteria we observed it to be 75% sensitive and 93.8% specific with a PPV of 75% and NPV of 93.8% and an accuracy of 68.8%. Conclusion: Modified two component criteria can be used as for assessment, however, its efficacy against biopsy proven cases of Osteomalacia needs further evaluation apart from its validation in different population groups.
"Creature-101": A Serious Game to Promote Energy Balance-Related Behaviors Among Middle School Adolescents.

BACKGROUND Considering adolescents' heavy use of media, serious videogames may provide an engaging and innovative way to achieve positive impact on adolescents' diet and physical activity. The objective of this study was to evaluate the efficacy of playing a serious game, "Creature-101" (developed by Teachers College, Columbia University [New York, NY] and Stottler Henke Inc. [San Mateo, CA]), at promoting energy balance-related behaviors (EBRBs) such as increasing fruits and vegetables intake, water intake, and physical activity and decreasing processed snacks intake, sweetened beverages intake, and recreational screen time. SUBJECTS AND METHODS This pre-post intervention-control study (n=590) was conducted in New York City low-income public middle schools. The students (11-13 years of age, 51.6 percent male) played "Creature-101" online in science/health education classes (seven sessions, 30 minutes each session for 1 month). "Creature-101" used behavioral theories as the framework for "creature care" in a world "Tween. " Students were provided with scientific evidence that promoted energy balance through minigames, educational videos, and slideshows and were motivated with interactive dialogues with game characters. Students also assessed their own behaviors, created their own "real life" food and activity goals, and reported their progress. A self-reported, validated, online instrument that measured frequency and amount of targeted behaviors was administered at baseline and post-intervention. RESULTS Analysis of covariance compared post-test means between groups with pretest scores as covariates. Intervention students reported significant decreases in frequency and amount of consumption of sweetened beverages and processed snacks compared with the controls. No changes were observed for the other behaviors. CONCLUSIONS "Creature-101" was effective at reducing consumption of sweetened beverages and processed snacks, which are related to obesity risks, indicating that the game shows promise at promoting EBRBs.
An Overdose of the Arabidopsis Coreceptor BRASSINOSTEROID INSENSITIVE1-ASSOCIATED RECEPTOR KINASE1 or Its Ectodomain Causes Autoimmunity in a SUPPRESSOR OF BIR1-1-Dependent Manner1

Accumulation of an immune coreceptor or its ectodomain leads to detrimental effects on Arabidopsis growth and constitutive activation of immunity. The membrane-bound BRASSINOSTEROID INSENSITIVE1-ASSOCIATED RECEPTOR KINASE1 (BAK1) is a common coreceptor in plants and regulates distinct cellular programs ranging from growth and development to defense against pathogens. BAK1 functions through binding to ligand-stimulated transmembrane receptors and activating their kinase domains via transphosphorylation. In the absence of microbes, BAK1 activity may be suppressed by different mechanisms, like interaction with the regulatory BIR (for BAK1-INTERACTING RECEPTOR-LIKE KINASE) proteins. Here, we demonstrated that BAK1 overexpression in Arabidopsis (Arabidopsis thaliana) could cause detrimental effects on plant development, including growth arrest, leaf necrosis, and reduced seed production. Further analysis using an inducible expression system showed that BAK1 accumulation quickly stimulated immune responses, even under axenic conditions, and led to increased resistance to pathogenic Pseudomonas syringae pv tomato DC3000. Intriguingly, our study also revealed that the plasma membrane-associated BAK1 ectodomain was sufficient to induce autoimmunity, indicating a novel mode of action for BAK1 in immunity control. We postulate that an excess of BAK1 or its ectodomain could trigger immune receptor activation in the absence of microbes through unbalancing regulatory interactions, including those with BIRs. Consistently, mutation of SUPPRESSOR OF BIR1-1, which encodes an emerging positive regulator of transmembrane receptors in plants, suppressed the effects of BAK1 overexpression. In conclusion, our findings unravel a new role for the BAK1 ectodomain in the tight regulation of Arabidopsis immune receptors necessary to avoid inappropriate activation of immunity.
Hypertriglyceridemic waist and cardiometabolic risk in hypertensive women.

OBJECTIVE To evaluate the association between hypertriglyceridemic waist (HW) and cardiometabolic risk factors in women with hypertension. METHODS A cross-sectional study was performed in 218 patients monitored by HiperDia (Enrollment and Monitoring Program for Hypertensive and Diabetic Individuals) in two health units in São Luis, MA, Brazil. The dependent variable was HW and the independent variables were sociodemographics, lifestyle, anthropometrics, and health problems. RESULTS HW was present in 33% of the sample and was predominant in women aged > 60 years (56.4%), non-whites (81.7%), those with eight or fewer years of schooling (57.3%), and those belonging to socioeconomic class C (49%). Excess weight (68.8%) and hypercholesterolemia (68.8%) were observed. HW was associated with: smoking (PR: 2.08; p = 0.017), overweight (PR: 2.46; p = 0.010), obesity (PR: 4.13; p < 0.001), hypercholesterolemia (PR: 1.87; p = 0.015), high levels of high-density lipoproteins (HDL) cholesterol (PR: 3.41; p < 0.001), and fasting glycemia > 100 mg/dL or being diabetic (PR: 1.86; p = 0.006). After adjustment, total cholesterol (PR = 1.78; p = 0.012), HDL-cholesterol (PR: 3.03; p < 0.001), body mass index (BMI) > 25 to < 30 kg/m² (PR = 2.60; p = 0.005), and BMI > 30 kg/m² (PR = 3.61; p < 0.001) remained associated. CONCLUSION A high prevalence of HW and its association with altered lipid profile and excess body weight was observed. HW showed to be an important diagnostic tool for the monitoring of hypertensive women with metabolic risk, which is low cost, easily accessible, and useful in clinical practice, especially in primary health care in the Brazilian Unified Health System (Sistema Único de Saúde - SUS).
Premenstrual failure of alpha‐adrenergic stimulation on hypothalamus‐pituitary responses in menstrual migraine.

&NA; In nine women suffering from menstrual migraine (MM), and in six healthy asymptomatic volunteers, plasma beta‐endorphin (beta‐EP), growth hormone (GH), norepinephrine (NE), and 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MHPG) concentrations were measured in response to clonidine (0.075 mg, i.v.) stimulation. In MM patients clonidine testing was performed in both the early and the late luteal phases of the menstrual cycle. Premenstrual symptoms were prospectively evaluated in the actual cycle using the Moos Menstrual Distress Questionnaire. beta‐EP (after gel chromatography) and GH were measured using radioimmunoassay. NE and MHPG were evaluated by HPLC using electrochemical detection. In both phases of the menstrual cycle clonidine significantly reduced NE and MHPG levels in MM patients and controls in a similar way. In MM patients beta‐EP and GH plasma levels were stimulated by clonidine only in the early luteal phase, whereas they remained unchanged when they were stimulated in the premenstrual period. In controls the response of both hormones was not affected by the menstrual cycle. The lack of hormonal response to clonidine in MM may suggest a postsynaptic alpha 2‐adrenoreceptor hyposensitivity during the premenstrual period. This demonstrates a transient vulnerability of the neuroendocrine/neurovegetative systems, and could thus be a factor facilitating the precipitation of both behavioral changes and migraine attacks.