Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors

SNT adaptor proteins transduce activation of fibroblast growth factor receptors (FGFRs) and neurotrophin receptors (TRKs) to common signaling targets. The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine. Here, using NMR and mutational analyses, we show that the PTB domain utilizes distinct sets of amino acid residues to interact with FGFRs or TRKs in a mutually exclusive manner. The FGFR1 peptide wraps around the beta sandwich structure of the PTB domain, and its binding is possibly regulated by conformational change of a unique C-terminal beta strand in the protein. Our results suggest mechanisms by which SNTs serve as molecular switches to mediate the essential interplay between FGFR and TRK signaling during neuronal differentiation.     

Fine needle aspiration outcomes of masses detected by positron emission tomography: correlation with standard uptake value

OBJECTIVES: To characterize the cytopathologic outcome of lesions detected on positron emission tomography (PET) scan. STUDY DESIGN: Cases with fine needle aspiration (FNA) performed because of a PET-positive lesion over an 18-month period were reviewed. Correlation with the standard uptake value (SUV) (using 2.5 as a cutoff value) was carried out. RESULTS: A total of 112 FNAs were found, of which 83 had adequate tissue for evaluation and available corresponding SUVs to be included in the final study. Fisher's exact test was carried out for correlation between FNA diagnosis and SUV Sixty-one (73.5%) lesions had an SUV > or = 2.5, 53 (87%) ofwhich were malignant and 8 (13%) benign on cytology. Twenty-two (26.5%) lesions had an SUV < 2.5, of which 12 (54.5%) showed benign and 10 (45.5%) showed malignant cytology. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of SUV were 84%, 60%, 87%, 56% and 78%, respectively. CONCLUSION: Our data show that FNA procedures performed for PET-positive lesions have high PPV, but low NPV. Therefore interpretation of PET SUV values < 2.5 as benign should be made with extreme caution.     

Treatment of textile effluents with Pistia stratiotes,Eichhornia crassipes and Oedogonium sp.

Abstract

Phytoremediation by aquatic macrophytes is a promising technology with higher efficiency and no energy consumption. For this purpose, two macrophytes (Pistia stratiotes, Eichhornia crassipes), and an alga (Oedogonium sp.) were used to treat textile effluents rich in COD, BOD, dyes, and heavy metals (Pb, Fe, Cd, Cu). The aim of the study was to focus on comparative phytoremediation potential of these species by their metal removal capability. During 7?days experiment (day 0–day 6), the results showed that Oedogonium sp. was the best for COD removal and decolorization. Eichhornia crassipes was the best for BOD and heavy metal removal and proves more efficient than Pistia stratiotes and Oedogonium sp. However, Pistia stratiotes was found to accumulate more concentrations of Pb and Fe than Eichhornia stratiotes.     

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

Background

Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose→sorbitol→fructose) contributes to brain exposure to fructose.

Methods

In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section.

Results

As expected, CSF glucose was ~60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02) and sorbitol levels (ρ 0.75, p < 0.001). Cord blood sorbitol was also ~7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups.

Conclusions

These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption.     

Quantitative Drug-Susceptibility in Patients Treated for Multidrug-Resistant Tuberculosis in Bangladesh: Implications for Regimen Choice

BackgroundMultidrug-resistant tuberculosis (MDR-TB) treatment in Bangladesh is empiric or based on qualitative drug-susceptibility testing (DST) by comparative growth in culture media with and without a single drug concentration.MethodsAdult patients were enrolled throughout Bangladesh during the period of 2011–2013 at MDR-TB treatment initiation. Quantitative DST by minimum inhibitory concentration (MIC) testing for 12 first and second-line anti-TB drugs was compared to pretreatment clinical characteristics and treatment outcomes. MIC values at or one dilution lower than the resistance breakpoint used for qualitative DST were categorized as borderline susceptible, and MIC values one or two dilutions greater as borderline resistant.ResultsSeventy-four patients were enrolled with a mean age of 35 ±15 years, and 51 (69%) were men. Of the rifampin isolates with MIC >1.0 μg/ml, 12 (19%) were fully susceptible or borderline susceptible to rifabutin (MIC ≤0.5 μg/ml). Amikacin was fully susceptible in 73 isolates (99%), but kanamycin in only 54 (75%) (p<0.001). Ofloxacin was borderline susceptible in 64%, and fully susceptible in only 14 (19%) compared to 60 (81%) of isolates fully susceptible for moxifloxacin (p<0.001). Kanamycin non-susceptibility and receipt of the WHO Category IV regimen trended with interim treatment failure: adjusted odd ratios respectively of 5.4 [95% CI 0.82–36.2] (p = 0.08) and 7.2 [0.64–80.7] (p = 0.11).ConclusionsQuantitative MIC testing could impact MDR-TB regimen choice in Bangladesh. Comparative trials of higher dose or later generation fluoroquinolone, within class change from kanamycin to amikacin, and inclusion of rifabutin appear warranted.     

5′ and 3′ end modifications of spliceosomal RNAs in <Emphasis Type="Italic">Plasmodium falciparum</Emphasis>

5′ caps provide recognition sequences for the nuclear import of snRNAs. The 5′ and 3′ ends of snRNAs were studied in Plasmodium falciparum with a modified adapter ligation method, which showed that 5′ ends of U1, U2, U4, U5 and U6 snRNAs are capped. In P. falciparum, the 3′ ends of U1, U2, U4 and U5 snRNAs have free hydroxyl groups whereas U6 snRNA has a blocked 3′ end. An immunoprecipitation assay for trimethyl guanosine caps shows that the cap structures of parasite U1-U5 snRNAs are hypermethylated while U6 snRNA may be γ-mono-methylated. Bioinformatics analysis of proteins involved in hypermethylation and trafficking of snRNAs indicates that the methyltransferase TGS1 is present in the P. falciparum genome. PfTGS1 is larger than its orthologs and may have transmembrane domains in the C-terminus. Surprisingly, the snRNA trafficking protein Snurportin is absent from the P. falciparum genome suggesting that reminiscent of yeast, parasite snRNAs may be retained in the nucleus.     

Methyl jasmonate and salicylic acid elicitation induces ginsenosides accumulation, enzymatic and non-enzymatic antioxidant in suspension culture Panax ginseng roots in bioreactors

The effects of methyl jasmonate (MJ) and salicylic acid (SA) on changes of the activities of major antioxidant enzymes, superoxide anion accumulation (O₂ ⁻), ascorbate, total glutathione (TG), malondialdehyde (MDA) content and ginsenoside accumulation were investigated in ginseng roots (Panax ginseng L.) in 4 l (working volume) air lift bioreactors. Single treatment of 200 μM MJ and SA to P. ginseng roots enhanced ginsenoside accumulation compared to the control and harvested 3, 5, 7 and 9 days after treatment. MJ and SA treatment induced an oxidative stress in P. ginseng roots, as shown by an increase in lipid peroxidation due to rise in O₂ ⁻ accumulation. Activity of superoxide dismutase (SOD) was inhibited in MJ-treated roots, while the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), SOD, guaiacol peroxidase (G-POD), glutathione peroxidase (GPx) and glutathione reductase (GR) were induced in SA-treated roots. A strong decrease in the activity of catalase (CAT) was obtained in both MJ- and SA-treated roots. Activities of ascorbate peroxidase (APX) and glutathione S transferase (GST) were higher in MJ than SA while the contents of reduced ascorbate (ASC), redox state (ASC/(ASC+DHA)) and TG were higher in SA- than MJ-treated roots while oxidized ascorbate (DHA) decreased in both cases. The result of these analyses suggests that roots are better protected against the O₂ ⁻ stress, thus mitigating MJ and SA stress. The information obtained in this work is useful for efficient large-scale production of ginsenoside by plant-root cultures.     

Effect of carbon dioxide on antioxidant enzymes and ginsenoside production in root suspension cultures of Panax ginseng

The aim of this study was to investigate the effect of CO₂ at various concentrations (1, 2.5 and 5%) on antioxidant enzymes and ginsenoside accumulation in Panax ginseng roots in 5 l airlift bioreactors (working volume 4 l). One and 2.5% CO₂ was beneficial for root biomass accumulation, but 5% CO₂ decreased the biomass. Ginsenoside concentration decreased with increasing concentration of CO₂. No significant difference was observed in the malondialdehyde (MDA) content and lipoxygenase (LOX) activity between respective controls and CO₂ treated roots. Antioxidant enzymes such as ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), glutathione reductase (GR), catalase (CAT), guaiacol peroxidase (G-POD) including reduced ascorbate and total glutathione were induced in CO₂ exposed roots which emphasized the protective role of antioxidants against CO₂ induced stress. Superoxide dismutase activity (SOD) which was induced after 15 days was significantly inhibited after 45 days. Glutathione-S-transferase (GST) and glutathione peroxidase (GPX) activities also increased when the roots were subjected to 1 and 2.5% CO₂ compared to the respective controls but not at 5%. A higher reduced ascorbate to oxidized (ASC/DHA) ratio in CO₂ treated root indicates the plant's ability to tolerate CO₂ stress. These observations suggest that an increase in antioxidant enzymes may affect a defense response to the cellular damage induced by CO₂. Probably, this increase could not stop the deleterious effects of CO₂ concentration on ginsenoside concentration, but reduced stress severity and thereby allowing root growth to occur.