A Critical Comparative Assessment of Predictions of Protein-Binding Sites for Biologically Relevant Organic Compounds

SummaryProtein function annotation and rational drug discovery rely on the knowledge of binding sites for small organic compounds, and yet the quality of existing binding site predictors was never systematically evaluated. We assess predictions of ten representative geometry-, energy-, threading-, and consensus-based methods on a new benchmark data set that considers apo and holo protein structures with multiple binding sites for biologically relevant ligands. Statistical tests show that threading-based Findsite outperforms other predictors when its templates have high similarity with the input protein. However, Findsite is equivalent or inferior to some geometry-, energy-, and consensus-based methods when the similarity is lower. We demonstrate that geometry-, energy-, and consensus-based predictors benefit from the usage of holo structures and that the top four methods, Findsite, Q-SiteFinder, ConCavity, and MetaPocket, perform better for larger binding sites. Predictions from these four methods are complementary, and our simple meta-predictor improves over the best single predictor

Testing oil saturation distribution in migration paths using MRI

International audienceMagnetic Resonance Imaging (MRI) method allows to observe the distribution of different fluids in situ in porous media, and to measure oil and water saturation. Although this technique has great advantages compared to others, there remains large space for assessing the method and improving the accuracy of measurement. Using MRI, the oil secondary migration paths are scanned to measure the saturation distribution during the laboratory experiments. The resulting map can be calibrated using a device with the same pore structure as the probed sample and fully saturated with oil. This device is scanned with the probed sample at the same time in order to calibrate the saturation. The Spin-echo multi-slices sequence (SEMS) is adopted for MRI to ensure that the oil saturation in migration paths is accurately measured. The relevant spatial resolution of the mapping is defined according to the concept of REV (representative elementary volume). The oil saturation resulting from data obtained using different image formats are compared and the resulting saturation evaluation is compared to direct bulk saturation measurements. This comparison demonstrates that the calculated MRI oil saturation using DICOM image format is quite accurate, with a relative error less than 2%

Discrimination of homocysteine, cysteine and glutathione using an aggregation-induced-emission-active hemicyanine dye

Elevated levels of homocysteine (Hcy) in blood are indicative of many high risk cardiovascular and neurodegenerative diseases. Thus, development of highly efficient and selective dyes for monitoring Hcy levels has attracted much attention. This paper reports the utilization of TPE-Cy, an aggregation-induced-emission active hemicyanine dye, as a probe for the detection of Hcy. More interestingly, this dye shows high selectivity to Hcy over cysteine, glutathione and other amino acids in weakly basic buffer solution

Crafting NPB with tetraphenylethene: a win–win strategy to create stable and efficient solid-state emitters with aggregation-induced emission feature, high hole-transporting property and efficient electroluminescence

N,N′-Di-(1-naphthyl)-N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine (NPB) possesses high thermal and morphological stability and is one of the well-known hole-transporting materials for the fabrication of organic light-emitting diodes (OLEDs). Modification of NPB by the covalent integration of tetraphenylethene (TPE) into its structure dramatically changes its emission behavior: the resulting adduct (TPE–NPB) is highly emissive in the aggregated state, showing a novel phenomenon of aggregation-induced emission (AIE). The adduct is thermally and morphologically stable. Non-doped multilayer electroluminescence (EL) devices using TPE–NPB as an emitting layer were fabricated, which emitted green light with a maximum luminance and current efficiency of 11[thin space (1/6-em)]981 cd m−2 and 11.9 cd A−1, respectively. Even better device performances are observed in the bilayer device without NPB. Our strategy takes the full advantage of the AIE property in the solid state and retains the inherent properties of conventional luminophores. It opens a new avenue in the development of stable and efficient solid-state fluorescent materials for OLED application

Preparation and biomedical application of a non-polymer coated superparamagnetic nanoparticle

We report the preparation of a non-polymer coated superparamagnetic nanoparticle that is stable and biocompatible both in vitro and in vivo. The non-polymer, betaine, is a natural methylating agent in mammalian liver with active surface property. Upon systemic administration, the nanoparticle has preferential biodistribution in mammalian liver and exhibits good reduction of relaxivity time and negative enhancement for the detection of hepatoma nodules in rats using MRI. Our data demonstrate that the non-polymer coated superparamagnetic nanoparticle should have potential applications in biomedicine

Transferability and Fine Mapping of Type 2 Diabetes Loci in African Americans: The Candidate Gene Association Resource Plus Study

Type 2 diabetes (T2D) disproportionally affects African Americans (AfA) but, to date, genetic variants identified from genome-wide association studies (GWAS) are primarily from European and Asian populations. We examined the single nucleotide polymorphism (SNP) and locus transferability of 40 reported T2D loci in six AfA GWAS consisting of 2,806 T2D case subjects with or without end-stage renal disease and 4,265 control subjects from the Candidate Gene Association Resource Plus Study. Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D (P < 0.05). The strongest association was observed at TCF7L2 rs7903146 (odds ratio [OR] 1.30; P = 6.86 × 10−8). Locus-wide analysis demonstrated significant associations (Pemp < 0.05) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive signals in KCNQ1 after correction for the effective number of SNPs at each locus. Of these loci, the regional best SNPs were in differential linkage disequilibrium (LD) with the index and adjacent SNPs. Our findings suggest that some loci discovered in prior reports affect T2D susceptibility in AfA with similar effect sizes. The reduced and differential LD pattern in AfA compared with European and Asian populations may facilitate fine mapping of causal variants at loci shared across populations

Impact of an Innovative Financing and Payment Model on Tuberculosis Patients’ Financial Burden: is Tuberculosis Care More Affordable for the Poor?

Background: In response to the high financial burden of health services facing tuberculosis (TB) patients in China, the China-Gates TB project, Phase II, has implemented a new financing and payment model as an important component of the overall project in three cities in eastern, central and western China. The model focuses on increasing the reimbursement rate for TB patients and reforming provider payment methods by replacing fee-for-service with a case-based payment approach. This study investigated changes in out-of-pocket (OOP) health expenditure and the financial burden on TB patients before and after the interventions, with a focus on potential differential impacts on patients from different income groups

Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats

Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&amp;E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis.Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG.Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis

Admixture Mapping of Coronary Artery Calcified Plaque in African Americans With Type 2 Diabetes Mellitus

The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping (AM) may be informative for identifying genetic variants associated with subclinical cardiovascular disease (CVD)