bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanisms of tributyltin‐induced alterations in cholesterol homeostasis and steroidogenesis in hamster testis: In vivo and in vitro studies
Authors: Kanimozhi Veerasamy , Palanivel Kandasamy , Akbarsha Mohammad A. , Kadalmani Balamuthu 
Published: December 2017

AbstractTributyltins (TBT) are ubiquitous and persistent environmental contaminants that disturb normal endocrine function including gonadal function in humans and marine organisms. TBT was administered through oral route to male Syrian hamsters at daily doses of 50, 100, and 150 ppm/kg for 65 days. Changes in testis morphology, immunohistochemistry of iNOS, 3β‐HSD, and 17β‐HSD, cholesterol transport receptor, nuclear receptors, and transcription factors were analyzed. TBT treatment affected each of these parameters to significant levels in a dose‐dependent manner compared to vehicle treated control. Real‐time PCR and protein analyses revealed that expression levels of ApoE and LDL‐R mRNA were up‐regulated in the testis of TBT‐treated animals while the expression levels of SR‐B1, LXR, PPARs α, β, and γ, SCAP, SREBP 1 and 2, 3β‐HSD, 17β‐HSD, CYP17A1, and P450SCC were down‐regulated. Leydig cells were isolated and separated adopting percoll gradient centrifugation under aseptic condition. The viability of Leydig cell was affected by TBT treatment in a dose‐ and time‐dependent manner. Further, the mechanism of action of TBT was ascertained by siRNA transfection of ApoE, which was upregulated, and SREBP, which was down‐regulated. These observations led us to infer that exposure to TBT hinders intracellular cholesterol transport resulting in abnormal sex steroid biosynthesis and alteration of steroidogenic enzyme activities. Finally, we could recognize ApoE and SREBP as the major factors regulating genes that control cholesterol biosynthesis and steroidogenesis that ultimately inhibit the synthesis of testosterone. Therefore, ApoE is one of the important molecular targets that can be intercepted in context of male infertility/male contraception.
Molecular dynamics insights into the structure, function, and substrate binding mechanism of mucin desulfating sulfatase of gut microbe Bacteroides fragilis
Authors: Praharaj Ardhendu Bhusan , Dehury Budheswar , Mahapatra Namita , Kar Shantanu Kumar , Behera Santosh Kumar 
Published: December 2017

AbstractThe complex and dynamic consortia of microbiota that harbors the human gastrointestinal tract contributes ominously to the maintenance of health, the onset and progression of diverse spectrum of disorders. The capability of these enteric microbes to bloom within the gut mucosal milieu is often associated to the glycan metabolism of mucin‐degrading bacteria. Accruing evidences suggests that the desulfation of mucin is a rate‐limiting step in mucin degradation mechanism by colonic bacterial mucin‐desulfating sulfatase enzymes (MDS) enzymes. Till date no experimental evidence is available on how conformational flexibility influences structure and substrate specificity by MDS of gut microbe Bacteroides fragilis. Henceforth, to gain deep insights into the missing but very imperative mechanism, we performed a comprehensive molecular dynamics study, principal component analysis and MM/PBSA binding free energies to gain insights into (i) the domain architecture and mode of substrate binding (ii) conformational dynamics and flexibility that influence the orientation of substrate, (iii) energetic contribution that plays very decisive role to the overall negative binding free energy and stabilities of the complexes (iv) critical residues of active site which influence binding and aid in substrate recognition. This is the first ever report, depicting the molecular basis of recognition of substrates and provides insights into the mode of catalysis by mucin desulfating sulfatase enzymes in gut microbiota. Overall, our study shed new insights into the unmapped molecular mechanisms underlying the recognition of various substrates by mucin desulfating sulfatase, which could be of great relevance in therapeutic implications in human gut microbiota associated disorders.
GANT‐61 and GDC‐0449 induce apoptosis of prostate cancer stem cells through a GLI‐dependent mechanism
Authors: Tong Wangxia , Qiu Lei , Qi Meng , Liu Jianbing , Hu Kaihui , Lin Wenxiong , Huang Yan , Fu Junsheng 
Published: December 2017

AbstractAberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway promotes prostate cancer (PC) growth and progression by regulating cancer‐related genes through its downstream effectors GLI1 and GLI2. Therefore, targeting the SHH‐GLI pathway provides an alternative approach to avoid cancer progression. The aim of this study was to delineate the underlying molecular mechanisms by which GDC‐0449 (a SMO receptor inhibitor) and GANT‐61 (a GLI transcription factor inhibitor) regulate cellular proliferation and self‐renewal in human PC stem cells (ProCSCs). Inhibition of the SHH signaling pathway by GANT‐61 induced apoptosis with more efficacy than by GDC‐0449 in ProCSCs and PC cell lines. GLI1 and GLI2 expression, promoter‐binding activity and GLI‐responsive luciferase reporter activity were all decreased with either GDC‐0449 or GANT‐61 treatment. Expression of Fas, DR4, DR5, and cleavage of caspase‐3 and PARP were increased, whereas levels of PDGFR‐α and Bcl‐2 were reduced. Double knockout of GLI1 and GLI2 using shRNA abolished the effects observed with either GDC‐0449 or GANT‐61 treatment. Collectively, our results showed that GANT‐61 and GDC‐0449 induced ProCSC apoptosis by directly or indirectly inhibiting the activities of the GLI family transcription factors, may enhance the efficacy of PC treatment.
Integration of molecular dynamics simulation and hotspot residues grafting for de novo scFv design against Salmonella Typhi TolC protein
Authors: Leong Siew Wen , Lim Theam Soon , Ismail Asma , Choong Yee Siew 
Published: December 2017

AbstractWith the development of de novo binders for protein targets from non‐related scaffolds, many possibilities for therapeutics and diagnostics have been created. In this study, we described the use of de novo design approach to create single‐chain fragment variable (scFv) for Salmonella enterica subspecies enterica serovar Typhi TolC protein. Typhoid fever is a global health concern in developing and underdeveloped countries. Rapid typhoid diagnostics will improve disease management and therapy. In this work, molecular dynamics simulation was first performed on a homology model of TolC protein in POPE membrane bilayer to obtain the central structure that was subsequently used as the target for scFv design. Potential hotspot residues capable of anchoring the binders to the target were identified by docking “disembodied” amino acid residues against TolC surface. Next, scFv scaffolds were selected from Protein Data Bank to harbor the computed hotspot residues. The hotspot residues were then incorporated into the scFv scaffold complementarity determining regions. The designs recapitulated binding energy, shape complementarity, and interface surface area of natural protein‐antibody interfaces. This approach has yielded 5 designs with high binding affinity against TolC that may be beneficial for the future development of antigen‐based detection agents for typhoid diagnostics.
Myocardial Perfusion Reserve Index in Children With Kawasaki Disease
Authors: Friesen Richard M. , Schäfer Michal , Jone Pei‐Ni , Appiawiah Nana , Vargas Daniel , Fonseca Brian , DiMaria Michael V. , Truong Uyen , Malone LaDonna , Browne Lorna P. 
Published: December 2017

BackgroundCoronary artery lesions in patients with Kawasaki disease (KD) can impair myocardial perfusion, yet evaluation of perfusion defects by cardiac magnetic resonance (MR) in children is often qualitative.PurposeIn this study we aimed to use a quantitative method of myocardial perfusion using stress cardiac MR‐derived myocardial perfusion reserve index (MPRI) in children with KD and compare MPRI with ventricular mechanical performance evaluated by cardiac MR strain analysis.Study TypeThis study was a retrospective review.SubjectsTwenty‐one children with a diagnosis of KD who underwent stress perfusion cardiac MR were compared with nine controls.Field Strength/SequenceFirst‐pass perfusion imaging using a T1‐weighted gradient echo sequence was performed at rest and stress after administration of adenosine with 1.5T or 3T magnets.AssessmentThe MPRI was calculated as the ratio of maximum slope of myocardial enhancement during stress compared to rest and was evaluated with the American Heart Association 17 segment model.Statistical TestsDemographic and clinical characteristics among KD patients and controls were compared using Student's t‐test for normally distributed continuous variables, Wilcoxon‐rank sum test for nonnormally distributed variables, and χ2 for categorical variables.ResultsThere was a significant decrease in MPRI in Segment 7 (1.53 vs. 2.23, P = 0.0058) in KD patients compared with controls. The reduction in MPRI in Segment 12 approached statistical significance (1.58 vs. 2.31, P = 0.0636). Three patients who underwent serial studies had decreased MPRI longitudinally. No differences were seen in circumferential or radial strain.Data ConclusionMPRI shows impaired myocardial perfusion in patients with KD. MPRI can change over time, suggestive of progressive coronary artery changes, which may precede fibrosis and mechanical decline. MPRI can assess segmental and global perfusion defects in patients with KD and should be a part of routine cardiac MR evaluation in KD.Level of Evidence: 3Technical Efficacy Stage 3J. Magn. Reson. Imaging 2017.
A role for autophagy in long‐term spatial memory formation in male rodents
Authors: Hylin Michael J. , Zhao Jing , Tangavelou Karthikeyan , Rozas Natalia S. , Hood Kimberly N. , MacGowan Jacalyn S. , Moore Anthony N. , Dash Pramod K. 
Published: December 2017

AbstractA hallmark of long‐term memory formation is the requirement for protein synthesis. Administration of protein synthesis inhibitors impairs long‐term memory formation without influencing short‐term memory. Rapamycin is a specific inhibitor of target of rapamycin complex 1 (TORC1) that has been shown to block protein synthesis and impair long‐term memory. In addition to regulating protein synthesis, TORC1 also phosphorylates Unc‐51‐like autophagy activating kinase‐1 (Ulk‐1) to suppress autophagy. As autophagy can be activated by rapamycin (and rapamycin inhibits long‐term memory), our aim was to test the hypothesis that autophagy inhibitors would enhance long‐term memory. To examine if learning alters autophagosome number, we used male reporter mice carrying the GFP‐LC3 transgene. Using these mice, we observed that training in the Morris water maze task increases the number of autophagosomes, a finding contrary to our expectations. For learning and memory studies, male Long Evans rats were used due to their relatively larger size (compared to mice), making it easier to perform intrahippocampal infusions in awake, moving animals. When the autophagy inhibitors 3‐methyladenine (3‐MA) or Spautin‐1 were administered bilaterally into the hippocampii prior to training in the Morris water maze task, the drugs did not alter learning. In contrast, when memory was tested 24 hours later by a probe trial, significant impairments were observed. In addition, intrahippocampal infusion of an autophagy activator peptide (TAT‐Beclin‐1) improved long‐term memory. These results indicate that autophagy is not necessary for learning, but is required for long‐term memory formation.
Toward a Science of Creativity: Considerable Progress but Much Work to be Done
Authors: Plucker Jonathan A. 
Published: December 2017

AbstractThe past 50 years have seen a tremendous strengthening of the field of creativity studies. Developments over the past couple decades, in particular, have led to a burgeoning science of creativity. But major methodological and substantive issues remain and must be addressed in order for the science of creativity to reach its potential to improve the well‐being of people around the globe.
Interdisciplinary Invigoration of Creativity Studies
Authors: Ambrose Don 
Published: December 2017

AbstractThe forces of globalization are magnifying the importance of interdisciplinary creative work. While the field of creativity studies always has been more open to interdisciplinary idea borrowing than many other fields, it can and should do more interdisciplinary synthesizing. This article begins with a discussion of the rationale for encouraging interdisciplinary work in the field and then explores several examples of constructs imported from various disciplines that can enrich theory and research in creativity studies. These constructs include market fundamentalism from economics, and networked science from various STEM fields. Some other candidates for importation also are discussed briefly.
Linking sorghum nutrition and production with arbuscular mycorrhizal fungi and alternative soil amendments
Authors: Cobb Adam B. , Wilson Gail W. T. , Goad Carla L. 
Published: December 2017

AbstractMounting fertilizer costs are disproportionally affecting farmers in developing countries. Alternative soil fertility amendments [worm compost, pyrolyzed carbon (biochar)] and arbuscular mycorrhizal fungi have the potential to reduce these costs while promoting soil health. Our greenhouse study investigated the role of mycorrhizal associations and alternative fertility amendments on the productivity and plant nutrition of grain sorghum. We assessed sorghum (Sorghum bicolor cv. Macia) grown with ten different treatments (combinations of biochar, worm compost, and commercial N and P fertilizers) plus a non‐amended control. An amendment blend containing worm compost, biochar, and 50% of the typically recommended commercial fertilizer rate produced similar plant biomass and protein, similar total tissue mineral contents (Ca, Fe, K, Mg, P, and Zn), and supported ≈ 60% more mycorrhizal fungi in the host plant's roots, compared to sorghum grown with the recommended rate of commercial fertilizer (N and P). Our results indicate the potential of biochar and worm compost to enhance the benefits of mycorrhizal fungi for grain sorghum production and plant nutrition while reducing commercial fertilizer applications.
Ammonium and nitrate transport during saturated and unsaturated water flow through sandy soils
Authors: Kadyampakeni Davie M. , Nkedi-Kizza Peter , Leiva Jorge A. , Muwamba Augustine , Fletcher Evelyn , Morgan Kelly T. 
Published: December 2017

AbstractCitrus production in Florida accounts for ≈ 60% of national production in USA. The sandy soil characteristic (> 95% sand) makes water and nutrient management extremely difficult, raising concerns about environmental sustainability as a result of nutrient inputs in citrus producing regions where sandy soils dominate. Thus, laboratory column and field experiments were conducted to better understand the leaching patterns of and ions in Florida's sandy soils. The soil columns were first saturated from the bottom with two pore volumes of simulated Florida rain followed by pumping a pulse of fertilizer mixture at a steady Darcy flux of 14 cm h−1. Nitrate and Cl− appeared earlier in the effluent than in the A and Bh horizons, due to cation exchange of . Essentially identical breakthrough curves (BTCs) for and were observed in the E‐horizon, due to very low sorption of . The convective and dispersive equilibrium (CDE) model simulations were in good agreement with measured breakthrough curves (BTCs) for , , and Cl−. However, the sorption coefficient (KD) values used in the CDE model to simulate the BTCs for were about 10 times less than the batch isotherm KD values. This was attributed to differences in pH, cation composition, and ionic strength between batch (static) and dynamic (leaching) systems. The field experiment showed that under unsaturated flow, improved short‐pulse fertigation systems (drip and microsprinkler) limited and transport beyond the root zone (top 30 cm), which might have promoted nutrient and water uptake in citrus. The column study revealed that under extreme weather events such as hurricanes or storm surge in Florida, saturated soil conditions can trigger N mobility below the root zone to surficial or groundwater aquifers. In the field experiment, the use of judicious, minimal and split applications and accurate placement of N‐fertilizers reduced leaching of N especially during heavy storms in the summer rainy months of Florida. The field experiment demonstrated that it is possible to manage inorganic N forms for optimal residence time for uptake and minimal leaching concerns.
Relationship between Raman spectral features and fugacity in mixtures of gases
Authors: Lamadrid Hector M. , Steele‐MacInnis Matthew , Bodnar Robert J. 
Published: December 2017

AbstractRaman spectroscopy yields information about the internal vibrational modes of covalently bonded molecules, which are sensitive to the local molecular environment. As such, Raman spectra of a gas composed of covalently bonded molecules collected at different temperatures and/or pressures show variations in band positions and other spectral features, reflecting molecular‐scale interactions (attraction and repulsion) among gas particles associated with the local physical and chemical environment. Because the molecules interact, gases are nonideal, and fugacity is the fundamental thermodynamic quantity that describes partial pressures of gases, adjusted to account for the nonideality. The fugacity of a substance is generally obtained from thermodynamic calculations rather than by direct analysis or measurement and, as such, is conceptually nebulous. Here, we perform spectroscopic analyses of a gas mixture of known composition at variable and known pressures and couple these results with thermodynamic calculations of gas fugacities. We show that Raman peak shifts in gas mixtures are directly correlated to fugacities of the component gas species. Our results thus provide experimental evidence that fugacities of gases can be estimated from Raman spectra collected in situ. By this approach, the thermodynamic quantities fugacity and the related thermodynamic property activity are linked directly with underlying molecular‐scale phenomena, according to the vibrational properties of molecular species. This represents a tractable method to efficiently obtain large datasets on thermodynamic properties of gas mixtures, and with some adjustments, may lead to a viable method for developing nonideal mixing rules for other substances, such as crystalline solid solutions, aqueous ions, and electrolytes.
In vitro bioaccessibility of individual carotenoids from persimmon (Diospyros kaki, cv. Rojo Brillante) used as an ingredient in a model dairy food
Authors: García‐Cayuela Tomás , Nuño‐Escobar Beatriz , Welti‐Chanes Jorge , Cano M Pilar 
Published: December 2017

AbstractBACKGROUNDAddition of persimmon fruit, which is highly rich in carotenoids, to dairy products represents an alternative to obtain functional foods. However, carotenoid bioaccessibility is strongly influenced by fat content and food composition. That is why in vitro bioaccessibility of individual carotenoids was evaluated in persimmon‐based dairy products formulated with whole (3.6% fat) or skimmed milk (0.25% fat) and different freeze‐dried persimmon tissues.RESULTSUnambiguous identification of seven xanthophylls (neoxanthin, violaxanthin, antheraxanthin, lutein, zeaxanthin, lutein epoxide and β‐cryptoxanthin) and three hydrocarbon carotenes (α‐carotene, β‐carotene and lycopene) was achieved using high‐performance liquid chromatography with a reverse‐phase C‐30 column. Total carotenoid content declined up 71% through the digestion process. In vitro bioaccessibility of carotenoids was significantly higher in dairy products formulated with whole milk than those with skimmed milk, representing a difference of more than 21% (in the formulation using persimmon whole fruit as ingredient). Furthermore, addition of whole milk to any type of persimmon tissue significantly improved the bioaccessibility of total provitamin A carotenoids, reaching the highest values (38%) with whole fruit and whole milk.CONCLUSIONThe higher fat content in whole milk exerted a significant influence on carotenoid bioaccessibility, especially when using freeze‐dried persimmon whole fruit. © 2017 Society of Chemical Industry
Occurrence of variable levels of health‐promoting fruit compounds in horn‐shaped Italian sweet pepper varieties assessed by a comprehensive approach
Authors: Mennella Giuseppe , D'Alessandro Antonietta , Francese Gianluca , Fontanella Daniela , Parisi Mario , Tripodi Pasquale 
Published: December 2017

AbstractBACKGROUNDCultivated pepper is a rich source of diverse bioactive compounds with potential properties related to the prevention of major degenerative and proliferative diseases. In the present study, 15 sweet pepper varieties, highly appreciated on the Italian market, were assessed for variation in the content of ascorbic acid, isoprenoids and flavonoids, as well as morpho‐agronomic performances and molecular diversity.RESULTSThe collection under study showed a wide variability for all traits considered. Traditional cultivars, although less productive, were characterized by a high content of β‐carotene and ascorbic acid, reaching maximum concentrations of 230.5 mg kg–1 fresh weight (fw) and 2750 mg kg–1 fw, respectively. Strong correlations were demonstrated between neoxanthin and luteolins. Fruit weight was positively correlated with α‐tocopherol content and negatively correlated with luteolins content. The genotyping by sequencing platform allowed the identification of 1833 single nucleotide polymorphism, which better defined the relationships among cultivars, based on provenance and improvement rate.CONCLUSIONSThe present study provides an overview of the variability in the expression of fruit nutritional traits in a collection of horn‐shaped pepper cultivars, integrating agronomic and molecular data. The impact for breeding and consumers is discussed. © 2017 Society of Chemical Industry
Electroless‐coated magnetic three‐dimensional graphene with silver nanoparticles used for the determination of pesticides in fruit samples
Authors: Sereshti Hassan , Afsharsaveh Zahra , Gaikani Hamid , Rashidi Nodeh Hamid 
Published: December 2017

AbstractA new type of adsorbent composed of magnetic three‐dimensional graphene coated with silver nanoparticles was synthesized by an electroless technique and used in the magnetic solid‐phase extraction of selected pesticides (fenitrothion, chlorpyrifos, and hexaconazole) before gas chromatography with a micro‐electron capture detector. The adsorbent was characterized using Fourier‐transform infrared spectroscopy, X‐ray diffraction, vibrating sample magnetometry, and field‐emission scanning electron microscopy. The important extraction parameters such as pH, adsorbent dose, extraction time, and desorption conditions were investigated. Under the optimal conditions, the analytical figures of merit were obtained as: linear dynamic range of 0.1–5 ng/g with determination coefficients of 0.991–0.996; limit of detection of 0.07–0.13 ng/g; limit of quantification of 0.242–0.448 ng/g; and the intraday and interday relative standard deviations (C = 5 ng/g, n = 3) were 3.8–8.7 and 6.6–8.9%, respectively. The developed method was successfully applied for analysis of the selected pesticides in tomato and grape with extraction recoveries in the range of 72.8–109.6%.