Flavonol Intake and Cognitive Decline in Middle-Aged Adults

Martin Root,Erin Ravine,Anne Harper 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.12

Cognitive decline occurs with age and may be slowed by dietary measures, including increased intake of dietary phytochemicals. However, evidence from large and long-term studies of flavonol intake is limited. Dietary intakes of flavonols were assessed from a large biracial study of 10,041 subjects, aged 45–64, by analysis of a food frequency questionnaire administered at visit 1 of triennial visits. Cognitive function was assessed at visits 2 and 4 with the following three cognitive performance tests: the delayed word recall test, the revised Wechsler Adult Intelligence Scale digit symbol subtest, and the word fluency test of the Multilingual Aphasia Examination. The change in each score over 6 years was calculated, and a combined standardized change score was calculated. Generalized linear models controlled for age, ethnicity, gender,education level, energy intake, current smoking, physical activity, body mass index, diabetes, and vitamin C intake. Total flavonols across quintiles of intake were positively associated with preserved combined cognitive function (P < .001). This pattern with preserved combined cognitive function was consistent for the three major individual flavonols in the diet, myricetin, kaempferol, and quercetin (each P < .001). The positive association with total flavonols was strongest for the digit symbol subtest (P < .001). In this cohort, flavonol intake was correlated with protected cognitive function over time.

Effects of the incorporation of alkali elements on Cu(In,Ga)Se₂ thin film solar cells

Shin, Donghyeop,Kim, Jekyung,Gershon, Talia,Mankad, Ravin,Hopstaken, Marinus,Guha, Supratik,Ahn, Byung Tae,Shin, Byungha Elsevier 2016 Solar energy materials and solar cells Vol.157 No.-

<P><B>Abstract</B></P> <P>This study describes in detail the effects of sodium and potassium on Cu(In,Ga)Se<SUB>2</SUB> (CIGS) absorbers and solar cells. We report on the influence of these species on the surface and bulk composition as well as bulk defect structure of CIGS films as revealed by X-ray photoelectron spectroscopy (XPS), secondary ion mass spectroscopy (SIMS), and photoluminescence (PL). From the XPS studies it is found that Na and K promote oxygen absorption onto the CIGS films. Furthermore, potassium accelerates the formation of indium and gallium oxides on the film surface, making the surface Cu-deficient. Low temperature PL studies suggest that (i) Na and K help passivate non-radiative recombination centers, presumably at the grain boundaries, and (ii) Na further impacts the bulk defect structure inside of CIGS grains, which is not observed with K. This change in bulk defect structure is attributed to the greater diffusivity of Na in CIGS relative to K due to the smaller atomic size. This in-depth study (integration of XPS, SIMS, PL, and device characteristics) reveals that the surface chemistry and the grain boundary passivation have stronger influences on the device performance than the bulk defect structure.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Effects of alkali elements-Na and K-onCIGS are studied using SIMS, XPS, and PL. </LI> <LI> Alkali elements passivate non-radiative recombination centers at grain boundaries. </LI> <LI> The device with Na and K shows the highest efficiencies due to <I>surface</I> passivation. </LI> <LI> Passivation of both <I>external interfaces</I> and <I>internal grain boundaries</I> is crucial. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Characterization of Fibrinogen Binding by Glycoproteins Srr1 and Srr2 of <i>Streptococcus agalactiae</i>

Seo, Ho Seong,Minasov, George,Seepersaud, Ravin,Doran, Kelly S.,Dubrovska, Ievgeniia,Shuvalova, Ludmilla,Anderson, Wayne F.,Iverson, Tina M.,Sullam, Paul M. American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.50

<▼1><P><B>Background:</B> The serine-rich repeat glycoproteins Srr1 and Srr2 are surface adhesins of <I>Streptococcus agalactiae</I> important for pathogenicity.</P><P><B>Results:</B> Both Srrs bind tandem repeats of the fibrinogen Aα chain, but Srr2 has greater affinity explained by structure-function analysis of the Srrs.</P><P><B>Conclusion:</B> A dock, lock, and latch mechanism describes the Srr-fibrinogen interaction.</P><P><B>Significance:</B> The higher affinity of Srr2 may contribute to the hypervirulence of Srr2-expressing strains.</P></▼1><▼2><P>The serine-rich repeat glycoproteins of Gram-positive bacteria comprise a large family of cell wall proteins. <I>Streptococcus agalactiae</I> (group B <I>streptococcus</I>, GBS) expresses either Srr1 or Srr2 on its surface, depending on the strain. Srr1 has recently been shown to bind fibrinogen, and this interaction contributes to the pathogenesis of GBS meningitis. Although strains expressing Srr2 appear to be hypervirulent, no ligand for this adhesin has been described. We now demonstrate that Srr2 also binds human fibrinogen and that this interaction promotes GBS attachment to endothelial cells. Recombinant Srr1 and Srr2 bound fibrinogen <I>in vitro</I>, with affinities of <I>K<SUB>D</SUB></I> = 2.1 × 10<SUP>−5</SUP> and 3.7 × 10<SUP>−6</SUP><SMALL>M</SMALL>, respectively, as measured by surface plasmon resonance spectroscopy. The binding site for Srr1 and Srr2 was localized to tandem repeats 6–8 of the fibrinogen Aα chain. The structures of both the Srr1 and Srr2 binding regions were determined and, in combination with mutagenesis studies, suggest that both Srr1 and Srr2 interact with a segment of these repeats via a “dock, lock, and latch” mechanism. Moreover, properties of the latch region may account for the increased affinity between Srr2 and fibrinogen. Together, these studies identify how greater affinity of Srr2 for fibrinogen may contribute to the increased virulence associated with Srr2-expressing strains.</P></▼2>

Assessment and Comparison of Three Dimensional Exoscopes for Near-Infrared Fluorescence-Guided Surgery Using Second-Window Indocyanine-Green

Cho, Steve S.,Teng, Clare W.,Ravin, Emma De,Singh, Yash B.,Lee, John Y.K. The Korean Neurosurgical Society 2022 Journal of Korean neurosurgical society Vol.65 No.4

Objective : Compared to microscopes, exoscopes have advantages in field-depth, ergonomics, and educational value. Exoscopes are especially well-poised for adaptation into fluorescence-guided surgery (FGS) due to their excitation source, light path, and image processing capabilities. We evaluated the feasibility of near-infrared FGS using a 3-dimensional (3D), 4 K exoscope with near-infrared fluorescence imaging capability. We then compared it to the most sensitive, commercially-available near-infrared exoscope system (3D and 960 p). In-vitro and intraoperative comparisons were performed. Methods : Serial dilutions of indocyanine-green (1-2000 ㎍/mL) were imaged with the 3D, 4 K Olympus Orbeye (system 1) and the 3D, 960 p VisionSense Iridium (system 2). Near-infrared sensitivity was calculated using signal-to-background ratios (SBRs). In addition, three patients with brain tumors were administered indocyanine-green and imaged with system 1, with two also imaged with system 2 for comparison. Results : Systems 1 and 2 detected near-infrared fluorescence from indocyanine green concentrations of >250 ㎍/L and >31.3 ㎍/L, respectively. Intraoperatively, system 1 visualized strong near-infrared fluorescence from two, strongly gadolinium-enhancing meningiomas (SBR=2.4, 1.7). The high-resolution, bright images were sufficient for the surgeon to appreciate the underlying anatomy in the near-infrared mode. However, system 1 was not able to visualize fluorescence from a weakly-enhancing intraparenchymal metastasis. In contrast, system 2 successfully visualized both the meningioma and the metastasis but lacked high resolution stereopsis. Conclusion : Three-dimensional exoscope systems provide an alternative visualization platform for both standard microsurgery and near-infrared fluorescent guided surgery. However, when tumor fluorescence is weak (i.e., low fluorophore uptake, deep tumors), highly sensitive near-infrared visualization systems may be required.

Novel Endoxylanases of the Moderately Thermophilic Polysaccharide-Degrading Bacterium Melioribacter roseus

( Andrey L Rakitin ),( Alexandra Y Ermakova ),( Nikolai V Ravin ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.9

Three endoxylanase-encoding genes from the moderately themophilic chemoorganotrophic bacterium Melioribacter roseus were cloned and expressed in Escherichia coli. Genes xyl2091 (Mros_2091) and xyl2495 (Mros_2495) encode GH10 family hydrolases, whereas xyl2090 (Mros_2090) represents the GH30 family. In addition to catalytic domains, Xyl2090 and Xyl2091 contain carbohydrate-binding modules that could facilitate their binding to xylans and Por sorting domains associated with the sorting of proteins from the periplasm to the outer membrane, where they are covalently attached. Recombinant endoxylanase Xyl2495 exhibited a high specific activity of 1,920 U/mg on birchwood xylan at 40oC. It is active at low temperatures, exhibiting more than 30% of the maximal activity even at 0oC. Endoxylanases Xyl2090 and Xyl2091 have lower specific activities but higher temperature optima at 80oC and 65oC, respectively. Analysis of xylan hydrolysis products revealed that Xyl2090 generates xylo-oligosaccharides longer than xylopentaose. Xylose and xylobiose are the major products of xylan hydrolysis by the recombinant Xyl2091 and Xyl2495. No activity against cellulose was observed for all enzymes. The presence of three xylanases ensures efficient xylan hydrolysis by M. roseus. The highly processive “free” endoxylanase Xyl2495 could hydrolyze xylan under moderate temperatures. Xylan hydrolysis at elevated temperatures could be accomplished by concerted action of two cell-bound xylanases; Xyl2090 that probably degrades xylans to long xylo-oligosaccharides, and Xyl2091 hydrolyzing them to xylose and xylobiose. The new endoxylanases could be useful for saccharification of lignocellulosic biomass in biofuels production, bleaching of paper pulp, and obtaining low molecular weight xylooligosaccharides.

Structural insights into Rab21 GTPase activation mechanism by molecular dynamics simulations

Shahbaaz, Mohd.,Amir, Mohd.,Rahman, Safikur,Mustafa Hasan, Gulam,Dohare, Ravins,Bisetty, Krishna,Ahmad, Faizan,Kim, Jihoe,Hassan, Md. Imtaiyaz Taylor Francis 2018 Molecular simulation Vol.44 No.3

Targeted Repair of CYBB in X-CGD iPSCs Requires Retention of Intronic Sequences for Expression and Functional Correction

Sweeney, Colin L.,Zou, Jizhong,Choi, Uimook,Merling, Randall K.,Liu, Alexander,Bodansky, Aaron,Burkett, Sandra,Kim, Jung-Woong,De Ravin, Suk See,Malech, Harry L. Elsevier 2017 Molecular therapy Vol.25 No.2

<P>X-linked chronic granulomatous disease (X-CGD) is an immune deficiency resulting from defective production of microbicidal reactive oxygen species (ROS) by phagocytes. Causative mutations occur throughout the CYBB gene, resulting in absent or defective gp91(phox) protein expression. To correct CYBB exon 5 mutations while retaining normal gene regulation, we utilized TALEN or Cas9 for exon 5 replacement in induced pluripotent stem cells (iPSCs) from patients, which restored gp91phox expression and ROS production in iPSC derived granulocytes. Alternate approaches for correcting the majority of X-CGD mutations were assessed, involving TALEN- or Cas9-mediated insertion of CYBB minigenes at exon 1 or 2 of the CYBB locus. Targeted insertion of an exon 1-13 minigene into CYBB exon 1 resulted in no detectable gp91phox expression or ROS activity in iPSC-derived granulocytes. In contrast, targeted insertion of an exon 2-13 minigene into exon 2 restored both gp91phox and ROS activity. This demonstrates the efficacy of two correction strategies: seamless repair of specific CYBB mutations by exon replacement or targeted insertion of an exon 2-13 minigene to CYBB exon 2 while retaining exon/intron 1. Furthermore, it highlights a key issue for targeted insertion strategies for expression from an endogenous promoter: retention of intronic elements can be necessary for expression.</P>