bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle‐type 6‐phosphofructo‐1‐kinase and aldolase associate conferring catalytic advantages for both enzymes
Authors: Marcondes Mariah Celestino , Sola‐Penna Mauro , Torres Renan da Silva Gianoti , Zancan Patricia 
Published: June 2011

Abstract6‐Phosphofructo‐1‐kinase (PFK) and aldolase are two sequential glycolytic enzymes that associate forming heterotetramers containing a dimer of each enzyme. Although free PFK dimers present a negligible activity, once associated to aldolase these dimers are as active as the fully active tetrameric conformation of the enzyme. Here we show that aldolase‐associated PFK dimers are not inhibited by clotrimazole, an antifulgal azole derivative proposed as an antineoplastic drug due to its inhibitory effects on PFK. In the presence of aldolase, PFK is not modulated by its allosteric activators, ADP and fructose‐2,6‐bisphosphate, but is still inhibited by citrate and lactate. The association between the two enzymes also results on the twofold stimulation of aldolase maximal velocity and affinity for its substrate. These results suggest that the association between PFK and aldolase confers catalytic advantage for both enzymes and may contribute to the channeling of the glycolytic metabolism. © 2011 IUBMB IUBMB Life, 63(6): 435–445, 2011
Brief update on different roles of tau in neurodegeneration
Authors: Ittner Arne , Ke Yazi D. , Eersel Janet van , Gladbach Amadeus , Götz Jürgen , Ittner Lars M. 
Published: June 2011

AbstractBoth Alzheimer's disease (AD) and almost every second case of frontotemporal lobar degeneration (FTLD) are characterized by the deposition of hyperphosphorylated forms of the microtubule‐associated protein tau in neurons and/or glia. This unifying pathology led to coining the umbrella term “tauopathies” for these conditions. While the deposition of tau ultimately results in the formation of typical histopathological lesions, such as the neurofibrillary tangles (NFTs) in AD, it is now well accepted that tau interferes with normal functions in neurons already before its deposition. Together with the identification of pathogenic mutations in the tau‐encoding gene MAPT in FTLD and evidence from a rising number of in vivo animal models a central role of tau in neurodegeneration has emerged. Here, we review the role of pathological tau in axonal transport, mitochondrial respiration, and in mediating amyloid‐β toxicity in AD. Furthermore, we review recent findings regarding the spreading of tau pathology throughout the brain as disease progresses. © 2011 IUBMB IUBMB Life, 63(7): 495–502, 2011
Moonlighting characteristics of G protein‐coupled receptors: Focus on receptor heteromers and relevance for neurodegeneration
Authors: Borroto‐Escuela Dasiel O. , Tarakanov Alexander O. , Guidolin Diego , Ciruela Francisco , Agnati Luigi F. , Fuxe Kjell 
Published: June 2011

AbstractIt is proposed that the moonlighting concept can be applied to G protein coupled receptors (GPCRs) as, obviously, they can carry out different types of functions. The same motifs in, for example, the third intracellular loop, can moonlight by switching between receptor–receptor interactions and interactions with signaling proteins such as G proteins or calmodulin. A “guide‐and‐clasp” manner of receptor–receptor interactions has been proposed where the “adhesive guides” may be the triplet homologies. As an example, the triplets AAR (or RAA) and AAE (or EAA) homologies in A2AR‐D2R heteromers may guide‐and‐clasp binding not only of the two protomers but also of calmodulin and Gi. A beautiful moonlighting phenomenon in the A2AR‐D2R heteromer is that the positively charged D2R N‐terminal third intracellular loop epitope (VLRRRRKRVN) may switch between bindings to the negatively charged A2AR epitope (SAQEpSQGNT), localized in the medium segment of the C terminus of the A2A receptor to several negative epitopes of calmodulin. Furthermore, overlapping motifs may favor moonlighting to Gi/o via inter alia electrostatic interaction between triplets AAR(in D2R third intracellular loop) and AAE (Gi/alpha1) (and/or their symmetric variants) contributing to guide‐and‐clasp D2R‐Gi interactions Thus, moonlighting in GPCR heteromers can take place via allosteric receptor–receptor interactions and is also described in D1R‐D2R, D2R‐5‐HT2R,and A1R‐P2Y1 heteromers. Allosteric receptor–receptor interactions in GPCR‐receptor tyrosine kinases (RTKs) heteromers and postulated ion channel receptor‐RTK heteromers‐like, for example, AMPA‐NMDA‐TrkB heteromers may lead to moonlighting of the participating GPCR and RTK protomers altering, for example, the pattern of the five major signaling pathways of the RTKs favoring MAPK and/or mTOR signaling with high relevance for neurodegenerative processes and depression induced atrophy of neurons. Moonlighting may also develop in the intracellular loops and C‐terminal of the GPCRs as a result of dynamic allosteric interactions between different types of G proteins and other receptor interacting proteins in these domains of the receptor. ©2011 IUBMB IUBMB Life, 63(7): 463‐472, 2011
How a neutral evolutionary ratchet can build cellular complexity
Authors: Lukeš Julius , Archibald John M. , Keeling Patrick J. , Doolittle W. Ford , Gray Michael W. 
Published: June 2011

AbstractComplex cellular machines and processes are commonly believed to be products of selection, and it is typically understood to be the job of evolutionary biologists to show how selective advantage can account for each step in their origin and subsequent growth in complexity. Here, we describe how complex machines might instead evolve in the absence of positive selection through a process of “presuppression,” first termed constructive neutral evolution (CNE) more than a decade ago. If an autonomously functioning cellular component acquires mutations that make it dependent for function on another, pre‐existing component or process, and if there are multiple ways in which such dependence may arise, then dependence inevitably will arise and reversal to independence is unlikely. Thus, CNE is a unidirectional evolutionary ratchet leading to complexity, if complexity is equated with the number of components or steps necessary to carry out a cellular process. CNE can explain “functions” that seem to make little sense in terms of cellular economy, like RNA editing or splicing, but it may also contribute to the complexity of machines with clear benefit to the cell, like the ribosome, and to organismal complexity overall. We suggest that CNE‐based evolutionary scenarios are in these and other cases less forced than the selectionist or adaptationist narratives that are generally told. © 2011 IUBMB IUBMB Life, 63(7): 528–537, 2011
Ligand‐ and proton‐linked conformational changes of the ferrous 2/2 hemoglobin of Pseudoalteromonas haloplanktis TAC125
Authors: Giordano Daniela , Russo Roberta , Ciaccio Chiara , Howes Barry D. , di Prisco Guido , Marden Michael C. , Hui Bon Hoa Gaston , Smulevich Giulietta , Coletta Massimo , Verde Cinzia 
Published: June 2011

AbstractThe spectroscopic and ligand‐binding properties of a 2/2 globin from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 have been studied in the ferrous state. It displays two major conformations characterized by CO‐association rates that differ by a factor of 20, with relative fractions that depend on pH. A dynamic equilibrium is found between the two conformations, as indicated by an enhanced slower phase when lower CO levels were used to allow a longer time to facilitate the transition. The deoxy form, in the absence of external ligands, is a mixture of a predominant six‐coordinate low spin form and a five‐coordinate high‐spin state; the proportion of low spin increasing at alkaline pH. In addition, at temperatures above the physiological temperature of 1 °C, an enhanced tendency of the protein to oxidize is observed. © 2011 IUBMB IUBMB Life, 63(7): 566–573, 2011
Tyr306 near the C‐terminus of protein phosphatase‐1 affects enzyme stability and inhibitor binding
Authors: Wang Bai J. , Tang Wei , Zhang Peng , Wei Qun 
Published: June 2011

AbstractPrevious deletion studies have suggested that Tyr306 has an important influence on the properties of protein phosphatase‐1 (PP1). To test this inference, we constructed three site‐directed mutants, PP1Y306A, PP1Y306K, and PP1Y306E. The specific activity of PP1Y306A was 3.5‐fold higher than that of PP1wt, especially with K‐R‐Tp‐I‐R‐R as substrate, and it also had a 13‐fold higher Kcat and a 43‐fold higher Kcat/Km. PP1Y306K and PP1Y306E, in that order, and were next in terms of increased activity. Use of the denaturant guanidine hydrochloride (GdnHCl) demonstrated that mutation of this site decreased enzyme stability. PP1Y306A and PP1Y306E lost all activity when incubated for 24 h in 0.6 M GdnHCl, and their fluorescence spectra confirmed the loss of stability. Because all three substitutions had a similar effect, we infer that the aromatic group of Tyr plays a crucial role in maintaining enzyme stability. Our results show that Tyr306 does affect the spatial conformation of the catalytic subunit of PP1 molecule. The IC50 of PP1Y306A for the inhibitor microcystin‐LR was threefold higher than that of PP1wt, whereas those of PP1Y306E for tautomycin and norcantharidin were 15‐fold and 10‐fold higher, respectively. We conclude that Tyr306 plays an important role in enzyme stability and inhibitor binding. © 2011 IUBMB IUBMB Life, 63(7): 574–581, 2011
Intrinsically unstructured proteins and neurodegenerative diseases: Conformational promiscuity at its best
Authors: Das Samir , Mukhopadhyay Debashis 
Published: June 2011

AbstractNeurodegenerative diseases are complex, multifactorial disorders where misfolding of proteins cause aberrant protein–protein interactions. They are not usually characterized by specific mutations especially for nonfamilial disease types. Most of the causative proteins, however, are intrinsically unstructured (IUP), loss of whose fine balance could play pivotal role in these processes. Very fast conformational switch of these IUPs between different functional forms, so as to choose different interaction partners and different functional niches within the cell, is the basic premise on which these proteins maintain their interaction network. We are working on the hypothesis that even small perturbations in conformation leads to disruption of the network and to the disease phenotype. Based on a comprehensive data search, the evidence was obtained for the role of IUPs in neurodegenerative disorders, and their mode of action through conformational promiscuity is elaborated through three case studies. © 2011 IUBMB IUBMB Life, 63(7): 478–488, 2011
Moonlighting cytochrome P450 monooxygenases
Authors: Zhao Bin , Waterman Michael R. 
Published: June 2011

AbstractRecently, cytochrome P450 170A1 (CYP170A1) has been found to be a bifunctional protein, which catalyzes both monooxygenase activity and terpene synthase activity by two distinct active sites in the well‐established P450 protein structure. Therefore, CYP170A1 is identified clearly as a moonlighting protein. The known activities of a small number of the 13,000 members of the P450 superfamily fall into two general classes: promiscuous enzymes that are not considered as moonlighting and forms that participate in biosynthesis of endogenous compounds, such as steroids, vitamins and play different roles in different tissues, sometimes being moonlighting enzymes. Here, we review examples of moonlighting P450, which add to our understanding of the large CYP superfamily. © 2011 IUBMB IUBMB Life, 63(7): 473–477, 2011
Titania–hydroxyapatite nanocomposite coatings support human mesenchymal stem cells osteogenic differentiation
Authors: Dimitrievska Sashka , Bureau Martin N. , Antoniou John , Mwale Fackson , Petit Alain , Lima Rogerio S. , Marple Basil R. 
Published: June 2011

AbstractIn addition to mechanical and chemical stability, the third design goal of the ideal bone‐implant coating is the ability to support osteogenic differentiation of mesenchymal stem cells (MSCs). Plasma‐sprayed TiO2‐based bone‐implant coatings exhibit excellent long‐term mechanical properties, but their applications in bone implants are limited by their bioinertness. We have successfully produced a TiO2 nanostructured (grain size <50 nm) based coating charged with 10% wt hydroxyapatite (TiO2–HA) sprayed by high‐velocity oxy‐fuel. On Ti64 substrates, the novel TiO2–HA coating bond 153× stronger and has a cohesive strength 4× higher than HA coatings. The HA micro‐ and nano‐sized particles covering the TiO2–HA coating surface are chemically bound to the TiO2 coating matrix, producing chemically stable coatings under high mechanical solicitations. In this study, we elucidated the TiO2–HA nanocomposite coating surface chemistry, and in vitro osteoinductive potential by culturing human MSCs (hMSCs) in basal and in osteogenic medium (hMSC‐ob). We assessed the following hMSCs and hMSC‐ob parameters over a 3‐week period: (i) proliferation; (ii) cytoskeleton organization and cell–substrate adhesion; (iii) coating–cellular interaction morphology and growth; and (iv) cellular mineralization. The TiO2–HA nanocomposite coatings demonstrated 3× higher hydrophilicity than HA coatings, a TiO2‐nanostructured surface in addition to the chemically bound HA micron‐ and nano‐sized rod to the surface. hMSCs and hMSC‐ob demonstrated increased proliferation and osteoblastic differentiation on the nanostructured TiO2–HA coatings, suggesting the TiO2–HA coatings nanostructure surface properties induce osteogenic differentiation of hMSC and support hMSC‐ob osteogenic potential better than our current golden standard HA coating. Published 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
A generalized strategy for designing 19F/1H dual‐frequency MRI coil for small animal imaging at 4.7 Tesla
Authors: Hu Lingzhi , Hockett Frank D. , Chen Junjie , Zhang Lei , Caruthers Shelton D. , Lanza Gregory M. , Wickline Samuel A. 
Published: June 2011

AbstractPurpose:To propose and test a universal strategy for building 19F/1H dual‐frequency RF coil that permits multiple coil geometries.Materials and Methods:The feasibility to design 19F/1H dual‐frequency RF coil based on coupled resonator model was investigated. A series capacitive matching network enables robust impedance matching for both harmonic oscillating modes of the coupled resonator. Two typical designs of 19F/1H volume coils (birdcage and saddle) at 4.7T were implemented and evaluated with electrical bench test and in vivo 19F/1H dual‐nuclei imaging.Results:For various combinations of internal resistances of the sample coil and secondary resonator, numerical solutions for the tunable capacitors to optimize impedance matching were obtained using a root‐seeking program. Identical and homogeneous B1 field distribution at 19F and 1H frequencies were observed in bench test and phantom image. Finally, in vivo mouse imaging confirmed the sensitivity and homogeneity of the 19F/1H dual‐frequency coil design.Conclusion:A generalized strategy for designing 19F/1H dual‐frequency coils based on the coupled resonator approach was developed and validated. A unique feature of this design is that it preserves the B1 field homogeneity of the RF coil at both resonant frequencies. Thus it minimizes the susceptibility effect on image co‐registration. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Intracranial arterial wall imaging using three‐dimensional high isotropic resolution black blood MRI at 3.0 Tesla
Authors: Qiao Ye , Steinman David A. , Qin Qin , Etesami Maryam , Schär Michael , Astor Brad C. , Wasserman Bruce A. 
Published: June 2011

AbstractPurpose:To develop a high isotropic‐resolution sequence to evaluate intracranial vessels at 3.0 Tesla (T).Materials and Methods:Thirteen healthy volunteers and 4 patients with intracranial stenosis were imaged at 3.0T using 0.5‐mm isotropic‐resolution three‐dimensional (3D) Volumetric ISotropic TSE Acquisition (VISTA; TSE, turbo spin echo), with conventional 2D‐TSE for comparison. VISTA was repeated for 6 volunteers and 4 patients at 0.4‐mm isotropic‐resolution to explore the trade‐off between SNR and voxel volume. Wall signal‐to‐noise‐ratio (SNRwall), wall‐lumen contrast‐to‐noise‐ratio (CNRwall‐lumen), lumen area (LA), wall area (WA), mean wall thickness (MWT), and maximum wall thickness (maxWT) were compared between 3D‐VISTA and 2D‐TSE sequences, as well as 3D images acquired at both resolutions. Reliability was assessed by intraclass correlations (ICC).Results:Compared with 2D‐TSE measurements, 3D‐VISTA provided 58% and 74% improvement in SNRwall and CNRwall‐lumen, respectively. LA, WA, MWT and maxWT from 3D and 2D techniques highly correlated (ICCs of 0.96, 0.95, 0.96, and 0.91, respectively). CNRwall‐lumen using 0.4‐mm resolution VISTA decreased by 27%, compared with 0.5‐mm VISTA but with reduced partial‐volume‐based overestimation of wall thickness. Reliability for 3D measurements was good to excellent.Conclusion:The 3D‐VISTA provides SNR‐efficient, highly reliable measurements of intracranial vessels at high isotropic‐resolution, enabling broad coverage in a clinically acceptable time. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Dynamic late gadolinium enhancement simply quantified using myocardium to lumen signal ratio: Normal range of ratio and diffuse abnormal enhancement of cardiac amyloidosis
Authors: Kono Atsushi K. , Yamada Naoaki , Higashi Masahiro , Kanzaki Suzu , Hashimura Hiromi , Morita Yoshiaki , Sakuma Toshiharu , Noguchi Teruo , Naito Hiroaki , Sugimura Kazuro 
Published: June 2011

AbstractPurpose:To detect abnormal myocardial tissue in patients with diffuse myocardial disease, we propose a simple technique of late gadolinium enhancement (LGE) using routine myocardial imaging modalities.Materials and Methods:We retrospectively reviewed LGE images from 51 patients with normal myocardium and 10 patients with pathologically proven cardiac amyloidosis (CA). We obtained sequential LGE images from patients at 2, 5, 10, and 20 minutes after injection of Gd‐DTPA (0.15 mmol/kg) with a fixed inversion time of 300 msec. We evaluated the signal intensity ratio of the myocardium to the left ventricular lumen (M/L) in one long and two short axial sections within 463 and 120 segments of normal myocardium and CA, respectively. Visually unenhanced and enhanced regions of myocardium were evaluated in each segment of patients with CA.Results:Among normal myocardium, M/L (means ± standard deviation; SD) was stable with time (2, 5, 10, and 20 min: 0.34 ± 0.03, 0.31 ± 0.05, 0.34 ± 0.07, and 0.42 ± 0.11, respectively). The calculated M/L of unenhanced (0.60 ± 0.20, 0.68 ± 0.19, 0.76 ± 0.20, and 1.09 ± 0.25, respectively) and enhanced myocardium (0.77 ± 0.27, 0.99 ± 0.29, 1.20 ± 0.40, and 1.45 ± 0.54, respectively) in patients with CA was significantly greater than that seen for the normal myocardium at each time and increased over time.Conclusion:In patients with CA, diffuse myocardial abnormalities can be demonstrated using M/L, and this technique may be useful for the characterization of other myocardial diseases. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
The relationships among spatiotemporal collagen gene expression, histology, and biomechanics following full‐length injury in the murine patellar tendon
Authors: Dyment Nathaniel A. , Kazemi Namdar , Aschbacher‐Smith Lindsey E. , Barthelery Nicolas J. , Kenter Keith , Gooch Cynthia , Shearn Jason T. , Wylie Christopher , Butler David L. 
Published: June 2011

AbstractTendon injuries are major orthopedic problems that worsen as the population ages. Type‐I (Col1) and type‐II (Col2) collagens play important roles in tendon midsubstance and tendon‐to‐bone insertion healing, respectively. Using double transgenic mice, this study aims to spatiotemporally monitor Col1 and Col2 gene expression, histology, and biomechanics up to 8 weeks following a full‐length patellar tendon injury. Gene expression and histology were analyzed weekly for up to 5 weeks while mechanical properties were measured at 1, 2, 5, and 8 weeks. At week 1, the healing region displayed loose granulation tissue with little Col1 expression. Col1 expression peaked at 2 weeks, but the ECM was highly disorganized and hypercellular. By 3 weeks, Col1 expression had reduced and by 5 weeks, the ECM was generally aligned along the tendon axis. Col2 expression was not seen in the healing midsubstance or insertion at any time point. The biomechanics of the healing tissue was inadequate at all time points, achieving ultimate loads and stiffnesses of 48% and 63% of normal values by 8 weeks. Future studies will further characterize the cells within the healing midsubstance and insertion using tenogenic markers and compare these results to those of tendon cells during normal development. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:28–36, 2012
Mid‐scale free‐flow electrophoresis with gravity‐induced uniform flow of background buffer in chamber for the separation of cells and proteins
Authors: Dong Yu‐Chao , Shao Jing , Yin Xiao‐Yang , Fan Liu‐yin , Cao Cheng‐Xi 
Published: June 2011

AbstractA large‐scale free‐flow electrophoresis (LS‐FFE) is often too large for cell separation of lab scale, whereas micro‐FFE (μFFE) has great difficulty in cell isolation due to easy blockage by cell accumulation in μFFE. In this study, a mid‐scale FFE (MS‐FFE) is developed for cell and protein separations. The volume of the separation chamber (70×40×0.1–0.8 mm) is from 280 μL to 2.24 mL, much lower than that in an LS‐FFE but higher than that in a μFFE. Gravity is used for uniform flow of the background buffer only via a single pump with 16 channels and the sample is injected via an adjuster originally used for clinical intravenous injection. The experiments reveal that the hydrodynamic and electrohydrodynamic flows are much stable, and the Joule heat can be effectively dispersed without obvious positive or negative deviation as shown by the omega plots. By the device, Escherichia coli and Staphylococcus aureus, which easily accumulate to block μFFE and are separated with difficulty due to their same negative charges carried, can be well isolated under the conditions of 4.5 mM pH 8.5 Tris‐boric buffer (4.5 mM Tris, 4.5 mM boric acid) with 0.10 mM ethylene diamine tetraacetic acid and 5% m/v sucrose, 200 μL/min, 800 V, and sample injection via inlet 4. The mid‐scale FFE device could also be used for the separation of three model proteins of horse heart cytochrome c, myoglobin and bovine serum albumin. The device has clear significance for mid‐scale separation of cells and proteins.
Quick Polymerization from Electrospun Macroinitiators for Making Thermoresponsive Nanofibers
Authors: Brandl Christian , Greiner Andreas , Agarwal Seema 
Published: June 2011

AbstractThermoresponsive nanofibers by very fast grafting of N,N‐isopropylacrylamide (NIPAAm) from electrospun atom transfer radical polymerization (ATRP) macroinitiator are presented in this work. The heterogenous grafting of NIPAAm onto macroinitiator fibers could be done in few minutes, i.e., in less than 5 min. The procedure involved electrospinning of an ATRP macroinitiator and subsequent PNIPAAm grafting using “grafting from” technique. The ATRP Macroinitiator was based on a copolymer of methyl methacrylate (MMA) and 2‐hydroxyethyl methacrylate (HEMA). The growth of the PNIPAAm layer on electrospun fibers was followed by IR‐spectroscopy and SEM analysis. The temperature‐dependent‐phase transition was proven by contact angle measurements and could be shown on the same surface for many cycles. magnified image