bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing the robustness of the MM/PBSA free energy calculation method: Application to DNA conformational transitions
Authors: Brice Allyn R. , Dominy Brian N. 
Published: February 2011

AbstractThe ability to predict and characterize free energy differences associated with conformational equilibria or the binding of biomolecules is vital to understanding the molecular basis of many important biological functions. As biological studies focus on larger molecular complexes and properties of the genome, proteome, and interactome, the development and characterization of efficient methods for calculating free energy becomes increasingly essential. The aim of this study is to examine the robustness of the end‐point free energy method termed the molecular mechanics Poisson‐Boltzmann solvent accessible surface area (MM/PBSA) method. Specifically, applications of MM/PBSA to the conformational equilibria of nucleic acid (NA) systems are explored. This is achieved by comparing A to B form DNA conformational free energy differences calculated using MM/PBSA with corresponding free energy differences determined with a more rigorous and time‐consuming umbrella sampling algorithm. In addition, the robustness of NA MM/PBSA calculations is also evaluated in terms of the sensitivity towards the choice of force field and the choice of solvent model used during conformational sampling. MM/PBSA calculations of the free energy difference between A‐form and B‐form DNA are shown to be in very close agreement with the PMF result determined using an umbrella sampling approach. Further, it is found that the MM/PBSA conformational free energy differences were also in agreement using either the CHARMM or AMBER force field. The influence of ionic strength on conformational stability was particularly insensitive to the choice of force field. Finally, it is also shown that the use of a generalized Born implicit solvent during conformational sampling results in free energy estimates that deviate slightly from those obtained using explicitly solvated MD simulations in these NA systems. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Electron localization function and electron localizability indicator applied to study the bonding in the peroxynitrous acid HOONO
Authors: Berski Slawomir , Latajka Zdzislaw , Gordon Agnieszka J. 
Published: February 2011

AbstractThe ground‐state electronic structure of peroxynitrous acid (HOONO) and its singlet biradicaloid form (HO···ONO) have been studied using topological analysis of the electron localization function (ELF), together with the electron localizability indicator (ELI‐D), at the DFT (B3LYP, M05, M052X, and M06), CCSD, and CASSCF levels. Three isomers of HOONO (cis‐cis, cis‐perp, and trans‐perp) have been considered. The results show that from all functionals applied, only B3LYP yields the correct geometrical structure. The ELF and ELI‐D‐topology of the OO and central NO bonds strongly depends on the wave function used for analysis. Calculations carried out at CAS (14,12)/aug‐cc‐pVTZ//CCSD(T)/aug‐cc‐pVTZ level reveal two bonds of the charge‐shift type: a protocovalent NO bond with a basin population of 0.82–1.08e, and a more electron depleted OO bond with a population of 0.66–0.71e. The most favorable dissociation channel (HOONO → HO + ONO) corresponds to breaking of the most electron‐deficient bond (OO). In the case of cis‐ and trans‐HO···ONO, the ELF, ELI‐D, and electron density fields results demonstrate a closed‐shell O···O interaction. The α‐spin electrons are found mainly (0.64e) in the lone pairs of oxygen Vi
= 1,2 (O) from the OH group. The β‐spin electrons are delocalized over the ONO group, with the largest concentration (0.34e) on the lone pair of nitrogen V(N). © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Conformational searching using a population‐based incremental learning algorithm
Authors: Long Stephen M. , Tran Tran T. , Adams Peter , Darwen Paul , Smythe Mark L. 
Published: February 2011

AbstractA new population‐based incremental learning algorithm for conformational searching of molecules is presented. This algorithm is particularly effective at determining, by relatively small number of energy minimizations, global energy minima of large flexible molecules. The algorithm is also able to find a large set of low energy conformations of more rigid small molecules. The performance of the algorithm is relation to other algorithm is examined via the test molecules: C18H38, C39H80, cycloheptadecane and a set of five drug‐like molecules. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Enumeration and classification of benzenoid hydrocarbons
Authors: Brunvoll J. , Cyvin S. J. , Cyvin B. N. 
Published: February 2011

AbstractThe enumeration of benzenoids is studied with the aid of different modifications of a computer program. Known values for the number of cata‐condensed and of all benzenoids with h (number of hexagons) up to eight are reproduced. These benzenoids are classified into (a) unbranched of different symmetries and branched cata‐condensed, and (b) normal, essentially disconnected and non‐Kekuléan peri‐condensed. Within the normal benzenoids a more detailed classification is performed: basic benzenoids, fused, or annelated. For h = 9 an almost complete classification along the same lines was achieved.
Electronic structure of clusters modeling silica
Authors: Lopez Jesus P. , Yang Cary Y. , Helms C. R. 
Published: February 2011

AbstractSelf‐consistent‐field‐Xα‐scattered wave calculations on clusters Si2O76− and H6Si2O7 modeling silica have been performed. Incorporation of Si 3d orbitals produces significant changes in the overall valence structure. In addition to σ Si — O bonds, there exists a bonding π character due to the participation of O 2p and Si 3d. Hydrogen terminators do not seem to correct edge effects for these π states.
Small imines and oximes as model compounds in the optimization of a consistent force field potential energy function
Authors: Huige C. J. M. , Hezemans A. M. F. , Rasmussen Kjeld 
Published: February 2011

AbstractParameters have been optimized for a potential energy function to be used in molecular mechanics calculations of small imines as a preliminary step to calculations on larger systems. A consistent force field (CFF) program was used, and a new damping algorithm due to Sundius was introduced in the optimization procedure. Optimization of parameters has been done on structural and vibrational data of five small imines and one oxime. The quality of the derived potential energy function is examined by calculations on larger oximes.
Model potentials for molecular calculations. II. The spd‐MP set for transition metal atoms Sc through Hg
Authors: Sakai Yoshiko , Miyoshi Eisaku , Klobukowski Mariusz , Huzinaga Sigeru 
Published: February 2011

AbstractModel potential parameters and valence orbitals were generated for the transition metal atoms Sc through Hg. They are named the spd‐MPs and are supplementary to the sd‐MPs presented in the preceding article. The outermost core np electrons were treated explicitly together with valence nd and (n + 1)s electrons, and the remaining electrons were replaced by a model potential. The model potential parameters and valence orbitals were determined in the same way as the sd‐MPs. Major relativistic effects (via the mass velocity and Darwin terms) were also incorporated in the spd‐MPs for the second‐and third‐row transition metal atoms. The results of numerical nonrelativistic Hartree‐Fock (HF) calculations for the first‐row transition metal atoms and of the quasirelativistic HF calculations with Cowan and Griffin's method for the second‐row and third‐row transition metal atoms were used as reference data in determination of the spd‐MPs.
Interaction energy studies of 8‐azapurine during transcription
Authors: Sanyal Nitish K. , Ojha Rajendra Prasad , Roychoudhury M. 
Published: February 2011

AbstractThe quantum mechanical perturbation method has been utilized to explain the biological function of 8‐azapurine nucleoside analogs. The possibility of binding of the analog has been discussed in terms of interaction energy, which includes the electrostatic, polarization, dispersion, and repulsion terms. The stacking and the hydrogen bonding energy of the analog with nucleic acid bases and base pairs have been computed in all possible orientations. The model developed by Sanyal et al. for the incorporation of nucleoside analogs has been used to find out the inhibitory effect of the drug on nucleic acid and protein synthesis. It has been observed that these results are in broad agreement with the experimental observations.
Knock‐down of amphiregulin inhibits cellular invasion in inflammatory breast cancer
Authors: Baillo Andrea , Giroux Craig , Ethier Stephen P. 
Published: February 2011

AbstractWe have previously shown that SUM‐149 human breast cancer cells require an amphiregulin (AREG) autocrine loop for cell proliferation. We also demonstrated that AREG can increase epidermal growth factor receptor (EGFR) stability and promote EGFR localization to the plasma membrane. In the present studies we successfully knocked‐down AREG expression in SUM‐149 cells by lentiviral infection of AREG shRNA. In the absence of AREG expression, SUM‐149 cell growth was slowed, but not completely inhibited. Furthermore, cells infected with AREG shRNA constructs showed an increase in EGFR protein expression by Western blot. Immunofluorescence and confocal microscopy showed that following AREG knock‐down, EGFR continued to localize to the cell surface. Soft agar assays demonstrated that AREG knock‐down cells retain anchorage‐independent growth capacity. Additionally mammosphere forming assays and Adefluor staining analysis showed that knock‐down of AREG expression did not affect the expression of stem cell phenotypes. However, following AREG knock‐down, SUM‐149 cells demonstrated a dramatic decrease in their ability to invade a Matrigel matrix. Consistent with this observation, microarray analysis comparing cells infected with a non‐silencing vector to the AREG knock‐down cells, identified genes associated with the invasive phenotype such as RHOB and DKK1, and networks associated with cell motility such as integrin‐linked kinase signaling, and focal adhesion kinase signaling. AREG was also found to modulate WNT and Notch signaling in these cells. Thus, AREG functions in regulating the invasive phenotype, and we propose that this regulation may be through altered signaling that occurs when AREG activates plasma membrane localized EGFR. J. Cell. Physiol. 226: 2691–2701, 2011. © 2011 Wiley‐Liss, Inc.
Characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress
Authors: White Stephen J. , Hayes Elaine M. , Lehoux Stéphanie , Jeremy Jamie Y. , Horrevoets Anton J.G. , Newby Andrew C. 
Published: February 2011

AbstractMost acute coronary events occur in the upstream region of stenotic atherosclerotic plaques that experience laminar shear stress (LSS) elevated above normal physiological levels. Many studies have described the atheroprotective effect on endothelial behavior of normal physiological LSS (approximately 15 dynes/cm2) compared to static or oscillatory shear stress (OSS), but it is unknown whether the levels of elevated shear stress imposed by a stenotic plaque would preserve, enhance or reverse this effect. Therefore we used transcriptomics and related functional analyses to compare human endothelial cells exposed to laminar shear stress of 15 (LSS15‐normal) or 75 dynes/cm2 (LSS75‐elevated). LSS75 upregulated expression of 145 and downregulated expression of 158 genes more than twofold relative to LSS15. Modulation of the metallothioneins (MT1‐G, ‐M, ‐X) and NADPH oxidase subunits (NOX2, NOX4, NOX5, and p67phox) accompanied suppression of reactive oxygen species production at LSS75. Shear induced changes in dual specificity phosphatases (DUSPs 1, 5, 8, and 16 increasing and DUSPs 6 and 23 decreasing) were observed as well as reduced ERK1/2 but increased p38 MAP kinase phosphorylation. Amongst vasoactive substances, endothelin‐1 expression decreased whereas vasoactive intestinal peptide (VIP) and prostacyclin expression increased, despite which intracellular cAMP levels were reduced. Promoter analysis by rVISTA identified a significant over representation of ATF and Nrf2 transcription factor binding sites in genes upregulated by LSS75 compared to LSS15. In summary, LSS75 induced a specific change in behavior, modifying gene expression, reducing ROS levels, altering MAP kinase signaling and reducing cAMP levels, opening multiple avenues for future study. J. Cell. Physiol. 226: 2841–2848, 2011. © 2011 Wiley‐Liss, Inc.
Insulin‐stimulated L‐arginine transport requires SLC7A1 gene expression and is associated with human umbilical vein relaxation
Authors: González Marcelo , Gallardo Victoria , Rodríguez Natalia , Salomón Carlos , Westermeier Francisco , Gutiérrez Enrique Guzmán‐ , Abarzúa Fernando , Leiva Andrea , Casanello Paola , Sobrevia Luis 
Published: February 2011

AbstractInsulin causes endothelium‐derived nitric oxide (NO)‐dependent vascular relaxation, and increases L‐arginine transport via cationic amino acid transporter 1 (hCAT‐1) and endothelial NO synthase (eNOS) expression and activity in human umbilical vein endothelium (HUVEC). We studied insulin effect on SLC7A1 gene (hCAT‐1) expression and hCAT‐transport activity role in insulin‐modulated human fetal vascular reactivity. HUVEC were used for L‐arginine transport and L‐[3H]citrulline formation (NOS activity) assays in absence or presence of N‐ethylmaleimide (NEM) or L‐lysine (L‐arginine transport inhibitors). hCAT‐1 protein abundance was estimated by Western blot, mRNA quantification by real time PCR, and SLC7A1 promoter activity by Luciferase activity (−1,606 and −650 bp promoter fragments from ATG). Specific protein 1 (Sp1), and total or phosphorylated eNOS protein was determined by Western blot. Sp1 activity (at four sites between −177 and −105 bp from ATG) was assayed by chromatin immunoprecipitation (ChIP) and vascular reactivity in umbilical vein rings. Insulin increased hCATs–L‐arginine transport, maximal transport capacity (Vmax/Km), and hCAT‐1 expression. NEM and L‐lysine blocked L‐arginine transport. In addition, it was trans‐stimulated (∼7.8‐fold) by L‐lysine in absence of insulin, but unaltered (∼1.4‐fold) in presence of insulin. Sp1 nuclear protein abundance and binding to DNA, and SLC7A1 promoter activity was increased by insulin. Insulin increased NO synthesis and caused endothelium‐dependent vessel relaxation and reduced U46619‐induced contraction, effects blocked by NEM and L‐lysine, and dependent on extracellular L‐arginine. We suggest that insulin induces human umbilical vein relaxation by increasing HUVEC L‐arginine transport via hCATs (likely hCAT‐1) most likely requiring Sp1‐activated SLC7A1 expression. J. Cell. Physiol. 226: 2916–2924, 2011. © 2011 Wiley‐Liss, Inc.
Importance of serum source for the in vitro replicative senescence of human bone marrow derived mesenchymal stem cells
Authors: Duggal Shivali , Brinchmann Jan E. 
Published: February 2011

AbstractHuman mesenchymal stem cells (hMSCs) may be used for therapeutic applications. Culture conditions such as the serum source may impact on cell quality and the onset of replicative senescence. We have examined the effect of culturing hMSCs in autologous serum (AS) versus fetal bovine serum (FBS) on factors involved in in vitro replicative senescence. hMSCs from four donors were cultured in 10% FBS or 10% AS until they reached senescence. Cells were harvested at early passage and near senescence to study factors known to be involved in cellular senescence. The number of population doublings till senescence was similar for cells cultured in FBS, but varied greatly for hMSCs cultured in AS. FBS cells accumulated in S phase of cell cycle. This could not be explained by increased expression of cell cycle inhibitor proteins. Heat shock proteins were upregulated in AS compared to FBS cells. Reactive oxygen species and nitric oxide were upregulated in senescent FBS cells. Telomeres were shorter in senescent cells, more significantly in FBS cells. The source of serum was a determinant for the time till senescence in cultured hMSC. Serum source affected aspects of cell cycle regulation and the levels of heat shock proteins. Several mechanisms are likely to be responsible for replicative senescence in hMSC. Insight into the molecular details of how serum factors impacts on these mechanisms is important for the safe use of hMSCs in clinical applications. J. Cell. Physiol. 226: 2908–2915, 2011. © 2011 Wiley‐Liss, Inc.
HAX‐1: A family of apoptotic regulators in health and disease
Authors: Yap Solomon V. , Koontz Jason M. , Kontrogianni‐Konstantopoulos Aikaterini 
Published: February 2011

AbstractHAX‐1 comprises a family of ubiquitously expressed proteins that play important roles in the regulation of programmed cell death. Herein, we provide a comprehensive review of the expression profile of HAX‐1 and its functional implications during health and disease, highlighting its direct involvement in the development of congenital neutropenia and neural abnormalities, when absent, and its contribution to the progression of psoriasis and cancer, when overexpressed. Moreover, we provide new information on the differential expression of the HAX‐1 subfamily in three distinct types of epithelial cancers, including breast, skin, and colon. Our results demonstrate a significant up‐regulation of the anti‐apoptotic HAX‐1 variant 001 in skin and colon, but not in breast and cancer cells, indicating tissue‐specific differences in its expression pattern and properties during cancer formation and progression. Our findings further reveal a considerable down‐regulation, if not abrogation, of three distinct, yet to be characterized, HAX‐1 isoforms in breast cancer cells, suggesting that they may function in an opposite manner to the anti‐apoptotic variant 001. This study aims to summarize our current knowledge on the physiological implications of the expression profile of the HAX‐1 subfamily in health and disease, and provide new information on the differential expression and activities of HAX‐1 members in three distinct types of cancer. J. Cell. Physiol. 226: 2752–2761, 2011. © 2011 Wiley‐Liss, Inc.
Exposure to 50 Hz electromagnetic field raises the levels of the anti‐apoptotic protein BAG3 in melanoma cells
Authors: Basile Anna , Zeppa Rosario , Pasquino Nicola , Arra Claudio , Ammirante Massimo , Festa Michelina , Barbieri Antonio , Giudice Aldo , Pascale Maria , Turco Maria Caterina , Rosati Alessandra 
Published: February 2011

AbstractThe expression of the anti‐apoptotic protein BAG3 is induced in several cell types by exposure to high temperature, oxidants, and other stressful agents. We investigated whether exposure to 50 Hz electromagnetic fields raised BAG3 levels in the human melanoma cell line M14, in vitro and in orthotopic xenografts. Exposure of cultured cells or xenografts for 6 h or 4 weeks, respectively, produced a significant (P < 0.01) increase in BAG3 protein amounts. Interestingly, at the same times, we could not detect any significant variation in the levels of HSP70/72 protein or cell apoptosis. These results confirm the stressful effect of exposure to ELF in human cells, by identifying BAG3 protein as a marker of ELF‐induced stress. Furthermore, they suggest that BAG3 induction by ELF may contribute to melanoma cell survival and/or resistance to therapy. J. Cell. Physiol. 226: 2901–2907, 2011. © 2011 Wiley‐Liss, Inc.
Apo‐ and holo‐lactoferrin are both internalized by lactoferrin receptor via clathrin‐mediated endocytosis but differentially affect ERK‐signaling and cell proliferation in caco‐2 cells
Authors: Jiang Rulan , Lopez Veronica , Kelleher Shannon L. , Lönnerdal Bo 
Published: February 2011

AbstractLactoferrin (Lf) is a major iron‐binding and multi‐functional protein in exocrine fluids such as breast milk and mucosal secretions. The functions of Lf appear dependent upon the iron saturation of the Lf protein and are postulated to be mediated through Lf internalization by a Lf receptor (LfR). However, mechanisms by which LfR mediates Lf internalization in enterocytes are unknown. We now demonstrate that a LfR previously cloned from the small intestine mediates Lf endocytosis in a human enterocyte model (Caco‐2 cells). LfR was detected at the plasma membrane by cell surface biotinylation; both apo‐Lf and holo‐Lf uptake were significantly inhibited in cells transfected with LfR siRNA. Treatments of hypertonic sucrose and clathrin siRNA and co‐immunoprecipitation of LfR with clathrin adaptor AP2 indicate that LfR regulates Lf endocytosis via clathrin‐mediated endocytosis. Although both iron‐free Lf (apo‐Lf) and iron‐saturated Lf (holo‐Lf) enter Caco‐2 cells via a similar mechanism and no significant differences were observed in the binding and uptake of apo‐ and holo‐Lf in Caco‐2 cells, apo‐Lf but not holo‐Lf stimulates proliferation of Caco‐2 cells. Interestingly, apo‐Lf stimulated extracellular signal‐regulated mitogen‐activated protein kinase (ERK) cascade to a significantly greater extent than holo‐Lf and the apo‐Lf induced proliferation was significantly inhibited by an ERK cascade inhibitor (U0126) and clathrin siRNA. Taken together, our data suggest that LfR is a major pathway through which Lf is taken up by enterocytes, which occurs independently of iron saturation through clathrin‐mediated endocytosis. The differential effects of apo‐ and holo‐Lf are not due to differences in cellular internalization mechanisms. J. Cell. Physiol. 226: 3022–3031, 2011. © 2011 Wiley‐Liss, Inc.
Normal atmospheric oxygen tension and the use of antioxidants improve hepatocyte spheroid viability and function
Authors: Lillegard Joseph B. , Fisher James E. , Nedredal Geir , Luebke‐Wheeler Jennifer , Bao Ji , Wang William , Amoit Bruce , Nyberg Scott L. 
Published: February 2011

AbstractHepatocyte spheroids have been proposed for drug metabolism studies and in bioartificial liver devices. However, the optimal conditions required to meet the aerobic demands of mitochondria‐rich hepatocyte spheroids is not well studied. We hypothesized that an optimal concentration of oxygen could be identified and that the health of hepatocyte spheroids might be further improved by antioxidant therapy. Rat hepatocyte spheroids were maintained in suspension culture for 7 days under a mixture of 5% CO2 plus O2:N2 to achieve fractional oxygen contents of 6% (C1), 21% (C2), 58% (C3), and 95% (C4). Spheroid health was assessed under each condition by vital staining, TEM, oxygen consumption, and mitochondrial counts. Hepatocyte differentiation was assessed by expression of 10 liver‐related genes (HNF4a, HNF6, Cyp1A1, albumin, Nags, Cps1, Otc, Ass, Asl, Arg1). Functional markers (albumin and urea) were measured. The influence of oxygen tension and antioxidant treatment on the production of reactive oxygen species (ROS) was assessed by confocal microscopy. We observed that the hepatocyte spheroids were healthiest under normal atmospheric (C2) conditions with antioxidants ascorbic acid and L‐carnitine. Cell death and reduced functionality of hepatocyte spheroids correlated with the formation of ROS. Normal atmospheric conditions provided the optimal oxygen tension for suspension culture of hepatocyte spheroids. The formation and deleterious effects of ROS were further reduced by adding antioxidants to the culture medium. These findings have direct application to development of the spheroid reservoir bioartificial liver and the use of hepatocyte spheroids in drug metabolism studies. J. Cell. Physiol. 226: 2987–2996, 2011. © 2011 Wiley‐Liss, Inc.