bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homeostasis of Human NK Cells Is Not IL-15 Dependent
Authors: Lebrec Herve , Horner Michelle J. , Gorski Kevin S. , Tsuji Wayne , Xia Dong , Pan Wei-Jian , Means Gary , Pietz Greg , Li Nianyu , Retter Marc , Shaffer Kathy , Patel Neha , Narayanan Padma K. , Butz Eric A. 
Published: November 2013

Abstract
IL-15 is a proinflammatory cytokine that plays an important role in the development and activation of NK cells and is a potential target for inflammatory disease therapy. Studies conducted in IL-15- and IL-15R knockout mice identified IL-15 as an important cytokine for NK cell homeostasis. Consistent with this information derived from genetically modified mice, we demonstrated that neutralizing IL-15 with a mouse anti-mouse IL-15 mAb (M96) depletes C57BL/6 mouse NK cells. An mAb directed against macaque IL-15 (Hu714MuXHu) was manufactured and demonstrated to block IL-15–induced activation of nonhuman primate (NHP) NK cells in vitro. Neutralization of macaque IL-15 by parenteral administration of Hu714MuXHu reduces (&gt;95%) circulating NK cell counts in NHPs. A blocking mAb directed against human IL-15 (huIL-15; AMG 714) was manufactured. Unexpectedly, when human subjects were treated with the blocking anti–IL-15 Ab AMG 714 in clinical trials, no reductions in circulating NK cell counts were observed despite achieving significantly higher exposures than the levels of Hu714MuXHu needed to cause NK cell count reductions in NHPs in vivo. Both AMG 714 and Hu714MuXHu are able to block huIL-15 activity in a human T cell blast proliferation and IFN-γ production assay. Both Abs block huIL-15–mediated Stat5 activation and CD69 expression in human NK cells. Collectively, these results demonstrate that NK cell homeostasis is obligatorily dependent upon IL-15 in both mice and NHPs, but that IL-15 is dispensable for maintenance of circulating human NK cells.
The Road to Memory: An Early Rest for the Long Journey
Authors: Ho Liam Pock , Yit Pui San , Ng Lee Hui , Linn Yeh Ching , Zhao Yi , Sun Li , Ling Khoon Lin , Chai Koh Mickey Boon , Monica Shih Meng-Chun , Li Shang , Wang Xue Ying , Tien Sim Leng , Goh Yeow Tee 
Published: November 2013

Abstract
Central memory T lymphocytes were reported to develop after acute but not chronic infection, which prompted this feasibility study on generating long-term CD8 T cells ex vivo, by applying a culture condition that simulates an acute infection. During 35 d of culture, naive T cells (CD45RA+, CD127+, CCR7+, CD62L+, CXCR3+) first developed into effector T cells (CD45RA+/−, CD127+/−, CCR7+/−, CD62L+, CXCR3+), followed by three intermediate stages: intermediate T cells 1 (CD45RO+, CD127+/−, CCR7+, CD62L+, CXCR3+), intermediate T cells 2 (CD45RO+, CD127−, CCR7−, CD62L+, CXCR3+), and intermediate T cells 3 (CD45RO+/−, CD127+, CCR7+, CD62L−, CXCR3+) before reverting to stable CD45RA+ central memory T cells (CD45RA+, CD127+, CCR7+, CD62L+, CXCR3+). If both anti-CD3 and the inflammatory milieu persisted beyond day 10, intermediate T cells 2 gradually developed into effector memory T cells (CD45RO+, CD127−, CCR7−, CD62L−, CXCR3+). Furthermore, intermediate T cells 2 or effector memory T cells, when cultured in persistent inflammatory cytokines devoid of anti-CD3, were converted to central memory T cells (CD45RO+, CCR7+, CD62L+). Overall, these results support ex vivo memory-like T lymphocyte production and favor a developmental pathway including both divergent and linear relationships.
Mannose Receptor 1 Mediates Cellular Uptake and Endosomal Delivery of CpG-Motif Containing Oligodeoxynucleotides
Authors: Moseman Annie Park , Moseman E. Ashley , Schworer Stephen , Smirnova Irina , Volkova Tatyana , von Andrian Ulrich , Poltorak Alexander 
Published: November 2013

Abstract
Recognition of microbial components is critical for activation of TLRs, subsequent innate immune signaling, and directing adaptive immune responses. The DNA sensor TLR9 traffics from the endoplasmic reticulum to endolysosomal compartments where it is cleaved by resident proteases to generate a competent receptor. Activation of TLR9 by CpG-motif containing oligodeoxynucleotides (CpG ODNs) is preceded by agonist endocytosis and delivery into the endolysosomes. The events that dictate this process remain largely unknown; furthermore, it is unclear whether the receptors involved in mediating uptake of exogenous DNA are conserved for both naturally derived pathogenic DNA and synthetic ODNs. In this study, we report that peritoneal macrophages from a wild-derived inbred mouse strain, MOLF/Ei, are hyporesponsive to CpG ODN but are fully responsive to bacterial DNA, thus implying that microbial recognition is not fully recapitulated by a synthetic analog. To identify the gene responsible for the CpG ODN defect, we have performed genome-wide linkage analysis. Using N2 backcross mice, we mapped the trait with high resolution to a single locus containing Mrc1 as the gene conferring the trait. We show that mannose receptor 1 (MRC1; CD206) is involved in CpG ODN uptake and trafficking in wild-derived MOLF/Ei peritoneal macrophages. Furthermore, we show that other strains of wild-derived mice also require MRC1 for CpG-induced cytokine responses. These findings reveal novel functions for MRC1 and demonstrate that wild-derived mice are important and indispensable model for understanding naturally occurring regulators of inflammatory responses in innate immune pathways.
Exosomes Secreted by Human Placenta Carry Functional Fas Ligand and TRAIL Molecules and Convey Apoptosis in Activated Immune Cells, Suggesting Exosome-Mediated Immune Privilege of the Fetus
Authors: Stenqvist Ann-Christin , Nagaeva Olga , Baranov Vladimir , Mincheva-Nilsson Lucia 
Published: November 2013

AbstractApoptosis is crucially important in mediating immune privilege of the fetus during pregnancy. We investigated the expression and in vitro apoptotic activity of two physiologically relevant death messengers, the TNF family members Fas ligand (FasL) and TRAIL in human early and term placentas. Both molecules were intracellularly expressed, confined to the late endosomal compartment of the syncytiotrophoblast, and tightly associated to the generation and secretion of placental exosomes. Using immunoelectron microscopy, we show that FasL and TRAIL are expressed on the limiting membrane of multivesicular bodies where, by membrane invagination, intraluminal microvesicles carrying membranal bioactive FasL and TRAIL are formed and released in the extracellular space as exosomes. Analyzing exosomes secreted from placental explant cultures, to our knowledge, we demonstrate for the first time that FasL and TRAIL are clustered on the exosomal membrane as oligomerized aggregates ready to form death-inducing signaling complex. Consistently, placental FasL- and TRAIL-carrying exosomes triggered apoptosis in Jurkat T cells and activated PBMC in a dose-dependent manner. Limiting the expression of functional FasL and TRAIL to exosomes comprise a dual benefit: 1) storage of exosomal FasL and TRAIL in multivesicular bodies is protected from proteolytic cleavage and 2) upon secretion, delivery of preformed membranal death molecules by exosomes rapidly triggers apoptosis. Our results suggest that bioactive FasL- and TRAIL-carrying exosomes, able to convey apoptosis, are secreted by the placenta and tie up the immunomodulatory and protective role of human placenta to its exosome-secreting ability.
Care and Handling of Laboratory Mice
Authors: Donovan John , Brown Patricia 
Published: November 2013

AbstractThe importance of laboratory mice in experimental microbiology and biomedical research is indisputable, and their care and handling is a contributing factor to the quality of the science resulting from their use. This unit provides guidelines for practical housing, handling, and the methodology for sample collection to ensure animal health and minimize variable experimental parameters. Curr. Protoc. Microbiol. 31:A.3N.1‐A.3N.18. © 2013 by John Wiley & Sons, Inc.
Cognitive, sensory, and psychosocial characteristics in patients with Bardet–Biedl syndrome
Authors: Brinckman Danielle D. , Keppler‐Noreuil Kim M. , Blumhorst Catherine , Biesecker Leslie G. , Sapp Julie C. , Johnston Jennifer J. , Wiggs Edythe A. 
Published: November 2013

AbstractForty‐two patients with a clinical diagnosis of Bardet–Biedl syndrome ages 2–61 years were given a neuropsychological test battery to evaluate cognitive, sensory, and behavioral functioning. These tests included the Wechsler scales of intelligence, Rey Auditory Verbal Learning Test, Boston Naming Test, D‐KEFS Verbal Fluency Test, D‐KEFS Color‐Word Interference Test, D‐KEFS Sorting Test, Wide Range Achievement Test: Math and Reading Subtests, Purdue Pegboard, The University of Pennsylvania Smell Identification Test, Social Communication Questionnaire, Social Responsiveness Scale, and Behavior Assessment System for Children, Second Edition, Parent Rating Scale. On the age appropriate Wechsler scale, the mean Verbal Comprehension was 81 (n = 36), Working Memory was 81 (n = 36), Perceptual Reasoning was 78 (n = 24) and Full Scale IQ was 75 (n = 26). Memory for a word list (Rey Auditory Verbal Learning Test) was in the average range with a mean of 89 (n = 19). Fine motor speed was slow on the Purdue with mean scores 3–4 standard deviations below norms. All subjects were microsmic on the University of Pennsylvania Smell Identification Test. Of these 42 patients, only 6 were able to complete all auditory and visual tests; 52% were unable to complete the visual tests due to impaired vision. A wide range of behavioral issues were endorsed on questionnaires given to parents. Most had social skill deficits but no pattern of either externalizing or internalizing problems. We identify a characteristic neuro‐behavioral profile in our cohort comprised of reduced IQ, impaired fine‐motor function, and decreased olfaction. © 2013 Wiley Periodicals, Inc.
Hydrogen‐Bonding Effect on Spin‐Center Transfer of Tetrathiafulvalene‐Linked 6‐Oxophenalenoxyl Evaluated Using Temperature‐Dependent Cyclic Voltammetry and Theoretical Calculations
Authors: Nishida Shinsuke , Fukui Kozo , Morita Yasushi 
Published: November 2013

AbstractThe stable tetrathiafulvalene (TTF)‐linked 6‐oxophenalenoxyl neutral radical exhibits a spin‐center transfer with a continuous color change in solution caused by an intramolecular electron transfer, which is dependent on solvent and temperature. Cyclic voltammetry measurements showed that addition of 2,2,2‐trifluoroethanol (TFE) to a benzonitrile solution of the neutral radical induces a redox potential shift that is favorable for the spin‐center transfer. Temperature‐dependent cyclic voltammetry of the neutral radical using a novel low‐temperature electrochemical cell demonstrated that the redox potentials change with decreasing temperature in a 199:1 CH2Cl2/TFE mixed solvent. Furthermore, theoretical calculation revealed that the energy levels of the frontier molecular orbitals involved in the spin‐center transfer are lowered by the hydrogen‐bonding interaction of TFE with the neutral radical. These results indicate that the hydrogen‐bonding effect is a key factor for the occurrence of the spin‐center transfer of TTF‐linked 6‐oxophenalenoxyl.
Numerical Investigation of the Gas‐Solid Flow Characteristics in a Three‐Dimensional Spouted Bed with a Draft Tube
Authors: Yang S.‐L. , Luo K. , Fang M.‐M. , Zhang K. , Fan J.‐R. 
Published: November 2013

AbstractGas‐solid motions in a three‐dimensional conical spouted bed with a draft tube are investigated based on a simulation carried out by the coupling approach of computational fluid dynamics combined with the discrete‐element method. The distribution properties of the velocity, the concentration, and the flux of the solid phase are discussed. The vertical solid velocity in the central region initially increases, diminishes gradually, and finally decreases sharply in the region above the draft tube. Vigorous lateral solid motion occurs in the periphery of the fountain and the spout‐annulus interface. In addition, the vertical solid flux shows a large value in the spout. A larger vertical velocity but a more dilute solid concentration can be detected along the axial direction when enlarging the gas flow rate.
Theoretical Aspects of Hydrolysis of Peptide Bonds by Zinc Metalloenzymes
Authors: Navrátil Václav , Klusák Vojtěch , Rulíšek Lubomír 
Published: November 2013

AbstractActivation and reaction energies for four model systems capturing the essential physicochemical features of the hydrolysis of the peptide bond have been calculated at various level of theory, including the presumably accurate CCSD(T) calculations. The models studied covered a part of the spectrum encountered in biological systems: the hydrolysis in the absence of metal ions (represented by formamide and Ala–Ala) and the hydrolysis in the presence of one and two zinc(II) ions, mimicking the active sites of mono‐ and dizinc metallopeptidases, respectively (by using thermolysin and glutamate carboxypeptidase II as the model catalytic systems and formamide as the model substrate). The results obtained using CCSD(T)/def2‐TZVP and CCSD(T)/aug‐cc‐pVTZ calculations were used as the benchmark values to which the set of cheaper methods, such as (RI‐)DFT, (RI‐)MP2, and SCS‐MP2, were referenced. It was shown that deviations of 3–5 kcal mol−1 (translating to 2–3 orders in reaction constants) with respect to the reference CCSD(T) barriers are frequently encountered for many correlated methods and most of studied DFT functionals. It has been concluded that from the set of wave‐function methods, both MP2 and SCS‐MP2 methods can be recommended for smaller models (measured by the mean absolute deviation of the activation barriers over the four systems studied), whereas among the popular DFT functionals, B3LYP and especially M06‐2X are likely to be reasonable choices for calculating the activation barriers of zinc metallopeptidases. Finally, with the model of glutamate carboxypeptidase II, issues related to the convergence of the calculated barriers with the size of the model system used as the representative of the enzyme active site were addressed. The intricacies related to system truncation are demonstrated, and suggest that the correlated wave‐function methods may suffer from problems, such as intramolecular BSSE, which make their usage for the larger system questionable. Altogether, the presented data should contribute to efforts to understand enzymatic catalysis more deeply and to gain control of the accuracy and deficiencies of the available theoretical methods and computational approaches.
Nomogram for predicting the benefit of neoadjuvant chemoradiotherapy for patients with esophageal cancer: A SEER‐Medicare analysis
Authors: Eil Robert , Diggs Brian S. , Wang Samuel J. , Dolan James P. , Hunter John G. , Thomas Charles R. 
Published: November 2013

BACKGROUNDThe survival impact of neoadjuvant chemoradiotherapy (CRT) on esophageal cancer remains difficult to establish for specific patients. The aim of the current study was to create a Web‐based prediction tool providing individualized survival projections based on tumor and treatment data.METHODSPatients diagnosed with esophageal cancer between 1997 and 2005 were selected from the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database. The covariates analyzed were sex, T and N classification, histology, total number of lymph nodes examined, and treatment with esophagectomy or CRT followed by esophagectomy. After propensity score weighting, a log‐logistic regression model for overall survival was selected based on the Akaike information criterion.RESULTSA total of 824 patients with esophageal cancer who were treated with esophagectomy or trimodal therapy met the selection criteria. On multivariate analysis, age, sex, T and N classification, number of lymph nodes examined, treatment, and histology were found to be significantly associated with overall survival and were included in the regression analysis. Preoperative staging data and final surgical margin status were not available within the SEER‐Medicare data set and therefore were not included. The model predicted that patients with T4 or lymph node disease benefitted from CRT. The internally validated concordance index was 0.72.CONCLUSIONSThe SEER‐Medicare database of patients with esophageal cancer can be used to produce a survival prediction tool that: 1) serves as a counseling and decision aid to patients and 2) assists in risk modeling. Patients with T4 or lymph node disease appeared to benefit from CRT. This nomogram may underestimate the benefit of CRT due to its variable downstaging effect on pathologic stage. It is available at skynet.ohsu.edu/nomograms. Cancer 2014;120:492–498. © 2013 American Cancer Society.
Integrated Catalytic Process to Directly Convert Furfural to Levulinate Ester with High Selectivity
Authors: Chen Bingfeng , Li Fengbo , Huang Zhijun , Lu Tao , Yuan Yin , Yuan Guoqing 
Published: November 2013

AbstractLevulinic acid is an important platform molecule from biomass‐based renewable resources. A sustainable manufacturing process for this chemical and its derivatives is the enabling factor to harness the renewable resource. An integrated catalytic process to directly convert furfural to levulinate ester was developed based on a bifunctional catalyst of Pt nanoparticles supported on a ZrNb binary phosphate solid acid. The hydrogenation of furfural and the following alcoholysis of furfuryl alcohol were performed over this catalyst in a one‐pot conversion model. Mesoporous ZrNb binary phosphate was synthesized by a sol–gel method and had a high surface area of 170.1 m2 g−1 and a large average pore size of around 8.0 nm. Pt nanoparticles remained in a monodisperse state on the support, and the reaction over Pt/ZrNbPO4 (Pt loading: 2.0 wt %; Zr/Nb, 1:1) gave a very high selectivity to levulinate derivatives (91 % in total). The sustainability of this conversion was greatly improved by the process intensification based on the new catalyst, mild reaction conditions, cost abatement in separation and purification, and utilization of green reagents and solvents.
Polyvinylidene Fluoride/Siloxane Nanofibrous Membranes for Long‐Term Continuous CO2‐Capture with Large Absorption‐Flux Enhancement
Authors: Lin Yi‐Feng , Wang Chi‐Sen , Ko Chia‐Chieh , Chen Chien‐Hua , Chang Kai‐Shiun , Tung Kuo‐Lun , Lee Kueir‐Rarn 
Published: November 2013

AbstractIn a CO2 membrane contactor system, CO2 passes through a hydrophobic porous membrane in the gas phase to contact the amine absorbent in the liquid phase. Consequently, additional CO2 gas is absorbed by amine absorbents. This study examines highly porous polyvinylidene fluoride (PVDF)/siloxane nanofibrous layers that are modified with hydrophobic fluoroalkylsilane (FAS) functional groups and successfully coated onto a macroporous Al2O3 membrane. The performance of these materials in a membrane contactor system for CO2 absorption is also investigated. Compared with pristine PVDF nanofibrous membranes, the PVDF/siloxane nanofibrous membranes exhibit greater solvent resistance and mechanical strength, making them more suitable for use in CO2 capture by the membrane contactor. The PVDF/siloxane nanofibrous layer in highly porous FAS‐modified membranes can prevent the wetting of the membrane by the amine absorbent; this extends the periods of continuous CO2 absorption and results in a high CO2 absorption flux with a minimum of 500 % enhancement over that of the uncoated membranes. This study suggests the potential use of an FAS‐modified PVDF/siloxane nanofibrous membrane in a membrane contactor system for CO2 absorption. The resulting hydrophobic membrane contactor also demonstrates the potential for large‐scale CO2 absorption during post‐combustion processes in power plants.
Analysis of αSMA-Labeled Progenitor Cell Commitment Identifies Notch Signaling as an Important Pathway in Fracture Healing
Authors: Matthews Brya G , Grcevic Danka , Wang Liping , Hagiwara Yusuke , Roguljic Hrvoje , Joshi Pujan , Shin Dong-Guk , Adams Douglas J , Kalajzic Ivo 
Published: November 2013

ABSTRACT

Fracture healing is a regenerative process that involves coordinated responses of many cell types, but characterization of the roles of specific cell populations in this process has been limited. We have identified alpha smooth muscle actin (αSMA) as a marker of a population of mesenchymal progenitor cells in the periosteum that contributes to osteochondral elements during fracture healing. Using a lineage tracing approach, we labeled αSMA-expressing cells, and characterized changes in the periosteal population during the early stages of fracture healing by histology, flow cytometry, and gene expression profiling. In response to fracture, the αSMA-labeled population expanded and began to differentiate toward the osteogenic and chondrogenic lineages. The frequency of mesenchymal progenitor cell markers such as Sca1 and PDGFRα increased after fracture. By 6 days after fracture, genes involved in matrix production and remodeling were elevated. In contrast, genes associated with muscle contraction and Notch signaling were downregulated after fracture. We confirmed that activating Notch signaling in αSMA-labeled cells inhibited differentiation into osteogenic and adipogenic lineages in vitro and ectopic bone formation in vivo. By characterizing changes in a selected αSMA-labeled progenitor cell population during fracture callus formation, we have shown that modulation of Notch signaling may determine osteogenic potential of αSMA-expressing progenitor cells during bone healing. © 2014 American Society for Bone and Mineral Research.
Reproducibility of MRI renal artery blood flow and BOLD measurements in patients with chronic kidney disease and healthy controls
Authors: Khatir Dinah S. , Pedersen Michael , Jespersen Bente , Buus Niels H. 
Published: November 2013

PurposeDetermine the reproducibility of renal artery blood flow (RABF) and blood‐oxygenation level dependent (R2*) in patients with chronic kidney disease (CKD) and healthy controls.Materials and MethodsRABF and R2* were measured in 11 CKD patients and 9 controls twice with 1‐ to 2‐week interval. R2* in the cortex and medulla were determined after breathing atmospheric air and 100% oxygen. Reproducibility was evaluated by coefficients of variation (CV), limits of agreements and intra‐class coefficient calculated by variance components by maximum likelihood modeling.ResultsSingle‐kidney RABF (mL/min) for patients was: 170 ± 130 and 186 ± 137, and for controls: 365 ± 119 and 361 ± 107 (P < 0.05 versus patients), for first and second scans, respectively. RABF measurements were reproducible with a CV of 12.9% and 8.3% for patients and controls, respectively. Renal cortical R2* was: 13.6 ± 0.9 and 13.5 ± 1.2 in patients (CV = 8.0%), and 13.8 ± 1.6 and 14.0 ± 1.5 in controls (CV = 5.6%), while medullary R2*(s−1) was: 26.9 ± 2.0 and 27.0 ± 4.0 (CV = 8.0%) in patients, and 26.0 ± 2.4 and 26.1 ± 2.1 (CV = 3.6%) in controls, for first and second scans, respectively. In both groups R2* in medulla decreased after breathing 100% oxygen.ConclusionThe reproducibility was high for both RABF and R2* in patients and controls, particularly in the cortex. Inhalation of 100% oxygen reduced medullary R2*. J. Magn. Reson. Imaging 2014;40:1091–1098. © 2013 Wiley Periodicals, Inc.