bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNAM-1 Mediates Epithelial Cell-Specific Cytotoxicity of Aberrant Intraepithelial Lymphocyte Lines from Refractory Celiac Disease Type II Patients
Authors: Tjon Jennifer M.-L. , Kooy-Winkelaar Yvonne M. C. , Tack Greetje J. , Mommaas A. Mieke , Schreurs Marco W. J. , Schilham Marco W. , Mulder Chris J. , van Bergen Jeroen , Koning Frits 
Published: April 2011

Abstract
In refractory celiac disease (RCD), intestinal epithelial damage persists despite a gluten-free diet. Characteristic for RCD type II (RCD II) is the presence of aberrant surface TCR-CD3− intraepithelial lymphocytes (IELs) that can progressively replace normal IELs and eventually give rise to overt lymphoma. Therefore, RCD II is considered a malignant condition that forms an intermediate stage between celiac disease (CD) and overt lymphoma. We demonstrate in this study that surface TCR-CD3− IEL lines isolated from three RCD II patients preferentially lyse epithelial cell lines. FACS analysis revealed that DNAM-1 was strongly expressed on the three RCD cell lines, whereas other activating NK cell receptors were not expressed on all three RCD cell lines. Consistent with this finding, cytotoxicity of the RCD cell lines was mediated mainly by DNAM-1 with only a minor role for other activating NK cell receptors. Furthermore, enterocytes isolated from duodenal biopsies expressed DNAM-1 ligands and were lysed by the RCD cell lines ex vivo. Although DNAM-1 on CD8+ T cells and NK cells is known to mediate lysis of tumor cells, this study provides, to our knowledge, the first evidence that (pre)malignant cells themselves can acquire the ability to lyse epithelial cells via DNAM-1. This study confirms previous work on epithelial lysis by RCD cell lines and identifies a novel mechanism that potentially contributes to the gluten-independent tissue damage in RCD II and RCD-associated lymphoma.
Programmed Death 1 Regulates Development of Central Memory CD8 T Cells after Acute Viral Infection
Authors: Allie S. Rameeza , Zhang Weijun , Fuse Shinchiro , Usherwood Edward J. 
Published: April 2011

Abstract
The T cell response possesses a number of inhibitory receptors to regulate the extent of the antiviral response and prevent immune pathology. These receptors are generally transiently upregulated during an effector response and then downregulated during memory. Some inhibitory receptors, such as programmed death 1 (PD-1) and LAG-3, were shown to be aberrantly upregulated during memory to chronic lymphocytic choriomeningitis virus infection, limiting functional capabilities. However, little is known about the impact of inhibitory receptors on memory development during a normal CD8 T cell response to acute virus infection. Our previous data showed that PD-1 is aberrantly upregulated during a secondary response by memory CD8 T cells that were generated without CD4 T cell help. Therefore, we examined the role of PD-1 in memory differentiation during acute vaccinia virus infection in intact mice. In the absence of PD-1, the primary and memory CD8 T cell responses were enhanced. Moreover, there were distinct phenotypic and functional changes in the memory PD-1−/− CD8 T cells. Higher levels of CD62L, CD27, and CCR7 were detected; cells produced more IL-2 and made an enhanced secondary response. These changes indicate a skewing of the memory population toward the central memory phenotype in the absence of PD-1 signaling.
Somatically Diversified and Proliferating Transitional B Cells: Implications for Peripheral B Cell Homeostasis
Authors: Yeramilli Venkata A. , Knight Katherine L. 
Published: April 2011

Abstract
The peripheral B cell compartment in mice and humans is maintained by continuous production of transitional B cells in the bone marrow. In other species, however, including rabbits, B lymphopoiesis in the bone marrow abates early in life, and it is unclear how the peripheral B cell compartment is maintained. We identified transitional B cells in rabbits and classified them into T1 (CD24highCD21low) and T2 (CD24highCD21+) B cell subsets. By neutralizing B cell-activating factor in vivo, we found an arrest in peripheral B cell development at the T1 B cell stage. Surprisingly, T1 B cells were present in GALT, blood, and spleen of adult rabbits, long after B lymphopoiesis was arrested. T1 B cells were distinct from their counterparts in other species because they are proliferating and the Ig genes are somatically diversified. We designate these newly described cells as T1d B cells and propose a model in which they develop in GALT, self renew, continuously differentiate into mature B cells, and thereby maintain peripheral B cell homeostasis in adults in the absence of B lymphopoiesis.
A New Subset of CD103+CD8α+ Dendritic Cells in the Small Intestine Expresses TLR3, TLR7, and TLR9 and Induces Th1 Response and CTL Activity
Authors: Fujimoto Kosuke , Karuppuchamy Thangaraj , Takemura Naoki , Shimohigoshi Masaki , Machida Tomohisa , Haseda Yasunari , Aoshi Taiki , Ishii Ken J. , Akira Shizuo , Uematsu Satoshi 
Published: April 2011

Abstract
CD103+ dendritic cells (DCs) are the major conventional DC population in the intestinal lamina propria (LP). Our previous report showed that a small number of cells in the LP could be classified into four subsets based on the difference in CD11c/CD11b expression patterns: CD11chiCD11blo DCs, CD11chiCD11bhi DCs, CD11cintCD11bint macrophages, and CD11cintCD11bhi eosinophils. The CD11chiCD11bhi DCs, which are CD103+, specifically express TLR5 and induce the differentiation of naive B cells into IgA+ plasma cells. These DCs also mediate the differentiation of Ag-specific Th17 and Th1 cells in response to flagellin. We found that small intestine CD103+ DCs of the LP (LPDCs) could be divided into a small subset of CD8α+ cells and a larger subset of CD8α− cells. Flow cytometry analysis revealed that CD103+CD8α+ and CD103+CD8α− LPDCs were equivalent to CD11chiCD11blo and CD11chiCD11bhi subsets, respectively. We analyzed a novel subset of CD8α+ LPDCs to elucidate their immunological function. CD103+CD8α+ LPDCs expressed TLR3, TLR7, and TLR9 and produced IL-6 and IL-12p40, but not TNF-α, IL-10, or IL-23, following TLR ligand stimulation. CD103+CD8α+ LPDCs did not express the gene encoding retinoic acid-converting enzyme Raldh2 and were not involved in T cell-independent IgA synthesis or Foxp3+ regulatory T cell induction. Furthermore, CD103+CD8α+ LPDCs induced Ag-specific IgG in serum, a Th1 response, and CTL activity in vivo. Accordingly, CD103+CD8α+ LPDCs exhibit a different function from CD103+CD8α− LPDCs in active immunity. This is the first analysis, to our knowledge, of CD8α+ DCs in the LP of the small intestine.
Stat4 Is Critical for the Balance between Th17 Cells and Regulatory T Cells in Colitis
Authors: Xu Jiangnan , Yang Yu , Qiu Guixing , Lal Girdhari , Yin Na , Wu Zhihong , Bromberg Jonathan S. , Ding Yaozhong 
Published: April 2011

Abstract
Th17 play a central role in autoimmune inflammatory responses. Th1 are also necessary for autoimmune disease development. The interplay of Th1 signals and how they coordinate with Th17 during inflammatory disease pathogenesis are incompletely understood. In this study, by adding Stat4 deficiency to Stat6/T-bet double knockout, we further dissected the role of Stat4 in Th1 development and colitis induction. We showed that in the absence of the strong Th2 mediator Stat6, neither Stat4 nor T-bet is required for IFN-γ production and Th1 development. However, addition of Stat4 deficiency abolished colitis induced by Stat6/T-bet double-knockout cells, despite Th1 and Th17 responses. The failure of colitis induction by Stat4/Stat6/T-bet triple-knockout cells is largely due to elevated Foxp3+ regulatory T cell (Treg) development. These results highlight the critical role of Stat4 Th1 signals in autoimmune responses in suppressing Foxp3+ Treg responses and altering the balance between Th17 and Tregs to favor autoimmune disease.
IL-2 Controls the Stability of Foxp3 Expression in TGF-β–Induced Foxp3+ T Cells In Vivo
Authors: Chen Qian , Kim Yong Chan , Laurence Arian , Punkosdy George A. , Shevach Ethan M. 
Published: April 2011

Abstract
Stimulation of naive mouse CD4+Foxp3− T cells in the presence of TGF-β results in the induction of Foxp3 expression and T suppressor function. However, Foxp3 expression in these induced regulatory T cells (iTreg) is unstable, raising the possibility that iTreg would not be useful for treatment of autoimmune diseases. To analyze the factors that control the stability of Foxp3 expression in iTreg, we generated OVA-specific iTreg from OT-II Foxp3-GFP knockin mice. Following transfer to normal C57BL/6 mice, OT-II GFP+ cells maintained high levels of Foxp3 expression for 8 d. However, they rapidly lost Foxp3 expression upon stimulation with OVA in IFA in vivo. This unstable phenotype was associated with a strong methylation of the Treg-specific demethylated region within the Foxp3 locus. Administration of IL-2/anti–IL-2 complexes expanded the numbers of transferred Foxp3+ iTreg in the absence of Ag challenge. Notably, when the iTreg were stimulated with Ag, treatment with IL-2/anti–IL-2 complexes stabilized Foxp3 expression and resulted in enhanced demethylation of the Treg-specific demethylated region. Conversely, neutralization of IL-2 or disruption of its signaling by deletion of Stat5 diminished the level of Foxp3 expression resulting in decreased suppressor function of the iTreg in vivo. Our data suggest that stimulation with TGF-β in vitro is not sufficient for imprinting T cells with stable expression of Foxp3. Administration of IL-2 in vivo results in stabilization of Foxp3 expression and may prove to be a valuable adjunct for the use of iTreg for the treatment of autoimmune diseases.
Analysis and Modeling of the Variable Region of Camelid Single-Domain Antibodies
Authors: Sircar Aroop , Sanni Kayode A. , Shi Jiye , Gray Jeffrey J. 
Published: April 2011

Abstract
Camelids have a special type of Ab, known as heavy chain Abs, which are devoid of classical Ab light chains. Relative to classical Abs, camelid heavy chain Abs (cAbs) have comparable immunogenicity, Ag recognition diversity and binding affinities, higher stability and solubility, and better manufacturability, making them promising candidates for alternate therapeutic scaffolds. Rational engineering of cAbs to improve therapeutic function requires knowledge of the differences of sequence and structural features between cAbs and classical Abs. In this study, amino acid sequences of 27 cAb variable regions (VHH) were aligned with the respective regions of 54 classical Abs to detect amino acid differences, enabling automatic identification of cAb VHH CDRs. CDR analysis revealed that the H1 often (and sometimes the H2) adopts diverse conformations not classifiable by established canonical rules. Also, although the cAb H3 is much longer than classical H3 loops, it often contains common structural motifs and sometimes a disulfide bond to the H1. Leveraging these observations, we created a Monte Carlo-based cAb VHH structural modeling tool, where the CDR H1 and H2 loops exhibited a median root-mean-square deviation to natives of 3.1 and 1.5 Å, respectively. The protocol generated 8–12, 14–16, and 16–24 residue H3 loops with a median root-mean-square deviation to natives of 5.7, 4.5, and 6.8 Å, respectively. The large deviation of the predicted loops underscores the challenge in modeling such long loops. cAb VHH homology models can provide structural insights into interaction mechanisms to enable development of novel Abs for therapeutic and biotechnological use.
Quantitative Trait Locus Analysis, Pathway Analysis, and Consomic Mapping Show Genetic Variants of Tnni3k, Fpgt, or H28 Control Susceptibility to Viral Myocarditis
Authors: Wiltshire Sean A. , Leiva-Torres Gabriel André , Vidal Silvia M. 
Published: April 2011

Abstract
Coxsackievirus B3 (CVB3) infection is the most common cause of viral myocarditis. The pathogenesis of viral myocarditis is strongly controlled by host genetic factors. Although certain indispensable components of immunity have been identified, the genes and pathways underlying natural variation between individuals remain unclear. Previously, we isolated the viral myocarditis susceptibility 1 (Vms1) locus on chromosome 3, which influences pathogenesis. We hypothesized that confirmation and further study of Vms1 controlling CVB3-mediated pathology, combined with pathway analysis and consomic mapping approaches, would elucidate both pathological and protective mechanisms accounting for natural variation in response to CVB3 infection. Vms1 was originally mapped to chromosome 3 using a segregating cross between susceptible A/J and resistant B10.A mice. To validate Vms1, C57BL/6J-Chr 3A/NaJ (a chromosome substitution strain that carries a diploid A/J chromosome 3) were used to replicate susceptibility compared with resistant C57BL/6J (B6). A second segregating F2 cross was generated between these, confirming both the localization and effects of Vms1. Microarray analysis of the four strains (A/J, B10.A, C57BL/6J, and C57BL/6J-Chr 3A/NaJ) illuminated a core program of response to CVB3 in all strains that is comprised mainly of IFN-stimulated genes. Microarray analysis also revealed strain-specific differential expression programs and genes that may be prognostic or diagnostic of susceptibility to CVB3 infection. A combination of analyses revealed very strong evidence for the existence and location of Vms1. Differentially expressed pathways were identified by microarray, and candidate gene analysis revealed Fpgt, H28, and Tnni3k as likely candidates for Vms1.
Manual lymph drainage improving upper extremity edema and hand function in patients with systemic sclerosis in edematous phase
Authors: Bongi Susanna Maddali , Del Rosso Angela , Passalacqua Mauro , Miccio Sara , Cerinic Marco Matucci 
Published: April 2011

AbstractObjectiveIn systemic sclerosis (SSc; scleroderma) patients in edematous phase, hand edema is often present. Manual lymph drainage (MLD) stimulates the lymphatic system and reduces edema. Our aim was to evaluate the efficacy of MLD in reducing edema and in improving functionality of the hands and perceived quality of life (QOL) in SSc patients in edematous phase.MethodsOf 35 SSc patients with edematous hands, 20 were treated with MLD according to the Vodder technique once a week for 5 weeks (intervention group), and 15 served as the observation group. Patients were evaluated at enrollment, at the end of treatment (T1), and after 9 weeks of followup (T2) by volumetric test (assessing hand volume), the Hand Mobility in Scleroderma (HAMIS) test, and 4 visual analog scales (VAS; scored 0–10) evaluating the perception of hand edema and pain and their interference on daily activities. QOL and disability were assessed by the physical synthetic index (PSI) and mental synthetic index (MSI) of the Short Form 36 (SF‐36) and by the Health Assessment Questionnaire (HAQ).ResultsIn the intervention group, hand volume, the HAMIS test, and the 4 VAS were improved significantly at the end of treatment (P < 0.001). The results were maintained at T2 (P < 0.001). The HAQ and the PSI and MSI of the SF‐36 also improved significantly at T1 (P < 0.001), but only PSI improvement was maintained at T2 (P < 0.001). In the observation group, no improvement at T1 and at T2 was observed.ConclusionIn SSc, MLD significantly reduces hand edema and improves hand function and perceived QOL.
Neutron and X‐Ray Techniques for Biological and Biomaterials Studies
Authors: Willumeit Regine 
Published: April 2011

AbstractThe study of biological and biomaterials with X‐rays and neutrons provides an important contribution to the understanding of the structure–function relationship in natural and artificial materials. Aside from the fundamental knowledge gained by these insights—which is of value already in itself—it helps to create new materials which are either bio‐inspired or modified such that they can interact in an optimized way with the biological environment. Usually the methods applied are noninvasive and deliver information about the structure of the specimen or material parameters, in some cases even in vivo. In this paper, an overview of most recent developments in the field of biological and biomaterials studies with neutron and X‐rays is given.
Comparison of the Consequences of Shot Peening Treatment Methods on the Surface Layer Characteristics of Ti6246
Authors: Feldmann Goetz G. , Hennig Wolfgang , Haubold Thomas , Zinn Wolfgang , Scholtes Berthold 
Published: April 2011

AbstractShot peening, as a technique to enhance the surface characteristics of rotating parts in aircraft engines is well known as a way to prevent the initiation and propagation of cracks. However, shot peening generally increases the surface roughness and therefore, reduces aerodynamic efficiency on aerofoil. This paper aims to compare different shot peening procedures as regards roughness, hardness, residual stress magnitude and depth in Ti6246, in order to identify a method, which leads to the required mechanical properties, but keeps the increase of surface roughness to a minimum. Therefore, Ti6246 specimens, processed similarly to integral bladed compressor disks, are treated with defined target intensity and coverage. The changes in surface roughness, residual stress, and hardness are measured and discussed.
Highly Sensitive Glucose Biosensors Based on Organic Electrochemical Transistors Using Platinum Gate Electrodes Modified with Enzyme and Nanomaterials
Authors: Tang Hao , Yan Feng , Lin Peng , Xu Jianbin , Chan Helen L. W. 
Published: April 2011

AbstractOrganic electrochemical transistors with glucose oxidase‐modified Pt gate electrodes are successfully used as highly sensitive glucose sensors. The gate electrodes are modified with nanomaterials (multi‐wall carbon nanotubes or Pt nanoparticles) for the first time, which results in a dramatic improvement in the sensitivity of the devices. The detection limit of the device modified with Pt nanoparticles on the gate electrode is about 5 nM, which is three orders of magnitude better than a device without the nanoparticles. The improvement of the device performance can be attributed to the excellent electrocatalytic properties of the nanomaterials and more effective immobilization of enzyme on the gate electrodes. Based on the same principle, many other types of enzyme sensors with high sensitivity and low cost are expected to be realized by modifying the gate electrodes of organic electrochemical transistors with specific enzymes and nanomaterials.
Critical Role of Triplet Exciton Interface Trap States in Bilayer Films of NPB and Ir(piq)3
Authors: Jankus Vygintas , Winscom Chris , Monkman Andrew P. 
Published: April 2011

AbstractInvestigations are carried out into triplet transfer in bilayer films of NPB (N,N´‐diphenyl‐N,N´‐bis(1‐naphthyl)‐1,1´‐biphenyl‐4,4˝‐diamine) and Ir(piq)3 (Iridium (III) Tris(1‐phenylisoquinoline) using laser light pulses to excite the upper surface of the NPB, and thereafter observing the decay dynamics in the Ir(piq)3 layer situated beneath the NPB. The NPB layer thickness is varied from 13 nm to 80 nm. The results show that up to 200 ns after excitation, the multiexponential decay of directly excited Ir(piq)3 is observed, thereafter the decay is monoexponential. It is concluded that this monoexponential decay after 200 ns is due to triplets that are transferred to the Ir(piq)3 via migration from the NPB. The thicker the NPB layer the longer it takes for the reservoir of NPB triplets to deplete via the Ir(piq)3, with the result that the apparent monoexponential lifetime of the Ir(piq)3 increases as the thickness of the NPB films increases. Based on time resolved spectra and decays, it is concluded that triplets arriving from NPB are trapped at interface sites of Ir(piq)3 and do not migrate directly to the bulk states of Ir(piq)3. A model based on exciton diffusion kinetics, including the presence of interface trap sites, is described, which accurately predicts this behavior.
Fe3O4 Nanoparticles Confined in Mesocellular Carbon Foam for High Performance Anode Materials for Lithium‐Ion Batteries
Authors: Kang Eunae , Jung Yoon Seok , Cavanagh Andrew S. , Kim Gi‐Heon , George Steven M. , Dillon Anne C. , Kim Jin Kon , Lee Jinwoo 
Published: April 2011

AbstractFe3O4 nanocrystals confined in mesocellular carbon foam (MSU‐F‐C) are synthesized by a “host–guest” approach and tested as an anode material for lithium‐ion batteries (LIBs). Briefly, an iron oxide precursor, Fe(NO3)3·9H2O, is impregnated in MSU‐F‐C having uniform cellular pores ∼30 nm in dia­meter, followed by heat‐treatment at 400 °C for 4 h under Ar. Magnetite Fe3O4 nanocrystals with sizes between 13–27 nm are then successfully fabricated inside the pores of the MSU‐F‐C, as confirmed by transmission electron microscopy (TEM), dark‐field scanning transmission electron microscopy (STEM), energy dispersive X‐ray spectroscopy (EDS), X‐ray diffraction (XRD), and nitrogen sorption isotherms. The presence of the carbon most likely allows for reduction of some of the Fe3+ ions to Fe2+ ions via a carbothermoreduction process. A Fe3O4/MSU‐F‐C nanocomposite with 45 wt% Fe3O4 exhibited a first charge capacity of 1007 mA h g−1 (Li+ extraction) at 0.1 A g−1 (∼0.1 C rate) with 111% capacity retention at the 150th cycle, and retained 37% capacity at 7 A g−1 (∼7 C rate). Because the three dimensionally interconnected open pores are larger than the average nanosized Fe3O4 particles, the large volume expansion of Fe3O4 upon Li‐insertion is easily accommodated inside the pores, resulting in excellent electrochemical performance as a LIB anode. Furthermore, when an ultrathin Al2O3 layer (<4 Å) was deposited on the composite anode using atomic layer deposition (ALD), the durability, rate capability and undesirable side reactions are significantly improved.
A Composite Formation Route to Well‐Crystalline Manganese Oxide Nanocrystals: High Catalytic Activity of Manganate–Alumina Nanocomposites
Authors: Kim Tae Woo , Yoo Hana , Kim In Young , Ha Hyung‐Wook , Han Ah Reum , Chang Jong‐San , Lee Ji Sun , Hwang Seong‐Ju 
Published: April 2011

AbstractManganese oxide nanocrystals are combined with aluminum oxide nanocrystals to improve their crystallinity via calcination without a significant increase of crystal size. A nanocomposite, consisting of two metal oxides, can be synthesized by the reaction between permanganate anions and aluminum oxyhydroxide keggin cations. The as‐prepared manganese oxide–aluminum oxide nanocomposite is X‐ray amorphous whereas heat‐treatment gives rise to the crystallization of an α‐MnO2 phase at 600 °C and Mn3O4/Mn2O3 and γ‐Al2O3 phases at 800 °C. Electron microscopy and N2 adsorption‐desorption‐isotherm analysis clearly demonstrate that the as‐prepared nanocomposite is composed of a porous assembly of monodisperse primary particles with a size of ∼20 nm and a surface area of >410 m2 g−1. Of particular interest is that the small particle size of the as‐prepared nanocomposite is well‐maintained up to 600 °C, a result of the prevention of the growth of manganate grains through nanoscale mixing with alumina grains. The calcined nanocomposite shows very‐high catalytic activity for the oxidation of cyclohexene with an extremely high conversion efficiency of >95% within 15 min. The present results show that the improvement of the crystallinity without significant crystal growth is very crucial for optimizing the catalytic activity of manganese oxide nanocrystals.