bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mismatch Repair Proteins and AID Activity Are Required for the Dominant Negative Function of C-Terminally Deleted AID in Class Switching
Authors: Ucher Anna J. , Ranjit Sanjay , Kadungure Tatenda , Linehan Erin K. , Khair Lyne , Xie Elaine , Limauro Jennifer , Rauch Katherina S. , Schrader Carol E. , Stavnezer Janet 
Published: June 2014

Abstract
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes. The AID C terminus is required for CSR, but not for S-region DNA double-strand breaks (DSBs) during CSR, and it is not required for SHM. AID lacking the C terminus (ΔAID) is a dominant negative (DN) mutant, because human patients heterozygous for this mutant fail to undergo CSR. In agreement, we show that ΔAID is a DN mutant when expressed in AID-sufficient mouse splenic B cells. To have DN function, ΔAID must have deaminase activity, suggesting that its ability to induce DSBs is important for the DN function. Supporting this hypothesis, Msh2-Msh6 have been shown to contribute to DSB formation in S regions, and we find in this study that Msh2 is required for the DN activity, because ΔAID is not a DN mutant in msh2−/− cells. Our results suggest that the DNA DSBs induced by ΔAID are unable to participate in CSR and might interfere with the ability of full-length AID to participate in CSR. We propose that ΔAID is impaired in its ability to recruit nonhomologous end joining repair factors, resulting in accumulation of DSBs that undergo aberrant resection. Supporting this hypothesis, we find that the S–S junctions induced by ΔAID have longer microhomologies than do those induced by full-length AID. In addition, our data suggest that AID binds Sμ regions in vivo as a monomer.
Human Hematopoietic Reconstitution and HLA-Restricted Responses in Nonpermissive Alymphoid Mice
Authors: Serra-Hassoun Malika , Bourgine Maryline , Boniotto Michele , Berges Julien , Langa Francina , Michel Marie-Louise , Freitas Antonio A. , Garcia Sylvie 
Published: June 2014

Abstract
We generated a new humanized mouse model to study HLA-restricted immune responses. For this purpose, we created unique murine hosts by enforcing the expression of human SIRPα by murine phagocytes in murine MHC-deficient HLA-transgenic alymphoid hosts, an approach that allowed the immune reconstitution of nonpermissive mice following injection of human hematopoietic stem cells. We showed that these mouse/human chimeras were able to generate HLA-restricted responses to immunization. These new humanized mice may offer attractive models to study immune responses to human diseases, such as HIV and EBV infections, as well as to assay new vaccine strategies.
Critical Roles of TIPE2 Protein in Murine Experimental Colitis
Authors: Lou Yunwei , Sun Honghong , Morrissey Samantha , Porturas Thomas , Liu Suxia , Hua Xianxin , Chen Youhai H. 
Published: June 2014

Abstract
Both commensal bacteria and infiltrating inflammatory cells play essential roles in the pathogenesis of inflammatory bowel disease. The molecular mechanisms whereby these pathogenic factors are regulated during the disease are not fully understood. We report in this article that a member of the TNF-α–induced protein 8 (TNFAIP8) family called TIPE2 (TNFAIP8-like 2) plays a crucial role in regulating commensal bacteria dissemination and inflammatory cell function in experimental colitis induced by dextran sodium sulfate (DSS). Following DSS treatment, TIPE2-deficient mice, or chimeric mice that are deficient in TIPE2 only in their hematopoietic cells, lost less body weight and survived longer than wild-type controls. Consistent with this clinical observation, TIPE2-deficient mice exhibited significantly less severe colitis and colonic damage. This was associated with a marked reduction in the colonic expression of inflammatory cytokines, such as TNF-α, IL-6, and IL-12. Importantly, the ameliorated DSS-induced colitis in TIPE2−/− mice also was associated with reduced local dissemination of commensal bacteria and a weaker systemic inflammatory response. Combined with our previous report that TIPE2 is a negative regulator of antibacterial immunity, these results indicate that TIPE2 promotes colitis by inhibiting mucosal immunity to commensal bacteria.
Cutting Edge: CXCR4 Is Critical for CD8+ Memory T Cell Homeostatic Self-Renewal but Not Rechallenge Self-Renewal
Authors: Chaix Julie , Nish Simone A. , Lin Wen-Hsuan W. , Rothman Nyanza J. , Ding Lei , Wherry E. John , Reiner Steven L. 
Published: June 2014

Abstract
Central memory (CM) CD8+ T cells “remember” prior encounters because they maintain themselves through cell division in the absence of ongoing challenge (homeostatic self-renewal), as well as reproduce the CM fate while manufacturing effector cells during secondary Ag encounters (rechallenge self-renewal). We tested the consequence of conditional deletion of the bone marrow homing receptor CXCR4 on antiviral T cell responses. CXCR4-deficient CD8+ T cells have impaired memory cell maintenance due to defective homeostatic proliferation. Upon rechallenge, however, CXCR4-deficient T cells can re-expand and renew the CM pool while producing secondary effector cells. The critical bone marrow–derived signals essential for CD8+ T cell homeostatic self-renewal appear to be dispensable to yield self-renewing, functionally asymmetric cell fates during rechallenge.
CXCL17 Is a Major Chemotactic Factor for Lung Macrophages
Authors: Burkhardt Amanda M. , Maravillas-Montero José L. , Carnevale Christina D. , Vilches-Cisneros Natalia , Flores Juan P. , Hevezi Peter A. , Zlotnik Albert 
Published: June 2014

Abstract
Chemokines are a superfamily of chemotactic cytokines that direct the movement of cells throughout the body under homeostatic and inflammatory conditions. The mucosal chemokine CXCL17 was the last ligand of this superfamily to be characterized. Several recent studies have provided greater insight into the basic biology of this chemokine and have implicated CXCL17 in several human diseases. We sought to better characterize CXCL17’s activity in vivo. To this end, we analyzed its chemoattractant properties in vivo and characterized a Cxcl17 −/− mouse. This mouse has a significantly reduced number of macrophages in its lungs compared with wild-type mice. In addition, we observed a concurrent increase in a new population of macrophage-like cells that are F4/80+CDllcmid. These results indicate that CXCL17 is a novel macrophage chemoattractant that operates in mucosal tissues. Given the importance of macrophages in inflammation, these observations strongly suggest that CXCL17 is a major regulator of mucosal inflammatory responses.
Prolonged Triglyceride Storage in Macrophages: pHo Trumps pO2 and TLR4
Authors: Lu Mingfang , Kho Terry , Munford Robert S. 
Published: June 2014

Abstract
Lipid-laden macrophages contribute to pathologies as diverse as atherosclerosis and tuberculosis. Three common stimuli are known to promote macrophage lipid storage: low tissue oxygen tension (pO2), low extracellular pH (pHo), and exposure to agonists such as bacterial LPS. Noting that cells responding to low pO2 or agonistic bacterial molecules often decrease pHo by secreting lactic and other carboxylic acids, we studied how pHo influences the stimulation of triacylglycerol (TAG) storage by low pO2 and LPS. We found that TAG retention after incubation for 48–72 h was inversely related to pHo when primary macrophages were cultured in 21% oxygen, 4% oxygen, or with LPS at either oxygen concentration. Maintaining pHo at ∼7.4 was sufficient to prevent the increase in prolonged TAG storage induced by either low pO2 or LPS. The strong influence of pHo on TAG retention may explain why lipid-laden macrophages are found in some tissue environments and not in others. It is also possible that other long-term cellular changes currently attributed to low pO2 or bacterial agonists may be promoted, at least in part, by the decrease in pHo that these stimuli induce.
RAG1/2 Knockout Pigs with Severe Combined Immunodeficiency
Authors: Huang Jiao , Guo Xiaogang , Fan Nana , Song Jun , Zhao Bentian , Ouyang Zhen , Liu Zhaoming , Zhao Yu , Yan Quanmei , Yi Xiaoling , Schambach Axel , Frampton Jon , Esteban Miguel A. , Yang Dongshan , Yang Huaqiang , Lai Liangxue 
Published: June 2014

Abstract
Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research.
Antitumor Effects of CD40 Ligand-Expressing Endothelial Progenitor Cells Derived From Human Induced Pluripotent Stem Cells in a Metastatic Breast Cancer Model
Authors: Purwanti Yovita Ida , Chen Can , Lam Dang Hoang , Wu Chunxiao , Zeng Jieming , Fan Weimin , Wang Shu 
Published: June 2014

AbstractGiven their intrinsic ability to home to tumor sites, endothelial progenitor cells (EPCs) are attractive as cellular vehicles for targeted cancer gene therapy. However, collecting sufficient EPCs is one of the challenging issues critical for effective clinical translation of this new approach. In this study, we sought to explore whether human induced pluripotent stem (iPS) cells could be used as a reliable and accessible cell source to generate human EPCs suitable for cancer treatment. We used an embryoid body formation method to derive CD133+CD34+ EPCs from human iPS cells. The generated EPCs expressed endothelial markers such as CD31, Flk1, and vascular endothelial-cadherin without expression of the CD45 hematopoietic marker. After intravenous injection, the iPS cell-derived EPCs migrated toward orthotopic and lung metastatic tumors in the mouse 4T1 breast cancer model but did not promote tumor growth and metastasis. To investigate their therapeutic potential, the EPCs were transduced with baculovirus encoding the potent T cell costimulatory molecule CD40 ligand. The systemic injection of the CD40 ligand-expressing EPCs stimulated the secretion of both tumor necrosis factor-α and interferon-γ and increased the caspase 3/7 activity in the lungs with metastatic tumors, leading to prolonged survival of the tumor bearing mice. Therefore, our findings suggest that human iPS cell-derived EPCs have the potential to serve as tumor-targeted cellular vehicles for anticancer gene therapy.
Noise statistics identification for Kalman filtering of the electron radiation belt observations: 2. Filtration and smoothing
Authors: Podladchikova T. V. , Shprits Y. Y. , Kellerman A. C. , Kondrashov D. 
Published: June 2014

AbstractIn this study we present the further improvement of data assimilation using the 1‐D radial diffusion model for relativistic electron phase space density (PSD) and observations of CRRES satellite. The main purpose of our study is estimation of the radiation belt dynamics for the prediction and mitigation of space weather effects in the hazardous space environment. We develop further noise statistics identification technique presented in the companion paper to estimate the observation error statistics that are crucially important for optimal performance of data assimilation. Assimilation of satellite observations into first‐principles physics model of radiation belts, when both model and observation error statistics are poorly known, may cause large errors in the PSD estimation and lead to failure of a data assimilation algorithm. We identify the coefficients of proportionality characterizing the dependence of observation errors on satellite observations. The effectiveness of the proposed identification technique is illustrated by applying the Kalman filter with optimal identified and nonoptimal observation errors statistics to the sparse CRRES observations over a period of 441 days, from 28 July 1990 to 11 October 1991. Further improvement and the accuracy increase of PSD reconstruction is demonstrated by the implementation of the backward smoothing procedure applied to the forward Kalman filter estimates.
Gravity wave effects on postsunset equatorial F region stability
Authors: Hysell D. L. , Jafari R. , Fritts D. C. , Laughman B. 
Published: June 2014

AbstractThe influence of gravity waves on the stability of the postsunset equatorial F region ionosphere is investigated numerically. For this investigation, we use the output of a direct numerical simulation of waves and turbulence in the mesosphere and lower thermosphere to force a simulation of ionospheric dynamics. Both simulations are cast in three dimensions. The effectiveness of the neutral‐plasma coupling involved is generally thought to depend on the dynamo efficiency and spatial resonance of the forcing, which we evaluate. In our simulations, the postsunset equatorial ionosphere could be deformed by neutral waves after 5–15 min most severely when the wavefronts were aligned approximately with the magnetic meridian, despite the fact that the dynamo efficiency is modest even in that case. However, poor spatial resonance limits the subsequent growth of the deformations in our simulations, and the seeding of interchange instabilities does not occur. The coupled simulations predict the formation of intermediate layers in the equatorial valley region (150–250 km apex altitude) under some circumstances that could serve as telltales in nature of the presence of the kind of neutral forcing we simulate.
Observations and simulations of the ionospheric lunar tide: Seasonal variability
Authors: Pedatella N. M. 
Published: June 2014

AbstractThe seasonal variability of the ionospheric lunar tide is investigated using a combination of Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) observations and thermosphere‐ionosphere‐mesosphere electrodynamics general circulation model (TIME‐GCM) simulations. The present study focuses on the seasonal variability of the lunar tide in the ionosphere and its potential connection to the occurrence of stratosphere sudden warmings (SSWs). COSMIC maximum F region electron density (NmF2) and total electron content observations reveal a primarily annual variation of the ionospheric lunar tide, with maximum amplitudes occurring at low latitudes during December–February. Simulations of the lunar tide climatology in TIME‐GCM display a similar annual variability as the COSMIC observations. This leads to the conclusion that the annual variability of the lunar tide in the ionosphere is not solely due to the occurrence of SSWs. Rather, the annual variability of the lunar tide in the ionosphere is generated by the seasonal variability of the lunar tide at E region altitudes. However, compared to the observations, the ionospheric lunar tide annual variability is weaker in the climatological simulations which is attributed to the occurrence of SSWs during the majority of the years included in the observations. Introducing a SSW into the TIME‐GCM simulation leads to an additional enhancement of the lunar tide during Northern Hemisphere winter, increasing the lunar tide annual variability and resulting in an annual variability that is more consistent with the observations. The occurrence of SSWs can therefore potentially bias lunar tide climatologies, and it is important to consider these effects in studies of the lunar tide in the atmosphere and ionosphere.
Global representation of aerosol vertical profiles by sums of lognormal modes: Consequences for the passive remote sensing of aerosol heights
Authors: Hollstein A. , Filipitsch F. 
Published: June 2014

AbstractAerosol extinction profiles from a climatology of CALIPSO measurements are analyzed with respect to their representation by truncated sums of up to three lognormal functions. Discussed are results for the climatological mean and a realistic profile, which is constructed from the climatological mean and its standard deviation. The realistic profile shows, in general, a more feature‐rich structure and is used as proxy for actual measurements. It was found that a single lognormal mode is on global scale able to explain 59% of the vertical profile, while a sum of two modes is able to explain 74%. Including a third lognormal mode leads only to a minor improvement to 79%. The strong regional and weaker seasonal dependency of the reconstruction accuracy with respect to the number of used lognormal modes is presented and discussed in detail. These findings have implications for the design of future operational aerosol height retrievals for upcoming instruments such as Tropospheric Monitoring Instrument on board European Space Agency's Sentinel 5 precursor or Sentinel 4.
Parent feeding behavior and child appetite: Associations depend on feeding style
Authors: Carnell Susan , Benson Leora , Driggin Elissa , Kolbe Laura 
Published: June 2014

ABSTRACTObjectiveEating behavior traits measured in early life predict eating behavior and weight trajectories later in development, and may be associated with certain parental feeding behaviors. Our goal was to investigate the relationship between a range of feeding behaviors, and preschoolers' appetitive traits.MethodFour hundred thirty‐nine parents of UK 3–5 year olds completed scales measuring authoritarian vs. authoritative forms of limiting (Restriction vs. Monitoring) and promoting (Pressuring vs. Prompting) intake, as well as Emotional and Instrumental Feeding. Parents also completed scales measuring child Food responsiveness and Satiety responsiveness. Child BMI z‐scores were calculated based on measured heights and weights.ResultsParental Restriction was significantly associated with greater child Food responsiveness (p < .001), but parental Monitoring was not. Parental Pressuring was significantly associated with greater child Satiety responsiveness (p < .001), while parental Prompting was not. Parental Instrumental and Emotional feeding were both associated with greater child Food responsiveness (p < .001). All relationships were independent of child BMI z‐score.DiscussionProspective data are needed to determine whether the parent–child feeding relationships identified here promote, or protect against, the development of eating pathology in children. However, our results suggest that cross‐sectional associations depend on the style (e.g., authoritarian vs. authoritative), as well as the type of feeding behavior measured. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:705–709)
Identification of microRNAs differentially expressed in prostatic secretions of patients with prostate cancer
Authors: Guzel Esra , Karatas Omer F. , Semercioz Atilla , Ekici Sinan , Aykan Serdar , Yentur Serhat , Creighton Chad J. , Ittmann Michael , Ozen Mustafa 
Published: June 2014

Prostate cancer (PCa) is one of the leading causes of cancer deaths in men. Since there are limited treatment options available for the advanced tumors, there is an urgent need for novel diagnostic tools for PCa. Prostate secretion samples (PSS) from 23 PCa and 25 benign prostate hyperplasia (BPH) patients were obtained from Urology Department of Bagcilar Educational and Research Hospital (Istanbul). MicroRNA (miRNA) profiling of eight PSS (four from BPH, four from PCa patients) was performed using microarray. Four of significantly deregulated miRNAs were further confirmed using quantitative reverse‐transcription PCR (qRT‐PCR). Statistical analysis was performed using Student's t‐test. ROC curves were plotted with SPSS‐15.0.In this study, we aimed to identify a miRNA expression signature that could be used to distinguish PCa from BPH. MiRNA profiling of four PCa and four BPH patients with microarray revealed that miR‐361‐3p, miR‐133b and miR‐221 were significantly downregulated and miR‐203 was upregulated in PSS of PCa patients. Further qRT‐PCR analysis confirmed the altered expressions of these four miRNAs in PSS of 23 PCa and 25 BPH patients. Four miRNAs, together and individually have much power (AUC; 0.950) than PSA has (AUC; 0.463) to discriminate PCa from BPH patients.We have shown for the first time in the literature the presence of miRNAs in the PSS. We suggest PSS as a powerful non‐invasive source for evaluation of prognosis in PCa, since prostate massages can be easily applied during routine examination. Our results showed that certain differentially expressed miRNAs in PSS could be used as diagnostics markers.
In vitroandin vivocorrosion properties of new iron–manganese alloys designed for cardiovascular applications
Authors: Drynda Andreas , Hassel Thomas , Bach Friedrich Wilhelm , Peuster Matthias 
Published: June 2014

AbstractThe principle of biodegradation for the production of temporary implant materials (e.g. stents) plays an important role in the treatment of congenital heart defects. In the last decade several attempts have been made with different alloy materials—mainly based on iron and magnesium. None of the currently available materials in this field have demonstrated satisfying results and have therefore not found entry into broad clinical practice. While magnesium or magnesium alloy systems corrode too fast, the corrosion rate of pure iron‐stents is too slow for cardiovascular applications. In the last years FeMn alloy systems were developed with the idea that galvanic effects, caused by different electrochemical properties of Fe and Mn, would increase the corrosion rate.In vitrotests with alloys containing up to 30% Mn showed promising results in terms of biocompatibility. This study deals with the development of new FeMn alloy systems with lower Mn concentrations (FeMn 0.5 wt %, FeMn 2.7 wt %, FeMn 6.9 wt %) to avoid Mn toxicity. Our results show, that these alloys exhibit good mechanical features as well as suitablein vitrobiocompatibility and corrosion properties. In contrast, the evaluation of these alloys in a mouse model led to unexpected results—even after 9 months no significant corrosion was detectable. Preliminary SEM investigations showed that passivation layers (FeMn phosphates) might be the reason for corrosion resistance. If this can be proved in further experiments, strategies to prevent or dissolve those layers need to be developed to expedite thein vivocorrosion of FeMn alloys. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 649–660, 2015.