bluuebunny/crossref_metadata_2025_split huggingface dataset:
CXCL13 Responsiveness but Not CXCR5 Expression by Late Transitional B Cells Initiates Splenic White Pulp Formation
Authors: Neely Harold R. , Flajnik Martin F. 
Published: February 2015

Abstract
Secondary lymphoid organs (SLO) provide the structural framework for coconcentration of Ag and Ag-specific lymphocytes required for an efficient adaptive immune system. The spleen is the primordial SLO, and evolved concurrently with Ig/TCR:pMHC-based adaptive immunity. The earliest cellular/histological event in the ontogeny of the spleen’s lymphoid architecture, the white pulp (WP), is the accumulation of B cells around splenic vasculature, an evolutionarily conserved feature since the spleen’s emergence in early jawed vertebrates such as sharks. In mammals, B cells are indispensable for both formation and maintenance of SLO microarchitecture; their expression of lymphotoxin α1β2 (LTα1β2) is required for the LTα1β2:CXCL13 positive feedback loop without which SLO cannot properly form. Despite the spleen’s central role in the evolution of adaptive immunity, neither the initiating event nor the B cell subset necessary for WP formation has been identified. We therefore sought to identify both in mouse. We detected CXCL13 protein in late embryonic splenic vasculature, and its expression was TNF-α and RAG-2 independent. A substantial influx of CXCR5+ transitional B cells into the spleen occurred 18 h before birth. However, these late embryonic B cells were unresponsive to CXCL13 (although responsive to CXCL12) and phenotypically indistinguishable from blood-derived B cells. Only after birth did B cells acquire CXCL13 responsiveness, accumulate around splenic vasculature, and establish the uniquely splenic B cell compartment, enriched for CXCL13-responsive late transitional cells. Thus, CXCL13 is the initiating component of the CXCL13:LTα1β2 positive feedback loop required for WP ontogeny, and CXCL13-responsive late transitional B cells are the initiating subset.
Functional Heterogeneity in the CD4+ T Cell Response to Murine γ-Herpesvirus 68
Authors: Hu Zhuting , Blackman Marcia A. , Kaye Kenneth M. , Usherwood Edward J. 
Published: February 2015

Abstract
CD4+ T cells are critical for the control of virus infections, T cell memory, and immune surveillance. We studied the differentiation and function of murine γ-herpesvirus 68 (MHV-68)–specific CD4+ T cells using gp150-specific TCR-transgenic mice. This allowed a more detailed study of the characteristics of the CD4+ T cell response than did previously available approaches for this virus. Most gp150-specific CD4+ T cells expressed T-bet and produced IFN-γ, indicating that MHV-68 infection triggered differentiation of CD4+ T cells largely into the Th1 subset, whereas some became follicular Th cells and Foxp3+ regulatory T cells. These CD4+ T cells were protective against MHV-68 infection in the absence of CD8+ T cells and B cells, and protection depended on IFN-γ secretion. Marked heterogeneity was observed in the CD4+ T cells, based on lymphocyte Ag 6C (Ly6C) expression. Ly6C expression positively correlated with IFN-γ, TNF-α, and granzyme B production; T-bet and KLRG1 expression; proliferation; and CD4+ T cell–mediated cytotoxicity. Ly6C expression inversely correlated with survival, CCR7 expression, and secondary expansion potential. Ly6C+ and Ly6C− gp150-specific CD4+ T cells were able to interconvert in a bidirectional manner upon secondary Ag exposure in vivo. These results indicate that Ly6C expression is closely associated with antiviral activity in effector CD4+ T cells but is inversely correlated with memory potential. Interconversion between Ly6C+ and Ly6C− cells may maintain a balance between the two Ag-specific CD4+ T cell populations during MHV-68 infection. These findings have significant implications for Ly6C as a surface marker to distinguish functionally distinct CD4+ T cells during persistent virus infection.
Effects of photodemethylation on the methylmercury budget of boreal Norwegian lakes
Authors: Poste Amanda E. , Braaten Hans Fredrik Veiteberg , de Wit Heleen A. , Sørensen Kai , Larssen Thorjørn 
Published: February 2015

Abstract

Methylmercury (MeHg) concentrations in freshwater fish from southeastern Norway continue to increase, highlighting the need for a comprehensive understanding of MeHg sources, cycling, and degradation in the aquatic environment. The authors assessed the importance of photodemethylation in the MeHg budget of 4 Norwegian lakes. Photodemethylation rates were determined using incubation experiments with MeHg-spiked natural lake water. The authors determined full-spectrum exposure rates at all study sites and waveband-specific rates (photosynthetically active radiation, ultraviolet-A radiation, and ultraviolet-B radiation) at 1 clear-water (Sognsvann) and 1 humic (Langtjern) site. No significant differences in photodemethylation rates between the sites were found, and the authors' observed rates agreed with available literature for lake and wetland waters. The authors paired experimentally derived photodemethylation rates with lake-specific incident irradiation, light attenuation, and MeHg concentrations to estimate MeHg loss through photodemethylation for the study sites. For Langtjern, losses through photodemethylation equalled 27% of total annual inputs, highlighting the importance of photodemethylation in the MeHg budget. Furthermore, the authors assessed how changes in terrestrial dissolved organic carbon (DOC) exported to freshwaters and climate-driven reductions in ice cover duration may affect MeHg losses through photodemethylation. Results suggest that future increases in DOC may lead to higher aqueous MeHg concentrations in boreal lakes due to increased DOC-associated MeHg inputs paired with significant decreases in the loss of MeHg through photodemethylation due to increased light attenuation. Environ Toxicol Chem 2015;34:1213–1223. © 2015 SETAC
Adverse effects of thiram-treated seed ingestion on the reproductive performance and the offspring immune function of the red-legged partridge
Authors: Lopez-Antia Ana , Ortiz-Santaliestra Manuel E. , Blas Esther García-de , Camarero Pablo R. , Mougeot Francois , Mateo Rafael 
Published: February 2015

Abstract

Pesticide research traditionally has focused on compounds with high acute toxicity or persistence, but the adverse sublethal effects of pesticides with different properties also may have important consequences on exposed wildlife. The authors studied the effects of thiram, a fungicide used for seed coating with known effects as endocrine disruptor. Red-legged partridges (Alectoris rufa; n = 15 pairs per treatment group) were fed wheat treated with 0%, 20%, or 100% of the thiram application rate used in autumn (25 d) and late winter (10 d) to mimic cereal sowing periods. The authors studied the effects on reproductive performance, carotenoid-based ornamentation and cellular immune responsiveness of adult partridges, and their relationship with changes in oxidative stress biomarkers and plasma biochemistry. The authors also studied the effect of parental exposure on egg antioxidant content and on the survival, growth, and cellular immune response of offspring. Exposure to thiram-coated seeds delayed egg laying, reduced clutch size, and affected egg size and eggshell thickness. Partridges exposed to the 20% thiram dose exhibited reduced egg fertility and brood size (55% and 28% of controls, respectively). Chick survival was unaffected by parental exposure to treated seeds, but adverse effects on their growth rate and cellular immune response were apparent. These effects on reproduction and immune function may have important demographic consequences on farmland bird populations. Environ Toxicol Chem 2015;34:1320–1329. © 2015 SETAC
Modeling ready biodegradability of fragrance materials
Authors: Ceriani Lidia , Papa Ester , Kovarich Simona , Boethling Robert , Gramatica Paola 
Published: February 2015

Abstract

In the present study, quantitative structure activity relationships were developed for predicting ready biodegradability of approximately 200 heterogeneous fragrance materials. Two classification methods, classification and regression tree (CART) and k-nearest neighbors (kNN), were applied to perform the modeling. The models were validated with multiple external prediction sets, and the structural applicability domain was verified by the leverage approach. The best models had good sensitivity (internal ≥80%; external ≥68%), specificity (internal ≥80%; external 73%), and overall accuracy (≥75%). Results from the comparison with BIOWIN global models, based on group contribution method, show that specific models developed in the present study perform better in prediction than BIOWIN6, in particular for the correct classification of not readily biodegradable fragrance materials. Environ Toxicol Chem 2015;34:1224–1231. © 2015 SETAC
Substrate tunnels in enzymes: Structure–function relationships and computational methodology
Authors: Kingsley Laura J. , Lill Markus A. 
Published: February 2015

ABSTRACTIn enzymes, the active site is the location where incoming substrates are chemically converted to products. In some enzymes, this site is deeply buried within the core of the protein, and, in order to access the active site, substrates must pass through the body of the protein via a tunnel. In many systems, these tunnels act as filters and have been found to influence both substrate specificity and catalytic mechanism. Identifying and understanding how these tunnels exert such control has been of growing interest over the past several years because of implications in fields such as protein engineering and drug design. This growing interest has spurred the development of several computational methods to identify and analyze tunnels and how ligands migrate through these tunnels. The goal of this review is to outline how tunnels influence substrate specificity and catalytic efficiency in enzymes with buried active sites and to provide a brief summary of the computational tools used to identify and evaluate these tunnels. Proteins 2015; 83:599–611. © 2015 Wiley Periodicals, Inc.
Renal responses produced by microinjection of the kappa opioid receptor agonist, U50‐488H, into sites within the rat lamina terminalis
Authors: Franklin Cynthia , Fortepiani Lourdes , Nguyen Tin , Rangel Yolanda , Strong Randy , Gottlieb Helmut B. 
Published: February 2015

AbstractActivation of central kappa opioid receptors (KOR) has been demonstrated to produce marked free water diuresis with a concurrent increase in renal sympathetic nerve activity (RSNA). This study investigated the cardiovascular (CV) and renal effects evoked by central activation of KOR in two lamina terminalis sites, the median preoptic area (MPA) and anterolateral division of the bed nuclei of the stria terminalis (BST). Rats anesthetized with urethane alpha‐chloralose were instrumented to record mean arterial pressure, heart rate, RSNA, and urine output (V). Rats were infused with isotonic saline (25 μL/min) and urine samples were collected during two 10‐min control periods and six consecutive 10‐min experimental periods following microinjection of vehicle, U50‐448H (U50, KOR agonist) alone or norbinaltorphimine (nor‐BNI, KOR antagonist) plus U50. Microinjection of U50 into the BST increased V (peak at 30 min, 84.8 ± 12.9 μL/min) as compared to its respective control, vehicle, or nor‐BNI plus U50. This diuretic effect occurred without any significant changes in CV parameters, RSNA, or urinary sodium excretion. In contrast, U50 injection into the MPA significantly increased RSNA (peak at 20 mins: 129 ± 9.9) without increasing the other parameters. This study demonstrated novel sites through which activation of KOR selectively increases V and RSNA. The ability of U50 to increase V without affecting sodium excretion and RSNA raises the possibility that LT neurons could be an important substrate through which drugs targeting KOR could selectively facilitate water excretion in sodium‐retaining diseases such as congestive heart failure.
Inhibition of adenosine deaminase (ADA)‐mediated metabolism of cordycepin by natural substances
Authors: Li Gen , Nakagome Izumi , Hirono Shuichi , Itoh Tomoo , Fujiwara Ryoichi 
Published: February 2015

AbstractCordycepin, which is an analogue of a nucleoside adenosine, exhibits a wide variety of pharmacological activities including anticancer effects. In this study, ADA1‐ and ADA2‐expressing HEK293 cells were established to determine the major ADA isoform responsible for the deamination of cordycepin. While the metabolic rate of cordycepin deamination was similar between ADA2‐expressing and Mock cells, extensive metabolism of cordycepin was observed in the ADA1‐expressing cells with Km and Vmax values of 54.9 μmol/L and 45.8 nmole/min/mg protein. Among five natural substances tested in this study (kaempferol, quercetin, myricetin, naringenin, and naringin), naringin strongly inhibited the deamination of cordycepin with Ki values of 58.8 μmol/L in mouse erythrocytes and 168.3 μmol/L in human erythrocytes. A treatment of Jurkat cells with a combination of cordycepin and naringin showed significant cytotoxicity. Our in silico study suggests that not only small molecules such as adenosine derivatives but also bulky molecules like naringin can be a potent ADA1 inhibitor for the clinical usage.
On Critical Behaviour in Systems of Hamiltonian Partial Differential Equations
Authors: Dubrovin Boris , Grava Tamara , Klein Christian , Moro Antonio 
Published: February 2015

Abstract
We study the critical behaviour of solutions to weakly dispersive Hamiltonian systems considered as perturbations of elliptic and hyperbolic systems of hydrodynamic type with two components. We argue that near the critical point of gradient catastrophe of the dispersionless system, the solutions to a suitable initial value problem for the perturbed equations are approximately described by particular solutions to the Painlevé-I (P

$$_I$$

I

) equation or its fourth-order analogue P

$$_I^2$$

I
2

. As concrete examples, we discuss nonlinear Schrödinger equations in the semiclassical limit. A numerical study of these cases provides strong evidence in support of the conjecture.
Predictive factors of functional capacity and real-world functioning in patients with schizophrenia
Authors: Menendez-Miranda I. , Garcia-Portilla M.P. , Garcia-Alvarez L. , Arrojo M. , Sanchez P. , Sarramea F. , Gomar J. , Bobes-Bascaran M.T. , Sierra P. , Saiz P.A. , Bobes J. 
Published: February 2015

AbstractPurposeThis study was performed to identify the predictive factors of functional capacity assessed by the Spanish University of California Performance Skills Assessment (Sp-UPSA) and real-world functioning assessed by the Spanish Personal and Social Performance scale (PSP) in outpatients with schizophrenia.MethodsNaturalistic, 6-month follow-up, multicentre, validation study. Here, we report data on 139 patients with schizophrenia at their baseline visit. Assessment: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), Sp-UPSA and PSP. Statistics: Pearson's correlation coefficient (r) was used to determine the relationships between variables, and multivariable stepwise linear regression analyses to identify predictive variables of Sp-UPSA and PSP total scores.ResultsFunctional capacity: scores on the PSP and PANSS-GP entered first and second atP< 0.0001 and accounted for 21% of variance (R2= 0.208, modeldf= 2,F= 15.724,P< 0.0001). Real-world functioning: scores on the CGI-S (B= −5.406), PANSS-N (B= −0.657) and Sp-UPSA (B= 0.230) entered first, second and third, and accounted for 51% of variance (modeldf= 3,F= 37.741,P< 0.0001).ConclusionIn patients with schizophrenia, functional capacity and real-world functioning are two related but different constructs. Each one predicts the other along with other factors; general psychopathology for functional capacity, and severity of the illness and negative symptoms for real-world functioning. These findings have important clinical implications: (1) both types of functioning should be assessed in patients with schizophrenia and (2) strategies for improving them should be different.
Does it pay to beat around the bush? The case of the obfuscating salesperson
Authors: Bickart Barbara , Morrin Maureen , Ratneshwar S. 
Published: February 2015

AbstractHow often do salespeople obfuscate in response to a customer's question? And when and why does obfuscating help or hurt the prospects of a sale? We investigate these questions in three studies, developing and testing a framework based on theory from persuasion, social cognition, and communication theory. The results show that most consumers report having experienced obfuscation in the marketplace and believe that it is more prevalent in professions where people have strong monetary motives to obfuscate. Further, we find that when consumers' prior expectations of a dishonest response to a question are heightened, either because the construct of honesty is chronically salient to the individual or because of the presence of a monetary motive for the salesperson, obfuscation undermines purchase intentions relative to a straightforward “don't know” response. In contrast, when expectations of a dishonest response are low, an obfuscatory response is as persuasive as an admission of lack of knowledge. These effects are mediated by perceived trust in the salesperson. Implications are discussed for persuasion theory, salesperson influence tactics, and consumer welfare.
Comparison of Two Scaling Methods in Preoperative Digital Templating of Total Hip Replacement
Authors: Leo Leung Kin-Ho , Joanna Mak , On-Bong Lee , Wai-Leuk Tsang , Jennifer Khoo 
Published: February 2015

Background/Purpose Preoperative templating is essential for the planning of total hip replacement. Digital templating has gained popularity due to the availability of digital images. Scaling is the critical step that calibrates magnified digital images to the actual dimension, for subsequent digital templating. We compared the accuracy of two scaling methods: (1) radiological marker; and (2) fixed magnification factor. Methods Forty-five postoperative radiographs in 21 patients who had undergone either total hip replacement or hip hemiarthroplasty were evaluated. The sizes of femoral head components in the digital radiographs were estimated using the two scaling methods. The estimated values were then compared to the true values stated in operation records. The absolute error (AE) and relative error (RE) of both scaling methods were calculated and compared. Results Both the mean AE and RE were smaller in Method 2 (fixed magnification factor), and were statistically significant (p < 0.05). Conclusion We recommend fixed magnification factor as the scaling method for digital templating.
MicroRNA‐30c‐2‐3p negatively regulates NF‐κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer
Authors: Shukla Kirti , Sharma Ashwini Kumar , Ward Aoife , Will Rainer , Hielscher Thomas , Balwierz Aleksandra , Breunig Christian , Münstermann Ewald , König Rainer , Keklikoglou Ioanna , Wiemann Stefan 
Published: February 2015

Nuclear Factor kappa B (NF‐κB) signaling is frequently deregulated in a variety of cancers and is constitutively active in estrogen receptor negative (ER‐) breast cancer subtypes. These molecular subtypes of breast cancer are associated with poor overall survival. We focused on mechanisms of NF‐κB regulation by microRNAs (miRNAs), which regulate eukaryotic gene expression at the post‐transcriptional level. In a previous genome‐wide miRNA screen, we had identified miR‐30c‐2‐3p as one of the strongest negative regulators of NF‐κB signaling. Here we have uncovered the underlying molecular mechanisms and its consequences in breast cancer. In vitro results show that miR‐30c‐2‐3p directly targets both TNFRSF1A‐associated via death domain (TRADD), an adaptor protein of the TNFR/NF‐κB signaling pathway, and the cell cycle protein Cyclin E1 (CCNE1). Ectopic expression of miR‐30c‐2‐3p downregulated essential cytokines IL8, IL6, CXCL1, and reduced cell proliferation as well as invasion in MDA‐MB‐231 breast cancer cells. RNA interference (RNAi) induced silencing of TRADD phenocopied the effects on invasion and cytokine expression caused by miR‐30c‐2‐3p, while inhibition of CCNE1 phenocopied the effects on cell proliferation. We further confirmed the tumor suppressive role of this miRNA using a dataset of 781 breast tumors, where higher expression was associated with better survival in breast cancer patients. In summary we have elucidated the mechanism by which miR‐30c‐2‐3p negatively regulates NF‐κB signaling and cell cycle progression in breast cancer.
Infection Prevention and Control Practices in Children’s Hospitals
Authors: Bender Jeffrey M. , Virgallito Mary , Newland Jason G. , Sammons Julia S. , Thorell Emily A. , Coffin Susan E. , Pavia Andrew T. , Sandora Thomas J. , Hersh Adam L. 
Published: February 2015

AbstractWe surveyed hospital epidemiologists at 28 Children’s Hospital Association member hospitals regarding their infection prevention and control programs. We found substantial variability between children’s hospitals in both the structure and the practice of these programs. Research and the development of evidence-based guidelines addressing infection prevention in pediatrics are needed.Infect Control Hosp Epidemiol2015;00(0): 1–4
TMT pay dispersion and firm performance: the moderating role of organizational governance effectiveness
Authors: Sanchez-Marin Gregorio , Baixauli-Soler J. Samuel 
Published: February 2015

AbstractThis study supports tournament theory in relation to high levels of organizational hierarchies, indicating that the job complexity facing the top management team supposes that pay dispersion positively influences firm performance. Examining a sample of 709 firm-year observations of Spanish listed companies spanning the period 2004–2012, our results indicate that the association between firm performance and top management team pay dispersion is conditional on the effectiveness of corporate governance. High top management team pay dispersion is associated with better performance in owner-controlled firms, where more effective monitoring is exerted by the board of directors.
A framework for organizational learning: zero, adaptive and generative learning
Authors: Chiva Ricardo , Habib Johanna 
Published: February 2015

AbstractAlthough organizational learning types like adaptive and generative learning are considered to follow different processes, a general framework of organizational learning that includes them has remained elusive. In order to do so, we propose a framework that embraces them and incorporates facets such as consciousness and emotions, which are strongly related to organizational learning but had not been included in any model. These facets are essential in the framework as they bind the process together and represent a sequence and progression through the learning process.