bluuebunny/crossref_metadata_2025_split huggingface dataset:
Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma
Authors: Fozza Claudio , Corda Giovanna , Virdis Patrizia , Contini Salvatore , Barraqueddu Francesca , Galleu Antonio , Isoni Antonella , Cossu Antonella , Dore Fausto , Careddu Maria G. , Bonfigli Silvana , Giannico Barbara , Longinotti Maurizio 
Published: July 2014

AbstractAlthough a number of studies suggest that different immune pathways may play a role in the pathogenesis of non‐Hodgkin's lymphomas (NHL), the shape of the T‐cell compartment has been only superficially explored in these patients. In our study, we analyzed the peripheral T‐cell receptor (TCR) repertoire and the distribution of different T‐cell subsets – including regulatory T cells (Treg) – in 30 patients with NHL, by combining flow cytometry and spectratyping. We first demonstrated by flow cytometry an increased frequency of expanded T‐cell subpopulations expressing the same TCR beta variable (BV) subfamilies in CD8+ cells from NHL patients when compared with healthy controls, beside a higher frequency of Treg. Moreover, NHL patients were characterized by a higher percentage of BVs showing a skewed CDR3 profile both in CD4+ and CD8+ cells when analyzed by spectratyping. Our data suggest that the T‐cell branch of the immune system of patients with B‐cell NHL is deeply deranged, as witnessed by the increased degree of activation and skewing of their TCR repertoire along with the higher frequency of Treg.
Collapsin response‐mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition
Authors: Brot Sébastien , Smaoune Hinda , Youssef‐Issa Mina , Malleval Céline , Benetollo Claire , Besançon Roger , Auger Carole , Moradi‐Améli Mahnaz , Honnorat Jérôme 
Published: July 2014

AbstractThe collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth.
The Ephrin receptor EphA4 restricts axonal sprouting and enhances branching in the injured mouse optic nerve
Authors: Joly Sandrine , Jordi Noémie , Schwab Martin E. , Pernet Vincent 
Published: July 2014

AbstractThe lack of axonal regeneration in the adult central nervous system is in part attributable to the presence of inhibitory molecules present in the environment of injured axons such as the myelin‐associated proteins Nogo‐A and MAG and the repulsive guidance molecules Ephrins, Netrins and Semaphorins. In the present study, we hypothesized that EphA4 and one of its potential binding partners EphrinA3 may participate in the inhibition of adult axon regeneration in the model of adult mouse optic nerve injury. Axonal regeneration was analysed in three dimensions after tissue clearing of EphA4 knockout (KO), EphrinA3 KO and wild‐type (WT) optic nerves. By immunohistochemistry, EphA4 was highly expressed in Müller glia endfeet in the retina and in astrocytes in the retina and the optic nerve, while EphrinA3 was present in retinal ganglion cells and oligodendrocytes. Optic nerve crush did not cause expression changes. Significantly more axons grew in the crushed optic nerve of EphA4 KO mice than in WT or EphrinA3 KO animals. Single axon analysis revealed that EphA4 KO axons were less prone to form aberrant branching than axons in the other mouse groups. The expression of growth‐associated proteins Sprr1a and Gap‐43 did not vary between EphA4 KO and WT retinae. However, glial fibrillary acidic protein‐expressing astrocytes were withdrawn from the perilesional area in EphA4 KO, suggesting that gliosis down‐regulation may locally contribute to improve axonal growth at the injury site. In summary, our three‐dimensional analysis of injured mouse optic nerves reveals beneficial effects of EphA4 ablation on the intensity and the pattern of optic nerve axon regeneration.
Top‐down inputs from the olfactory cortex in the postprandial period promote elimination of granule cells in the olfactory bulb
Authors: Komano‐Inoue Sayaka , Manabe Hiroyuki , Ota Mizuho , Kusumoto‐Yoshida Ikue , Yokoyama Takeshi K. , Mori Kensaku , Yamaguchi Masahiro 
Published: July 2014

AbstractElimination of granule cells (GCs) in the olfactory bulb (OB) is not a continual event but is promoted during a short time window in the postprandial period, typically with postprandial sleep. However, the neuronal mechanisms for the enhanced GC elimination during the postprandial period are not understood. Here, we addressed the question of whether top‐down inputs of centrifugal axons from the olfactory cortex (OC) during the postprandial period are involved in the enhanced GC elimination in the OB. Electrical stimulation of centrifugal axons from the OC of anesthetized mice increased GC apoptosis. Furthermore, pharmacological suppression of top‐down inputs from the OC to the OB during the postprandial period of freely behaving mice by γ‐aminobutyric acid (GABA)A receptor agonist injection in the OC significantly decreased GC apoptosis. Remarkable apoptotic GC elimination in the sensory‐deprived OB was also suppressed by pharmacological blockade of top‐down inputs. These results indicate that top‐down inputs from the OC to the OB during the postprandial period are the crucial signal promoting GC elimination, and suggest that the life and death decision of GCs in the OB is determined by the interplay between bottom‐up sensory inputs from the external world and top‐down inputs from the OC.
Costs of antibiotic resistance – separating trait effects and selective effects
Authors: Hall Alex R. , Angst Daniel C. , Schiessl Konstanze T. , Ackermann Martin 
Published: July 2014

AbstractAntibiotic resistance can impair bacterial growth or competitive ability in the absence of antibiotics, frequently referred to as a ‘cost’ of resistance. Theory and experiments emphasize the importance of such effects for the distribution of resistance in pathogenic populations. However, recent work shows that costs of resistance are highly variable depending on environmental factors such as nutrient supply and population structure, as well as genetic factors including the mechanism of resistance and genetic background. Here, we suggest that such variation can be better understood by distinguishing between the effects of resistance mechanisms on individual traits such as growth rate or yield (‘trait effects’) and effects on genotype frequencies over time (‘selective effects’). We first give a brief overview of the biological basis of costs of resistance and how trait effects may translate to selective effects in different environmental conditions. We then review empirical evidence of genetic and environmental variation of both types of effects and how such variation may be understood by combining molecular microbiological information with concepts from evolution and ecology. Ultimately, disentangling different types of costs may permit the identification of interventions that maximize the cost of resistance and therefore accelerate its decline.
Linking Northeast Pacific recruitment synchrony to environmental variability
Authors: Stachura Megan M. , Essington Timothy E. , Mantua Nathan J. , Hollowed Anne B. , Haltuch Melissa A. , Spencer Paul D. , Branch Trevor A. , Doyle Miriam J. 
Published: July 2014

AbstractWe investigated the hypothesis that synchronous recruitment is due to a shared susceptibility to environmental processes using stock–recruitment residuals for 52 marine fish stocks within three Northeast Pacific large marine ecosystems: the Eastern Bering Sea and Aleutian Islands, Gulf of Alaska, and California Current. There was moderate coherence in exceptionally strong and weak year‐classes and correlations across stocks. Based on evidence of synchrony from these analyses, we used Bayesian hierarchical models to relate recruitment to environmental covariates for groups of stocks that may be similarly influenced by environmental processes based on their life histories. There were consistent relationships among stocks to the covariates, especially within the Gulf of Alaska and California Current. The best Gulf of Alaska model included Northeast Pacific sea surface height as a predictor of recruitment, and was particularly strong for stocks dependent on cross‐shelf transport during the larval phase for recruitment. In the California Current the best‐fit model included San Francisco coastal sea level height as a predictor, with higher recruitment for many stocks corresponding to anomalously high sea level the year before spawning and low sea level the year of spawning. The best Eastern Bering Sea and Aleutian Islands model included several environmental variables as covariates and there was some consistent response across stocks to these variables. Future research may be able to utilize these across‐stock environmental influences, in conjunction with an understanding of ecological processes important across early life history stages, to improve identification of environmental drivers of recruitment.
A global assessment of forest surface albedo and its relationships with climate and atmospheric nitrogen deposition
Authors: Leonardi Stefano , Magnani Federico , Nolè Angelo , Van Noije Twan , Borghetti Marco 
Published: July 2014

AbstractWe present a global assessment of the relationships between the short‐wave surface albedo of forests, derived from theMODISsatellite instrument product at 0.5° spatial resolution, with simulated atmospheric nitrogen deposition rates (Ndep), and climatic variables (mean annual temperatureTmand total annual precipitationP), compiled at the same spatial resolution. The analysis was performed on the following five forest plant functional types (PFTs): evergreen needle‐leaf forests (ENF); evergreen broad‐leaf forests (EBF); deciduous needle‐leaf forests (DNF); deciduous broad‐leaf forests (DBF); and mixed‐forests (MF). Generalized additive models (GAMs) were applied in the exploratory analysis to assess the functional nature of short‐wave surface albedo relations to environmental variables. The analysis showed evident correlations of albedo with environmental predictors when data were pooled acrossPFTs:TmandNdepdisplayed a positive relationship with forest albedo, while a negative relationship was detected withP. These correlations are primarily due to surface albedo differences between conifer and broad‐leaf species, and different species geographical distributions. However, the analysis performed within individualPFTs, strengthened by attempts to select ‘pure’ pixels in terms of species composition, showed significant correlations with annual precipitation and nitrogen deposition, pointing toward the potential effect of environmental variables on forest surface albedo at the ecosystem level. Overall, our global assessment emphasizes the importance of elucidating the ecological mechanisms that link environmental conditions and forest canopy properties for an improved parameterization of surface albedo in climate models.
Cognitive Value and Numerical Accuracy in Geocomputation: Choosing a Method to Compute the Log‐Jacobian Term
Authors: Smirnov Oleg A. 
Published: July 2014

This article addresses the importance of cognitive value, numerical accuracy, and technical feasibility for geospatial models and methods. Researchers pursue large spatial data in an analysis to improve the statistical efficiency of parameter estimates and the cognitive value of the results. The critical requirement for this strategy is the availability of numerically accurate computational methods, without which parameter estimates lose their cognitive value. This article illustrates the relationship between cognitive value and numerical accuracy by establishing properties of popular polynomial schemes for approximating the log‐Jacobian term in spatial autoregressive models. It shows that numerical inaccuracies might be more misleading than is commonly assumed.En este artículo se aborda la importancia del valor cognitivo, la precisión numérica, y la viabilidad técnica de los modelos y métodos geoespaciales. Los investigadores interesados en análisis espacial tienden a preferir el uso de bases de datos de gran tamaño con el fin de mejorar la eficiencia estadística de sus estimaciones de parámetros y el valor cognitivo de los resultados. El requisito crítico para esta estrategia es la disponibilidad de métodos computacionales numéricamente precisos, sin los cuales las estimaciones de parámetros pierden su valor cognitivo. En este artículo se ilustra la relación entre el valor cognitivo y precisión numérica mediante la determinante jacobiano tipo log en modelos espaciales autorregresivos (spatial autorregresive models‐SAR). El estudio demuestra que las imprecisiones numéricas pueden ser más engañosas de lo que se asume comúnmente.本文描述了地理空间模型和方法中认知价值、数值精度、技术可行性的重要性。研究者一般倾向于通过追求大规模空间数据，来提升参数估计的统计有效性和结果的认知价值。这一策略的关键是有实用的精确数值计算方法，否则参数估计将失去其认知价值。本文通过建立普遍使用的多项式方案来逼近空间自回归（SAR）模型中的Log‐Jacobian，从而说明认知价值和数值精度间的关系。结果表明数值不确定性可能比通常假设的误导性更大。
Long‐chain alcohols did not improve predictions of the composition of tall fescue and red clover mixtures over n‐alkanes alone
Authors: Vargas Jurado N. , Tanner A. E. , Blevins S. R. , McNair H. M. , Mayes R. W. , Lewis R. M. 
Published: July 2014

AbstractFeed intake and diet choice affect production efficiency in livestock. Plant waxes, in particular n‐alkanes, have been used as markers to predict intake and diet preferences. Still, when n‐alkane profiles of plants within mixed swards are similar, they alone may not produce reliable predictions. Including long‐chain alcohols (LCOHs) may help. In this study, the reliability of predicting forage mixtures was assessed using n‐alkanes and LCOH separately and in combination. Reliability was characterized as the regression of observed on predicted fescue proportion in forage mixtures and the Kulczyński similarity index. Two technicians performed extractions of n‐alkanes and LCOHs of pure red clover and ‘Fawn’ tall fescue, and nine mixtures of them. The concentrations of n‐alkanes C27, C29, C31 and C33 and alcohols C26‐OH, C28‐OH and C30‐OH were compared among forage mixtures and between technicians. Technicians were consistent in their measures of n‐alkanes (P > 0·12), but differed in their measures of C26‐OH and C28‐OH (P < 0·002). Longer‐chained compounds were more consistently quantified. Forage delineations were not improved by C26‐OH. With n‐alkanes alone, estimated and actual fescue proportions closely agreed. Including LCOH offered no improvement. Despite variation in measured concentrations between technicians, fescue and red clover mixtures were reliably predicted using n‐alkanes alone.
Uncertainty Analysis of a Groundwater Flow Model in East‐Central Florida
Authors: Sepúlveda Nicasio , Doherty John 
Published: July 2014

AbstractA groundwater flow model for east‐central Florida has been developed to help water‐resource managers assess the impact of increased groundwater withdrawals from the Floridan aquifer system on heads and spring flows originating from the Upper Floridan Aquifer. The model provides a probabilistic description of predictions of interest to water‐resource managers, given the uncertainty associated with system heterogeneity, the large number of input parameters, and a nonunique groundwater flow solution. The uncertainty associated with these predictions can then be considered in decisions with which the model has been designed to assist. The “Null Space Monte Carlo” method is a stochastic probabilistic approach used to generate a suite of several hundred parameter field realizations, each maintaining the model in a calibrated state, and each considered to be hydrogeologically plausible. The results presented herein indicate that the model's capacity to predict changes in heads or spring flows that originate from increased groundwater withdrawals is considerably greater than its capacity to predict the absolute magnitudes of heads or spring flows. Furthermore, the capacity of the model to make predictions that are similar in location and in type to those in the calibration dataset exceeds its capacity to make predictions of different types at different locations. The quantification of these outcomes allows defensible use of the modeling process in support of future water‐resources decisions. The model allows the decision‐making process to recognize the uncertainties, and the spatial or temporal variability of uncertainties that are associated with predictions of future system behavior in a complex hydrogeological context.
Parameter Estimation for Groundwater Models under Uncertain Irrigation Data
Authors: Demissie Yonas , Valocchi Albert , Cai Ximing , Brozovic Nicholas , Senay Gabriel , Gebremichael Mekonnen 
Published: July 2014

AbstractThe success of modeling groundwater is strongly influenced by the accuracy of the model parameters that are used to characterize the subsurface system. However, the presence of uncertainty and possibly bias in groundwater model source/sink terms may lead to biased estimates of model parameters and model predictions when the standard regression‐based inverse modeling techniques are used. This study first quantifies the levels of bias in groundwater model parameters and predictions due to the presence of errors in irrigation data. Then, a new inverse modeling technique called input uncertainty weighted least‐squares (IUWLS) is presented for unbiased estimation of the parameters when pumping and other source/sink data are uncertain. The approach uses the concept of generalized least‐squares method with the weight of the objective function depending on the level of pumping uncertainty and iteratively adjusted during the parameter optimization process. We have conducted both analytical and numerical experiments, using irrigation pumping data from the Republican River Basin in Nebraska, to evaluate the performance of ordinary least‐squares (OLS) and IUWLS calibration methods under different levels of uncertainty of irrigation data and calibration conditions. The result from the OLS method shows the presence of statistically significant (p < 0.05) bias in estimated parameters and model predictions that persist despite calibrating the models to different calibration data and sample sizes. However, by directly accounting for the irrigation pumping uncertainties during the calibration procedures, the proposed IUWLS is able to minimize the bias effectively without adding significant computational burden to the calibration processes.
Tubulin β‐III: a novel immunohistochemical marker for intrahepatic peripheral cholangiocarcinoma
Authors: Zen Yoh , Britton David , Mitra Vikram , Pike Ian , Sarker Debashis , Itoh Tomoo , Heaton Nigel , Quaglia Alberto 
Published: July 2014

AimsOur recent proteomic study identified tubulin β‐III (TUBB3) as a potential tissue marker for intrahepatic cholangiocarcinomas (CCs). This validation study was conducted to see whether or not TUBB3 can serve as a novel immunohistochemical marker for peripheral CCs, using a large cohort (n = 197) covering various liver tumours and premalignant conditions.Methods and resultsImmunostaining using a monoclonal antibody demonstrated TUBB3 expression in 14/28 cases of peripheral CCs (50%), while its expression was significantly less common in perihilar CCs (6/40, 15%) (P = 0.002). No significant difference was identified in clinicopathological features between TUBB3‐positive and ‐negative cases. TUBB3 expression was entirely negative in hepatocellular carcinomas, biliary premalignant lesions (i.e., biliary intraepithelial neoplasias, intraductal papillary neoplasms), peribiliary gland hamartomas (bile duct adenomas), and non‐neoplastic biliary epithelium. TUBB3 expression was only focally noted in 2/12 cases of mixed hepatocellular and cholangiocarcinomas (<10% of cancer cells). Compared with other biliary (CK7 and CK19) and malignant markers (p53 and MUC1), TUBB3 was less sensitive but more specific for peripheral CCs. TUBB3 was also expressed in 40% of metastatic colorectal or breast cancers.ConclusionsThis study revealed that TUBB3 is a moderately sensitive and highly specific tissue marker for discriminating peripheral CCs from other primary liver tumours.
Stratified mucin‐producing intraepithelial lesion (SMILE): report of a case series with associated pathological findings
Authors: Boyle David P , McCluggage W Glenn 
Published: July 2014

AimsStratified mucin‐producing intraepithelial lesion (SMILE) is an uncommon premalignant cervical lesion showing morphological overlap with cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS)/cervical glandular intraepithelial neoplasia. Given the limited literature on SMILE, we aimed to document its frequency and assess the associated pathology in a large series of cases.Methods and resultsOver a 6‐year period, we documented all cases of SMILE and the associated findings. SMILE was diagnosed in 69 specimens from 60 patients (50 loop excisions and 19 punch biopsy specimens), constituting 0.6% of cervical specimens. Overall, SMILE coexisted with high‐grade CIN in 93% of cases, AIS in 42%, and a carcinoma in 10%. When SMILE was diagnosed on a cervical punch biopsy, there was high‐grade CIN in the follow‐up loop in most cases. SMILE was consistently diffusely p16‐positive and IMP3‐negative.ConclusionsGiven the morphological overlap and significant association with high‐grade CIN and AIS, we believe that SMILE is best regarded as a form of high‐grade reserve cell dysplasia, probably arising from reserve or stem cells with the capacity for multidirectional differentiation. We recommend that management of SMILE should be as for AIS.