bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats
Authors: de Queiroz D B , Sastre E , Caracuel L , Callejo M , Xavier F E , Blanco‐Rivero J , Balfagón G 
Published: July 2015

Background and PurposeWe have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect.Experimental ApproachDiabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium‐denuded vascular rings from the offspring of control (O‐CR) and diabetic rats (O‐DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA‐NO were studied. The expressions of neuronal NOS (nNOS) and phospho‐nNOS (P‐nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence.Key ResultsBlood pressure was higher in O‐DR animals. EFS‐induced vasoconstriction was greater in O‐DR animals. This response was decreased by phentolamine more in O‐DR animals than their controls. L‐NAME increased EFS‐induced vasoconstriction more strongly in O‐DR than in O‐CR segments. Vasomotor responses to NA or DEA‐NO were not modified. NA, ATP and NO release was increased in segments from O‐DR. nNOS expression was not modified, whereas P‐nNOS expression was increased in O‐DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups.Conclusions and ImplicationsThe activity of sympathetic and nitrergic innervation is increased in SMA from O‐DR animals. The net effect is an increase in EFS‐induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats.
Down‐regulation of IL‐8 by high‐dose vitamin D is specific to hyperinflammatory macrophages and involves mechanisms beyond up‐regulation of DUSP1
Authors: Dauletbaev N , Herscovitch K , Das M , Chen H , Bernier J , Matouk E , Bérubé J , Rousseau S , Lands L C 
Published: July 2015

Background and PurposeThere is current interest in vitamin D as a potential anti‐inflammatory treatment for chronic inflammatory lung disease, including cystic fibrosis (CF). Vitamin D transcriptionally up‐regulates the anti‐inflammatory gene DUSP1, which partly controls production of the inflammatory chemokine IL‐8. IL‐8 is overabundant in CF airways, potentially due to hyperinflammatory responses of CF macrophages. We tested the ability of vitamin D metabolites to down‐regulate IL‐8 production in CF macrophages.Experimental ApproachCF and healthy monocyte‐derived macrophages (MDM) were treated with two vitamin D metabolites, 25‐hydroxyvitamin D3 (25OHD3) and 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3), or paricalcitol, synthetic analogue of 1,25(OH)2D3. 25OHD3 was tested at doses of 25–150 nM, whereas 1,25(OH)2D3 and paricalcitol at doses of up to 100 nM. IL‐8 was stimulated by bacterial virulence factors. As potential anti‐inflammatory mechanism of vitamin D metabolites, we assessed up‐regulation of DUSP1.Key ResultsMDM from patients with CF and some healthy donors showed excessive production of stimulated IL‐8, highlighting their hyperinflammatory phenotype. Vitamin D metabolites down‐regulated stimulated IL‐8 only in those hyperinflammatory MDM, and only when used at high doses (>100 nM for 25OHD3, or >1 nM for 1,25(OH)2D3 and paricalcitol). The magnitude of IL‐8 down‐regulation by vitamin D metabolites or paricalcitol was moderate (∼30% vs. >70% by low‐dose dexamethasone). Transcriptional up‐regulation of DUSP1 by vitamin D metabolites was seen in all tested MDM, regardless of IL‐8 down‐regulation.Conclusions and ImplicationsVitamin D metabolites and their analogues moderately down‐regulate IL‐8 in hyperinflammatory macrophages, including those from CF. This down‐regulation appears to go through DUSP1‐independent mechanisms.
Tectonic and oceanographic control of sedimentary patterns in a small oceanic basin: Dove Basin (Scotia Sea, Antarctica)
Authors: Pérez Lara F. , Maldonado Andrés , Hernández‐Molina Francisco Javier , Lodolo Emanuele , Bohoyo Fernando , Galindo‐Zaldívar Jesús 
Published: July 2015

AbstractDove Basin, a small oceanic domain located within the southern Scotia Sea, evidences a complex tectonic evolution linked to the development of the Scotia Arc. The basin also straddles the junction between the main Southern Ocean water masses: the Antarctic Circumpolar Current (ACC), the Southeast Pacific Deep Water (SPDW) and the Weddell Sea Deep Water (WSDW). Analysis of multichannel seismic reflection profiles, together with swath bathymetry data, reveals the main structure and sediment distribution of the basin, allowing a reconstruction of the tectonostratigraphic evolution of the basin and assessment of the main bottom water flows that influenced its depositional development. Sediment dispersed in the basin was largely influenced by gravity‐driven transport from adjacent continental margins, later modified by deep bottom currents. Sediments derived from melting icebergs and extensive ice sheets also contributed to a fraction of the basin deposits. We identify four stages in the basin evolution which – based on regional age assumptions – took place during the early Miocene, middle Miocene, late Miocene–early Pliocene and late Pliocene–Quaternary. The onsets of the ACC flow in Dove Basin during the early Miocene, the WSDW flow during the middle Miocene, and the SPDW during the late Miocene were influenced by tectonic events that facilitated the opening of new oceanic gateways in the region. The analysis of Dove Basin reveals that tectonics is a primary factor influencing its sedimentary stacking patterns, the structural development of new oceanic gateways permitting the inception of deep‐water flows that have since controlled the sedimentary processes.
How Should Ecologists Define Sampling Effort? The Potential of Procrustes Analysis for Studying Variation in Community Composition
Authors: Saito Victor S. , Fonseca‐Gessner Alaide A. , Siqueira Tadeu 
Published: July 2015

AbstractAppropriate sampling effort is crucial for ecologists. Procrustes analysis can be used to tackle this question by quantifying the match between subsamples and the complete dataset. We used stream macroinvertebrates to show how sampling design can be optimized by reducing the number of subsamples and increasing the number of sites.
STX11 functions as a novel tumor suppressor gene in peripheral T‐cell lymphomas
Authors: Yoshida Noriaki , Tsuzuki Shinobu , Karube Kennosuke , Takahara Taishi , Suguro Miyuki , Miyoshi Hiroaki , Nishikori Momoko , Shimoyama Masanori , Tsukasaki Kunihiro , Ohshima Koichi , Seto Masao 
Published: July 2015

Peripheral T‐cell lymphomas (PTCL) are a heterogeneous group of non‐Hodgkin lymphomas with poor prognosis. Their molecular pathogenesis has not been entirely elucidated. We previously showed that 6q24 is one of the most frequently deleted regions in primary thyroid T‐cell lymphoma. In this study, we extended the analysis to other subtypes of PTCL and performed functional assays to identify the causative genes of PTCL that are located on 6q24. Genomic loss of 6q24 was observed in 14 of 232 (6%) PTCL cases. The genomic loss regions identified at 6q24 always involved only two known genes, STX11 and UTRN. The expression of STX11, but not UTRN, was substantially lower in PTCL than in normal T‐cells. STX11 sequence analysis revealed mutations in two cases (one clinical sample and one T‐cell line). We further analyzed the function of STX11 in 14 cell lines belonging to different lineages. STX11 expression only suppressed the proliferation of T‐cell lines bearing genomic alterations at the STX11 locus. Interestingly, expression of a novel STX11 mutant (p.Arg78Cys) did not exert suppressive effects on the induced cell lines, suggesting that this mutant is a loss‐of‐function mutation. In addition, STX11‐altered PTCL not otherwise specified cases were characterized by the presence of hemophagocytic syndrome (67% vs 8%, P = 0.04). They also tended to have a poor prognosis compared with those without STX11 alteration. These results suggest that STX11 plays an important role in the pathogenesis of PTCL and they may contribute to the future development of new drugs for the treatment of PTCL.
Design, Synthesis and Molecular Docking Studies of Novel Indole–Pyrimidine Hybrids as Tubulin Polymerization Inhibitors
Authors: Hu Meng‐Jin , Zhang Bei , Yang Hai‐Kui , Liu Yang , Chen Yu‐Rong , Ma Tian‐Zhu , Lu Ling , You Wen‐Wei , Zhao Pei‐Liang 
Published: July 2015

A series of novel hybrids of indole–pyrimidine‐containing piperazine moiety were designed, synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. The results indicated that most of these compounds possessed significant cytotoxic potency against four cancer cell lines, HT‐29, A549, MDA‐MB‐231 and MCF‐7. Particularly, the most promising compound 34 showed more potent and broad‐spectrum cytotoxic activities with the IC50 values ranged from 5.01 to 14.36 μm against A549, MDA‐MB‐231 and MCF‐7 cell lines. Meanwhile, 34 also displayed the most potent tubulin polymerization inhibitory activity with IC50 value of 11.2 μm. Furthermore, molecular docking analysis demonstrated 34 interacts and binds efficiently with the tubulin protein at the colchicine‐binding site. It was worth noting that the compound did not affect the normal human embryonic kidney cells, HEK‐293. These results suggest that this novel class of indole–pyrimidine hybrids may have potential to be developed as new a class of tubulin polymerization inhibitors.
Severe congenital malformations, family functioning and parents' separation/divorce: a longitudinal study
Authors: Brenner M. , Côté S. M. , Boivin M. , Tremblay R. E. 
Published: July 2015

AbstractBackgroundWe aim to explore the association of a severe congenital malformation (SCM) with postnatal family functioning and parents' separation/divorce and to examine if this association might be moderated by birth order of the child and parental level of education. SCM refers to malformations that, without medical intervention, cause handicap or death.MethodsUsing the Quebec Longitudinal Study of Child Development, an ongoing population‐based birth cohort study initiated in 1998, we compared 1675 families of children with and without a SCM to identify if having a child with a SCM was associated with maternal perception of family functioning. We examined if an SCM was associated with parents' separation and examined parents' education level and birth order of the children to evaluate whether these factors had any moderating effect on the results.ResultsThere were no significant differences in family functioning between families with and without a SCM child at 5 and 17 months. At 5 months, family functioning was significantly better (P = 0.03) for families with a SCM firstborn child than for families with a SCM child that is not firstborn. For parental separation, no significant differences were observed at 5 and 29 months and 4 years. No significant moderating effects were observed for birth order and parental education on parental separation.ConclusionsFamilies of children with a SCM do not appear to be at higher risk of family dysfunction within the first 17 months after birth nor of parental separation within the first 4 years after birth. Family functioning tends to be worst in families where the child with SCM is the second or subsequent child born.
Development of Inductive Generalization
Authors: Fisher Anna V. 
Published: July 2015

AbstractInductive generalization (i.e., making generalizations from instances) is ubiquitous in human cognition. In the developmental literature, researchers have proposed two theoretical accounts of this important process: a naïve theory account and a similarity‐based account. However, neither of these theoretical accounts explains marked developmental changes in inductive generalization with familiar categories that have been documented in prior research. In this article, I describe briefly a revised version of the similarity‐based account of inductive generalization that can explain individual variability as well as developmental change in inductive generalization with familiar categories. I also highlight several unresolved issues in the study of development of inductive generalization.
Oral mucosal lesions’ impact on oral health‐related quality of life in preschool children
Authors: de Oliveira Luísa Jardim Corrêa , Torriani Dione Dias , Correa Marcos Britto , Peres Marco Aurélio , Peres Karen Glazer , Matijasevich Alicia , dos Santos Iná da Silva , Barros Aluisio J.D. , Demarco Flávio Fernando , Tarquinio Sandra Beatriz Chaves 
Published: July 2015

AbstractObjectivesThe aim of this study was to assess the prevalence of oral mucosal lesions and their impact on oral health‐related quality of life (OHRQoL) in children aged 5 years.MethodsA sample of 1118 children from Pelotas’ birth cohort, born in 2004 (response rate of 85.8%), were selected to participate in the study. Data were collected using a questionnaire applied to mothers and from the oral examinations of the children. OML were identified by type, site, and size. Early Childhood Oral Health Impact Scale (ECOHIS) was used to assess caregivers’ perception on children's OHRQoL. Descriptive, bivariate, and multivariate Poisson regression analyses were carried out, considering the impact on OHRQoL (total ECOHIS score) as the outcome.ResultsThe prevalence of the OML was 30.1% (95% CI 27.5–32.9). Ulcers were the more prevalent type of lesion (29.4%), and the most affected site was the gums (31.0%). In bivariate analysis, there was a positive association between the presence of OML and OHRQoL impact measured by the following: mean overall score of ECOHIS (P < 0.001); extent (P < 0.001); prevalence (P = 0.030); and intensity (P = 0.010). After adjustments for sociodemographic and oral health variables, children with OML presented higher impact on OHRQoL [rate ratio (RR) 1.38 95% CI 1.11; 1.72] comparing with their counterparts. Analyzing specific domains, children with OML also presented higher impact on children symptoms (RR 1.46 95% CI 1.20; 1.66) and family functional (RR 3.14 95% CI 1.59; 6.22) domains.ConclusionAlmost one‐third of children presented with oral mucosal lesions, and these lesions impaired children's oral health‐related quality of life.
Pathogenesis of drug allergy – current concepts and recent insights
Authors: Schnyder B. , Brockow K. 
Published: July 2015

SummaryDrug hypersensitivity reactions (DHRs) may be caused by immunologic and non‐immunologic mechanisms. According to the World Allergy Organization, drug allergy (DA) encompasses the subgroup of immunologic DHRs which are mediated either by specific antibodies or specific T lymphocytes. Due to the immunologic memory, DA reactions bear an increased risk for dramatically enhanced reactions on re‐exposure. Some current concepts of DA were described decades ago. Drug allergies to soluble macromolecular protein drugs such as biopharmaceuticals are predominantly T cell‐dependent drug‐specific antibody responses leading to IgE‐or IgG‐mediated allergy. However, most drugs are too small to be directly recognized by specific B and T cells. Immune reactions to low‐molecular drugs have been explained by the hapten model: a hapten drug can bind covalently to soluble autologous proteins (e.g. serum albumin). Resulting compounds may then be recognized by matching B cell receptors (BCRs) and induce a specific T cell‐dependent IgE‐or IgG‐antibody production. Drug haptens may bind to extra‐ or intracellular proteins, which are processed and presented by various professional antigen‐presenting cells (APCs). Depending on the APC, they may induce not only specific antibody production, but also non‐immediate T cell‐mediated DA. More recently, a supplementary effector mechanism for non‐immediate DA to low‐molecular drugs has been described, namely the pharmacological interaction of native low‐molecular drugs with immune receptors (p‐i‐concept). Low‐molecular drugs may directly and reversibly attach to immune receptors. These non‐covalent interactions may modify the affinity between autologous major histocompatibility complex (MHC), presented peptides and specifically primed T cell receptors (TCRs) and thereby stimulate T cells. A special type of p‐i‐reaction has been recently described between the antiviral drug abacavir and the F pocket of HLA‐B*57:01. This interaction causes an alteration of the MHC‐presented self‐peptide repertoire and may consecutively lead to a kind of auto‐reactivity. Such types of reactions can explain the strong MHC‐HLA associations which have been found for some T cell‐mediated DHRs.
T regulatory cell phenotypes in peripheral blood and bronchoalveolar lavage from non‐asthmatic and asthmatic subjects
Authors: Baatjes A. J. , Smith S. G. , Watson R. , Howie K. , Murphy D. , Larché M. , Denburg J. A. , Inman M. D. , O'Byrne P. M. 
Published: July 2015

SummaryBackgroundAn unresolved issue in T regulatory cells' cell biology is the lack of consensus on phenotypic markers that accurately define the natural Treg (nTreg) population.ObjectivesTo examine nTreg frequency and functional capacity in healthy controls and their frequency in asthmatic subjects using three different phenotypic strategies. We hypothesized that phenotypically different nTreg are quantitatively and functionally different.MethodsThirty‐four healthy, non‐asthmatic and 17 asthmatic subjects were studied. Three nTreg phenotypes were defined as follows: nTreg1 (CD4+CD25+Foxp3+), nTreg2 (CD4+CD25+CD127lowFoxp3+), and nTreg3 (CD4+CD25highFoxp3+). The flow cytometric determination of nTreg frequency in peripheral blood (PB) and bronchoalveolar lavage (BAL) was performed using fluorescently labelled antibodies. Peripheral blood nTreg functional capacity was assessed using a CFSE‐based suppression assay.ResultsThere was a significantly lower frequency of PB nTreg3 compared to nTreg2 and nTreg1 (P < 0.05). Both nTreg2 and nTreg3 had a significantly greater suppressive capacity than nTreg1 at T responder (Tresp) to nTreg ratios of 16 : 1 up to 1 : 1 (P < 0.01). Asthmatics exhibited a significantly lower PB nTreg3 and nTreg1 frequency than healthy controls (P < 0.05). There were no differences between healthy controls and asthmatic subjects when comparing BAL nTreg frequency.Conclusions and Clinical RelevancePhenotypically different nTreg subsets are quantitatively and functionally different and are variably observed in asthma. The CD4+CD25highFoxp3+ phenotype was the least frequent, but demonstrated the greatest suppression, and was significantly lower in PB of asthmatic subjects. Consequently, it is imperative that nTreg phenotypes be clearly defined and that the interpretation of their frequency and function be phenotype specific.
Epstein–Barr virus-specific CD8+ T lymphocytes from diffuse large B cell lymphoma patients are functionally impaired
Authors: Cárdenas D , Vélez G , Orfao A , Herrera M V , Solano J , Olaya M , Uribe A M , Saavedra C , Duarte M , Rodríguez M , López M , Fiorentino S , Quijano S 
Published: July 2015

SummaryEpstein–Barr virus (EBV) is a persistent virus with oncogenic capacity that has been implicated in the development of aggressive B cell lymphomas, primarily in immunosuppressed individuals, although it can be present in immunocompetent individuals. Changes in the function and clonal diversity of T lymphocytes might be implied by viral persistence and lymphoma development. The aim of the present study was to evaluate the frequency, phenotype, function and clonotypical distribution of EBV-specific T cells after peripheral blood stimulation with a virus lysate in newly diagnosed patients with diffuse large B cell lymphoma (DLBCL) aged more than 50 years without prior histories of clinical immunosuppression compared with healthy controls. Our results showed impaired EBV-specific immune responses among DLBCL patients that were associated primarily with decreased numbers of central and effector memory CD8+ T lymphocytes. In contrast to healthy controls, only a minority of the patients showed CD4+/tumour necrosis factor (TNF)-α+ T cells expressing T cell receptor (TCR)-Vβ17 and CD8+/TNF-α+ T cells with TCR-Vβ5·2, Vβ9 and Vβ18 in response to EBV. Notably, the production of TNF-α was undetectable among TCR-Vβ5·3+, Vβ11+, Vβ12+, Vβ16+ and Vβ23+ CD8+ T cells. In addition, we observed decreased numbers of CD4+/TNF-α+ and CD8+/TNF-α+, CD8+/interleukin (IL)-2+ and CD8+/TNF-α+/IL-2+ T lymphocytes in the absence of T cells capable of producing TNF-α, IL-2 and IFN-γ after EBV stimulation simultaneously. Moreover, DLBCL patients displayed higher IL-10 levels both under baseline conditions and after EBV stimulation. These findings were also observed in patients with positive EBV viral loads. Prospective studies including a large number of patients are needed to confirm these findings.
Neuron–microglia interactions in neuroinflammation
Authors: Mizuno Tetsuya 
Published: July 2015

AbstractNeuron–microglia interactions play pivotal roles in the development and maintenance of the central nervous system. Microglia promote synaptic pruning in the developing brain and survey neuronal activity in the mature brain. Neurons regulate microglial function through the production of various cytokines and chemokines. In central nervous system diseases, including neurodegenerative diseases, demyelinating disease and brain ischemia, neuroinflammation induced by activated microglia contributes to the disruption of beneficial neuron–microglia interactions. Activated microglia exert neurotoxicity by producing pro‐inflammatory cytokines, glutamate and reactive oxygen species. Damaged neurons release soluble factors known as “eat me” signals, which enhance microglial phagocytosis and inflammatory response. However, damaged neurons also suppress microglial activation through the induction of anti‐inflammatory cytokines and chemokines, thereby reducing neuroinflammation. Here, the roles of neurons and microglia in neuroinflammation in Alzheimer's disease are reviewed.
Effects of 13 developmentally toxic chemicals on the migration of rat cephalic neural crest cells in vitro
Authors: Usami Makoto , Mitsunaga Katsuyoshi , Miyajima Atsuko , Takamatu Mina , Kazama Shugo , Irie Tomohiko , Doi Osamu , Takizawa Tatsuya 
Published: July 2015

AbstractThe inhibition of neural crest cell (NCC) migration has been considered as a possible pathogenic mechanism underlying chemical developmental toxicity. In this study, we examined the effects of 13 developmentally toxic chemicals on the migration of rat cephalic NCCs (cNCCs) by using a simple in vitro assay. cNCCs were cultured for 48 h as emigrants from rhombencephalic neural tubes explanted from rat embryos at day 10.5 of gestation. The chemicals were added to the culture medium at 24 h of culture. Migration of cNCCs was measured as the change in the radius (radius ratio) calculated from the circular spread of cNCCs between 24 and 48 h of culture. Of the chemicals examined, 13‐cis‐retinoic acid, ethanol, ibuprofen, lead acetate, salicylic acid, and selenate inhibited the migration of cNCCs at their embryotoxic concentrations; no effects were observed for acetaminophen, caffeine, indium, phenytoin, selenite, tributyltin, and valproic acid. In a cNCC proliferation assay, ethanol, ibuprofen, salicylic acid, selenate, and tributyltin inhibited cell proliferation, suggesting the contribution of the reduced cell number to the inhibited migration of cNCCs. It was determined that several developmentally toxic chemicals inhibited the migration of cNCCs, the effects of which were manifested as various craniofacial abnormalities.