bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epistatic Interaction between Genetic Variants in Susceptibility Gene ETS1 Correlates with IL‐17 Levels in SLE Patients
Authors: Zhang Jing , Zhang Yan , Zhang Lu , Yang Jing , Ying Dingge , Zeng Shuai , Lee Tsz Leung , Lau Chak Sing , Chan Tak Mao , Leung Alexander Moon Ho , Mok Chi Chiu , Wong Sik Nin , Lee Ka Wing , Ho Marco Hok Kung , Lee Pamela Pui Wah , Hon‐Yin Chung Brian , Chong Chun Yin , Wong Raymond Woon Sing , Mok Mo Yin , Wong Wilfred Hing Sang , Lau Yu Lung , Yang Wanling 
Published: April 2013

SummaryT‐helper cells that produce IL‐17 (Th17 cells) are a subset of CD4+ T‐cells with pathological roles in autoimmune diseases including systemic lupus erythematosus (SLE), and ETS1 is a negative regulator of Th17 cell differentiation. Our previous work on genome‐wide association study (GWAS) identified two variants in the ETS1 gene (rs10893872 and rs1128334) as being associated with SLE. However, like many other risk alleles for complex diseases, little is known on how these genetic variants might affect disease pathogenesis. In this study, we examined serum IL‐17 levels from 283 SLE cases and observed a significant correlation between risk variants in ETS1 and serum IL‐17 concentration in patients, which suggests a potential mechanistic link between these variants and the disease. Furthermore, we found that the two variants act synergistically in influencing IL‐17 production, with evidence of significant genetic interaction between them as well as higher correlation between the haplotype formed by the risk alleles and IL‐17 level in patient serum. In addition, the correlation between ETS1 variants and IL‐17 level seems to be more significant in SLE patients manifesting renal involvement, dsDNA autoantibody production or early‐onset.
Cytokine Patterns Differ Seasonally between Women with and without Uterine Leiomyomata
Authors: Wegienka Ganesa , Day Baird Donna , Cooper Tracy , Woodcroft Kimberley J. , Havstad Suzanne 
Published: April 2013

ProblemUterine leiomyomata are the most common reproductive tumor in women, and their cause is not known.Methods of StudyPlasma samples from 155 women (74 with and 81 without ultrasound‐confirmed leiomyoma) from a new study of leiomyoma risk factors in the Detroit, Michigan area, were examined for any cross‐sectional associations between commonly examined cytokines and leiomyoma presence.ResultsAssociations varied by season of sample collection defined a priori as winter (December–February) and non‐winter seasons. In the winter months, interleukin (IL)13 and IL17 were positively and IP10 was inversely associated with having a leiomyoma. In the non‐winter samples, VEGF, G‐CSF, and IP10 were positively associated and Monocyte chemotactic protein‐1, IL13, and IL17 were inversely associated with having a leiomyoma. Associations were not changed by adjustment for age or BMI.ConclusionsThese data suggest that new insight into leiomyoma formation may be acquired through investigation of the immune system.
Skin test concentrations for systemically administered drugs – anENDA/EAACIDrug Allergy Interest Group position paper
Authors: Brockow K. , Garvey L. H. , Aberer W. , Atanaskovic‐Markovic M. , Barbaud A. , Bilo M. B. , Bircher A. , Blanca M. , Bonadonna B. , Campi P. , Castro E. , Cernadas J. R. , Chiriac A. M. , Demoly P. , Grosber M. , Gooi J. , Lombardo C. , Mertes P. M. , Mosbech H. , Nasser S. , Pagani M. , Ring J. , Romano A. , Scherer K. , Schnyder B. , Testi S. , Torres M. , Trautmann A. , Terreehorst I. ,   The ENDA/EAACI Drug Allergy Interest Group
Published: April 2013

AbstractSkin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, theEuropeanNetwork andEuropeanAcademy ofAllergy andClinicalImmunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration inMEDLINEandEMBASE, reviewed and evaluated the literature in five languages using theGRADEsystem for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.
The pathophysiology of retinopathy of prematurity: an update of previous and recent knowledge
Authors: Cavallaro Giacomo , Filippi Luca , Bagnoli Paola , La Marca Giancarlo , Cristofori Gloria , Raffaeli Genny , Padrini Letizia , Araimo Gabriella , Fumagalli Monica , Groppo Michela , Dal Monte Massimo , Osnaghi Silvia , Fiorini Patrizio , Mosca Fabio 
Published: April 2013

Abstract.Retinopathy of prematurity (ROP) is a disease that can cause blindness in very low birthweight infants. The incidence of ROP is closely correlated with the weight and the gestational age at birth. Despite current therapies, ROP continues to be a highly debilitating disease. Our advancing knowledge of the pathogenesis of ROP has encouraged investigations into new antivasculogenic therapies. The purpose of this article is to review the findings on the pathophysiological mechanisms that contribute to the transition between the first and second phases of ROP and to investigate new potential therapies. Oxygen has been well characterized for the key role that it plays in retinal neoangiogenesis. Low or high levels of pO2 regulate the normal or abnormal production of hypoxia‐inducible factor 1 and vascular endothelial growth factors (VEGF), which are the predominant regulators of retinal angiogenesis. Although low oxygen saturation appears to reduce the risk of severe ROP when carefully controlled within the first few weeks of life, the optimal level of saturation still remains uncertain. IGF‐1 and Epo are fundamentally required during both phases of ROP, as alterations in their protein levels can modulate disease progression. Therefore, rhIGF‐1 and rhEpo were tested for their abilities to prevent the loss of vasculature during the first phase of ROP, whereas anti‐VEGF drugs were tested during the second phase. At present, previous hypotheses concerning ROP should be amended with new pathogenetic theories. Studies on the role of genetic components, nitric oxide, adenosine, apelin and β‐adrenergic receptor have revealed new possibilities for the treatment of ROP. The genetic hypothesis that single‐nucleotide polymorphisms within the β‐ARs play an active role in the pathogenesis of ROP suggests the concept of disease prevention using β‐blockers. In conclusion, all factors that can mediate the progression from the avascular to the proliferative phase might have significant implications for the further understanding and treatment of ROP.
Relationship between body condition score and ultrasound measurement of backfat thickness in multiparous Holstein dairy cows at different production phases
Authors: Hussein HA , Westphal A , Staufenbiel R 
Published: April 2013

BackgroundThe validity of the body condition score (BCS) for evaluating subcutaneous fat has been questioned because of its subjectivity. With the advent of ultrasonography, backfat thickness (BFT) can be objectively measured and used to assess the energy status of dairy cows in conjunction with BCS.ObjectiveDetermine the relationship between BCS and ultrasound measurements of BFT throughout the lactation cycle.MethodsCows (n = 1123) were selected randomly and classified according to their lactation stage into four different groups. BCS was determined using a 5‐point scale and BFT measurements were obtained using a 5‐MHz linear transducer.ResultsThe correlation coefficient (r) for the relationship between BCS and BFT varied according to the stage of lactation. There was a high correlation (r = 0.96–0.98) and relationship (r2 = 0.92–0.96) between BCS and BFT. The highest correlation was found at BFT values of 10–35 mm and BCS of 2–4.5 units.ConclusionBCS is a practical tool for evaluating body condition; furthermore, it may be as valid as BFT for the estimation of subcutaneous fat in Holstein dairy cows over time.
Fifty years of tree line change in the Khibiny Mountains, Russia: advantages of combined remote sensing and dendroecological approaches
Authors: Mathisen Ingrid E. , Mikheeva Anna , Tutubalina Olga V. , Aune Sigrun , Hofgaard Annika 
Published: April 2013

AbstractQuestionsTree line ecotone regions are expected to respond swiftly to climate changes. In this paper, remote sensing‐ and ground‐based tree population data are used to examine past and on‐going changes of the tree line ecotone in a sub‐arctic region characterized by precipitation increase. Questions addressed are: (1) at what rate has the tree line ecotone changed since the mid‐20th century; (2) can specific temporal dynamics be identified; and (3) do combined remote sensing and tree population analyses add essential knowledge for the interpretation of tree line changes?LocationKhibiny Mountains, Kola Peninsula, northwest Russia.MethodsAerial photos from 1958, high‐resolution satellite imagery from 2006/2008 and age structure data for dominant tree line species (birch and pine) were used to analyse rate of change and temporal and species‐specific tree line recruitment patterns. This was accomplished using digital elevation models, resolution‐merging procedures, visual interpretation and dendroecological methods.ResultsMean tree line advance for birch and pine was recorded as 29 and 27 altitudinal metres (0.6 and 0.5 m·yr−1), respectively. The advance was accompanied by an apparent infilling of pre‐established tree populations and by recruitment beyond the tree line. Evident increased recruitment occurred in the late 1980s for birch and in the 1970s and 1990s for pine. Establishment showed no strong correlations with climate variables, but the importance of non‐growing season variables was indicated.ConclusionsThe recorded tree line advance is modest compared to global model predictions for advance at high latitudes, but in accordance with results from a number of high‐latitude areas. Concomitantly, the apparent increased recruitment is indicative of a more rapidly advancing tree line zone. Studies combining remote sensing and ground‐based data minimize the risk of under‐ or overestimating potential tree line advance. Low detectability of small seedlings and saplings by remote sensing can cause underestimation of the current potential, while ground‐based data used alone can overestimate potential advance. A balance between the two approaches is beneficial and enhances quality in production of change scenarios related to high latitudinal tree line areas at local to large regional scales.
Carbohydrate as Fuel for Foraging, Resource Defense and Colony Growth – a Long‐term Experiment with the Plant‐ant Crematogaster nigriceps
Authors: Rudolph Kathleen P. , Palmer Todd M. 
Published: April 2013

AbstractMismatches in nutrient composition (e.g., protein, carbohydrates, lipids, etc.) between consumers and the resources they depend on can have ecological consequences, affecting traits from individual behavior to community structure. In many terrestrial ecosystems, ants depend on plant and insect mutualist partners for carbohydrate‐rich rewards that are nutritionally unbalanced (especially in protein) relative to colony needs. Despite imbalances, many carbohydrate‐feeding ant mutualists dominate communities—both competitively and numerically—raising the question of whether excess carbohydrates ‘fuel’ colony acquisition of limiting resources and growth. In a 10‐month field study, we manipulated carbohydrate access for the obligate plant‐ant Crematogaster nigriceps to test whether carbohydrate availability could be mechanistically linked to ecological dominance via heightened territory defense, increased protein foraging, and colony growth. Supplementation increased aggressive defense of hosts after only two weeks, but was also strongly linked to variation in rainfall. Contrary to predictions, we did not find that supplemented colonies increased protein foraging. Instead, colonies with reduced carbohydrate access discovered a greater proportion of protein baits, suggesting that carbohydrate deprivation increases foraging intensity. We found no significant effect of carbohydrate manipulation on brood or alate production. These results contrast with findings from several recent short‐term and lab‐based nutrient supplementation studies and highlight the role of seasonality and biotic context in colony‐foraging and reproductive decisions. These factors may be essential to understanding the consequences of carbohydrate access in natural plant‐ant systems.
Managing renal transplant ischemia reperfusion injury: novel therapies in the pipeline
Authors: Powell Jaclyn T. , Tsapepas Demetra S. , Martin Spencer T. , Hardy Mark A. , Ratner Lloyd E. 
Published: April 2013

AbstractIschemia reperfusion injury (IRI) is an early, non‐specific inflammatory response that follows perfusion of warm blood into a cold asanguinous organ following transplantation. The occurrence of IRI may have a pivotal impact on acute and long‐term renal allograft function. Initially, IRI contributes to delayed graft function (DGF), a term typically defined as the need for dialysis within one wk after renal transplantation. DGF frequently leads to prolonged hospital stay, increased healthcare costs, and potentially worse prognosis. Strategies to prevent IRI have so far been fairly limited, poorly defined, inadequately studied, and mostly anecdotal. The purpose of this review is to summarize the existing and novel therapies, which may mitigate IRI in renal transplantation. Agents currently in the pipeline include: Diannexin, which reduces endothelial cell injury by shielding phosphatidylserine; YSPSL, which mimics the binding portion of P‐selectin glycoprotein ligand‐1 to competitively inhibit translocation of P‐selectin and recruitment of polymorphonuclear leukocytes to the surface of endothelial cells; and I5NP, a synthetic small interfering ribonucleic acid that results in the inhibition of p53 expression. These agents represent an exciting frontier in transplant pharmacotherapy; they are in various phases of investigation and may have broader benefits in reducing complications of DGF.
Infrared laser‐induced gene expression in targeted single cells of Caenorhabditis elegans
Authors: Suzuki Motoshi , Toyoda Naoya , Shimojou Masaki , Takagi Shin 
Published: April 2013

Since the dawn of transgenic technology some 40 years ago, biologists have sought ways to manipulate, at their discretion, the expression of particular genes of interest in living organisms. The infrared laser‐evoked gene operator (IR‐LEGO) is a recently developed system for inducing gene expression in living organisms in a targeted fashion. It exploits the highly efficient capacity of an infrared laser for heating cells, to provide a high level of gene expression driven by heat‐inducible promoters. By irradiating living specimens with a laser under a microscope, heat shock responses can be induced in individual cells, thereby inducing a particular gene, under the control of a heat shock promoter, in specifically targeted cells. In this review we first summarize previous attempts to drive transgene expression in organisms by using heat shock promoters, and then introduce the basic principle of the IR‐LEGO system, and its applications.
Hyperglycaemia promotes cerebral barrier dysfunction through activation of protein kinase C‐β
Authors: Shao B. , Bayraktutan U. 
Published: April 2013

AimTo examine whether protein kinase C (PKC) and associated downstream mechanisms are involved in hyperglycaemia (HG)‐evoked blood–brain barrier (BBB) damage.MethodsThe activities of total PKC (Peptag assay), NADPH oxidase (lucigenin assay) and matrix metalloproteinase‐2 (MMP‐2; gelatin zymography) were measured in human brain microvascular endothelial cells (HBMEC) exposed to normoglycaemia (5.5 mM) or HG (25 mM) using the specific assays indicated in parentheses. The integrity and function of the in vitro models of human BBB were assessed by measurements of transendothelial electrical resistance and paracellular flux of permeability markers, respectively. Occludin protein expression was studied by immunoblotting.ResultsHG significantly compromised the BBB integrity and enhanced total PKC activity to which increases in PKC‐β and PKC‐βII isoforms contributed the most. Elevations in NADPH oxidase and MMP‐2 activities and decreases in occludin levels contributed to barrier dysfunction. Selective inhibition of PKC‐β isoform prevented the changes observed in occludin expression and the aforementioned enzyme activities and thus effectively preserved barrier integrity. Similarly, apocynin, a specific NADPH oxidase inhibitor, also effectively neutralized the effects of HG on barrier integrity, MMP‐2 activity, occludin expression and PKC‐β activity.ConclusionHG promotes cerebral‐barrier dysfunction through activation of PKC‐β and consequent stimulations of oxidative stress and tight junction dissolution.
Impact of treated/untreated traumatic dental injuries on quality of life among Brazilian schoolchildren
Authors: Ramos‐Jorge Joana , Paiva Saul M. , Tataounoff Juliana , Pordeus Isabela A. , Marques Leandro S. , Ramos‐Jorge Maria L. 
Published: April 2013

AbstractBackground/AimThe joint evaluation of oral health‐related quality of life and traumatic dental injury (TDI) is an important tool for setting priorities in public oral health programs. The purpose of the present study was to compare the impact of treated TDI, untreated TDI, and absence of TDI on the quality of life of schoolchildren aged 11–14 years.Material and methodsA cross‐sectional study was carried out with 668 schoolchildren from the city of Diamantina, Brazil. The clinical examination involved the determination of the presence and type of TDI based on the criteria proposed by O'Brien. Malocclusion was evaluated using the criteria of the Dental Aesthetic Index, and dental caries was diagnosed using the DMFT/dmft index. The impact of TDI on quality of life was assessed using the Child Oral Impact on Daily Performances (Child‐OIDP). The outcome was the absence (Child‐OIDP = 0) or presence (Child‐OIDP ≥ 1) of impact on quality of life.ResultsThe prevalence of TDI was 34.3%. Schoolchildren with untreated TDI experienced a greater impact on eating (P = 0.016) and smiling (P < 0.001) in comparison with those without TDI. No significant differences were found in the Child‐OIDP score between schoolchildren with treated TDI and those without trauma. The unadjusted and adjusted results of the Poisson regression analysis of the Child‐OIDP demonstrated that schoolchildren with untreated TDI were more likely to experience an impact on ‘eating and enjoying food’, ‘smiling and showing teeth’, and ‘overall score’.ConclusionsUntreated TDI was associated with a negative impact on the quality of life of schoolchildren, whereas treated TDI and absence of TDI were not associated with impact on quality of life.
Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy
Authors: Ma Yunyong , Ramachandran Anu , Ford Naomi , Parada Isabel , Prince David A. 
Published: April 2013

SummaryPurposeTo determine whether developmental synaptic pruning defects in epileptic C1q‐knockout (KO) mice are accompanied by postsynaptic abnormalities in dendrites and/or spines.MethodsImmunofluorescence staining was performed on biocytin‐filled layer Vb pyramidal neurons in sensorimotor cortex. Basal dendritic arbors and their spines were reconstructed with NEUROLUCIDA software, and their morphologic characteristics were quantitated in Neuroexplorer.Key FindingsSeven to nine completely filled pyramidal neurons were analyzed from the wild‐type (WT) and C1q KO groups. Compared to WT controls, KO mice showed significant structural modifications in their basal dendrites including (1) higher density of dendritic spines (0.60 ± 0.03/μm vs. 0.49 ± 0.03/μm dendritic length in WT, p < 0.05); (2) remarkably increased occurrence of thin spines (0.26 ± 0.02/μm vs. 0.14 ± 0.02/μm dendritic length in control, p < 0.01); (3) longer dendritic length (2,680 ± 159 μm vs. 2,119 ± 108 μm in control); and (4) increased branching (22.6 ± 1.9 vs. 16.2 ± 1.3 in WT at 80 μm from soma center, p < 0.05; 12.4 ± 1.4 vs. 8.2 ± 0.6 in WT at 120 μm from soma center, respectively, p < 0.05). Dual immunolabeling demonstrated the expression of putative glutamate receptor 2 (GluR2) on some thin spines. These dendritic alterations are likely postsynaptic structural consequences of failure of synaptic pruning in the C1q KO mice.SignificanceFailure to prune excessive excitatory synapses in C1q KO mice is a likely mechanism underlying abnormalities in postsynaptic dendrites, including increased branching and alterations in spine type and density. It is also possible that seizure activity contributes to these abnormalities. These structural abnormalities, together with increased numbers of excitatory synapses, likely contribute to epileptogenesis in C1q KO mice.
The Last Bite of the BITs—Supremacy of EU Law versus Investment Treaty Arbitration
Authors: Miron Smaranda 
Published: April 2013

AbstractAccording to Article 267 TFEU, national courts of the EU Member States can (and sometimes must) ask for a preliminary ruling from the Court of Justice on the interpretation and application of Community law, including international treaties and recommendations, and on the validity of Community secondary legislation. In this way, it is ensured that EU citizens are treated equally throughout the Union. However, this is not applicable when it comes to arbitral proceedings, be they commercial or investment arbitrations. The Court does not accept references for preliminary rulings from arbitral tribunals. For this reason, respondent states in international arbitral proceedings have argued that arbitration and EU law are utterly incompatible. In their submissions as respondents in arbitral proceedings, EU Member States have argued that, as a result of EU accession, bilateral investment treaties (BITs) have been automatically terminated. In subsidiary, they sometimes claim that, due to their incompatibility with EU law, BITs cannot apply. But if BITs are not applicable anymore, there are few remedies left for investors within the EU.