bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone deacetylase 2 is decreased in peripheral blood pro‐inflammatory CD8+ T and NKT‐like lymphocytes following lung transplant
Authors: Hodge Greg , Hodge Sandra , Holmes‐Liew Chien‐Li , Reynolds Paul N. , Holmes Mark 
Published: November 2016

ABSTRACTBackground and objectiveImmunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro‐inflammatory cytokines in peripheral blood T and natural killer T (NKT)‐like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro‐inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown. We hypothesized decreased HDAC2 expression and increased HAT expression in pro‐inflammatory lymphocytes following lung transplant.MethodsBlood was collected from 18 stable lung transplant patients and 10 healthy age‐matched controls. Intracellular pro‐inflammatory cytokines and HAT/HDAC2 expression were determined in lymphocyte subsets following culture using flow cytometry.ResultsA loss of HDAC2 in cluster of differentiation (CD) 8+ T and NKT‐like cells in transplant patients compared with controls was noted (CD8+ T: 28 ± 10 (45 ± 10), CD8+NKT‐like: 30 ± 13 (54 ± 16) (mean ± SD transplant) (control)). Loss of HDAC2 was associated with an increased percentage of CD8+ T and NKT‐like cells expressing perforin, granzyme b, interferon gamma (IFN‐γ) and TNF‐α (no change in HAT expression in any lymphocyte subset). There was a negative correlation between loss of HDAC2 expression by CD8+ T cells with cumulative dose of prednisolone and time post‐transplant. Treatment with 10 mg/L theophylline + 1 µmol/L prednisolone or 2.5 ng/mL cyclosporine A synergistically upregulated HDAC2 and inhibited IFN‐γ and TNF‐α production by CD8+ T and NKT‐like lymphocytes.Conclusion
HDAC2 is decreased in CD8+ T and NKT‐like pro‐inflammatory lymphocytes following lung transplant. Treatment options that increase HDAC2 may improve graft survival.
Estimating the Cumulative Incidence Function of Dynamic Treatment Regimes
Authors: Yavuz Idil , Chng Yu , Wahed Abdus S. 
Published: November 2016

Summary
Recently personalized medicine and dynamic treatment regimes have drawn considerable attention. Dynamic treatment regimes are rules that govern the treatment of subjects depending on their intermediate responses or covariates. Two-stage randomization is a useful set-up to gather data for making inference on such regimes. Meanwhile, the number of clinical trials involving competing risk censoring has risen, where subjects in a study are exposed to more than one possible failure and the specific event of interest may not be observed because of competing events. We aim to compare several treatment regimes from a two-stage randomized trial on survival outcomes that are subject to competing risk censoring. The cumulative incidence function (CIF) has been widely used to quantify the cumulative probability of occurrence of the target event over time. However, if we use only the data from those subjects who have followed a specific treatment regime to estimate the CIF, the resulting estimator may be biased. Hence, we propose alternative non-parametric estimators for the CIF by using inverse probability weighting, and we provide inference procedures including procedures to compare the CIFs from two treatment regimes. We show the practicality and advantages of the proposed estimators through numerical studies.
Heterozoan carbonate deposition on a steep basement escarpment (Late Miocene, Almería, south‐east Spain)
Authors: Sola Fernando , Puga‐Bernabéu Ángel , Aguirre Julio , Braga Juan C. 
Published: November 2016

AbstractHeterozoan temperate‐water carbonates mixed with varying amounts of terrigenous grains and muddy matrix (Azagador limestone) accumulated on and at the toe of an inherited escarpment during the late Tortonian–early Messinian (late Miocene) at the western margin of the Almería–Níjar Basin in south‐east Spain. The escarpment was the eastern end of an uplifting antiform created by compressive folding of Triassic rocks of the Betic basement. Channelized coralline‐algal/bryozoan rudstone to coarse‐grained packstone, together with matrix‐supported conglomerate, are the dominant lithofacies in the higher outcrops, comprising the deposits on the slope. These sediments mainly fill small canyon‐shaped, half‐graben depressions formed by normal faults active before, during and after carbonate sedimentation. Roughly bedded and roughly laminated coralline‐algal/bryozoan rudstone to coarse‐grained packstone are the main lithofacies forming an apron of four small (kilometre‐scale) lobes at the toe of the south‐eastern side of the escarpment (Almería area). Channelized and roughly bedded coralline‐algal/bryozoan rudstone to coarse‐grained packstone, conglomerates, packstone and sandy silt accumulated in a small channel‐lobe system at the toe of the north‐eastern side of the escarpment (Las Balsas area). Carbonate particles and terrigenous grains were sourced from shallow‐water settings and displaced downslope by sediment density flows that preferentially followed the canyon‐shaped depressions. Roughly laminated rudstone to packstone formed by grain flows on the initially very steep slope, whereas the rest of the carbonate lithofacies were deposited by high‐density turbidite currents. The steep escarpment and related break‐in‐slope at the toe favoured hydraulic jumps and the subsequent deposition of coarse‐grained, low‐transport efficiency skeletal‐dominated sediment in the apron lobes. Accelerated uplift of the basement caused a relative sea‐level fall resulting in the formation of outer‐ramp carbonates on the apron lobes, which were in turn overlain by lower Messinian coral reefs. The Almería example is the first known ‘base of slope’ apron within temperate‐water carbonate systems.
Centre‐Periphery Conflict and Ideological Distance in Turkey
Authors: Röth Leonce , Kaiser André , Varol Çağan , Sadioğlu Uğur 
Published: November 2016

AbstractThis article integrates ideology into a game‐theoretical model of centre‐periphery bargains. Ideological differences between national and sub‐national elites constitute a major obstacle for the accommodation of autonomy claims. While reforms bringing about decentralization are often analysed systematically as well as through case studies, cases where, despite claims to autonomy, decentralization does not occur have been largely neglected by scholars of territorial politics. Turkey is such a ‘negative case’. We argue that ideological distance prevents national parties from accommodating peripheral authority claims. We test our expectation with a mixed‐methods approach that combines quantitative analysis of party positions with in‐depth qualitative analysis of party documents showing how the different ideological positions of national and Kurdish parties affect decentralization demand and national response in Turkey between 1987 and 2015. Our findings support the theoretical expectations, but also point to additional inferences. Whereas asymmetric authority demands have been widely ignored, symmetric local autonomy has become an important issue in territorial politics.
Soil organic carbon pools in ploughed and no‐till Alfisols of central Ohio
Authors: Nakajima T. , Shrestha R. K. , Jacinthe P.‐A. , Lal R. , Bilen S. , Dick W. 
Published: November 2016

AbstractNo‐till (NT) farming can restore the soil organic carbon (SOC) pool of agricultural soils, but the SOC pool size and retention rate can vary with soil type and duration of NT. Therefore, the objectives of this study were to determine the effects of NT and soil drainage characteristics on SOC accumulation across a series of NT fields on Alfisols in Ohio, USA. Sites under NT for 9 (NT9), 13 (NT13), 36 (NT36), 48 (NT48) and 49 (NT49) years were selected for the study. Soil was somewhat poorly drained at the NT48 site but moderately well drained at the other sites. The NT48 and NT49 on‐station sites were under continuous corn (Zea mays), while the other sites were farmers' fields in a corn–soybean (Glycine max) rotation. At each location, the SOC pool (0–30 cm) in the NT field was compared to that of an adjacent plough‐till (PT) and woodlot (WL). At the NT36, NT48 and NT49 sites, the retention rate of corn‐derived C was determined using stable C isotope (13C) techniques. In the 0‐ to 10‐cm soil layer, SOC concentration was significantly larger under NT than PT, but a tillage effect was rarely detected below that depth. Across sites, the SOC pool in that layer averaged 36.4, 20 and 40.8 Mg C/ha at the NT, PT and WL sites, respectively. For the 0‐ to 30‐cm layer, the SOC pool for NT (83.4 Mg C/ha) was still 57% greater than under PT. However, there was no consistent trend in the SOC pool with NT duration probably due to the legacy of past management practices and SOC content differences that may have existed among the study sites prior to their conversion to NT. The retention rate of corn‐derived C was 524, 263 and 203 kg C/ha/yr at the NT36, NT48 and NT49 sites. In contrast, the retention rate of corn‐C under PT averaged 25 and 153 kg C/ha/yr at the NT49 (moderately well‐drained) and NT48 (somewhat poorly drained) sites, respectively. The conversion from PT to NT resulted in greater retention of corn‐derived C. Thus, adoption of NT would be beneficial to SOC sequestration in agricultural soils of the region.
Natural variation for gene expression responses to abiotic stress in maize
Authors: Waters Amanda J. , Makarevitch Irina , Noshay Jaclyn , Burghardt Liana T. , Hirsch Candice N. , Hirsch Cory D. , Springer Nathan M. 
Published: November 2016

SummaryPlants respond to abiotic stress through a variety of physiological, biochemical, and transcriptional mechanisms. Many genes exhibit altered levels of expression in response to abiotic stress, which requires concerted action of both cis‐ and trans‐regulatory features. In order to study the variability in transcriptome response to abiotic stress, RNA sequencing was performed using 14‐day‐old maize seedlings of inbreds B73, Mo17, Oh43, PH207 and B37 under control, cold and heat conditions. Large numbers of genes that responded differentially to stress between parental inbred lines were identified. RNA sequencing was also performed on similar tissues of the F1 hybrids produced by crossing B73 and each of the three other inbred lines. By evaluating allele‐specific transcript abundance in the F1 hybrids, we were able to measure the abundance of cis‐ and trans‐regulatory variation between genotypes for both steady‐state and stress‐responsive expression differences. Although examples of trans‐regulatory variation were observed, cis‐regulatory variation was more common for both steady‐state and stress‐responsive expression differences. The genes with cis‐allelic variation for response to cold or heat stress provided an opportunity to study the basis for regulatory diversity.
Cover Image, Volume 14, Issue 4
Authors: Noguchi S. , Kumazaki M. , Mori T. , Baba K. , Okuda M. , Mizuno T. , Akao Y. 
Published: November 2016

The cover image, by Shunsuke Noguchi et al., is based on the Original Article Analysis of microRNA‐203 function in CREB/MITF/RAB27a pathway: comparison between canine and human melanoma cells, DOI: 10.1111/vco.12118.
image
Comparison of a rapid immunochromatographic assay with an immunofluorescent antibody test for detection of Leishmania infantum antibodies in dogs
Authors: Proverbio Daniela , Spada Eva , Perego Roberta , Baggiani Luciana , Bagnagatti De Giorgi Giada , Migliazzo Antonella , Vitale Fabrizio 
Published: November 2016

BackgroundIdentification of Leishmania infantum‐infected dogs is crucial for control of canine leishmaniosis. In particular, in areas where access to specialized laboratories is limited, the availability of reliable and rapid in‐clinic serologic tests may support immediate diagnosis in suspected cases and permit detection of asymptomatic canine carriers of L infantum infection.ObjectiveThe purpose of the study was to validate the immunochromatographic test (ICT) Anigen Rapid Leishmania Ab Test kit for detection of L infantum antibodies in naturally exposed dogs in comparison with the immunofluorescence antibody test (IFAT).MethodsSerum samples from 66 dogs, including 20 healthy control dogs and 46 dogs suspected or confirmed with canine leishmaniosis, were measured by both tests. Anti‐Leishmania IgG titers ≥ 1:40 by IFAT were considered positive. Kappa statistic with a 95% CI was calculated to evaluate agreement between the 2 testing methods, and sensitivity, specificity, and positive and negative likelihood ratio were calculated.ResultsAnti‐L infantum IgG antibodies were found in 35 of 66 samples using the IFAT test (titers 1:40–1:5120). Thirty‐one out of 66 samples tested positive with the qualitative ICT. Four IFAT‐positive (titers < 1:80) samples were ICT‐negative. The Kappa value of 0.853 demonstrated very good agreement between the 2 tests.ConclusionThe Anigen Rapid Leishmania Ab Test kit reliably identified canine sera with anti‐L infantum IgG antibody titers ≥ 1:40. The ICT requires neither special preparation of the serum nor specialized equipment and can be stored at ambient temperature. The test is applicable as a field test because it is easy to use and provides rapid results.
Epidermolysis bullosa simplex in sibling Eurasier dogs is caused by a PLEC non‐sense variant
Authors: Mauldin Elizabeth A. , Wang Ping , Olivry Thierry , Henthorn Paula S. , Casal Margret L. 
Published: November 2016

BackgroundPlectin, a large linker protein found in many tissues, acts to connect components of the cytoskeleton to each other. In the epidermis, plectin binds keratin intermediate filaments to hemidesmosomes. A deficiency of plectin in the skin leads to blister formation in the basal layer and the disease epidermolysis bullosa simplex (EBS).Hypothesis/ObjectivesTo describe a novel blistering disease that arose spontaneously in a litter of puppies.AnimalsTwo female and one male 20‐day‐old Eurasier puppies, from a litter of six, were presented for evaluation of failure to thrive and then euthanized due to poor prognosis. The puppies had ulcers on the lips, tongue, nasal planum, paw pads and abdomen.ResultsImmunolabelling on frozen skin for basement membrane proteins revealed patchy and weak to absent staining for plectin as compared with strong linear staining in normal dogs. Ultrastructurally, hemidesmosomes were irregularly shaped and had loss of distinction between inner and outer plaques. Pedigree analysis supported an autosomal recessive mode of inheritance. A premature stop codon was discovered in exon 27 of PLEC that resulted in the production of a severely truncated protein.ConclusionThe study describes the first documented spontaneous EBS associated with a PLEC variant in domestic animals.
Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing
Authors: Kuo Anderson H. , Li Cun , Li Jinqi , Huber Hillary F. , Nathanielsz Peter W. , Clarke Geoffrey D. 
Published: November 2016

Key points
Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short‐term and long‐term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental‐fetal development indicate a need for models in precocial species for translation to human development.
We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood.
Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls.
Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort.
Understanding early cardiac biomarkers of IUGR using non‐invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies.
AbstractExtensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years – human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two‐way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non‐human primate model. Further studies across the life span will determine progression of cardiac dysfunction.
Acute and chronic effects of noradrenergic enhancement on transcranial direct current stimulation‐induced neuroplasticity in humans
Authors: Kuo Hsiao‐I. , Paulus Walter , Batsikadze Giorgi , Jamil Asif , Kuo Min‐Fang , Nitsche Michael A. 
Published: November 2016

Key points
Chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) increased and prolonged the long‐term potentiation‐like plasticity induced by anodal transcranial direct current stimulation (tDCS) for over 24 h.
Chronic administration of RBX converted cathodal tDCS‐induced long‐term depression‐like plasticity into facilitation for 120 min.
Chronic noradrenergic activity enhancement on plasticity of the human brain might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases.
AbstractNoradrenaline affects cognition and motor learning processes via its impact on long‐term potentiation (LTP) and depression (LTD). We aimed to explore the impact of single dose and chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) on plasticity induced by transcranial direct current stimulation (tDCS) in healthy humans via a double‐blinded, placebo‐controlled, randomized crossover study. Sixteen healthy volunteers received placebo or single dose RBX (8 mg) before anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took RBX (8 mg day−1) consecutively for 21 days. During this period, two additional interventions were performed (RBX with anodal or cathodal tDCS), to explore the impact of chronic RBX treatment on plasticity. Plasticity was monitored by motor‐evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic administration of RBX increased and prolonged the LTP‐like plasticity induced by anodal tDCS for over 24 h. Chronic RBX significantly converted cathodal tDCS‐induced LTD‐like plasticity into facilitation, as compared to the single dose condition, for 120 min after stimulation. The results show a prominent impact of chronic noradrenergic enhancement on plasticity of the human brain that might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases.
Tonotopic action potential tuning of maturing auditory neurons through endogenous ATP
Authors: Jovanovic Saša , Radulovic Tamara , Coddou Claudio , Dietz Beatrice , Nerlich Jana , Stojilkovic Stanko S. , Rübsamen Rudolf , Milenkovic Ivan 
Published: November 2016

Key points
Following the genetically controlled formation of neuronal circuits, early firing activity guides the development of sensory maps in the auditory, visual and somatosensory system. However, it is not clear whether the activity of central auditory neurons is specifically regulated depending on the position within the sensory map.
In the ventral cochlear nucleus, the first central station along the auditory pathway, we describe a mechanism through which paracrine ATP signalling enhances firing in a cell‐specific and tonotopically‐determined manner.
Developmental down‐regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, suggesting a high‐to‐low frequency maturation pattern.
Facilitated action potential (AP) generation, measured as higher firing rate, shorter EPSP‐AP delay in vivo and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP.
The long lasting change in intrinsic neuronal excitability is mediated by the heteromeric P2X2/3 receptors.
AbstractSynaptic refinement and strengthening are activity‐dependent processes that establish orderly arranged cochleotopic maps throughout the central auditory system. The maturation of auditory brainstem circuits is guided by action potentials (APs) arising from the inner hair cells in the developing cochlea. The AP firing of developing central auditory neurons can be modulated by paracrine ATP signalling, as shown for the cochlear nucleus bushy cells and principal neurons in the medial nucleus of the trapezoid body. However, it is not clear whether neuronal activity may be specifically regulated with respect to the nuclear tonotopic position (i.e. sound frequency selectivity). Using slice recordings before hearing onset and in vivo recordings with iontophoretic drug applications after hearing onset, we show that cell‐specific purinergic modulation follows a precise tonotopic pattern in the ventral cochlear nucleus of developing gerbils. In high‐frequency regions, ATP responsiveness diminished before hearing onset. In low‐to‐mid frequency regions, ATP modulation persisted after hearing onset in a subset of low‐frequency bushy cells (characteristic frequency< 10 kHz). Down‐regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, thus suggesting a high‐to‐low frequency maturation pattern. Facilitated AP generation, measured as higher firing frequency, shorter EPSP‐AP delay in vivo, and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP. Finally, by combining recordings and pharmacology in vivo, in slices, and in human embryonic kidney 293 cells, it was shown that the long lasting change in intrinsic neuronal excitability is mediated by the P2X2/3R.