University of Strathclyde at TREC HARD

The motivation behind the University of Strathclyde's approach to this years HARD track was inspired from previous experiences by other participants, in particular research by [1], [3] and [4]. A running theme throughout these papers was the underlying hypothesis that a user's familiarity in a topic (i.e. their previous experience searching a subject), will form the basis for what type or style of document they will perceive as relevant. In other words, the user's context with regards to their previous search experience will determine what type of document(s) they wish to retrieve

Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation

Adenosine kinase (ADK) is considered to be the key regulator of the brain's endogenous anticonvulsant, adenosine. In adult brain, ADK is primarily expressed in a subpopulation of astrocytes and striking upregulation of ADK in these cells has been associated with astrogliosis after kainic acid-induced status epilepticus (KASE) in the kainic acid mouse model of temporal lobe epilepsy. To investigate the causal relationship between KASE-induced astrogliosis, upregulation of ADK and seizure activity, we have developed a novel mouse model [the Adktm1−/−-Tg(UbiAdk) mouse] lacking the endogenous astrocytic enzyme due to a targeted disruption of the endogenous gene, but containing an Adk transgene under the control of a human ubiquitin promoter. Mutant Adktm1−/−-Tg(UbiAdk) mice were characterized by increased brain ADK activity and constitutive overexpression of transgenic ADK throughout the brain, with particularly high levels in hippocampal pyramidal neurons. This ADK overexpression was associated with increased baseline levels of locomotion. Most importantly, two-thirds of the mutant mice analysed exhibited spontaneous seizure activity in the hippocampus and cortex. This was the direct consequence of transgene expression, since this seizure activity could be prevented by systemic application of the ADK inhibitor 5-iodotubercidin. Intrahippocampal injection of kainate in the mutant mice resulted in astrogliosis to the same extent as that observed in wild-type mice despite the absence of endogenous astrocytic ADK. Therefore, KASE-induced upregulation of endogenous ADK in wild-type mice is a consequence of astrogliosis. However, seizures in kainic acid-injected mutants displayed increased intra-ictal spike frequency compared with wild-type mice, indicating that, once epilepsy is established, increased levels of ADK aggravate seizure severity. We therefore conclude that therapeutic strategies that augment the adenosine system after astrogliosis-induced upregulation of ADK constitute a neurochemical rationale for the prevention of seizures in epileps

Produção de Tifton 85 no primeiro ciclo de pastejo em área irrigada e de sequeiro: 2012/2013.

Salão do conhecimento

Spatial Distribution of Dung in Integrated Dairy Systems

Animals in grazing work as catalyst in the nutrient cycling processes of the ecosystems. Part of biomass that animal intake returning to soil in the degraded way like faeces and urine. The return is around 90% of the mineral nutrients, including nitrogen. However, it is necessary to know how these dejects are distributed on the area by animals. The environment management affects directly spatial distribution of these dejects. Drinking fountain, salt and feed trough, portress, rest area and shadow are structures that change the way that animal graze. Sward structure and herbage morphology affect the grazing behaviour as well. So, the objective this experiment was evaluate the spatial distribution of dung from dairy heifers in integrated systems of production at Mato Grosso, Brazil. The experiment was accomplished at Embrapa (Sinop/Mato Grosso/ Brazil). The experimental area was 10 ha divided in three systems: full sun, marginal shadowing (300 trees per ha) and intensive shadowing (750 trees per ha). Each system had different sizes, but 2.4 ha was useful area for all systems divided in 10 paddocks each. The tree used was Eucalyptus urograndis, H13 clone and the pasture was piata Grass (Urochloa brizantha). The grazing was done when the sward reached 95% light interception. It was evaluated a group of 24 breed heifers with 350 kg in three periods of year. Each paddock was divided in 25 grids for count of faeces boards. The spatial faeces distribution was evaluated with GPS, by walking and capturing points where there was faeces boards in all steps for the grassland paddocks, in three periods of year (rainy, rainy-drought transition and dry period). The dataset was analysed by SAS 9.2 version, using PROC MIXED and PDIFF to 5% of significance. The spatial distribution of dung had significant difference only in rainy-drought transition period (P=0.0165) and interaction effect between shadowing and site (P=0.0025) in this period of year and dry period as well (P=0. 0465). In both periods, the distribution was the same. The full sun system promoted more concentration of faeces boards in sites next portress and border fence in site opposite to portress. In marginal shadowing system, the major concentration was in the central area and under shadow. In intensive shadowing system, the major concentration of dung boards was under shadow, sites preferred by heifers for rumination and leisure activities. The kind of shade and the year periods affected in spatial dung distribution. There were places with more dung concentration, in all kind of shade, but when the pasture had the intensive shade, the dispersion was more homogeneous. Unlike expected, the dung deposition didn?t happens only under treetops. The distribution is more homogeneous when trees are in large quantities. The shadow area available in the grassland affected the spatial dung distribution, and can be more homogeneous than no shadow

HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning.

White adipose tissue (WAT) can undergo a phenotypic switch, known as browning, in response to environmental stimuli such as cold. Post-translational modifications of histones have been shown to regulate cellular energy metabolism, but their role in white adipose tissue physiology remains incompletely understood. Here we show that histone deacetylase 3 (HDAC3) regulates WAT metabolism and function. Selective ablation of Hdac3 in fat switches the metabolic signature of WAT by activating a futile cycle of de novo fatty acid synthesis and β-oxidation that potentiates WAT oxidative capacity and ultimately supports browning. Specific ablation of Hdac3 in adipose tissue increases acetylation of enhancers in Pparg and Ucp1 genes, and of putative regulatory regions of the Ppara gene. Our results unveil HDAC3 as a regulator of WAT physiology, which acts as a molecular brake that inhibits fatty acid metabolism and WAT browning.Histone deacetylases, such as HDAC3, have been shown to alter cellular metabolism in various tissues. Here the authors show that HDAC3 regulates WAT metabolism by activating a futile cycle of fatty acid synthesis and oxidation, which supports WAT browning

Age-related changes in bile acid synthesis and hepatic nuclear receptor expression

BACKGROUND:Recent data highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme of bile acid synthesis, cholesterol 7alpha-hydroxylase, in cellular and animal models. This study was designed to analyze the effects of age on cholesterol 7alpha-hydroxylase and related nuclear receptor expression in human livers.DESIGN:Surgical liver biopsies were obtained in 23 patients requiring operation on the gastrointestinal tract. mRNA levels of cholesterol 7alpha-hydroxylase and related nuclear receptors and co-activators were assayed by quantitative real-time RT-PCR. Serum levels of 7alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis, were assayed by gas-liquid chromatography:mass spectrometry.RESULTS:Ageing was inversely correlated with serum 7alpha-hydroxy-4-cholesten-3-one and with cholesterol 7alpha-hydroxylase mRNA levels (r = -0.44 and r = -0.45 on a semi-log scale, respectively, P < 0.05). Among different nuclear factors, cholesterol 7alpha-hydroxylase mRNA best correlated with hepatocyte nuclear factor-4 (r = 0.55 on a log scale, P < 0.05); hepatocyte nuclear factor-4 levels were also inversely correlated with age (r = -0.64 on a semi-log scale, P < 0.05). Age was inversely correlated with serum insulin-like growth factor-I levels, which were directly correlated with hepatocyte nuclear factor-4 and cholesterol 7alpha-hydroxylase expression. No suppressive effect of short heterodimer partner expression on cholesterol 7alpha-hydroxylase was observed.CONCLUSIONS:Ageing associates with reduced bile acid synthesis, possibly related to decreased hepatic expression of hepatocyte nuclear factor-4 and consequently of cholesterol 7alpha-hydroxylase. Age-related modifications of the growth hormone/insulin-like growth factor axis might play a role. These findings may help to elucidate the pathophysiology of age-related modifications of cholesterol metabolism

Ensemble Kalman filter versus ensemble smoother for assessing hydraulic conductivity via tracer test data assimilation

Abstract. Estimating the spatial variability of hydraulic conductivity K in natural aquifers is important for predicting the transport of dissolved compounds. Especially in the nonreactive case, the plume evolution is mainly controlled by the heterogeneity of K. At the local scale, the spatial distribution of K can be inferred by combining the Lagrangian formulation of the transport with a Kalman-filter-based technique and assimilating a sequence of time-lapse concentration C measurements, which, for example, can be evaluated on site through the application of a geophysical method. The objective of this work is to compare the ensemble Kalman filter (EnKF) and the ensemble smoother (ES) capabilities to retrieve the hydraulic conductivity spatial distribution in a groundwater flow and transport modeling framework. The application refers to a two-dimensional synthetic aquifer in which a tracer test is simulated. Moreover, since Kalman-filter-based methods are optimal only if each of the involved variables fit to a Gaussian probability density function (pdf) and since this condition may not be met by some of the flow and transport state variables, issues related to the non-Gaussianity of the variables are analyzed and different transformation of the pdfs are considered in order to evaluate their influence on the performance of the methods. The results show that the EnKF reproduces with good accuracy the hydraulic conductivity field, outperforming the ES regardless of the pdf of the concentrations

eRisk 2023: Depression, Pathological Gambling, and Eating Disorder Challenges

Presented at: 45th European Conference on Information Retrieval, ECIR 2023, Dublin, 2 April 2023 through 6 April 2023.This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/978-3-031-28241-6_67[Abstract]: In 2017, we launched eRisk as a CLEF Lab to encourage research on early risk detection on the Internet. Since then, thanks to the participants’ work, we have developed detection models and datasets for depression, anorexia, pathological gambling and self-harm. In 2023, it will be the seventh edition of the lab, where we will present a new type of task on sentence ranking for depression symptoms. This paper outlines the work that we have done to date, discusses key lessons learned in previous editions, and presents our plans for eRisk 2023.The first and second authors thank the financial support supplied by the Consellería de Cultura, Educación, Formación Profesional e Universidades (accreditation 2019–2022 ED431G/01, ED431B 2022/33) and the European Regional Development Fund, which acknowledges the CITIC Research Center in ICT of the University of A Coruña as a Research Center of the Galician University System. The third author thanks the financial support supplied by the Consellería de Cultura, Educación, Formación Profesional e Universidades (accreditation 2019–2022 ED431G-2019/04, ED431C 2022/19) and the European Regional Development Fund, which acknowledges the CiTIUS-Research Center in Intelligent Technologies of the University of Santiago de Compostela as a Research Center of the Galician University System. The first, second, and third author also thank the funding of project PLEC2021-007662 (MCIN/AEI/10.13039/501100011033, Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación, Plan de Recuperación, Transformación y Resiliencia, Unión Europea-Next Generation EU).Xunta de Galicia; ED431G/01Xunta de Galicia; ED431B 2022/33Xunta de Galicia; ED431G-2019/04Xunta de Galicia; ED431C 2022/1

Mitochondrial dysfunction increases fatty acid &#946;-oxidation and translates into impaired neuroblast maturation

The metabolic transition from anaerobic glycolysis and fatty acid \u3b2-oxidation to glycolysis coupled to oxidative phosphorylation is a key process for the transition of quiescent neural stem cells to proliferative neural progenitor cells. However, a full characterization of the metabolic shift and the involvement of mitochondria during the last step of neurogenesis, from neuroblasts to neuron maturation, is still elusive. Here, we describe a model of neuroblasts, Neuro2a cells, with impaired differentiation capacity due to mitochondrial dysfunction. Using a detailed biochemical characterization consisting of steady-state metabolomics and metabolic flux analysis, we find increased fatty acid \u3b2-oxidation as a peculiar feature of neuroblasts with altered mitochondria. The consequent metabolic switch favors neuroblast proliferation at the expense of neuron maturation

Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis

FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants. Longitudinal analysis showed persistent T cell lymphopenia during infancy, often associated with nail dystrophy. Adult individuals with heterozygous FOXN1 variants had in most cases normal CD4+ but lower than normal CD8+ cell counts. We hypothesized a FOXN1 gene dosage effect on the function of thymic epithelial cells (TECs) and thymopoiesis and postulated that these effects would be more prominent early in life. To test this hypothesis, we analyzed TEC subset frequency and phenotype, early thymic progenitor (ETP) cell count, and expression of FOXN1 target genes (Ccl25, Cxcl12, Dll4, Scf, Psmb11, Prss16, and Cd83) in Foxn1nu/+ (nu/+) mice and age-matched wild-type (+/+) littermate controls. Both the frequency and the absolute count of ETP were significantly reduced in nu/+ mice up to 3 weeks of age. Analysis of the TEC compartment showed reduced expression of FOXN1 target genes and delayed maturation of the medullary TEC compartment in nu/+ mice. These observations establish a FOXN1 gene dosage effect on thymic function and identify FOXN1 haploinsufficiency as an important genetic determinant of T cell lymphopenia at birth