Microarray gene expression profiling of neural tissues in bovine spastic paresis

Abstract: Background: Bovine Spastic Paresis (BSP) is a neuromuscular disorder which affects both male and female cattle. BSP is characterized by spastic contraction and overextension of the gastrocnemious muscle of one or both limbs and is associated with a scarce increase in body weight. This disease seems to be caused by an autosomal and recessive gene, with incomplete penetration, although no genes clearly involved with its onset have been so far identified. We employed cDNA microarrays to identify metabolic pathways affected by BSP in Romagnola cattle breed. Investigation of those pathways at the genome level can help to understand this disease. Results: Microarray analysis of control and affected individuals resulted in 268 differentially expressed genes. These genes were subjected to KEGG pathway functional clustering analysis, revealing that they are predominantly involved in Cell Communication, Signalling Molecules and Interaction and Signal Transduction, Diseases and Nervous System classes. Significantly enriched KEGG pathway's classes for the differentially expressed genes were calculated; interestingly, all those significantly under-expressed in the affected samples are included in Neurodegenerative Diseases. To identify genome locations possibly harbouring gene(s) involved in the disease, the chromosome distribution of the differentially expressed genes was also investigated. Conclusions: The cDNA microarray we used in this study contains a brain library and, even if carrying an incomplete transcriptome representation, it has proven to be a valuable tool allowing us to add useful and new information to a poorly studied disease. By using this tool, we examined nearly 15000 transcripts and analysed gene pathways affected by the disease. Particularly, our data suggest also a defective glycinergic synaptic transmission in the development of the disease and an alteration of calcium signalling proteins. We provide data to acquire knowledge of a genetic disease for which literature still presents poor results and that could be further and specifically analysed in the next future. Moreover this study, performed in livestock, may also harbour molecular information useful for understanding human diseases

Ontology-based Domain Diversity Profiling of User Comments

Diversity has been the subject of study in various disciplines from biology to social science and computing. Respecting and utilising the diversity of the population is increasingly important to broadening knowledge. This paper describes a pipeline for diversity profiling of a pool of text in order to understand its coverage of an underpinning domain. The application is illustrated by using a domain ontology on presentation skills in a case study with 38 postgraduates who made comments while learning pitch presentations with the Active Video Watching system (AVW-Space). The outcome shows different patterns of coverage on the domain by the comments in each of the eight videos

Integrality gaps of integer knapsack problems

We obtain optimal lower and upper bounds for the (additive) integrality gaps of integer knapsack problems. In a randomised setting, we show that the integrality gap of a “typical” knapsack problem is drastically smaller than the integrality gap that occurs in a worst case scenario

Seagrass can mitigate negative ocean acidification effects on calcifying algae

The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm structure and experimental assistance.info:eu-repo/semantics/publishedVersio

Influence of design and material characteristics on 3D printed flow-cells for heat transfer-based analytical devices

Redesigning 3D-printed flow cells is reported used for heat transfer based detection of biomolecules from a flow-through system to an addition-type measurement cell. The aim of this study is to assess the performance of this new measurement design and critically analyse the influence of material properties and 3D printing approach on thermal analysis. Particular attention is paid to reduce the time to stabilisation, the sample volume in order to make the technique suitable for clinical applications, and improving the sensitivity of the platform by decreasing the noise and interference of air bubbles. The three different approaches that were studied included a filament polylactic acid cell using only fused filament fabrication (FFF), a resin cell printed using stereolitography (SLA), and finally a design made of copper, which was manufactured by combining metal injection moulding (MIM) with fused filament fabrication (FFF). Computational fluid dynamic (CFD) modelling was undertaken using ANSYS Fluent V18.1 to provide insight into the flow of heat within the measurement cell, facilitating optimisation of the system and theoretical response speed. It was shown that the measurement cells using SLA had the lowest noise (~ 0.6%) and shortest measurement time (15 min), whereas measurement cells produced using other approaches had lower specificity or suffered from voiding issues. Finally, we assessed the potential of these new designs for detection of biomolecules and amoxicillin, a commonly used beta lactam antibiotic, to demonstrate the proof of concept. It can be concluded that the resin addition-type measurement cells produced with SLA are an interesting affordable alternative, which were able to detect amoxicillin with high sensitivity and have great promise for clinical applications due to the disposable nature of the measurement cells in addition to small sample volumes

Rapid electrochemical detection of levodopa using polyaniline-modified screen-printed electrodes for the improved management of Parkinson's disease

A portable test to rapidly determine levels of levodopa, the drug used to treat Parkinson's disease, can improve clinical management of the disease. In this study, screen-printed electrodes (SPEs) were modified with polymers to facilitate the electrochemical detection of levodopa. Cyclic voltammetry was used to deposit a thin layer of polyaniline on the electrode surface. Scanning electron microscopy revealed high surface coverage, which did not impact the electrode's conductivity. Differential pulse voltammetry measurements with the polyaniline-modified electrodes enabled the measurement of levodopa at physiologically relevant concentrations with discrimination between a common interferent (ascorbic acid) and a structurally similar compound (L-tyrosine). However, the use of the polymer layer did not permit differentiation between levodopa and dopamine; the only difference in these molecules is that levodopa has an amino acid moiety whereas dopamine has a free amine group. Density functional theory calculations demonstrated that aniline formed a hydrogen bond between the amino group of the monomer and the meta-hydroxyl group, which is present in both levodopa and dopamine, with similar binding energies (−53.36 vs −50.08 kJ mol−1). Thus, the polymer-functionalised SPEs are a valuable tool to measure compounds important in Parkinson's disease, but further refinement is needed to achieve selective detection

Early respiratory morbidity in a multicultural birth cohort: the Generation R Study

Ethnic disparities in the prevalence of asthma symptoms in children have been described. We evaluated to what extent the association between ethnic background and respiratory symptoms during the first 2 years of life could be explained by the mediating effect of risk factors for respiratory morbidity. The Generation R Study is a multiethnic, population-based birth cohort study. Pre and postnatal risk factors for respiratory morbidity were prospectively assessed by questionnaires. Information about ethnicity was available for 5,684 infants. The associations between ethnic background and lower respiratory symptoms at 12 and 24 months were evaluated with log-binomial regression models. Relative risks and 95 % confidence intervals (RR [95 % CI]) were computed for Cape Verdean, Moroccan, Antillean, Surinamese and Turkish ethnicity with Dutch ethnicity as the reference category. We found an increased risk of lower respiratory symptoms at 24 months in Antillean infants (1.32 [95 % CI 1.12–1.57]) that was mediated by early postnatal exposures (pets keeping, siblings, breastfeeding, daycare attendance, smoke exposure). Turkish infants also had an increased risk of lower respiratory symptoms at 12 and 24 months (1.14 [95 % CI 1.02–1.27] and 1.21 [95 % CI 1.07–1.38], respectively), partly explained by previous morbidity (eczema, infections and upper respiratory symptoms). There were no differences for Cape Verdean, Moroccan or Surinamese, as compared to Dutch infants. Hence, ethnic background was associated with respiratory symptoms during the first 2 years of life and this association was largely explained by mediating effects of known pre and postnatal risk factors for respiratory morbidity

Mitochondrial Changes in Ageing Caenorhabditis elegans – What Do We Learn from Superoxide Dismutase Knockouts?

One of the most popular damage accumulation theories of ageing is the mitochondrial free radical theory of ageing (mFRTA). The mFRTA proposes that ageing is due to the accumulation of unrepaired oxidative damage, in particular damage to mitochondrial DNA (mtDNA). Within the mFRTA, the “vicious cycle” theory further proposes that reactive oxygen species (ROS) promote mtDNA mutations, which then lead to a further increase in ROS production. Recently, data have been published on Caenorhabditis elegans mutants deficient in one or both forms of mitochondrial superoxide dismutase (SOD). Surprisingly, even double mutants, lacking both mitochondrial forms of SOD, show no reduction in lifespan. This has been interpreted as evidence against the mFRTA because it is assumed that these mutants suffer from significantly elevated oxidative damage to their mitochondria. Here, using a novel mtDNA damage assay in conjunction with related, well established damage and metabolic markers, we first investigate the age-dependent mitochondrial decline in a cohort of ageing wild-type nematodes, in particular testing the plausibility of the “vicious cycle” theory. We then apply the methods and insights gained from this investigation to a mutant strain for C. elegans that lacks both forms of mitochondrial SOD. While we show a clear age-dependent, linear increase in oxidative damage in WT nematodes, we find no evidence for autocatalytic damage amplification as proposed by the “vicious cycle” theory. Comparing the SOD mutants with wild-type animals, we further show that oxidative damage levels in the mtDNA of SOD mutants are not significantly different from those in wild-type animals, i.e. even the total loss of mitochondrial SOD did not significantly increase oxidative damage to mtDNA. Possible reasons for this unexpected result and some implications for the mFRTA are discussed

Stability in Ecosystem Functioning across a Climatic Threshold and Contrasting Forest Regimes

Classical ecological theory predicts that changes in the availability of essential resources such as nitrogen should lead to changes in plant community composition due to differences in species-specific nutrient requirements. What remains unknown, however, is the extent to which climate change will alter the relationship between plant communities and the nitrogen cycle. During intervals of climate change, do changes in nitrogen cycling lead to vegetation change or do changes in community composition alter the nitrogen dynamics? We used long-term ecological data to determine the role of nitrogen availability in changes of forest species composition under a rapidly changing climate during the early Holocene (16k to 8k cal. yrs. BP). A statistical computational analysis of ecological data spanning 8,000 years showed that secondary succession from a coniferous to deciduous forest occurred independently of changes in the nitrogen cycle. As oak replaced pine under a warming climate, nitrogen cycling rates increased. Interestingly, the mechanism by which the species interacted with nitrogen remained stable across this threshold change in climate and in the dominant tree species. This suggests that changes in tree population density over successional time scales are not driven by nitrogen availability. Thus, current models of forest succession that incorporate the effects of available nitrogen may be over-estimating tree population responses to changes in this resource, which may result in biased predictions of future forest dynamics under climate warming