2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine

Gate-tuned normal and superconducting transport at the surface of a topological insulator

Three-dimensional topological insulators are characterized by the presence of a bandgap in their bulk and gapless Dirac fermions at their surfaces. New physical phenomena originating from the presence of the Dirac fermions are predicted to occur, and to be experimentally accessible via transport measurements in suitably designed electronic devices. Here we study transport through superconducting junctions fabricated on thin Bi2Se3 single crystals, equipped with a gate electrode. In the presence of perpendicular magnetic field B, sweeping the gate voltage enables us to observe the filling of the Dirac fermion Landau levels, whose character evolves continuously from electron- to hole-like. When B=0, a supercurrent appears, whose magnitude can be gate tuned, and is minimum at the charge neutrality point determined from the Landau level filling. Our results demonstrate how gated nano-electronic devices give control over normal and superconducting transport of Dirac fermions at an individual surface of a three-dimensional topological insulator.Comment: 28 pages, 5 figure

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2

ZNF804a was identified by a genome-wide association study (GWAS) in which a single nucleotide polymorphism (SNP rs1344706) in ZNF804a reached genome-wide statistical significance for association with a combined diagnosis of schizophrenia (SZ) and bipolar disorder. Although the molecular function of ZNF804a is unknown, the amino acid sequence is predicted to contain a C2H2-type zinc-finger domain and suggests ZNF804a plays a role in DNA binding and transcription. Here, we confirm that ZNF804a directly contributes to transcriptional control by regulating the expression of several SZ associated genes and directly interacts with chromatin proximal to the promoter regions of PRSS16 and COMT, the two genes we find upregulated by ZNF804a. Using immunochemistry we establish that ZNF804a is localized to the nucleus of rat neural progenitor cells in culture and in vivo. We demonstrate that expression of ZNF804a results in a significant increase in transcript levels of PRSS16 and COMT, relative to GFP transfected controls, and a statistically significant decrease in transcript levels of PDE4B and DRD2. Furthermore, we show using chromatin immunoprecipitation assays (ChIP) that both epitope-tagged and endogenous ZNF804a directly interacts with the promoter regions of PRSS16 and COMT, suggesting a direct upregulation of transcription by ZNF804a on the expression of these genes. These results are the first to confirm that ZNF804a regulates transcription levels of four SZ associated genes, and binds to chromatin proximal to promoters of two SZ genes. These results suggest a model where ZNF804a may modulate a transcriptional network of SZ associated genes

Microarray analysis of Foxa2 mutant mouse embryos reveals novel gene expression and inductive roles for the gastrula organizer and its derivatives

<p>Abstract</p> <p>Background</p> <p>The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. Despite its important role during development, there are still relatively few genes with specific expression in the organizer and its derivatives. Foxa2 is a forkhead transcription factor that is absolutely required for formation of the mammalian equivalent of the organizer, the node, the axial mesoderm and the definitive endoderm (DE). However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined.</p> <p>Results</p> <p>To identify genes specific to the Spemann/Mangold organizer, we performed a microarray-based screen that compared wild-type and <it>Foxa2 </it>mutant embryos at late gastrulation stage (E7.5). We could detect genes that were consistently down-regulated in replicate pools of mutant embryos versus wild-type, and these included a number of known node and DE markers. We selected 314 genes without previously published data at E7.5 and screened for expression by whole mount <it>in situ </it>hybridization. We identified 10 novel expression patterns in the node and 5 in the definitive endoderm. We also found significant reduction of markers expressed in secondary tissues that require interaction with the organizer and its derivatives, such as cardiac mesoderm, vasculature, primitive streak, and anterior neuroectoderm.</p> <p>Conclusion</p> <p>The genes identified in this screen represent novel Spemann/Mangold organizer genes as well as potential Foxa2 targets. Further investigation will be needed to define these genes as novel developmental regulatory factors involved in organizer formation and function. We have placed these genes in a Foxa2-dependent genetic regulatory network and we hypothesize how Foxa2 may regulate a molecular program of Spemann/Mangold organizer development. We have also shown how early loss of the organizer and its inductive properties in an otherwise normal embryo, impacts on the molecular profile of surrounding tissues.</p

Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

BACKGROUND: Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. METHODS AND FINDINGS: We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005-2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). CONCLUSIONS: The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Agronomic Management of Indigenous Mycorrhizas

Many of the advantages conferred to plants by arbuscular mycorrhiza (AM) are associated to the ability of AM plants to explore a greater volume of soil through the extraradical mycelium. Sieverding (1991) estimates that for each centimetre of colonized root there is an increase of 15 cm3 on the volume of soil explored, this value can increase to 200 cm3 depending on the circumstances. Due to the enhancement of the volume of soil explored and the ability of the extraradical mycelium to absorb and translocate nutrients to the plant, one of the most obvious and important advantages resulting from mycorrhization is the uptake of nutrients. Among of which the ones that have immobilized forms in soil, such as P, assume particular significance. Besides this, many other benefits are recognized for AM plants (Gupta et al, 2000): water stress alleviation (Augé, 2004; Cho et al, 2006), protection from root pathogens (Graham, 2001), tolerance to toxic heavy metals and phytoremediation (Audet and Charest, 2006; Göhre and Paszkowski, 2006), tolerance to adverse conditions such as very high or low temperature, high salinity (Sannazzaro et al, 2006), high or low pH (Yano and Takaki, 2005) or better performance during transplantation shock (Subhan et al, 1998). The extraradical hyphae also stabilize soil aggregates by both enmeshing soil particles (Miller e Jastrow, 1992) and producing a glycoprotein, golmalin, which may act as a glue-like substance to adhere soil particles together (Wright and Upadhyaya, 1998). Despite the ubiquous distribution of mycorrhizal fungi (Smith and Read, 2000) and only a relative specificity between host plants and fungal isolates (McGonigle and Fitter, 1990), the obligate nature of the symbiosis implies the establishment of a plant propagation system, either under greenhouse conditions or in vitro laboratory propagation. These techniques result in high inoculum production costs, which still remains a serious problem since they are not competitive with production costs of phosphorus fertilizer. Even if farmers understand the significance of sustainable agricultural systems, the reduction of phosphorus inputs by using AM fungal inocula alone cannot be justified except, perhaps, in the case of high value crops (Saioto and Marumoto, 2002). Nurseries, high income horticulture farmers and no-agricultural application such as rehabilitation of degraded or devegetated landscapes are examples of areas where the use of commercial inoculum is current. Another serious problem is quality of commercial available products concerning guarantee of phatogene free content, storage conditions, most effective application methods and what types to use. Besides the information provided by suppliers about its inoculum can be deceiving, as from the usually referred total counts, only a fraction may be effective for a particular plant or in specific soil conditions. Gianinazzi and Vosátka (2004) assume that progress should be made towards registration procedures that stimulate the development of the mycorrhizal industry. Some on-farm inoculum production and application methods have been studied, allowing farmers to produce locally adapted isolates and generate a taxonomically diverse inoculum (Mohandas et al, 2004; Douds et al, 2005). However the inocula produced this way are not readily processed for mechanical application to the fields, being an obstacle to the utilization in large scale agriculture, especially row crops, moreover it would represent an additional mechanical operation with the corresponding economic and soil compaction costs. It is well recognized that inoculation of AM fungi has a potential significance in not only sustainable crop production, but also environmental conservation. However, the status quo of inoculation is far from practical technology that can be widely used in the field. Together a further basic understanding of the biology and diversity of AM fungi is needed (Abbott at al, 1995; Saito and Marumoto, 2002). Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species introductions and the potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. Schwartz et al, (2006) recommend that a careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Agricultural practices such as crop rotation, tillage, weed control and fertilizer apllication all produce changes in the chemical, physical and biological soil variables and affect the ecological niches available for occupancy by the soil biota, influencing in different ways the symbiosis performance and consequently the inoculum development, shaping changes and upset balance of native populations. The molecular biology tools developed in the latest years have been very important for our perception of these changes, ensuing awareness of management choice implications in AM development. In this context, for extensive farming systems and regarding environmental and economic costs, the identification of agronomic management practices that allow controlled manipulation of the fungal community and capitalization of AM mutualistic effect making use of local inoculum, seem to be a wise option for mycorrhiza promotion and development of sustainable crop production

Mechanistic Basis of Branch-Site Selection in Filamentous Bacteria

Many filamentous organisms, such as fungi, grow by tip-extension and by forming new branches behind the tips. A similar growth mode occurs in filamentous bacteria, including the genus Streptomyces, although here our mechanistic understanding has been very limited. The Streptomyces protein DivIVA is a critical determinant of hyphal growth and localizes in foci at hyphal tips and sites of future branch development. However, how such foci form was previously unknown. Here, we show experimentally that DivIVA focus-formation involves a novel mechanism in which new DivIVA foci break off from existing tip-foci, bypassing the need for initial nucleation or de novo branch-site selection. We develop a mathematical model for DivIVA-dependent growth and branching, involving DivIVA focus-formation by tip-focus splitting, focus growth, and the initiation of new branches at a critical focus size. We quantitatively fit our model to the experimentally-measured tip-to-branch and branch-to-branch length distributions. The model predicts a particular bimodal tip-to-branch distribution results from tip-focus splitting, a prediction we confirm experimentally. Our work provides mechanistic understanding of a novel mode of hyphal growth regulation that may be widely employed

Recovery in Stroke Rehabilitation through the Rotation of Preferred Directions Induced by Bimanual Movements: A Computational Study

Stroke patients recover more effectively when they are rehabilitated with bimanual movement rather than with unimanual movement; however, it remains unclear why bimanual movement is more effective for stroke recovery. Using a computational model of stroke recovery, this study suggests that bimanual movement facilitates the reorganization of a damaged motor cortex because this movement induces rotations in the preferred directions (PDs) of motor cortex neurons. Although the tuning curves of these neurons differ during unimanual and bimanual movement, changes in PD, but not changes in modulation depth, facilitate such reorganization. In addition, this reorganization was facilitated only when encoding PDs are rotated, but decoding PDs are not rotated. Bimanual movement facilitates reorganization because this movement changes neural activities through inter-hemispheric inhibition without changing cortical-spinal-muscle connections. Furthermore, stronger inter-hemispheric inhibition between motor cortices results in more effective reorganization. Thus, this study suggests that bimanual movement is effective for stroke rehabilitation because this movement rotates the encoding PDs of motor cortex neurons