The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates

Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinson's disease. The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinson's disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as L-glutamate could be involved in neurodegenerative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinson's disease

Zero modes of six-dimensional Abelian vortices

We analyze the fluctuations of Nielsen-Olesen vortices arising in the six-dimensional Abelian-Higgs model. The regular geometry generated by the defect breaks spontaneously six-dimensional Poincar\'e symmetry leading to a warped space-time with finite four-dimensional Planck mass. As a consequence, the zero mode of the spin two fluctuations of the geometry is always localized but the graviphoton fields, corresponding to spin one metric fluctuations, give rise to zero modes which are not localized either because of their behaviour at infinity or because of their behaviour near the core of the vortex. A similar situation occurs for spin zero fluctuations. Gauge field fluctuations exhibit a localized zero mode.Comment: 45 pages in Revtex style with 4 figure

Estimation of the solubility parameters of model plant surfaces and agrochemicals: a valuable tool for understanding plant surface interactions

Background Most aerial plant parts are covered with a hydrophobic lipid-rich cuticle, which is the interface between the plant organs and the surrounding environment. Plant surfaces may have a high degree of hydrophobicity because of the combined effects of surface chemistry and roughness. The physical and chemical complexity of the plant cuticle limits the development of models that explain its internal structure and interactions with surface-applied agrochemicals. In this article we introduce a thermodynamic method for estimating the solubilities of model plant surface constituents and relating them to the effects of agrochemicals. Results Following the van Krevelen and Hoftyzer method, we calculated the solubility parameters of three model plant species and eight compounds that differ in hydrophobicity and polarity. In addition, intact tissues were examined by scanning electron microscopy and the surface free energy, polarity, solubility parameter and work of adhesion of each were calculated from contact angle measurements of three liquids with different polarities. By comparing the affinities between plant surface constituents and agrochemicals derived from (a) theoretical calculations and (b) contact angle measurements we were able to distinguish the physical effect of surface roughness from the effect of the chemical nature of the epicuticular waxes. A solubility parameter model for plant surfaces is proposed on the basis of an increasing gradient from the cuticular surface towards the underlying cell wall. Conclusions The procedure enabled us to predict the interactions among agrochemicals, plant surfaces, and cuticular and cell wall components, and promises to be a useful tool for improving our understanding of biological surface interactions

D-Theory: Field Quantization by Dimensional Reduction of Discrete Variables

D-theory is an alternative non-perturbative approach to quantum field theory formulated in terms of discrete quantized variables instead of classical fields. Classical scalar fields are replaced by generalized quantum spins and classical gauge fields are replaced by quantum links. The classical fields of a d-dimensional quantum field theory reappear as low-energy effective degrees of freedom of the discrete variables, provided the (d+1)-dimensional D-theory is massless. When the extent of the extra Euclidean dimension becomes small in units of the correlation length, an ordinary d-dimensional quantum field theory emerges by dimensional reduction. The D-theory formulation of scalar field theories with various global symmetries and of gauge theories with various gauge groups is constructed explicitly and the mechanism of dimensional reduction is investigated.Comment: 30 pages, no figure

The legal and ethical framework governing Body Donation in Europe-1st update on current practice

Previously, we have reported on the legal and ethical aspects and current practice of body donation in several European countries, reflecting cultural and religious variations as well as different legal and constitutional frameworks. We have also established good practice in body donation. Here we shall further extend the legal and ethical frameworks in place and also focus on novelties in the law and different directives. Of particular interest are points that address the commercialization of human bodies and body parts and weaknesses in the legal directives. Therefore, it is important to define what is ethical and what needs to be considered unethical in body donation and the subsequent utilisation of human bodies for teaching and research.peer-reviewe

Letter to the editor - round table unites to tackle culture change in an effort to improve animal research reporting.

A round table discussion was held during the LAVA-ESLAV-ECLAM conference on Reproducibility of Animal Studies on the 25th of September 2017 in Edinburgh. The aim of the round table was to discuss how to enhance the rate at which the quality of reporting animal research can be improved. This signed statement acknowledges the efforts that participant organizations have made towards improving the reporting of animal studies and confirms an ongoing commitment to drive further improvements, calling upon both academics and laboratory animal veterinarians to help make this cultural change

The impact of chronic stress on the rat brain lipidome

Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits.Funding by Fundação para a Ciência e Tecnologia (PTDC/SAU-NMC/118971/2010) and by the North Region Operational Program (ON.2-O Novo Norte), under Quadro de Referência Estratégico Nacional (QREN) and through Fundo Europeu de Desenvolvimento Regional (FEDER). GDP is funded by NIH grants R01 NS056049 and P50 AG008702 (to Scott Small)

Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease

Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer’s disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins. We correlate this with the use of an in silico analysis tool VisANT to elucidate possible pathways through which the involvement of Keratin 9 may take place. We identify possible links with Dickkopf-1, a negative regulator of the wnt pathway, and propose that the abnormal expression of Keratin 9 in AD blood and cerebrospinal fluid may be a result of blood brain barrier dysregulation and disruption of the ubiquitin proteasome system. Our findings suggest that dysregulated Keratin 9 expression is a consequence of AD pathology but, as it interacts with a broad range of proteins, it may have other, as yet uncharacterized, downstream effects which could contribute to AD onset and progression

Occipital transcranial direct current stimulation in episodic migraine patients: effect on cerebral perfusion

Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic migraine patients and healthy controls and investigates the influence of anodal transcranial direct current stimulation (tDCS) over the occipital cortex. We included healthy adult controls and episodic migraineurs. After a 28-day baseline period and the baseline visit, migraine patients received daily active or sham anodal tDCS over the occipital lobe for 28 days. All participants underwent a MRI scan at baseline; migraineurs were also scanned shortly after the stimulation period and about five months later. At baseline, brain perfusion of migraine patients and controls differed in several areas; among the stimulated areas, perfusion was increased in the cuneus of healthy controls. At the first visit, the active tDCS group had an increased blood flow in regions processing visual stimuli and a decreased perfusion in other areas. Perfusion did not differ at the second follow-up visit. The lower perfusion level in migraineurs in the cuneus indicates a lower preactivation level. Anodal tDCS over the occipital cortex increases perfusion of several areas shortly after the stimulation period, but not 5 months later. An increase in the cortical preactivation level could mediate the transient reduction of the migraine frequency.Trial registration: NCT03237754 (registered at clincicaltrials.gov; full date of first trial registration: 03/08/2017)