Comparative analysis of four medicinal floras: phylogenetic methods to identify cross-cultural patterns

Summary Four medicinal floras were compared using phylogenetic methods, to test whether there are shared patterns in medical plant use at the level of the whole medicinal floras, or for specific therapeutic applications. Checklists of the native plants and medicinal plants of Oman were compiled, and analyzed alongside existing checklists for Nepal, the Cape of South Africa and New Zealand. We reconstructed a plant phylogeny at generic level for Oman, and a new, more inclusive phylogeny to represent the genera found in all four local floras. Methods from community phylogenetics were used to identify clustering and overdispersion of the plants used. The impacts of using local or more inclusive phylogenies and different null model selections were explored. We found that Omani medicinal plant use emphasizes the same deep lineages of flowering plants as the other three medicinal floras, most strongly when comparing Omani and Nepalese medicinal plants. Drivers of this similarity might be floristic composition, opportunity for exchange of knowledge and shared beliefs in the causation of illness. Phylogenetic patterns among therapeutic applications are cross‐predictive within and between cultures, and must be interpreted with care since inappropriate use of null models can result in spurious similarity. High levels of cross‐predictivity suggest that targeting plants used for specific therapeutic applications to identify specific bioactives may have limited value. We outline the questions that might be addressed using a global phylogeny and medicinal plant checklists, suggest the best methods for future studies and propose how findings might be interpreted

Geostationary Coastal and Air Pollution Events (GeoCAPE) Wide Angle Spectrometer (WAS)

The GeoCAPE Wide Angle Spectrometer (WAS) Study was a revisit of the COEDI Study from 2012. The customer primary goals were to keep mass, volume and cost to a minimum while meeting the science objectives and maximizing flight opportunities by fitting on the largest number of GEO accommodations possible. Riding on a commercial GEO satellite minimizes total mission costs. For this study, it is desired to increase the coverage rate,km2min, while maintaining ground sample size, 375m, and spectral resolution, 0.4-0.5nm native resolution. To be able to do this, the IFOV was significantly increased, hence the wide angle moniker. The field of view for COEDI was +0.6 degrees or (2048) 375m ground pixels. The WAS Threshold (the IDL study baseline design) is +2.4 degrees IDL study baseline design) is +2.4 degrees

Removing situation descriptions from situational judgment test items: Does the impact differ for video-based versus text-based formats?

Recent research has shown that many text-based situational judgment test (SJT) items can be solved even when the situational descriptions in the item stems are not presented to test takers. This finding challenges the traditional view of SJTs as low-fidelity simulations that rely on 'situational' (context-dependent) judgment. However, media richness theory and construal level theory suggest that situation descriptions presented in a richer and more concrete format (video format) will reduce uncertainty about inherent requirements and facilitate the perception that the situation is taking place in the here and now. Therefore, we hypothesized that situational judgment would be more important in video situation descriptions than in text situation descriptions. We adapted a leadership SJT to realize a 3 (situation description in the item stem: video vs. text vs. none) x 2 (response format: video response options vs. text response options) between-subjects design (N = 279). Participants were randomly assigned to one of the six conditions. The removal of video-based situation descriptions in item stems led to an equivalent decrease in SJT scores as the removal of text-based situation descriptions in item stems (video-based version: Cohen's d = 0.535 vs. text-based version: Cohen's d = 0.531). SJT scores were also contingent on the presentation format of both situation descriptions and response options: The highest scores were observed when situation descriptions and response options were presented in the same format. Implications for SJT theory and research are discussed. Practitioner points The presentation format did not moderate the effect of omitting situation descriptions in SJTs - that is, the context dependency of SJT performance did not increase when the SJT was administered in a video-based rather than a text-based format. The elimination of situation descriptions in item stems had a medium effect on overall test scores: SJT scores were significant lower without situation descriptions in comparison to SJT scores with situation descriptions (video-based version: Cohen's d = 0.535 vs. text-based version: Cohen's d = 0.531). It is important to match the stimulus and response formats in SJTs

Striatal Dopamine Transmission Is Subtly Modified in Human A53Tα-Synuclein Overexpressing Mice

Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn), cause familial Parkinson's disease (PD). Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA) signalling. In addition A53Tα-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53Tα-syn, and explored whether A53Tα-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53Tα-syn overexpressors, and in particular showed slight deficiency when the confounding effects of striatal ACh acting at presynaptic nicotinic receptors (nAChRs) were antagonized. The re-release of DA was unmodified after single-pulse stimuli, but after prolonged stimulation trains, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-syn overexpression in mice causes subtle changes in the regulation of DA release in the striatum. While modest, these modifications may indicate or contribute to striatal dysfunction

Partial Loss of Ataxin-1 Function Contributes to Transcriptional Dysregulation in Spinocerebellar Ataxia Type 1 Pathogenesis

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a CAG repeat that encodes a polyglutamine tract in ATAXIN1 (ATXN1). Molecular and genetic data indicate that SCA1 is mainly caused by a gain-of-function mechanism. However, deletion of wild-type ATXN1 enhances SCA1 pathogenesis, whereas increased levels of an evolutionarily conserved paralog of ATXN1, Ataxin 1-Like, ameliorate it. These data suggest that a partial loss of ATXN1 function contributes to SCA1. To address this possibility, we set out to determine if the SCA1 disease model (Atxn1154Q/+ mice) and the loss of Atxn1 function model (Atxn1−/− mice) share molecular changes that could potentially contribute to SCA1 pathogenesis. To identify transcriptional changes that might result from loss of function of ATXN1 in SCA1, we performed gene expression microarray studies on cerebellar RNA from Atxn1−/− and Atxn1154Q/+ cerebella and uncovered shared gene expression changes. We further show that mild overexpression of Ataxin-1-Like rescues several of the molecular and behavioral defects in Atxn1−/− mice. These results support a model in which Ataxin 1-Like overexpression represses SCA1 pathogenesis by compensating for a partial loss of function of Atxn1. Altogether, these data provide evidence that partial loss of Atxn1 function contributes to SCA1 pathogenesis and raise the possibility that loss-of-function mechanisms contribute to other dominantly inherited neurodegenerative diseases

A53T-alpha-synuclein-overexpression in the mouse nigrostriatal pathway leads to early increase of 14-3-3 epsilon and late increase of GFAP

Parkinson’s disease (PD) is a neurodegenerative disorder frequent at old age characterized by atrophy of the nigrostriatal projection. Overexpression and A53T-mutation of the presynaptic, vesicle-associated chaperone alpha-synuclein are known to cause early-onset autosomal dominant PD. We previously generated mice with transgenic overexpression of human A53T-alpha-synuclein (A53T-SNCA) in dopaminergic substantia nigra neurons as a model of early PD. To elucidate the early and late effects of A53T-alpha-synuclein on the proteome of dopaminergic nerve terminals in the striatum, we now investigated expression profiles of young and old mice using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) and mass spectrometry. In total, 15 proteins were upregulated and 2 downregulated. Mice before the onset of motor anomalies showed an upregulation of the spot containing 14-3-3 proteins, in particular the epsilon isoform, as well as altered levels of chaperones, vesicle trafficking and bioenergetics proteins. In old mice, the persistent upregulation of 14-3-3 proteins was aggravated by an increase of glial fibrillary acidic protein (GFAP) suggesting astrogliosis due to initial neurodegeneration. Independent immunoblots corroborated GFAP upregulation and 14-3-3 upregulation for the epsilon isoform, and also detected significant eta and gamma changes. Only for 14-3-3 epsilon a corresponding mRNA increase was observed in midbrain, suggesting it is transcribed in dopaminergic perikarya and accumulates as protein in presynapses, together with A53T-SNCA. 14-3-3 proteins associate with alpha-synuclein in vitro and in pathognomonic Lewy bodies of PD brains. They act as chaperones in signaling, dopamine synthesis and stress response. Thus, their early dysregulation probably reflects a response to alpha-synuclein toxicity

α-Synuclein Expression Selectively Affects Tumorigenesis in Mice Modeling Parkinson's Disease

Alpha Synuclein (α-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson's disease (PD). α-Syn is primarily a neuronal protein, however, its expression is found in various tumors including ovarian, colorectal and melanoma tumors. It has been hypothesized that neurodegeneration may share common mechanisms with oncogenesis. We tested whether α-Syn expression affects tumorigenesis of three types of tumors. Specifically, B16 melanoma, E0771 mammary gland adenocarcinoma and D122 Lewis lung carcinoma. For this aim, we utilized transgenic mice expression the human A53T α-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T α-Syn mice. The effect on tumorigenesis was not detected in age-matched APP/PS1 mice, modeling Alzheimer's disease (AD), suggesting a specific effect for α-Syn- dependent neurodegeneration. Importantly, transgenic α-Syn expression was detected within the three tumor types. We further show uptake of exogenously added, purified α-Syn, by the cultured tumor cells. In accord, with the affected tumorigenesis in the young A53T α-Syn mice, over- expression of α-Syn in cultured B16 and E0771 cells enhanced proliferation, however, had no effect on the proliferation of D122 cells. Based on these results, we suggest that certain forms of α-Syn may selectively accelerate cellular mechanisms leading to cancer

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease

BACKGROUND: Parkinson’s disease (PD) is one of the most common causes of dementia and motor deficits in the elderly. PD is characterized by the abnormal accumulation of the synaptic protein alpha-synuclein (α-syn) and degeneration of dopaminergic neurons in substantia nigra, which leads to neurodegeneration and neuroinflammation. Currently, there are no disease modifying alternatives for PD; however, targeting neuroinflammation might be a viable option for reducing motor deficits and neurodegeneration. Lenalidomide is a thalidomide derivative designed for reduced toxicity and increased immunomodulatory properties. Lenalidomide has shown protective effects in an animal model of amyotrophic lateral sclerosis, and its mechanism of action involves modulation of cytokine production and inhibition of NF-κB signaling. METHODS: In order to assess the effect of lenalidomide in an animal model of PD, mThy1-α-syn transgenic mice were treated with lenalidomide or the parent molecule thalidomide at 100 mg/kg for 4 weeks. RESULTS: Lenalidomide reduced motor behavioral deficits and ameliorated dopaminergic fiber loss in the striatum. This protective action was accompanied by a reduction in microgliosis both in striatum and hippocampus. Central expression of pro-inflammatory cytokines was diminished in lenalidomide-treated transgenic animals, together with reduction in NF-κB activation. CONCLUSION: These results support the therapeutic potential of lenalidomide for reducing maladaptive neuroinflammation in PD and related neuropathologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0320-x) contains supplementary material, which is available to authorized users