Multiple roles for UV RESISTANCE LOCUS8 in regulating gene expression and metabolite accumulation in arabidopsis under solar ultraviolet radiation

Photomorphogenic responses triggered by low fluence rates of ultraviolet B radiation (UV-B; 280–315 nm) are mediated by the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8). Beyond our understanding of the molecular mechanisms of UV-B perception by UVR8, there is still limited information on how the UVR8 pathway functions under natural sunlight. Here, wild-type Arabidopsis (Arabidopsis thaliana) and the uvr8-2 mutant were used in an experiment outdoors where UV-A (315–400 nm) and UV-B irradiances were attenuated using plastic films. Gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation, and leaf metabolite signatures were analyzed. The results show that UVR8 is required for transcript accumulation of genes involved in UV protection, oxidative stress, hormone signal transduction, and defense against herbivores under solar UV. Under natural UV-A irradiance, UVR8 is likely to interact with UV-A/blue light signaling pathways to moderate UV-B-driven transcript and PDX1 accumulation. UVR8 both positively and negatively affects UV-A-regulated gene expression and metabolite accumulation but is required for the UV-B induction of phenolics. Moreover, UVR8-dependent UV-B acclimation during the early stages of plant development may enhance normal growth under long-term exposure to solar UV

Comparison of a high and a low intensity smoking cessation intervention in a dentistry setting in Sweden – a randomized trial

<p>Abstract</p> <p>Background</p> <p>Tobacco is still the number one life style risk factor for ill health and premature death and also one of the major contributors to oral problems and diseases. Dentistry may be a potential setting for several aspects of clinical public health interventions and there is a growing interest in several countries to develop tobacco cessation support in dentistry setting. The aim of the present study was to assess the relative effectiveness of a high intensity intervention compared with a low intensity intervention for smoking cessation support in a dental clinic setting.</p> <p>Methods</p> <p>300 smokers attending dental or general health care were randomly assigned to two arms and referred to the local dental clinic for smoking cessation support. One arm received support with low intensity treatment (LIT), whereas the other group was assigned to high intensity treatment (HIT) support. The main outcome measures included self-reported point prevalence and continuous abstinence (≥ 183 days) at the 12-month follow-up.</p> <p>Results</p> <p>Follow-up questionnaires were returned from 86% of the participants. People in the HIT-arm were twice as likely to report continuous abstinence compared with the LIT-arm (18% vs. 9%, p = 0.02). There was a difference (not significant) between the arms in point prevalence abstinence in favour of the HIT-protocol (23% vs. 16%). However, point prevalence cessation rates in the LIT-arm reporting additional support were relatively high (23%) compared with available data assessing abstinence in smokers trying to quit without professional support.</p> <p>Conclusion</p> <p>Screening for willingness to quit smoking within the health care system and offering smoking cessation support within dentistry may be an effective model for smoking cessation support in Sweden. The LIT approach is less expensive and time consuming and may be appropriate as a first treatment option, but should be integrated with other forms of available support in the community. The more extensive and expensive HIT-protocol should be offered to those who are unable to quit with the LIT approach in combination with other support.</p> <p>Trial Registration</p> <p>Trial registration number: NCT00670514</p

How does solar ultraviolet-B radiation improve drought tolerance of silver birch (Betula pendula Roth.) seedlings?

We hypothesized that solar ultraviolet (UV) radiation would protect silver birch seedlings from the detrimental effects of water stress through a coordinated suite of trait responses, including morphological acclimation, improved control of water loss through gas exchange and hydraulic sufficiency. To better understand how this synergetic interaction works, plants were grown in an experiment under nine treatment combinations attenuating ultraviolet-A and ultraviolet-B (UVB) from solar radiation together with differential watering to create water-deficit conditions. In seedlings under water deficit, UV attenuation reduced height growth, leaf production and leaf length compared with seedlings receiving the full spectrum of solar radiation, whereas the growth and morphology of well-watered seedlings was largely unaffected by UV attenuation. There was an interactive effect of the treatment combination on water relations, which was more apparent as a change in the water potential at which leaves wilted or plants died than through differences in gas exchange. This suggests that changes occur in the cell wall elastic modulus or accumulation of osmolites in cells under UVB. Overall, the strong negative effects of water deficit are partially ameliorated by solar UV radiation, whereas well-watered silver birch seedlings are slightly disadvantaged by the solar UV radiation they receive. We hypothesized that solar ultraviolet (UV) radiation would protect silver birch seedlings from the detrimental effects of water stress. Plants were grown under nine combinations of solar UV treatments and water deficit conditions. In seedlings under water deficit, UV attenuation reduced growth compared with seedlings receiving the full spectrum of solar radiation; whereas the growth and morphology of well-watered seedlings was largely unaffected by UV attenuation. There was an interactive effect of the treatment combination on water relations, which was more apparent as a change in the water potential at which leaves wilted or plants died than through differences in gas exchange.Peer reviewe

Gene Expression Alterations in the Cerebellum and Granule Neurons of Cstb(-/-) Mouse Are Associated with Early Synaptic Changes and Inflammation

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Cystatin B: mutation detection, alternative splicing and expression in progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients

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Brain inflammation is accompanied by peripheral inflammation in Cstb(-/-) mice, a model for progressive myoclonus epilepsy

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb(-/-)) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb(-/-) mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb(-/-) mice and higher CXCL13 expression in activated microglia in Cstb(-/-) compared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstb(-/-) mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb(-/-)mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.Peer reviewe

Gene-Expression Profiling Suggests Impaired Signaling via the Interferon Pathway in Cstb(-/-) Microglia

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1, OMIM254800) is an autosomal recessive neurodegenerative disorder characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic epileptic seizures, and ataxia. Loss-of-function mutations in the gene encoding the cysteine protease inhibitor cystatin B (CSTB) underlie EPM1. The deficiency of CSTB in mice (Cstb(-/-) mice) generates a phenotype resembling the symptoms of EPM1 patients and is accompanied by microglial activation at two weeks of age and an upregulation of immune system-associated genes in the cerebellum at one month of age. To shed light on molecular pathways and processes linked to CSTB deficiency in microglia we characterized the transcriptome of cultured Cstb(-/-) mouse microglia using microarray hybridization and RNA sequencing (RNA-seq). The gene expression profiles obtained with these two techniques were in good accordance and not polarized to either pro- or anti-inflammatory status. In Cstb(-/-) microglia, altogether 184 genes were differentially expressed. Of these, 33 genes were identified by both methods. Several interferon-regulated genes were weaker expressed in Cstb(-/-) microglia compared to control. This was confirmed by quantitative real-time PCR of the transcripts Irf7 and Stat1. Subsequently, we explored the biological context of CSTB deficiency in microglia more deeply by functional enrichment and canonical pathway analysis. This uncovered a potential role for CSTB in chemotaxis, antigen-presentation, and in immune-and defense response-associated processes by altering JAK-STAT pathway signaling. These data support and expand the previously suggested involvement of inflammatory processes to the disease pathogenesis of EPM1 and connect CSTB deficiency in microglia to altered expression of interferon-regulated genes.Peer reviewe

Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo.

Synapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3-/- 33 mouse model of a juvenile form of NCL. We profiled and compared the molecular composition of anatomically-distinct, differentially-affected pre-synaptic populations from the Cln3-/- 35 mouse brain using proteomics followed by bioinformatic analyses. Identified protein candidates were then tested using a Drosophila CLN3 model to study their ability to modify the CLN3-neurodegenerative phenotype in vivo. We identified differential perturbations in a range of molecular cascades correlating with synaptic vulnerability, including valine catabolism and rho signalling pathways. Genetic and pharmacological targeting of key ‘hub’ proteins in such pathways was sufficient to modulate phenotypic presentation in a Drosophila CLN3 model. We propose that such a workflow provides a target rich method for the identification of novel disease regulators which could be applicable to the study of other conditions where appropriate models exist