Fourteen degrees of latitude and a continent apart: comparison of lichen activity over two years at continental and maritime Antarctic sites

There are marked declines in precipitation, mean temperatures and the number of lichen species with increasing latitude in Antarctica. However, it is not known which factors are the predominant controllers of biodiversity changes. Results are presented from over two years of almost continuous monitoring of both microclimate and activity in lichens at Livingston Island, South Shetland Islands, 62°S, and Botany Bay, Ross Sea region, 77°S. Lichen activity was evident over a much longer period at Livingston Island, (3694 versus 897 hours) and could occur in any month whereas it was almost completely confined to the period November–February at Botany Bay. Mean air temperatures were much lower at Botany Bay (-18° compared to -1.5°C at Livingston Island), but the temperatures at which the lichens were active were almost identical at around 2°C at both sites. When the lichens were active incident light at Botany Bay was very much higher. The differences are related to the availability of meltwater which only occurs at times of high light and warm temperatures at Botany Bay. Temperature as a direct effect does not seem to explain the differences in biodiversity between the sites, but an indirect effect through active hours is much more probable. In addition there are negative effects of stresses such as high light and extreme winter cold at Botany Bay

Peripheral Nerve Ultrasound for the Differentiation between ALS, Inflammatory, and Hereditary Polyneuropathies

Background and Objectives: Ultrasound (US) is a non-invasive tool for the in vivo detection of peripheral nerve alterations. Materials and Methods: In this study, we applied nerve US to assist the discrimination between the spectrum of amyotrophic lateral sclerosis (ALS, n = 11), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 5), and genetically confirmed Charcot–Marie–Tooth disease (CMT, n = 5). All participants and n = 15 controls without neurological diseases underwent high-resolution US of the bilateral tibial nerve. The nerve cross-sectional area (CSA) and nerve microvascular blood flow were compared between the groups and related to cerebrospinal fluid (CSF) measures, clinical symptoms, and nerve conduction studies. The analyses are part of a larger multimodal study on the comparison between US and 7 Tesla (7T) magnetic resonance neurography (MRN). Results: The patients and controls were matched with respect to their demographical data. CMT had the longest disease duration, followed by CIDP and ALS. CSA was related to age, weight, and disease duration. CSA was larger in CMT and CIDP compared to ALS and controls. The blood flow was greatest in CIDP, and higher than in CMT, ALS, and controls. In ALS, greater CSA was correlated with greater CSF total protein and higher albumin quotient. The US measures did not correlate with clinical scores or nerve conduction studies in any of the subgroups. Conclusion: Our results point towards the feasibility of CSA and blood flow to discriminate between ALS, CIDP, and CMT, even in groups of small sample size. In ALS, larger CSA could indicate an inflammatory disease subtype characterized by reduced blood–nerve barrier integrity. Our upcoming analysis will focus on the additive value of 7T MRN in combination with US to disentangle the spectrum between more inflammatory or more degenerative disease variants among the disease groups

Functional characterization of two novel 5' untranslated exons reveals a complex regulation of NOD2 protein expression

<p>Abstract</p> <p>Background</p> <p>NOD2 is an innate immune receptor for the bacterial cell wall component muramyl-dipeptide. Mutations in the leucine-rich repeat region of NOD2, which lead to an impaired recognition of muramyl-dipeptide, have been associated with Crohn disease, a human chronic inflammatory bowel disease. Tissue specific constitutive and inducible expression patterns of NOD2 have been described that result from complex regulatory events for which the molecular mechanisms are not yet fully understood.</p> <p>Results</p> <p>We have identified two novel exons of the <it>NOD2 </it>gene (designated exon 1a and 1b), which are spliced to the canonical exon 2 and constitute the 5' untranslated region of two alternative transcript isoforms (i.e. exon 1a/1b/2 and exon 1a/2). The two novel transcripts are abundantly expressed and seem to comprise the majority of NOD2 transcripts under physiological conditions. We confirm the expression of the previously known canonical first exon (designated exon 1c) of the gene in unstimulated mononuclear cells. The inclusion of the second alternative exon 1b, which harbours three short upstream open reading frames (uORFs), is downregulated upon stimulation with TNF-α or under pro-inflammatory conditions in the inflamed intestinal mucosa <it>in vivo</it>. Using the different 5' UTR splice forms fused to a firefly luciferase (LUC) reporter we demonstrate a rapamycin-sensitive inhibitory effect of the uORFs on translation efficacy.</p> <p>Conclusion</p> <p>The differential usage of two alternative promoters in the <it>NOD2 </it>gene leads to tissue-specific and context-dependent <it>NOD2 </it>transcript isoform patterns. We demonstrate for the first time that context-dependent alternative splicing is linked to uORF-mediated translational repression. The results suggest complex parallel control mechanisms that independently regulate NOD2 expression in the context of inflammatory signaling.</p

CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection

Epidemiological studies have indicated a relationship between coronary heart disease (CHD) and periodontitis. Recently, CDKN2BAS was reported as a shared genetic risk factor of CHD and aggressive periodontitis (AgP), but the causative variant has remained unknown. To identify and validate risk variants in different European populations, we first explored 150 kb of the genetic region of CDKN2BAS including the adjacent genes CDKN2A and CDKN2B, covering 51 tagging single nucleotide polymorphisms (tagSNPs) in AgP and chronic periodontitis (CP) in individuals of Dutch origin (n=313). In a second step, we tested the significant SNP associations in an independent AgP and CP population of German origin (n=1264). For the tagSNPs rs1360590, rs3217992, and rs518394, we could validate the associations with AgP before and after adjustment for the covariates smoking, gender and diabetes, with SNP rs3217992 being the most significant (OR 1.48, 95% CI 1.19 to 1.85; p=0.0004). We further showed in vivo gene expression of CDKN2BAS, CDKN2A, CDKN2B, and CDK4 in healthy and inflamed gingival epithelium (GE) and connective tissue (CT), and detected a significantly higher expression of CDKN2BAS in healthy CT compared to GE (p=0.004). After 24 h of stimulation with Porphyromonas gingivalis in Streptococcus gordonii pre-treated gingival fibroblast (HGF) and cultured gingival epithelial cells (GECs), we observed a 25-fold and fourfold increase of CDKN2BAS gene expression in HGFs (p=0.003) and GECs (p=0.004), respectively. Considering the global importance of CDKN2BAS in the disease risk of CHD, this observation supports the theory of inflammatory components in the disease physiology of CHD

2D, 2.5D, or 3D? An Exploratory Study on Multilayer Network Visualisations in Virtual Reality

Relational information between different types of entities is often modelled by a multilayer network (MLN) -- a network with subnetworks represented by layers. The layers of an MLN can be arranged in different ways in a visual representation, however, the impact of the arrangement on the readability of the network is an open question. Therefore, we studied this impact for several commonly occurring tasks related to MLN analysis. Additionally, layer arrangements with a dimensionality beyond 2D, which are common in this scenario, motivate the use of stereoscopic displays. We ran a human subject study utilising a Virtual Reality headset to evaluate 2D, 2.5D, and 3D layer arrangements. The study employs six analysis tasks that cover the spectrum of an MLN task taxonomy, from path finding and pattern identification to comparisons between and across layers. We found no clear overall winner. However, we explore the task-to-arrangement space and derive empirical-based recommendations on the effective use of 2D, 2.5D, and 3D layer arrangements for MLNs.Comment: IEEE Transactions on Visualization and Computer Graphics, In press, To appear. Accepted to IEEE VIS 202

X-ray phase contrast imaging of biological specimens with tabletop synchrotron radiation

Since their discovery in 1896, x-rays have had a profound impact on science, medicine and technology. Here we show that the x-rays from a novel tabletop source of bright coherent synchrotron radiation can be applied to phase contrast imaging of biological specimens, yielding superior image quality and avoiding the need for scarce or expensive conventional sources

Unifying candidate gene and GWAS Approaches in Asthma.

The first genome wide association study (GWAS) for childhood asthma identified a novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene, but the role of previous asthma candidate genes was not specifically analyzed in this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously associated with asthma in >3 independent study populations. We re-genotyped 39 SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658 reference children. Genotyping data were compared to imputation data derived from Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and VDR showed effects with p-values <0.0035 (corrected for multiple testing). Combining genotyping and imputation, polymorphisms in DPP10, EDN1, IL12B, IL13, IL4, IL4R and TNF showed associations at a significance level between p = 0.05 and p = 0.0035. These data indicate that (a) GWAS coverage is insufficient for many asthma candidate genes, (b) imputation based on these data is reliable but incomplete, and (c) SNPs in three previously identified asthma candidate genes replicate in our GWAS population with significance after correction for multiple testing in 14 genes

The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.

The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice

CSF Neurofilament Light Chain Levels in Primary Progressive MS: Signs of Axonal Neurodegeneration

Objectives: Elevated neurofilament light chain (NFL) levels within the cerebrospinal fluid (CSF) are a biomarker representing axonal neurodegeneration in rapid progressive neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). It is unclear to what extent the levels of NFL increase in the CSF (CSF-NFL) in a chronic neuroinflammatory process with axonal neurodegeneration, as found in primary progressive multiple sclerosis (PPMS).Methods: We used a multicenter approach to statistically compare CSF-NFL levels between PPMS patients (n = 50), ALS patients (n = 50), and healthy controls (n = 50). Clinical findings, including disease duration, expanded disability status scale (EDSS), electrophysiological recordings such as visual evoked potentials or spinal and cerebral MRI, and previously administered treatment were selected as experimental parameters retrospectively.Results: Median [range] CSF-NFL concentrations in PPMS patients were significantly higher than in the controls [1724 (799–4275) pg/ml vs. 1202 (612–2934) pg/ml, p = 0.015], and significantly lower compared to ALS patients [1724 (799–4275) pg/ml vs. 10238 (2610–35138) pg/ml, p &lt; 0.001]. There was no correlation between CSF-NFL and disease duration (p = 0.5), EDSS (p = 0.2) or treatment (p = 0.3).Conclusion: We conclude that CSF-NFL may mirror the proposed slow axonal degeneration in PPMS, but does not reflect the disease severity