New Pyridine Derivatives from Essential Oils

Four new pyridines 1–4 have been isolated from jonquil absolute and their structures confirmed by synthesis. These pyridines also occur in other essential oils

ISA and IBFVS: image space-based visualization of flow on surfaces

We present a side-by-side analysis of two recent image space approaches for the visualization of vector fields on surfaces. The two methods, Image Space Advection (ISA) and Image Based Flow Visualization for Curved Surfaces (IBFVS) generate dense representations of time-dependent vector fields with high spatio-temporal correlation. While the 3D vector fields are associated with arbitrary surfaces represented by triangular meshes, the generation and advection of texture properties is confined to image space. Fast frame rates are achieved by exploiting frame-to-frame coherency and graphics hardware. In our comparison of ISA and IBFVS we point out the strengths and weaknesses of each approach and give recommendations as to when and where they are best applied

INDOBIOSYS – DNA BARCODING AS A TOOL FOR THE RAPID ASSESSMENT OF HYPERDIVERSE INSECT TAXA IN INDONESIA: A STATUS REPORT

A status report with preliminary results for the IndoBioSys project is presented and the impact of the project results for our knowledge of the Indonesian fauna is discussed. Using the REST API available on the Barcode of Life Data System we recover 21,153 public records (3,390 BINs) from Indonesia and compare against the 21,813 records (3,580 BINs) generated by the IndoBioSys project. From all IndoBioSys BINs, 3,366 (94%) are new to Indonesia. IndoBioSys is responsible for a BIN increase of 36.5% in Lepidoptera, 62.6% in Trichoptera, 986% in Coleoptera, and 1,086% in Hymenoptera. After two years of the IndoBioSys project, the Museum Zoologicum Bogoriense became the depository institution of 51.9% of Lepidoptera records, 95.8% of Coleoptera records, 97.6% of Hymenoptera records and 59.4% of Trichoptera records for Indonesia available on Barcode of Life Data System (BOLD). Now, with 55% of all Indonesian records available on BOLD, it is the most important depository for records of Indonesian genetic biodiversity, housing more than 23,000 new voucher specimens in their collections. Before IndoBioSys, the Museum Zoologicum Bogoriense was responsible for only 9% of all records available in the Barcode of Life Data System for Indonesia, showing the importance of those pipelines in empowering the local institutions in becoming the reference depository of the local fauna

Stroma AReactive Invasion Front Areas (SARIFA) proves prognostic relevance in gastric carcinoma and is based on a tumor–adipocyte interaction indicating an altered immune response

Background Recently, we presented Stroma AReactive Invasion Front Areas (SARIFA) as a new histomorphologic negative prognostic biomarker in gastric cancer. It is defined as direct contact between tumor cells and fat cells. The aim of this study was to further elucidate the underlying genomic, transcriptional, and immunological mechanisms of the SARIFA phenomenon. Methods To address these questions, SARIFA was classified on H&E-stained tissue sections of three cohorts: an external cohort (n = 489, prognostic validation), the TCGA-STAD cohort (n = 194, genomic and transcriptomic analysis), and a local cohort (n = 60, digital spatial profiling (whole transcriptome) and double RNA in situ hybridization/immunostaining of cytokines). Results SARIFA status proved to be an independent negative prognostic factor for overall survival in an external cohort of gastric carcinomas. In TCGA-STAD cohort, SARIFA is not driven by distinct genomic alterations, whereas the gene expression analyses showed an upregulation of FABP4 in SARIFA-positive tumors. In addition, the transcriptional regulations of white adipocyte differentiation, triglyceride metabolism, and catabolism were upregulated in pathway analyses. In the DSP analysis of SARIFA-positive tumors, FABP4 and the transcriptional regulation of white adipocyte differentiation were upregulated in macrophages. Additionally, a significantly lower expression of the cytokines IL6 and TNFα was observed at the invasion front. Conclusions SARIFA proves to be a strong negative prognostic biomarker in advanced gastric cancer, implicating an interaction of tumor cells with tumor-promoting adipocytes with crucial changes in tumor cell metabolism. SARIFA is not driven by tumor genetics but is very likely driven by an altered immune response as a causative mechanism

Five years of ocrelizumab in relapsing multiple sclerosis : OPERA studies open-label extension

Objective: To assess over 3 years of follow-up the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA: I/II studies in relapsing multiple sclerosis. Methods:After 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN)-β-1a (44 g 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression (CDP)/improvement (CDP), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), and percentage brain volume change were analyzed. Results:Of patients entering the OLE phase, 88.6% completed year 5. The cumulative proportion with 24-week CDP was lower in patients who initiated OCR earlier vs patients initially receiving IFN-β-1a (16.1% vs 21.3% at year 5; p = 0.014). Patients continuing OCR maintained and those switching from IFN-β-1a to OCR attained near complete and sustained suppression of new brain MRI lesion activity from years 3-5. Over the OLE phase, patients continuing OCR exhibited less whole brain volume loss from double-blind study baseline vs those switching from IFN-β-1a (-1.87% vs-2.15% at year 5; p < 0.01). Adverse events were consistent with past reports and no new safety signals emerged with prolonged treatment.ConclusionCompared with patients switching from IFN-β-1a, earlier and continuous OCR treatment up to 5 years provided sustained benefit on clinical and MRI measures of disease progression.Classification of evidenceThis study provides Class III evidence that earlier and continuous treatment with OCR provided sustained benefit on clinical and MRI outcomes of disease activity and progression compared with patients switching from IFN-β-1a. The study is rated Class III because of the initial treatment randomization disclosure that occurred after inclusion in OLE.Clinical trial identifiersNCT01247324/NCT01412333

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB