Networks from gene expression time series: characterization of correlation patterns

This paper describes characteristic features of networks reconstructed from gene expression time series data. Several null models are considered in order to discriminate between informations embedded in the network that are related to real data, and features that are due to the method used for network reconstruction (time correlation).Comment: 10 pages, 3 BMP figures, 1 Table. To appear in Int. J. Bif. Chaos, July 2007, Volume 17, Issue

A Simple Biomimetic Receptor Selectively Recognizing the GlcNAc2 Disaccharide in Water

AbstractGlcNAc2 is the core disaccharide fragment present in N‐glycans exposed on the surface of enveloped viruses of high health concern, such as coronaviruses. Because N‐glycans are directly involved in the docking of viruses to host cells, recognition of GlcNAc2 by a biomimetic receptor may be a convenient alternative to the use of lectins to interfere with viral entry and infection. Herein, we describe a simple biomimetic receptor recognizing the methyl‐β‐glycoside of GlcNAc2 in water with an unprecedented affinity of 160 μM, exceeding that of more structurally complex receptors reported in the literature. The tweezers‐shaped acyclic structure exhibits marked selectivity among structurally related disaccharides, and complete discrimination between mono‐ and disaccharides. Molecular modelling calculations supported by NOE data provided a three‐dimensional description of the binding mode, shedding light on the origin of the affinities and selectivities exhibited by the receptor

POS0250 SIGNIFICANT DAMAGE OCCURS EARLY IN THE COURSE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS AND IS MAINLY DUE TO DISEASE-RELATED SEQUELAE

Background:Following the introduction of effective immunosuppressive treatments, ANCA-associated vasculitides (AAV) have become chronic diseases with a remitting-relapsing course. Therefore, preventing chronic damage accrual during follow-up is critical, as relapses, treatment-related side effects, and comorbidities may significantly affect the long-term outcomes of AAV patients. At present, no study specifically evaluated the burden of damage in patients with eosinophilic granulomatosis with polyangiitis (EGPA).Objectives:To describe short-term (6 months) and long-term (5 years) damage accrual in patients with newly diagnosed EGPA.Methods:Patients diagnosed with EGPA, according to ACR criteria and/or Chapel Hill definitions and regularly followed-up in our vasculitis center for ≥5 years were included. Damage accrual was assessed with the Vasculitis Damage Index (VDI). Short-term and long-term damage accrual was defined by VDI at 6 months and at 5 years, respectively, and categorized as related to vasculitis or its treatment.Results:VDI data at 6 months were available for 45 EGPA patients: 24 (53.3%) female, mean age at diagnosis 51.6±13.0 years. ANCA were positive in 17 patients (37.8%), with MPO being the only detected enzyme immunoassay (EIA)-specificity. At 6 months mean VDI was 2.8±1.3; 25/45 (55.6%) and 6/45 patients (13.3%) presented ≥3 and ≥5 items, respectively, whilst only 1 patient (2.2%) showed no items of damage. VDI data at 5 years were available for 32/45 EGPA patients (71.1%): 16 (50%) female, mean age at diagnosis 51.5±13.1 years. MPO-ANCA were positive in 13 patients (40.6%). At 5 years mean VDI was 3.5±1.3, with 26/32 (81.3%) and 7/32 patients (21.9%) presenting ≥3 and ≥5 items, respectively; notably, no patients presented a VDI=0 at 5 years.The most frequent disease-related VDI items at 6 months and at 5 years were asthma, chronic sinusitis, peripheral neuropathy, cardiomyopathy, pulmonary function tests abnormalities and nasal blockage (Figure 1). Osteoporotic fractures, diabetes and systemic hypertension were the most commonly reported treatment-related items at 6 months and at 5 years (Figure 1). Damage accrual progressively rose during the 5-year follow-up (P=0.023), mainly due to disease-related items rather than treatment-related items both at 6 months (disease related VDI 2.6±1.2, treatment-related VDI 0.3±0.6) and at 5 years (disease related VDI 2.9±1.2, treatment-related VDI 0.6±0,7). No significant difference in terms of damage accrual was observed between ANCA-positive and ANCA-negative patients (P >0.5).Conclusion:In our cohort of EGPA patients damage accrual occurs early, with more than half of the patients displaying ≥3 VDI items already at 6 months. Poor control of previous disease activity, particularly ENT and respiratory manifestations, contributes to progressive damage accrual more than treatment side effects.Figure 1.Disease-related and treatment-related VDI items at 6 months and at 5 years in patients with EGPA.Disclosure of Interests:None declare

Study of tributary inflows in Lake Iseo with a rotating physical model

The influence of Coriolis force on the currents of large lakes is well acknowledged; very few contributions, however, investigate this aspect in medium-size lakes where its relevance could be questionable. In order to study the area of influence of the two major tributary rivers in Lake Iseo, a rotating vertically distorted physical model of the northern part of this lake was prepared and used, respecting both Froude and Rossby similarity. The model has a horizontal length scale factor of 8000 and a vertical scale factor of 500 and was used both in homogeneous and in thermally stratified conditions. We explored the pattern of water circulation in front of the entrance mouth for dif- ferent hydrologic scenarios at the beginning of spring and in summer. We neglected the influence of winds. The primary purposes of the model were twofold: i) to increase our level of knowledge of the hydrodynamics of Lake Iseo by verifying the occurrence of dynamical effects related to the Earth’s rotation on the plume of the two tributaries that enter the northern part of the lake and ii) to identify the areas of the lake that can be directly influenced by the tributaries’ waters, in order to provide guidance on water quality monitoring in zones of relevant environmental and touristic value. The results of the physical model confirm the relevant role played by the Coriolis force in the northern part of the lake. Under ordinary flow conditions, the model shows a systematic deflection of the inflowing waters towards the western shore of the lake. The inflow triggers a clockwise gyre within the Lovere bay, to the West of the inflow, and a slow counter-clockwise gyre, to the East of the inflow, that returns water towards the river mouth along the eastern shore. For discharges with higher return period, when only the contribution by Oglio River is relevant, the effect of the Earth’s rotation weakens in the entrance zone and the plume has a more rectilinear pattern, whilst in the far field the current driven by the inflows keeps moving along the western shore. On the basis of these results one could expect that the north-western part of the lake between Castro and Lovere, although not aligned with the tributaries’ axes, is more sensitive to accumulation effects related to river-borne pollution. The results obtained with the physical model are critically compared with data obtained from different sources: the trajectory of a lagrangian drogue; a map of reflectivity data from the lake floor; a map of water turbidity at the intrusion depth. The findings are also confirmed by the results of a 3D numerical model of the lake

Detection and whole genome sequencing of CPMMV in common bean resistant to BGMV from Paraná State.

Cowpea mild mottle virus (CPMMV) is a Carlavirus from the family Betaflexiviridae which has a linear single stranded positive sense rna genome of approximately 8,200 nt and infects a wide range of cultivated plants from the Fabaceae family. It is transmitted by the whitefly Bemisia tabaci

POS0830 FACTORS INFLUENCING PATIENT-REPORTED OUTCOMES IN ANCA-ASSOCIATED VASCULITIS

Background:Patient-reported outcomes (PROs) are currently poorly integrated in the clinical evaluation of disease activity in patients with ANCA-associated vasculitis (AAV).Objectives:To assess the distribution of the Patient Global Assessment (PtGA) in patients with AAV in stable remission, and to identify correlates of PtGA; to assess the discordance between PtGA score and PhGA.Methods:Patients with a diagnosis of AAV [eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, microscopic polyangiitis] in stable, complete remission (defined by a BVAS=0) and with a Physician Global Assessment (PhGA)=0 were included. A questionnaire including several aspects of disease captured by PROs was collected. PtGA on a 0-100 mm visual analogue scale (VAS) was assessed, with higher scores representing higher/worse levels of disease activity. Similarly, VAS for pain, chronic damage according to the patient's opinion, general health (GH), fatigue, and sleep quality were collected. The worst symptom in the patient's opinion affecting the overall assessment of disease activity was recorded. The Cragg Hurdle model was used to assess the predictors of PtGA.Results:65 patients were included, female 57%, mean age 61±12 years. Mean disease duration at enrollment was 8±6 years. Mean vasculitis damage index (VDI) was 4.4 ±2.3, with 45% of patients having a VDI ≥ 5. Despite having been classified as being in remission, PtGA was elevated in 37% of patients. We explored several correlates of PtGA. Higher degree of damage accrual (VDI) did not influence the patient's evaluation of current disease activity. Similarly, we did not identify a correlation between older age, educational level, number of organ-systems involved, number of comorbidities, the number of previous major or minor relapses, higher disease duration, nor the type of AAV diagnosis (figure 1, panel A). Only sex significantly correlated with PtGA scores: 19 (51%) of female patients reported an elevated PtGA compared to only 5 (18%) of male (p=0.009). PtGA resulted to be significantly correlated with other (mostly modifiable) PROs including VAS pain, perception of the level of chronic damage accrual, GH, and fatigue (figure 1, panel B). The agreement between patients' and physicians' assessments of disease activity was 63%. Patients reported pain, followed by chronic respiratory symptoms to be the worst-experienced ongoing manifestations affecting their evaluation of disease activity.Conclusion:A significant proportion of patients with AAV considered to be in remission by the physician still declares to have persistent aspects of uncontrolled disease. PtGA is significantly influenced by persistent pain and fatigue, which warrant better assessment in the future.Disclosure of Interests:None declare