Prenatal BoBsTM in the cytogenetic analysis of products of spontaneous miscarriage

Background. Fifty percent of spontaneous miscarriages (SMs) are attributed to chromosomal abnormalities. Cytogenetic analysis is an important tool for patient counselling and assessment of the risk of recurrence in future pregnancies. Conventional karyotyping has been the gold standard for chromosomal investigation of products of conception (POC), but it has limitations due to sample maceration, culture failure and maternal cell contamination. Molecular cytogenetic approaches have therefore been developed and found valuable in the cytogenetic investigation of these samples. The Prenatal BoBsTM and KaryoLite BoBsTM, based on the newly developed BACs-on-BeadsTM technology, have been described as reliable tests for rapid detection of aneuploidies in prenatal and POC samples, respectively.Objective. To describe our clinical experience of routine screening of POC samples with Prenatal BoBsTM, the test used by our laboratory in France.Methods. Seventeen samples collected at the University Hospital of Sidi Bel Abbès (Western Algeria) and a further 60 from the University Hospital of Clermont-Ferrand (France) were analysed (19 chorionic villi from products of curettage, 12 placentas, 9 amniotic cells and 37 biopsy specimens). All were screened for the frequent aneuploidies (chromosomes 13, 18, 21, X and Y) in addition to nine microdeletion/ microduplication syndrome regions by Prenatal BoBsTM. Standard karyotyping was performed on 51 samples, but failed in 38 cases.Results. Prenatal BoBsTM identified one trisomy 21 and one deletion of 17p13.3. Furthermore, it provided a conclusive result in cases of culture failure (n=38) and in samples with macerated tissue (n=19). The overall failure rate was 11.4%.Conclusions. Prenatal BoBsTM is a promising technology that represents a fast, sensitive and robust alternative to routine screening for chromosomal abnormality in products of SM. Furthermore, it overcomes the limitations of conventional karyotyping and current molecular cytogenetic techniques

Thiahelicene-grafted halloysite nanotubes: Characterization, biological studies and pH triggered release

A novel drug delivery nanosystem was here designed, linking thiahelicenes to halloysite nanotubes. Tetrathia[7]helicenes are very promising DNA intercalators, whose usage in biomedical field has been so far limited by their poor bioavailability. The study of appropriate drug delivery systems is needed to exploit helicenes as therapeutics. In this work, imine chemistry was adopted to covalently attach the bioactive compound and release it in acidic environments such as those surrounding tumour cells. To this aim, halloysite nanotubes were functionalized with (3-aminopropyl)triethoxysilane. The latter acted as linker providing NH2 groups to react with the formyl moiety of the thiahelicene derivative. The nanoconstruct preparation was studied in depth by surface-sensitive spectroscopies and angle-resolved X-ray absorption, to investigate the attachment mode, surface coverage and molecular orientation of the thiahelicene units. Release tests were carried out also in vitro on two tumour cell lines with different extracellular pH values. Mildly acidic pH conditions catalyzed the hydrolysis of the imine bond and promoted the cytotoxic compound release, which proved selective to slight pH differences, confirming the potential of this novel nanoconstruct

Anomaly detection in quasi-periodic energy consumption data series: a comparison of algorithms

The diffusion of domotics solutions and of smart appliances and meters enables the monitoring of energy consumption at a very fine level and the development of forecasting and diagnostic applications. Anomaly detection (AD) in energy consumption data streams helps identify data points or intervals in which the behavior of an appliance deviates from normality and may prevent energy losses and break downs. Many statistical and learning approaches have been applied to the task, but the need remains of comparing their performances with data sets of different characteristics. This paper focuses on anomaly detection on quasi-periodic energy consumption data series and contrasts 12 statistical and machine learning algorithms tested in 144 different configurations on 3 data sets containing the power consumption signals of fridges. The assessment also evaluates the impact of the length of the series used for training and of the size of the sliding window employed to detect the anomalies. The generalization ability of the top five methods is also evaluated by applying them to an appliance different from that used for training. The results show that classical machine learning methods (Isolation Forest, One-Class SVM and Local Outlier Factor) outperform the best neural methods (GRU/LSTM autoencoder and multistep methods) and generalize better when applied to detect the anomalies of an appliance different from the one used for training

Sub-3 Å Apoferritin Structure Determined With Full Range of Phase Shifts Using A Single Position Of Volta Phase Plate

Volta Phase Plate (VPP) has become an invaluable tool for cryo-EM structural determination of small protein complexes by increasing image contrast. Currently, the standard protocol of VPP usage periodically changes the VPP position to a fresh spot during data collection. Such a protocol was to target the phase shifts to a relatively narrow range (around 90°) based on the observations of increased phase shifts and image blur associated with more images taken with a single VPP position. Here, we report a 2.87 Å resolution structure of apoferritin reconstructed from a dataset collected using only a single position of VPP. The reconstruction resolution and map density features are nearly identical to the reconstruction from the control dataset collected with periodic change of VPP positions. Further experiments have verified that similar results, including a 2.5 Å resolution structure, could be obtained with a full range of phase shifts, different spots of variable phase shift increasing rates, and at different ages of the VPP post-installation. Furthermore, we have found that the phase shifts at low resolutions, probably related to the finite size of the Volta spots, could not be correctly modeled by current CTF model using a constant phase shift at all frequencies. In dataset III, severe beam tilt issue was identified but could be computationally corrected with iterative refinements. The observations in this study may provide new insights into further improvement of both the efficiency and robustness of VPP, and to help turn VPP into a plug-and-play device for high-resolution cryo-EM

Direct comparison of B-Type Natriuretic Peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data

Background: The B-type or brain natriuretic peptides (BNP) and the amino-terminal probrain natriuretic peptide (NT-proBNP) are good markers of prognosis and diagnosis in chronic heart failure (HF). It is unclear, however, whether differences in their biological characteristics modify their clinical correlates and prognostic performance in HF. This work aimed to provide a direct comparison of the prognostic value of BNP and NTproBNP in patients with chronic and stable HF. Methods: We measured BNP and NT-proBNP at baseline in 3916 patients enrolled in the Valsartan Heart Failure Trial. To identify the variables associated with both peptides, we conducted simple and multivariable linear regression analyses. We used Cox multivariable regression models to evaluate the independent prognostic value for all-cause mortality, mortality and morbidity, and hospitalization for HF. Prognostic performance was assessed by pairwise comparisons of the area under the curve of receiver-operator characteristic curves. Results: NT-proBNP and BNP had similar relationships with age, left ventrical ejection fraction, and internal diameter and creatinine clearance. Either peptide ranked as the first independent predictor of outcome after adjustment for major confounding clinical characteristics. ROC curves were almost superimposable for all-cause mortality (area under the curve (SE): BNP 0.665 (0.011) vs NT-proBNP 0.679 (0.011); P 0.0734), but NT-proBNP was superior to BNP for predicting mortality and morbidity (P 0.032) or hospitalization for HF (P 0.0143). Overall sensitivity and specificity ranged from 0.590 to 0.696. Conclusions: The natriuretic peptides BNP and NTproBNP showed subtle differences in their relation to clinical characteristics and prognostic performance in a large population of patients with chronic and stable HF. They were the most powerful independent markers of outcome in HF

First Record of Fusarium verticillioides as an Entomopathogenic Fungus of Grasshoppers

Fusarium verticillioides (Saccardo) Nirenberg (Ascomycota: Hypocreales) is the most common fungus reported on infected corn kernels and vegetative tissues, but has not yet been documented as being entomopathogenic for grasshoppers. Grasshoppers and locusts represent a large group of insects that cause economic damage to forage and crops. Tropidacris collaris (Stoll) (Orthoptera: Acridoidea: Romaleidae) is a large and voracious grasshopper that in recent years has become an increasingly recurrent and widespread pest in progressively more greatly extended areas of some of in Argentina's northern provinces, with chemical insecticides being currently the only means of control. During February and March of 2008–09, nymphs and adults of T. collaris were collected with sweep nets in dense woodland vegetation at a site near Tres Estacas in western Chaco Province, Argentina, and kept in screened cages. F. verticillioides was isolated from insects that died within 10 days and was cultured in PGA medium. Pathogenicity tests were conducted and positive results recorded. Using traditional and molecular-biological methods, an isolate of F. verticillioides was obtained from T. collaris, and its pathogenecity in the laboratory was shown against another harmful grasshopper, Ronderosia bergi (Stål) (Acridoidea: Acrididae: Melanoplinae). The mortality caused by F. verticillioides on R. bergi reached 58 ± 6.53% by 10 days after inoculation. This is the first record of natural infection caused by F. verticillioides in grasshoppers

Membrane-binding peptides for extracellular vesicles on-chip analysis

Small extracellular vesicles (sEVs) present fairly distinctive lipid membrane features in the extracellular environment. These include high curvature, lipid-packing defects and a relative abundance in lipids such as phosphatidylserine and ceramide. sEV membrane could be then considered as a "universal" marker, alternative or complementary to traditional, characteristic, surface-associated proteins. Here, we introduce the use of membrane-sensing peptides as new, highly efficient ligands to directly integrate sEV capturing and analysis on a microarray platform. Samples were analysed by label-free, single-particle counting and sizing, and by fluorescence co-localisation immune staining with fluorescent anti-CD9/anti-CD63/anti-CD81 antibodies. Peptides performed as selective yet general sEV baits and showed a binding capacity higher than anti-tetraspanins antibodies. Insights into surface chemistry for optimal peptide performances are also discussed, as capturing efficiency is strictly bound to probes surface orientation effects. We anticipate that this new class of ligands, also due to the versatility and limited costs of synthetic peptides, may greatly enrich the molecular toolbox for EV analysis