Preferences for a non-invasive prenatal test as first-line screening for Down Syndrome: A discrete choice experiment.

OBJECTIVE: To investigate preferences of pregnant women for the characteristics of prenatal testing, and to quantify their willingness-to-pay (WTP) for non-invasive prenatal testing (NIPT) as first-line screening for Down Syndrome. METHOD: A cross-sectional discrete choice experiment survey including five testing attributes was administered to 192 pregnant women (≤14 weeks' gestation) who were aged ≥21 years in Singapore. We calculated marginal WTP for improvements in testing characteristics and NIPT. RESULTS: We identified two groups of women with distinct preferences for prenatal testing. Women aged ≥35 years, with at least a university education, and with intention to terminate pregnancy of an affected fetus were more likely to be in the group with higher WTP for improvements in test characteristics. While participants valued increased detection rate and lower screen positive rate associated with NIPT, they also valued no risk of test failure and ability to test for birth defects using standard testing. The participants, on average, were not willing to pay for NIPT over the standard testing as a first-line screening test. CONCLUSIONS: As a first-line screening, NIPT was not preferred over standard testing. The prenatal consultations should focus on each testing characteristic equally as our findings show diverse preferences for testing characteristics.

Machine Learning Pipeline for Segmentation and Defect Identification from High-Resolution Transmission Electron Microscopy Data.

In the field of transmission electron microscopy, data interpretation often lags behind acquisition methods, as image processing methods often have to be manually tailored to individual datasets. Machine learning offers a promising approach for fast, accurate analysis of electron microscopy data. Here, we demonstrate a flexible two-step pipeline for the analysis of high-resolution transmission electron microscopy data, which uses a U-Net for segmentation followed by a random forest for the detection of stacking faults. Our trained U-Net is able to segment nanoparticle regions from the amorphous background with a Dice coefficient of 0.8 and significantly outperforms traditional image segmentation methods. Using these segmented regions, we are then able to classify whether nanoparticles contain a visible stacking fault with 86% accuracy. We provide this adaptable pipeline as an open-source tool for the community. The combined output of the segmentation network and classifier offer a way to determine statistical distributions of features of interest, such as size, shape, and defect presence, enabling the detection of correlations between these features.

Odor Memory and Discrimination Covary as a Function of Delay between Encoding and Recall in Rats.

Nonassociative odor learning paradigms are often used to assess memory, social recognition and neuromodulation of olfactory pathways. We here use a modified object recognition paradigm to investigate how an important task parameter, delay between encoding and recall trials, affects the properties of this memory. We show that both memory for a previously investigated odorant and discrimination of a novel odorant decay with delay time and that rats can remember an odorant for up to 45min after a single trial encoding event. The number of odorants that can be encoded, as well as the specificity of the encoded memory, decrease with increased delay and also depend on stimulus concentration. Memory for an odorant and discrimination of a novel odorant decay at approximately the same rate, whereas the specificity of the formed memory decays faster than the memory itself. These results have important implications for the interpretation of behavioral data obtained with this paradigm.

The germinal zones of the basal ganglia but not the septum generate GABAergic interneurons for the cortex.

Cortical interneurons originate from subpallial precursors and migrate into the cortex during development. Using genetic lineage tracing in transgenic mice we examine the contribution of two germinal zones, the septum and the lateral ganglionic eminence/caudal ganglionic eminence (LGE/CGE) to interneurons of the cortex. We find that the septal neuroepithelium does not generate interneurons for the neocortex. There is, however, clear migration of cells from the LGE/CGE to the cortex. Comparison of the dynamics of cortical colonization by the two major cohorts of interneurons originating in the medial ganglionic eminence (MGE) and the LGE/CGE has shown differences in the timing of migration and initial route of entry into the cortex. LGE/CGE-derived interneurons enter the cortex later than the MGE-derived ones. They invade the cortex through the subventricular/intermediate zone route and only later disperse within the cortical plate and the marginal zone. During the first postnatal week MGE interneurons move extensively to acquire their laminar position within the cortical plate whereas LGE/CGE-derived cells remain largely within the upper layers of the cortex. The two populations intermingle in the adult cortex but have distinct neurochemical properties and different overall distributions. LGE/CGE-derived interneurons account for one third of the total GABAergic interneuron population in the adult cortex.

Characterization of Brassica rapa RAP2.4-Related Proteins in Stress Response and as CUL3-Dependent E3 Ligase Substrates.

The turnip Brassica rapa has important economic value and represents a good model system to study gene function in crop plants. ERF/AP2 transcription factors are a major group of proteins that are often involved in regulating stress-responses and developmental programs. Some ERF/AP2 proteins are targets of CULLIN3-based E3 ligases that use BTB/POZ-MATH proteins as substrate receptors. These receptors bind the transcription factor and facilitate their ubiquitylation and subsequent degradation via the 26S proteasome. Here, we show tissue and stress-dependent expression patterns for three Brassica rapa ERF/AP2 proteins that are closely related to Arabidopsis thaliana AtRAP2.4. Cloning of the Brassica genes showed that the corresponding proteins can assemble with a BPM protein and CULLIN3, and that they are instable in a 26S proteasome dependent manner. This work demonstrates the conserved nature of the ERF/AP2-CULLIN3-based E3 ligase interplay, and represents a first step to analyze their function in a commercially relevant crop plant.

Recombinant RquA catalyzes the in vivo conversion of ubiquinone to rhodoquinone in Escherichia coli and Saccharomyces cerevisiae.

Terpenoid quinones are liposoluble redox-active compounds that serve as essential electron carriers and antioxidants. One such quinone, rhodoquinone (RQ), couples the respiratory electron transfer chain to the reduction of fumarate to facilitate anaerobic respiration. This mechanism allows RQ-synthesizing organisms to operate their respiratory chain using fumarate as a final electron acceptor. RQ biosynthesis is restricted to a handful of prokaryotic and eukaryotic organisms, and details of this biosynthetic pathway remain enigmatic. One gene, rquA, was discovered to be required for RQ biosynthesis in Rhodospirillum rubrum. However, the function of the gene product, RquA, has remained unclear. Here, using reverse genetics approaches, we demonstrate that RquA converts ubiquinone to RQ directly. We also demonstrate the first in vivo synthetic production of RQ in Escherichia coli and Saccharomyces cerevisiae, two organisms that do not natively produce RQ. These findings help clarify the complete RQ biosynthetic pathway in species which contain RquA homologs.

Are pregnant women adequately equipped for autonomy in pregnancy screening?

INTRODUCTION: Aneuploidy screening is widely practised in the field of obstetrics in current times. This study thus aims to gain an insight on pregnant women's knowledge and risk perception of Down syndrome and first trimester screening (FTS), as well as their views on various potential pregnancy outcomes and how these may affect their decision-making processes. MATERIALS AND METHODS: A cross-sectional questionnaire-based qualitative study of consecutive 50 women choosing to undergo FTS at KK Women's and Children's Hospital (KKH), Singapore was conducted. The women completed a questionnaire after their FTS pretest counselling session. Basic knowledge of Down syndrome and FTS as well as participants' risk perception with regards to various cut-off values used in FTS were examined. Patients' views of various potential pregnancy outcomes were also studied. RESULTS: Most patients had good retention and comprehension of what FTS entailed after a FTS counselling session at the KKH Antenatal Monitoring Clinic. However, knowledge of the risks of invasive diagnostic testing was poor. Patients also did not possess an adequate understanding of FTS risk values. With regards to risk perception, patients had very different views on acceptable pregnancy outcomes and what constituted a high-risk FTS value to them personally. A significant number of women were concerned even at medically low-risk values of 1:500 and 1:1000 in FTS. The majority of patients viewed highest detection rate followed by a lowest false positive rate as the more important factors impacting their choice of a Down syndrome screening test. CONCLUSION: This study demonstrates the diversity of pregnant women's risk perception, risk aversion and participation in decision processes when there are 2 different values in competition. The study also highlights our patients' gaps in knowledge and lack of understanding of risk values used in FTS.

Composition, roles, and regulation of cullin-based ubiquitin e3 ligases.

Due to their sessile nature, plants depend on flexible regulatory systems that allow them to adequately regulate developmental and physiological processes in context with environmental cues. The ubiquitin proteasome pathway, which targets a great number of proteins for degradation, is cellular tool that provides the necessary flexibility to accomplish this task. Ubiquitin E3 ligases provide the needed specificity to the pathway by selectively binding to particular substrates and facilitating their ubiquitylation. The largest group of E3 ligases known in plants is represented by CULLIN-REALLY INTERESTING NEW GENE (RING) E3 ligases (CRLs). In recent years, a great amount of knowledge has been generated to reveal the critical roles of these enzymes across all aspects of plant life. This review provides an overview of the different classes of CRLs in plants, their specific complex compositions, the variety of biological processes they control, and the regulatory steps that can affect their activities.