A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs

Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-16A) or dephosphorylate (syp-16D) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1BRCA1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.Cancer Research UK FC0010048UK Medical Research Council FC0010048Wellcome Trust FC0010048Ministerio de Economía y Competitividad BFU2016-75058-PEuropean Research Council ERC2014 AdG669898 TARLOO

Evaluating Performance of the Single Leg Squat Exercise with a Single Inertial Measurement Unit

The single leg squat (SLS) is an important component of lower limb rehabilitation and injury risk screening tools. This study sought to investigate whether a single lumbar-worn IMU is capable of discriminating between correct and incorrect performance of the SLS. Nineteen healthy volunteers (15 males, 4 females, age: 26.09±3.98 years, height: 1.75±0.14m, body mass: 75.2±14.2kg) were fitted with a single IMU on the lumbar spine and asked to perform 10 left leg SLS. These repetitions were recorded and labelled by a chartered physiotherapist. Features were extracted from the labelled sensor data. These features were used to train and evaluate a random-forests classifier. The system achieved an average of 92% accuracy, 78% sensitivity and 97% specificity. These results indicate that a single IMU has the potential to differentiate between a correctly and incorrectly completed SLS. This may allow such devices to be used by clinicians to help track rehabilitation of patients and screen for potential injury risks. Furthermore, the classifier described may be a useful input to an exercise biofeedback application

Evaluating Performance of the Single Leg Squat Exercise with a Single Inertial Measurement Unit

The single leg squat (SLS) is an important component of lower limb rehabilitation and injury risk screening tools. This study sought to investigate whether a single lumbar-worn IMU is capable of discriminating between correct and incorrect performance of the SLS. Nineteen healthy volunteers (15 males, 4 females, age: 26.09±3.98 years, height: 1.75±0.14m, body mass: 75.2±14.2kg) were fitted with a single IMU on the lumbar spine and asked to perform 10 left leg SLS. These repetitions were recorded and labelled by a chartered physiotherapist. Features were extracted from the labelled sensor data. These features were used to train and evaluate a random-forests classifier. The system achieved an average of 92% accuracy, 78% sensitivity and 97% specificity. These results indicate that a single IMU has the potential to differentiate between a correctly and incorrectly completed SLS. This may allow such devices to be used by clinicians to help track rehabilitation of patients and screen for potential injury risks. Furthermore, the classifier described may be a useful input to an exercise biofeedback application

Demodex-Associated Bacillus Proteins Induce an Aberrant Wound Healing Response in a Corneal Epithelial Cell Line: Possible Implications for Corneal Ulcer Formation in Ocular Rosacea

PURPOSE. The aim of the work presented here was to establish the response of a corneal epithelial cell line (hTCEpi) to protein extracted from a bacterium (Bacillus oleronius) previously isolated from a Demodex mite from a rosacea patient. METHODS. The response of the corneal epithelial cell line to Bacillus proteins was measured in terms of alterations in cell migration and invasiveness. Changes in the expression of metalloproteinase genes and proteins were also assessed. RESULTS. The results indicated increased cell migration (14.5- fold, P ¼ 0.001) as measured using 8-lm PET inserts (BD Falcon) in a transwell assay and invasiveness (1.7-fold, P ¼ 0.003) as measured using 8-lm Matrigel (BD Biocoat) invasion inserts in a 24-well plate assay format, following exposure to the Bacillus proteins. Cells exposed to the Bacillus protein showed a dose-dependent increase in expression of genes coding for matrix metalloprotease (MMP)-3 (61-fold) and MPP-9 (301-fold). This dose-dependent increase in gene expression was also reflected in elevated levels of MMP-9 protein (1.34- fold, P ¼ 0.033) and increased matrix metalloprotease activity (1.96-fold, P¼0.043) being present in the culture supernatant. Cells also displayed reduced levels of b-integrin (1.25-fold, P ¼ 0.01), indicative of increased motility and elevated levels of vinculin (2.7-fold, P ¼ 0.0009), suggesting altered motility. CONCLUSIONS. The results indicate that exposure of corneal epithelial cells to Bacillus proteins results in an aberrant wound healing response as visualized using a scratch wound assay. These results suggest a possible link between the high density of Demodex mites on the eyelashes of ocular rosacea patients and the development of corneal ulcers. (Invest Ophthalmol Vis Sci. 2012;53:3250–3259) DOI:10.1167/ iovs.11-929

Demodex-Associated Bacillus Proteins Induce an Aberrant Wound Healing Response in a Corneal Epithelial Cell Line: Possible Implications for Corneal Ulcer Formation in Ocular Rosacea

PURPOSE. The aim of the work presented here was to establish the response of a corneal epithelial cell line (hTCEpi) to protein extracted from a bacterium (Bacillus oleronius) previously isolated from a Demodex mite from a rosacea patient. METHODS. The response of the corneal epithelial cell line to Bacillus proteins was measured in terms of alterations in cell migration and invasiveness. Changes in the expression of metalloproteinase genes and proteins were also assessed. RESULTS. The results indicated increased cell migration (14.5- fold, P ¼ 0.001) as measured using 8-lm PET inserts (BD Falcon) in a transwell assay and invasiveness (1.7-fold, P ¼ 0.003) as measured using 8-lm Matrigel (BD Biocoat) invasion inserts in a 24-well plate assay format, following exposure to the Bacillus proteins. Cells exposed to the Bacillus protein showed a dose-dependent increase in expression of genes coding for matrix metalloprotease (MMP)-3 (61-fold) and MPP-9 (301-fold). This dose-dependent increase in gene expression was also reflected in elevated levels of MMP-9 protein (1.34- fold, P ¼ 0.033) and increased matrix metalloprotease activity (1.96-fold, P¼0.043) being present in the culture supernatant. Cells also displayed reduced levels of b-integrin (1.25-fold, P ¼ 0.01), indicative of increased motility and elevated levels of vinculin (2.7-fold, P ¼ 0.0009), suggesting altered motility. CONCLUSIONS. The results indicate that exposure of corneal epithelial cells to Bacillus proteins results in an aberrant wound healing response as visualized using a scratch wound assay. These results suggest a possible link between the high density of Demodex mites on the eyelashes of ocular rosacea patients and the development of corneal ulcers. (Invest Ophthalmol Vis Sci. 2012;53:3250–3259) DOI:10.1167/ iovs.11-929

Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast.

INTRODUCTION: Normal gene expression variation is thought to play a central role in inter-individual variation and susceptibility to disease. Regulatory polymorphisms in cis-acting elements result in the unequal expression of alleles. Differential allelic expression (DAE) in heterozygote individuals could be used to develop a new approach to discover regulatory breast cancer susceptibility loci. As access to large numbers of fresh breast tissue to perform such studies is difficult, a suitable surrogate test tissue must be identified for future studies. METHODS: We measured differential allelic expression of 12 candidate genes possibly related to breast cancer susceptibility (BRCA1, BRCA2, C1qA, CCND3, EMSY, GPX1, GPX4, MLH3, MTHFR, NBS1, TP53 and TRXR2) in breast tissue (n = 40) and fresh blood (n = 170) of healthy individuals and EBV-transformed lymphoblastoid cells (n = 19). Differential allelic expression ratios were determined by Taqman assay. Ratio distributions were compared using t-test and Wilcoxon rank sum test, for mean ratios and variances respectively. RESULTS: We show that differential allelic expression is common among these 12 candidate genes and is comparable between breast and blood (fresh and transformed lymphoblasts) in a significant proportion of them. We found that eight out of nine genes with DAE in breast and fresh blood were comparable, as were 10 out of 11 genes between breast and transformed lymphoblasts. CONCLUSIONS: Our findings support the use of differential allelic expression in blood as a surrogate for breast tissue in future studies on predisposition to breast cancer.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Open-source magnetic resonance imaging : Improving access, science, and education through global collaboration

The authors would like to thank all the authors that are sharing their work open-source and all the supporters of the Open Source Imaging Initiative (OSI2). The project (21NRM05 and 22HLT02 A4IM) has received funding from the European Partnership on Metrology, co-financed by the European Union's Horizon Europe Research and Innovation Programme and by the Participating States. This research is funded by dtec.bw- Digitalization and Technology Research Center of the Bundeswehr. dtec.bw is funded by the European Union - NextGeneration EU. Part of the image reconstruction used here was developed by the CCP PETMR and CCP SynerBi (https://www.ccppetmr.ac.uk/), UK EPSRC grants EP/P022200/1, EP/M022587/1 and EP/T026693/1. This work made use of computational support by CoSeC, the Computational Science Centre for Research Communities via CCP-SyneRBI and CCPi. RG Nunes acknowledges funding from Fundação para a Ciência e a Tecnologia (grants UIDP/50009/2020 and LA/P/0083/2020). Ruben Pellicer-Guridi has been funded by the European Union's Marie Skłodowska-Curie project nr. 101030868. Open Access funding enabled and organized by Projekt DEAL.Peer reviewe

An Examination of Wearable Sensors and Video Data Capture for Human Exercise Classification

Wearable sensors such as Inertial Measurement Units (IMUs) are often used to assess the performance of human exercise. Common approaches use handcrafted features based on domain expertise or automatically extracted features using time series analysis. Multiple sensors are required to achieve high classification accuracy, which is not very practical. These sensors require calibration and synchronization and may lead to discomfort over longer time periods. Recent work utilizing computer vision techniques has shown similar performance using video, without the need for manual feature engineering, and avoiding some pitfalls such as sensor calibration and placement on the body. In this paper, we compare the performance of IMUs to a video-based approach for human exercise classification on two real-world datasets consisting of Military Press and Rowing exercises. We compare the performance using a single camera that captures video in the frontal view versus using 5 IMUs placed on different parts of the body. We observe that an approach based on a single camera can outperform a single IMU by 10 percentage points on average. Additionally, a minimum of 3 IMUs are required to outperform a single camera. We observe that working with the raw data using multivariate time series classifiers outperforms traditional approaches based on handcrafted or automatically extracted features. Finally, we show that an ensemble model combining the data from a single camera with a single IMU outperforms either data modality. Our work opens up new and more realistic avenues for this application, where a video captured using a readily available smartphone camera, combined with a single sensor, can be used for effective human exercise classification