Monomethylated and unmethylated FUS exhibit increased binding to Transportin and distinguish FTLD-FUS from ALS-FUS.

Deposition of the nuclear DNA/RNA-binding protein Fused in sarcoma (FUS) in cytosolic inclusions is a common hallmark of some cases of frontotemporal lobar degeneration (FTLD-FUS) and amyotrophic lateral sclerosis (ALS-FUS). Whether both diseases also share common pathological mechanisms is currently unclear. Based on our previous finding that FUS deposits are hypomethylated in FTLD-FUS but not in ALS-FUS, we have now investigated whether genetic or pharmacological inactivation of Protein arginine methyltransferase 1 (PRMT1) activity results in unmethylated FUS or in alternatively methylated forms of FUS. To do so, we generated FUS-specific monoclonal antibodies that specifically recognize unmethylated arginine (UMA), monomethylated arginine (MMA) or asymmetrically dimethylated arginine (ADMA). Loss of PRMT1 indeed not only results in an increase of UMA FUS and a decrease of ADMA FUS, but also in a significant increase of MMA FUS. Compared to ADMA FUS, UMA and MMA FUS exhibit much higher binding affinities to Transportin-1, the nuclear import receptor of FUS, as measured by pull-down assays and isothermal titration calorimetry. Moreover, we show that MMA FUS occurs exclusively in FTLD-FUS, but not in ALS-FUS. Our findings therefore provide additional evidence that FTLD-FUS and ALS-FUS are caused by distinct disease mechanisms although both share FUS deposits as a common denominator.

Patients' experiences in magnetic resonance imaging (MRI) and their experiences of breath holding techniques.

AIMS: To describe patients' experiences of magnetic resonance examination of the liver and their experiences of two breath-hold techniques. BACKGROUND: Traditionally, patients are instructed by the radiographer to hold their breath during the examination. Alternatively, the patient can initiate the breath hold and start the image acquisition. Studies have revealed that magnetic resonance examinations can be experienced as challenging. DESIGN: Descriptive qualitative. METHODS: Semi-structured interviews were conducted with 28 patients and analysed using qualitative content analysis. The data collection was carried out from autumn 2010 to spring 2011. RESULTS: The patients' main experience was that they felt loss of control. This was described in terms of feeling trapped, being lost in time and lost as a result of uncertainty. They had many questions in their mind that they did not ask. Although their statements often revealed no clear preference regarding the techniques, almost half of the patients seemed to prefer self-initiated breath hold, as it was easier and less stressful. Those who preferred the radiographer-directed technique felt more confident leaving the responsibility to the radiographer. In general, the patients understood the importance of achieving the best quality images possible. CONCLUSION: Magnetic resonance examination can be experienced as being in loss of control. Nevertheless, not all patients wished to actively participate in magnetic resonance examination. Some preferred to hand over the responsibility to the radiographer. These results can form a base for radiographers' reflections of how to individualize and optimize the nursing care of patients undergoing magnetic resonance examinations.

Three-Dimensional Histological Characterization of the Placental Vasculature Using Light Sheet Microscopy.

The placenta is the first embryonic organ, representing the connection between the embryo and the mother, and is therefore necessary for the embryo's growth and survival. To meet the ever-growing need for nutrient and gas exchange, the maternal spiral arteries undergo extensive remodeling, thus increasing the uteroplacental blood flow by 16-fold. However, the insufficient remodeling of the spiral arteries can lead to severe pregnancy-associated disorders, including but not limited to pre-eclampsia. Insufficient endovascular trophoblast invasion plays a key role in the manifestation of pre-eclampsia; however, the underlying processes are complex and still unknown. Classical histopathology is based on two-dimensional section microscopy, which lacks a volumetric representation of the vascular remodeling process. To further characterize the uteroplacental vascularization, a detailed, non-destructive, and subcellular visualization is beneficial. In this study, we use light sheet microscopy for optical sectioning, thus establishing a method to obtain a three-dimensional visualization of the vascular system in the placenta. By introducing a volumetric visualization method of the placenta, we could establish a powerful tool to deeply investigate the heterogeneity of the spiral arteries during the remodeling process, evaluate the state-of-the-art treatment options, effects on vascularization, and, ultimately, reveal new insights into the underlying pathology of pre-eclampsia.

Patients' and radiographers' experiences of dose reducing abdominal compression in radiographic examinations-A qualitative study.

Aim: To describe patients' and radiographers' experiences of abdominal compression using conventional and patient-controlled compression methods. Design: Qualitative descriptive design. Methods: Forty-five patients who had used both a conventional and a patient-controlled compression device answered questionnaires. Five radiographers were interviewed. The data-collection took place between September 2015 and February 2017. Data were analysed by qualitative content analysis. Results: Patient-controlled compression was preferred by slightly more patients because of fear of pain due to excessively hard pressure, maintaining control over the pressure and shorter duration. It was more comfortable, and patients felt they could participate in the examinations. Conventional compression was preferred by some because of more stable pressure and uncertainty of own capacity to provide the optimal compression. Discomfort was more often mentioned concerning the conventional compression method. The radiographers experienced the patient-controlled method as less time-consuming and more comfortable, but uncertainty about correct compression technique and its effect on radiation dose and image quality was reported.

Nuclear egress of TDP-43 and FUS occurs independently of Exportin-1/CRM1.

TDP-43 and FUS are nuclear proteins with multiple functions in mRNA processing. They play key roles in ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia), where they are partially lost from the nucleus and aggregate in the cytoplasm of neurons and glial cells. Defects in nucleocytoplasmic transport contribute to this pathology, hence nuclear import of both proteins has been studied in detail. However, their nuclear export routes remain poorly characterized and it is unclear whether aberrant nuclear export contributes to TDP-43 or FUS pathology. Here we show that predicted nuclear export signals in TDP-43 and FUS are non-functional and that both proteins are exported independently of the export receptor CRM1/Exportin-1. Silencing of Exportin-5 or the mRNA export factor Aly/REF, as well as mutations that abrogate RNA-binding do not impair export of TDP-43 and FUS. However, artificially enlarging TDP-43 or FUS impairs their nuclear egress, suggesting that they could leave the nucleus by passive diffusion. Finally, we found that inhibition of transcription causes accelerated nuclear egress of TDP-43, suggesting that newly synthesized RNA retains TDP-43 in the nucleus, limiting its egress into the cytoplasm. Our findings implicate reduced nuclear retention as a possible factor contributing to mislocalization of TDP-43 in ALS/FTD.

Patient-initiated breath-holds in MRI: an alternative for reducing respiratory artifacts and improving image quality.

PURPOSE: To investigate MRI image quality using two different breath-hold techniques. MATERIALS AND METHODS: Thirty patients remitted for MRI, 2D-dual gradient echo acquisition of the liver conducted two separate breath-hold acquisitions in randomized order, operator-instructed and patient-initiated. The images were reviewed by two radiologists. RESULTS: There were no significant differences in image quality between the two breath-hold techniques either in overall image quality or respiratory motion artifacts. This assessment was equal and concordant for both radiologists. CONCLUSION: In terms of image quality, the patient self-initiated breath-hold was shown to be an equal alternative to conventional breath-hold imaging.