Translational perspectives on MSMB and CRISP3 expression and regulation in prostate cancer

Prostate cancer is currently the most common form of cancer in Sweden. Currently, the only biomarker used in the clinic is serum PSA, and there is a great need for new biomarkers that may increase the diagnostic and prognostic information so that better predictions can be made, and treatment may be tailored. Here, we have investigated two proposed biomarkers microseminoprotein-β (MSMB) and cysteine-rich secretory protein-3 (CRISP3). Firstly, we wanted to validate previous findings, that MSMB and CRISP3 are predictors of recurrence in patients undergoing radical prostatectomy for localized prostate cancer. Using a novel automated image analysis tool, IHC-MARK, we found that MSMB was an independent predictor of recurrence in a large patient cohort. Further, we showed that expression of both MSMB and CRISP3 was induced by androgen in vitro, and MSMB was decreased in patients receiving androgen deprivation therapy prior to radical prostatectomy. MSMB was virtually lost in advanced prostate cancer, in contrast to CRISP3 which was highly expressed. Inflammation has been suggested to be a primary aetiological event in prostate cancer and the presence of putative binding elements for inflammatory transcription factors in the promoter region of CRISP3 led us to hypothesise that CRISP3 may be regulated by inflammatory stimuli. Instead, stimulation of prostate cancer cells with interleukin (IL)-6 strongly induced MSMB expression but had no effect on CRISP3 expression. A long-term IL-6 stimulated cell line, however, had no MSMB expression, probably due to DNA methylation. Finally, expression of MSMB in cell lines without endogenous MSMB resulted in decreased cyclin D1 expression and reduced proliferation. In conclusion, MSMB is an independent predictor of recurrence, whereas the value of CRISP3 as a biomarker remains to be elucidated. In vitro studies show that MSMB may be important for prostate cancer proliferation, but more studies on MSMB and CRISP3 functions are warranted

Eye Tracking during High Speed Navigation at Sea

Purpose: Professional high speed sea navigational procedures are based on turn points, courses, dangers and steering cues in the environment. Since navigational aids have become less expensive and due to the fact that electronic sea charts can be integrated with both radar and transponder information, it may be assumed that traditional navigation by using paper based charts and radar will play a less significant role in the future, especially among less experienced navigators. Possible navigational differences between experienced and non-experienced boat drivers is thus of interest with regards to their use of navigational aids. It may be assumed that less experienced navigators rely too much on the information given by the electronic sea chart, despite the fact that it is based on GPS information that can be questioned, especially in littoral waters close to land.Method: This eye tracking study investigates gaze behaviour from 16 experienced and novice boat drivers during high speed navigation at sea.Results: The results show that the novice drivers look at objects that are close to themselves, like instrumentation, while the experienced look more at objects far away from the boat. This is in accordance with previous research on car drivers. Further, novice boat drivers used the electronic navigational aids to a larger extent than the experienced, especially during high speed conditions. The experienced drivers focused much of their attention on objects outside the boat.Conclusions: The findings verify that novice boat drivers tend to rely on electronic navigational aids. Experienced drivers presumably use the navigational aids to verify what they have observed in the surrounding environment and further use the paper based sea chart to a larger extent than the novice drivers

Inclusive Residential Areas - a report on a fieldtrip to the Netherlands

This report discusses seven residential areas in the Netherlands from the perspective of social inclusiveness – EVA Lanxmeer, Park Rosendaal, Bijlmermeer, Diagoon Housing, Spangen, Ypenburg and Java Island. The material was collected during a field trip to the Netherlands in spring 2020, as part of a Call for Ideas initiative from SLU Landscape. Jointly, we have compiled our experiences from the field trip in this publication, for inspirational use within educational settings

Vitamin D Status during Pregnancy in a Multi-Ethnic Population-Representative Swedish Cohort

There is currently little information on changes in vitamin D status during pregnancy and its predictors. The aim was to study the determinants of change in vitamin D status during pregnancy and of vitamin D deficiency (<30 nmol/L) in early pregnancy. Blood was drawn in the first (T1) and third trimester (T3). Serum 25-hydroxyvitamin D (25(OH)D) (N = 1985) was analysed by liquid chromatography tandem-mass spectrometry. Season-corrected 25(OH)D was calculated by fitting cosine functions to the data. Mean (standard deviation) 25(OH)D was 64.5(24.5) nmol/L at T1 and 74.6(34.4) at T3. Mean age was 31.3(4.9) years, mean body mass index (BMI) was 24.5(4.2) kg/m2 and 74% of the women were born in Sweden. Vitamin D deficiency was common among women born in Africa (51%) and Asia (46%) and prevalent in 10% of the whole cohort. Determinants of vitamin D deficiency at T1 were of non-North European origin, and had less sun exposure, lower vitamin D intake and lower age. Season-corrected 25(OH)D increased by 11(23) nmol/L from T1 to T3. The determinants of season-corrected change in 25(OH)D were origin, sun-seeking behaviour, clothing style, dietary vitamin D intake, vitamin D supplementation and recent travel <35° N. In conclusion, season-corrected 25(OH)D concentration increased during pregnancy and depended partly on lifestyle factors. The overall prevalence of vitamin D deficiency was low but common among women born in Africa and Asia. Among them, the determinants of both vitamin D deficiency and change in season-corrected vitamin D status were fewer, indicating a smaller effect of sun exposure

Fatty Acids Derived from Royal Jelly Are Modulators of Estrogen Receptor Functions

Royal jelly (RJ) excreted by honeybees and used as a nutritional and medicinal agent has estrogen-like effects, yet the compounds mediating these effects remain unidentified. The possible effects of three RJ fatty acids (FAs) (10-hydroxy-2-decenoic-10H2DA, 3,10-dihydroxydecanoic-3,10DDA, sebacic acid-SA) on estrogen signaling was investigated in various cellular systems. In MCF-7 cells, FAs, in absence of estradiol (E2), modulated the estrogen receptor (ER) recruitment to the pS2 promoter and pS2 mRNA levels via only ERβ but not ERα, while in presence of E2 FAs modulated both ERβ and ERα. Moreover, in presence of FAs, the E2-induced recruitment of the EAB1 co-activator peptide to ERα is masked and the E2-induced estrogen response element (ERE)-mediated transactivation is inhibited. In HeLa cells, in absence of E2, FAs inhibited the ERE-mediated transactivation by ERβ but not ERα, while in presence of E2, FAs inhibited ERE-activity by both ERβ and ERα. Molecular modeling revealed favorable binding of FAs to ERα at the co-activator-binding site, while binding assays showed that FAs did not bind to the ligand-binding pocket of ERα or ERβ. In KS483 osteoblasts, FAs, like E2, induced mineralization via an ER-dependent way. Our data propose a possible molecular mechanism for the estrogenic activities of RJ's components which, although structurally entirely different from E2, mediate estrogen signaling, at least in part, by modulating the recruitment of ERα, ERβ and co-activators to target genes

Physiological and Cognitive Performance in F-22 Pilots During Day and Night Flying

The article of record as published may be found at https://doi.org/10.3357/AMHP.5508.2021Many workers routinely transition between day and night shifts—including pilots, where night flights are commonly considered more stressful. The physiological toll from this transition is not fully understood, though fatigue is a factor in many aviation accidents. This research investigated the changes in physiological markers of stress and cognitive performance as F-22 pilots transitioned from day flying to night flying

Could sound be used as a strategy for reducing symptoms of perceived motion sickness?

<p>Abstract</p> <p>Background</p> <p>Working while exposed to motions, physically and psychologically affects a person. Traditionally, motion sickness symptom reduction has implied use of medication, which can lead to detrimental effects on performance. Non-pharmaceutical strategies, in turn, often require cognitive and perceptual attention. Hence, for people working in high demand environments where it is impossible to reallocate focus of attention, other strategies are called upon. The aim of the study was to investigate possible impact of a mitigation strategy on perceived motion sickness and psychophysiological responses, based on an artificial sound horizon compared with a non-positioned sound source.</p> <p>Methods</p> <p>Twenty-three healthy subjects were seated on a motion platform in an artificial sound horizon or in non-positioned sound, in random order with one week interval between the trials. Perceived motion sickness (Mal), maximum duration of exposure (ST), skin conductance, blood volume pulse, temperature, respiration rate, eye movements and heart rate were measured continuously throughout the trials.</p> <p>Results</p> <p>Mal scores increased over time in both sound conditions, but the artificial sound horizon, applied as a mitigation strategy for perceived motion sickness, showed no significant effect on Mal scores or ST. The number of fixations increased with time in the non-positioned sound condition. Moreover, fixation time was longer in the non-positioned sound condition compared with sound horizon, indicating that the subjects used more time to fixate and, hence, assumingly made fewer saccades.</p> <p>Conclusion</p> <p>A subliminally presented artificial sound horizon did not significantly affect perceived motion sickness, psychophysiological variables or the time the subjects endured the motion sickness triggering stimuli. The number of fixations and fixation times increased over time in the non-positioned sound condition.</p

Naturally Occurring Osmolyte, Trehalose Induces Functional Conformation in an Intrinsically Disordered Activation Domain of Glucocorticoid Receptor

Intrinsically disordered (ID) regions are frequently found in the activation domains of many transcription factors including nuclear hormone receptors. It is believed that these ID regions promote molecular recognition by creating large surfaces suitable for interactions with their specific protein binding partners, which is a critical component of gene regulation by transcription factors. It has been hypothesized that conditional folding of these activation domains may be a prerequisite for their efficient interaction with specific coregulatory proteins, and subsequent transcriptional activity leading to the regulation of target gene(s). In this study, we tested whether a naturally occurring osmolyte, trehalose can promote functionally ordered conformation in glucocorticoid receptor's major activation function domain, AF1, which is found to exist as an ID protein, and requires an efficient interaction with coregulatory proteins for optimal activity. Our data show that trehalose induces an ordered conformation in AF1 such that its interaction with steroid receptor coactivator-1 (SRC-1), a critical coregulator of glucocorticoid receptor's activity, is greatly enhanced

Usability of the SAFEWAY@SCHOOL system in children with cognitive disabilities

PurposeSAFEWAY2SCHOOL is a programme based on several systems for the enhancement of school transportation safety for children. The aim of the study was to explore whether children with cognitive disabilities will notice, realise, understand, trust and accept the SAFEWAY2SCHOOL system and act in accordance with its instructions. Methods Fourteen children with cognitive disabilities and a control group of 23 children were shown five videos of scenarios involving journeys to and from school. During the first viewing visual scanning patterns were recorded with an eye tracking device. After a second viewing the participant was asked ten questions per scenario. Five questions addressed what the children saw on the video, and the remaining five what they would need to know and/or do within the scenario. Additional ratings of trust, likability, acceptability and usability were also collected. Results Very few differences were found in the visual scanning patterns of children with disabilities compared to children who participated in the control group. Of the 50 questions regarding what children saw or needed to know and/or do, only one significant difference between groups was found. No significant differences were found regarding self-reported ratings of trust, acceptability or usability of the system. Despite some significant differences across five of the 11 likability aspects, ratings were consistently high for both groups. Conclusions Children with cognitive disabilities proved that the SAFEWAY2SCHOOL system is as useful for them as it was for children in the control group. However, a valid estimation of the full utility of SAFEWAY2SCHOOL requires in situ testing of the system with these children