Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Variable-focus microlenses as a potential technology for endoscopy

Using a new device which contains an array of microlenses whose focal lengths can be electrically varied, we have been able to control the input from one microlens to a single mode fibre using an applied voltage. For such a microlens array many closely-spaced focal spots can be generated in parallel, and electrically switched to address, potentially, an array of receiver fibres. We show how the particular switching characteristics of the device, whereby the lenses switch from diverging to converging, serves in turn to disperse light and to focus it into the fibre

Use of intravitreal bevacizumab in a patient with a Von Hippel-Lindau-associated retinal haemangioblastoma of the optic nerve head: a case report

<p>Abstract</p> <p>Introduction</p> <p>The optimum management of a capillary haemangioblastoma affecting the optic nerve head is not clear. A number of treatment modalities have been used to treat the tumours and their consequences. Ocular haemangioblastomas express high levels of vascular endothelial growth factor and levels have been correlated with tumour growth and activity. Treatment with vascular endothelial growth factor inhibitors would therefore seem a logical approach.</p> <p>Case presentation</p> <p>We describe a 23-year-old man with an exophytic capillary haemangioblastoma of the optic nerve head that was treated with intravitreal bevacizumab injections.</p> <p>Conclusion</p> <p>Unfortunately, treatment with intravitreal bevacizumab on three occasions had no effect on either tumour size or exudation in this patient.</p

Neuronal Plasticity and Multisensory Integration in Filial Imprinting

Many organisms sample their environment through multiple sensory systems and the integration of multisensory information enhances learning. However, the mechanisms underlying multisensory memory formation and their similarity to unisensory mechanisms remain unclear. Filial imprinting is one example in which experience is multisensory, and the mechanisms of unisensory neuronal plasticity are well established. We investigated the storage of audiovisual information through experience by comparing the activity of neurons in the intermediate and medial mesopallium of imprinted and naïve domestic chicks (Gallus gallus domesticus) in response to an audiovisual imprinting stimulus and novel object and their auditory and visual components. We find that imprinting enhanced the mean response magnitude of neurons to unisensory but not multisensory stimuli. Furthermore, imprinting enhanced responses to incongruent audiovisual stimuli comprised of mismatched auditory and visual components. Our results suggest that the effects of imprinting on the unisensory and multisensory responsiveness of IMM neurons differ and that IMM neurons may function to detect unexpected deviations from the audiovisual imprinting stimulus

Physiological demands of singing for lung health compared with treadmill walking

© Author(s) (or their employer(s)) 2021. Introduction Participating in singing is considered to have a range of social and psychological benefits. However, the physiological demands of singing and its intensity as a physical activity are not well understood. Methods We compared cardiorespiratory parameters while completing components of Singing for Lung Health sessions, with treadmill walking at differing speeds (2, 4 and 6 km/hour). Results Eight healthy adults were included, none of whom reported regular participation in formal singing activities. Singing induced acute physiological responses that were consistent with moderate intensity activity (metabolic equivalents: Median 4.12, IQR 2.72-4.78), with oxygen consumption, heart rate and volume per breath above those seen walking at 4 km/hour. Minute ventilation was higher during singing (median 22.42 L/min, IQR 16.83-30.54) than at rest (11 L/min, 9-13), lower than 6 km/hour walking (30.35 L/min, 26.94-41.11), but not statistically different from 2 km/hour (18.77 L/min, 16.89-21.35) or 4 km/hour (23.27 L/min, 20.09-26.37) walking. Conclusions Our findings suggest the acute metabolic demands of singing are comparable with walking at a moderately brisk pace, hence, physical effects may contribute to the health and well-being benefits attributed to singing participation. However, if physical training benefits result remains uncertain. Further research including different singing styles, singers and physical performance impacts when used as a training modality is encouraged.KEJP was supported by the Imperial College Clinician Investigator Scholarship (no specific grant number/code). DF was supported by the Wellcome Trust (205407/Z/16/Z)

‘Do i care?’ young adults' recalled experiences of early adolescent overweight and obesity: a qualitative study

&lt;p&gt;Objective: Individual behaviour change to reduce obesity requires awareness of, and concern about, weight. This paper therefore describes how young adults, known to have been overweight or obese during early adolescence, recalled early adolescent weight-related awareness and concerns. Associations between recalled concerns and weight-, health- and peer-related survey responses collected during adolescence are also examined.&lt;/p&gt; &lt;p&gt;Design: Qualitative semi-structured interviews with young adults; data compared with responses to self-report questionnaires obtained in adolescence.&lt;/p&gt; &lt;p&gt;Participants: A total of 35 participants, purposively sub-sampled at age 24 from a longitudinal study of a school year cohort, previously surveyed at ages 11, 13 and 15. Physical measures during previous surveys allowed identification of participants with a body mass index (BMI) indicative of overweight or obesity (based on British 1990 growth reference) during early adolescence. Overall, 26 had been obese, of whom 11 had BMI99.6th centile, whereas 9 had been overweight (BMI=95th–97.9th centile).&lt;/p&gt; &lt;p&gt;Measures: Qualitative interview responses describing teenage life, with prompts for school-, social- and health-related concerns. Early adolescent self-report questionnaire data on weight-worries, self-esteem, friends and victimisation (closed questions).&lt;/p&gt; &lt;p&gt;Results: Most, but not all recalled having been aware of their overweight. None referred to themselves as having been obese. None recalled weight-related health worries. Recollection of early adolescent obesity varied from major concerns impacting on much of an individual's life to almost no concern, with little relation to actual severity of overweight. Recalled concerns were not clearly patterned by gender, but young adult males recalling concerns had previously reported more worries about weight, lower self-esteem, fewer friends and more victimisation in early adolescence; no such pattern was seen among females. Conclusion: The popular image of the unhappy overweight teenager was not borne out. Many obese adolescents, although well aware of their overweight recalled neither major dissatisfaction nor concern. Weight-reduction behaviours are unlikely in such circumstances.&lt;/p&gt

Multidimensional sexual perfectionism and female sexual function: A longitudinal investigation

Research on multidimensional sexual perfectionism differentiates four forms of sexual perfectionism: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. Self-oriented sexual perfectionism reflects perfectionistic standards people apply to themselves as sexual partners; partner-oriented sexual perfectionism reflects perfectionistic standards people apply to their sexual partner; partner-prescribed sexual perfectionism reflects people’s beliefs that their sexual partner imposes perfectionistic standards on them; and socially prescribed sexual perfectionism reflects people’s beliefs that society imposes such standards on them. Previous studies found partner-prescribed and socially prescribed sexual perfectionism to be maladaptive forms of sexual perfectionism associated with a negative sexual self-concept and problematic sexual behaviors, but only examined cross-sectional relationships. The present article presents the first longitudinal study examining whether multidimensional sexual perfectionism predicts changes in sexual self-concept and sexual function over time. A total of 366 women aged 17-69 years completed measures of multidimensional sexual perfectionism, sexual esteem, sexual anxiety, sexual problem self-blame, and female sexual function (cross-sectional data). Three to six months later, 164 of the women completed the same measures again (longitudinal data). Across analyses, partner-prescribed sexual perfectionism emerged as the most maladaptive form of sexual perfectionism. In the cross-sectional data, partner-prescribed sexual perfectionism showed positive relationships with sexual anxiety, sexual problem self-blame, and intercourse pain and negative relationships with sexual esteem, desire, arousal, lubrication, and orgasmic function. In the longitudinal data, partner-prescribed sexual perfectionism predicted increases in sexual anxiety and decreases in sexual esteem, arousal, and lubrication over time. The findings suggest that partner-prescribed sexual perfectionism contributes to women’s negative sexual self-concept and female sexual dysfunction

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention