Conserved cis-regulatory modules control robustness in Msx1 expression at single cell resolution

The process of transcription is highly stochastic leading to cell-to-cell variations and noise in gene expression levels. However, key essential genes have to be precisely expressed at the correct amount and time to ensure proper cellular development and function. Studies in yeast and bacterial systems have shown that gene expression noise decreases as mean expression levels increase, a relationship that is controlled by promoter DNA sequence. However, the function of distal cis-regulatory modules (CRMs), an evolutionary novelty of metazoans, in controlling transcriptional robustness and variability is poorly understood. In this study, we used live cell imaging of transfected reporters combined with a mathematical modelling and statistical inference scheme to quantify the function of conserved Msx1 CRMs and promoters in modulating single-cell real-time transcription rates in C2C12 mouse myoblasts. The results show that the mean expression–noise relationship is solely promoter controlled for this key pluripotency regulator. In addition, we demonstrate that CRMs modulate single-cell basal promoter rate distributions in a graded manner across a population of cells. This extends the rheostatic model of CRM action to provide a more detailed understanding of CRM function at single-cell resolution. We also identify a novel CRM transcriptional filter function that acts to reduce intracellular variability in transcription rates and show that this can be phylogenetically separable from rate modulating CRM activities. These results are important for understanding how the expression of key vertebrate developmental transcription factors is precisely controlled both within and between individual cells

The Dictyostelium type V myosin MyoJ is responsible for the cortical association and motility of contractile vacuole membranes

The contractile vacuole (CV) complex in Dictyostelium is a tubulovesicular osmoregulatory organelle that exhibits extensive motility along the actin-rich cortex, providing a useful model for investigating myosin-dependent membrane transport. Here, we show that the type V myosin myoJ localizes to CV membranes and is required for efficient osmoregulation, the normal accumulation of CV membranes in the cortex, and the conversion of collapsed bladder membranes into outwardly radiating cortical CV tubules. Complementation of myoJ-null cells with a version of myoJ containing a shorter lever arm causes these radiating tubules to move at a slower speed, confirming myoJ's role in translocating CV membranes along the cortex. MyoJ-null cells also exhibit a dramatic concentration of CV membranes around the microtubule-organizing center. Consistently, we demonstrate that CV membranes also move bi-directionally on microtubules between the cortex and the centrosome. Therefore, myoJ cooperates with plus and minus end–directed microtubule motors to drive the normal distribution and dynamics of the CV complex in Dictyostelium

Innovative public procurement guide

Podeu consultar la versió en català a: http://hdl.handle.net/11703/113907Podeu consultar la versió en castellà a: http://hdl.handle.net/11703/11563

Elementary modelling and behavioural analysis for emergency evacuations using social media

YesSocial media usage in evacuations and emergency management represents a rapidly expanding field of study. Our paper thus provides quantitative insight into a serious practical problem. Within this context a behavioural approach is key. We discuss when facilitators should consider model-based interventions amid further implications for disaster communication and emergency management. We model the behaviour of individual people by deriving optimal contrarian strategies. We formulate a Bayesian algorithm which enables the optimal evacuation to be conducted sequentially under worsening conditions.Supported by EPSRC (IDEAS Factory - Game theory and adaptive networks for smart evacuations, EP/I005765/1

Barcelona City Council ICT Public Procurement Guide

Les mencions de responsabilitat s'han basat en els crèdits facilitats per l'àrea responsablePodeu consultar la versió en català a: http://hdl.handle.net/11703/106505Podeu consultar la versió en castellà a: http://hdl.handle.net/11703/115663Directrius per a definir el nou model de relació amb els proveïdors de tecnologia basat en el Codi de Pràctiques Tecnològique

Daily Rhythms of Plasma Melatonin, but Not Plasma Leptin or Leptin mRNA, Vary between Lean, Obese and Type 2 Diabetic Men

Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM). We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45–65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO), nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01) and lean controls (p<0.05). Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001) effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual’s 24-hour mean, plasma leptin showed significant (p<0.001) diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05) of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither obesity nor T2DM changed 24-hour rhythms of plasma leptin relative to cycle mean, or expression of subcutaneous adipose leptin gene expression, compared with lean subjects

The ends justifies the means: A global research agenda for political marketing and public affairs

This is the peer reviewed version of the following article: Harris, P., & Sun, H. (2017). The ends justify the means: A global research agenda for political marketing and public affairs. Journal of Public Affairs, 14(4), e1693 which has been published in final form at http://dx.doi.org/10.1002/pa.1693 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Political marketing has developed into an increasingly mainstream discipline in universities globally over the last decade. There are many schools of political marketing with different approaches, such as the North American approach, the Western and Eastern European perspectives, and the Asian position. The study and application of political marketing has been categorised with different perspectives, such as electoral, governmental, and international aspects. It is becoming increasingly evident that political marketing needs further classification like any matured and established discipline. A close analysis of political marketing practices and academic research leads one to perceive two distinct areas of political exchanges in two different markets: the intranational market and the international market

Guia de contractació pública innovadora

Podeu consultar la versió en castellà a: http://hdl.handle.net/11703/115635Podeu consultar la versió en anglès a: http://hdl.handle.net/11703/115653Podeu consultar la versió editada per Imatge i Serveis Editorials a: http://hdl.handle.net/11703/11574