Frequency doubling in the cyanobacterial circadian clock

Organisms use circadian clocks to generate 24-h rhythms in gene expression. However, the clock can interact with other pathways to generate shorter period oscillations. It remains unclear how these different frequencies are generated. Here, we examine this problem by studying the coupling of the clock to the alternative sigma factor $\textit{sigC}$ in the cyanobacterium $\textit{Synechococcus elongatus}$. Using single-cell microscopy, we find that $\textit{psbAI}$, a key photosynthesis gene regulated by both $\textit{sigC}$ and the clock, is activated with two peaks of gene expression every circadian cycle under constant low light. This two-peak oscillation is dependent on $\textit{sigC}$, without which $\textit{psbAI}$ rhythms revert to one oscillatory peak per day. We also observe two circadian peaks of elongation rate, which are dependent on $\textit{sigC}$, suggesting a role for the frequency doubling in modulating growth. We propose that the two-peak rhythm in $\textit{psbAI}$ expression is generated by an incoherent feedforward loop between the clock, $\textit{sigC}$ and $\textit{psbAI}$. Modelling and experiments suggest that this could be a general network motif to allow frequency doubling of outputs.This research was made possible by the award of a European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 338060. The work in the Locke laboratory is further supported by a fellowship from the Gatsby Foundation (GAT3272/GLC) and a Fellowship from the Human Frontier Science Program (CDA00068/2012)

Patterns of Individual Shopping Behavior

Much of economic theory is built on observations of aggregate, rather than individual, behavior. Here, we present novel findings on human shopping patterns at the resolution of a single purchase. Our results suggest that much of our seemingly elective activity is actually driven by simple routines. While the interleaving of shopping events creates randomness at the small scale, on the whole consumer behavior is largely predictable. We also examine income-dependent differences in how people shop, and find that wealthy individuals are more likely to bundle shopping trips. These results validate previous work on mobility from cell phone data, while describing the unpredictability of behavior at higher resolution.Comment: 4 pages, 5 figure

Dark halo baryons not in ancient halo white dwarfs

Having ruled out the possibility that stellar objects are the main contributor of the dark matter embedding galaxies, microlensing experiments cannot exclude the hypothesis that a significant fraction of the Milky Way dark halo might be made of MACHOs with masses in the range 0.5-0.8 \msun. Ancient white dwarfs are generally considered the most plausible candidates for such MACHOs. We report the results of a search for such white dwarfs in a proper motion survey covering a 0.16 sqd field at three epochs at high galactic latitude, and 0.938 sqd at two epochs at intermediate galactic latitude (VIRMOS survey), using the CFH telescope. Both surveys are complete to I = 23, with detection efficiency fading to 0 at I = 24.2. Proper motion data are suitable to separate unambiguously halo white dwarfs identified by belonging to a non rotating system. No candidates were found within the colour-magnitude-proper motion volume where such objects can be safely discriminated from any standard population as well as from possible artefacts. In the same volume, we estimate the maximum white dwarf halo fraction compatible with this observation at different significance levels if the halo is at least 14 gigayears old and under different ad hoc initial mass functions. Our data alone rules out a halo fraction greater than 14% at 95% confidence level. Combined with two previous investigations exploring comparable volumes pushes the limit below 4 % (95% confidence level) or below 1.3% (64% confidence), this implies that if baryonic dark matter is present in galaxy halos, it is not, or it is only marginally in the form of faint hydrogen white dwarfs.Comment: accepted in Astronomy and Astrophysics (19-05-2004

Burgers velocity fields and dynamical transport processes

We explore a connection of the forced Burgers equation with the Schr\"{o}dinger (diffusive) interpolating dynamics in the presence of deterministic external forces. This entails an exploration of the consistency conditions that allow to interpret dispersion of passive contaminants in the Burgers flow as a Markovian diffusion process. In general, the usage of a continuity equation $\partial_t\rho =-\nabla (\vec{v}\rho)$, where $\vec{v}=\vec{v}(\vec{x},t)$ stands for the Burgers field and $\rho$ is the density of transported matter, is at variance with the explicit diffusion scenario. Under these circumstances, we give a complete characterisation of the diffusive matter transport that is governed by Burgers velocity fields. The result extends both to the approximate description of the transport driven by an incompressible fluid and to motions in an infinitely compressible medium.Comment: Latex fil

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Cross-cultural adaptation and validation of the “spinal cord injury-falls concern scale” in the Italian population

Study design: Psychometrics study. Objective: The objective of this study was to develop an Italian version of the Spinal Cord Injury-Falls Concern Scale (SCI-FCS) and examine its reliability and validity. Setting: Multicenter study in spinal units in Northern and Southern Italy. The scale also was administered to non-hospitalized outpatient clinic patients. Methods: The original scale was translated from English to Italian using the “Translation and Cultural Adaptation of Patient-Reported Outcomes Measures” guidelines. The reliability and validity of the culturally adapted scale were assessed following the “Consensus-Based Standards for the Selection of Health Status Measurement Instruments” checklist. The SCI-FCS-I internal consistency, inter-rater, and intra-rater reliability were examined using Cronbach’s alpha coefficient and the intraclass correlation coefficient, respectively. Concurrent validity was evaluated using Pearson’s correlation coefficient with the Italian version of the short form of the Wheelchair Use Confidence Scale for Manual Wheelchair Users (WheelCon-M-I-short form). Results: The Italian version of the SCI-FCS-I was administered to 124 participants from 1 June to 30 September 2017. The mean ± SD of the SCI-FCS-I score was 16.73 ± 5.88. All SCI-FCS items were either identical or similar in meaning to the original version’s items. Cronbach’s α was 0.827 (p < 0.01), the inter-rater reliability was 0.972 (p < 0.01), and the intra-rater reliability was 0.973 (p < 0.01). Pearson’s correlation coefficient of the SCI-FCS-I scores with the WheelCon-M-I-short form was 0.56 (p < 0.01). Conclusions: The SCI-FCS-I was found to be reliable and a valid outcome measure for assessing manual wheelchair concerns about falling in the Italian population