Mixed Magnetism for Refrigeration and Energy Conversion

The efficient coupling between lattice degrees of freedom and spin degrees of freedom in magnetic materials can be used for refrigeration and energy conversion. This coupling is enhanced in materials exhibiting the giant magnetocaloric effect. First principle electronic structure calculations on hexagonal MnFe(P, Si) reveal a new form of magnetism: the coexistence of strong and weak magnetism in alternate atomic layers. The weak magnetism of Fe layers (disappearance of local magnetic moments at the Curie temperature) is responsible for a strong coupling with the crystal lattice while the strong magnetism in adjacent Mn‐layers ensures Curie temperatures high enough to enable operation at and above room temperature. Varying the composition on these magnetic sublattices gives a handle to tune the working temperature and to achieve a strong reduction of the undesired thermal hysteresis. In this way we design novel materials based on abundantly available elements with properties matched to the requirements of an efficient refrigeration or energy‐conversion cycle.     

Quantifying the emergence of dengue in Hanoi, Vietnam: 1998-2009

Background

An estimated 2.4 billion people live in areas at risk of dengue transmission, therefore the factors determining the establishment of endemic dengue in areas where transmission suitability is marginal is of considerable importance. Hanoi, Vietnam is such an area, and following a large dengue outbreak in 2009, we set out to determine if dengue is emerging in Hanoi.

Methods and Principal Findings

We undertook a temporal and spatial analysis of 25,983 dengue cases notified in Hanoi between 1998 and 2009. Age standardized incidence rates, standardized age of infection, and Standardized Morbidity Ratios (SMR) were calculated. A quasi-Poisson regression model was used to determine if dengue incidence was increasing over time. Wavelet analysis was used to explore the periodicity of dengue transmission and the association with climate variables. After excluding the two major outbreak years of 1998 and 2009 and correcting for changes in population age structure, we identified a significant annual increase in the incidence of dengue cases over the period 1999–2008 (incidence rate ratio  = 1.38, 95% confidence interval  = 1.20–1.58, p value  = 0.002). The age of notified dengue cases in Hanoi is high, with a median age of 23 years (mean 26.3 years). After adjusting for changes in population age structure, there was no statistically significant change in the median or mean age of dengue cases over the period studied. Districts in the central, highly urban, area of Hanoi have the highest incidence of dengue (SMR>3).

Conclusions

Hanoi is a low dengue transmission setting where dengue incidence has been increasing year on year since 1999. This trend needs to be confirmed with serological surveys, followed by studies to determine the underlying drivers of this emergence. Such studies can provide insights into the biological, demographic, and environmental changes associated with vulnerability to the establishment of endemic dengue.     

Nucleosome-remodelling machines and other molecular motors observed at the single-molecule level

Through its capability to transiently pack and unpack our genome, chromatin is a key player in the regulation of gene expression. Single-molecule approaches have recently complemented conventional biochemical and biophysical techniques to decipher the complex mechanisms ruling chromatin dynamics. Micromanipulations with tweezers (magnetic or optical) and imaging with molecular microscopy (electron or atomic force) have indeed provided opportunities to handle and visualize single molecules, and to measure the forces and torques produced by molecular motors, along with their effects on DNA or nucleosomal templates. By giving access to dynamic events that tend to be blurred in traditional biochemical bulk experiments, these techniques provide critical information regarding the mechanisms underlying the regulation of gene activation and deactivation by nucleosome and chromatin structural changes. This minireview describes some single-molecule approaches to the study of ATP-consuming molecular motors acting on DNA, with applications to the case of nucleosome-remodelling machines.     

Predictive integration of gene functional similarity and co-expression defines treatment response of endothelial progenitor cells

Background  

Endothelial progenitor cells (EPCs) have been implicated in different processes crucial to vasculature repair, which may offer the basis for new therapeutic strategies in cardiovascular disease. Despite advances facilitated by functional genomics, there is a lack of systems-level understanding of treatment response mechanisms of EPCs. In this research we aimed to characterize the EPCs response to adenosine (Ado), a cardioprotective factor, based on the systems-level integration of gene expression data and prior functional knowledge. Specifically, we set out to identify novel biosignatures of Ado-treatment response in EPCs.     

Large-scale structural analysis of the core promoter in mammalian and plant genomes

DNA encodes at least two independent levels of functional information. The first level is for encoding proteins and sequence targets for DNA-binding factors, while the second one is contained in the physical and structural properties of the DNA molecule itself. Although the physical and structural properties are ultimately determined by the nucleotide sequence itself, the cell exploits these properties in a way in which the sequence itself plays no role other than to support or facilitate certain spatial structures. In this work, we focus on these structural properties, comparing them between different organisms and assessing their ability to describe the core promoter. We prove the existence of distinct types of core promoters, based on a clustering of their structural profiles. These results indicate that the structural profiles are much conserved within plants (Arabidopsis and rice) and animals (human and mouse), but differ considerably between plants and animals. Furthermore, we demonstrate that these structural profiles can be an alternative way of describing the core promoter, in addition to more classical motif or IUPAC-based approaches. Using the structural profiles as discriminatory elements to separate promoter regions from non-promoter regions, reliable models can be built to identify core-promoter regions using a strictly computational approach.     

Hypoxic alterations of cortisol circadian rhythm in man after simulation of a long duration flight

Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurisation may be involved in this effect through disruption of circadian rhythms, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the circadian rhythm of plasma cortisol, a marker of the circadian time structure. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 h (08:00-16:00 h) to 8000 ft, followed 4 weeks later to 12,000 ft. Plasma cortisol was assayed during two 24-h cycles (control and hypoxic exposure) every 2h in all subjects. We found a significant change in the pattern of cortisol secretion during both hypoxic exposures, with an initial fall in cortisol followed by a transient rebound, whereas the phase and the 24-h mean level remained unchanged. The change in cortisol pattern followed the alterations in autonomic balance assessed by heart rate variability (HRV) spectral analysis. The normalised high frequencies and the low-to-high frequencies ratio showed a significant shift toward sympathetic dominance with some differences in time course for both altitudes studied. HRV analysis improved the interpretation of cortisol 24-h profiles. Our data, which strongly suggest that prolonged mild hypoxia alters the expression of cortisol circadian rhythm, should be taken into account to interpret secretory rhythm changes after transmeridian flights.     

Diazepam affects both level and amplitude of rat locomotor activity rhythm but has no effect on core body temperature

The present study investigates the effects of a chronic administration of diazepam, a benzodiazepine widely used as an anxiolytic, on locomotor activity and body core temperature rhythms in male Wistar rats housed under 12:12 light:dark (LD) cycle conditions. Diazepam was administered subcutaneously for 3 wks in a dosage of 3 mg/kg body weight/day, 1 h before the onset of darkness. Diazepam increased the level of locomotor activity from the first day until the end of treatment, and also increased the amplitude of the activity circadian rhythm, but only on the third wk of treatment. Diazepam exerted no effects on the length of the period and did not affect the phase of the locomotor activity rhythm. The body temperature rhythm of rats was affected neither by short-term (a single injection) nor by long-term (every day for 3 wks) diazepam treatment. Diazepam lacked effect on body core temperature even on the first day of administration, thereby ruling out the possibility of drug tolerance development. The fact that diazepam affects locomotor activity, but not core body temperature, suggests that different mechanisms mediate the actions of diazepam on locomotor activity and on core body temperature.     

Efficient production of Clostridium botulinum exotoxin C3 in bacteria: a screening method to optimize production yields

Clostridium botulinum exoenzyme C3 is responsible for the inactivation of members of the Rho GTPase family that are implicated in actin-cytoskeleton reorganization. This property has been extensively used in the field to investigate the functionality of the Rho GTPases. However, systematic analysis of Rho GTPase functions requires large amounts of such inhibitors and consequently an optimization of the production yield of these proteins. Bacterial production of soluble proteins often requires a refolding step that noticeably affects the production yields and necessitates additional experiments to verify functional activity. This is particularly true for TAT-C3, the production yields of which are generally low. In this report, we describe a rapid and efficient method for the production of soluble C3 exoenzyme developed by screening a collection of bacterial strains. The recombinant C3 protein was fused to the TAT protein-transduction domain from HIV, to allow protein delivery into cells, and to a hexahistidine tag, that permitted purification by Nickel affinity chromatography. We have demonstrated the production of large amounts of soluble and functional protein using the bacterial strain AD494 (DE3)pLysS. This rapid and efficient method for the production of soluble C3 exoenzyme could also be useful for the production of other proteins with solubility problems.     

The Arg482His mutation in the beta-galactosidase gene is responsible for a high frequency of GM1 gangliosidosis carriers in a Cypriot village

GM1 gangliosidosis is a lysosomal storage disorder caused by deficiency of beta-galactosidase. It is mainly characterized by progressive neurodegeneration, and in its most severe infantile form, it leads to death before the age of 4. The GLB1 gene gives rise to two alternatively spliced mRNAs that encode the beta-galactosidase and the elastin binding protein (EBP). The diagnosis of two patients with the infantile form of GM1 gangliosidosis and 11 carriers in a small mountainous village in Cyprus prompted us to carry out a study in order to establish the frequency of carriers in the village and identify the mutations involved. Carrier detection was initially based on the measurement of beta-galactosidase activity in leucocytes. Among 85 random samples from the village, 10 were classified as carriers. Sequencing of the GLB1 gene in a Cypriot patient identified the missense mutation c.1445G>A (p.Arg482His) in the homozygous state. Seven of the 10 carriers identified using the enzyme assay were found to carry the same mutation by NspI restriction enzyme analysis. The three individuals who were negative for the c.1445G>A had borderline enzyme results and were probably wrongly classified as carriers. The frequency of GM1 gangliosidosis carriers in this village is approximately 8% (1:12). Western blot analysis showed a marked decrease of the 64-kDa mature form of the enzyme protein and a similar reduction of the 67-kDa EBP. Our results indicate that the c.1445G>A mutation, which appears to be responsible for all GM1 gangliosidosis alleles in this Cypriot village, affects protein conformation.     

Nuclear transfer: a new tool for reproductive biotechnology in cattle

Recent evolutions of somatic cloning by nuclear transfer are reported, especially in the bovine species where potential applications are underway for biomedicine in association with transgenesis, or for agriculture by improving livestock. The overall efficiency of this biotechnology remains low in terms of viable offspring, but significant progress has been achieved on the different steps of the technique. However, the in vivo development of bovine blastocysts derived from somatic nuclear transfer is characterised by some important features that lead to the "cloning syndrome". Important losses occur during the peri-implantation period and further late foetal loss is observed in association with the Large Offspring Syndrome. About 60-70% of the cloned calves born survive normally to the adult stage and present an apparently normal physiology. Recent data already available on bovine somatic clones of both sexes indicate that they have a zootechnical performance similar to non cloned animals and they are able to reproduce normally without the pathologies associated to cloning thus confirming that the deviations observed in clones are of epigenetic origin and not transmitted to the progeny.