Determinants of plasma uric acid

Summary Obesity, alcohol consumption, and hematocrit provide an index of plasma uric acid, which in path analysis has a cultural heritability of 0.11 in children and 0.23 in parents, a small maternal effect, and a genetic heritability of 0.25 in both generations. Preliminary evidence for a major locus is destroyed by the omission of one exceptional child. There is no evidence against the polygenic hypothesis for hyperuricemia in the Japanese-American population studied.     

Asymmetric synthesis of the four diastereoisomers of a novel non-steroidal farnesoid X receptor (FXR) agonist: Role of the chirality on the biological activity

An asymmetric synthetic strategy was designed for the preparation of the four possible diastereoisomers of 3,6-dimethyl-1-(2-methylphenyl)-4-(4-phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one, a non-steroidal FXR agonist, we recently discovered following a virtual screening approach. The results obtained from an AlphaScreen assay clearly demonstrated that only the isomer endowed with 4R,6S absolute configuration is responsible for the biological activity. A deep investigation of the different putative binding modes adopted by these enantiomerically pure ligands using computational modeling studies confirmed the enantioselectivity of FXR towards this class of molecules.     

Comparison of visual and objective quantification of elbow and shoulder movement in children with obstetric brachial plexus palsy

Background

Animal studies have demonstrated complex cortical reorganization following peripheral nerve lesion. Central projection fields of intact nerves supplying skin areas which border denervated skin, extended into the deafferentiated cortical representation area. As a consequence of nerve lesions and subsequent reorganization an increase of the somatosensory evoked potentials (SEPs) was observed in cats when intact neighbouring nerves were stimulated. An increase of SEP-components of patients with nerve lesions may indicate a similar process of posttraumatic plastic cortical reorganization.

Methods

To test if a similar process of post-traumatic plastic cortical reorganization does occur in humans, the SEP of intact neighbouring hand nerves were recorded in 29 patients with hand nerve lesions. To hypothetically explain the observed changes of SEP-components, SEP recording following paired stimulation of the median nerve was performed in 12 healthy subjects.

Results

Surprisingly 16 of the 29 patients (55.2%) showed a reduction or elimination of N35, P45 and N60. Patients with lesions of two nerves showed more SEP-changes than patients with a single nerve lesion (85.7%; 6/7 nerves; vs. 34.2%; 13/38 nerves; Fisher's exact test, p < 0.05). With paired stimulation a suppression of the amplitude of N20, P25 and P45 (p < 0.05; sign test), and a marked increment of N35 (p < 0.05; sign test) and N60 (not significant; sign test) of the second response could be observed.

Conclusion

The results of the present investigation do not provide evidence of collateral innervation of peripherally denervated cortical neurons by neurons of adjacent cortical representation areas. They rather suggest that secondary components of the excitatory response to nerve stimulation are lost in cortical areas, which surround the denervated region.     

Population recovery of alien black rats Rattus rattus: A test of reinvasion theory

Reinvasion of pest animals after incomplete control is a major challenge for invasive species management, yet little is known about the behavioural and demographic categories of reinvaders or the mechanisms that drive population‐level responses to control. To understand the fine‐scale mechanisms of reinvasion, we examined changes in demography, movements and activity patterns of reinvading alien black rats Rattus rattus in the short (4 weeks) and longer term (3 months) following localised experimental pest removal. Using recovery and invasion theory, we tested three hypothesised mechanisms of reinvasion: the ‘in situ effect’, the ‘trickle effect’ and the ‘vacuum effect’. We created space for reinvasion by removing black rats from the core of replicate 1‐ha plots (short‐term experiment) and later by removing animals from the entire plot (longer‐term experiment). Reinvaders were characterised as dispersing juveniles, floaters or neighbours. Radio‐tracking quantified home range changes for adjacent resident animals (short‐term experiment only). In the short term, there was no net influx of rats after targeted removal. Radio‐tracked residents’ movements were highly variable and displayed no directional changes after nearby conspecifics were removed. However, in the longer term, removal led to slow population recovery through a mix of reinvading floaters, dispersing juveniles and shifting residents. These responses best support a hypothesis of reinvasion through a trickle effect, with rats being extremely mobile and having a high degree of population turnover, even in untreated sites. Our findings provide the first test of reinvasion theory at a small scale, demonstrating the importance of understanding the differing categories of reinvaders and mechanisms of reinvasion after population control. These mechanisms drive the rate of population recovery and, in turn, should help determine which strategy of pest control should be used, and the frequency with which they are implemented, in order to slow the recovery of pest populations.     

2-D DIGE analysis of UV-C radiation-responsive proteins in globe artichoke leaves

Plants respond to ultraviolet stress inducing a self-defence through the regulation of specific gene family members. The UV acclimation is the result of biochemical and physiological processes, such as enhancement of the antioxidant enzymatic system and accumulation of UV-absorbing phenolic compounds (e.g. flavonoids). Globe artichoke is an attractive species for studying the protein network involved in UV stress response, being characterized by remarkable levels of inducible antioxidants. Proteomic tools can assist the evaluation of the expression patterns of UV-responsive proteins and we applied the difference in-gel electrophoresis (DIGE) technology for monitoring the globe artichoke proteome variation at four time points following an acute UV-C exposure. A total of 145 UV-C-modulated proteins were observed and 119 were identified by LC-MS/MS using a ～144,000 customized Compositae protein database, which included about 19,000 globe artichoke unigenes. Proteins were Gene Ontology (GO) categorized, visualized on their pathways and their behaviour was discussed. A predicted protein interaction network was produced and highly connected hub-like proteins were highlighted. Most of the proteins differentially modulated were chloroplast located, involved in photosynthesis, sugar metabolisms, protein folding and abiotic stress. The identification of UV-C-responsive proteins may contribute to shed light on the molecular mechanisms underlying plant responses to UV stress.     

Mitotic checkpoint gene expression is tuned by codon usage bias

The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half‐lives and long protein half‐lives supports stable SAC protein levels. For the SAC genes mad2 ⁺ and mad3 ⁺, their short mRNA half‐lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1 ⁺ mRNA has a short half‐life despite a higher frequency of optimal codons, and despite the lack of known RNA‐destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co‐translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine‐tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.     

Understanding photosynthetic biofilm productivity and structure through 2D simulation

We present a spatial model describing the growth of a photosynthetic microalgae biofilm. In this 2D-model we consider photosynthesis, cell carbon accumulation, extracellular matrix excretion, and mortality. The rate of each of these mechanisms is given by kinetic laws regulated by light, nitrate, oxygen and inorganic carbon. The model is based on mixture theory and the behaviour of each component is defined on one hand by mass conservation, which takes into account biological features of the system, and on the other hand by conservation of momentum, which expresses the physical properties of the components. The model simulates the biofilm structural dynamics following an initial colonization phase. It shows that a 75 μm thick active region drives the biofilm development. We then determine the optimal harvesting period and biofilm height which maximize productivity. Finally, different harvesting patterns are tested and their effect on biofilm structure are discussed. The optimal strategy differs whether the objective is to recover the total biofilm or just the algal biomass.