Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness

Genetic variability in CYP3A4 and CYP3A5 in primary liver, gastric and colorectal cancer patients

<p>Abstract</p> <p>Background</p> <p>Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not been analyzed so far. This study aims to examine associations between common CYP3A4 and CYP3A5 polymorphisms and digestive cancer risk.</p> <p>Methods</p> <p>CYP3A4 and CYP3A5 genotypes were determined in 574 individuals including 178 patients with primary liver cancer, 82 patients with gastric cancer, 151 patients with colorectal cancer, and 163 healthy individuals.</p> <p>Results</p> <p>The variant allele frequencies for patients with liver cancer, gastric cancer, colorectal cancer and healthy controls, respectively, were: <it>CYP3A4*1B</it>, 4.8 % (95% C.I. 2.6–7.0), 3.7 % (0.8–6.6) 4.3% (2.0–6.6) and 4.3% (2.1–6.5); <it>CYP3A5*3</it>, 91.8 % (93.0–97.4), 95.7% (92.6–98.8), 91.7% (88.6–94.8) and 90.8% (87.7–93.9). The association between <it>CYP3A4*1B </it>and <it>CYP3A5*3 </it>variant alleles did not significantly differ among patients and controls. No differences in genotypes, allele frequencies, or association between variant alleles were observed with regard to gender, age at diagnosis, tumour site or stage.</p> <p>Conclusion</p> <p>Common polymorphisms on <it>CYP3A4 </it>and <it>CYP3A5 </it>genes do not modify the risk of developing digestive cancers in Western Europe.</p

Elastically flexible crystals have disparate mechanisms of molecular movement induced by strain and heat

Elastically flexible crystals form an emerging class of materials that exhibit a range of notable properties. The mechanism of thermal expansion in flexible crystals of bis(acetylacetonato)copper(II) is compared with the mechanism of molecular motion induced by bending and it is demonstrated that the two mechanisms are distinct. Upon bending, individual molecules within the crystal structure reversibly rotate, while thermal expansion results predominantly in an increase in intermolecular separations with only minor changes to molecular orientation through rotation

Erratum to: Elastically Flexible Crystals have Disparate Mechanisms of Molecular Movement Induced by Strain and Heat (Angewandte Chemie International Edition, (2018), 57, 35, (11325-11328), 10.1002/anie.201806431)

The introduction of this paper was amended by the authors following feedback from the community

Elastically flexible crystals have disparate mechanisms of molecular movement induced by strain and heat

Elastically flexible crystals are an emerging class of materials that exhibit a range of notable properties. Here, we compare the mechanism of thermal expansion in flexible crystals of bis(acetylacetonato)copper(II) with the mechanism of molecular motion induced by bending and show that they are distinct. Upon bending individual molecules within the crystal structure reversibly rotate, while thermal expansion results predominantly in an increase in intermolecular separations with only minor changes to molecular orientation through rotation

Controlling spin switching with anionic supramolecular frameworks

Encasing the classic spin-crossover (SCO) complex cation [Co(terpy)(2)](2+) in different anionic supramolecular frameworks modulates its SCO behavior, tuning both its T-1/2 (shift of up to 200 K) and the cooperativity of the system. The SCO behavior is influenced by the organization of the complex cations within supramolecular anionic frameworks comprising iodoperfluoroben-zenes and iodide anions, with tighter packing of complexes leading to a more abrupt transition. This approach for the control of magnetic properties is applicable to any complex with suitable counterions and hence provides significant opportunity for further developing the properties of many such stimuli-responsive complexes, without requiring changes to their chemical structures. The magnetic properties of the materials presented herein are investigated through variable-temperature magnetic susceptibility measurements and -pressure molecular variable-temperature structure studies