The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures

Cellular stress conditions activate p53-dependent pathways to counteract the inflicted damage. To achieve the required functional diversity, p53 is subjected to numerous post-translational modifications and the expression of isoforms. Little is yet known how p53 has evolved to respond to different stress pathways. The p53 isoform p53/47 (p47 or ΔNp53) is linked to aging and neural degeneration and is expressed in human cells via an alternative cap-independent translation initiation from the 2nd in-frame AUG at codon 40 (+118) during endoplasmic reticulum (ER) stress. Despite an AUG codon in the same location, the mouse p53 mRNA does not express the corresponding isoform in either human or mouse-derived cells. High-throughput in-cell RNA structure probing shows that p47 expression is attributed to PERK kinase-dependent structural alterations in the human p53 mRNA, independently of eIF2α. These structural changes do not take place in murine p53 mRNA. Surprisingly, PERK response elements required for the p47 expression are located downstream of the 2nd AUG. The data show that the human p53 mRNA has evolved to respond to PERKmediated regulation of mRNA structures in order to control p47 expression. The findings highlight how p53 mRNA co-evolved with the function of the encoded protein to specify p53-activities under different cellular conditions

Carpal tunnel syndrome

✓ The presenting symptomatology and clinical findings of 464 patients with the carpal tunnel syndrome are reviewed. The results of decompression by section of the transverse carpal ligament are presented, with particular reference to the use of the Paine retinaculotome. Approximately 90% of patients achieved very satisfactory results and complications were minimal. The commonest reason for failure is incomplete division of the flexor retinaculum. The detailed procedure is presented.</jats:p

Stability of UiO-66 under acidic treatment: Opportunities and limitations for post-synthetic modifications

In chemical and functional modification of Metal-organic frameworks (MOFs), preserving their structure and topology is a challenging goal, due to the high sensitivity of these materials to moisture, chemical and thermal treatments. The porous material UiO-66 is one of the most stable MOFs, retaining its properties under a relative wide range of chemical and physical conditions. The unique robustness of UiO-66 derives from the 12-coordinated Zr-6-clusters that constitute the framework. Nevertheless, variation on the synthetic pathways may lead to different coordination of the Zirconium sites, influencing the stability and activity of this MOF during applications such as catalysis. Herein a survey of the stability of UiO-66 under acidic treatment is presented. The porous metal-organic framework has been synthesized according to two alternative procedures; these two solid materials and a commercially available UiO-66 sample have been suspended in several aqueous acids and have been characterized after the impregnation tests. These results lead to a better understanding of the matter of acidic stability of the selected MOF, clarifying whether it is possible to enhance its stability by choosing a dedicated synthesis route and providing essential information in order to proceed with a large number of post-synthetic modifications. Among these reactions, the sulfonation of UiO-66, which is an example of outstanding importance, has been investigated. The stability of UiO-66 versus mineral acids has been confirmed; however this MOF does not tolerate the use of electrophilic cationic species

Continuous synthesis of UiO-66 in microreactor: Pursuing the optimum between intensified production and structural properties

The increasing demand for MOFs can only be satisfied by establishing robust and reproducible synthesis routes which allow a profitable scale-up of the requested materials while preserving their textural properties and stability. A scalable MOF synthesis may provide a technology platform for the further development and modification of the product, from both a chemical and an engineering perspective. And, above all, MOFs could be delivered to the market at a substantially reduced price. In this work UiO-66 was synthesized continuously by employing micro reactors and the concept of flow chemistry. The microreaction technology (MRT) process turned out to be a viable alternative to the time and energy consuming conventional synthesis processes, as significantly faster reaction rates could be achieved compared to the conventional batch processes (Zhou et al., 2014; Frameworks for Commercial Success, 2016). Microreactors are characterized in particular by high surface-to-volume ratios and channel dimensions in the submillimeter range, which offer a significant enhancement of heat and mass transfer within the reactor, additionally the chemical reactions can be accelerated by orders of magnitude and can thus be processed close to their kinetic optimum conditions. Different reaction parameters were studied in order to elucidate their influence on the product properties. All synthesized MOF crystals were characterized by X-ray diffraction, scanning electron microscopy, thermogravimetric analysis and nitrogen adsorption measurements. The MRT approach allowed the continuous fabrication of MOF crystals with distinct morphological characteristics in a time-efficient manner. The obtained results represent a faster and energy-efficient route to continuously produce UiO-66, compared to the standard synthetic protocols. The materials prepared in this work have a lower coordination of the Zr sites in comparison to the UiO-66 that can be produced in batch (Cavka et al. 2008); nevertheless the presence of coordinative unsaturated sites is a preferred feature of MOFs for some specific application such as catalysis (Shearer et al., 2014)

Continuous microreactor synthesis of ZIF-8 with high space-time-yield and tunable particle size

The continuous synthesis of the metal–organic framework ZIF-8 is described, employing microreaction technology which provides highly controlled mass and heat transport conditions. Using a T-type micromixer connected with a residence time capillary, crystalline ZIF-8 with excellent product characteristics and remarkable reproducibility is produced within seconds. The product is obtained at production rates of up to 640 g/day which corresponds to a theoretical space–time yield of 210,000 kg/m3*day. The modular process setup allows easy scale-up into the several kilogram range. Additionally, by modifying the reaction and process conditions it is possible to intentionally tailor both, the microscopic (crystal form and size) and macroscopic morphology of the product