Preventing Ischial Pressure Ulcers: II. Biomechanics

Background: Pressure ulcers (PUs) are common and debilitating wounds that arise when immobilized patients cannot shift their weight. Neuromuscular Electrical Stimulation (NMES) has been investigated for Pressure Ulcer Prevention (PUP) for over 20 years. Historically gluteus maximus (GM) has been considered an important actuator in attempting to redistribute seated pressures through NMES

Structure-function study of maize ribosome-inactivating protein: implications for the internal inactivation region and the sole glutamate in the active site

Maize ribosome-inactivating protein is classified as a class III or an atypical RNA N-glycosidase. It is synthesized as an inactive precursor with a 25-amino acid internal inactivation region, which is removed in the active form. As the first structural example of this class of proteins, crystals of the precursor and the active form were diffracted to 2.4 and 2.5 Å, respectively. The two proteins are similar, with main chain root mean square deviation (RMSD) of 0.519. In the precursor, the inactivation region is found on the protein surface and consists of a flexible loop followed by a long α-helix. This region diminished both the interaction with ribosome and cytotoxicity, but not cellular uptake. Like bacterial ribosome-inactivating proteins, maize ribosome-inactivating protein does not have a back-up glutamate in the active site, which helps the protein to retain some activity if the catalytic glutamate is mutated. The structure reveals that the active site is too small to accommodate two glutamate residues. Our structure suggests that maize ribosome-inactivating protein may represent an intermediate product in the evolution of ribosome-inactivating proteins. © 2007 The Author(s).published_or_final_versio

The C-terminal fragment of the ribosomal P protein complexed to trichosanthin reveals the interaction between the ribosome-inactivating protein and the ribosome

Ribosome-inactivating proteins (RIPs) inhibit protein synthesis by enzymatically depurinating a specific adenine residue at the sarcin-ricin loop of the 28S rRNA, which thereby prevents the binding of elongation factors to the GTPase activation centre of the ribosome. Here, we present the 2.2 Å crystal structure of trichosanthin (TCS) complexed to the peptide SDDDMGFGLFD, which corresponds to the conserved C-terminal elongation factor binding domain of the ribosomal P protein. The N-terminal region of this peptide interacts with Lys173, Arg174 and Lys177 in TCS, while the C-terminal region is inserted into a hydrophobic pocket. The interaction with the P protein contributes to the ribosome-inactivating activity of TCS. This 11-mer C-terminal P peptide can be docked with selected important plant and bacterial RIPs, indicating that a similar interaction may also occur with other RIPs

Constructing climate policy : the European Union and China

Climate change as an impeding catastrophe has prompted heated debates on the sharing of mitigation responsibilities among nation states. How do climate protection norms come about to influence climate policy-making, especially in major greenhouse gases emitters—the European Union and China? This thesis sets out to examine from the economic, strategic and normative perspectives what considerations are underpinning climate policy-making in the world, the EU, and China. A constructivist approach was taken, with a stress on bottom-up normative influence and mutual constitution of the international and local contexts. Building on primary sources from the speech, policy directives and reports by both state and non-state actors and others, analysis was carried out with the assistance of scholarly literature from the field of political economy, international relations and global environmental politic. Energy policy is elucidated to show how climate policy is mainstreamed and how reconciliation is possible among competing considerations. Findings of this thesis indicate that economic competitiveness is the primary consideration factor. While strategic interests often go parallel with economic ones, normative considerations sometimes contradict economic competitiveness in the short-term. It is also found that openness of political system and international status and identity seem to govern the extent of normative influence on climate policy-making. Despite rhetorical commitment, China‘s growth imperative and strong belief in the “common but differentiated responsibilities” present great obstacles to adoption of climate protection norms. In Europe, recession gives rise to a two-fold challenge—to deliver promises of green growth and to prevent erosion of public support for climate actions. Finally, as the thesis strongly recognizes the agency of non-state actors and citizens, it draws a number of implications on how they can influence climate policy-making in Europe and China.published_or_final_versionModern Languages and CulturesMasterMaster of Philosoph

Preventing ischial pressure ulcers: II. Biomechanics

Abstract. Background: Pressure ulcers (PUs) are common and debilitating wounds that arise when immobilized patients cannot shift their weight. Neuromuscular Electrical Stimulation (NMES) has been investigated for Pressure Ulcer Prevention (PUP) for over 20 years. Historically gluteus maximus (GM) has been considered an important actuator in attempting to redistribute seated pressures through NMES. Methods: Analysis of skeletal biomechanics to quantify the value of GM relative to hamstring hip extensors (HS), using muscle moment models based on torques and rigid body mass estimates from the literature. Surface stimulation experiments (n = 10 + 1, non-paralyzed) to validate model and identify promising stimulation sites and treatment strategies that would approximate healthy biomechanics. Results: Literature values and Rigid Body Analysis estimate: ∼63 Nm extensor torque requirement calculated for complete ipsilateral unloading of the buttocks. Muscle Moment Analysis: GM can provide 70% of total hip extensor torque when walking vs. 18% when seated. HS can provide 100 Nm hip extension torque when seated, exceeding 63 Nm requirement. Surface Stimulation: ipsilateral seated interface pressure mean −26% during HS stimulation vs. +16% with GM; peak pressure area −94% HS vs. +213% GM. Conclusions: GM activation reduces disuse atrophy and improves circulation, but appears neither required, nor desired, for unloading when seated. HS stimulation alone should be capable of sufficient unloading. This new proposed approach is explored clinically in companion paper III

Maize ribosome-inactivating protein uses Lys158-lys161 to interact with ribosomal protein P2 and the strength of interaction is correlated to the biological activities.

Ribosome-inactivating proteins (RIPs) inactivate prokaryotic or eukaryotic ribosomes by removing a single adenine in the large ribosomal RNA. Here we show maize RIP (MOD), an atypical RIP with an internal inactivation loop, interacts with the ribosomal stalk protein P2 via Lys158-Lys161, which is located in the N-terminal domain and at the base of its internal loop. Due to subtle differences in the structure of maize RIP, hydrophobic interaction with the 'FGLFD' motif of P2 is not as evidenced in MOD-P2 interaction. As a result, interaction of P2 with MOD was weaker than those with trichosanthin and shiga toxin A as reflected by the dissociation constants (K(D)) of their interaction, which are 1037.50 ± 65.75 µM, 611.70 ± 28.13 µM and 194.84 ± 9.47 µM respectively.Despite MOD and TCS target at the same ribosomal protein P2, MOD was found 48 and 10 folds less potent than trichosanthin in ribosome depurination and cytotoxicity to 293T cells respectively, implicating the strength of interaction between RIPs and ribosomal proteins is important for the biological activity of RIPs. Our work illustrates the flexibility on the docking of RIPs on ribosomal proteins for targeting the sarcin-ricin loop and the importance of protein-protein interaction for ribosome-inactivating activity

A case of idiopathic inflammatory myopathy complicated by Epstein-Barr virus-associated lymphoma

We report a male patient who had refractory idiopathic inflammatory myopathy (IIM) presented with antisynthetase syndrome, being treated by potent immunosuppressants for years, developed Epstein-Barr virus (EBV)-associated lymphoma. Despite the stepping down of the immunosuppressives and active lymphoma therapy, the patient died. On top of the typical association of IIM and malignancy, rare EBV-associated tumors related to EBV infection secondary to the use of potent immunosuppressive therapies could occur. Further investigations are advisable if there are new symptoms and signs or in refractory IIM cases. This report serves as a diagnostic alert that the causation by EBV infection in unusual tumors found in patients with IIM should be considered, as both the treatment and prognosis may differ. A balance between the risks and benefits of immunosuppressive therapies should always be achieved