The low pKa value of iron-binding ligand Tyr188 and its implication in iron release and anion binding of human transferrin

2D NMR-pH titrations were used to determine pKa values for four conserved tyrosine residues, Tyr45, Tyr85, Tyr96 and Tyr188, in human transferrin. The low pKa of Tyr188 is due to the fact that the iron-binding ligand interacts with Lys206 in open-form and with Lys296 in the closed-form of the protein. Our current results also confirm the anion binding of sulfate and arsenate to transferrin and further suggest that Tyr188 is the actual binding site for the anions in solution. These data indicate that Tyr188 is a critical residue not only for iron binding but also for chelator binding and iron release in transferrin. © 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.postprin

Molecular profiling of cervical cancer progression

Most cancer patients die of metastatic or recurrent disease, hence the importance to identify target genes upregulated in these lesions. Although a variety of gene signatures associated with metastasis or poor prognosis have been identified in various cancer types, it remains a critical problem to identify key genes as candidate therapeutic targets in metastatic or recurrent cancer. The aim of our study was to identify genes consistently upregulated in both lymph node micrometastases and recurrent tumours compared to matched primary tumours in human cervical cancer. Taqman Low-Density Arrays were used to analyse matched tumour samples, obtained after laser-capture microdissection of tumour cell islands for the expression of 96 genes known to be involved in tumour progression. Immunohistochemistry was performed for a panel of up- and downregulated genes. In lymph node micrometastases, most genes were downregulated or showed expressions equal to the levels found in primary tumours. In more than 50% of lymph node micrometastases studied, eight genes (AKT, BCL2, CSFR1, EGFR1, FGF1, MMP3, MMP9 and TGF-β) were upregulated at least two-fold. Some of these genes (AKT and MMP3) are key regulators of epithelial–mesenchymal transition in cancer. In recurrent tumours, almost all genes were upregulated when compared to the expression profiles of the matched primary tumours, possibly reflecting their aggressive biological behaviour. The two genes showing a consistent downregulated expression in almost all lymph node metastases and recurrent tumours were BAX and APC. As treatment strategies are very limited for metastatic and recurrent cervical cancer, the upregulated genes identified in this study are potential targets for new molecular treatment strategies in metastatic or recurrent cervical cancer

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Nerve Contour tracking for Ultrasound-Guided Regional Anesthesia

International audienceUltrasound-Guided Regional Anesthesia is a technique to provide regional anesthesia aided by ultrasound visualization of the region on which the anesthesia will be applied. A proper detection and tracking of the nerve contour is necessary to decide where anesthesia should be applied. If the needle is too far from the nerve contour, the anesthesia could be ineffective, but if it touch the nerve could harm the patient. In this paper we address a model to track nerve contours in ul-trasonic videos to assist the doctors during Ultrasound-Guided Regional Anesthesia procedures. The experimental results show that our model performs good within an acceptable margin of error

Soft bottom species richness and diversity as a function of depth and iceberg scour in Arctic glacial Kongsfjorden (Svalbard)

Macrozoobenthic soft-sediment communities inhabiting six depth zones of central Arctic Kongsfjorden were analysed comparatively using SCUBA-diving. 63 taxa were found, 30 of which had not been reported for Kongsfjorden and seven for Svalbard. Suspensivorous or surface and sub-surface detritivorous polychaetes and deposit-feeding amphipods were dominant. Only eleven taxa of 45 species and additional 18 families identified inhabited the complete depth range. Biomass ranged from 3.5 to 25.0 g ash free dry mass m-2 and mean Shannon diversity (Log e) was 2.06. Similarity clustering from abun-dance and biomass data showed a significant difference between the shal-low station (5m) and the rest. The latter formed two subgroups (10-20m, 25-30m). These differences together with information on ice-scouring support the intermediate disturbance hypothesis indicating that habitats impacted by moderate iceberg scouring enable higher diversity. In contrast, biotopes frequently affected only host pioneer communities, while mature, less diverse assemblages dominate depths of low impact