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

On the relation between action selection and movement control in 5- to 9-month-old infants

Although 5-month-old infants select action modes that are adaptive to the size of the object (i.e., one- or two-handed reaching), it has largely remained unclear whether infants of this age control the ensuing movement to the size of the object (i.e., scaling of the aperture between hands). We examined 5-, 7-, and 9-month-olds’ reaching behaviors to gain more insight into the developmental changes occurring in the visual guidance of action mode selection and movement control, and the relationship between these processes. Infants were presented with a small set of objects (i.e., 2, 3, 7, and 8 cm) and a large set of objects (i.e., 6, 9, 12, and 15 cm). For the first set of objects, it was found that the infants more often performed two-handed reaches for the larger objects based on visual information alone (i.e., before making contact with the object), thus showing adaptive action mode selection relative to object size. Kinematical analyses of the two-handed reaches for the second set of objects revealed that inter-trial variance in aperture between the hands decreased with the approach toward the object, indicating that infants’ reaching is constrained by the object. Subsequent analysis showed that between hand aperture scaled to object size, indicating that visual control of the movement is adjusted to object size in infants as young as 5 months. Individual analyses indicated that the two processes were not dependent and followed distinct developmental trajectories. That is, adaptive selection of an action mode was not a prerequisite for appropriate aperture scaling, and vice versa. These findings are consistent with the idea of two separate and independent visual systems (Milner and Goodale in Neuropsychologia 46:774–785, 2008) during early infancy

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

Remote Center of Motion for Redundant Robotic-Assisted Ultrasound Guided Regional Anesthesia

International audienc