Anatomical relationship between the internal jugular vein and the vertebral artery: An observational study in pre-school children using ultrasound imaging.

Background and Aims: Central venous cannulation is performed in children requiring vasopressor use, long-term antibiotics, chemotherapy or parenteral nutrition. The internal jugular vein is the preferred site for cannulation. Though, there are several studies describing the relation of the common carotid artery (CCA) and internal jugular vein (IJV) in the neck, there is a paucity of data regarding the anatomical relationship between the vertebral artery (VA) and the IJV. This study aims to describe the anatomical relationship between the IJV and the VA using ultrasound imaging in pre-school children in India. Material and Methods: Prospective observational cross-sectional study of 67 randomly selected children (age <5 years) who underwent an ultrasound examination of the right side of the neck, in a position mimicking central venous cannulation, to identify the relationship between the IJV and VA. The skin to the vertebral artery depth (D), width of the VA (W), distance between the IJV and the VA (DIV) was measured. Based on these, children were classified into high risk, moderate risk and low risk category for VA puncture. Results: Of the 67 children, 15 (22.4%) patients belonged to the high-risk group, 25 (37.3%) belonged to the moderate-risk group and 27 (40.23%) belonged to the low-risk group. Conclusion: In addition to localizing the carotid artery, pre-procedural scanning or real-time ultrasound examination to establish the anatomical relation of the IJV to the VA is imperative to alert the clinician of the possible risk of VA puncture.

Mapping the allosteric effects that define functional activity of SARS-CoV-2 specific antibodies

Previous studies on the structural relationship between human antibodies and SARS-CoV-2 have focused on generating static snapshots of antibody complexes with the Spike trimer. However, antibody-antigen interactions are dynamic, with significant binding-induced allosteric effects on conformations of antibody and its target antigen. In this study, we employ hydrogen-deuterium exchange mass spectrometry, in vitro assays, and molecular dynamics simulations to investigate the allosteric perturbations linked to binding events between a group of human antibodies with differential functional activities, and the Spike trimer from SARS-CoV-2. Our investigations have revealed key dynamic features that define weakly or moderately neutralizing antibodies versus those with strong neutralizing activity. These results provide mechanistic insights into the functional modes of human antibodies against COVID-19, and provide a rationale for effective antiviral strategies. TeaserDifferent neutralizing antibodies induce site-specific allosteric effects across SARS-CoV-2 Spike protein

Molecular interfaces of the galactose-binding protein Tectonin domains in host-pathogen interaction.

Beta-propeller proteins function in catalysis, protein-protein interaction, cell cycle regulation, and innate immunity. The galactose-binding protein (GBP) from the plasma of the horseshoe crab, Carcinoscorpius rotundicauda, is a beta-propeller protein that functions in antimicrobial defense. Studies have shown that upon binding to Gram-negative bacterial lipopolysaccharide (LPS), GBP interacts with C-reactive protein (CRP) to form a pathogen-recognition complex, which helps to eliminate invading microbes. However, the molecular basis of interactions between GBP and LPS and how it interplays with CRP remain largely unknown. By homology modeling, we showed that GBP contains six beta-propeller/Tectonin domains. Ligand docking indicated that Tectonin domains 6 to 1 likely contain the LPS binding sites. Protein-protein interaction studies demonstrated that Tectonin domain 4 interacts most strongly with CRP. Hydrogen-deuterium exchange mass spectrometry mapped distinct sites of GBP that interact with LPS and with CRP, consistent with in silico predictions. Furthermore, infection condition (lowered Ca(2+) level) increases GBP-CRP affinity by 1000-fold. Resupplementing the system with a physiological level of Ca(2+) did not reverse the protein-protein affinity to the basal state, suggesting that the infection-induced complex had undergone irreversible conformational change. We propose that GBP serves as a bridging molecule, participating in molecular interactions, GBP-LPS and GBP-CRP, to form a stable pathogen-recognition complex. The interaction interfaces in these two partners suggest that Tectonin domains can differentiate self/nonself, crucial to frontline defense against infection. In addition, GBP shares architectural and functional homologies to a human protein, hTectonin, suggesting its evolutionarily conservation for approximately 500 million years, from horseshoe crab to human.