Possible usefulness of echocardiographic Z-scores in autopsy routine of the foetal great vessels

Background: Abnormal diameters of foetal vessels are common findings in congenital heart defects. However, it is difficult for pathologist to assess whether the diameters of the vessels are normal or not and to compare with echocardiographic data. The Z-score is a dimensionless quantity representing the distance between the raw score and population mean in standard deviation units. Using Z-score, we can compare single cases to average standards in the population. Aim: To compare diameters of great arteries measured in specimens fixed in 10% formalin solution to normal values obtained on echocardiography using Z-scores. Material and methods: The study was performed on 43 formalin-fixed normal foetal hearts aged from 19 to 40 weeks of gestation. Each specimen was dissected and the following diameters were measured: aortic valve (AoV), ascending aorta (AAo), descending aorta (DAo), aortic isthmus (AoI), ductus arteriosus (DA), pulmonary trunk valve (PV), and pulmonary arteries (RPA and LPA). Z-score parameters were calculated for all structures using the Foetal Echo Z-score Calculator. Results: Z-score values of all measured foetuses were mostly found to fit within the echocardiographic norms, although the most reliable results were obtained for foetuses aged 23 weeks. This group was represented by the highest number of specimens. The minimal and maximal Z-score values were, respectively: AoV –3.45, 1.4; AAo –4.24, –0.11; DAo –2.12, 1.29; PV –3.21, 0.69; RPA –3.4, 0.84; LPA –2.25, 0.31; AoI –1.97, 0.96; DA –3.56, –1.52. Conclusions: The diameters of great arteries measured on autopsy are comparable to the results obtained from echocardiographic measurement. Z-score values for foetal echocardiography can be applied to post-mortem examination

Retinoid-Binding Proteins: Similar Protein Architectures Bind Similar Ligands via Completely Different Ways

Background: Retinoids are a class of compounds that are chemically related to vitamin A, which is an essential nutrient that plays a key role in vision, cell growth and differentiation. In vivo, retinoids must bind with specific proteins to perform their necessary functions. Plasma retinol-binding protein (RBP) and epididymal retinoic acid binding protein (ERABP) carry retinoids in bodily fluids, while cellular retinol-binding proteins (CRBPs) and cellular retinoic acid-binding proteins (CRABPs) carry retinoids within cells. Interestingly, although all of these transport proteins possess similar structures, the modes of binding for the different retinoid ligands with their carrier proteins are different. Methodology/Principal Findings: In this work, we analyzed the various retinoid transport mechanisms using structure and sequence comparisons, binding site analyses and molecular dynamics simulations. Our results show that in the same family of proteins and subcellular location, the orientation of a retinoid molecule within a binding protein is same, whereas when different families of proteins are considered, the orientation of the bound retinoid is completely different. In addition, none of the amino acid residues involved in ligand binding is conserved between the transport proteins. However, for each specific binding protein, the amino acids involved in the ligand binding are conserved. The results of this study allow us to propose a possible transport model for retinoids. Conclusions/Significance: Our results reveal the differences in the binding modes between the different retinoid-bindin

Stress-induced lipocalin-2 controls dendritic spine formation and neuronal activity in the amygdala.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Behavioural adaptation to psychological stress is dependent on neuronal plasticity and dysfunction at this cellular level may underlie the pathogenesis of affective disorders such as depression and post-traumatic stress disorder. Taking advantage of genome-wide microarray assay, we performed detailed studies of stress-affected transcripts in the amygdala - an area which forms part of the innate fear circuit in mammals. Having previously demonstrated the role of lipocalin-2 (Lcn-2) in promoting stress-induced changes in dendritic spine morphology/function and neuronal excitability in the mouse hippocampus, we show here that the Lcn-2 gene is one of the most highly upregulated transcripts detected by microarray analysis in the amygdala after acute restraint-induced psychological stress. This is associated with increased Lcn-2 protein synthesis, which is found on immunohistochemistry to be predominantly localised to neurons. Stress-naïve Lcn-2(-/-) mice show a higher spine density in the basolateral amygdala and a 2-fold higher rate of neuronal firing rate compared to wild-type mice. Unlike their wild-type counterparts, Lcn-2(-/-) mice did not show an increase in dendritic spine density in response to stress but did show a distinct pattern of spine morphology. Thus, amygdala-specific neuronal responses to Lcn-2 may represent a mechanism for behavioural adaptation to psychological stress.Marie Curie Excellence Grant from the European Commission.Medical Research Council Project GrantCOST Action ECMNe

Energetic Selection of Topology in Ferredoxins

Models of early protein evolution posit the existence of short peptides that bound metals and ions and served as transporters, membranes or catalysts. The Cys-X-X-Cys-X-X-Cys heptapeptide located within bacterial ferredoxins, enclosing an Fe4S4 metal center, is an attractive candidate for such an early peptide. Ferredoxins are ancient proteins and the simple α+β fold is found alone or as a domain in larger proteins throughout all three kingdoms of life. Previous analyses of the heptapeptide conformation in experimentally determined ferredoxin structures revealed a pervasive right-handed topology, despite the fact that the Fe4S4 cluster is achiral. Conformational enumeration of a model CGGCGGC heptapeptide bound to a cubane iron-sulfur cluster indicates both left-handed and right-handed folds could exist and have comparable stabilities. However, only the natural ferredoxin topology provides a significant network of backbone-to-cluster hydrogen bonds that would stabilize the metal-peptide complex. The optimal peptide configuration (alternating αL,αR) is that of an α-sheet, providing an additional mechanism where oligomerization could stabilize the peptide and facilitate iron-sulfur cluster binding

Banff 2022 liver group meeting report: monitoring long term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participantsincluded hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists.Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimisation and long-term structural changes.Potential revision of the rejection classification scheme to better accommodate and communicate lateT cell-mediated rejection patterns and related structural changes, such as nodular regenerativehyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression tomatch the heterogeneity of patient settings will be central to improving long-term patient survival.Such personalised therapeutics are in turn contingent on better understanding and monitoring ofallograft status within a rational decision-making approach, likely to be facilitated in implementationwith emerging decision support tools. Proposed revisions to rejection classification emerging fromthe meeting include incorporation of interface hepatitis and fibrosis staging. These will be opened toonline testing, modified accordingly and subject to consensus discussion leading up to the next Banffconference