👤 Marina Giovannini

Direct measurement of apolipoprotein B (ApoB) is not always standardized and is relatively expensive, making it unavailable in several low-income settings. To address this issue, several formulas have been developed to estimate ApoB levels. Therefore, our study aims to compare the reliability of 23 formulas for estimating ApoB levels in a large cohort of South-European individuals. We retrospectively assessed 4.577 clinical records in which ApoB measurements were obtained using the same standardized method. Overall concordance was defined as the proportion of cases where the directly measured ApoB level fell within the same category as the estimated ApoB level, based on ApoB quartiles (<80 mg/dL, 80-94 mg/dL, 95-114 mg/dL, and ≥115 mg/dL). In addition, overall concordance was assessed for different lipoprotein(a) (Lp(a)) and non-high density lipoprotein cholesterol (non-HDL-C) sub-levels. Ordinary least squares linear regression analyses were performed to compare estimated and measured ApoB values. Residual error plots were generated to visualize the difference between each estimation method and the actual ApoB measurements, stratified by Lp(a) and non-HDL-C levels. Plasma ApoB levels were best predicted by a non-HDL-C based formula and a formula using Friedewald's low-density lipoprotein cholesterol (LDL-C), regardless of ApoB plasma levels. Non-HDL-C levels did not significantly affect the concordance between measured and estimated ApoB across the different formulas, except at low non-HDL-C levels. Similarly, Lp(a) levels did not significantly impact concordance. However, the highest concordance level was 41 %. Some simple formulas based on low-cost and widely available parameters can estimate ApoB levels independently of ApoB, non-HDL-C, and Lp(a) plasma levels. This approach may be particularly useful for estimating ApoB levels in low-resource settings. Show less

The axon initial segment (AIS) plays a crucial role: it is the site where neurons initiate their electrical outputs. Its composition in terms of voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels, as well as its length and localization determine the neuron's spiking properties. Some neurons are able to modulate their AIS length or distance from the soma in order to adapt their excitability properties to their activity level. It is therefore crucial to characterize all these parameters and determine where the myelin sheath begins in order to assess a neuron's excitability properties and ability to display such plasticity mechanisms. If the myelin sheath starts immediately after the AIS, another question then arises as to how would the axon be organized at its first myelin attachment site; since AISs are different from nodes of Ranvier, would this particular axonal region resemble a hemi-node of Ranvier? We have characterized the AIS of mouse somatic motor neurons. In addition to constant determinants of excitability properties, we found heterogeneities, in terms of AIS localization and Nav composition. We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins. We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS. Their expression in the AIS and JXP-AIS is independent from transient axonal glycoprotein-1 (TAG-1)/Caspr2, in contrast to juxtaparanodes, and independent from PSD-93. Data from mice lacking the cytoskeletal linker protein 4.1B show that this protein is necessary to form the Caspr+ para-AIS barrier, ensuring the compartmentalization of Kv1 channels and the segregation of the AIS, para-AIS and JXP-AIS. α Motor neurons have heterogeneous AISs, which underlie different spiking properties. However, they all have a para-AIS and a JXP-AIS contiguous to their AIS, where the myelin sheath begins, which might limit some AIS plasticity. Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region. Show less

Neural crest (NC) cells are a multipotent, highly migratory cell population that generates most of the components of the peripheral nervous system (PNS), including the glial Schwann cells (SC) and boundary cap (BC) cells. These latter cells are located at the interface between the central nervous system and PNS, at the exit/entry points of ventral motor/dorsal sensory axons and give rise to all SC in the nerve roots and to a subset of nociceptive neurons and satellite cells in the dorsal root ganglia. In the present study we have compared BC cells with two closely related cell types, NC and Schwann cell precursors (SCpr), by RNA profiling. This led to the definition of a set of 10 genes that show specific expression in BC cells and/or in their derivatives along the nerve roots. Analysis of the expression of these genes during mouse development revealed novel features, of those most important are: (i) dorsal and ventral nerve root BC cell derivatives express different sets of genes, suggesting that they have distinct properties; (ii) these cells undergo major modifications in their gene expression pattern between embryonic days 14.5 and 17.5, possibly linked to the SCpr-immature Schwann cell transition; (iii) nerve roots SC differ from more distal SC not only in their origins and locations, but also in their gene expression patterns. In conclusion, the identification of these novel makers opens the way for a detailed characterization of BC cells in both mouse and man. Show less