Possible implication of undescribed SMN1-SMN2 genotype in chronic EMG-pattern of SMA with transitory acute denervation

Spinal muscular atrophy (SMA) refers to a group of genetic neuromuscular disorders affecting lower motor neurons causative of numerous phenotypes. To date, according to the age of onset, maximum muscular activity achieved, and life expectation four types of SMA are recognized, all caused by mutations in the SMN1 gene with SMN2 copy number influencing disease severity. Herein, we describe the case of a 31-year-old young male with normal psychomotor development who has experienced fatigue, cramps, and muscle fasciculations in the lower limbs for a period of 2 months. Based on electrophysiological and clinical findings we performed SMA genetic, clinical exome and RNA expression of candidate genes which led us to suggest SMN1-SMN2 genes [(2+0) and (0+0)] combination as possibly being implicated in the phenotype.     

Effect of positive charges in the structural interaction of crabrolin isoforms with lipopolysaccharide

Antimicrobial peptides (AMPs) appear as chemical compounds of increasing interest for their role in killing bacteria and, more recently, for their ability to bind endotoxin (lipopolysaccharide, LPS) that is released during bacterial infection and that may lead to septic shock. This dual role in the mechanism of action can further be enhanced in a synergistic way when two or more AMPs are combined together. Not all AMPs are able to bind LPS, suggesting that several modes of binding to the bacterial surface may exist. Here we analyze a natural AMP, crabrolin, and two mutated forms, one with increased positive charge (Crabrolin Plus) and the other with null charge (Crabrolin Minus), and compare their binding abilities to LPS. While Crabrolin WT as well Crabrolin Minus do not show binding to LPS, the mutated Crabrolin Plus exhibits binding and forms a well defined structure in the presence of LPS. The results strengthen the importance of positive charges for the binding to LPS and suggest the mutated form with increased positive charge as a promising candidate for antimicrobial and antiseptic activity.     

Comparing the binding properties of peptides mimicking the Envelope protein of SARS‐CoV and SARS‐CoV‐2 to the PDZ domain of the tight junction‐associated PALS1 protein

The Envelope protein (E) is one of the four structural proteins encoded by the genome of SARS‐CoV and SARS‐CoV‐2 Coronaviruses. It is an integral membrane protein, highly expressed in the host cell, which is known to have an important role in Coronaviruses maturation, assembly and virulence. The E protein presents a PDZ‐binding motif at its C‐terminus. One of the key interactors of the E protein in the intracellular environment is the PDZ containing protein PALS1. This interaction is known to play a key role in the SARS‐CoV pathology and suspected to affect the integrity of the lung epithelia. In this paper we measured and compared the affinity of peptides mimicking the E protein from SARS‐CoV and SARS‐CoV‐2 for the PDZ domain of PALS1, through equilibrium and kinetic binding experiments. Our results support the hypothesis that the increased virulence of SARS‐CoV‐2 compared to SARS‐CoV may rely on the increased affinity of its Envelope protein for PALS1.     

Carbohydrate based meningococcal vaccines: past and present overview

Glycoconjugate Journal - Neisseria meningitidis is a major cause of bacterial meningitidis worldwide. Children less than five years and adolescents are particularly affected. Nearly all invasive...