Background: Malnutrition is associated with both structural and functional pathology of the brain. A wide range of cognitive deficits has been reported in malnourished children. Effect of chronic protein energy malnutrition (PEM) causing stunting and wasting in children could also affect the ongoing development of higher cognitive processes during childhood (>5 years of age). The present study examined the effect of stunted growth on the rate of development of cognitive processes using neuropsychological measures.

This study examines the characteristics of binding of berberine to the human telomeric d[AG3(T2AG3)3] quadruplex. By employing UV‐visible spectroscopy, fluorescence spectroscopy and isothermal titration calorimetry, we found that the binding affinity of berberine to the human telomeric quadruplex is 106. The complete thermodynamic profile for berberine binding to the quadruplex, at 25 °C, shows a small negative enthalpy (ΔH) of −1.7 kcal·mol−1, an entropy change with TΔS of +6.5 kcal·mol−1, and an overall favorable free energy (ΔG) of −8.2 kcal·mol−1 .Through the temperature dependence of ΔH, we obtained a heat capacity (ΔCp) of −94 (± 5) cal·mol−1·K−1. The osmotic stress method revealed that there is an uptake of 13 water molecules in the complex relative to the free reactants. Furthermore, the molecular modeling studies on different quadruplex–berberine complexes show that berberine stacking at the external G‐quartet is mainly aided by the π–π interaction and the stabilization of the high negative charge density of O6 of guanines by the positively charged N7 of berberine. The theoretical heat capacity (ΔCp) values for quadruplex–berberine models are −89 and −156 cal·mol−1·K−1.

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia. Molecular dynamics simulations predicted long-range and/or local structural perturbations associated with the disease-causing mutations. Biochemical analyses documented variably reduced levels of TBCD, indicating relative instability of mutant proteins, and defective β-tubulin binding in a subset of the tested mutants. Reduced or defective TBCD function resulted in decreased soluble α/β-tubulin levels and accelerated microtubule polymerization in fibroblasts from affected subjects, demonstrating an overall shift toward a more rapidly growing and stable microtubule population. These cells displayed an aberrant mitotic spindle with disorganized, tangle-shaped microtubules and reduced aster formation, which however did not alter appreciably the rate of cell proliferation. Our findings establish that defective TBCD function underlies a recognizable encephalopathy and drives accelerated microtubule polymerization and enhanced microtubule stability, underscoring an additional cause of altered microtubule dynamics with impact on neuronal function and survival in the developing brain.

In this paper, we have extended to the calculation of hyperfine coupling constants, the model recently proposed by some of the present authors [Giovannini et al., J. Chem. Theory Comput. 13, 4854–4870 (2017)] to include Pauli repulsion and dispersion effects in Quantum Mechanical/Molecular Mechanics (QM/MM) approaches. The peculiarity of the proposed approach stands in the fact that repulsion/dispersion contributions are explicitly introduced in the QM Hamiltonian. Therefore, such terms not only enter the evaluation of energetic properties but also propagate to molecular properties and spectra. A novel parametrization of the electrostatic fluctuating charge force field has been developed, thus allowing a quantitative reproduction of reference QM interaction energies. Such a parametrization has been then tested against the prediction of EPR parameters of prototypical nitroxide radicals in aqueous solutions.