Delayed Imitation of Lipsmacking Gestures by Infant Rhesus Macaques (Macaca mulatta)

Human infants are capable of accurately matching facial gestures of an experimenter within a few hours after birth, a phenomenon called neonatal imitation. Recent studies have suggested that rather than being a simple reflexive-like behavior, infants exert active control over imitative responses and ‘provoke’ previously imitated gestures even after a delay of up to 24 h. Delayed imitation is regarded as the hallmark of a sophisticated capacity to control and flexibly engage in affective communication and has been described as an indicator of innate protoconversational readiness. However, we are not the only primates to exhibit neonatal imitation, and delayed imitation abilities may not be uniquely human. Here we report that 1-week-old infant rhesus macaques (Macaca mulatta) who show immediate imitation of a lipsmacking gesture also show delayed imitation of lipsmacking, facilitated by a tendency to refrain from lipsmacking toward a still face during baseline measurements. Individual differences in delayed imitation suggest that differentially matured cortical mechanisms may be involved, allowing some newborns macaques to actively participate in communicative exchanges from birth. Macaque infants are endowed with basic social competencies of intersubjective communication that indicate cognitive and emotional commonality between humans and macaques, which may have evolved to nurture an affective mother-infant relationship in primates

Defined neuronal populations drive fatal phenotype in a mouse model of leigh syndrome

Altres ajuts: Seattle Children's Research Institute: Seed Funds;NINDS: R01 NIH/NS 102796; University of Washington Neurological Surgery Department: Ellenbogen Neurological Surgery Research Funds; University of Washington: The Ryan J. Murphy SUDEP Research Funds; Mitochondrial Research Guild: Seed FundsMitochondrial deficits in energy production cause untreatable and fatal pathologies known as mitochondrial disease (MD). Central nervous system affectation is critical in Leigh Syndrome (LS), a common MD presentation, leading to motor and respiratory deficits, seizures and premature death. However, only specific neuronal populations are affected. Furthermore, their molecular identity and their contribution to the disease remains unknown. Here, using a mouse model of LS lacking the mitochondrial complex I subunit Ndufs4, we dissect the critical role of genetically-defined neuronal populations in LS progression. Ndufs4 inactivation in Vglut2expressing glutamatergic neurons leads to decreased neuronal firing, brainstem inflammation, motor and respiratory deficits, and early death. In contrast, Ndufs4 deletion in GABAergic neurons causes basal ganglia inflammation without motor or respiratory involvement, but accompanied by hypothermia and severe epileptic seizures preceding death. These results provide novel insight in the cell type-specific contribution to the pathology, dissecting the underlying cellular mechanisms of MD

[Copper(II)-aryltetraazannulene]Ix complexes as conductive materials. Solid state synthesis and characterization

Cu(dibenzo[b,i][1,4,8,11]tetraaza[14]annulene), Cu(dbTAA), Cu(dinaphtho- [b,il[1,4,8,11]tetraaza[14]annulene), Cu(dnTAA), Cu(diphenanthro[b,i][1,4,8,11]tetraaza [14]annulene) and Cu(dpTAA) complexes have been used for synthesizing new conductive materials. Chemical oxidation of the three compounds in acetone slurries by variable amounts of iodine yielded microcrystalline conductive powders with a wide range of stoichiometries. Thermal stability of the oxidized materials was investigated by TGA and DTGA techniques showing a relationship between solid phase stability and iodine content and, together with IR data, suggests the presence of a single phase. Raman spectra show strong scatterings attributable to I3− (107 cm−1) and (160 cm−1) I5− polyiodides, the latter occurs only in highly iodinated complexes (I/Cu ratio larger than three) and the I2 presence can be excluded. Electrical conductivity measurements of powder samples of the oxidized compounds exhibit some dependence on the iodine content in the I/Cu ratio range 0–0.9. The temperature response of the conductivity of the oxidized compounds, in the range 70–220 K, is interpretable in terms of an activated formation of carriers. ESR spectra, static magnetic susceptibility and IR data as a function of the I/Cu ratio suggest that the oxidative process involves not only the copper unpaired electron, but also electrons associated with delocalized ligand orbitals on the macrocycle. Large enhancement of the conductivity is shown by Cu(dpTAA)I0.2 (1.5 S cm−1) and the temperature dependence of conductivity shows metallic behaviour starting from 200 K

Peptides from chiral Cα,α-disubstituted glycines Synthesis and characterization, conformational energy computations and solution conformational analysis of Cα-methyl, Cα-isopropylglycine [(αMe)Val] derivatives and model peptides

Conformational energy computations on Ac-l-(αMe)Val-NHMe indicate that turns and right-handed helical structures are particularly stable conformations for this chiral Cα-methyl, Cα-alkylglycyl residue. We have synthesized and characterized a variety of l-(αMe)Val derivatives and peptides (to the pentamer level). The results of the solution conformational analysis, performed using infrared absorption, 1H nuclear magnetic resonance, and circular dichroism, are in general agreement with those obtained from the theoretical investigation, in the sense that the l-(αMe)Val residue turns out to be a strong β-turn and right-handed helix former. A comparison is also made with the conclusions extracted from published work on peptides rich in other Cα-methyl, Cα-alkylglycyl residues

Human KCNQ5 de novo Mutations Underlie Epilepsy and Intellectual Disability

We identified six novel de novo human KCNQ5 variants in children with motor/language delay, intellectual disability (ID) and/or epilepsy by whole-exome sequencing. These variants comprised of two nonsense and four missense alterations, were functionally characterized by electrophysiology in HEK293/CHO cells, together with four previously reported KCNQ5 missense variants (Lehman, et al., 2017). Surprisingly, all eight missense variants resulted in gain-of-function (GOF) due to hyperpolarized voltage-dependence of activation or slowed deactivation kinetics, while the two nonsense variants were confirmed to be loss-of-function (LOF). One severe GOF allele (P369T) was tested and found to extend a dominant GOF effect to heteromeric KCNQ5/3 channels. Clinical presentations were associated with altered KCNQ5 channel gating: Milder presentations with LOF or smaller GOF shifts in voltage-dependence (DV50= ~-15 mV), and severe presentations with larger GOF shifts in voltage-dependence (DV50= ~-30 mV). To examine LOF pathogenicity, two Kcnq5 LOF mouse lines were created using CRISPR/Cas9. Both lines exhibited handling- and thermal-induced seizures, and abnormal cortical EEGs consistent with epileptiform activity. Our study thus provides evidence for in vivo KCNQ5 LOF pathogenicity and strengthens the contribution of both LOF and GOF mutations to global pediatric neurological impairment, including ID/epilepsy