Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis

Complicated hereditary spastic paraplegias (HSP) are a heterogeneous group of HSP characterized by spasticity associated with a variable combination of neurologic and extra-neurologic signs and symptoms. Among them, HSP with thin corpus callosum and intellectual disability is a frequent subtype, often inherited as a recessive trait (ARHSP-TCC). Within this heterogeneous subgroup, SPG11 and SPG15 represent the most frequent subtypes. We analyzed the mutation frequency of three genes associated with early-onset forms of ARHSP with and without TCC, CYP2U1/SPG56, DDHD2/SPG54 and GBA2/SPG46, in a large population of selected complicated HSP patients by using a combined approach of traditional-based and amplicon-based high-throughput pooled-sequencing. Three families with mutations were identified, one for each of the genes analyzed. Novel homozygous mutations were identified in CYP2U1 (c.1A>C/p.Met1?) and in GBA2 (c.2048G>C/ p.Gly683Arg), while the homozygous mutation found in DDHD2 (c.1978G>C/p.Asp660His) had been previously reported in a compound heterozygous state. The phenotypes associated with the CYP2U1 and DDHD2 mutations overlap the SPG56 and the SPG54 subtypes, respectively, with few differences. By contrast, the GBA2 mutated patients show phenotypes combining typical features of both the SPG46 subtype and the recessive ataxia form, with marked intrafamilial variability thereby expanding the spectrum of clinical entities associated with GBA2 mutations. Overall, each of three genes analyzed shows a low mutation frequency in a general population of complicated HSP (<1% for either CYP2U1 or DDHD2 and approximately 2% for GBA2 ). These findings underline once again the genetic heterogeneity of ARHSP-TCC and the clinical overlap between complicated HSP and the recessive ataxia syndromes

Crossovers in Unitary Fermi Systems

Universality and crossover is described for attractive and repulsive interactions where, respectively, the BCS-BEC crossover takes place and a ferromagnetic phase transition is claimed. Crossovers are also described for optical lattices and multicomponent systems. The crossovers, universal parameters and phase transitions are described within the Leggett and NSR models and calculated in detail within the Jastrow-Slater approximation. The physics of ultracold Fermi atoms is applied to neutron, nuclear and quark matter, nuclei and electrons in solids whenever possible. Specifically, the differences between optical lattices and cuprates is discussed w.r.t. antiferromagnetic, d-wave superfluid phases and phase separation.Comment: 50 pages, 15 figures. Contribution to Lecture Notes in Physics "BCS-BEC crossover and the Unitary Fermi Gas" edited by W. Zwerge

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research