Sleep abnormalities in the synaptopathies—SYNGAP1-related intellectual disability and Phelan–McDermid syndrome

Neurodevelopmental disorders are frequently associated with sleep disturbances. One class of neurodevelopmental disorders, the genetic synaptopathies, is caused by mutations in genes encoding proteins found at the synapse. Mutations in these genes cause derangement of synapse development and function. We utilized a validated sleep instrument, Children’s Sleep Habits Questionnaire (CSHQ) to examine the nature of sleep abnormalities occurring in individuals with two synaptopathies—Phelan–McDermid syndrome (PMD) (N = 47, male = 23, female = 24, age 1–46 years) and SYNGAP1-related intellectual disability (SYNGAP1-ID) (N = 64, male = 31, female = 33, age 1–64 years), when compared with unaffected siblings (N = 61, male = 25, female = 36, age 1–17 years). We found that both PMD and SYNGAP1-ID have significant sleep abnormalities with SYNGAP1-ID having greater severity of sleep disturbance than PMD. In addition, sleep disturbances were more severe for PMD in individuals 11 years and older compared with those less than 11 years old. Individuals with either disorder were more likely to use sleep aids than unaffected siblings. In conclusion, sleep disturbances are a significant phenotype in the synaptopathies PMD and SYNGAP1-ID. Improved sleep is a viable endpoint for future clinical trials for these neurodevelopmental disorders

Mannosidosis: two brothers with different degrees of disease severity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65926/1/j.1399-0004.1981.tb01829.x.pd

Distinct migratory and non-migratory ecotypes of an endemic New Zealand eleotrid (Gobiomorphus cotidianus) – implications for incipient speciation in island freshwater fish species

Background: Many postglacial lakes contain fish species with distinct ecomorphs. Similar evolutionary scenarios might be acting on evolutionarily young fish communities in lakes of remote islands. One process that drives diversification in island freshwater fish species is the colonization of depauperate freshwater environments by diadromous (migratory) taxa, which secondarily lose their migratory behaviour. The loss of migration limits dispersal and gene flow between distant populations, and, therefore, is expected to facilitate local morphological and genetic differentiation. To date, most studies have focused on interspecific relationships among migratory species and their non-migratory sister taxa. We hypothesize that the loss of migration facilitates intraspecific morphological, behavioural, and genetic differentiation between migratory and non-migratory populations of facultatively diadromous taxa, and, hence, incipient speciation of island freshwater fish species. Results: Microchemical analyses of otolith isotopes (Sr-88, Ba-137 and Ca-43) differentiated migratory and non-migratory stocks of the New Zealand endemic Gobiomorphus cotidianus McDowall (Eleotridae). Samples were taken from two rivers, one lake and two geographically-separated outgroup locations. Meristic analyses of oculoscapular lateral line canals documented a gradual reduction of these structures in the non-migratory populations. Amplified fragment length polymorphism (AFLP) fingerprints revealed considerable genetic isolation between migratory and non-migratory populations. Temporal differences in reproductive timing (migratory = winter spawners, non-migratory = summer spawners; as inferred from gonadosomatic indices) provide a prezygotic reproductive isolation mechanism between the two ecotypes. Conclusion: This study provides a holistic look at the role of diadromy in incipient speciation of island freshwater fish species. All four analytical approaches (otolith microchemistry, morphology, spawning timing, population genetics) yield congruent results, and provide clear and independent evidence for the existence of distinct migratory and non-migratory ecotypes within a river in a geographically confined range. The morphological changes within the non-migratory populations parallel interspecific patterns observed in all non-migratory New Zealand endemic Gobiomorphus species and other derived gobiid taxa, a pattern suggesting parallel evolution. This study indicates, for the first time, that distinct ecotypes of island freshwater fish species may be formed as a consequence of loss of migration and subsequent diversification. Therefore, if reproductive isolation persists, these processes may provide a mechanism to facilitate speciation

Field-temperature phase diagram and entropy landscape of CeAuSb2

We report a field-temperature phase diagram and an entropy map for the heavy-fermion compound CeAuSb2. CeAuSb2 orders antiferromagnetically below TN=6.6 K and has two metamagnetic transitions, at 2.8 and 5.6 T. The locations of the critical end points of the metamagnetic transitions, which may play a strong role in the putative quantum criticality of CeAuSb2 and related compounds, are identified. The entropy map reveals an apparent entropy balance with Fermi-liquid behavior, implying that above the Néel transition the Ce moments are incorporated into the Fermi liquid. High-field data showing that the magnetic behavior is remarkably anisotropic are also reported

Nutrient limitations to bacterial and fungal growth during cellulose decomposition in tropical forest soils

Nutrients constrain the soil carbon cycle in tropical forests, but we lack knowledge on how these constraints vary within the soil microbial community. Here, we used in situ fertilization in a montane tropical forest and in two lowland tropical forests on contrasting soil types to test the principal hypothesis that there are different nutrient constraints to different groups of microorganisms during the decomposition of cellulose. We also tested the hypotheses that decomposers shift from nitrogen to phosphorus constraints from montane to lowland forests, respectively, and are further constrained by potassium and sodium deficiency in the western Amazon. Cellulose and nutrients (nitrogen, phosphorus, potassium, sodium, and combined) were added to soils in situ, and microbial growth on cellulose (phospholipid fatty acids and ergosterol) and respiration were measured. Microbial growth on cellulose after single nutrient additions was highest following nitrogen addition for fungi, suggesting nitrogen as the primary limiting nutrient for cellulose decomposition. This was observed at all sites, with no clear shift in nutrient constraints to decomposition between lowland and montane sites. We also observed positive respiration and fungal growth responses to sodium and potassium addition at one of the lowland sites. However, when phosphorus was added, and especially when added in combination with other nutrients, bacterial growth was highest, suggesting that bacteria out-compete fungi for nitrogen where phosphorus is abundant. In summary, nitrogen constrains fungal growth and cellulose decomposition in both lowland and montane tropical forest soils, but additional nutrients may also be of critical importance in determining the balance between fungal and bacterial decomposition of cellulose.This study is a product of the Andes Biodiversity and Ecosystem Research Group consortium (www.andesconservation.org) and was financed by the UK Natural Environment Research Council NE/G018278/1 to PM, a European Union Marie-Curie Fellowship FP7-2012-329360 to ATN and ARC award DP170104091 to PM

Hierarchy of Lifshitz transitions in the surface electronic structure of Sr2RuO4 under uniaxial compression

Funding: We gratefully acknowledge support from the Engineering and Physical Sciences Research Council (Grant Nos. EP/T02108X/1 and EP/R031924/1), the European Research Council (through the QUESTDO project, 714193), and the Leverhulme Trust (Grant No. RL-2016-006). E.A.M., A.Z., and I.M. gratefully acknowledge studentship support from the International Max-Planck Research School for Chemistry and Physics of Quantum Materials. N.K. is supported by a KAKENHI Grants-in-Aids for Scientific Research (Grant Nos.18K04715, and 21H01033), and Core-to-Core Program (No. JPJSCCA20170002) from the Japan Society for the Promotion of Science (JSPS) and by a JST-Mirai Program (Grant No. JPMJMI18A3). APM and CWH acknowledge support from the Deutsche Forschungsgemeinschaft - TRR 435 288 - 422213477 (project A10). We thank Diamond Light Source for access to Beamline I05 (Proposals SI27471 and SI28412), which contributed to the results presented here.We report the evolution of the electronic structure at the surface of the layered perovskiteSr2RuO4 under large in-plane uniaxial compression, leading to anisotropic B1g strains of εxx − εyy = −0.9 ± 0.1%. From angle-resolved photoemission, we show how this drives a sequence of Lifshitz transitions, reshaping the low-energy electronic structure and the rich spectrum of van Hove singularities that the surface layer of Sr2RuO4 hosts. From comparison to tight-binding modelling, we find that the strain is accommodated predominantly by bond-length changes rather than modifications of octahedral tilt and rotation angles. Our study sheds new light on the nature of structural distortions at oxide surfaces, and how targeted control of these can be used to tune density of states singularities to the Fermi level, in turn paving the way to the possible realisation of rich collective states at the Sr2RuO4 surface.PostprintPeer reviewe

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP