Pre-Pulse Inhibition of an escape response in adult fruit fly, Drosophila melanogaster.

Pre-Pulse Inhibition (PPI) is a neural process where suppression of a startle response is elicited by preceding the startling stimulus (Pulse) with a weak, non-startling one (Pre-Pulse). Defective PPI is widely employed as a behavioural endophenotype in humans and mammalian disorder-relevant models for neuropsychiatric disorders. We have developed a user-friendly, semi-automated, high-throughput-compatible Drosophila light-off jump response PPI paradigm, with which we demonstrate that PPI, with similar parameters measured in mammals, exists in adults of this model organism. We report that Drosophila PPI is affected by reduced expression of Dysbindin and both reduced and increased expression of Nmdar1 (N-methyl-D-aspartate receptor 1), perturbations associated with schizophrenia. Studying the biology of PPI in an organism that offers a plethora of genetic tools and a complex and well characterized connectome will greatly facilitate our efforts to gain deeper insight into the aetiology of human mental disorders, while reducing the need for mammalian models.

Outstanding Thermal Conductivity of Single Atomic Layer Isotope-Modified Boron Nitride.

Materials with high thermal conductivities (κ) are valuable to solve the challenge of waste heat dissipation in highly integrated and miniaturized modern devices. Herein, we report the first synthesis of atomically thin isotopically pure hexagonal boron nitride (BN) and its one of the highest κ among all semiconductors and electric insulators. Single atomic layer (1L) BN enriched with ^{11}B has a κ up to 1009 W/mK at room temperature. We find that the isotope engineering mainly suppresses the out-of-plane optical (ZO) phonon scatterings in BN, which subsequently reduces acoustic-optical scatterings between ZO and transverse acoustic (TA) and longitudinal acoustic phonons. On the other hand, reducing the thickness to a single atomic layer diminishes the interlayer interactions and hence umklapp scatterings of the out-of-plane acoustic (ZA) phonons, though this thickness-induced κ enhancement is not as dramatic as that in naturally occurring BN. With many of its unique properties, atomically thin monoisotopic BN is promising on heat management in van der Waals devices and future flexible electronics. The isotope engineering of atomically thin BN may also open up other appealing applications and opportunities in 2D materials yet to be explored.

From Rare Copy Number Variants to Biological Processes in ADHD.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric disorder. The objective of this study was to define ADHD-associated candidate genes and their associated molecular modules and biological themes, based on the analysis of rare genetic variants. METHODS: The authors combined data from 11 published copy number variation studies in 6,176 individuals with ADHD and 25,026 control subjects and prioritized genes by applying an integrative strategy based on criteria including recurrence in individuals with ADHD, absence in control subjects, complete coverage in copy number gains, and presence in the minimal region common to overlapping copy number variants (CNVs), as well as on protein-protein interactions and information from cross-species genotype-phenotype annotation. RESULTS: The authors localized 2,241 eligible genes in the 1,532 reported CNVs, of which they classified 432 as high-priority ADHD candidate genes. The high-priority ADHD candidate genes were significantly coexpressed in the brain. A network of 66 genes was supported by ADHD-relevant phenotypes in the cross-species database. Four significantly interconnected protein modules were found among the high-priority ADHD genes. A total of 26 genes were observed across all applied bioinformatic methods. Lookup in the latest genome-wide association study for ADHD showed that among those 26 genes, POLR3C and RBFOX1 were also supported by common genetic variants. CONCLUSIONS: Integration of a stringent filtering procedure in CNV studies with suitable bioinformatics approaches can identify ADHD candidate genes at increased levels of credibility. The authors' analytic pipeline provides additional insight into the molecular mechanisms underlying ADHD and allows prioritization of genes for functional validation in validated model organisms.

In situ production of a two-dimensional molybdenum disulfide/graphene hybrid nanosheet anode for lithium-ion batteries.

A solvent-free, low-cost, high-yield and scalable single-step ball milling process is developed to construct 2D MoS2/graphene hybrid electrodes for lithium-ion batteries. Electron microscopy investigation reveals that the obtained hybrid electrodes consist of numerous nanosheets of MoS2 and graphene which are randomly distributed. The MoS2/graphene hybrid anodes exhibit excellent cycling stability with high reversible capacities (442 mA h g-1 for MoS2/graphene (40 h); 553 mA h g-1 for MoS2/graphene (20 h); 342 mA h g-1 for MoS2/graphene (10 h)) at a high current rate of 250 mA g-1 after 100 cycles, whereas the pristine MoS2 electrode shows huge capacity fading with a retention of 37 mA h g-1 at 250 mA g-1 current after 100 cycles. The incorporation of graphene into MoS2 has an extraordinary effect on its electrochemical performance. This work emphasises the importance of the construction of the 2D MoS2/graphene hybrid structure to prevent capacity fading issues with the MoS2 anode in lithium-ion batteries.

Habituation Learning Is a Widely Affected Mechanism in Drosophila Models of Intellectual Disability and Autism Spectrum Disorders.

BACKGROUND: Although habituation is one of the most ancient and fundamental forms of learning, its regulators and its relevance for human disease are poorly understood. METHODS: We manipulated the orthologs of 286 genes implicated in intellectual disability (ID) with or without comorbid autism spectrum disorder (ASD) specifically in Drosophila neurons, and we tested these models in light-off jump habituation. We dissected neuronal substrates underlying the identified habituation deficits and integrated genotype-phenotype annotations, gene ontologies, and interaction networks to determine the clinical features and molecular processes that are associated with habituation deficits. RESULTS: We identified >100 genes required for habituation learning. For 93 of these genes, a role in habituation learning was previously unknown. These genes characterize ID disorders with macrocephaly and/or overgrowth and comorbid ASD. Moreover, individuals with ASD from the Simons Simplex Collection carrying damaging de novo mutations in these genes exhibit increased aberrant behaviors associated with inappropriate, stereotypic speech. At the molecular level, ID genes required for normal habituation are enriched in synaptic function and converge on Ras/mitogen-activated protein kinase (Ras/MAPK) signaling. Both increased Ras/MAPK signaling in gamma-aminobutyric acidergic (GABAergic) neurons and decreased Ras/MAPK signaling in cholinergic neurons specifically inhibit the adaptive habituation response. CONCLUSIONS: Our work supports the relevance of habituation learning to ASD, identifies an unprecedented number of novel habituation players, supports an emerging role for inhibitory neurons in habituation, and reveals an opposing, circuit-level-based mechanism for Ras/MAPK signaling. These findings establish habituation as a possible, widely applicable functional readout and target for pharmacologic intervention in ID/ASD.

Systematic Phenomics Analysis Deconvolutes Genes Mutated in Intellectual Disability into Biologically Coherent Modules.

Intellectual disability (ID) disorders are genetically and phenotypically extremely heterogeneous. Can this complexity be depicted in a comprehensive way as a means of facilitating the understanding of ID disorders and their underlying biology? We provide a curated database of 746 currently known genes, mutations in which cause ID (ID-associated genes [ID-AGs]), classified according to ID manifestation and associated clinical features. Using this integrated resource, we show that ID-AGs are substantially enriched with co-expression, protein-protein interactions, and specific biological functions. Systematic identification of highly enriched functional themes and phenotypes revealed typical phenotype combinations characterizing process-defined groups of ID disorders, such as chromatin-related disorders and deficiencies in DNA repair. Strikingly, phenotype classification efficiently breaks down ID-AGs into subsets with significantly elevated biological coherence and predictive power. Custom-made functional Drosophila datasets revealed further characteristic phenotypes among ID-AGs and specific clinical classes. Our study and resource provide systematic insights into the molecular and clinical landscape of ID disorders, represent a significant step toward overcoming current limitations in ID research, and prove the utility of systematic human and cross-species phenomics analyses in highly heterogeneous genetic disorders.

WeGET: predicting new genes for molecular systems by weighted co-expression.

We have developed the Weighted Gene Expression Tool and database (WeGET, http://weget.cmbi.umcn.nl) for the prediction of new genes of a molecular system by correlated gene expression. WeGET utilizes a compendium of 465 human and 560 murine gene expression datasets that have been collected from multiple tissues under a wide range of experimental conditions. It exploits this abundance of expression data by assigning a high weight to datasets in which the known genes of a molecular system are harmoniously up- and down-regulated. WeGET ranks new candidate genes by calculating their weighted co-expression with that system. A weighted rank is calculated for human genes and their mouse orthologs. Then, an integrated gene rank and p-value is computed using a rank-order statistic. We applied our method to predict novel genes that have a high degree of co-expression with Gene Ontology terms and pathways from KEGG and Reactome. For each query set we provide a list of predicted novel genes, computed weights for transcription datasets used and cell and tissue types that contributed to the final predictions. The performance for each query set is assessed by 10-fold cross-validation. Finally, users can use the WeGET to predict novel genes that co-express with a custom query set.

High-Performance Supercapacitor Electrode Materials from Cellulose-Derived Carbon Nanofibers.

Nitrogen-functionalized carbon nanofibers (N-CNFs) were prepared by carbonizing polypyrrole (PPy)-coated cellulose NFs, which were obtained by electrospinning, deacetylation of electrospun cellulose acetate NFs, and PPy polymerization. Supercapacitor electrodes prepared from N-CNFs and a mixture of N-CNFs and Ni(OH)2 showed specific capacitances of ∼236 and ∼1045 F g(-1), respectively. An asymmetric supercapacitor was further fabricated using N-CNFs/Ni(OH)2 and N-CNFs as positive and negative electrodes. The supercapacitor device had a working voltage of 1.6 V in aqueous KOH solution (6.0 M) with an energy density as high as ∼51 (W h) kg(-1) and a maximum power density of ∼117 kW kg(-1). The device had excellent cycle lifetime, which retained ∼84% specific capacitance after 5000 cycles of cyclic voltammetry scans. N-CNFs derived from electrospun cellulose may be useful as an electrode material for development of high-performance supercapacitors and other energy storage devices.

Facile preparation and thermoelectric properties of Bi2Te3 based alloy nanosheet/PEDOT:PSS composite films.

Bi2Te3 based alloy nanosheet (NS)/poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) composite films were prepared separately by spin coating and drop casting techniques. The drop cast composite film containing 4.10 wt % Bi2Te3 based alloy NSs showed electrical conductivity as high as 1295.21 S/cm, which is higher than that (753.8 S/cm) of a dimethyl sulfoxide doped PEDOT:PSS film prepared under the same condition and that (850-1250 S/cm) of the Bi2Te3 based alloy bulk material. The composite film also showed a very high power factor value, ∼32.26 µWm(-1) K(-2). With the content of Bi2Te3 based alloy NSs increasing from 0 to 4.10 wt %, the electrical conductivity and Seebeck coefficient of the composite films increase simultaneously.