Genetic basis of human circadian rhythm disorders.

Circadian rhythm disorders constitute a group of phenotypes that usually present as altered sleep-wake schedules. Until a human genetics approach was applied to investigate these traits, the genetic components regulating human circadian rhythm and sleep behaviors remained mysterious. Steady advances in the last decade have dramatically improved our understanding of the genes involved in circadian rhythmicity and sleep regulation. Finding these genes presents new opportunities to use a wide range of approaches, including in vitro molecular studies and in vivo animal modeling, to elevate our understanding of how sleep and circadian rhythms are regulated and maintained. Ultimately, this knowledge will reveal how circadian and sleep disruption contribute to various ailments and shed light on how best to maintain and recover good health

Influence of solvent quality on polymer solutions: a Monte Carlo study of bulk and interfacial properties

The effect of solvent quality on dilute and semi-dilute regimes of polymers in solution is studied by means of Monte Carlo simulations. The equation of state, adsorptions near a hard wall, wall-polymer surface tension and effective depletion potentials are all calculated as a function of concentration and solvent quality. We find important differences between polymers in good and theta solvents. In the dilute regime, the physical properties for polymers in a theta solvent closely resemble those of ideal polymers. In the semi-dilute regime, however, significant differences are found.Comment: 10 pages, 13 figure

Princess and the Pea at the nanoscale: Wrinkling and delamination of graphene on nanoparticles

Thin membranes exhibit complex responses to external forces or geometrical constraints. A familiar example is the wrinkling, exhibited by human skin, plant leaves, and fabrics, resulting from the relative ease of bending versus stretching. Here, we study the wrinkling of graphene, the thinnest and stiffest known membrane, deposited on a silica substrate decorated with silica nanoparticles. At small nanoparticle density monolayer graphene adheres to the substrate, detached only in small regions around the nanoparticles. With increasing nanoparticle density, we observe the formation of wrinkles which connect nanoparticles. Above a critical nanoparticle density, the wrinkles form a percolating network through the sample. As the graphene membrane is made thicker, global delamination from the substrate is observed. The observations can be well understood within a continuum elastic model and have important implications for strain-engineering the electronic properties of graphene.Comment: 11 pages, 8 figures. Accepted for publication in Physical Review

MicroRNA-23a promotes myelination in the central nervous system.

Demyelinating disorders including leukodystrophies are devastating conditions that are still in need of better understanding, and both oligodendrocyte differentiation and myelin synthesis pathways are potential avenues for developing treatment. Overexpression of lamin B1 leads to leukodystrophy characterized by demyelination of the central nervous system, and microRNA-23 (miR-23) was found to suppress lamin B1 and enhance oligodendrocyte differentiation in vitro. Here, we demonstrated that miR-23a-overexpressing mice have increased myelin thickness, providing in vivo evidence that miR-23a enhances both oligodendrocyte differentiation and myelin synthesis. Using this mouse model, we explored possible miR-23a targets and revealed that the phosphatase and tensin homologue/phosphatidylinositol trisphosphate kinase/Akt/mammalian target of rapamycin pathway is modulated by miR-23a. Additionally, a long noncoding RNA, 2700046G09Rik, was identified as a miR-23a target and modulates phosphatase and tensin homologue itself in a miR-23a-dependent manner. The data presented here imply a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin

Solvent effect on the ion adsorption from ionic liquid electrolyte into sub-nanometer carbon pores

This paper presents the results from the investigation of the influence of ion size on the capacitance behaviour of TiC-derived carbon (CDC) powders in the ethyl-methylimmidazolium-bis(trifluoromethane-sulfonyl)imide ionic liquid (EMI, TFSI) used as neat electrolyte at 60°C or as salt dissolved in acetonitrile and tested at room temperature. These studies were carried out with the assembly of conventional 3-electrode electrochemical cells as well as using the Cavity-MicroElectrode (CME) technique. The issues regarding the extents of desolvation of the electrolyte ions when adsorbed in the pores of the CDCs under applied potential were studied, the CME technique was found to be particularly efficient in the deduction of the effective ion size under solvated conditions

Evaluating the character and preservation of DNA within allophane clusters in buried soils on Holocene tephras, northern New Zealand

Clay minerals possess sorptive capacities for organic and inorganic matter, including DNA (Lorenz and Wackernagel, 1994), and hence reduce the utilization and degradation of organic matter or DNA by microorganisms. Buried allophane-rich soils on tephras (volcanic-ash beds) on the North Island, dated using tephrochronology, provide a valuable paleobiological ‘laboratory’ for studying the preservation of ancient DNA (aDNA) (Haile et al., 2007). Allophane comprises Al-rich nanocrystalline spherules ~3.5-5 nm in diameter (Fig. 1) with extremely large surface areas (up to 1000 m2 g-1). Moreover, allophanic soils are strongly associated with organic matter (Parfitt, 2009), and so we hypothesize that allophane also plays an important role for DNA protection within such soils

The origin recognition core complex regulates dendrite and spine development in postmitotic neurons

The origin recognition complex (ORC) ensures exactly one round of genome replication per cell cycle through acting as a molecular switch that precisely controls the assembly, firing, and inactivation of the replication initiation machinery. Recent data indicate that it may also coordinate the processes of mitosis and cytokinesis and ensure the proper distribution of replicated genome to daughter cells. We have found that the ORC core subunits are highly expressed in the nervous system. They are selectively localized to the neuronal somatodendritic compartment and enriched in the membrane fraction. siRNA knockdown of ORC subunits dramatically reduced dendritic branch formation and severely impeded dendritic spine emergence. Expression of ORC ATPase motif mutants enhanced the branching of dendritic arbors. The ORC core complex thus appears to have a novel role in regulating dendrite and dendritic spine development in postmitotic neurons

Acute Infection and Subsequent Subclinical Reactivation of Herpes Simplex Virus 2 after Vaginal Inoculation of Rhesus Macaques.

Herpes simplex virus 2 (HSV-2) is a common sexually transmitted infection with a highly variable clinical course. Many infections quickly become subclinical, with episodes of spontaneous virus reactivation. To study host-HSV-2 interactions, an animal model of subclinical HSV-2 infection is needed. In an effort to develop a relevant model, rhesus macaques (RM) were inoculated intravaginally with two or three HSV-2 strains (186, 333, and/or G) at a total dose of 1 × 107 PFU of HSV-2 per animal. Infectious HSV-2 and HSV-2 DNA were consistently shed in vaginal swabs for the first 7 to 14 days after each inoculation. Proteins associated with wound healing, innate immunity, and inflammation were significantly increased in cervical secretions immediately after HSV-2 inoculation. There was histologic evidence of acute herpesvirus pathology, including acantholysis in the squamous epithelium and ballooning degeneration of and intranuclear inclusion bodies in epithelial cells, with HSV antigen in mucosal epithelial cells and keratinocytes. Further, an intense inflammatory infiltrate was found in the cervix and vulva. Evidence of latent infection and reactivation was demonstrated by the detection of spontaneous HSV-2 shedding post-acute inoculation (102 to 103 DNA copies/swab) in 80% of RM. Further, HSV-2 DNA was detected in ganglia in most necropsied animals. HSV-2-specifc T-cell responses were detected in all animals, although antibodies to HSV-2 were detected in only 30% of the animals. Thus, HSV-2 infection of RM recapitulates many of the key features of subclinical HSV-2 infection in women but seems to be more limited, as virus shedding was undetectable more than 40 days after the last virus inoculation.IMPORTANCE Herpes simplex virus 2 (HSV-2) infects nearly 500 million persons globally, with an estimated 21 million incident cases each year, making it one of the most common sexually transmitted infections (STIs). HSV-2 is associated with increased human immunodeficiency virus type 1 (HIV-1) acquisition, and this risk does not decline with the use of antiherpes drugs. As initial acquisition of both HIV and HSV-2 infections is subclinical, study of the initial molecular interactions of the two agents requires an animal model. We found that HSV-2 can infect RM after vaginal inoculation, establish latency in the nervous system, and spontaneously reactivate; these features mimic some of the key features of HSV-2 infection in women. RM may provide an animal model to develop strategies to prevent HSV-2 acquisition and reactivation