Nonlinear viscoelastic dynamics of nano-confined water

The viscoelastic dynamics of nano-confined water is studied by means of atomic force microscopy (AFM). We observe a nonlinear viscoelastic behavior remarkably similar to that widely observed in metastable complex fluids. We show that the origin of the measured nonlinear viscoelasticity in nano-confined water is a strain rate dependent relaxation time and slow dynamics. By measuring the viscoelastic modulus at different frequencies and strains, we find that the intrinsic relaxation time of nano-confined water is in the range 0.1-0.0001 s, orders of magnitude longer than that of bulk water, and comparable to the dielectric relaxation time measured in supercooled water at 170-210 K.Comment: 4 Figure

WH2 and proline-rich domains of WASP-family proteins collaborate to accelerate actin filament elongation.

WASP-family proteins are known to promote assembly of branched actin networks by stimulating the filament-nucleating activity of the Arp2/3 complex. Here, we show that WASP-family proteins also function as polymerases that accelerate elongation of uncapped actin filaments. When clustered on a surface, WASP-family proteins can drive branched actin networks to grow much faster than they could by direct incorporation of soluble monomers. This polymerase activity arises from the coordinated action of two regulatory sequences: (i) a WASP homology 2 (WH2) domain that binds actin, and (ii) a proline-rich sequence that binds profilin-actin complexes. In the absence of profilin, WH2 domains are sufficient to accelerate filament elongation, but in the presence of profilin, proline-rich sequences are required to support polymerase activity by (i) bringing polymerization-competent actin monomers in proximity to growing filament ends, and (ii) promoting shuttling of actin monomers from profilin-actin complexes onto nearby WH2 domains. Unoccupied WH2 domains transiently associate with free filament ends, preventing their growth and dynamically tethering the branched actin network to the WASP-family proteins that create it. Collaboration between WH2 and proline-rich sequences thus strikes a balance between filament growth and tethering. Our work expands the number of critical roles that WASP-family proteins play in the assembly of branched actin networks to at least three: (i) promoting dendritic nucleation; (ii) linking actin networks to membranes; and (iii) accelerating filament elongation

Understanding Transport of an Elastic, Spherical Particle through a Confining Channel

The transport of soft particles through narrow channels or pores is ubiquitous in biological systems and industrial processes. On many occasions, the particles deform and temporarily block the channel, inducing a built-up pressure. This pressure buildup often has a profound effect on the behavior of the respective system; yet, it is difficult to be characterized. In this work, we establish a quantitative correlation between the built-up pressure and the material and geometry properties through experiments and mechanics analysis. We fabricate microgels with a controlled diameter and elastic modulus by microfluidics. We then force them to individually pass through a constrictive or straight confining channel and monitor the pressure variation across the channel. To interpret the pressure measurement, we develop an analytical model based on the Neo-Hookean material law to quantify the dependence of the maximum built-up pressure on the radius ratio of the elastic sphere to the channel, the elastic modulus of the sphere, and two constant parameters in the friction constitutive law between the sphere and the channel wall. This model not only agrees very well with the experimental measurement conducted at large microgel deformation but also recovers the classical theory of contact at small deformation. Featuring a balance between accuracy and simplicity, our result could shed light on understanding various biological and engineering processes involving the passage of elastic particles through narrow channels or pores

Quantized Media with Absorptive Scatterers and Modified Atomic Emission Rates

Modifications in the spontaneous emission rate of an excited atom that are caused by extinction effects in a nearby dielectric medium are analyzed in a quantummechanical model, in which the medium consists of spherical scatterers with absorptive properties. Use of the dyadic Green function of the electromagnetic field near a a dielectric sphere leads to an expression for the change in the emission rate as a series of multipole contributions for which analytical formulas are obtained. The results for the modified emission rate as a function of the distance between the excited atom and the dielectric medium show the influence of both absorption and scattering processes.Comment: 6 pages, 4 figure

INSIG1 influences obesity-related hypertriglyceridemia in humans

In our analysis of a quantitative trait locus (QTL) for plasma triglyceride (TG) levels [logarithm of odds (LOD) = 3.7] on human chromosome 7q36, we examined 29 single nucleotide polymorphisms (SNPs) across INSIG1, a biological candidate gene in the region. Insulin-induced genes (INSIGs) are feedback mediators of cholesterol and fatty acid synthesis in animals, but their role in human lipid regulation is unclear. In our cohort, the INSIG1 promoter SNP rs2721 was associated with TG levels (P = 2 × 10−3 in 1,560 individuals of the original linkage cohort, P = 8 × 10−4 in 920 unrelated individuals of the replication cohort, combined P = 9.9 × 10−6). Individuals homozygous for the T allele had 9% higher TG levels and 2-fold lower expression of INSIG1 in surgical liver biopsy samples when compared with individuals homozygous for the G allele. Also, the T allele showed additional binding of nuclear proteins from HepG2 liver cells in gel shift assays. Finally, the variant rs7566605 in INSIG2, the only homolog of INSIG1, enhances the effect of rs2721 (P = 0.00117). The variant rs2721 alone explains 5.4% of the observed linkage in our cohort, suggesting that additional, yet-undiscovered genes and sequence variants in the QTL interval also contribute to alterations in TG levels in humans

Heme Oxygenase-1, a Key Enzyme for the Cytoprotective Actions of Halophenols by Upregulating Nrf2 Expression via Activating Erk1/2 and PI3K/Akt in EA.hy926 Cells

Increasing evidence has demonstrated that heme oxygenase-1 (HO-1) is a key enzyme triggered by cellular stress, exhibiting cytoprotective, antioxidant, and anti-inflammatory abilities. Previously, we prepared a series of novel active halophenols possessing strong antioxidant activities in vitro and in vivo. In the present study, we demonstrated that these halophenols exhibited significant protective effects against H2O2-induced injury in EA.hy926 cells by inhibition of apoptosis and ROS and TNF-α production, as well as induction of the upregulation of HO-1, the magnitude of which correlated with their cytoprotective actions. Further experiments which aimed to determine the mechanistic basis of these actions indicated that the halophenols induced the activation of Nrf2, Erk1/2, and PI3K/Akt without obvious effects on the phosphorylation of p38, JNK, or the expression of PKC-δ. This was validated with the use of PD98059 and Wortmannin, specific inhibitors of Erk1/2 and PI3K, respectively. Overall, our study is the first to demonstrate that the cytoprotective actions of halophenols involve their antiapoptotic, antioxidant, and anti-inflammatory abilities, which are mediated by the upregulation of Nrf2-dependent HO-1 expression and reductions in ROS and TNF-α generation via the activation of Erk1/2 and PI3K/Akt in EA.hy926 cells. HO-1 may thus be an important potential target for further research into the cytoprotective actions of halophenols

Frequency and longitudinal clinical outcomes of Alzheimer's AT(N) biomarker profiles: A longitudinal study.

INTRODUCTION: We aimed to estimate the frequency of each AT(N) (β-amyloid deposition [A], pathologic tau [T], and neurodegeneration [N]) profile in different clinical diagnosis groups and to describe the longitudinal change in clinical outcomes of individuals in each group. METHODS: Longitudinal change in clinical outcomes and conversion risk of AT(N) profiles are assessed using linear mixed-effects models and multivariate Cox proportional-hazard models, respectively. RESULTS: Participants with A+T+N+ showed faster clinical progression than those with A-T-N- and A+T±N-. Compared with A-T-N-, participants with A+T+N± had an increased risk of conversion from cognitively normal (CN) to incident prodromal stage of Alzheimer's disease (AD), and from MCI to AD dementia. A+T+N+ showed an increased conversion risk when compared with A+T±N-. DISCUSSION: The 2018 research framework may provide prognostic information of clinical change and progression. It may also be useful for targeted recruitment of participants with AD into clinical trials

Foldable Conductive Cellulose Fiber Networks Modified by Graphene Nanoplatelet-Bio-Based Composites

Truly foldable flexible electronic components require a foldable substrate modified with a conducting material that can retain its electrical conductivity and mechanical integrity even after hard mechanical manipulations and multiple folding events. Here, such a material exploiting the combination of all-biodegradable components (substrate and the polymer matrix) and graphene nanoplatelets is designed and fabricated. A commercially available thermoplastic starch-based polymer (Mater-Bi) and graphene nanoplatelets are simultaneously dispersed in an organic solvent to formulate conductive inks. The inks are spray painted on pure cellulose sheets and hot-pressed into their fiber network after drying. The resultant nanostructured flexible composites display excellent isotropic electrical conductivity, reaching very low sheet resistance value ≈10 Ω sq−1, depending on the relative concentration between the biopolymer and the graphene nanoplatelets. Transmission electron microscopy results indicated that during hot-pressing, graphene nanoplatelets are physically embedded into the cellulose fibers, resulting in high electrical conductivity of the flexible composite. The paper-like flexible conductors can withstand many severe folding events, maintaining their mechanical and electrical properties and showing only a slight decrease of their electrical conductivity with respect to the unfolded counterparts. Unlike conductive paper technologies, the proposed paper-like flexible conductors demonstrate both sides isotropic conductivity due to pressure-induced impregnation

Binding enhancements of antibody functionalized natural and synthetic fibers

Development of low cost biosensing using convenient and environmentally benign materials is important for wide adoption and ultimately improved healthcare and sustainable development. Immobilized antibodies are often incorporated as an essential biorecognition element in point-of-care biosensors but these proteins are costly. We present a strategy of combining convenient and low-cost surface functionalization approaches for increasing the overall binding activity of antibody functionalized natural and synthetic fibers. We demonstrate a simple one-step in situ silica NP growth protocol for increasing the surface area available for functionalization on cotton and polyester fabrics as well as on nanoporous cellulose substrates. Comparing this effect with the widely adopted and low cost plant-based polyphenol coating to enhance antibody immobilization, we find that both approaches can similarly increase overall surface activity, and we illustrate conditions under which the two approaches can produce an additive effect. Furthermore, we introduce co-immobilization of antibodies with a sacrificial “steric helper” protein for further enhancing surface activities. In combination, several hundred percent higher activities compared to physical adsorption can be achieved while maintaining a low amount of antibodies used, thus paving a practical path towards low cost biosensing