Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5

Background The cyclic AMP specific phosphodiesterase, PDE4D5 interacts with the β-propeller protein RACK1 to form a signaling scaffold complex in cells. Two-hybrid analysis of truncation and mutant constructs of the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5 were used to define a domain conferring interaction with the signaling scaffold protein, RACK1. Results Truncation and mutagenesis approaches showed that the RACK1-interacting domain on PDE4D5 comprised a cluster of residues provided by Asn-22/Pro-23/Trp-24/Asn-26 together with a series of hydrophobic amino acids, namely Leu-29, Val-30, Leu-33, Leu-37 and Leu-38 in a 'Leu-Xaa-Xaa-Xaa-Leu' repeat. This was done by 2-hybrid analyses and then confirmed in biochemical pull down analyses using GST-RACK1 and mutant PDE4D5 forms expressed in COS cells. Mutation of Arg-34, to alanine, in PDE4D5 attenuated its interaction with RACK1 both in 2-hybrid screens and in pull down analyses. A 38-mer peptide, whose sequence reflected residues 12 through 49 of PDE4D5, bound to RACK1 with similar affinity to native PDE4D5 itself (Ka circa 6 nM). Conclusions The RACK1 Interaction Domain on PDE4D5, that we here call RAID1, is proposed to form an amphipathic helical structure that we suggest may interact with the C-terminal β-propeller blades of RACK1 in a manner akin to the interaction of the helical G-γ signal transducing protein with the β-propeller protein, G-β

Controlling the uncontrolled: Are there incidental experimenter effects on physiologic responding?

The degree to which experimenters shape participant behavior has long been of interest in experimental social science research. Here, we extend this question to the domain of peripheral psychophysiology, where experimenters often have direct, physical contact with participants, yet researchers do not consistently test for their influence. We describe analytic tools for examining experimenter effects in peripheral physiology. Using these tools, we investigate nine data sets totaling 1,341 participants and 160 experimenters across different roles (e.g., lead research assistants, evaluators, confederates) to demonstrate how researchers can test for experimenter effects in participant autonomic nervous system activity during baseline recordings and reactivity to study tasks. Our results showed (a) little to no significant variance in participants' physiological reactivity due to their experimenters, and (b) little to no evidence that three characteristics of experimenters that are well known to shape interpersonal interactions-status (using five studies with 682 total participants), gender (using two studies with 359 total participants), and race (in two studies with 554 total participants)-influenced participants' physiology. We highlight several reasons that experimenter effects in physiological data are still cause for concern, including the fact that experimenters in these studies were already restricted on a number of characteristics (e.g., age, education). We present recommendations for examining and reducing experimenter effects in physiological data and discuss implications for replication

Mitral Annular and Coronary Artery Calcification Are Associated with Mortality in HIV-Infected Individuals.

BackgroundHIV infection increases cardiovascular risk. Coronary artery calcification (CAC) and mitral annular calcification (MAC) identify patients at risk for cardiovascular disease (CVD). The purpose of this study was to examine the association between MAC, CAC and mortality in HIV-infected individuals.Methods and resultsWe studied 152 asymptomatic HIV-infected individuals with transthoracic echocardiography (TTE) and computed tomography (CT). MAC was identified on TTE using standardized criteria. Presence of CAC, CAC score and CAC percentiles were determined using the modified Agatston criteria. Mortality data was obtained from the Social Security and National Death Indices (SSDI/NDI). The median age was 49 years; 87% were male. The median duration of HIV was 16 years; 84% took antiretroviral therapy; 64% had an undetectable viral load. CVD risk factors included hypertension (35%), smoking (62%) and dyslipidemia (35%). Twenty-five percent of individuals had MAC, and 42% had CAC. Over a median follow-up of 8 years, 11 subjects died. Subjects with CAC had significantly higher mortality compared to those with MAC only or no MAC. The Harrell's C-statistic of CAC was 0.66 and increased to 0.75 when MAC was added (p = 0.05). MAC, prior CVD, age and HIV viral load were independently associated with higher age- and gender-adjusted CAC percentiles in an adjusted model (p < 0.05 for all).ConclusionIn HIV patients, the presence of MAC, traditional risk factors and HIV viral load were independently associated with CAC. Presence of CAC and MAC may be useful in identifying HIV-infected individuals at higher risk for death

A general method for controlled nanopatterning of oxide dots: a microphase separated block copolymer platform

We demonstrate a facile, generic method for the fabrication of highly dense long range hexagonally ordered various inorganic oxide nanodots on different substrates by using a microphase separated polystyrene-b-poly(ethylene oxide) (PS-b-PEO) block copolymer (BCP) thin film as a structural template. The method does not require complex co-ordination chemistry (between metal precursors and the polymer) and instead involves the simple, solution based chemistry applicable to a wide range of systems. A highly ordered PS-b-PEO thin film with perpendicularly oriented PEO cylinders is fabricated by solvent annealing over wafer scale. PEO cylinders are activated by ethanol to create a functional chemical pattern for nanodot development via spin coating and block selective metal ion inclusion. Subsequent UV/ozone treatment forms an ordered arrangement of oxide nanodots and removes the polymer components. The phase purity, crystallinity and thermal stability of these materials coupled to the ease of production may make them useful in technological applications. This method is particularly useful because the feature sizes can be tuned by changing the concentration of the precursors without changing the molecular weight and concentration of the block copolymer

Fluctuations in depression and well-being are associated with sexual risk episodes among HIV-positive men

Peer reviewedPostprin

Selective sidewall wetting of polymer blocks in hydrogen silsesquioxane directed self-assembly of PS-b-PDMS

We show the importance of sidewall chemistry for the graphoepitaxial alignment of PS-b-PDMS using prepatterns fabricated by electron beam lithography of hydrogen silsesquioxane (HSQ) and by deep ultraviolet (DUV) lithography on SiO2 thin films. Density multiplication of polystyrene-block-polydimethylsiloxane (PS-b-PDMS) within both prepatterns was achieved by using a room temperature dynamic solvent annealing environment. Selective tuning of PS and PDMS wetting on the HSQ template sidewalls was also achieved through careful functionalization of the template and substrate surface using either brush or a self-assembled trimethylsilyl monolayer. PDMS selectively wets HSQ sidewalls treated with a brush layer of PDMS, whiereas PS is found to selectively wet HSQ sidewalls treated with hexamethyldisilazane (HMDS) to produce a trimethylsilyl-terminated surface. The etch resistance of the aligned polymer was also evaluated to understand the implications of using block copolymer patterns which have high etch resistance, self-forming (PDMS) wetting layers at both interfaces. The results outlined in this work may have direct applications in nanolithography for continued device scaling toward the end-of-roadmap era

Polychromatic gap solitons and breathers in nonlinear waveguide arrays

We predict the spatial localization of multiple wavelength components in the form of stationary polychromatic gap solitons and dynamic multi-gap breathers, and observe experimentally tunable spatio-spectral trapping of supercontinuum radiation in nonlinear periodic photonic structures

Nonlinear spectral-spatial control and localization of supercontinuum radiation

We present the first observation of spatiospectral control and localization of supercontinuum light through the nonlinear interaction of spectral components in extended periodic structures. We use an array of optical waveguides in a LiNbO3 crystal and employ the interplay between diffraction and nonlinearity to dynamically control the output spectrum of the supercontinuum radiation. This effect presents an efficient scheme for optically tunable spectral filtering of supercontinua

Mental Health of Parents and Life Satisfaction of Children: A Within-Family Analysis of Intergenerational Transmission of Well-Being

This paper addresses the extent to which there is an intergenerational transmission of mental health and subjective well-being within families. Specifically it asks whether parents’ own mental distress influences their child’s life satisfaction, and vice versa. Whilst the evidence on daily contagion of stress and strain between members of the same family is substantial, the evidence on the transmission between parental distress and children’s well-being over a longer period of time is sparse. We tested this idea by examining the within-family transmission of mental distress from parent to child’s life satisfaction, and vice versa, using rich longitudinal data on 1,175 British youths. Results show that parental distress at year t-1 is an important determinant of child’s life satisfaction in the current year. This is true for boys and girls, although boys do not appear to be affected by maternal distress levels. The results also indicated that the child’s own life satisfaction is related with their father’s distress levels in the following year, regardless of the gender of the child. Finally, we examined whether the underlying transmission correlation is due to shared social environment, empathic reactions, or transmission via parent-child interaction