The HP1 Homolog Rhino Anchors a Nuclear Complex that Suppresses piRNA Precursor Splicing

SummarypiRNAs guide an adaptive genome defense system that silences transposons during germline development. The Drosophila HP1 homolog Rhino is required for germline piRNA production. We show that Rhino binds specifically to the heterochromatic clusters that produce piRNA precursors, and that binding directly correlates with piRNA production. Rhino colocalizes to germline nuclear foci with Rai1/DXO-related protein Cuff and the DEAD box protein UAP56, which are also required for germline piRNA production. RNA sequencing indicates that most cluster transcripts are not spliced and that rhino, cuff, and uap56 mutations increase expression of spliced cluster transcripts over 100-fold. LacI::Rhino fusion protein binding suppresses splicing of a reporter transgene and is sufficient to trigger piRNA production from a trans combination of sense and antisense reporters. We therefore propose that Rhino anchors a nuclear complex that suppresses cluster transcript splicing and speculate that stalled splicing differentiates piRNA precursors from mRNAs

Importance of electronic self-consistency in the TDDFT based treatment of nonadiabatic molecular dynamics

A mixed quantum-classical approach to simulate the coupled dynamics of electrons and nuclei in nanoscale molecular systems is presented. The method relies on a second order expansion of the Lagrangian in time-dependent density functional theory (TDDFT) around a suitable reference density. We show that the inclusion of the second order term renders the method a self-consistent scheme and improves the calculated optical spectra of molecules by a proper treatment of the coupled response. In the application to ion-fullerene collisions, the inclusion of self-consistency is found to be crucial for a correct description of the charge transfer between projectile and target. For a model of the photoreceptor in retinal proteins, nonadiabatic molecular dynamics simulations are performed and reveal problems of TDDFT in the prediction of intra-molecular charge transfer excitations.Comment: 9 pages, 8 figures. Minor changes in content wrt older versio

Tilt aftereffect following adaptation to translational Glass patterns

Glass patterns (GPs) consist of randomly distributed dot pairs (dipoles) whose orientations are determined by specific geometric transforms. We assessed whether adaptation to stationary oriented translational GPs suppresses the activity of orientation selective detectors producing a tilt aftereffect (TAE). The results showed that adaptation to GPs produces a TAE similar to that reported in previous studies, though reduced in amplitude. This suggests the involvement of orientation selective mechanisms. We also measured the interocular transfer (IOT) of the GP-induced TAE and found an almost complete IOT, indicating the involvement of orientation selective and binocularly driven units. In additional experiments, we assessed the role of attention in TAE from GPs. The results showed that distraction during adaptation similarly modulates the TAE after adapting to both GPs and gratings. Moreover, in the case of GPs, distraction is likely to interfere with the adaptation process rather than with the spatial summation of local dipoles. We conclude that TAE from GPs possibly relies on visual processing levels in which the global orientation of GPs has been encoded by neurons that are mostly binocularly driven, orientation selective and whose adaptation-related neural activity is strongly modulated by attention

Scoring docking conformations using predicted protein interfaces

BACKGROUND: Since proteins function by interacting with other molecules, analysis of protein-protein interactions is essential for comprehending biological processes. Whereas understanding of atomic interactions within a complex is especially useful for drug design, limitations of experimental techniques have restricted their practical use. Despite progress in docking predictions, there is still room for improvement. In this study, we contribute to this topic by proposing T-PioDock, a framework for detection of a native-like docked complex 3D structure. T-PioDock supports the identification of near-native conformations from 3D models that docking software produced by scoring those models using binding interfaces predicted by the interface predictor, Template based Protein Interface Prediction (T-PIP). RESULTS: First, exhaustive evaluation of interface predictors demonstrates that T-PIP, whose predictions are customised to target complexity, is a state-of-the-art method. Second, comparative study between T-PioDock and other state-of-the-art scoring methods establishes T-PioDock as the best performing approach. Moreover, there is good correlation between T-PioDock performance and quality of docking models, which suggests that progress in docking will lead to even better results at recognising near-native conformations. CONCLUSION: Accurate identification of near-native conformations remains a challenging task. Although availability of 3D complexes will benefit from template-based methods such as T-PioDock, we have identified specific limitations which need to be addressed. First, docking software are still not able to produce native like models for every target. Second, current interface predictors do not explicitly consider pairwise residue interactions between proteins and their interacting partners which leaves ambiguity when assessing quality of complex conformations

Characterization of the thermal and photoinduced reactions of photochromic spiropyrans in aqueous solution

Six water-soluble spiropyran derivatives have been characterized with respect to the thermal and photoinduced reactions over a broad pH-interval. A comprehensive kinetic model was formulated including the spiro- and the merocyanine isomers, the respective protonated forms, and the hydrolysis products. The experimental studies on the hydrolysis reaction mechanism were supplemented by calculations using quantum mechanical (QM) models employing density functional theory. The results show that (1) the substitution pattern dramatically influences the pKa-values of the protonated forms as well as the rates of the thermal isomerization reactions, (2) water is the nucleophile in the hydrolysis reaction around neutral pH, (3) the phenolate oxygen of the merocyanine form plays a key role in the hydrolysis reaction. Hence, the nonprotonated merocyanine isomer is susceptible to hydrolysis, whereas the corresponding protonated form is stable toward hydrolytic degradation

Reconciling disparate prevalence rates of PTSD in large samples of US male Vietnam veterans and their controls

BACKGROUND: Two large independent studies funded by the US government have assessed the impact of the Vietnam War on the prevalence of PTSD in US veterans. The National Vietnam Veterans Readjustment Study (NVVRS) estimated the current PTSD prevalence to be 15.2% while the Vietnam Experience Study (VES) estimated the prevalence to be 2.2%. We compared alternative criteria for estimating the prevalence of PTSD using the NVVRS and VES public use data sets collected more than 10 years after the United States withdrew troops from Vietnam. METHODS: We applied uniform diagnostic procedures to the male veterans from the NVVRS and VES to estimate PTSD prevalences based on varying criteria including one-month and lifetime prevalence estimates, combat and non-combat prevalence estimates, and prevalence estimates using both single and multiple indicator models. RESULTS: Using a narrow and specific set of criteria, we derived current prevalence estimates for combat-related PTSD of 2.5% and 2.9% for the VES and the NVVRS, respectively. Using a more broad and sensitive set of criteria, we derived current prevalence estimates for combat-related PTSD of 12.2% and 15.8% for the VES and NVVRS, respectively. CONCLUSION: When comparable methods were applied to available data we reconciled disparate results and estimated similar current prevalences for both narrow and broad definitions of combat-related diagnoses of PTSD