A Structural Mechanism for Noncanonical GPCR Signal Transduction in the Hedgehog Pathway.

The Hedgehog (Hh) signaling pathway is fundamental to embryogenesis, tissue homeostasis, and cancer. Hh signals are transduced via an unusual mechanism: upon agonist-induced phosphorylation, the noncanonical G protein-coupled receptor SMOOTHENED (SMO) binds the catalytic subunit of protein kinase A (PKA-C) and physically blocks its enzymatic activity. By combining computational structural approaches with biochemical and functional studies, we show that SMO mimics strategies prevalent in canonical GPCR and PKA signaling complexes, despite little sequence or secondary structural homology.

A genome-wide genetic association study reveals SNPs significantly associated with environmental variables and specific leaf area in European beech.

European beech is negatively affected by climate change and a further growth decline is predicted for large parts of its distribution range. Despite the importance of this species, little is known about its genetic adaptation and especially the genetic basis of its physiological traits. Here, we used genotyping by sequencing to identify SNPs in 43 German European beech populations growing under different environmental conditions.

Assessing psychological variables on mobile devices: an introduction to the experience sampling app .

The use of the Experience Sampling Method (ESM), which involves repeated assessments in people's daily lives, has increased in popularity in psychology and associated disciplines in recent years. A rather challenging aspect of ESM is its technical implementation. In this paper, after briefly introducing the history of ESM and the main reasons for its current popularity, we outline the experience sampling app which is currently being developed at the University of Vienna.

Correction: Evaluating the Clinical Feasibility of an Artificial Intelligence-Powered, Web-Based Clinical Decision Support System for the Treatment of Depression in Adults: Longitudinal Feasibility Study.

[This corrects the article DOI: 10.2196/31862.].

Uncovering epigenetic and transcriptional regulation of growth in Douglas-fir: identification of differential methylation regions in mega-sized introns.

Tree growth performance can be partly explained by genetics, while a large proportion of growth variation is thought to be controlled by environmental factors. However, to what extent DNA methylation, a stable epigenetic modification, contributes to phenotypic plasticity in the growth performance of long-lived trees remains unclear. In this study, a comparative analysis of targeted DNA genotyping, DNA methylation and mRNAseq profiling for needles of 44-year-old Douglas-fir trees (Pseudotsuga menziesii (Mirb.

GRK2 Kinases in the Primary Cilium Initiate SMOOTHENED-PKA Signaling in the Hedgehog Cascade.

During Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) communicates with GLI transcription factors by binding the protein kinase A catalytic subunit (PKA-C) and physically blocking its enzymatic activity. Here we show that GPCR kinase 2 (GRK2) orchestrates this process during endogenous Hh pathway activation in the vertebrate primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction.

A new species of from Madagascar (Coleoptera, Curculionidae, Cossoninae, Onycholipini).

Chamorro & Steiner, is described from Madagascar. This new species is the third known species of the genus and the first for Africa. is compared to other psammophilous, anophthalmous onycholipine cossonines.

Reablement - relevant factors for implementation: an exploratory sequential mixed-methods study design.

Background: Reablement is a multi-professional and internationally established home-based health care service for mainly older people with the aim to reduce the need for long-term care and to promote self-determination. However, it is unknown which factors would facilitate the implementation of reablement in health care services. Therefore, the aim of this work was to identify relevant factors for the implementation process and to elucidate their importance based on the perspectives of experts.

Evaluating the Clinical Feasibility of an Artificial Intelligence-Powered, Web-Based Clinical Decision Support System for the Treatment of Depression in Adults: Longitudinal Feasibility Study.

Background: Approximately two-thirds of patients with major depressive disorder do not achieve remission during their first treatment. There has been increasing interest in the use of digital, artificial intelligence-powered clinical decision support systems (CDSSs) to assist physicians in their treatment selection and management, improving the personalization and use of best practices such as measurement-based care. Previous literature shows that for digital mental health tools to be successful, the tool must be easy for patients and physicians to use and feasible within existing clinical workflows.

Temporal patterns of roe deer traffic accidents: Effects of season, daytime and lunar phase.

Wildlife-related accidents, especially deer-vehicle accidents, pose a serious problem for road safety and animal protection in many countries. Knowledge of spatial and temporal patterns of deer-vehicle accidents is inevitable for accident analysis and mitigation efforts with temporal deer-vehicle accident data being much more difficult to obtain in sufficient data quality. We described the temporal patterns of roe deer (Capreolus capreolus) roadkills occurring in the period 2002-2006 in southeastern Austria.

Diverse DNA Sequence Motifs Activate Meiotic Recombination Hotspots Through a Common Chromatin Remodeling Pathway.

In meiosis, multiple different DNA sequence motifs help to position homologous recombination at hotspots in the genome. How do the seemingly disparate -acting regulatory modules each promote locally the activity of the basal recombination machinery? We defined molecular mechanisms of action for five different hotspot-activating DNA motifs (, , , , ) located independently at the same site within the locus of the fission yeast Each motif promoted meiotic recombination (, is active) within this context, and this activity required the respective binding proteins (transcription factors Atf1, Pcr1, Php2, Php3, Php5, Rst2). High-resolution analyses of chromatin structure by nucleosome scanning assays revealed that each motif triggers the displacement of nucleosomes surrounding the hotspot motif in meiosis.

Transoral laser microsurgery for treatment of oropharyngeal cancer in 368 patients.

Background: Oncological and functional outcome of transoral laser microsurgery (TLM) for primary treatment of oropharyngeal cancer was examined using a multimodal treatment concept.

Methods: A total of 368 patients with oropharyngeal squamous cell carcinoma (pT1-4, pN0-2, M0) underwent TLM +/- neck dissection (85%), +/- (chemo)radiotherapy (57%). The majority of patients had advanced stage III and IVa disease (79%).

A frequency domain approach for parameter identification in multibody dynamics.

The adjoint method shows an efficient way to incorporate inverse dynamics to engineering multibody applications, as, e.g., parameter identification.

The discrete adjoint method for parameter identification in multibody system dynamics.

The is an elegant approach for the computation of the gradient of a cost function to identify a set of parameters. An additional set of differential equations has to be solved to compute the adjoint variables, which are further used for the gradient computation. However, the accuracy of the numerical solution of the adjoint differential equation has a great impact on the gradient.

Catalogue of Tenebrionidae (Coleoptera) of North America.

This catalogue includes all valid family-group (8 subfamilies, 52 tribes, 14 subtribes), genus-group (349 genera, 86 subgenera), and species-group names (2825 species, 215 subspecies) of darkling beetles (Coleoptera: Tenebrionidae) known to occur in North America and their available synonyms. Data on extant, subfossil and fossil taxa are given. For each name the author and year and page number of the description are provided, with additional information (e.

Sequence requirement of the ade6-4095 meiotic recombination hotspot in Schizosaccharomyces pombe.

Homologous recombination occurs at a greatly elevated frequency in meiosis compared to mitosis and is initiated by programmed double-strand DNA breaks (DSBs). DSBs do not occur at uniform frequency throughout the genome in most organisms, but occur preferentially at a limited number of sites referred to as hotspots. The location of hotspots have been determined at nucleotide-level resolution in both the budding and fission yeasts, and while several patterns have emerged regarding preferred locations for DSB hotspots, it remains unclear why particular sites experience DSBs at much higher frequency than other sites with seemingly similar properties.

Transoral laser microsurgery for treatment for hypopharyngeal cancer in 211 patients.

Background: The oncologic and functional outcome of transoral laser microsurgery (TLM) for primary treatment of hypopharyngeal cancer was examined in a multimodal treatment concept.

Methods: Two hundred eleven patients with squamous cell carcinoma (SCC) of the hypopharynx (pT1-4a, pN0-2, M0) were treated by TLM +/- neck dissection (88%) +/- (chemo)radiotherapy ([C]RT; 51%). The majority of cases were advanced stages III and IVa (85%).

Optimal input design for multibody systems by using an extended adjoint approach.

We present a method for optimizing inputs of multibody systems for a subsequently performed parameter identification. Herein, optimality with respect to identifiability is attained by maximizing the information content in measurements described by the Fisher information matrix. For solving the resulting optimization problem, the adjoint system of the sensitivity differential equation system is employed.

Primary cutaneous Mycobacterium avium complex infection following squamous cell carcinoma excision.

Primary cutaneous complex (MAC) infection is rare, particularly among immunocompetent patients. We present the case of a purportedly healthy patient with primary cutaneous MAC infection arising within the excision margins of multiple infiltrating squamous cell carcinomas.

Transoral laser microsurgery for T1b glottic cancer: review of 51 cases.

For the treatment of T1b glottic carcinoma, different treatment options, such as transoral laser microsurgery, open surgical techniques, and primary radiotherapy, are under discussion. In this context, the aim of the present study was to describe oncologic results and complication rates of transoral laser microsurgery in treatment of T1b glottic carcinoma. This is a retrospective unicenter chart review of patients treated at an academic tertiary referral center between 1986 and 2006.

Adaptive and plastic responses of Quercus petraea populations to climate across Europe.

How temperate forests will respond to climate change is uncertain; projections range from severe decline to increased growth. We conducted field tests of sessile oak (Quercus petraea), a widespread keystone European forest tree species, including more than 150 000 trees sourced from 116 geographically diverse populations. The tests were planted on 23 field sites in six European countries, in order to expose them to a wide range of climates, including sites reflecting future warmer and drier climates.

Unique properties of multiple tandem copies of the M26 recombination hotspot in mitosis and meiosis in Schizosaccharomyces pombe.

The M26 hotspot of the fission yeast Schizosaccharomyces pombe is one of the best-characterized eukaryotic hotspots of recombination. The hotspot requires a seven bp sequence, ATGACGT, that serves as a binding site for the Atf1-Pcr1 transcription factor, which is also required for activity. The M26 hotspot is active in meiosis but not mitosis and is active in some but not all chromosomal contexts and not on a plasmid.

On the rotational equations of motion in rigid body dynamics when using Euler parameters.

Many models of three-dimensional rigid body dynamics employ Euler parameters as rotational coordinates. Since the four Euler parameters are not independent, one has to consider the quaternion constraint in the equations of motion. This is usually done by the Lagrange multiplier technique.