Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring

The exosome is a complex of 3'-->5' exoribonucleases, which functions in a variety of cellular processes, all requiring the processing or degradation of RNA. Here we present a model for the assembly of the six human RNase PH-like exosome subunits into a hexameric ring structure. In part, this structure is on the basis of the evolutionarily related bacterial degradosome, the core of which consists of three copies of the PNPase protein, each containing two RNase PH domains. In our model three additional exosome subunits, which contain S1 RNA-binding domains, are positioned on the outer surface of this ring. Evidence for this model was obtained by the identification of protein-protein interactions between individual exosome subunits in a mammalian two-hybrid system. In addition, the results of co-immunoprecipitation assays indicate that at least two copies of hRrp4p and hRrp41p are associated with a single exosome, suggesting that at least two of these ring structures are present in this complex. Finally, the identification of a human gene encoding the putative human counterpart of the bacterial PNPase protein is described, which suggests that the exosome is not the eukaryotic equivalent of the bacterial degradosome, although they do share similar functional activities.     

Methylation of arginine residues interferes with citrullination by peptidylarginine deiminases in vitro

Peptidylarginine deiminase (PAD) enzymes catalyze the conversion of arginine residues in proteins to citrulline residues. Citrulline is a non-standard amino acid that is not incorporated in proteins during translation, but can be generated post-translationally by the PAD enzymes. Although the existence of citrulline residues in proteins has been known for a long time, only a few proteins have been reported to contain this amino acid under normal conditions. These include the nuclear histones, which also contain a wide variety of other post-translational modifications, as for instance methylation of arginine residues. It has been suggested that citrullination and methylation of arginine residues are competing processes and that PAD enzymes might "reverse" the methylation of arginine residues by converting monomethylated arginine into citrulline. However, conflicting data have been reported on the capacity of PADs to citrullinate monomethylated peptidylarginine. Using synthetic peptides that contain either arginine or methylated arginine residues, we show that the human PAD2, PAD3 and PAD4 enzymes and PAD enzyme present in several mouse tissues in vitro can only convert non-methylated peptidylarginine into peptidylcitrulline and that hPAD6 does not show any deiminating activity at all. A comparison of bovine histones either treated or untreated with PAD by amino acid analysis also supported the interference of deimination by arginine methylation. Taken together, these data indicate that it is unlikely that methyl groups at the guanidino position of peptidylarginine can be removed by peptidylarginine deiminases, which has important implications for the recently reported role of these enzymes in gene regulation.     

Contribution-based prioritization of LCI database improvements: the most important unit processes in ecoinvent

The International Journal of Life Cycle Assessment - Improving the quality and quantity of unit process datasets in Life Cycle Inventory (LCI) databases affects every LCA they are used in. However,...     

Improving Executive Functioning in Children with ADHD: Training Multiple Executive Functions within the Context of a Computer Game. A Randomized Double-Blind Placebo Controlled Trial

Introduction

Executive functions (EFs) training interventions aimed at ADHD-symptom reduction have yielded mixed results. Generally, these interventions focus on training a single cognitive domain (e.g., working memory [WM], inhibition, or cognitive-flexibility). However, evidence suggests that most children with ADHD show deficits on multiple EFs, and that these EFs are largely related to different brain regions. Therefore, training multiple EFs might be a potentially more effective strategy to reduce EF-related ADHD symptoms.

Methods

Eighty-nine children with a clinical diagnosis of ADHD (aged 8–12) were randomized to either a full-active-condition where visuospatial WM, inhibition and cognitive-flexibility were trained, a partially-active-condition where inhibition and cognitive-flexibility were trained and the WM-training task was presented in placebo-mode, or to a full placebo-condition. Short-term and long-term (3-months) effects of this gamified, 25-session, home-based computer-training were evaluated on multiple outcome domains.

Results

During training compliance was high (only 3% failed to meet compliance criteria). After training, only children in the full-active condition showed improvement on measures of visuospatial short-term-memory (STM) and WM. Inhibitory performance and interference control only improved in the full-active- and the partially-active condition. No Treatment-condition x Time interactions were found for cognitive-flexibility, verbal WM, complex-reasoning, nor for any parent-, teacher-, or child-rated ADHD behaviors, EF-behaviors, motivational behaviors, or general problem behaviors. Nonetheless, almost all measures showed main Time-effects, including the teacher-ratings.

Conclusions

Improvements on inhibition and visuospatial STM and WM were specifically related to the type of treatment received. However, transfer to untrained EFs and behaviors was mostly nonspecific (i.e., only interference control improved exclusively in the two EF training conditions). As such, in this multiple EF-training, mainly nonspecific treatment factors – as opposed to the specific effects of training EFs—seem related to far transfer effects found on EF and behavior.

Trial Registration

trialregister.nl NTR2728. Registry name: improving executive functioning in children with ADHD: training executive functions within the context of a computer game; registry number: NTR2728.     

Toward a solution of allocation in life cycle inventories: the use of least-squares techniques

Purpose  

The matrix method for the solution of the so-called inventory problem in LCA generally determines the inventory vector related to a specific system of processes by solving a system of linear equations. The paper proposes a new approach to deal with systems characterized by a rectangular (and thus non-invertible) coefficients matrix. The approach, based on the application of regression techniques, allows solving the system without using computational expedients such as the allocation procedure.     

Towards a general framework for including noise impacts in LCA

Purpose  

Several damages have been associated with the exposure of human beings to noise. These include auditory effects, i.e., hearing impairment, but also non-auditory physiological ones such as hypertension and ischemic heart disease, or psychological ones such as annoyance, depression, sleep disturbance, limited performance of cognitive tasks or inadequate cognitive development. Noise can also interfere with intended activities, both in daytime and nighttime. ISO 14'040 also indicated the necessity of introducing noise, together with other less developed impact categories, in a complete LCA study, possibly changing the results of many LCA studies already available. The attempts available in the literature focused on the integration of transportation noise in LCA. Although being considered the most frequent source of intrusive impact, transportation noise is not the only type of noise that can have a malign impact on public health. Several other sources of noise such as industrial or occupational need to be taken into account to have a complete consideration of noise into LCA. Major life cycle inventories (LCI) typically do not contain data on noise emissions yet and characterisation factors are not yet clearly defined. The aim of the present paper is to briefly review what is already available in the field and propose a new framework for the consideration of human health impacts of any type of noise that could be of interest in the LCA practice, providing indications for the introduction of noise in LCI and analysing what data is already available and, in the form of a research agenda, what other resources would be needed to reach a complete coverage of the problem.     

Attempted Training of Alcohol Approach and Drinking Identity Associations in US Undergraduate Drinkers: Null Results from Two Studies

There is preliminary evidence that approach avoid training can shift implicit alcohol associations and improve treatment outcomes. We sought to replicate and extend those findings in US undergraduate social drinkers (Study 1) and at-risk drinkers (Study 2). Three adaptations of the approach avoid task (AAT) were tested. The first adaptation – the approach avoid training – was a replication and targeted implicit alcohol approach associations. The remaining two adaptations – the general identity and personalized identity trainings – targeted implicit drinking identity associations, which are robust predictors of hazardous drinking in US undergraduates. Study 1 included 300 undergraduate social drinkers. They were randomly assigned to real or sham training conditions for one of the three training adaptations, and completed two training sessions, spaced one week apart. Study 2 included 288 undergraduates at risk for alcohol use disorders. The same training procedures were used, but the two training sessions occurred within a single week. Results were not as expected. Across both studies, the approach avoid training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. The general identity training also yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes with one exception; individuals who completed real training demonstrated no changes in drinking refusal self-efficacy whereas individuals who completed sham training had reductions in self-efficacy. Finally, across both studies, the personalized identity training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. Despite having relatively large samples and using a well-validated training task, study results indicated all three training adaptations were ineffective at this dose in US undergraduates. These findings are important because training studies are costly and labor-intensive. Future research may benefit from focusing on more severe populations, pairing training with other interventions, increasing training dose, and increasing gamification of training tasks.     

Lights and shadows in consequential LCA

Purpose

Consequential LCA (CLCA) is becoming widely used in the scientific community as a modelling technique which describes the consequences of a decision. However, despite the increasing number of case studies published, a proper systematization of the approach has not yet been achieved. This paper investigates the methodological implications of CLCA and the extent to which the applications are in line with the theoretical dictates. Moreover, the predictive and explorative nature of CLCA is discussed, highlighting the role of scenario modelling in further structuring the methodology.

Methods

An extensive literature review was performed, involving around 60 articles published over a period of approximately 18?years, and addressing both methodological issues and applications. The information was elaborated according to two main aspects: what for (questions and modes of LCA) and what (methodological implications of CLCA), with focus on the nature of modelling and on the identification of the affected processes.

Results and discussion

The analysis points out that since the modelling principles of attributional LCA (ALCA) and CLCA are the same, what distinguishes the two modes of LCA is the choice of the processes to be included in the system (i.e. in CLCA, those that are affected by the market dynamics). However, the identification of those processes is often done inconsistently, using different arguments, which leads to different results. We suggest the use of scenario modelling as a way to support CLCA in providing a scientifically sound basis to model specific product-related futures with respect to technology development, market shift, and other variables.

Conclusions

The CLCA is a sophisticated modelling technique that provides a way to assess the environmental consequences of an action/decision by including market mechanisms into the analysis. There is still room for improvements of the method and for further research, especially in relation to the following aspects: clarifying when and which market information is important and necessary; understanding the role of scenario modelling within CLCA; and developing a procedure to support the framing of questions to better link questions to models. Moreover, we suggest that the logic of mechanisms could be the reading guide for overcoming the dispute between ALCA and CLCA. Going further, this logic could also be extended, considering CLCA as an approach??rather than as a modelling principle with defined rules??to deepen LCA, providing the conceptual basis for including more mechanisms than just the market ones.