A Posttermination Ribosomal Complex Is the Guanine Nucleotide Exchange Factor for Peptide Release Factor RF3

AbstractThe mechanism by which peptide release factor RF3 recycles RF1 and RF2 has been clarified and incorporated in a complete scheme for translation termination. Free RF3 is in vivo stably bound to GDP, and ribosomes in complex with RF1 or RF2 act as guanine nucleotide exchange factors (GEF). Hydrolysis of peptidyl-tRNA by RF1 or RF2 allows GTP binding to RF3 on the ribosome. This induces an RF3 conformation with high affinity for ribosomes and leads to rapid dissociation of RF1 or RF2. Dissociation of RF3 from the ribosome requires GTP hydrolysis. Our data suggest that RF3 and its eukaryotic counterpart, eRF3, have mechanistic principles in common

Relationships between riverine and terrestrial dissolved organic carbon: Concentration, radiocarbon signature, specific UV absorbance

The transfer of dissolved organic carbon (DOC) from land to watercourses plays a major role in the carbon cycle, and in the transport and fate of associated organic and inorganic contaminants. We investigated, at global scale, how the concentrations and properties of riverine DOC depend upon combinations of terrestrial source solutions. For topsoil, subsoil, groundwater and river solutions in different Köppen-Geiger climatic zones, we compiled published and new values of DOC concentration ([DOC]), radiocarbon signature (DO14C), and specific UV absorbance (SUVA). The average value of each DOC variable decreased significantly in magnitude from topsoil to subsoil to groundwater, permitting the terrestrial sources to be distinguished. We used the terrestrial data to simulate the riverine distributions of each variable, and also relationships between pairs of variables. To achieve good matches between observed and simulated data, it was necessary to optimise the distributions of water fractions contributed by each of the three terrestrial sources, and also to reduce the mean input terrestrial [DOC] values, to about 60% of the measured ones. One possible explanation for the required lowering of the modelled terrestrial [DOC] values might be unrepresentative sampling of terrestrial DOC, including dilution effects; another is the loss of DOC during riverine transport. High variations in simulated riverine DOC variables, which match observed data, are due predominantly to variations in source solution values, with a lesser contribution from the different combinations of source waters. On average, most DOC in rivers draining catchments with forest and/or grass-shrub land cover comes in similar amounts from topsoil and subsoil, with about 10% from groundwater. In rivers draining croplands, subsoil and groundwater solutions are the likely dominant DOC sources, while in wetland rivers most DOC is from topsoil

Program Innovations and Character in Cub Scouts: Findings from Year 1 of a Mixed-Methods, Longitudinal Study

Youth development programs seek to promote positive development through mentoring and engaging youth in opportunities for individual growth and community connectedness. We present findings from the initial phase of a mixed-methods, longitudinal study aimed at assessing the impact of one such program, Cub Scouts, on character development. We assessed if Scouting, and a recent innovation in Scouting focused on program quality, are associated with the development of character and other positive youth outcomes. Participants were 1,083 Scouts and non-Scouts, aged 5-12 years. At the start of the study, there was no difference in indicators of character between Scouts and non-Scouts, once matched through propensity score analyses. Through content analyses of interviews and short- answer questionnaires administered to leaders, we found that leaders’ views of character and of their roles corresponded to those envisioned by Cub Scouts. Implications for character development, and for the role of program components in character development, are discussed

Aesthetics by Numbers: Links between Perceived Texture Qualities and Computed Visual Texture Properties.

Our world is filled with texture. For the human visual system, this is an important source of information for assessing environmental and material properties. Indeed-and presumably for this reason-the human visual system has regions dedicated to processing textures. Despite their abundance and apparent relevance, only recently the relationships between texture features and high-level judgments have captured the interest of mainstream science, despite long-standing indications for such relationships. In this study, we explore such relationships, as these might be used to predict perceived texture qualities. This is relevant, not only from a psychological/neuroscience perspective, but also for more applied fields such as design, architecture, and the visual arts. In two separate experiments, observers judged various qualities of visual textures such as beauty, roughness, naturalness, elegance, and complexity. Based on factor analysis, we find that in both experiments, ~75% of the variability in the judgments could be explained by a two-dimensional space, with axes that are closely aligned to the beauty and roughness judgments. That a two-dimensional judgment space suffices to capture most of the variability in the perceived texture qualities suggests that observers use a relatively limited set of internal scales on which to base various judgments, including aesthetic ones. Finally, for both of these judgments, we determined the relationship with a large number of texture features computed for each of the texture stimuli. We find that the presence of lower spatial frequencies, oblique orientations, higher intensity variation, higher saturation, and redness correlates with higher beauty ratings. Features that captured image intensity and uniformity correlated with roughness ratings. Therefore, a number of computational texture features are predictive of these judgments. This suggests that perceived texture qualities-including the aesthetic appreciation-are sufficiently universal to be predicted-with reasonable accuracy-based on the computed feature content of the textures

Mechanism of activation of methyltransferases involved in translation by the Trm112 ‘hub’ protein

Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases

Neural Correlates of Experience-Induced Deficits in Learned Vocal Communication

Songbirds are one of the few vertebrate groups (including humans) that evolved the ability to learn vocalizations. During song learning, social interactions with adult models are crucial and young songbirds raised without direct contacts with adults typically produce abnormal songs showing phonological and syntactical deficits. This raises the question of what functional representation of their vocalizations such deprived animals develop. Here we show that young starlings that we raised without any direct contact with adults not only failed to differentiate starlings' typical song classes in their vocalizations but also failed to develop differential neural responses to these songs. These deficits appear to be linked to a failure to acquire songs' functions and may provide a model for abnormal development of communicative skills, including speech

Contribution of Distinct Homeodomain DNA Binding Specificities to Drosophila Embryonic Mesodermal Cell-Specific Gene Expression Programs

Homeodomain (HD) proteins are a large family of evolutionarily conserved transcription factors (TFs) having diverse developmental functions, often acting within the same cell types, yet many members of this family paradoxically recognize similar DNA sequences. Thus, with multiple family members having the potential to recognize the same DNA sequences in cis-regulatory elements, it is difficult to ascertain the role of an individual HD or a subclass of HDs in mediating a particular developmental function. To investigate this problem, we focused our studies on the Drosophila embryonic mesoderm where HD TFs are required to establish not only segmental identities (such as the Hox TFs), but also tissue and cell fate specification and differentiation (such as the NK-2 HDs, Six HDs and identity HDs (I-HDs)). Here we utilized the complete spectrum of DNA binding specificities determined by protein binding microarrays (PBMs) for a diverse collection of HDs to modify the nucleotide sequences of numerous mesodermal enhancers to be recognized by either no or a single subclass of HDs, and subsequently assayed the consequences of these changes on enhancer function in transgenic reporter assays. These studies show that individual mesodermal enhancers receive separate transcriptional input from both I–HD and Hox subclasses of HDs. In addition, we demonstrate that enhancers regulating upstream components of the mesodermal regulatory network are targeted by the Six class of HDs. Finally, we establish the necessity of NK-2 HD binding sequences to activate gene expression in multiple mesodermal tissues, supporting a potential role for the NK-2 HD TF Tinman (Tin) as a pioneer factor that cooperates with other factors to regulate cell-specific gene expression programs. Collectively, these results underscore the critical role played by HDs of multiple subclasses in inducing the unique genetic programs of individual mesodermal cells, and in coordinating the gene regulatory networks directing mesoderm development.National Institutes of Health (U.S.) (Grant R01 HG005287

Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

Contains fulltext : 110505.pdf (publisher's version ) (Open Access)BACKGROUND: Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. METHODS: Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. RESULTS: Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217). CONCLUSIONS: In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00761813