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Geronimo and his friends go back in time to find the original Rosetta Stone, which the Pirate Cats have stolen and replaced with their own version.

Brain-imaging research has predominantly generated insight by means of classical statistics, including regression-type analyses and null-hypothesis testing using -test and ANOVA. Throughout recent years, statistical learning methods enjoy increasing popularity especially for applications in rich and complex data, including cross-validated out-of-sample prediction using pattern classification and sparsity-inducing regression. This concept paper discusses the implications of inferential justifications and algorithmic methodologies in common data analysis scenarios in neuroimaging. It is retraced how classical statistics and statistical learning originated from different historical contexts, build on different theoretical foundations, make different assumptions, and evaluate different outcome metrics to permit differently nuanced conclusions. The present considerations should help reduce current confusion between model-driven classical hypothesis testing and data-driven learning algorithms for investigating the brain with imaging techniques.

This mixed-methods study examined the effectiveness of Rosetta Stone, a mobile-based language learning application, on Chinese EFL students’ listening, speaking, foreign language enjoyment (FLE), and foreign language anxiety (FLA). Two groups of intermediate Chinese EFL students from a language institute, with 33 students in the control group and 36 in the experimental group, were recruited as the participants. The treatment lasted for 3 months, with the experimental group using Rosetta Stone in addition to in-class instruction whereas the control group received only the regular in-class instruction. Data collection involved administering IELTS module tests of speaking and listening, FLE and FLA scales, as well as semi-structured interviews. ANCOVA, paired samples test, and content analysis were used for the data analysis of the quantitative and qualitative data. The results indicate that the experimental group showed significant improvements in their listening, speaking, FLE, and reduced FLA more than the control group. The results of the qualitative data indicated that the students had positive attitudes toward mobile-based language learning. The qualitative findings provided further support to the quantitative results and highlighted the convenience, flexibility, and engaging nature of the application. The outcomes stressed the potential benefits of using mobile-based language learning tools like Rosetta Stone as an effective supplementary method for improving EFL learning outcomes and promoting positive affective variables. Plain language summary This study looked at how a mobile language learning app called Rosetta Stone affected Chinese students’ listening, speaking, enjoyment of learning a foreign language, and anxiety about learning a foreign language. The researchers had two groups of intermediate Chinese students: one group used Rosetta Stone along with regular classroom instruction, and the other group only had regular classroom instruction. The study lasted for 3 months. The researchers tested the students’ listening and speaking skills, as well as their levels of enjoyment and anxiety in learning a foreign language. They also conducted interviews with the students. The results showed that the group using Rosetta Stone had significant improvements in listening, speaking, enjoyment, and reduced anxiety compared to the group that only had classroom instruction. The interviews supported these findings and showed that the students liked using the mobile app because it was convenient, flexible, and engaging. Overall, this study suggests that using mobile language learning apps like Rosetta Stone can be a helpful addition to regular classroom instruction, improving language learning outcomes and students’ positive attitudes. However, it’s important to note that this study had some limitations, such as the small sample size and focus on a specific language app, so further research is needed to confirm these findings in different contexts and with larger groups of students.

In previous studies, we have identified the tumor suppressor proteins Fhit (fragile histidine triad) and Nit1 (Nitrilase1) as interaction partners of β-catenin both acting as repressors of the canonical Wnt pathway. Interestingly, in D. melanogaster and C. elegans these proteins are expressed as NitFhit fusion proteins. According to the Rosetta Stone hypothesis, if proteins are expressed as fusion proteins in one organism and as single proteins in others, the latter should interact physically and show common signaling function. Here, we tested this hypothesis and provide the first biochemical evidence for a direct association between Nit1 and Fhit. In addition, size exclusion chromatography of purified recombinant human Nit1 showed a tetrameric structure as also previously observed for the NitFhit Rosetta Stone fusion protein Nft-1 in C. elegans. Finally, in line with the Rosetta Stone hypothesis we identified Hsp60 and Ubc9 as other common interaction partners of Nit1 and Fhit. The interaction of Nit1 and Fhit may affect their enzymatic activities as well as interaction with other binding partners.

MonocotJRLs are Poaceae-specific two-domain proteins that consist of a jacalin-related lectin (JRL) and a dirigent (DIR) domain which participate in multiple developmental processes, including disease resistance. For OsJAC1, a monocotJRL from rice, it has been confirmed that constitutive expression in transgenic rice or barley plants facilitates broad-spectrum disease resistance. In this process, both domains of OsJAC1 act cooperatively, as evidenced from experiments with artificially separated JRL- or DIR-domain-containing proteins. Interestingly, these chimeric proteins did not evolve in dicotyledonous plants. Instead, proteins with a single JRL domain, multiple JRL domains or JRL domains fused to domains other than DIR domains are present. In this study, we wanted to test if the cooperative function of JRL and DIR proteins leading to pathogen resistance was conserved in the dicotyledonous plant Arabidopsis thaliana. In Arabidopsis, we identified 50 JRL and 24 DIR proteins, respectively, from which seven single-domain JRL and two single-domain DIR candidates were selected. A single-cell transient gene expression assay in barley revealed that specific combinations of the Arabidopsis JRL and DIR candidates reduced the penetration success of barley powdery mildew. Strikingly, one of these pairs, AtJAX1 and AtDIR19, is encoded by genes located next to each other on chromosome one. However, when using natural variation and analyzing Arabidopsis ecotypes that express full-length or truncated versions of AtJAX1, the presence/absence of the full-length AtJAX1 protein could not be correlated with resistance to the powdery mildew fungus Golovinomyces orontii. Furthermore, an analysis of the additional JRL and DIR candidates in a bi-fluorescence complementation assay in Nicotiana benthamiana revealed no direct interaction of these JRL/DIR pairs. Since transgenic Arabidopsis plants expressing OsJAC1-GFP also did not show increased resistance to G. orontii, it was concluded that the resistance mediated by the synergistic activities of DIR and JRL proteins is specific for members of the Poaceae, at least regarding the resistance against powdery mildew. Arabidopsis lacks the essential components of the DIR-JRL-dependent resistance pathway.

English learners (ELs) in K–12 schools must acquire English while simultaneously mastering content knowledge. Educational technology may support students’ learning through the affordance of individualized language practice. The current randomized controlled trial intervention study examined the effects of Rosetta Stone Foundations software on English learning among middle school ELs. The study took place in Grades 6 to 8 of an urban U.S. school district (N = 221). Predictors of interest included time of testing (pretest vs. posttest) and software usage, and covariates included grade level, sex, and attendance. Additionally, socioeconomic status and home language were accounted for due to sample homogeneity. Multilevel models indicated that treatment group students showed larger gains than control group students on oral/aural outcomes. These results indicate that the software intervention enables individualized practice that can produce proficiency-related gains over and above the typical classroom curriculum.

Several recently developed computational approaches in comparative genomics go beyond sequence comparison. By analyzing phylogenetic profiles of protein families, domain fusions, gene adjacency in genomes, and expression patterns, these methods predict many functional interactions between proteins and help deduce specific functions for numerous proteins. Although some of the resultant predictions may not be highly specific, these developments herald a new era in genomics in which the benefits of comparative analysis of the rapidly growing collection of complete genomes will become increasingly obvious.

Background Drug target identification is a fast-growing field of research in many human diseases. Many strategies have been devised in the post-genomic era to identify new drug targets for infectious diseases. Analysis of protein sequences from different organisms often reveals cases of exon/ORF shuffling in a genome. This results in the fusion of proteins/domains, either in the same genome or that of some other organism, and is termed Rosetta stone sequences. They help link disparate proteins together describing local and global relationships among proteomes. The functional role of proteins is determined mainly by domain-domain interactions and leading to the corresponding signaling mechanism. Putative proteins can be identified as drug targets by re-annotating their functional role through domain-based strategies. Results This study has utilized a bioinformatics approach to identify the putative proteins that are ideal drug targets for pneumonia infection by re-annotating the proteins through position-specific iterations. The putative proteome of two pneumonia-causing pathogens was analyzed to identify protein domain abundance and versatility among them. Common domains found in both pathogens were identified, and putative proteins containing these domains were re-annotated. Among many druggable protein targets, the re-annotation of EJJ83173 (which contains the GFO_IDH_MocA domain) showed that its probable function is glucose-fructose oxidoreduction. This protein was found to have sufficient interactor proteins and homolog in both pathogens but no homolog in the host (human), indicating it as an ideal drug target. 3D modeling of the protein showed promising model parameters. The model was utilized for virtual screening which revealed several ligands with inhibitory activity. These ligands included molecules documented in traditional Chinese medicine and currently marketed drugs. Conclusions This novel strategy of drug target identification through domain-based putative protein re-annotation presents a prospect to validate the proposed drug target to confer its utility as a typical protein targeting both pneumonia-causing species studied herewith.

Nitrilase1 was classified as a tumour suppressor in association with the fragile histidine-triad protein Fhit. However, knowledge about nitrilase1 and its tumour suppressor function is still limited. Whereas nitrilase1 and Fhit are discrete proteins in mammals, they are merged in Drosophila melanogaster and Caenorhabditis elegans . According to the Rosetta-Stone hypothesis, proteins encoded as fusion proteins in one organism and as separate proteins in another organism may act in the same signalling pathway. Although a direct interaction of human nitrilase1 and Fhit has not been shown, our previous finding that Fhit interacts with β-catenin and represses its transcriptional activity in the canonical Wnt pathway suggested that human nitrilase1 also modulates Wnt signalling. In fact, human nitrilase1 forms a complex with β-catenin and LEF-1/TCF-4, represses β-catenin-mediated transcription and shows an additive effect together with Fhit. Knockdown of human nitrilase1 enhances Wnt target gene expression. Moreover, our experiments show that β-catenin competes away human nitrilase1 from LEF-1/TCF and thereby contributes to the activation of Wnt-target gene transcription. Inhibitory activity of human nitrilase1 on vertebrate Wnt signalling was confirmed by repression of Wnt-induced double axis formation in Xenopus embryogenesis. In line with this finding, the Drosophila fusion protein Drosophila NitFhit directly binds to Armadillo and represses the Wingless pathway in reporter gene assays. Genetic experiments confirmed the repressive activity of Drosophila NitFhit on Wingless signalling in the Drosophila wing imaginal disc. In addition, colorectal tumour microarray analysis revealed a significantly reduced expression of human nitrilase1 in poorly differentiated tumours. Taken together, repression of the canonical Wnt pathway represents a new mechanism for the human nitrilase1 tumour suppressor function.

The genetic code is implemented by aminoacyl-tRNA synthetases (aaRS). These 20 enzymes are divided into two classes that, despite performing same functions, have nothing common in structure. The mystery of this striking partition of aaRSs might have been concealed in their sterically complementary modes of tRNA recognition that, as we have found recently, protect the tRNAs with complementary anticodons from confusion in translation. This finding implies that, in the beginning, life increased its coding repertoire by the pairs of complementary codons (rather than one-by-one) and used both complementary strands of genes as templates for translation. The class I and class II aaRSs may represent one of the most important examples of such primordial sense-antisense (SAS) coding (Rodin and Ohno, Orig Life Evol Biosph 25:565-589, 1995). In this report, we address the issue of SAS coding in a wider scope. We suggest a variety of advantages that such coding would have had in exploring a wider sequence space before translation became highly specific. In particular, we confirm that in Achlya klebsiana a single gene might have originally coded for an HSP70 chaperonin (class II aaRS homolog) and an NAD-specific GDH-like enzyme (class I aaRS homolog) via its sense and antisense strands. Thus, in contrast to the conclusions in Williams et al. (Mol Biol Evol 26:445-450, 2009), this could indeed be a “Rosetta stone” gene (Carter and Duax, Mol Cell 10:705-708, 2002) (eroded somewhat, though) for the SAS origin of the two aaRS classes.