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Peer-reviewed

Context-dependent dual role of SKI8 homologs in mRNA synthesis and turnover.

Eukaryotic mRNA transcription and turnover is controlled by an enzymatic machinery that includes RNA polymerase II and the 3' to 5' exosome. The activity of these protein complexes is modulated by additional factors, such as the nuclear RNA polymerase II-associated factor 1 (Paf1c) and the cytoplasmic Superkiller (SKI) complex, respectively. Their components are conserved across uni- as well as multi-cellular organisms, including yeast, Arabidopsis, and humans. Among them, SKI8 displays multiple facets on top of its cytoplasmic role in the SKI complex. For instance, nuclear yeast ScSKI8 has an additional function in meiotic recombination, whereas nuclear human hSKI8 (unlike ScSKI8) associates with Paf1c. The Arabidopsis SKI8 homolog VERNALIZATION INDEPENDENT 3 (VIP3) has been found in Paf1c as well; however, whether it also has a role in the SKI complex remains obscure so far. We found that transgenic VIP3-GFP, which complements a novel vip3 mutant allele, localizes to both nucleus and cytoplasm. Consistently, biochemical analyses suggest that VIP3-GFP associates with the SKI complex. A role of VIP3 in the turnover of nuclear encoded mRNAs is supported by random-primed RNA sequencing of wild-type and vip3 seedlings, which indicates mRNA stabilization in vip3. Another SKI subunit homolog mutant, ski2, displays a dwarf phenotype similar to vip3. However, unlike vip3, it displays neither early flowering nor flower development phenotypes, suggesting that the latter reflect VIP3's role in Paf1c. Surprisingly then, transgenic ScSKI8 rescued all aspects of the vip3 phenotype, suggesting that the dual role of SKI8 depends on species-specific cellular context.

In conspectu prope totius urbis: an application of different visual methods at the ager Tarraconensis landscape

We present in this paper the results of the application of several visual methods on a group of locations, dated between VI and I centuries BC, of the ager Tarraconensis (Tarragona, Spain) a Hinterland of the roman colony of Tarraco. The difficulty in interpreting the diverse results in a combined way has been resolved by means of the use of statistical methods, such as Principal Components Analysis (PCA) and K-means clustering analysis. These methods have allowed us to carry out site classifications in function of the landscape's visual structure that contains them and of the visual relationships that could be given among them.

Position Document of the Secretariat on System-Wide Coherence in the context of UN Reform Processes

The present document should be seen as one more contribution to the debate to the reform processes and a small guide to these processes and their latest outcomes.

Coarse Global Visual Localization of a Mobile Robot

Localization, which is the ability of a mobile robot to estimate its position within its environment, is a key capability for autonomous operation of any mobile robot. This thesis presents a system for indoor coarse and global localization of a mobile robot based on visual information. The system is based on image matching and uses SIFT features as natural landmarks. Features extracted from training images arestored in a database for use in localization later. During localization an image of the scene is captured using the on-board camera of the robot, features are extracted from the image and the best match is searched from the database. Feature matching is done using the k-d tree algorithm. Experimental results showed that localization accuracy increases with the number of training features used in the training database, while, on the other hand, increasing number of features tended to have a negative impact on the computational time. For some parts of the environment the error rate was relatively high due to a strong correlation of features taken from those places across the environment.

Assigning and combining probabilities in single-case studies

There is currently a considerable diversity of quantitative measures available for summarizing the results in single-case studies. Given that the interpretation of some of them is difficult due to the lack of established benchmarks, the current paper proposes an approach for obtaining further numerical evidence on the importance of the results, complementing the substantive criteria, visual analysis, and primary summary measures. This additional evidence consists of obtaining the statistical significance of the outcome when referred to the corresponding sampling distribution. This sampling distribution is formed by the values of the outcomes (expressed as data nonoverlap, R-squared, etc.) in case the intervention is ineffective. The approach proposed here is intended to offer the outcome"s probability of being as extreme when there is no treatment effect without the need for some assumptions that cannot be checked with guarantees. Following this approach, researchers would compare their outcomes to reference values rather than constructing the sampling distributions themselves. The integration of single-case studies is problematic, when different metrics are used across primary studies and not all raw data are available. Via the approach for assigning p values it is possible to combine the results of similar studies regardless of the primary effect size indicator. The alternatives for combining probabilities are discussed in the context of single-case studies pointing out two potentially useful methods one based on a weighted average and the other on the binomial test.

Correlations between vocal input and visual response apparently enhance presence in a virtual environment

This work investigates novel alternative means of interaction in a virtual environment (VE).We analyze whether humans can remap established body functions to learn to interact with digital information in an environment that is cross-sensory by nature and uses vocal utterances in order to influence (abstract) virtual objects. We thus establish a correlation among learning, control of the interface, and the perceived sense of presence in the VE. The application enables intuitive interaction by mapping actions (the prosodic aspects of the human voice) to a certain response (i.e., visualization). A series of single-user and multiuser studies shows that users can gain control of the intuitive interface and learn to adapt to new and previously unseen tasks in VEs. Despite the abstract nature of the presented environment, presence scores were generally very high.

The effect of virtual reality on visual vertigo symptoms in patients with peripheral vestibular dysfunction: a pilot study

Individuals with vestibular dysfunction may experience visual vertigo (VV), in which symptoms are provoked or exacerbated by excessive or disorientating visual stimuli (e.g. supermarkets). VV can significantly improve when customized vestibular rehabilitation exercises are combined with exposure to optokinetic stimuli. Virtual reality (VR), which immerses patients in realistic, visually challenging environments, has also been suggested as an adjunct to VR to improve VV symptoms. This pilot study compared the responses of sixteen patients with unilateral peripheral vestibular disorder randomly allocated to a VR regime incorporating exposure to a static (Group S) or dynamic (Group D) VR environment. Participants practiced vestibular exercises, twice weekly for four weeks, inside a static (Group S) or dynamic (Group D) virtual crowded square environment, presented in an immersive projection theatre (IPT), and received a vestibular exercise program to practice on days not attending clinic. A third Group D1 completed both the static and dynamic VR training. Treatment response was assessed with the Dynamic Gait Index and questionnaires concerning symptom triggers and psychological state. At final assessment, significant betweengroup differences were noted between Groups D (p = 0.001) and D1 (p = 0.03) compared to Group S for VV symptoms with the former two showing a significant 59.2% and 25.8% improvement respectively compared to 1.6% for the latter. Depression scores improved only for Group S (p = 0.01) while a trend towards significance was noted for Group D regarding anxiety scores (p = 0.07). Conclusion: Exposure to dynamic VR environments should be considered as a useful adjunct to vestibular rehabilitation programs for patients with peripheral vestibular disorders and VV symptoms.

Exploration of the visual system: Part 1: Dissection of the mouse eye for RNA, protein, and histological analyses

Due to the power of genetics, the mouse has become a widely used animal model in vision research. However, its eyeball has an axial length of only about 2 mm. The present protocol describes how to easily dissect the small rodent eye post mortem. This allows collecting different tissues of the eye, i.e., cornea, lens, iris, retina, optic nerve, retinal pigment epithelium (RPE), and sclera. We further describe in detail how to process these eye samples in order to obtain high‐quality RNA for RNA expression profiling studies. Depending on the eye tissue to be analyzed, we present appropriate lysis buffers to prepare total protein lysates for immunoblot and immuno‐precipitation analyses. Fixation, inclusion, embedding, and cryosectioning of the globe for routine histological analyses (HE staining, DAPI staining, immunohistochemistry, in situ hybridization) is further presented. These basic protocols should allow novice investigators to obtain eye tissue samples rapidly for their experiments.

Visual vertigo: an observational case series of eleven patients.

BACKGROUND: Dizziness is a common symptom which is frequently due to either peripheral or central vestibular dysfunction. However, some patients may lack typical signs suggesting a vestibular or cerebellar lesion and they mostly complain of vertigo or posture imbalance induced by visual stimulation. The symptoms immediately improve either on cessation of the visual input or upon closure of the eyes. Such a presentation is typical of visual vertigo. PATIENTS AND METHODS: From 1993 to 2003, 242 patients were examined for either "vertigo" or "dizziness". The diagnosis of visual vertigo was based on both history and clinical examination and was present in 11 patients. RESULTS: Visual vertigo was diagnosed in 11/242 patients (4.5 %). Age range was 31 - 77 years (mean 47 years) with a sex ratio of 8 females for 3 males. Neuro-ophthalmological examination was normal in all cases. CONCLUSIONS: Visual vertigo is not a rare condition but the disease is underdiagnosed. The symptoms result from a mismatch between vestibular, proprioceptive and visual inputs. Neuro-ophthalmological, neurological and neuro-otological examination are often normal or not relevant and the diagnosis is largely based on history. It is important to recognize this entity because the symptoms might improve if the patients are treated with psycho-motor rehabilitation.

Hes1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation.

Although canonical Notch signaling regulates multiple hematopoietic lineage decisions including T cell and marginal zone B cell fate specification, the downstream molecular mediators of Notch function are largely unknown. We showed here that conditional inactivation of Hes1, a well-characterized Notch target gene, in adult murine bone marrow (BM) cells severely impaired T cell development without affecting other Notch-dependent hematopoietic lineages such as marginal zone B cells. Competitive mixed BM chimeras, intrathymic transfer experiments, and in vitro culture of BM progenitors on Delta-like-expressing stromal cells further demonstrated that Hes1 is required for T cell lineage commitment, but dispensable for Notch-dependent thymocyte maturation through and beyond the beta selection checkpoint. Furthermore, our data strongly suggest that Hes1 is essential for the development and maintenance of Notch-induced T cell acute lymphoblastic leukemia. Collectively, our studies identify Hes1 as a critical but context-dependent mediator of canonical Notch signaling in the hematopoietic system.