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Mammalian nucleostemin (NS) is a nucleolar guanosine triphosphate-binding protein implicated in cell cycle progression, stem cell proliferation, and ribosome assembly. Drosophila melanogaster contains a four-member nucleostemin family (NS1-4). NS1 is the closest orthologue to human NS; it shares 33% identity and 67% similarity with human NS. We show that NS1 has intrinsic GTPase and ATPase activity and that it is present within nucleoli of most larval and adult cells. Endogenous NS1 and lightly expressed green fluorescent protein (GFP)-NS1 enrich within the nucleolar granular regions as expected, whereas overexpressed GFP-NS1 localized throughout the nucleolus and nucleoplasm, and to several transcriptionally active interbands of polytene chromosomes. Severe overexpression correlated with the appearance of melanotic tumors and larval/pupal lethality. Depletion of 60% of NS1 transcripts also lead to larval and pupal lethality. NS1 protein depletion correlated with the loss of imaginal island (precursor) cells in the larval midgut and to an apparent block in the nucleolar release of large ribosomal subunits in terminally differentiated larval midgut polyploid cells. Ultrastructural examination of larval Malpighian tubule cells depleted for NS1 showed a loss of cytoplasmic ribosomes and a concomitant appearance of cytoplasmic preautophagosomes and lysosomes. We interpret the appearance of these structures as indicators of cell stress response. INTRODUCTIONMammalian nucleostemin (NS) is a nucleolar guanosine triphosphate (GTP)-binding protein first characterized in embryonic and neuronal stem cells and in certain cancer cells where it probably plays regulatory roles in cell cycle progression and ribosome biogenesis McKay, 2002, 2005; reviewed by Ma and Pederson, 2008b). Steadystate concentrations of NS drop to undetectable levels just before rat cortical stem cell differentiation (Tsai and McKay, 2002), suggesting that reduced expression of NS regulates stem cell proliferation and differentiation by triggering exit from the cell cycle (Normile, 2002;Tsai and McKay, 2002;Beekman et al., 2006). Mammalian NS rapidly cycles between the nucleolus and the nucleoplasm. Retention of NS within the nucleolus is prolonged when it binds GTP (Misteli, 2005;Tsai and McKay, 2005;Meng et al., 2006Meng et al., , 2007. GTP bound to the central region of NS is thought to stabilize interactions between its amino-terminal basic domain and other nucleolar components, whereas NS redistributes to the nucleoplasm when GTP binding is impaired by mutation (Tsai and McKay, 2005). Coimmunoprecipitation, yeast twohybrid, and bimolecular fluorescence complementation assays demonstrated an interaction between NS and nucleophosmin (B23) (Ma and Pederson, 2008a), a multifunctional chaperone that probably participates in the later stages of ribosome assembly within the granular component of nucleoli. Similar to NS, nucleophosmin probably plays a role in cell proliferation (Szebeni et al., 2003;Grisendi et al., 2006). Recent studies suggest that NS ...

As the biomedical impact of small RNAs grows, so does the need to understand competing structural alternatives for regions of functional interest. Suboptimal structure analysis provides significantly more RNA base pairing information than a single minimum free energy prediction. Yet computational enhancements like Boltzmann sampling have not been fully adopted by experimentalists since identifying meaningful patterns in this data can be challenging. Profiling is a novel approach to mining RNA suboptimal structure data which makes the power of ensemble-based analysis accessible in a stable and reliable way. Balancing abstraction and specificity, profiling identifies significant combinations of base pairs which dominate low-energy RNA secondary structures. By design, critical similarities and differences are highlighted, yielding crucial information for molecular biologists. The code is freely available via http://gtfold.sourceforge.net/profiling.html.

Data from this study prove that further education regarding safe pubic hair removal methods is needed, especially for those who initiate pubic hair removal and sexual behaviours concurrently.

A Control SidebarFigure 1: With BLUFF, users interactively visualize how adversarial attacks penetrate a deep neural network to induce incorrect outcomes. Here, a user inspects why INCEPTIONV1 misclassifies adversarial giant panda images, crafted by the Projected Gradient Descent (PGD) attack, as armadillo. PGD successfully perturbed pixels to induce the "brown bird" feature, an appearance more likely shared by an armadillo (small, roundish, brown body) than a panda, activating more features that contribute to the armadillo (mis)classification (e.g., "scales," "bumps," "mesh"). The adversarial pathways, formed by these neurons and their connections, overwhelm the benign panda pathways and lead to the ultimate misclassification. (A) Control Sidebar allows users to specify what data is to be included and highlighted. (B) Graph Summary View visualizes pathways most activated or changed by an attack as a network graph of neurons (each labeled by the channel ID in its layer) and their connections. When hovering over a neuron, (C) Detail View displays its feature visualization, representative dataset examples, and activation patterns over attack strengths.

Purpose This paper aims to report the findings of a qualitative investigation of student patrons’ experiences with research consultations provided by reference librarians at a comprehensive university located in the southern USA during 2014. Design/methodology/approach Data were collected through recorded interviews with patrons who had recently experienced a reference consultation with one of eight professional reference librarians during a semester. The recorded data were transcribed verbatim and the transcripts subjected to content analysis. The qualitative data analysis model selected was that of a conventional, inductive content analysis. Findings One principal finding demonstrates the need for marketing of the reference consultation service; participants were surprised at the service’s availability. Other findings illustrate the value participants placed on individual attention from a librarian, perceived librarian expertise, the consultation environment and student/librarian engagement. Research limitations/implications Limitations to this study include a small participant pool of undergraduate student patrons, mainly majoring in humanities disciplines. The findings therefore are limited in the confidence with which they can be generalized to larger populations. Practical implications The reference consultation remains an integral part of the services offered by an academic library’s reference department; libraries should market consultations accordingly. Academic libraries that do not operate on a subject specialist model should consider strategies for maximizing benefit when matching available staff to consultation requests. Social implications This study provides evidence for the value of one-to-one reference service through research consultations provided to library patrons in academic libraries serving institutions of the type described in the research. Originality/value A qualitative methodology, using content analysis of lengthy interviews with participants, provides considerable insight into academic library patrons’ attitudes toward the reference consultation service.

A widening gap exists between the best practices for RNA secondary structure prediction developed by computational researchers and the methods used in practice by experimentalists. Minimum free energy (MFE) predictions, although broadly used, are outperformed by methods which sample from the Boltzmann distribution and data mine the results. In particular, moving beyond the single structure prediction paradigm yields substantial gains in accuracy. Furthermore, the largest improvements in accuracy and precision come from viewing secondary structures not at the base pair level but at lower granularity/higher abstraction. This suggests that random errors affecting precision and systematic ones affecting accuracy are both reduced by this “fuzzier” view of secondary structures. Thus experimentalists who are willing to adopt a more rigorous, multilayered approach to secondary structure prediction by iterating through these levels of granularity will be much better able to capture fundamental aspects of RNA base pairing.

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