UtpA and UtpB chaperone nascent pre-ribosomal RNA and U3 snoRNA to initiate eukaryotic ribosome assembly

Early eukaryotic ribosome biogenesis involves large multi-protein complexes, which co-transcriptionally associate with pre-ribosomal RNA to form the small subunit processome. The precise mechanisms by which two of the largest multi-protein complexes—UtpA and UtpB—interact with nascent pre-ribosomal RNA are poorly understood. Here, we combined biochemical and structural biology approaches with ensembles of RNA–protein cross-linking data to elucidate the essential functions of both complexes. We show that UtpA contains a large composite RNA-binding site and captures the 5′ end of pre-ribosomal RNA. UtpB forms an extended structure that binds early pre-ribosomal intermediates in close proximity to architectural sites such as an RNA duplex formed by the 5′ ETS and U3 snoRNA as well as the 3′ boundary of the 18S rRNA. Both complexes therefore act as vital RNA chaperones to initiate eukaryotic ribosome assembly

Association of Polymorphisms of the Apolipoprotein(a) Gene with Lipoprotein(a) Levels and Myocardial Infarction.

Background— Serum lipoprotein(a) [Lp(a)] concentration is largely determined by variability at the apolipoprotein(a) gene locus. Most prominent effects relate to polymorphisms in the promoter (a pentanucleotide [PN] repeat) and coding regions (a kringle IV [K4] repeat), the latter of which also affects Lp(a) particle size. The impact of these polymorphisms on cardiovascular risk is poorly understood. Methods and Results— We studied both polymorphisms and Lp(a) levels in 834 registry-based myocardial infarction (MI) patients (38% women) and 1548 population-based controls. Lp(a) concentrations were inversely related with the numbers of K4 and PN repeats. However, the effect of the PN polymorphism was restricted to subjects producing small Lp(a) particles (≤8 PN 66.1 mg/dL versus >8 PN 8.7 mg/dL; P<0.0001). The odds to present with MI were elevated in individuals producing small Lp(a) particles (≤22 K4 repeats; OR 1.47 for men and 1.69 for women; P<0.002) and in women with ≤8 PN repeats (OR 1.46, P=0.009). Interestingly, in women, the frequent haplotype with ≤8 PN and ≤22 K4 repeats, which is related to high levels of small Lp(a) particles, resulted in an elevated OR for MI (1.79; P=0.01) independently of Lp(a) serum concentration. Conclusions— The K4 and PN repeat polymorphisms largely explain the high variability of serum Lp(a) levels. A haplotype with ≤8 PN and ≤22 K4 repeats is characterized by high concentrations of small Lp(a) particles. Our observation that this haplotype was associated with MI independently of Lp(a) serum levels may suggest that Lp(a) particle size in addition to its concentration may modulate MI risk in women

Semantic Interoperability. Final Report of Task Group IST-075

There is a need in NATO for semantically correct interoperability, created by knowledge based systems that flexibly bridge the semantic gaps among heterogeneous C4I systems. To achieve situational awareness in a joint/combined coalition the meaning of the exchanged information and the purpose of the information exchange must be understood identically everywhere and at all times. This requires a broad attention to the context of information and the concepts contained within the information. The research initiative of IST-075 has resulted in the construction of a conceptual framework, known as the Semantic Interoperability Logical Framework (SILF), which is composed of methodologies, guidelines for workflows, concepts for tools and their application in a context of heterogeneous information sources and information streams. SILF is intended to allow users the ability to achieve semantic interoperability between disparate systems. The IST-075 group also recognizes the need to bring semantic interoperability to the attention of all levels of decision makers (operational users, policy makers, procurers, project managers, etc.). Ontologies and semantic descriptions of concepts must be a component of the delivered system

Towards an inclusive methodology for the measurement of in-house use

Introduces the background to the EQLIPSE (Evaluation and Quality in Library Performance: System for Europe) project and the work done in compiling a core set of performance indicators for evaluating libraries. Describes the collection of in house library use data at the University of Central Lancashire Library test site, where EQLIPSE staff gathered data as part of the data collection exercise to test the feasibility of the indicators and to accumulate data in the EQLIPSE system. Some of the difficulties encountered in the process are noted along with the measures taken to address them. In addition to measuring actual use, attempts were also made to establish whether users habitually reshelve items they consult, both when at the shelf and when working at study spaces. Unobtrusive direct observation eventually formed the mainstay of the methods used to measure this. Results suggest that users consulting items at the shelf would change every 10 minutes on average and that the number of users would fall or rise gradually during the two hours between counts. Future developments to the EQLIPSE methodology are discussed