A crystallographic map of the transition from B-DNA to A-DNA

The transition between B- and A-DNA was first observed nearly 50 years ago. We have now mapped this transformation through a set of single-crystal structures of the sequence d(GGCGCC)2, with various intermediates being trapped by methylating or brominating the cytosine bases. The resulting pathway progresses through 13 conformational steps, with a composite structure that pairs A-nucleotides with complementary B-nucleotides serving as a distinct transition intermediate. The details of each step in the conversion of B- to A-DNA are thus revealed at the atomic level, placing intermediates for this and other sequences in the context of a common pathway.

Activation of NF-κB by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK–IKKα/β–IκBα and MKK3/6–p38 MAP kinase signaling pathways in epithelial cells

Nontypeable Hemophilus influenzae (NTHi) is an important human pathogen in both children and adults. In children, it causes otitis media, the most common childhood infection and the leading cause of conductive hearing loss in the United States. In adults, it causes lower respiratory tract infections in the setting of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. The molecular mechanisms underlying the pathogenesis of NTHi-induced infections remain undefined, but they may involve activation of NF-κB, a transcriptional activator of multiple host defense genes involved in immune and inflammatory responses. Here, we show that NTHi strongly activates NF-κB in human epithelial cells via two distinct signaling pathways, NF-κB translocation-dependent and -independent pathways. The NF-κB translocation-dependent pathway involves activation of NF-κB inducing kinase (NIK)–IKKα/β complex leading to IκBα phosphorylation and degradation, whereas the NF-κB translocation-independent pathway involves activation of MKK3/6–p38 mitogen-activated protein (MAP) kinase pathway. Bifurcation of NTHi-induced NIK–IKKα/β-IκBα and MKK3/6–p38 MAP kinase pathways may occur at transforming growth factor-β activated kinase 1 (TAK1). Furthermore, we show that toll-like receptor 2 (TLR2) is required for NTHi-induced NF-κB activation. In addition, several key inflammatory mediators including IL-1β, IL-8, and tumor necrosis factor-α are up-regulated by NTHi. Finally, P6, a 16-kDa lipoprotein highly conserved in the outer membrane of all NTHi and H. influenzae type b strains, appears to also activate NF-κB via similar signaling pathways. Taken together, our results demonstrate that NTHi activates NF-κB via TLR2–TAK1-dependent NIK–IKKα/β-IκBα and MKK3/6–p38 MAP kinase signaling pathways. These studies may bring new insights into molecular pathogenesis of NTHi-induced infections and open up new therapeutic targets for these diseases.

An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis H37Rv, and comparison with Mycobacterium leprae.

An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis, was constructed by using a twin-pronged approach. Pulsed-field gel electrophoretic analysis enabled cleavage sites for Asn I and Dra I to be positioned on the 4.4-Mb circular chromosome, while, in parallel, clones from two cosmid libraries were ordered into contigs by means of fingerprinting and hybridization mapping. The resultant contig map was readily correlated with the physical map of the genome via the landmarked restriction sites. Over 165 genes and markers were localized on the integrated map, thus enabling comparisons with the leprosy bacillus, Mycobacterium leprae, to be undertaken. Mycobacterial genomes appear to have evolved as mosaic structures since extended segments with conserved gene order and organization are interspersed with different flanking regions. Repetitive sequences and insertion elements are highly abundant in M. tuberculosis, but the distribution of IS6110 is apparently nonrandom.

A pictorial and descriptive guide to London and the British empire exhibition, 1925; with two large section plans of central London; map of London and twelve miles round; railway and motor bus maps; main roads out of London; Hyde park and Kensington gardens, and twenty other maps and plans. Over one hundred illustrations.

Mode of access: Internet.

The map, XV-XVIII centuries; an exhibition illustrating the history of cartography from the collection of Frederick B. Artz.

"Five hundred copies ... printed."

James B. Angell seated in office with map of state behind, ca. June 1897

Made for The Michigan Alumnus. "It is the only picture ever taken of Dr. Angell at his desk in the "President's Office." reproduced MI Alumnus, Vol. 3, no. 27, July, 1897

James B. Angell working at desk in office with map of state behind, ca. June 1897

Made for The Michigan Alumnus. "It is the only picture ever taken of Dr. Angell at his desk in the "President's Office." reproduced MI Alumnus, Vol. 3, no. 27, July, 1897

Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B

Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. They are required for a host of physiological processes including mitogen-activated protein kinase (MAPK) regulation, steroidogenesis, appetite control and energy regulation. While some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatially and temporally complex. This study dissects the different G-protein signalling and MAPK pathways activated in a pluripotent human adrenal H295R cell line capable of all the physiological steps involved in steroidogenesis. Both extracellular receptor kinase 1/2 (ERK1/2) and p38 were phosphorylated rapidly with a subsequent decline, in a time- and dose-dependent manner, in response to both ORA and ORB. Conversely, there was little or no direct activation of the ERK5 or JNK pathway. Analysis using signalling and MAPK inhibitors as well as receptor-specific antagonists determined the precise mediators of the orexin response in these cells. Both ERK1/2 and p38 activation were predominantly Gq- and to a lesser extent Gs-mediated; p38 activation even had a small Gi-component. Effects were broadly comparable for both orexin sub-types ORA and ORB and although most of the effects were transmitted through the orexin receptor-1 subtype, we did observe a role for orexin receptor-2-mediated activation of both ERK1/2 and p38. Cortisol secretion also differed in response to ORA and ORB. These data suggest multiple roles for orexin-mediated MAPK activation in an adrenal cell-line, this complexity may help to explain the diverse biological actions of orexins with wide-ranging consequences for our understanding of the mechanisms initiated by these steroidogenic molecules.

10Gbit/s dispersion managed soliton transmission over 16,500km in standard fibre by reduction of soliton interactions

We show experimentally and numerically that in high-speed strongly dispersion-managed standard fiber soliton systems nonlinear interactions limit the propagation distance. We present results that show that the effect of these interactions can be significantly reduced by appropriate location of the amplifier within the dispersion map. Using this technique, we have been able to extend the propagation distance of 10-Gbit/s 231–1pseudorandom binary sequence soliton data to 16, 500km over standard fiber by use of dispersion compensation. To our knowledge this distance is the farthest transmission over standard fiber without active control ever reported, and it was achieved with the amplifier placed after the dispersion-compensating fiber in a recirculating loop.

10Gbit/s dispersion managed soliton transmission over 16,500km in standard fibre by reduction of soliton interactions

We show experimentally and numerically that in high-speed strongly dispersion-managed standard fiber soliton systems nonlinear interactions limit the propagation distance. We present results that show that the effect of these interactions can be significantly reduced by appropriate location of the amplifier within the dispersion map. Using this technique, we have been able to extend the propagation distance of 10-Gbit/s 231–1pseudorandom binary sequence soliton data to 16, 500km over standard fiber by use of dispersion compensation. To our knowledge this distance is the farthest transmission over standard fiber without active control ever reported, and it was achieved with the amplifier placed after the dispersion-compensating fiber in a recirculating loop.

The UK MPharm (1) - are we over reliant on traditional teaching methods?

Introduction-The design of the UK MPharm curriculum is driven by the Royal Pharmaceutical Society of Great Britain (RPSGB) accreditation process and the EU directive (85/432/EEC).[1] Although the RPSGB is informed about teaching activity in UK Schools of Pharmacy (SOPs), there is no database which aggregates information to provide the whole picture of pharmacy education within the UK. The aim of the teaching, learning and assessment study [2] was to document and map current programmes in the 16 established SOPs. Recent developments in programme delivery have resulted in a focus on deep learning (for example, through problem based learning approaches) and on being more student centred and less didactic through lectures. The specific objectives of this part of the study were (a) to quantify the content and modes of delivery of material as described in course documentation and (b) having categorised the range of teaching methods, ask students to rate how important they perceived each one for their own learning (using a three point Likert scale: very important, fairly important or not important). Material and methods-The study design compared three datasets: (1) quantitative course document review, (2) qualitative staff interview and (3) quantitative student self completion survey. All 16 SOPs provided a set of their undergraduate course documentation for the year 2003/4. The documentation variables were entered into Excel tables. A self-completion questionnaire was administered to all year four undergraduates, using a pragmatic mixture of methods, (n=1847) in 15 SOPs within Great Britain. The survey data were analysed (n=741) using SPSS, excluding non-UK students who may have undertaken part of their studies within a non-UK university. Results and discussion-Interviews showed that individual teachers and course module leaders determine the choice of teaching methods used. Content review of the documentary evidence showed that 51% of the taught element of the course was delivered using lectures, 31% using practicals (includes computer aided learning) and 18% small group or interactive teaching. There was high uniformity across the schools for the first three years; variation in the final year was due to the project. The average number of hours per year across 15 schools (data for one school were not available) was: year 1: 408 hours; year 2: 401 hours; year 3: 387 hours; year 4: 401 hours. The survey showed that students perceived lectures to be the most important method of teaching after dispensing or clinical practicals. Taking the very important rating only: 94% (n=694) dispensing or clinical practicals; 75% (n=558) lectures; 52% (n=386) workshops, 50% (n=369) tutorials, 43% (n=318) directed study. Scientific laboratory practices were rated very important by only 31% (n=227). The study shows that teaching of pharmacy to undergraduates in the UK is still essentially didactic through a high proportion of formal lectures and with high levels of staff-student contact. Schools consider lectures still to be the most cost effective means of delivering the core syllabus to large cohorts of students. However, this does limit the scope for any optionality within teaching, the scope for small group work is reduced as is the opportunity to develop multi-professional learning or practice placements. Although novel teaching and learning techniques such as e-learning have expanded considerably over the past decade, schools of pharmacy have concentrated on lectures as the best way of coping with the huge expansion in student numbers. References [1] Council Directive. Concerning the coordination of provisions laid down by law, regulation or administrative action in respect of certain activities in the field of pharmacy. Official Journal of the European Communities 1985;85/432/EEC. [2] Wilson K, Jesson J, Langley C, Clarke L, Hatfield K. MPharm Programmes: Where are we now? Report commissioned by the Pharmacy Practice Research Trust., 2005.

The Monitoring and Assessment Plan (MAP) Greater Everglades Wetlands Module- Landscape Pattern- Ridge, Slough, and Tree Island Mosaics: Year 1 Annual Report

In the current managed Everglades system, the pre-drainage, patterned mosaic of sawgrass ridges, sloughs and tree islands has been substantially altered or reduced largely as a result of human alterations to historic ecological and hydrological processes that sustained landscape patterns. The pre-compartmentalization ridge and slough landscape was a mosaic of sloughs, elongated sawgrass ridges (50-200m wide), and tree islands. The ridges and sloughs and tree islands were elongated in the direction of the water flow, with roughly equal area of ridge and slough. Over the past decades, the ridge-slough topographic relief and spatial patterning have degraded in many areas of the Everglades. Nutrient enriched areas have become dominated by Typha with little topographic relief; areas of reduced flow have lost the elongated ridge-slough topography; and ponded areas with excessively long hydroperiods have experienced a decline in ridge prevalence and shape, and in the number of tree islands (Sklar et al. 2004, Ogden 2005).

Map of Holmes Island and the adjoining upland : the property of R. B. Mason Esq.

Scale not given.