The Importance of Academic Deans\u27 Interpersonal/Negotiating Skills as Leaders

Four academic deans investigated when and how they used interpersonal/negotiating skills to function effectively in their positions. For two full weeks, the deans coded their on-the-job interactions during scheduled meetings, informal meetings, spontaneous encounters/meetings, telephone calls, and select email. Analyses revealed that the interpersonal/negotiating skills used, from most to least prevalent, were: working closely with others, being responsive to key persons, negotiating key players\u27 roles, and keeping key persons in the organisation informed. Across these engagements, the deans interacted with 35 different categories of stakeholders inside and outside their institutions for 32 different purposes. Given the nature and range of interactions, the deans concluded that practicing and prospective deans should likely have access to professional development opportunities explicitly focused on working closely with others. Future research would need to confirm, however, whether interpersonal/negotiating skills are essential for deans\u27 job survival and, if so, whether such skills can authentically be developed

Late-Onset Erythropoietic Porphyria Caused by a Chromosome 18q Deletion in Erythroid Cells

The erythropoietic porphyrias, erythropoietic protoporphyria and congenital erythropoietic porphyria, result from germline mutations in the ferrochelatase gene and uroporphyrinogen III synthase gene, respectively. Both conditions normally present in childhood but rare cases with onset past the age of 40 y have been reported. Here we show that late-onset erythropoietic protoporphyria can be caused by deletion of the ferrochelatase gene in hematopoietic cells with clonal expansion as part of the myelodysplastic process. This is the first direct demonstration of porphyria produced by an acquired molecular defect restricted to one tissue. Some other cases of late-onset erythropoietic porphyria may be explained by a similar mechanism

The Hubble constant inferred from 18 time-delay lenses

We present a simultaneous analysis of 18 galaxy lenses with time delay measurements. For each lens we derive mass maps using pixelated simultaneous modeling with shared Hubble constant. We estimate the Hubble constant to be 66_{-4}^{+6} km/s/Mpc (for a flat Universe with \Omega_m=0.3, \Omega_\Lambda=0.7). We have also selected a subsample of five relatively isolated early type galaxies and by simultaneous modeling with an additional constraint on isothermality of their mass profiles we get H_0=76 +/-3 km/s/Mpc.Comment: 11 page, 4 figures, Accepted for publication in Ap

Intervening with Urinary Tract Infections Using Anti-Adhesives Based on the Crystal Structure of the FimH–Oligomannose-3 Complex

Escherichia coli strains adhere to the normally sterile human uroepithelium using type 1 pili, that are long, hairy surface organelles exposing a mannose-binding FimH adhesin at the tip. A small percentage of adhered bacteria can successfully invade bladder cells, presumably via pathways mediated by the high-mannosylated uroplakin-Ia and alpha3beta1 integrins found throughout the uroepithelium. Invaded bacteria replicate and mature into dense, biofilm-like inclusions in preparation of fluxing and of infection of neighbouring cells, being the major cause of the troublesome recurrent urinary tract infections.We demonstrate that alpha-D-mannose based inhibitors of FimH not only block bacterial adhesion on uroepithelial cells but also antagonize invasion and biofilm formation. Heptyl alpha-D-mannose prevents binding of type 1-piliated E. coli to the human bladder cell line 5637 and reduces both adhesion and invasion of the UTI89 cystitis isolate instilled in mouse bladder via catheterization. Heptyl alpha-D-mannose also specifically inhibited biofilm formation at micromolar concentrations. The structural basis of the great inhibitory potential of alkyl and aryl alpha-D-mannosides was elucidated in the crystal structure of the FimH receptor-binding domain in complex with oligomannose-3. FimH interacts with Man alpha1,3Man beta1,4GlcNAc beta1,4GlcNAc in an extended binding site. The interactions along the alpha1,3 glycosidic bond and the first beta1,4 linkage to the chitobiose unit are conserved with those of FimH with butyl alpha-D-mannose. The strong stacking of the central mannose with the aromatic ring of Tyr48 is congruent with the high affinity found for synthetic inhibitors in which this mannose is substituted for by an aromatic group.The potential of ligand-based design of antagonists of urinary tract infections is ruled by the structural mimicry of natural epitopes and extends into blocking of bacterial invasion, intracellular growth and capacity to fluxing and of recurrence of the infection

Copper-Triggered Aggregation of Ubiquitin

Neurodegenerative disorders share common features comprising aggregation of misfolded proteins, failure of the ubiquitin-proteasome system, and increased levels of metal ions in the brain. Protein aggregates within affected cells often contain ubiquitin, however no report has focused on the aggregation propensity of this protein. Recently it was shown that copper, differently from zinc, nickel, aluminum, or cadmium, compromises ubiquitin stability and binds to the N-terminus with 0.1 micromolar affinity. This paper addresses the role of copper upon ubiquitin aggregation. In water, incubation with Cu(II) leads to formation of spherical particles that can progress from dimers to larger conglomerates. These spherical oligomers are SDS-resistant and are destroyed upon Cu(II) chelation or reduction to Cu(I). In water/trifluoroethanol (80∶20, v/v), a mimic of the local decrease in dielectric constant experienced in proximity to a membrane surface, ubiquitin incubation with Cu(II) causes time-dependent changes in circular dichroism and Fourier-transform infrared spectra, indicative of increasing β-sheet content. Analysis by atomic force and transmission electron microscopy reveals, in the given order, formation of spherical particles consistent with the size of early oligomers detected by gel electrophoresis, clustering of these particles in straight and curved chains, formation of ring structures, growth of trigonal branches from the rings, coalescence of the trigonal branched structures in a network. Notably, none of these ubiquitin aggregates was positive to tests for amyloid and Cu(II) chelation or reduction produced aggregate disassembly. The early formed Cu(II)-stabilized spherical oligomers, when reconstituted in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes and in POPC planar bilayers, form annular and pore-like structures, respectively, which are common to several neurodegenerative disorders including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, and prion diseases, and have been proposed to be the primary toxic species. Susceptibility to aggregation of ubiquitin, as it emerges from the present study, may represent a potential risk factor for disease onset or progression while cells attempt to tag and process toxic substrates

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Abrasive Grit Application in Organic Red Pepper: An Opportunity for Integrating Nitrogen and Weed Management

Weeds are a top management concern among organic vegetable growers. Abrasive weeding is a nonchemical tactic using air-propelled abrasive grit to destroy weed seedlings within crop rows. Many grit types are effective, but if organic fertilizers are used, this could integrate weed and nutrient management in a single field pass. Our objective was to quantify the effects of abrasive grit and mulch type on weed suppression, disease severity, soil nitrogen availability, and yield of pepper (Capsicum annuum L. ‘Carmen’). A 2-year experiment was conducted in organic red sweet pepper at Urbana, IL, with four replicates of five abrasive grit treatments (walnut shell grits, soybean meal fertilizer, composted turkey litter fertilizer, a weedy control, and a weed-free control) and four mulch treatments (straw mulch, bioplastic film, polyethylene plastic film, and a bare soil control). Abrasive weeding, regardless of grit type, paired with bioplastic or polyethylene plastic mulch reduced in-row weed density (67 and 87%, respectively) and biomass (81 and 84%); however there was no significant benefit when paired with straw mulch or bare ground. Despite the addition of 6 to 34 kg N/ha/yr through the application of soybean meal and composted turkey litter grits, simulated plant N uptake was most influenced by mulch composition (e.g., plastic vs. straw) and weed abundance. Nitrogen immobilization in straw mulch plots reduced leaf greenness, plant height, and yield. Bacterial spot (Xanthomonas campestris pv. Vesicatoria) was confirmed on peppers in both years, but abrasive weeding did not increase severity of the disease. Pepper yield was always greatest in the weed-free control and lowest in straw mulch and bare soil, but the combination of abrasive weeding (regardless of grit type) and bioplastic or polyethylene plastic mulch increased marketable yield by 47% and 21%, respectively, compared with the weedy control. Overall, results demonstrate that when abrasive weeding is paired with bioplastic or polyethylene mulch, growers can concurrently suppress weeds and increase crop N uptake for greater yields