Superconformal Multi-Black Hole Moduli Spaces in Four Dimensions

Quantum mechanics on the moduli space of N supersymmetric Reissner-Nordstrom black holes is shown to admit 4 supersymmetries using an unconventional supermultiplet which contains 3N bosons and 4N fermions. A near-horizon limit is found in which the quantum mechanics of widely separated black holes decouples from that of strongly-interacting, near-coincident black holes. This near-horizon theory is shown to have an enhanced D(2,1;0) superconformal symmetry. The bosonic symmetries are SL(2,R) conformal symmetry and SU(2)xSU(2) R-symmetry arising from spatial rotations and the R-symmetry of N=2 supergravity.Comment: 23 pages, harvmac. v2: many typos fixe

De novo formation of an aggregation pheromone precursor by an isoprenyl diphosphate synthase-related terpene synthase in the harlequin bug.

Insects use a diverse array of specialized terpene metabolites as pheromones in intraspecific interactions. In contrast to plants and microbes, which employ enzymes called terpene synthases (TPSs) to synthesize terpene metabolites, limited information from few species is available about the enzymatic mechanisms underlying terpene pheromone biosynthesis in insects. Several stink bugs (Hemiptera: Pentatomidae), among them severe agricultural pests, release 15-carbon sesquiterpenes with a bisabolene skeleton as sex or aggregation pheromones. The harlequin bug, Murgantia histrionica, a specialist pest of crucifers, uses two stereoisomers of 10,11-epoxy-1-bisabolen-3-ol as a male-released aggregation pheromone called murgantiol. We show that MhTPS (MhIDS-1), an enzyme unrelated to plant and microbial TPSs but with similarity to trans-isoprenyl diphosphate synthases (IDS) of the core terpene biosynthetic pathway, catalyzes the formation of (1S,6S,7R)-1,10-bisaboladien-1-ol (sesquipiperitol) as a terpene intermediate in murgantiol biosynthesis. Sesquipiperitol, a so-far-unknown compound in animals, also occurs in plants, indicating convergent evolution in the biosynthesis of this sesquiterpene. RNAi-mediated knockdown of MhTPS mRNA confirmed the role of MhTPS in murgantiol biosynthesis. MhTPS expression is highly specific to tissues lining the cuticle of the abdominal sternites of mature males. Phylogenetic analysis suggests that MhTPS is derived from a trans-IDS progenitor and diverged from bona fide trans-IDS proteins including MhIDS-2, which functions as an (E,E)-farnesyl diphosphate (FPP) synthase. Structure-guided mutagenesis revealed several residues critical to MhTPS and MhFPPS activity. The emergence of an IDS-like protein with TPS activity in M. histrionica demonstrates that de novo terpene biosynthesis evolved in the Hemiptera in an adaptation for intraspecific communication

From Basile to Barbie. Doll fantasies, toy princesses, and clockwork females

Few studies quantify spinal posture behaviour at both the thoracolumbar and lumbar spinal regions. This study compared spontaneous spinal posture in 50 asymptomatic participants ( 21 males ) during three conditions: 10-min computer task in sitting ( participants naïve to the measure ), during their perceived ‘correct’ sitting posture, and standing. Three-dimensional optical tracking quantified surface spinal angles at the thoracolumbar and lumbar regions, and spinal orientation with respect to the vertical. Despite popular belief that lordotic lumbar angles are ‘correct’ for sitting, this was rarely adopted for 10-min sitting. In 10-min sitting, spinal angles flexed 24( 7–9 )deg at lumbar and 12( 6–8 )deg at thoracolumbar regions relative to standing ( P < 0.001 ). When participants ‘corrected’ their sitting posture, their thoracolumbar angle −2( 7 )deg was similar to the angle in standing −1( 6 )deg ( P = 1.00 ). Males were flexed at the lumbar angle relative to females for 10-min sitting, ‘correct’ sitting and standing, but showed no difference at the thoracolumbar region

Different ways to balance the spine in sitting: Muscle activity in specific postures differs between individuals with and without a history of back pain in sitting

Previous research explored muscle activity in four distinct sitting postures with fine-wire electromyography, and found that lumbar multifidus muscle activity increased incrementally between sitting with flat thoracolumbar and lumbar regions, long thoracolumbar lordosis, or short lordosis confined to the lumbar region. This study used similar methods to explore whether people with a history of low back pain provoked by prolonged sitting used different patterns of trunk muscle activity in specific postures.Fine-wire electromyography electrodes were inserted into the right lumbar multifidus (deep and superficial), iliocostalis (lateral and medial), longissimus thoracis and transversus abdominis muscles. Superficial abdominal muscle activity was recorded with surface or fine-wire electrodes. Electromyography amplitude was compared between postures for the back pain group and observations were contrasted with the changes previously reported for pain-free controls. For comparison between groups normalised and non-normalised electromyography amplitudes were compared.Individuals with a history of back pain demonstrated greater activity of the longissimus thoracis muscle in the long lordosis compared with the flat posture [mean difference (95% CI): 46.6 (17.5-75.7)%, normalised to sitting posture peak activity], but pain-free participants did not [mean difference: 7.7 (minus 12-27.6)%]. Pain-free participants modulated lumbar multifidus activity with changes in lumbar curve, but people with a history of pain in prolonged sitting did not change multifidus activity between the long and short lordotic postures.In clinical ergonomic interventions that modify spinal curves and sagittal balance in sitting, the muscle activity used in those postures may differ between people with and without a history of back pain

Reproducibility of the Kids Balance Evaluation Systems Test (Kids-BESTest) and the Kids-Mini-BESTest for children with cerebral palsy

To evaluate the reproducibility, including reliability and agreement, of the Kids Balance Evaluation Systems Test (Kids-BESTest) and short-form Kids-Mini-BESTest for measuring postural control in school-aged children with cerebral palsy.Psychometric study of intra-rater, inter-rater and test-retest reliability and agreement; SETTING: Clinical laboratory and home.Convenience sample of 18 children aged 8 to 17 years with ambulant cerebral palsy (Gross Motor Function Classification System I-II) with spastic or ataxic motor type.Not applicable.Postural control was assessed using the Kids-BESTest and the short-form Kids-Mini-BESTest. An experienced physiotherapist assessed all children in real-time and the testing session was videoed. The same physiotherapist viewed and scored the video twice, at least two weeks apart, to assess intra-rater reproducibility. Another experienced physiotherapist scored the same video to determine inter-rater reproducibility. Thirteen children returned for a repeat assessment with the first physiotherapist within 6 weeks and their test-retest performance was rated in real time and with video.Excellent reliability was observed for both the Kids-BESTest (ICC 0.96 to 0.99) and Kids-Mini-BESTest (ICC 0.79 to 0.98). The Smallest Detectable Change was good to excellent for all Kids-BESTest agreement analyses (5% to 9%), but poor to good for Kids-Mini-BESTest analyses (9% to 16%).The Kids-BESTest shows an excellent ability to discriminate postural control abilities of school-aged children with cerebral palsy and it has a low Smallest Detectable Change, suitable for use as a pre-post intervention outcome measure. Although the Kids-Mini-BESTest is 5-10 min shorter to administer, it has poorer reproducibility and focuses only on falls-related balance, which excludes two domains of postural control

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin

New antibacterials are needed to tackle antibiotic-resistant bacteria. Type IIA topoisomerases (topo2As), the targets of fluoroquinolones, regulate DNA topology by creating transient double-strand DNA breaks. Here we report the first co-crystal structures of the antibacterial QPT-1 and the anticancer drug etoposide with Staphylococcus aureus DNA gyrase, showing binding at the same sites in the cleaved DNA as the fluoroquinolone moxifloxacin. Unlike moxifloxacin, QPT-1 and etoposide interact with conserved GyrB TOPRIM residues rationalizing why QPT-1 can overcome fluoroquinolone resistance. Our data show etoposide’s antibacterial activity is due to DNA gyrase inhibition and suggests other anticancer agents act similarly. Analysis of multiple DNA gyrase co-crystal structures, including asymmetric cleavage complexes, led to a ‘pair of swing-doors’ hypothesis in which the movement of one DNA segment regulates cleavage and religation of the second DNA duplex. This mechanism can explain QPT-1’s bacterial specificity. Structure-based strategies for developing topo2A antibacterials are suggested

Pre-surgical radiologic identification of peri-prosthetic osteolytic lesions around TKRs: a pre-clinical investigation of diagnostic accuracy

Background: Emerging longitudinal data appear to demonstrate an alarming trend towards an increasing prevalence of osteolysis-induced mechanical failure, following total knee replacement (TKR). Even with high-quality multi-plane X-rays, accurate pre-surgical evaluation of osteolytic lesions is often difficult. This is likely to have an impact on surgical management and provides reasonable indication for the development of a model allowing more reliable lesion assessment. The aim of this study, using a simulated cadaver model, was to explore the accuracy of rapid spiral computed tomography (CT) examination in the non-invasive evaluation of peri-prosthetic osteolytic lesions, secondary to TKR, and to compare this to conventional X-ray standards. Methods: A series of nine volume-occupying defects, simulating osteolytic lesions, were introduced into three human cadaveric knees, adjacent to the TKR implant components. With implants in situ, each knee was imaged using a two-stage conventional plain X-ray series and rapid-acquisition spiral CT. A beam-hardening artefact removal algorithm was employed to improve CT image quality. After random image sorting, 12 radiologists were independently shown the series of plain X-ray images and asked to note the presence, anatomic location and 'size' of osteolytic lesions observed. The same process was repeated separately for review of the CT images. The corresponding X-ray and CT responses were directly compared to elicit any difference in the ability to demonstrate the presence and size of osteolytic lesions. Results: Access to CT images significantly improved the accuracy of recognition of peri-prosthetic osteolytic lesions when compared to AP and lateral projections alone (P = 0.008) and with the addition of bi-planar oblique X-rays (P = 0.03). No advantage was obtained in accuracy of identification of such lesions through the introduction of the oblique images when compared with the AP and lateral projections alone (P = 0.13) Conclusion: The findings of this study suggest that peri-prosthetic osteolytic lesions can be reliably described non-invasively using a simple, rapid-acquisition CT-based imaging approach. The low sensitivity of conventional X-ray, even with provision of supplementary bi-planar 45° oblique views, suggests a limited role for use in situ for TKR implant screening where peri-prosthetic osteolytic lesions are clinically suspected. In contrast, the accuracy of CT evaluation, linked to its procedural ease and widespread availability, may provide a more accurate way of evaluating osteolysis around TKRs, at routine orthopaedic follow up. These findings have direct clinical relevance, as accurate early recognition and classification of such lesions influences the timing and aggressiveness of surgical and non-operative management strategies, and also the nature and appropriateness of planned implant revision or joint-salvaging osteotomy procedures.Timothy P. Kurmis, Andrew P. Kurmis, David G. Campbell and John P. Slavotine