LCCL protein complex formation in Plasmodium is critically dependent on LAP1.

Successful sporogony of Plasmodium berghei in vector mosquitoes requires expression of a family of six modular proteins named LCCL lectin domain adhesive-like proteins (LAPs). The LAPs share a subcellular localization in the crystalloid, a unique parasite organelle that forms during ookinete development. Here, LAP interactions in P. berghei were studied using a series of parasite lines stably expressing reporter-tagged LAPs combined with affinity purification and high accuracy label free quantitative mass spectrometry. Our results show that abundant complexes containing LAP1, LAP2 and LAP3 are formed in gametocytes through high avidity interactions. Following fertilization, LAP4, LAP5 and LAP6 are recruited to this complex, a process that is facilitated by LAP1 chiefly through its scavenger receptor cysteine-rich modules. These collective findings provide new insight into the temporal and molecular dynamics of protein complex formation that lead up to, and are required for, crystalloid biogenesis and downstream sporozoite transmission of malaria parasites

The Maine Annex, vol. 2, no. 8

The Maine Annex covers Erroll E. Murphy\u27s trip to Washington, D.C. as the University of Maine Annex campus representative to the National Association of Veteran Trainees. Murphy was among the World War II Veterans seeking support for Edith Nourse Rogers of Massachusetts bill H.R. 870, to increase Veterans\u27 subsistence payments

The effect of twisted magnetic field on the resonant absorption of MHD waves in coronal loops

The standing quasi modes in a cylindrical incompressible flux tube with magnetic twist that undergoes a radial density structuring is considered in ideal magnetohydrodynamics (MHD). The radial structuring is assumed to be a linearly varying density profile. Using the relevant connection formulae, the dispersion relation for the MHD waves is derived and solved numerically to obtain both the frequencies and damping rates of the fundamental and first-overtone modes of both the kink (m=1) and fluting (m=2,3) waves. It was found that a magnetic twist will increase the frequencies, damping rates and the ratio of the oscillation frequency to the damping rate of these modes. The period ratio P_1/P_2 of the fundamental and its first-overtone surface waves for kink (m=1) and fluting (m=2,3) modes is lower than 2 (the value for an untwisted loop) in the presence of twisted magnetic field. For the kink modes, particularly, the magnetic twists B_{\phi}/B_z=0.0065 and 0.0255 can achieve deviations from 2 of the same order of magnitude as in the observations. Furthermore, for the fundamental kink body waves, the frequency bandwidth increases with increasing the magnetic twist.Comment: 18 pages, 9 figure

Transverse oscillations of coronal loops

On 14 July 1998 TRACE observed transverse oscillations of a coronal loop generated by an external disturbance most probably caused by a solar flare. These oscillations were interpreted as standing fast kink waves in a magnetic flux tube. Firstly, in this review we embark on the discussion of the theory of waves and oscillations in a homogeneous straight magnetic cylinder with the particular emphasis on fast kink waves. Next, we consider the effects of stratification, loop expansion, loop curvature, non-circular cross-section, loop shape and magnetic twist. An important property of observed transverse coronal loop oscillations is their fast damping. We briefly review the different mechanisms suggested for explaining the rapid damping phenomenon. After that we concentrate on damping due to resonant absorption. We describe the latest analytical results obtained with the use of thin transition layer approximation, and then compare these results with numerical findings obtained for arbitrary density variation inside the flux tube. Very often collective oscillations of an array of coronal magnetic loops are observed. It is natural to start studying this phenomenon from the system of two coronal loops. We describe very recent analytical and numerical results of studying collective oscillations of two parallel homogeneous coronal loops. The implication of the theoretical results for coronal seismology is briefly discussed. We describe the estimates of magnetic field magnitude obtained from the observed fundamental frequency of oscillations, and the estimates of the coronal scale height obtained using the simultaneous observations of the fundamental frequency and the frequency of the first overtone of kink oscillations. In the last part of the review we summarise the most outstanding and acute problems in the theory of the coronal loop transverse oscillations

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Tolerability of NGX-4010, a capsaicin 8% dermal patch, following pretreatment with lidocaine 2.5%/prilocaine 2.5% cream in patients with post-herpetic neuralgia

<p>Abstract</p> <p>Background</p> <p>Post-herpetic neuralgia (PHN) is a common type of neuropathic pain that can severely affect quality of life. NGX-4010, a capsaicin 8% dermal patch, is a localized treatment that can provide patients with significant pain relief for up to 3 months following a single 60-minute application. The NGX-4010 application can be associated with application-site pain and in previous clinical trials pretreatment with a topical 4% lidocaine anesthetic was used to enhance tolerability. The aim of the current investigation was to evaluate tolerability of NGX-4010 after pretreatment with lidocaine 2.5%/prilocaine 2.5% anesthetic cream.</p> <p>Methods</p> <p>Twenty-four patients with PHN were pretreated with lidocaine 2.5%/prilocaine 2.5% cream for 60 minutes before receiving a single 60-minute application of NGX-4010. Tolerability was assessed by measuring patch application duration, the proportion of patients completing over 90% of the intended treatment duration, application site-related pain using the Numeric Pain Rating Scale (NPRS), and analgesic medication use to relieve such pain. Safety was assessed by monitoring adverse events (AEs) and dermal irritation using dermal assessment scores.</p> <p>Results</p> <p>The mean treatment duration of NGX-4010 was 60.2 minutes and all patients completed over 90% of the intended patch application duration. Pain during application was transient. A maximum mean change in NPRS score of +3.0 was observed at 55 minutes post-patch application; pain scores gradually declined to near pre-anesthetic levels (+0.71) within 85 minutes of patch removal. Half of the patients received analgesic medication on the day of treatment; by Day 7, no patients required medication. The most common AEs were application site-related pain, erythema, edema, and pruritus. All patients experienced mild dermal irritation 5 minutes after patch removal, which subsequently decreased; at Day 7, no irritation was evident. The maximum recorded dermal assessment score was 2.</p> <p>Conclusion</p> <p>NGX-4010 was well tolerated following pretreatment with lidocaine 2.5%/prilocaine 2.5% cream in patients with PHN. The tolerability of the patch application appeared comparable with that seen in other studies that used 4% lidocaine cream as the pretreatment anesthetic. This study is registered at <url>http://www.clinicaltrials.gov</url> as number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00916942">NCT00916942</a>.</p

Motor Adaptation Scaled by the Difficulty of a Secondary Cognitive Task

Background: Motor learning requires evaluating performance in previous movements and modifying future movements. The executive system, generally involved in planning and decision-making, could monitor and modify behavior in response to changes in task difficulty or performance. Here we aim to identify the quantitative cognitive contribution to responsive and adaptive control to identify possible overlap between cognitive and motor processes. Methodology/Principal Findings: We developed a dual-task experiment that varied the trial-by-trial difficulty of a secondary cognitive task while participants performed a motor adaptation task. Subjects performed a difficulty-graded semantic categorization task while making reaching movements that were occasionally subjected to force perturbations. We find that motor adaptation was specifically impaired on the most difficult to categorize trials. Conclusions/Significance: We suggest that the degree of decision-level difficulty of a particular categorization differentially burdens the executive system and subsequently results in a proportional degradation of adaptation. Our results suggest

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability