2007 Annual progress report synopsis of the Center for Structures of Membrane Proteins

A synopsis of the 2007 annual progress report for the Center for Structures of Membrane Proteins, a specialized center of the Protein Structure Initiative

Nitrogen transfer from forage legumes to nine neighbouring plants in a multi-species grassland

Legumes play a crucial role in nitrogen supply to grass-legume mixtures for ruminant fodder. To quantify N transfer from legumes to neighbouring plants in multi-species grasslands we established a grass-legume-herb mixture on a loamy-sandy site in Denmark. White clover (Trifolium repens L.), red clover (Trifolium pratense L.) and lucerne (Medicago sativa L.) were leaf-labelled with 15N enriched urea during one growing season. N transfer to grasses (Lolium perenne L. and xfestulolium), white clover, red clover, lucerne, birdsfoot trefoil (Lotus corniculatus L.), chicory (Cichorium intybus L.), plantain (Plantago lanceolata L.), salad burnet (Sanguisorba minor L.)and caraway (Carum carvi L.) was assessed. Neighbouring plants contained greater amounts of N derived from white clover (4.8 gm-2) compared with red clover (2.2 gm-2) and lucerne (1.1 gm-2). Grasses having fibrous roots received greater amounts of N from legumes than dicotyledonous plants which generally have taproots. Slurry application mainly increased N transfer from legumes to grasses. During the growing season the three legumes transferred approximately 40 kg N ha-1 to neighbouring plants. Below-ground N transfer from legumes to neighbouring plants differed among nitrogen donors and nitrogen receivers and may depend on root characteristics and regrowth strategies of plant species in the multi-species grassland

TOI-3235 b: A Transiting Giant Planet around an M4 Dwarf Star

We present the discovery of TOI-3235 b, a short-period Jupiter orbiting an M dwarf with a stellar mass close to the critical mass at which stars transition from partially to fully convective. TOI-3235 b was first identified as a candidate from TESS photometry and confirmed with radial velocities from ESPRESSO and ground-based photometry from HATSouth, MEarth-South, TRAPPIST-South, LCOGT, and ExTrA. We find that the planet has a mass of 0.665 ± 0.025 M J and a radius of 1.017 ± 0.044 R J. It orbits close to its host star, with an orbital period of 2.5926 days but has an equilibrium temperature of ≈ 604 K, well below the expected threshold for radius inflation of hot Jupiters. The host star has a mass of 0.3939 ± 0.0030 M ☉, a radius of 0.3697 ± 0.0018 R ☉, an effective temperature of 3389 K, and a J-band magnitude of 11.706 ± 0.025. Current planet formation models do not predict the existence of gas giants such as TOI-3235 b around such low-mass stars. With a high transmission spectroscopy metric, TOI-3235 b is one of the best-suited giants orbiting M dwarfs for atmospheric characterization

Evaluation of water properties in HEA–HEMA hydrogels swollen in aqueous-PEG solutions using thermoanalytical techniques

Hydrogels are polymeric materials used in many pharmaceutical and biomedical applications due to their ability to form 3D hydrophilic polymeric networks, which can absorb large amounts of water. In the present work, polyethylene glycols (PEG) were introduced into the hydrogel liquid phase in order to improve the mechanical properties of hydrogels composed of 2-hydroxyethylacrylate and 2-hydroxyethylmethacrylate (HEA–HEMA) synthesized with different co-monomer compositions and equilibrated in water or in 20 % water–PEG 400 and 600 solutions. The thermoanalytical techniques [differential scanning calorimetry (DSC) and thermogravimetry (TG)] were used to evaluate the amount and properties of free and bound water in HEA–HEMA hydrogels. The internal structure and the mechanical properties of hydrogels were studied using scanning electron microscopy and friability assay. TG “loss-on-drying” experiments were applied to study the water-retention properties of hydrogels, whereas the combination of TG and DSC allowed estimating the total amount of freezable and non-freezing water in hydrogels. The results show that the addition of viscous co-solvent (PEG) to the liquid medium results in significant improvement of the mechanical properties of HEA–HEMA hydrogels and also slightly retards the water loss from the hydrogels. A redistribution of free and bound water in the hydrogels equilibrated in mixed solutions containing 20 vol% of PEGs takes place

Radiographs and low field MRI (0.2T) as predictors of efficacy in a weight loss trial in obese women with knee osteoarthritis

<p>Abstract</p> <p>Background</p> <p>To study the predictive value of baseline radiographs and low-field (0.2T) MRI scans for the symptomatic outcome of clinically significant weight loss in obese patients with knee osteoarthritis.</p> <p>Methods</p> <p>In this study we hypothesize that imaging variables assessed with radiographs and MRI scans pre-treatment can predict the symptomatic changes following a recommended clinically significant weight reduction Patients were recruited from the Department of Rheumatology, Frederiksberg Hospital, Denmark. Eligibility criteria were: age >18 years; primary osteoarthritis according to ACR; BMI > 28 kg/m2; motivation for weight loss. Subjects were randomly assigned to either intervention by low-energy diet (LED) for 8 weeks followed by another 24 weeks of dietary instruction or control-group. MRI scans and radiographs were scored for structural changes and these parameters were examined as independent predictors of changes in osteoarthritis symptoms after 32 weeks. The outcome assessor and statistician were blinded to group allocation.</p> <p>Results</p> <p>No significant correlations were found between imaging variables and changes in Western Ontario and McMaster Universities Index of Osteoarthritis (Spearman's test, r < 0.33 and P > 0.07).</p> <p>Only the LED group achieved a weight loss, with a mean difference of 16.3 kg (95%CI: 13.4-19.2;P < 0.0001) compared to the control group. The total WOMAC index showed a significant difference favouring LED, with a group mean difference of - 321.3 mm (95%CI: -577.5 to -65.1 mm; P = 0.01). No significant adverse events were reported.</p> <p>Conclusion</p> <p>Stage of joint destruction, assessed on either radiographs or low-field MRI (0.2T), does not preclude a symptoms relief following a clinically relevant weight loss in elderly obese female patients with knee osteoarthritis.</p

The ANTOP study: focal psychodynamic psychotherapy, cognitive-behavioural therapy, and treatment-as-usual in outpatients with anorexia nervosa - a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Anorexia nervosa is a serious eating disorder leading to high morbidity and mortality as a result of both malnutrition and suicide. The seriousness of the disorder requires extensive knowledge of effective treatment options. However, evidence for treatment efficacy in this area is remarkably weak. A recent Cochrane review states that there is an urgent need for large, well-designed treatment studies for patients with anorexia nervosa. The aim of this particular multi-centre study is to evaluate the efficacy of two standardized outpatient treatments for patients with anorexia nervosa: focal psychodynamic (FPT) and cognitive behavioural therapy (CBT). Each therapeutic approach is compared to a "treatment-as-usual" control group.</p> <p>Methods/Design</p> <p>237 patients meeting eligibility criteria are randomly and evenly assigned to the three groups – two intervention groups (CBT and FPT) and one control group. The treatment period for each intervention group is 10 months, consisting of 40 sessions respectively. Body weight, eating disorder related symptoms, and variables of therapeutic alliance are measured during the course of treatment. Psychotherapy sessions are audiotaped for adherence monitoring. The treatment in the control group, both the dosage and type of therapy, is not regulated in the study protocol, but rather reflects the current practice of established outpatient care. The primary outcome measure is the body mass index (BMI) at the end of the treatment (10 months after randomization).</p> <p>Discussion</p> <p>The study design surmounts the disadvantages of previous studies in that it provides a randomized controlled design, a large sample size, adequate inclusion criteria, an adequate treatment protocol, and a clear separation of the treatment conditions in order to avoid contamination. Nevertheless, the study has to deal with difficulties specific to the psychopathology of anorexia nervosa. The treatment protocol allows for dealing with the typically occurring medical complications without dropping patients from the protocol. However, because patients are difficult to recruit and often ambivalent about treatment, a drop-out rate of 30% is assumed for sample size calculation. Due to the ethical problem of denying active treatment to patients with anorexia nervosa, the control group is defined as "treatment-as-usual".</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN72809357</p

L1TD1 Is a Marker for Undifferentiated Human Embryonic Stem Cells

Human embryonic stem cells (hESC) are stem cells capable of differentiating into cells representative of the three primary embryonic germ layers. There has been considerable interest in understanding the mechanisms regulating stem cell pluripotency, which will ultimately lead to development of more efficient methods to derive and culture hESC. In particular, Oct4, Sox2 and Nanog are transcription factors known to be important in maintenance of hESC. However, many of the downstream targets of these transcription factors are not well characterized. Furthermore, it remains unknown whether additional novel stem cell factors are involved in the establishment and maintenance of the stem cell state.Here we show that a novel gene, L1TD1 (also known as FLJ10884 or ECAT11), is abundantly expressed in undifferentiated hESC. Differentiation of hESC via embryoid body (EB) formation or BMP4 treatment results in the rapid down-regulation of L1TD1 expression. Furthermore, populations of undifferentiated and differentiated hESC were sorted using the stem cell markers SSEA4 and TRA160. Our results show that L1TD1 is enriched in the SSEA4-positive or TRA160-positive population of hESC. Using chromatin immunoprecipitation we found enriched association of Nanog to the predicted promoter region of L1TD1. Furthermore, siRNA-mediated knockdown of Nanog in hESC also resulted in downregulation of L1TD1 expression. Finally, using luciferase reporter assay we demonstrated that Nanog can activate the L1TD1 upstream promoter region. Altogether, these results provide evidence that L1TD1 is a downstream target of Nanog.Taken together, our results suggest that L1TD1 is a downstream target of Nanog and represents a useful marker for identifying undifferentiated hESC

"It doesn't do any harm, but patients feel better": a qualitative exploratory study on gastroenterologists' perspectives on the role of antidepressants in inflammatory bowel disease

Background: Interest in psychological factors in patients with inflammatory bowel disease (IBD) has increased in recent years. It has even been proposed that treating psychological co-morbidities with antidepressants may control disease activity and improve quality of life. Despite this, there is no data on gastroenterologists' attitudes to, and experiences with, antidepressant therapy in patients with IBD. Methods: We conducted semi-structured interviews with 18 gastroenterologists associated with metropolitan teaching hospitals. Qualitative content analysis was used to examine their responses. Results: Seventy-eight percent of gastroenterologists had treated IBD patients with antidepressants for pain, depression and/or anxiety, and insomnia. Antidepressants were reported to be useful in improving psychosocial well-being, quality of life, and self-management of the disease by patients. However, in this group of gastroenterologists, there appears to be skepticism towards psychological disorders themselves or antidepressant therapy having a central role in either the causation of IBD or its clinical course. Nevertheless, these gastroenterologists were receptive to the idea of conducting a trial of the role of antidepressants in IBD. Conclusion: While the majority of specialists have treated IBD patients with antidepressants, there is considerable skepticism with regard to efficacy of antidepressive therapy or the role of psychological factors in the outcome of IBD patients.Antonina A Mikocka-Walus, Deborah A Turnbull, Nicole T Moulding, Ian G Wilson, Jane M Andrews and Gerald J Holtman

Acoustic Oddball during NREM Sleep: A Combined EEG/fMRI Study

Background: A condition vital for the consolidation and maintenance of sleep is generally reduced responsiveness to external stimuli. Despite this, the sleeper maintains a level of stimulus processing that allows to respond to potentially dangerous environmental signals. The mechanisms that subserve these contradictory functions are only incompletely understood. Methodology/Principal Findings: Using combined EEG/fMRI we investigated the neural substrate of sleep protection by applying an acoustic oddball paradigm during light NREM sleep. Further, we studied the role of evoked K-complexes (KCs), an electroencephalographic hallmark of NREM sleep with a still unknown role for sleep protection. Our main results were: (1) Other than in wakefulness, rare tones did not induce a blood oxygenation level dependent (BOLD) signal increase in the auditory pathway but a strong negative BOLD response in motor areas and the amygdala. (2) Stratification of rare tones by the presence of evoked KCs detected activation of the auditory cortex, hippocampus, superior and middle frontal gyri and posterior cingulate only for rare tones followed by a KC. (3) The typical high frontocentral EEG deflections of KCs were not paralleled by a BOLD equivalent. Conclusions/Significance: We observed that rare tones lead to transient disengagement of motor and amygdala responses during light NREM sleep. We interpret this as a sleep protective mechanism to delimit motor responses and to reduce the sensitivity of the amygdala towards further incoming stimuli. Evoked KCs are suggested to originate from a brain state wit

Investigating the effect of intra-operative infiltration with local anaesthesia on the development of chronic postoperative pain after inguinal hernia repair. A randomized placebo controlled triple blinded and group sequential study design [NCT00484731]

<p>Abstract</p> <p>Background</p> <p>Inguinal hernia repair is one of the most frequently performed procedures in Switzerland (15'000/year). The most common complication postoperatively is development of chronic pain in up to 30% of all patients irrespective of the operative technique.</p> <p>Methods/Design</p> <p>264 patients scheduled for an inguinal hernia repair using one of three procedures (Lichtenstein, Barwell and TEP = total extraperitoneal hernioplasty) are being randomly allocated intra-operatively into two groups. Group I patients receive a local injection of 20 ml Carbostesin^®0.25% at the end of the operation according to a standardised procedure. Group II patients get a 20 ml placebo (0.9% Saline) injection. We use pre-filled identically looking syringes for blinded injection, i.e. the patient, the surgeon and the examinator who performs the postoperative clinical follow-ups remain unaware of group allocation. The primary outcome of the study is the occurrence of developing chronic pain (defined as persistent pain at 3 months FU) measured by VAS and Pain Matcher^®device (Cefar Medical AB, Lund, Sweden).</p> <p>The study started on July 2006. In addition to a sample size re-evaluation three interim analyses are planned after 120, 180 and 240 patients had finished their 3-months follow-up to allow for early study termination.</p> <p>Discussion</p> <p>Using a group sequential study design the minimum number of patients are enrolled to reach a valid conclusion before the end of the study.</p> <p>To limit subjectivity, both a VAS and the Pain Matcher^®device are used for the evaluation of pain. This allows us also to compare these two methods and further assess the use of Pain Matcher^®in clinical routine.</p> <p>The occurrence of chronic pain after inguinal hernia repair has been in focus of several clinical studies but the reduction of it has been rarely investigated. We hope to significantly reduce the occurrence of this complication with our investigated intervention.</p> <p>Trial Registration</p> <p>Our trial has been registered at ClinicalTrials.gov. The trial registration number is: [NCT00484731].</p