Identification of critical residues in loop E in the 5-HT(3AS)R binding site

BACKGROUND: The serotonin type 3 receptor (5-HT(3)R) is a member of a superfamily of ligand gated ion channels. All members of this family share a large degree of sequence homology and presumably significant structural similarity. A large number of studies have explored the structure-function relationships of members of this family, particularly the nicotinic and GABA receptors. This information can be utilized to gain additional insights into specific structural and functional features of other receptors in this family. RESULTS: Thirteen amino acids in the mouse 5-HT(3AS)R that correspond to the putative E binding loop of the nicotinic α7 receptor were chosen for mutagenesis. Due to the presence of a highly conserved glycine in this region, it has been suggested that this binding loop is comprised of a hairpin turn and may form a portion of the ligand-binding site in this ion channel family. Mutation of the conserved glycine (G147) to alanine eliminated binding of the 5-HT(3)R antagonist [(3)H]granisetron. Three tyrosine residues (Y140, Y142 and Y152) also significantly altered the binding of 5-HT(3)R ligands. Mutations in neighboring residues had little or no effect on binding of these ligands to the 5-HT(3AS)R. CONCLUSION: Our data supports a role for the putative E-loop region of the 5-HT(3)R in the binding of 5-HT, mCPBG, d-tc and lerisetron. 5-HT and mCPBG interact with Y142, d-tc with Y140 and lerisetron with both Y142 and Y152. Our data also provides support for the hypothesis that this region of the receptor is present in a loop structure

What does the Iowa farmer want from radio market news?

Most of the results in this report are based on a personal interview survey of Iowa open-country farmers. Ninety-six percent (178,000) of the operators of Iowa open-country farms sold one or more of Iowa\u27s six top cash farm income products in 1948. About 92 percent of the open-country zone farm operators listened to day-to-day broadcasts of market reports* before making their last sales of butcher hogs, cattle, corn, soybeans, cream or whole milk and eggs

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis. This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep. Other symptoms include cognitive problems, unrefreshing or disturbed sleep, generalized or localized pain, lightheadedness, and additional symptoms in multiple organ systems. While some young patients can attend school, on a full or part-time basis, many others are wheelchair dependent, housebound, or bedbound. Prevalence estimates for pediatric ME/CFS vary from 0.1 to 0.5%. Because there is no diagnostic test for ME/CFS, diagnosis is purely clinical, based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Co-existing medical conditions including orthostatic intolerance (OI) are common. Successful management is based on determining the optimum balance of rest and activity to help prevent post-exertional symptom worsening. Medications are helpful to treat pain, insomnia, OI and other symptoms. The published literature on ME/CFS and specifically that describing the diagnosis and management of pediatric ME/CFS is very limited. Where published studies are lacking, recommendations are based on the clinical observations and practices of the authors

CORE Technology and Exact Hamiltonian Real-Space Renormalization Group Transformations

The COntractor REnormalization group (CORE) method, a new approach to solving Hamiltonian lattice systems, is presented. The method defines a systematic and nonperturbative means of implementing Kadanoff-Wilson real-space renormalization group transformations using cluster expansion and contraction techniques. We illustrate the approach and demonstrate its effectiveness using scalar field theory, the Heisenberg antiferromagnetic chain, and the anisotropic Ising chain. Future applications to the Hubbard and t-J models and lattice gauge theory are discussed.Comment: 65 pages, 9 Postscript figures, uses epsf.st

Search for Millicharged Particles at SLAC

Particles with electric charge q < 10^(-3)e and masses in the range 1--100 MeV/c^2 are not excluded by present experiments. An experiment uniquely suited to the production and detection of such "millicharged" particles has been carried out at SLAC. This experiment is sensitive to the infrequent excitation and ionization of matter expected from the passage of such a particle. Analysis of the data rules out a region of mass and charge, establishing, for example, a 95%-confidence upper limit on electric charge of 4.1X10^(-5)e for millicharged particles of mass 1 MeV/c^2 and 5.8X10^(-4)e for mass 100 MeV/c^2.Comment: 4 pages, REVTeX, multicol, 3 figures. Minor typo corrected. Submitted to Physical Review Letter

Comparison of Hermetic Storage of Wheat with Traditional Storage Methods in India

India is among the countries experiencing high postharvest losses. Four hermetic bags, two metallic bins, and two gunny bag (also known as jute or burlap bag) piles each containing 1 tonne of wheat were instrumented with temperature, relative humidity, and carbon dioxide sensors. Representative samples from each structure were collected each month and tests for moisture, germination, insect-damaged grain, and milling yield were performed. After nine months, wheat stored in hermetic bags had higher germination (87%) and lower insect-damaged grain percentages (0% to 0.33% with a mean value of 0.2%). Hermetic bags with deliberately introduced Rhyzopertha dominica successfully eliminated the pests. Gunny bag piles had infestations; metallic bins also were infested. Wheat moisture content in all structures varied depending upon ambient conditions; moisture variation was largest in gunny bag piles. Milling yields were lowest for gunny bag piles. Hermetic bags can be an effective and environmentally friendly solution for reducing storage losses of wheat in India

Worldwide food recall patterns over an eleven month period: A country perspective.

<p>Abstract</p> <p>Background</p> <p>Following the World Health Organization Forum in November 2007, the Beijing Declaration recognized the importance of food safety along with the rights of all individuals to a safe and adequate diet. The aim of this study is to retrospectively analyze the patterns in food alert and recall by countries to identify the principal hazard generators and gatekeepers of food safety in the eleven months leading up to the Declaration.</p> <p>Methods</p> <p>The food recall data set was collected by the Laboratory of the Government Chemist (LGC, UK) over the period from January to November 2007. Statistics were computed with the focus reporting patterns by the 117 countries. The complexity of the recorded interrelations was depicted as a network constructed from structural properties contained in the data. The analysed network properties included degrees, weighted degrees, modularity and <it>k</it>-core decomposition. Network analyses of the reports, based on 'country making report' (<it>detector</it>) and 'country reported on' (<it>transgressor</it>), revealed that the network is organized around a dominant core.</p> <p>Results</p> <p>Ten countries were reported for sixty per cent of all faulty products marketed, with the top 5 countries having received between 100 to 281 reports. Further analysis of the dominant core revealed that out of the top five transgressors three made no reports (in the order China > Turkey > Iran). The top ten detectors account for three quarters of reports with three > 300 (Italy: 406, Germany: 340, United Kingdom: 322).</p> <p>Conclusion</p> <p>Of the 117 countries studied, the vast majority of food reports are made by 10 countries, with EU countries predominating. The majority of the faulty foodstuffs originate in ten countries with four major producers making no reports. This pattern is very distant from that proposed by the Beijing Declaration which urges all countries to take responsibility for the provision of safe and adequate diets for their nationals.</p

Venous thromboembolism research priorities: A scientific statement from the American Heart Association and the International Society on Thrombosis and Haemostasis

Venous thromboembolism (VTE) is a major cause of morbidity and mortality. The impact of the Surgeon General’s Call to Action in 2008 has been lower than expected given the public health impact of this disease. This scientific statement highlights future research priorities in VTE, developed by experts and a crowdsourcing survey across 16 scientific organizations. At the fundamental research level (T0), researchers need to identify pathobiologic causative mechanisms for the 50% of patients with unprovoked VTE and better understand mechanisms that differentiate hemostasis from thrombosis. At the human level (T1), new methods for diagnosing, treating, and preventing VTE will allow tailoring of diagnostic and therapeutic approaches to individuals. At the patient level (T2), research efforts are required to understand how foundational evidence impacts care of patients (eg, biomarkers). New treatments, such as catheter‐based therapies, require further testing to identify which patients are most likely to experience benefit. At the practice level (T3), translating evidence into practice remains challenging. Areas of overuse and underuse will require evidence‐based tools to improve care delivery. At the community and population level (T4), public awareness campaigns need thorough impact assessment. Large population‐based cohort studies can elucidate the biologic and environmental underpinings of VTE and its complications. To achieve these goals, funding agencies and training programs must support a new generation of scientists and clinicians who work in multidisciplinary teams to solve the pressing public health problem of VTE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156163/2/rth212373_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156163/1/rth212373.pd