A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the <em>Saccharomyces cerevisiae</em> Elongator complex

Elongator is a conserved, multi-protein complex discovered in Saccharomyces cerevisiae, loss of which confers a range of pleiotropic phenotypes. Elongator in higher eukaryotes is required for normal growth and development and a mutation in the largest subunit of human Elongator (Elp1) causes familial dysautonomia, a severe recessive neuropathy. Elongator promotes addition of mcm(5) and ncm(5) modifications to uridine in the tRNA anticodon ‘wobble’ position in both yeast and higher eukaryotes. Since these modifications are required for the tRNAs to function efficiently, a translation defect caused by hypomodified tRNAs may therefore underlie the variety of phenotypes associated with Elongator dysfunction. The Elp1 carboxy-terminal domain contains a highly conserved arginine/lysine-rich region that resembles a nuclear localization sequence (NLS). Using alanine substitution mutagenesis, we show that this region is essential for Elongator's function in tRNA wobble uridine modification. However, rather than acting to determine the nucleo-cytoplasmic distribution of Elongator, we find that the basic region plays a critical role in a novel interaction between tRNA and the Elp1 carboxy-terminal domain. Thus the conserved basic region in Elp1 may be essential for tRNA wobble uridine modification by acting as tRNA binding motif

Sequence variation in the haemagglutinin-neuraminidase gene of human parainfluenza virus type 3 isolates in the UK

The sequence variation in a 934 base-pair region of the gene encoding the haemagglutinin-neuraminidase of five human parainfluenza virus type 3 (HPIV3) isolates was determined together with that of a prototype UK strain. All of the clinical isolates were from the Manchester area of the UK and were obtained in 1990. 1991 and 1993. The gene segment was amplified by the polymerase chain reaction using HPIVB-specific oligonucleotide primers. The nucleotide homology of the strains was high, around 99% and specific differences in the UK sequences when compared with that of the US prototype strain were identified. In addition, a number of isolate-specific differences were seen. No correlation was detected between the observed nucleotide mutations and the year of isolation, which supports the hypothesis that HPIV3 shows cocirculation of a heterogeneous population of viruses rather than varying with time in a linear fashion. However, the data suggested that geographically-defined genetic lineages of HPIV3 may exist

A national survey of the chemotherapy regimens used to treat small cell lung cancer (SCLC) in the United Kingdom

Many chemotherapy regimens are used for treating SCLC in the United Kingdom, but it is not known, in any detail, which regimens are used, by which specialists, for which types of patient. We conducted a survey among all medical and clinical oncologists, respiratory physicians and general physicians with respiratory interest in the United Kingdom to find out. The questionnaire asked for the number of SCLC patients treated annually; how many were given chemotherapy; the drugs, doses and schedules chosen according to prognostic group (as defined by the clinician); and the reasons for choice of regimen. 1214 questionnaires were sent out, and responses were received from 1070 (88%) clinicians; 266 (25%) of these treated SCLC with chemotherapy. Of 4674 patients given chemotherapy annually, 36% were given it by clinical oncologists, 30% by medical oncologists, 27% by respiratory physicians, and 7% by general physicians. In all, 34 regimens were reported with 151 different combinations of dose and schedule. In 2311 good prognosis patients, 23 regimens were used, the commonest being ACE (doxorubicin, cyclophosphamide, etoposide), ICbE (ifosfamide, carboplatin, etoposide), CAV (cyclophosphamide, doxorubicin, vincristine), CbE (carboplatin, etoposide), and PE (cisplatin, etoposide). In 1517 poor prognosis patients, 21 regimens were used, the commonest being CAV, EV (etoposide, vincristine), CbE, CAV alternating with PE, and oral etoposide. 452 patients were treated regardless of prognosis and for 219 no prognostic criteria were specified. The remaining 175 were given second-line chemotherapy or were given regimens chosen to avoid toxicity or because of intercurrent disease or other reasons. The main reasons affecting choice of regimen were routine local practice, patients' convenience, quality of life considerations, trial results and cost. The results show wide variation in routine practice and will be useful in reporting and planning clinical trials and in deciding on local treatment policies. © 2001 Cancer Research Campaign http://www.bjcancer.co

Cold Induction of EARLI1, a Putative Arabidopsis Lipid Transfer Protein, Is Light and Calcium Dependent

As sessile organisms, plants must adapt to their environment. One approach toward understanding this adaptation is to investigate environmental regulation of gene expression. Our focus is on the environmental regulation of EARLI1, which is activated by cold and long-day photoperiods. Cold activation of EARLI1 in short-day photoperiods is slow, requiring several hours at 4ºC to detect an increase in mRNA abundance. EARLI1 is not efficiently cold-activated in etiolated seedlings, suggesting that photomorphogenesis is necessary for its cold activation. Cold activation of EARLI1 is inhibited in the presence of the calcium channel blocker lanthanum chloride or the calcium chelator EGTA. Addition of the calcium ionophore Bay K8644 results in cold-independent activation of EARLI1. These data suggest that EARLI1 is not an immediate target of the cold response, and that calcium flux affects its expression. EARLI1 is a putative secreted protein and has motifs found in lipid transfer proteins. Over-expression of EARLI1 in transgenic plants results in reduced electrolyte leakage during freezing damage, suggesting that EARLI1 may affect membrane or cell wall stability in response to low temperature stress

Prospect theory does not describe the feedback-related negativity value function.

Humans handle uncertainty poorly. Prospect theory accounts for this with a value function in which possible losses are overweighted compared to possible gains, and the marginal utility of rewards decreases with size. fMRI studies have explored the neural basis of this value function. A separate body of research claims that prediction errors are calculated by midbrain dopamine neurons. We investigated whether the prospect theoretic effects shown in behavioral and fMRI studies were present in midbrain prediction error coding by using the feedback-related negativity, an ERP component believed to reflect midbrain prediction errors. Participants' stated satisfaction with outcomes followed prospect theory but their feedback-related negativity did not, instead showing no effect of marginal utility and greater sensitivity to potential gains than losses

454-Pyrosequencing: A Molecular Battiscope for Freshwater Viral Ecology

Viruses, the most abundant biological entities on the planet, are capable of infecting organisms from all three branches of life, although the majority infect bacteria where the greatest degree of cellular diversity lies. However, the characterization and assessment of viral diversity in natural environments is only beginning to become a possibility. Through the development of a novel technique for the harvest of viral DNA and the application of 454 pyrosequencing, a snapshot of the diversity of the DNA viruses harvested from a standing pond on a cattle farm has been obtained. A high abundance of viral genotypes (785) were present within the virome. The absolute numbers of lambdoid and Shiga toxin (Stx) encoding phages detected suggested that the depth of sequencing had enabled recovery of only ca. 8% of the total virus population, numbers that agreed within less than an order of magnitude with predictions made by rarefaction analysis. The most abundant viral genotypes in the pond were bacteriophages (93.7%). The predominant viral genotypes infecting higher life forms found in association with the farm were pathogens that cause disease in cattle and humans, e.g. members of the Herpesviridae. The techniques and analysis described here provide a fresh approach to the monitoring of viral populations in the aquatic environment, with the potential to become integral to the development of risk analysis tools for monitoring the dissemination of viral agents of animal, plant and human diseases

Management of acute dental pain: a practical approach for primary health care providers

Reproduced with permission from Australian Prescriber The document attached has been archived with permission from the publisher/copyright holderA detailed history and examination will identify the cause of dentally-related pain in most emergency situations. Sharp, shooting pain can be caused by inflammation in the pulp or exposure of the dentine. Dull throbbing pain has several causes including ulcerative gingivitis, dental caries and food impaction. Simple treatment will usually alleviate the symptoms until patients can be seen by a dentist. Prescription of antibiotics is usually not indicated.John Wetherell, Lindsay Richards, Paul Sambrook, Grant Townsen

Selection for Catalytic Function with Nucleic Acids

For in vitro selection of catalytic polynucleotides, each new protocol must be designed to harness the desired catalytic activity to help propel the selection process itself. This unit gives guidelines for design of in vitro selection experiments for catalytic function. It outlines several representative protocols as examples of successful selection experiments, providing a conceptual basis for the design and implementation of new selective‐amplification protocols for nucleic acids.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143687/1/cpnc0904.pd