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Characterizing the stress/defense transcriptome of Arabidopsis.

BACKGROUND: To understand the gene networks that underlie plant stress and defense responses, it is necessary to identify and characterize the genes that respond both initially and as the physiological response to the stress or pathogen develops. We used PCR-based suppression subtractive hybridization to identify Arabidopsis genes that are differentially expressed in response to ozone, bacterial and oomycete pathogens and the signaling molecules salicylic acid (SA) and jasmonic acid. RESULTS: We identified a total of 1,058 differentially expressed genes from eight stress cDNA libraries. Digital northern analysis revealed that 55% of the stress-inducible genes are rarely transcribed in unstressed plants and 17% of them were not previously represented in Arabidopsis expressed sequence tag databases. More than two-thirds of the genes in the stress cDNA collection have not been identified in previous studies as stress/defense response genes. Several stress-responsive cis-elements showed a statistically significant over-representation in the promoters of the genes in the stress cDNA collection. These include W- and G-boxes, the SA-inducible element, the abscisic acid response element and the TGA motif. CONCLUSIONS: The stress cDNA collection comprises a broad repertoire of stress-responsive genes encoding proteins that are involved in both the initial and subsequent stages of the physiological response to abiotic stress and pathogens. This set of stress-, pathogen- and hormone-modulated genes is an important resource for understanding the genetic interactions underlying stress signaling and responses and may contribute to the characterization of the stress transcriptome through the construction of standardized specialized arrays.

Arabidopsis↗

Prime site binding inhibitors of a serine protease: NS3/4A of hepatitis C virus.

Serine proteases are the most studied class of proteolytic enzymes and a primary target for drug discovery. Despite the large number of inhibitors developed so far, very few make contact with the prime site of the enzyme, which constitutes an almost untapped opportunity for drug design. In the course of our studies on the serine protease NS3/4A of hepatitis C virus (HCV), we found that this enzyme is an excellent example of both the opportunities and the challenges of such design. We had previously reported on two classes of peptide inhibitors of the enzyme: (a) product inhibitors, which include the P(6)-P(1) region of the substrate and derive much of their binding energy from binding of their C-terminal carboxylate in the active site, and (b) decapeptide inhibitors, which span the S(6)-S(4)' subsites of the enzyme, whose P(2)'-P(4)' tripeptide fragment crucially contributes to potency. Here we report on further work, which combined the key binding elements of the two series and led to the development of inhibitors binding exclusively to the prime site of NS3/4A. We prepared a small combinatorial library of tripeptides, capped with a variety of constrained and unconstrained diacids. The SAR was derived from multiple analogues of the initial micromolar lead. Binding of the inhibitor(s) to the enzyme was further characterized by circular dichroism, site-directed mutagenesis, a probe displacement assay, and NMR to unequivocally prove that, according to our design, the bound inhibitor(s) occupies (occupy) the S' subsite and the active site of the protease. In addition, on the basis of the information collected, the tripeptide series was evolved toward reduced peptide character, reduced molecular weight, and higher potency. Beyond their interest as HCV antivirals, these compounds represent the first example of prime site inhibitors of a serine protease. We further suggest that the design of an inhibitor with an analogous binding mode may be possible for other serine proteases.

Amino Acid Sequence↗

How to acquire new biological activities in old compounds by computer prediction.

Due to the directed way of testing chemical compounds' in drug research and development many projects fail because serious adverse effects and toxicity are discovered too late, and many existing prospective activities remain unstudied. Evaluation of the general biological potential of molecules is possible using a computer program PASS that predicts more than 780 pharmacological effects, mechanisms of action, mutagenicity, carcinogenicity, etc. on the basis of structural formulae of compounds, with average accuracy approximately 85%. PASS applications to both databases of available samples included hundreds of thousands compounds, and small collections of compounds synthesized by separate medicinal chemists are described. It is shown that 880 compounds from Prestwick chemical library represent a very diverse pharmacological space. New activities can be found in existing compounds by prediction. Therefore, on this basis, the selection of compounds with required and without unwanted properties is possible. Even when PASS cannot predict very new activities, it may recognize some unwanted actions at the early stage of R&D, providing the medicinal chemist with the means to increase the efficiency of projects.

Computer Simulation↗

A two-step strategy for constructing specifically self-subtracted cDNA libraries.

We have developed a new strategy for producing subtracted cDNA libraries that is optimized for connective and epithelial tissues, where a few exceptionally abundant (super-prevalent) RNA species account for a large fraction of the total mRNA mass. Our method consists of a two-step subtraction of the most abundant mRNAs: the first step involves a novel use of oligo-directed RNase H digestion to lower the concentration of tissue-specific, super-prevalent RNAs. In the second step, a highly specific subtraction is achieved through hybridization with probes from a 3'-end ESTs collection. By applying this technique in skeletal muscle, we have constructed subtracted cDNA libraries that are effectively enriched for genes expressed at low levels. We further report on frequent premature termination of transcription in human muscle mitochondria and discuss the importance of this phenomenon in designing subtractive approaches. The tissue-specific collections of cDNA clones generated by our method are particularly well suited for expression profiling.

DNA, Complementary↗

Laparoscopic repair for perforated peptic ulcer disease.

BACKGROUND: Perforated peptic ulcer is a common abdominal disease that is treated by surgery. The development of laparoscopic surgery has changed the way to treat such abdominal surgical emergencies. The results of some clinical trials suggest that laparoscopic surgery could be a better strategy than open surgery in the correction of perforated peptic ulcer but the evidence is not strongly in favour or against this intervention. OBJECTIVES: To measure the effect of laparoscopic surgical treatment versus open surgical treatment in patients with a diagnosis of perforated peptic ulcer in relation to abdominal septic complications, surgical wound infection, extra-abdominal complications, hospital length of stay and direct costs. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 2, 2004), PubMed/MEDLINE (1966 to July 2004), EMBASE (1985 to November 2004) and LILACS (1988 to November 2004) as well as reference lists of relevant articles. SELECTION CRITERIA: Randomised clinical trials comparing laparoscopic surgery versus open surgery for the repair of perforated peptic ulcer using any mechanical method of closure (suture, omental patch or fibrin sealant). DATA COLLECTION AND ANALYSIS: Primary outcome measures included proportion of septic and other abdominal complications (surgical site infection, suture leakage, intra-abdominal abscess, postoperative ileus) and extra-abdominal complications (pulmonary). Secondary outcomes included mortality, time to return to normal diet, time of nasogastric aspiration, hospital length of stay and costs. Outcomes were summarized by reporting odds ratios and 95% confidence intervals, using the fixed-effect model. MAIN RESULTS: We included two randomised clinical trials, which were of acceptable quality. We found no statistically significant differences between laparoscopic and open surgery in the proportion of abdominal septic complications (OR 0.66, 95% CI 0.30 to 1.47), pulmonary complications (OR 0.37, 95% CI 0.11 to 1.31) or actual number of septic abdominal complications (OR 0.72, 95% CI 0.33 to 1.58). Heterogeneity was significant only for pulmonary complications. AUTHORS' CONCLUSIONS: This systematic review suggests that a decrease in septic abdominal complications may exist when laparoscopic surgery is used to correct perforated peptic ulcer. However, it is necessary to develop more randomised controlled trials that include a greater number of patients to confirm such an assumption, guaranteeing a long learning curve for participating surgeons. With the information provided by the available clinical trials it could be said that laparoscopic surgery results are not clinically different from those of open surgery.

Humans↗

Day care versus in-patient surgery for age-related cataract.

BACKGROUND: Age-related cataract accounts for more than 40% of cases of blindness in the world with the majority of people who are blind from cataract found in the developing world. With the increased number of people with cataract there is an urgent need for cataract surgery to be made available as a day-care procedure. OBJECTIVES: The objective of this review is to provide reliable evidence regarding the safety, feasibility, effectiveness and cost-effectiveness of cataract extraction performed as day-care versus in-patient procedure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register) on The Cochrane Library (Issue 4 2002), MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002) and LILACS (November 2002). SELECTION CRITERIA: This review includes randomised controlled trials comparing day-care and in-patient surgery for age-related cataract. The primary outcome was the achievement of a satisfactory visual acuity six weeks after the operation. DATA COLLECTION AND ANALYSIS: Although two trials are included in the review, adequate data were available for only one trial and therefore pooling of data from studies was not attempted. A descriptive summary is presented. MAIN RESULTS: Two trials, involving a total of 1284 people, are included in this review. One trial reported statistically significant differences in early postoperative complication rates in the day-care group, with an increased risk of increased intraocular pressure, which had no clinical relevance to visual outcomes four months postoperatively. The mean change in visual acuity (Snellen lines) of the operated eye four months postoperatively was 4.1 (standard deviation (SD) 2.3) for the day-care group and 4.1 (SD 2.2) for the in-patient group and not statistically significant. The four-month postoperative mean change in quality of life score measured using the VF14 showed minimal differences between the two groups. Costs were 20% more for the in-patient group and this was attributed to higher costs for overnight stay. One study only reported hotel costs for the non-hospitalised participants making aggregation of data on costs impossible. REVIEWER'S CONCLUSIONS: This review provides some evidence that there is a cost saving but no significant difference in outcome or risk of postoperative complications between day-care and in-patient cataract surgery. This is based on one detailed and methodologically sound trial conducted in the developed world. The success, safety and cost-effectiveness of cataract surgery as a day-care procedure appears to be acceptable but additional well-designed trials are required to confirm these perceptions.

Ambulatory Surgical Procedures↗

Searching for new antimalarial therapeutics amongst known drugs.

The need to discover and develop new antimalarial therapeutics is overwhelming. The annual mortality attributed to malaria, currently approximately 2.5 million, is increasing due primarily to widespread resistance to currently used drugs. One strategy to identify new treatment alternatives for malaria is to examine libraries of diverse compounds for the possible identification of novel scaffolds. Beginning with libraries of drug or drug-like compounds is an ideal starting point because, in the case of approved drugs, substantial pharmacokinetic and toxicologic data should be available for each compound series. We have employed a high-throughput screen of the MicroSource Spectrum and Killer Collections, a library of known drugs, bioactive compounds, and natural products. Our screening assay identifies compounds that inhibit growth of Plasmodium falciparum cultured in human erythrocytes. We have identified 36 novel inhibitors of P. falciparum, of which 19 are therapeutics, and five of these drugs exhibit effective 50% inhibitory concentrations within similar ranges to therapeutic serum concentrations for their recently indicated uses: propafenone, thioridazine, chlorprothixene, perhexiline, and azlocillin. The findings we report here indicate that this is an effective strategy to identify novel scaffolds and therefore aid in antimalarial drug discovery efforts.

Animals↗

Cytoplasmic RNA extraction from fresh and frozen mammalian tissues.

The quality of collections of expressed sequence tags andfull-length cDNAs is adversely affected by the presence of "junk" clones derivedfrom unspliced or partially spliced RNAs present in conventional total RNA preparations. One can overcome this problem by using intact cytoplasmic RNA to create cDNA libraries, but the methods in the literature that describe the preparation of RNA only work well for extracting cultured cells. Cell lines are not as diverse as one would like, and to clone comprehensive sets of human and model organism full-length cDNAs, libraries have to be prepared from tissue samples. Thus, we have developed a robust and inexpensive method that allows intact cytoplasmic RNA to be extracted from both fresh and frozen mammalian tissues. A mouse full-length, cap-trapped cDNA library prepared with RNA using this new procedure had excellent characteristics.

Animals↗

Circumventing T-cell tolerance to tumour antigens.

During past decades, many attempts have been made to induce or enhance tumour-specific T-cell immunity in cancer patients by vaccination. However, it has become apparent that in a large number of cases the naturally occurring tumour-specific T-cell repertoire is of low affinity and therefore inefficient in mediating tumour rejection. Because of the potential therapeutic value of high affinity TCRs with tumour/lineage specificities, we set out to develop a number of new technologies that can be used to create improved tumour-specific T-cell immunity. These strategies entail: (i) the efficient expansion of low affinity T cells specific for self antigens through the use of variant peptides with improved TCR-binding characteristics; (ii) a retroviral library-based technology to improve the affinity of (self-specific) T-cell receptors in vitro, and (iii) proof of principle for the feasibility of TCR gene transfer as a means to generate T-cell populations with a desired antigen-specificity in vivo. Collectively this toolbox should allow us to create improved T-cell receptors for human tumour antigens, which can subsequently be used to impose tumour-reactivity on to peripheral T cells.

Animals↗

Thimet oligopeptidase cleaves the full-length Alzheimer amyloid precursor protein at a beta-secretase cleavage site in COS cells.

We developed an assay method using a novel quenched fluorescent substrate (QFS) flanking the beta-cleavage site of amyloid precursor protein (APP), and purified a candidate beta-secretase from bovine brain. N-terminal amino acid analysis showed the candidate to be thimet oligopeptidase (TOP). The cDNA for human TOP was cloned from a human brain cDNA library and expressed in COS cells. The enzyme was further purified on a Ni2+-agarose column. TOP cleaved the Swedish Alzheimer's substrate (SEVNLDAEFR) as well as the normal substrate (SEVKMDAEFR). We then coexpressed TOP with APP695 in COS cells, collected transfected cells and conditioned media, and analyzed them by immunoblotting. The antibody against the specific secreted APP cleaved by beta-secretase (sAPPbeta) detected the secretion of sAPPbeta only from APP/hTOP-overexpressing cells, and not from cells overexpressing of antisense hTOP cDNA. Finally, we analyzed the immunolocalization of overexpressed hTOP in COS cells. Most hTOP was localized in the nuclei, but a small amount was localized in the Golgi or other organelles around the nuclei. These results suggest that TOP has a beta-secretase-like activity responsible for the processing of APP.

Amino Acid Sequence↗

Discovery of positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5).

This review provides an overview of the drug discovery process used to identify, develop and characterize the first positive allosteric modulators of the metabotropic glutamate receptor (mGluR) subtype 5 (mGluR5). Discovery and optimization of three series of positive allosteric modulators are described, each using different approaches. The symmetric benzaldazine series was discovered and optimized from samples already existing in our sample collection without an active synthetic program to further elucidate SAR. This series yielded a family of highly selective pharmacological tools that produced positive, negative and neutral allosteric modulation of mGluR5 activity. The original compound in the benzamide series was discovered from screening and this series was optimized using an iterative library synthesis approach to explore SAR in each of three regions of the molecule. This series produced more potent positive allosteric mGluR5 modulators than the benzaldazine series which could be evaluated for their effect on mGluR5 in brain slice electrophysiological studies. The pyrazole series used a fragment library approach based on small structural motives from the benzamide series to discover lead compounds and establish SAR. This series produced still more potent positive allosteric mGluR5 modulators with improved pharmacokinetic and physical properties. These modulators showed efficacy in animal behavioral models in which other antipsychotic drugs were active. Evaluation of assay data in mathematical models of allosterism to constrain possible mechanisms of action is briefly discussed. Other reviews of this emerging field with different emphases have been published recently [1-3].

Allosteric Regulation↗

Psychosocial treatment for opiate abuse and dependence.

BACKGROUND: Substance dependence is a major social and public health problem; therefore it is a priority to develop effective treatments. The treatment of opioid dependence is complex. Previous Cochrane reviews have explored the efficacy of pharmacotherapy for opiate dependence. This current review focuses on the role of psychosocial interventions alone for the treatment of opiate dependence. There are many different psychosocial interventions offered to opiate addicts, which are widely spread. There is some evidence for the effectiveness of psychosocial interventions, but no systematic review has even been carried out. OBJECTIVES: To assess the efficacy and acceptability of psychosocial interventions alone for treating opiate use disorders. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, and LILACS; reference searching; personal communication; conference abstracts; unpublished trials; book chapters on treatment of opioid abuse/ dependence. SELECTION CRITERIA: The inclusion criteria for all randomised-controlled trials were that they should focus on psychosocial interventions alone for treating opioid use disorders. DATA COLLECTION AND ANALYSIS: Reviewers extracted the data independently using relative risks, weighted mean difference and number needed to treat estimated, when possible. The reviewers assumed that people who died or dropped out had no improvement (intention to treat analysis) and tested the sensitivity of the final results to this assumption. MAIN RESULTS: Five studies fit the study criteria. These analysed Contingency Management, Brief Reinforcement Based Intensive Outpatient Therapy coupled with Contingency Management, Cue Exposure therapy, Alternative Program for Methadone Maintenance Treatment Program Drop-outs (MMTP) and Enhanced Outreach-Counselling Program. All the treatments were studied against the control (standard) treatment; therefore it was not possible to identify which type of psychosocial therapy was most effective. The main findings were that both Enhanced Outreach Counselling and Brief Reinforcement Based Intensive Outpatient Therapy coupled with Contingency Management had significantly better outcomes than standard therapy within treatment. This was regarding relapse to opioid use, re-enrollment in treatment and retention in treatment. At 1-month and 3- month follow up the effects of Reinforcement Based Intensive Outpatient Therapy were not sustained. There was no further follow up of the Enhanced Outreach Counselling group. The Alternative Program for MMTP Drop-outs and the behavioural therapies of Cue Exposure and Contingency Management alone were no better than the control (standard) therapy. As the studies were heterogeneous, it was not possible to pool the results and perform a meta-analysis. AUTHORS' CONCLUSIONS: The available evidence has low numbers and is heterogeneous. At present psychosocial treatments alone are not adequately proved treatment modalities or superior to any other type of treatment. It is important to develop a better evidence base for psychosocial interventions to assist in future rationale planning of opioid use drug treatment services. Large-scale randomised trials are required with longer follow up stating methods of randomisation, allocation concealment and blinding. Where possible this should include intention to treat analysis, with power calculations performed prior to the trial. These studies can be designed and delivered to provide usable data for better understanding of this important component of intervention in the field of dependence.

Humans↗

Introducing touchscreens to black and ethnic minority groups--a report of processes and issues in the Three Cities project.

There is a need for people to have access to health information but this may not be readily available for some black and ethnic minority groups living in England. This study aims to improve access to health information for ethnic minority groups by providing this in their own language, in an audio and visual format through a touchscreen computer. The study was led by health promotion and public health workers informed by advisory panels of representatives from local black and ethnic minority groups in the cities of Nottingham, Sheffield and Leicester. Discussion within the advisory panels and local epidemiological data helped to identify groups to be targeted and priority health issues to be addressed. Other issues covered during development included interface design, language translation and identification of accessible locations. A number of problems were addressed in establishing appropriate touchscreen facilities, mainly relating to producing information in an electronic format for multiple languages and populations not necessarily computer-literate. Three touchscreens, containing information on 10 health topics, translated into five languages are currently installed, one in each city. They are being rotated through a series of locations including a library, GP practice, and a temple. Their use, and satisfaction with use, is being evaluated over a 2-year period, by statistical analysis of computer logs and the collection of qualitative information by bi-lingual interviewers with users, over an 18-month period. Health information can be made available for ethnic minority groups even if they are unable to read their mother tongue. Touchscreens appear to be a suitable medium for achieving this.

Access to Information↗

GMD@CSB.DB: the Golm Metabolome Database.

UNLABELLED: Metabolomics, in particular gas chromatography-mass spectrometry (GC-MS) based metabolite profiling of biological extracts, is rapidly becoming one of the cornerstones of functional genomics and systems biology. Metabolite profiling has profound applications in discovering the mode of action of drugs or herbicides, and in unravelling the effect of altered gene expression on metabolism and organism performance in biotechnological applications. As such the technology needs to be available to many laboratories. For this, an open exchange of information is required, like that already achieved for transcript and protein data. One of the key-steps in metabolite profiling is the unambiguous identification of metabolites in highly complex metabolite preparations from biological samples. Collections of mass spectra, which comprise frequently observed metabolites of either known or unknown exact chemical structure, represent the most effective means to pool the identification efforts currently performed in many laboratories around the world. Here we present GMD, The Golm Metabolome Database, an open access metabolome database, which should enable these processes. GMD provides public access to custom mass spectral libraries, metabolite profiling experiments as well as additional information and tools, e.g. with regard to methods, spectral information or compounds. The main goal will be the representation of an exchange platform for experimental research activities and bioinformatics to develop and improve metabolomics by multidisciplinary cooperation. AVAILABILITY: http://csbdb.mpimp-golm.mpg.de/gmd.html CONTACT: Steinhauser@mpimp-golm.mpg.de SUPPLEMENTARY INFORMATION: http://csbdb.mpimp-golm.mpg.de/

Database Management Systems↗

The Medical Library Association Benchmarking Network: results.

OBJECTIVE: This article presents some limited results from the Medical Library Association (MLA) Benchmarking Network survey conducted in 2002. Other uses of the data are also presented. METHODS: After several years of development and testing, a Web-based survey opened for data input in December 2001. Three hundred eighty-five MLA members entered data on the size of their institutions and the activities of their libraries. The data from 344 hospital libraries were edited and selected for reporting in aggregate tables and on an interactive site in the Members-Only area of MLANET. The data represent a 16% to 23% return rate and have a 95% confidence level. RESULTS: Specific questions can be answered using the reports. The data can be used to review internal processes, perform outcomes benchmarking, retest a hypothesis, refute a previous survey findings, or develop library standards. The data can be used to compare to current surveys or look for trends by comparing the data to past surveys. CONCLUSIONS: The impact of this project on MLA will reach into areas of research and advocacy. The data will be useful in the everyday working of small health sciences libraries as well as provide concrete data on the current practices of health sciences libraries.

Benchmarking↗

Remacemide for drug-resistant localization related epilepsy.

BACKGROUND: Epilepsy is a common neurological condition, affecting 0.5 to 1% of the population. Nearly 30 per cent of people with epilepsy have seizures that are refractory to currently available drugs. In response to this problem, potential new drugs are being developed. Remacemide is one of these. OBJECTIVES: To evaluate the effects of add-on treatment with remacemide upon seizures, adverse effects, cognition and quality of life for people with drug-resistant localization related epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register (4 July 2002), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2002) and MEDLINE (28 May 2002). In addition, we contacted AstraZeneca (makers of remacemide) and colleagues in the field to see if they were aware of any trials that we had missed. SELECTION CRITERIA: Randomized placebo controlled add-on trials of people of any age with localization related seizures, in which an adequate method of concealment of randomization was used. The studies could be blinded or unblinded and be of parallel or crossover design. They had to have a minimum treatment period of eight weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted data. Any disagreements were resolved by discussion. Outcomes investigated included 50 per cent or greater reduction in seizure frequency, treatment withdrawal, adverse effects, effects on cognition and quality of life. The primary analyses were by intention-to-treat. Dose response was evaluated in regression models. MAIN RESULTS: Two parallel group trials were included representing 514 individuals. Daily doses of 300, 600, 800 and 1200mg of remacemide were tested. The overall relative risk (RR) for remacemide versus placebo with 95% confidence intervals(CI) for a 50 per cent or greater reduction in seizure frequency was 1.59(95% CI 0.91 to 2.79). Due to differences in response rates among trials, regression models were unable to provide reliable estimates of responses to individual doses. Regression models did however suggest a significant effect for 800-1200mg remacemide per day. Remacemide was more likely to be withdrawn than placebo, the RR for treatment withdrawal was 1.90(95% CI 1.00 to 3.60). The RR for dizziness indicates that it is significantly associated with remacemide 3.08(99% CI 1.37 to 6.95). Effects on cognition and quality of life were not reported. REVIEWER'S CONCLUSIONS: Given the modest effect on seizure frequency and significant withdrawal rate it is unlikely that remacemide will be further developed as an antiepileptic drug.

Acetamides↗

Strengthening professionals: a chapter-level formative evaluation of the Medical Library Association mentoring initiative.

OBJECTIVE: The main objective was to determine to what extent the Medical Library Association (MLA) mentoring initiative was implemented in the South Central Chapter of the Medical Library Association (SCC/ MLA) and to identify the needs, improvements, and adjustments in mentoring services for the future to improve the practice of librarianship. METHODS: The data were collected by administering an anonymous structured survey designed by the authors. The survey was mailed to all 335 chapter members. The authors elicited responses to determine the chapter members' mentoring needs, awareness of available resources, satisfaction with existing services and resources, needs for the future, and suggestions to meet those needs. DISCUSSION: Of the 335 delivered surveys, 184 were returned, yielding a return rate of 55%. Eighty percent had a mentor or mentors in their careers, and 74% were either very satisfied or satisfied with the relationship. The majority considered having a mentor a critical part of the professional experience. The mentoring activity chosen by respondents as the most important was improvement of job performance through skills development. Over 50% were aware of SCC/MLA's mentoring activities, and less than 50% were aware of MLA's mentoring Website. CONCLUSIONS: The rate of response and the wealth of comments provided by respondents document the high level of interest in mentoring by medical librarians in the region. The following mentoring services were equally important to SCC/MLA members and were recommended for improvement or development at the regional level: a formalized mentoring program in the region, Web-based mentoring resources on the SCC/MLA Website, and a continuing education course for mentors. Members are aware of mentoring activities in the region; however, participation levels need to be increased in activities that SCC/MLA and MLA provide. Mentoring continues to evolve as a service in the profession.

Consumer Behavior↗

A screen for sequences up-regulated during heterocyst development in Anabaena sp. strain PCC 7120.

A plasmid library of small genomic fragments from the cyanobacterium Anabaena sp. strain PCC 7120 was screened for sequences whose transcripts increase in abundance during a heterocyst development time course. A total of 350 clones were analyzed, representing 1-2% of the Anabaena sp. strain PCC 7120 genome. Twenty-seven clones (8%) showed some degree of up-regulation after nitrogen starvation. The increase in transcript abundance ranged from 1.2-fold to 3.5-fold. Further analysis of the expression of some of the sequences using Northern blots suggested that the up-regulation values calculated from the screen are underestimates. The collection of up-regulated clones includes novel genes, previously characterized genes, and genes identifiable by similarity to known genes. One of the novel genes has been shown to be required for heterocyst function, and the sequence similarities and expression patterns of some of the others suggest that they may play a role in heterocyst development.

Anabaena↗