Regulation of the human LAT gene by the Elf-1 transcription factor

BACKGROUND: The LAT gene encodes an intracellular adaptor protein that links cell-surface receptor engagement to numerous downstream signalling events, and thereby plays an integral role in the function of cell types that express the gene, including T cells, mast cells, natural killer cells, and platelets. To date, the mechanisms responsible for the transcriptional regulation of this gene have not been investigated. RESULTS: In this study we have mapped the transcriptional start sites for the human LAT gene and localized the 5' and 3' boundaries of the proximal promoter. We find that the promoter contains both positive and negative regulatory regions, and that two binding sites for the Ets family of transcription factors have a strong, positive effect on gene expression. Each site binds the Ets family member Elf-1, and overexpression of Elf-1 augments LAT promoter activity. The promoter also contains a Runx binding site adjacent to one of the Ets sites. This site, which is shown to bind Runx-1, has an inhibitory effect on gene expression. Finally, data is also presented indicating that the identified promoter may regulate cell-type specific expression. CONCLUSION: Collectively, these results provide the first insights into the transcriptional regulation of the LAT gene, including the discovery that the Ets transcription factor Elf-1 may play a central role in its expression

A Survey of Psychiatrists' Attitudes Toward Treatment Guidelines

We developed a survey to look at psychiatrists' attitudes toward psychotropic prescribing guidelines, specifically the Texas Medication Algorithm Project (TMAP) algorithms. The 22-page survey was distributed to 24 psychiatrists working in 4 CMHC's; 13 completed the survey. 90% agreed that guidelines should be general and flexible. The majority also agreed that guidelines should define how to measure response to a specific agent; fewer agreed guidelines should specify dosage, side effect management, or augmentation strategies. Psychiatrists were familiar with TMAP; none referred to it in their practice. In spite of this, psychiatrists' medication preferences were similar to those suggested by guidelines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44317/1/10597_2004_Article_484143.pd

Assessing Conformance to Medication Treatment Guidelines for Schizophrenia in a Community Mental Health Center (CMHC)

The feasibility of implementing current medication treatment guidelines in a community mental health clinic was examined in this cross-sectional and retrospective study. Specifically, two issues were addressed: 1) could we identify a set of clinical guidelines whose utilization could be monitored with a routine medical chart review; and 2) were the requisite data for such a review available in the medical records. An examination of three sets of published guidelines revealed 5 specific guidelines that could be operationalized and monitored. Records were reviewed for a random sample of two-thirds of all patients currently diagnosed with schizophrenia and schizoaffective disorder (n = 309). Information was collected from the medical record on patient demographics, diagnosis, duration of illness, symptoms and side effects, and medication information. Rates of conformance to the 5 guidelines ranged from a high of 97% to a low of 43%. The use of current guidelines to improve treatment in community clinics appears to be limited by the deficiencies in the medical record and the structure of the guidelines themselves. Standardized progress notes and computerized prescribing programs will improve conformance, and permit the rapid and accurate assessment of conformance to guidelines in community clinics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44313/1/10597_2004_Article_475195.pd

The Lantern Vol. 52, No. 1, Fall 1985

• Nudes • Orion • Fragments of an Epic • Sunrise • The Planting Season • Nursing Home • Hope Chest • Childhood Swing • Relationships • Elroy, Leopold, and Max • Urban Dragon • The Farmer\u27s Wife • A Ballad of Two Lovers • Betrayal • Choices • Letting Go • Emergence of a Butterfly • Poem for Every Man • Friction • Genesis • All\u27s Well • The Willow Tree • White Wasteland • Moe\u27s Happy Christmas • Rare Bird • Carnivalhttps://digitalcommons.ursinus.edu/lantern/1127/thumbnail.jp

Investigating the Bivalve Tree of Life -- an exemplar-based approach combining molecular and novel morphological characters.

To re-evaluate the relationships of the major bivalve lineages, we amassed detailed morpho-anatomical, ultrastructural and molecular sequence data for a targeted selection of exemplar bivalves spanning the phylogenetic diversity of the class. We included molecular data for 103 bivalve species (up to five markers) and also analysed a subset of taxa with four additional nuclear protein-encoding genes. Novel as well as historically employed morphological characters were explored, and we systematically disassembled widely used descriptors such as gill and stomach ‘types’. Phylogenetic analyses, conducted using parsimony direct optimisation and probabilistic methods on static alignments (maximum likelihood and Bayesian inference) of the molecular data, both alone and in combination with morphological characters, offer a robust test of bivalve relationships. A calibrated phylogeny also provided insights into the tempo of bivalve evolution. Finally, an analysis of the informativeness of morphological characters showed that sperm ultrastructure characters are among the best morphological features to diagnose bivalve clades, followed by characters of the shell, including its microstructure. Our study found support for monophyly of most broadly recognised higher bivalve taxa, although support was not uniform for Protobranchia. However, monophyly of the bivalves with protobranchiate gills was the best-supported hypothesis with incremental morphological and/or molecular sequence data. Autobranchia, Pteriomorphia, Heteroconchia, Palaeoheterodonta, Archiheterodonta, Euheterodonta, Anomalodesmata and Imparidentia new clade ( = Euheterodonta excluding Anomalodesmata) were recovered across analyses, irrespective of data treatment or analytical framework. Another clade supported by our analyses but not formally recognised in the literature includes Palaeoheterodonta and Archiheterodonta, which emerged under multiple analytical conditions. The origin and diversification of each of these major clades is Cambrian or Ordovician, except for Archiheterodonta, which diverged from Palaeoheterodonta during the Cambrian, but diversified during the Mesozoic. Although the radiation of some lineages was shifted towards the Palaeozoic (Pteriomorphia, Anomalodesmata), or presented a gap between origin and diversification (Archiheterodonta, Unionida), Imparidentia showed steady diversification through the Palaeozoic and Mesozoic. Finally, a classification system with six major monophyletic lineages is proposed to comprise modern Bivalvia: Protobranchia, Pteriomorphia, Palaeoheterodonta, Archiheterodonta, Anomalodesmata and Imparidentia

16th Annual Environmental Law Institute

Materials from the 16th Annual Environmental Law Institute held by UK/CLE in May 2000

Handing Out Guns at a Knife Fight: Behavioral Limitations of Subgame-Perfect Implementation

The assumption that payoff-relevant information is observable but not verifiable is important for many core results in contract, organizational and institutional economics. However, subgame-perfect implementation (SPI) mechanisms - which are based on off-equilibrium arbitration clauses that impose fines for lying and the inappropriate use of arbitration - can be used to render payoff-relevant observable information verifiable. Thus, if SPI mechanisms work as predicted they undermine the foundations of important economic results based on the observable but non-verifiable assumption. Empirical evidence on the effectiveness of SPI mechanisms is, however, scarce. In this paper we show experimentally that SPI mechanisms have severe behavioral limitations. They induce retaliation against legitimate uses of arbitration and thus make the parties reluctant to trigger arbitration. The inconsistent use of arbitration eliminates the incentives to take first-best actions and leads to costly disagreements such that individuals - if given the choice - opt out of the mechanism in the majority of the cases. Incentive compatible redesigns of the mechanism solve some of these problems but generate new ones such that the overall performance of the redesigned mechanisms remains low. Our results indicate that there is little hope for SPI mechanisms to solve verifiability problems unless they are made retaliation-proof and, more generally, robust to other-regarding preferences

Examining the stability of membrane proteins within SMALPs

Amphipathic co-polymers such as styrene-maleic acid (SMA) have gained popularity over the last few years due to their ability and ease of use in solubilising and purifying membrane proteins in comparison to conventional methods of extraction such as detergents. SMA2000 is widely used for membrane protein studies and is considered as the optimal polymer for this technique. In this study a side-by-side comparison of SMA2000 with the polymer SZ30010 was carried out as both these polymers have similar styrene:maleic acid ratios and average molecular weights. Ability to solubilise, purify and stabilise membrane proteins was tested using three structurally different membrane proteins. Our results show that both polymers can be used to extract membrane proteins at a comparable efficiency to conventional detergent dodecylmaltoside (DDM). SZ30010 was found to give a similar protein yield and, SMALP disc size as SMA2000, and both polymers offered an increased purity and increased thermostability compared to DDM. Further investigation was conducted to investigate SMALP sensitivity to divalent cations. It was found that the sensitivity is polymer specific and not dependent on the protein encapsulated. Neither is it affected by the concentration of SMALPs. Larger divalent cations such as Co2+ and Zn2+ resulted in an increased sensitivity

WalkMore: a randomized controlled trial of pedometer-based interventions differing on intensity messages

Pedometer-based programs have elicited increased walking behaviors associated with improvements in blood pressure in sedentary/low active postmenopausal women, a population at increased risk of cardiovascular disease. Such programs typically encourage increasing the volume of physical activity with little regard for its intensity. Recent advances in commercially available pedometer technology now permit tracking of both steps/day and time in moderate (or greater) intensity physical activity on a daily basis. It is not known whether the dual message to increase steps/day while also increasing time spent at higher intensity walking will elicit additional improvements in blood pressure relative to a message to only focus on increasing steps/day. The purpose of this paper is to present the rationale, study design, and protocols employed in WalkMore, a 3-arm 3-month blinded and randomized controlled trial (RCT) designed to compare the effects of two community pedometer-based walking interventions (reflecting these separate and combined messages) relative to a control group on blood pressure in sedentary/low active post-menopausal women, a population at increased risk of cardiovascular disease. 120 sedentary/low active post-menopausal women (45-74 years of age) will be randomly assigned (computer-generated) to 1 of 3 groups: A) 10,000 steps/day (with no guidance on walking intensity/speed/cadence; BASIC intervention, n = 50); B) 10,000 steps/day and at least 30 minutes in moderate intensity (i.e., a cadence of at least 100 steps/min; ENHANCED intervention, n = 50); or a Control group (n = 20). An important strength of the study is the strict control and quantification of the pedometer-based physical activity interventions. The primary outcome is systolic blood pressure. Secondary outcomes include diastolic blood pressure, anthropometric measurements, fasting blood glucose and insulin, flow mediated dilation, gait speed, and accelerometer-determined physical activity and sedentary behavior. This study can make important contributions to our understanding of the relative benefits that walking volume and/or intensity may have on blood pressure in a population at risk of cardiovascular disease. ClinicalTrials.gov Record NCT01519583, January 18, 2012