Inhibition of histone deacetylase as a treatment for cardiac hypertrophy

The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.Board of Regents, University of Texas Syste

Continuous data assimilation with blurred-in-time measurements of the surface quasi-geostrophic equation

An intrinsic property of almost any physical measuring device is that it makes observations which are slightly blurred in time. We consider a nudging-based approach for data assimilation that constructs an approximate solution based on a feedback control mechanism that is designed to account for observations that have been blurred by a moving time average. Analysis of this nudging model in the context of the subcritical surface quasi-geostrophic equation shows, provided the time-averaging window is sufficiently small and the resolution of the observations sufficiently fine, that the approximating solution converges exponentially fast to the observed solution over time. In particular, we demonstrate that observational data with a small blur in time possess no significant obstructions to data assimilation provided that the nudging properly takes the time averaging into account. Two key ingredients in our analysis are additional boundedness properties for the relevant interpolant observation operators and a non-local Gronwall inequality.Comment: 44 page

Current Comparative Table (CCT) automates customized searches of dynamic biological databases

The Current Comparative Table (CCT) software program enables working biologists to automate customized bioinformatics searches, typically of remote sequence or HMM (hidden Markov model) databases. CCT currently supports BLAST, hmmpfam and other programs useful for gene and ortholog identification. The software is web based, has a BioPerl core and can be used remotely via a browser or locally on Mac OS X or Linux machines. CCT is particularly useful to scientists who study large sets of molecules in today's evolving information landscape because it color-codes all result files by age and highlights even tiny changes in sequence or annotation. By empowering non-bioinformaticians to automate custom searches and examine current results in context at a glance, CCT allows a remote database submission in the evening to influence the next morning's bench experiment. A demonstration of CCT is available at and the open source software is freely available from

Reaper is regulated by IAP-mediated ubiquitination

In most cases, apoptotic cell death culminates in the activation of the caspase family of cysteine proteases, leading to the orderly dismantling and elimination of the cell. The IAPs (inhibitors of apoptosis) comprise a family of proteins that oppose caspases and thus act to raise the apoptotic threshold. Disruption of IAP-mediated caspase inhibition has been shown to be an important activity for pro-apoptotic proteins in Drosophila (Reaper, HID, and Grim) and in mammalian cells (Smac/DIABLO and Omi/HtrA2). In addition, in the case of the fly, these proteins are able to stimulate the ubiquitination and degradation of IAPs by a mechanism involving the ubiquitin ligase activity of the IAP itself. In this report, we show that the Drosophila RHG proteins (Reaper, HID, and Grim) are themselves substrates for IAP-mediated ubiquitination. This ubiquitination of Reaper requires IAP ubiquitin-ligase activity and a stable interaction between Reaper and the IAP. Additionally, degradation of Reaper can be blocked by mutating its potential ubiquitination sites. Most importantly, we also show that regulation of Reaper by ubiquitination is a significant factor in determining its biological activity. These data demonstrate a novel function for IAPs and suggest that IAPs and Reaper-like proteins mutually control each other's abundance

Commentary: The Use of Case-based Learning and Concept Mapping to Teach Students Clinical Reasoning

Introduction: Teaching students as inexperienced clinicians the process of evaluating athletic injuries and medical conditions is often challenging. Utilizing case-based learning and concept mapping as educational tools can facilitate growth in the clinical and diagnostic decision making process. Discussion: Experienced clinicians regularly employ case pattern recognition and hypothetico-deductive reasoning in clinical settings. Each type of reasoning is prone to anchoring and confirmation bias, devaluing relevant information, and framing effect if not utilized correctly. Classroom instructors and preceptors can use case-based learning and concept mapping to help students as inexperienced clinicians organize their thinking and more effectively apply their knowledge. Implications: The use of case-based learning and concept mapping to teach the process of evaluating athletic injuries and medical conditions can help students as inexperienced clinicians: improve clinical reasoning skills; decrease bias; develop more efficient and effective clinical reasoning; become more confident in what steps come next; value clinical data equally and impartially; and more effectively use hypothetico-deductive reasoning

Magnitude of behavioral deficits varies with job-related chlorpyrifos exposure levels among Egyptian pesticide workers.

Chronic occupational exposure to organophosphorus pesticides (OPs) is consistently associated with deficits on behavioral tests when compared to unexposed comparison groups. However, a dose-response relationship has yet to be established, leading some to doubt an association between occupational OP exposure and behavioral deficits. Pesticide application teams in Egypt who are primarily exposed to one OP, chlorpyrifos (CPF), were recruited into a field assessment. Trail Making A and the more challenging Trail Making B tests were administered to 54 engineers (who supervise the pesticide application process, usually from the side of the field), 59 technicians (who guide the pesticide applicators in the field), 31 applicators (who mix and apply pesticides using knapsack sprayers), and 150 controls (who did not work in the fields) at two different times during the OP application season as well as immediately after applications had ended and 1.5 months later. All participants were males since only males work on pesticide application teams in Egypt. Urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, confirmed the pattern of lower to higher CPF exposures from engineers to technicians to applicators, and these were all greater than urinary metabolite levels in controls. A consistent relationship between job title and performance speed on the behavioral task was observed: Controls had the best (fastest) performance on Trail Making A and B tests throughout the application season, and applicators had significantly slower performance than engineers on Trail Making A (p = 0.015) and B (p = 0.003). However, individual urinary TCPy, blood acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) levels did not predict individual performance. This study identifies a dose-related effect based on job title, which serves as a surrogate for chronic exposure in that differing job titles exhibit varying group exposure levels. The results establish that chronic occupational exposure to chlorpyrifos is neurotoxic and suggest that the classic biomarkers of recent CPF exposure are not predictive of chronic exposure effects

Drosophila Bruce Can Potently Suppress Rpr- and Grim-Dependent but Not Hid-Dependent Cell Death

Bruce is a large protein (530 kDa) that contains an N-terminal baculovirus IAP repeat (BIR) and a C-terminal ubiquitin conjugation domain (E2) 1, 2. BRUCE upregulation occurs in some cancers and contributes to the resistance of these cells to DNA-damaging chemotherapeutic drugs [2]. However, it is still unknown whether Bruce inhibits apoptosis directly or instead plays some other more indirect role in mediating chemoresistance, perhaps by promoting drug export, decreasing the efficacy of DNA damage-dependent cell death signaling, or by promoting DNA repair. Here, we demonstrate, using gain-of-function and deletion alleles, that Drosophila Bruce (dBruce) can potently inhibit cell death induced by the essential Drosophila cell death activators Reaper (Rpr) and Grim but not Head involution defective (Hid). The dBruce BIR domain is not sufficient for this activity, and the E2 domain is likely required. dBruce does not promote Rpr or Grim degradation directly, but its antiapoptotic actions do require that their N termini, required for interaction with DIAP1 BIR2, be intact. dBruce does not block the activity of the apical cell death caspase Dronc or the proapoptotic Bcl-2 family member Debcl/Drob-1/dBorg-1/Dbok. Together, these results argue that dBruce can regulate cell death at a novel point

Metaphase and Interphase Cytogenetics with Alu-PCR-amplified Yeast Artificial Chromosome Clones Containing the BCR Gene and the Protooncogenes c-raf-1, c-fms, and c-erbB-21

A human yeast artificial chromosome (YAC) library was screened by polymerase chain reaction with oligonucleotide primers defined for DNA sequences of the BCR gene and the protooncogenes c-raf-1, c-fms, and c-erB-2. Alu-PCR-generated human DNA sequences were obtained from the respective YAC clones and used for fluorescence in situ hybridization experiments under suppression conditions. After chromosomal in situ suppression hybridization to GTG-banded human prometaphase chromosomes, seven of nine initially isolated YAC clones yielded strong signals exclusively in the chromosome bands containing the respective genes. Two clones yielded additional signals on other chromosomes and were excluded from further tests. The band-specific YACs were successfully applied to visualize specific structural chromosome aberrations in peripheral blood cells from patients with myelodysplasia exhibiting del(5)(q13q34), chronic myeloid leukemia and acute lymphocytic leukemia with t(9;22)(q34;q11), acute promyelocytic leukemia (M3) with t(15;17)(q22;q21), and in a cell line established from a proband with the constitutional translocation t(3;8)(p14.2;q24). In addition to the analysis of metaphase spreads, we demonstrate the particular usefulness of these YAC clones in combination with whole chromosome painting to analyze specific chromosome aberrations directly in the interphase nucleus

The Texas Earth and Space Science (TXESS) Revolution: A Model for the Delivery of Earth Science Professional Development to Minority-Serving Teachers

At the time of publication K.K. Ellins, E. Snow, H.C. Olson, M. Willis, and J. Olson were at the University of Texas Austin, E. Stocks and M.R. Odell were at the University of Texas at Tyler.The Texas Earth and Space Science (TXESS) Revolution was a 5-y teacher professional development project that aimed to increase teachers' content knowledge in Earth science and preparing them to teach a 12th-grade capstone Earth and Space Science course, which is new to the Texas curriculum. The National Science Foundation–supported project was designed around six principles that proved to be critical to in its success: (1) model best practices in workshop presentations, (2) use authentic Earth science data and cybertechnology to teach up-to-date content, (3) provide ongoing training to cohorts of learners over a 2-y period, (4) involve geoscience consortia and programs that can provide proven content for classrooms, (5) use ongoing evaluations to guide future workshops, and (6) provide opportunities for leadership development through participation in research and curriculum development projects. The project served 177 science teachers by supporting them with the pedagogical, technological, and scientific tools to teach modern geoscience. TXESS Revolution teachers directly impacted more than 29,000 students, of which about 69% are nonwhite, by exposing students in Texas to the geosciences and planting the seeds for them to pursue geoscience as a field of study. Using a train-the-trainer approach, TXESS Revolution teachers shared their professional development with other Texas teachers, strengthening Earth science education at all K–12 levels throughout the state, an impact that extends beyond preparation in Earth and space science.Petroleum and Geosystems Engineerin