Dallas, TX, United States
Dallas, TX, United States

The Texas Institute of Letters is an organization devoted to the promotion of literature and literacy in Texas.Founded in 1936, the TIL offers awards to outstanding books written by Texas authors, or dealing with Texas subjects. The TIL also co-administrates the Dobie Paisano Fellowship, which awards residencies at the ranch of former TIL President J. Frank Dobie.Prominent members include: Larry McMurtry, Robert Caro, Dagoberto Gilb, Sandra Cisneros, Debra Monroe, James Hynes, and Chitra Divakaruni. Wikipedia.

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The Regents Of The University Of California, The Texas Institute and The Government Of The United States Of America As Represented By The Secretar | Date: 2015-11-17

Baboon Adenovirus (BaAdV)-2/4 and BaAdV-3 are disclosed herein. BaAdV-2/4 and BaAdV-3 polynucleotide, polypeptides and antibodies that specifically bind BaAdV-2/4 and/or BaAdV-3 are disclosed. Methods are disclosed for detecting BaAdV-2/4 and BaAdV-3. Methods are also disclosed for treating, preventing, and inducing an immune response to BaAdV-2/4 and/or BaAdV-3. Kits are also provided.

The Regents Of The University Of California, The Texas Institute and The Government Of The United States Of America | Date: 2014-01-15

Baboon Adenovirus (BaAdV)-2/4 and BaAdV-3 are disclosed herein. BaAdV-2/4 and BaAdV-3 polynucleotide, polypeptides and antibodies that specifically bind BaAdV-2/4 and/or BaAdV-3 are disclosed. Methods are disclosed for detecting BaAdV-2/4 and BaAdV-3. Methods are also disclosed for treating, preventing, and inducing an immune response to BaAdV-2/4 and/or BaAdV-3. Kits are also provided.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 438.48K | Year: 2015

DESCRIPTION provided by applicant The long term goal of this project is to gain FDA approval for commercialization of a broad spectrum small molecule antiviral agent that is effective in treating Ebola virus EBOV and Marburg virus MARV These pathogens are major biothreat agents for which there are no approved therapeutic options or vaccines The developed drug will inhibit a conserved human cellular target whose activity is necessary for infection by these and many other prominent human disease causing viruses Targeting the host factor minimizes the risk of resistance development while the widely used nature of the targeted protein allows for utility against multiple viral pathogens including newly emerging ones The lead molecule is a proprietary class of macrolactone inhibitors of the H vacuolar ATPase protein complex V ATPase V ATPases are responsible for acidification of endosomal compartments through which many viruses require passage before they can escape to the cytoplasm for replication The current lead being developed is saliphenylhalamide SaliPhe It has shown in vivo activity against influenza A IAV and unlike its predecessors shows significant selectivity indices Tests show it is active in vitro against drug resistant IAV EBOV Dengue fever virus DENV alphaviruses i e VEEV SVF and other viral pathogens First at least g of SaliPhe will be synthesized along with a late stage intermediate from which mg each of three analogs shown to have similar in vitro antiviral activities and selectivities will e made Second these compounds will be screened in vitro for EBOV and MARV efficacy to inhibit infection Vero cells will be used for the initial screens followed by isolated murine macrophages and human monocyte derived macrophages since such cells are initial and primary sites of EBOV infection Selectivity indices SI EC TC will be calculated for each virus and cell line and each will be submitted to specific toxicology assays including hERG and AIMs From these results a backup lead to SaliPhe will be chosen based on best selectivity for EBOV and MARV and toxicology assay results Third the preliminary effect s of SaliPhe on the entry of pseudotyped EBOV and MARV will be studied to see how the drug affects the virus glycoproteins GPs that respond to the decrease in endosomal pH created by the V ATPase pump This will validate SaliPheandapos s action and provide a basis for more extensive Phase II studies Fourth the ability of SaliPhe to inhibit EBOV infection in a pre exposure and post exposure mouse models will be shown SaliPhe will be given by subcutaneous continuous infusion at doses over days proven to be effective for IAV and cancer models Each arm will have female BALB c mice Blood and organs will be collected weighed and viral titers determined The overall aim is to show the feasibility of treating EBOV and MARV infections with SaliPhe to document its promise to be a broad spectrum antiviral with low potential for development of resistance PUBLIC HEALTH RELEVANCE The Ebola virus and Marburg viruses are significant pathogens and bioterror threats with mortality rates up to With March April outbreak killing at least in central Africa and nearly annual outbreaks virus spread by air travel or intentional release is of great concern as its disease would cause mass panic with major economic disruptions since there are no vaccines or drugs available The efforts proposed here are to show the feasibility of a new broad spectrum antiviral to treat infections of these pathogens

Nkhoma S.C.,The Texas Institute
Proceedings. Biological sciences / The Royal Society | Year: 2012

Malaria infections containing multiple parasite genotypes are ubiquitous in nature, and play a central role in models of recombination, intra-host dynamics, virulence, sex ratio, immunity and drug resistance evolution in Plasmodium. While these multiple infections (MIs) are often assumed to result from superinfection (bites from multiple infected mosquitoes), we know remarkably little about their composition or generation. We isolated 336 parasite clones from eight patients from Malawi (high transmission) and six from Thailand (low transmission) by dilution cloning. These were genotyped using 384 single-nucleotide polymorphisms, revealing 22 independent haplotypes in Malawi (2-6 per MI) and 15 in Thailand (2-5 per MI). Surprisingly, all six patients from Thailand and six of eight from Malawi contained related haplotypes, and haplotypes were more similar within- than between-infections. These results argue against a simple superinfection model. Instead, the observed kinship patterns may be explained by inoculation of multiple related haploid sporozoites from single mosquito bites, by immune suppression of parasite subpopulations within infections, and serial transmission of related parasites between people. That relatedness is maintained in endemic areas in the face of repeated bites from infected mosquitoes has profound implications for understanding malaria transmission, immunity and intra-host dynamics of co-infecting parasite genotypes.

Goring H.H.H.,The Texas Institute
Nature Genetics | Year: 2012

Gene expression is under partial genetic regulation, which may vary between different cell types and tissues. A new study finds that there is substantial but incomplete overlap among regulatory variants located near the regulated genes in three human tissues. © 2012 Nature America, Inc. All rights reserved.

Molinaro R.,The Texas Institute
Nature Materials | Year: 2016

A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles—which we refer to as leukosomes—retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation. © 2016 Nature Publishing Group

Almasy L.,The Texas Institute
Human Genetics | Year: 2012

As whole genome sequence becomes a routine component of gene discovery studies in humans, we will have an exhaustive catalog of genetic variation and the challenge becomes understanding the phenotypic consequences of these variants. Statistical genetic methods and analytical approaches that are concerned with optimizing phenotypes for gene discovery for complex traits offer two general categories of advantages. They may increase power to localize genes of interest and also aid in interpreting associations between genetic variants and disease outcomes by suggesting potential mechanisms and pathways through which genes may affect outcomes. Such phenotype optimization approaches include use of allied phenotypes such as symptoms or ages of onset to reduce genetic heterogeneity within a set of cases, study of quantitative risk factors or endophenotypes, joint analyses of related phenotypes, and derivation of new phenotypes designed to extract independent measures underlying the correlations among a set of related phenotypes through approaches such as principal components. New opportunities are also presented by technological advances that permit efficient collection of hundreds or thousands of phenotypes on an individual, including phenotypes more proximal to the level of gene action such as levels of gene expression, microRNAs, or metabolic and proteomic profiles. © Springer-Verlag 2012.

BACKGROUND: Congestive heart failure in the setting of a preserved left ventricular (LV) ejection fraction is increasing in prevalence among the senior population. The underlying pathophysiologic abnormalities in ventricular function and structure remain unclear for this disorder. We hypothesized that patients with heart failure with preserved ejection fraction (HFPEF) would have marked abnormalities in LV diastolic function with increased static diastolic stiffness and slowed myocardial relaxation compared with age-matched healthy controls. METHODS AND RESULTS: Eleven highly screened patients (4 men, 7 women) aged 73±7 years with HFPEF were recruited to participate in this study. Thirteen sedentary healthy controls (7 men, 6 women) aged 70±4 years also were recruited. All subjects underwent pulmonary artery catheterization with measurement of cardiac output, end-diastolic volumes, and pulmonary capillary wedge pressures at baseline; cardiac unloading (lower-body negative pressure or upright tilt); and cardiac loading (rapid saline infusion). The data were used to define the Frank-Starling and LV end-diastolic pressure-volume relationships. Doppler echocardiographic data (tissue Doppler velocities, isovolumic relaxation time, propagation velocity of early mitral inflow , E/A-wave ratio) were obtained at each level of cardiac preload. Compared with healthy controls, patients with HFPEF had similar LV contractile function and static LV compliance but reduced LV chamber distensibility with elevated filling pressures and slower myocardial relaxation as assessed by tissue Doppler imaging. CONCLUSIONS: In this small, highly screened patient population with hemodynamically confirmed HFPEF, increased end-diastolic static ventricular stiffness relative to age-matched controls was not a universal finding. Nevertheless, patients with HFPEF, even when well compensated, had elevated filling pressures, reduced distensibility, and increased diastolic wall stress compared with controls. In contrast, LV relaxation as assessed by tissue Doppler variables appeared consistently impaired in patients with HFPEF.

Owen G.T.,The Texas Institute
Pain physician | Year: 2012

The precise role of urine drug testing (UDT) in the practice of pain medicine is currently being defined. Confusion exists as to best practices, and even to what constitutes standard of care. A member survey by our state pain society revealed variability in practice and a lack of consensus. The authors sought to further clarify the importance of routine UDT as an important part of an overall treatment plan that includes chronic opioid prescribing. Further, we wish to clarify best practices based on consensus and data where available. A 20-item membership survey was sent to Texas Pain Society members. A group of chronic pain experts from the Texas Pain Society undertook an effort to review the best practices in the literature. The rationale for current UDT practices is clarified, with risk management strategies outlined, and recommendations for UDT outlined in detail. A detailed insight into the limitations of point-of-care (enzyme-linked immunosorbent assay, test cups, test strips) versus the more sensitive and specific laboratory methods is provided. Our membership survey was of a limited sample size in one geographic area in the United States and may not represent national patterns. Finally, there is limited data as to the efficacy of UDT practices in improving compliance and curtailing overall medication misuse. UDT must be done routinely as part of an overall best practice program in order to prescribe chronic opioid therapy. This program may include risk stratification; baseline and periodic UDT; behavioral monitoring; and prescription monitoring programs as the best available tools to monitor chronic opioid compliance.

The present invention provides for novel compositions and methods for delivering genes of interest to stem cells using vectors that contain differentiation-specific transcriptional regulatory elements. For example, stem cells in the internal epithelia could be transfected with a vaccine construct, which has an epithelial cell differentiation-specific promoter driving the expression of viral envelope proteins. When the promoter used is specific for terminally differentiated epithelial cells, then the viral envelope proteins will be expressed only in the upper part of the epithelia and therefore, stimulate the immune response. The infected epithelial stem cells in the basal layer will continue to produce new antigen-expressing cells, without being eliminated by the immune response. This invention will be useful in the development of vaccines against viral agents that target the internal mucosa like HIV.

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