Pollen flow and paternity in an isolated and non-isolated black walnut (Juglans nigra L.) timber seed orchard.

Artificial pollination of black walnut (Juglans nigra L.) is not practical and timber breeders have historically utilized only open-pollinated half-sib families. An alternate approach called "breeding without breeding," consists of genotyping open-pollinated progeny using DNA markers to identify paternal parents and then constructing full-sib families.

Community Response to Extreme Drought (CRED): a framework for drought-induced shifts in plant-plant interactions.

Contents Summary 52 I. Introduction 52 II. The Community Response to Extreme Drought (CRED) framework 55 III.

A systematic review of oral health outcomes produced by dental teams incorporating midlevel providers.

Background: The authors conducted a systematic review on this research question: “In populations where nondentists conduct diagnostic, treatment planning, and/or irreversible/ surgical dental procedures, is there a change in disease increment, untreated dental disease, and/or cost-effectiveness of dental care?”

Methods: The authors searched 12 electronic databases for articles published through February 2012 and hand searched relevant articles. They assessed the risk of bias of included studies and extracted data.

Results: The authors screened 7,701 citations, resulting in 18 observational studies that met the inclusion criteria.

Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas.

Background: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions.

Types Of Studies Reviewed: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies.

Evidence-based clinical recommendations on the prescription of dietary fluoride supplements for caries prevention: a report of the American Dental Association Council on Scientific Affairs.

Background: This article presents evidence-based clinical recommendations for the prescription of dietary fluoride supplements. The recommendations were developed by an expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs (CSA). The panel addressed the following questions: when and for whom should fluoride supplements be prescribed, and what should be the recommended dosage schedule for dietary fluoride supplements?

Types Of Studies Reviewed: A panel of experts convened by the ADA CSA, in collaboration with staff of the ADA Center for Evidence-based Dentistry, conducted a MEDLINE search to identify publications that addressed the research questions: systematic reviews as well as clinical studies published since the systematic reviews were conducted (June 1, 2006).

Treatment combining RU486 and Ad5IL-12 vector attenuates the growth of experimentally formed prostate tumors and induces changes in the sentinel lymph nodes of mice.

Background: Tumor immune responses are first generated and metastases often begin in tumor sentinel lymph nodes (TSLN). Therefore, it is important to promote tumor immunity within this microenvironment. Mifepristone (RU486) treatment can interfere with cortisol signaling that can lead to suppression of tumor immunity.

Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas.

Background: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions.

Types Of Studies Reviewed: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies.

Managing clinical risk: right person, right care, right time.

Dentists and the dental health care industry have a renewed interest in clinical risk assessment, because they offer the potential to identify a patient's clinical needs for oral health care more specifically, to maximize prevention by early intervention, and to educate patients to become more informed consumers of oral health care and direct resources where they are most needed and can produce the greatest value. To realize this potential, risk assessment must be applied appropriately, and its indirect ramifications for access to care should be considered. Several ideas for the appropriate application of risk assessment are discussed and the ramifications for access to care are explored.

Attenuation of the glucocorticoid response during Ad5IL-12 adenovirus vector treatment enhances natural killer cell-mediated killing of MHC class I-negative LNCaP prostate tumors.

Tumor cells can evolve to evade immune responses by down-modulating surface MHC class I expression and become refractory to T cell-directed immunotherapy. We employed a strategy to bypass this escape mechanism using a recombinant adenovirus vector expressing interleukin-12 (Ad5IL-12) to target natural killer (NK) cell-mediated killing of human prostate tumors in NOD.scid mice.

A convenient plasmid system for construction of helper-dependent adenoviral vectors and its application for analysis of the breast-cancer-specific mammaglobin promoter.

Background: Helper-dependent (HD) adenovirus (Ad) vectors, deleted of all viral coding sequences, have a higher cloning capacity, improved performance of tissue-specific promoters, and reduced toxicity in animals relative to first-generation Ad vectors, making these vectors promising tools for gene transfer in vitro and in vivo. However, the large size of HDAd precursor plasmids renders them relatively difficult to manipulate due to the paucity of unique restriction enzyme sites suitable for transgene insertion and to the size constraints imposed by the viral packaging machinery.

Methods: We have constructed a series of HDAd precursor plasmids that allows cassette insertion at a unique site in the vector backbone.

Correction of chromosomal mutation and random integration in embryonic stem cells with helper-dependent adenoviral vectors.

For gene therapy of inherited diseases, targeted integration/gene repair through homologous recombination (HR) between exogenous and chromosomal DNA would be an ideal strategy to avoid potentially serious problems of random integration such as cellular transformation and gene silencing. Efficient sequence-specific modification of chromosomes by HR would also advance both biological studies and therapeutic applications of a variety of stem cells. Toward these goals, we developed an improved strategy of adenoviral vector (AdV)-mediated HR and examined its ability to correct an insertional mutation in the hypoxanthine phosphoribosyl transferase (Hprt) locus in male mouse ES cells.

Life-long systemic protection in mice vaccinated with L. major and adenovirus IL-12 vector requires active infection, macrophages and intact lymph nodes.

Immunization with soluble leishmanial antigen (SLA) in IFA plus Ad5IL-12 vector induced protection confined to the immunized footpad in BALB/c mice. However, animals that controlled a primary infection with a Leishmania major challenge in the same immunized footpad, became resistant to subsequent contralateral rechallenges due to expansion of IFN-gamma secreting cells. This systemic immunity could be disrupted either by macrophage depletion during immunization or by lymphadenectomy after challenge.

Use of a murine secreted alkaline phosphatase as a non-immunogenic reporter gene in mice.

Background: The development of any vector system as a gene delivery system requires its optimization in vitro and in vivo. Preliminary studies frequently involve the use of a reporter gene, which allows for the rapid and simple assay of vector function through monitoring expression levels of the reporter gene. However, evaluation of vector efficacy can be compromised by immune responses directed against immunogenic reporter proteins.

Heterogeneity of the immune response to adenovirus-mediated factor VIII gene therapy in different inbred hemophilic mouse strains.

Background: The development of anti-factor VIII (FVIII) antibodies (inhibitors) is a critical concern when considering gene therapy as a potential treatment modality for hemophilia A. We used a hemophilia A mouse model bred on different genetic backgrounds to explore genetically controlled differences in the immune response to FVIII gene therapy.

Methods: C57BL/6 FVIII knockout (C57-FVIIIKO) mice were bred with normal BALB/c (BAL) mice, to generate a recombinant congenic BAL-FVIIIKO model of hemophilia A.

The human SCGB2A2 (mammaglobin-1) promoter/enhancer in a helper-dependent adenovirus vector directs high levels of transgene expression in mammary carcinoma cells but not in normal nonmammary cells.

Expression of secretoglobin family 2A member 2 (SCGB2A2, also known as mammaglobin-1) has been detected in a high percentage of primary and metastatic breast tumors, to a lesser extent in normal breast, but not in other normal tissues. Plasmid transfection studies in our lab and others, however, were unable to identify the genetic elements regulating this specificity. Here we demonstrate that a 25-kb DNA fragment derived from the human SCGB2A2 gene upstream of the protein coding sequence was highly active and preferentially expressed in breast cancer cells when introduced via a helper-dependent adenoviral (HDAd) vector.

Functional rescue of vitamin C synthesis deficiency in human cells using adenoviral-based expression of murine l-gulono-gamma-lactone oxidase.

l-Gulono-gamma-lactone oxidase (GULO) is a critical enzyme present in most mammalian species that is required for the terminal step in vitamin C biosynthesis. Primates are absolutely dependent on exogenously supplied dietary vitamin C due to inactivation of the Gulo gene by mutation over 40 million years ago. In this study, we report the cloning and expression of the murine l-gulono-gamma-lactone oxidase cDNA and gene.

Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression.

Sialidosis is an autosomal recessive disease resulting from a deficiency of lysosomal sialidase. Type II sialidosis is a rare disease characterized clinically by hydrops fetalis, hepatosplenomegaly, and severe psychomotor retardation. Genomic DNA from four unrelated sialidosis patients was screened for mutations within the sialidase gene NEU1.

Helper-dependent adenoviral vectors mediate therapeutic factor VIII expression for several months with minimal accompanying toxicity in a canine model of severe hemophilia A.

Two helper-dependent (HD) adenoviral vectors encoding a canine factor VIII B-domain-deleted transgene (cFVIII) were constructed and evaluated in 4 hemophilia A dogs. One vector was regulated by the cytomegalovirus (CMV) promoter (HD-CMV-cFVIII), while the other vector contained a tissue-restricted promoter comprised of the human FVIII proximal promoter with an upstream concatemer of 5 hepatocyte nuclear factor 1 binding sites (HD-HNF-cFVIII). We detected no toxicity at low dose (5 x 10(11) vp/kg), but at higher vector doses (> 1 x 10(12) vp/kg) transient hepatotoxicity and thrombocytopenia were observed.

A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer.

Preclinical studies demonstrate that intratumoral delivery of adenovirus expressing IL-2 eradicates pre-established tumors in mice and confers immune protection from rechallenge. To explore the activity of AdCAIL-2 in prostate cancer, a Phase I clinical trial was conducted in patients with localized disease and Gleason score >7 or prostate-specific antigen (PSA) >10 plus Gleason score 7. A total of 12 patients were injected 4 weeks prior to prostatectomy in a dose-escalation study at doses of 10(9), 5 x 10(9) and 10(10) PFU of virus.

Protection against experimental autoimmune encephalomyelitis generated by a recombinant adenovirus vector expressing the V beta 8.2 TCR is disrupted by coadministration with vectors expressing either IL-4 or -10.

Adenovirus vectors are increasingly being used for genetic vaccination and may prove highly suitable for intervention in different pathological conditions due to their capacity to generate high level, transient gene expression. In this study, we report the use of a recombinant adenovirus vector to induce regulatory responses for the prevention of autoimmune diseases through transient expression of a TCR beta-chain. Immunization of B10.

Adenoviral-mediated gene transfer of lymphotactin to the lungs of mice and rats results in infiltration and direct accumulation of CD4+, CD8+, and NK cells.

Chemokines are small 8-12-kDa chemotactic cytokines that were initially characterized for their ability to control leukocyte trafficking and, to a lesser extent, leukocyte function. Lymphotactin was first described as a T lymphocyte-specific chemotactic factor. However, it has since been shown to also be a potent attractant for natural killer (NK) cells.