Defoliation-induced changes in foliage quality may trigger broad-scale insect outbreaks.

Top-down effects, like predation, are drivers of insect outbreaks, but bottom-up effects, like host nutritional quality, also influence outbreaks and could in turn be altered by insect-caused defoliation. We evaluated the prediction that herbivory leads to a positive feedback on outbreak severity as nutrient concentration in plant tissues increases through improved soil nutrient availability from frass and litter deposition. Over seven years of a spruce budworm outbreak, we quantified litter nutrient fluxes, soil nitrogen availability, and host tree foliar nutrient status along a forest susceptibility gradient.

Improved performance of the eastern spruce budworm on black spruce as warming temperatures disrupt phenological defences.

Phenological shifts, induced by global warming, can lead to mismatch between closely interacting species. The eastern spruce budworm, Choristoneura fumiferana, an important outbreaking insect defoliator in North America, mainly feeds on balsam fir, Abies balsamea, which has historically been well synchronized with the insect. But as climate change pushes the northern range limit of the budworm further north into the boreal forest, the highly valuable black spruce, Picea mariana, historically protected against the budworm by its late budburst phenology, is suffering increased defoliation during the current outbreak.

Phenological synchrony between eastern spruce budworm and its host trees increases with warmer temperatures in the boreal forest.

Climate change is predicted to alter relationships between trophic levels by changing the phenology of interacting species. We tested whether synchrony between two critical phenological events, budburst of host species and larval emergence from diapause of eastern spruce budworm, increased at warmer temperatures in the boreal forest in northeastern Canada. Budburst was up to 4.

Model-specification uncertainty in future forest pest outbreak.

Climate change will modify forest pest outbreak characteristics, although there are disagreements regarding the specifics of these changes. A large part of this variability may be attributed to model specifications. As a case study, we developed a consensus model predicting spruce budworm (SBW, Choristoneura fumiferana [Clem.

Impact of anti-orthopoxvirus neutralizing antibodies induced by a heterologous prime-boost HIV-1 vaccine on insert-specific immune responses.

Background: The impact of anti-vector immunity on the elicitation of insert-specific immune responses is important to understand in vaccine development. HVTN 055 was a 150 person phase I randomized, controlled HIV vaccine trial of recombinant modified vaccinia Ankara (rMVA) and fowlpox (rFPV) with matched HIV-1 inserts which demonstrated increased CD8+ T-cell immune responses in the heterologous vaccine group. The controls used in this study were the empty vectors (MVA and FPV).

Thy1+ NK [corrected] cells from vaccinia virus-primed mice confer protection against vaccinia virus challenge in the absence of adaptive lymphocytes.

While immunological memory has long been considered the province of T- and B-lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for which no cognate germline-encoded receptor has been identified. This immune response results in viral clearance in the absence of classical adaptive T and B lymphocyte populations, and is mediated by a Thy1(+) subset of natural killer (NK) cells.

Safety and immunogenicity of modified vaccinia Ankara (ACAM3000): effect of dose and route of administration.

Background: We conducted a clinical trial of the safety and immunogenicity of modified vaccinia Ankara (MVA) to examine the effects of dose and route of administration.

Methods: Seventy-two healthy, vaccinia virus-naive subjects received 1 of 6 regimens of MVA (ACAM3000) or placebo consisting of 2 administrations given 1 month apart.

Results: MVA was generally well tolerated at all dose levels and by all routes.

Effect of vaccination with modified vaccinia Ankara (ACAM3000) on subsequent challenge with Dryvax.

Background: Despite the success of smallpox vaccination, the immunological correlates of protection are not fully understood. To investigate this question, we examined the effect of immunization with modified vaccinia Ankara (MVA) on subsequent challenge with replication-competent vaccinia virus (Dryvax).

Methods: Dryvax challenge by scarification was conducted in 36 healthy subjects who had received MVA (n = 29) or placebo (n = 7) in a previous study of doses and routes of immunization.

Breadth of neutralizing antibodies elicited by stable, homogeneous clade A and clade C HIV-1 gp140 envelope trimers in guinea pigs.

The native envelope (Env) spike on the surface of human immunodeficiency virus type 1 (HIV-1) is trimeric, and thus trimeric Env vaccine immunogens are currently being explored in preclinical immunogenicity studies. Key challenges have included the production and purification of biochemically homogeneous and stable trimers and the evaluation of these immunogens utilizing standardized virus panels for neutralization assays. Here we report the binding and neutralizing antibody (NAb) responses elicited by clade A (92UG037.

Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies.

The restricted neutralization breadth of vaccine-elicited antibodies is a major limitation of current human immunodeficiency virus-1 (HIV-1) candidate vaccines. In order to permit the efficient identification of vaccines with enhanced capacity for eliciting cross-reactive neutralizing antibodies (NAbs) and to assess the overall breadth and potency of vaccine-elicited NAb reactivity, we assembled a panel of 109 molecularly cloned HIV-1 Env pseudoviruses representing a broad range of genetic and geographic diversity. Viral isolates from all major circulating genetic subtypes were included, as were viruses derived shortly after transmission and during the early and chronic stages of infection.

Videoscopic phantom-based angiographic simulation: effect of brief angiographic simulator practice on vessel cannulation times.

Purpose: This study was performed to determine the effectiveness of videoscopic phantom-based angiographic simulation (VPAS) in providing effective endovascular procedural training for medical student and resident populations.

Materials And Methods: Medical students and radiology residents were separated equally into experimental and control groups (n = 20 each). The primary objective was to evaluate the efficiency of cannulating vessels with the use of the VPAS apparatus.

Immunogenicity of recombinant Modified Vaccinia Ankara following a single or multi-dose vaccine regimen in rhesus monkeys.

Modified Vaccinia Ankara (MVA) is a replication-defective strain of vaccinia virus (VV) that is being investigated in humans as an alternative vaccine against smallpox. Understanding the parameters of a MVA vaccine regimen that can effectively enhance protective immunity will be important for clinical development. The present studies utilize cohorts of rhesus monkeys immunized with recombinant MVA (rMVA) or recombinant VV (rVV) vaccine vectors to investigate the magnitude, breadth, and durability of anti-VV immunity elicited by a single or multi-dose vaccine regimen.

Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys.

A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys (Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 (ref. 3).

Differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice.

The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. Here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotype 35 (rAd35) vectors expressing the vaccinia virus intracellular mature virion (IMV) antigens A27L and L1R and extracellular enveloped virion (EEV) antigens A33R and B5R in a murine vaccinia virus challenge model.

LGD-5552, an antiinflammatory glucocorticoid receptor ligand with reduced side effects, in vivo.

Treatment of inflammation is often accomplished through the use of glucocorticoids. However, their use is limited by side effects. We have examined the activity of a novel glucocorticoid receptor ligand that binds the receptor efficiently and strongly represses inflammatory gene expression.

Standardized assessment of NAb responses elicited in rhesus monkeys immunized with single- or multi-clade HIV-1 envelope immunogens.

The genetic diversity of HIV-1 envelope glycoproteins (Env) remains a major obstacle to the development of an antibody-based AIDS vaccine. The present studies examine the breadth and magnitude of neutralizing antibody (NAb) responses in rhesus monkeys after immunization with DNA prime-recombinant adenovirus (rAd) boost vaccines encoding either single or multiple genetically distant Env immunogens, and subsequently challenged with a pathogenic simian-human immunodeficiency virus (SHIV-89.6P).

Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis.

Insulin-induced gene 1 (INSIG-1) is a key regulator in the processing of the sterol regulatory element-binding proteins (SREBPs). We demonstrated that Insig-1 is regulated by peroxisome proliferator-activated receptor gamma (PPARgamma) providing a link between insulin sensitization/glucose homeostasis and lipid homeostasis. Insig-1 was identified as a PPARgamma target gene using microarray analysis of mRNA from the white adipose tissue of diabetic (db/db) animals treated with PPARgamma agonists.

Effect of tamoxifen on breast tissue density in premenopausal breast cancer.

It has been established that hormone replacement therapy (HRT) increases breast tissue density on mammography in up to 30% of women receiving treatment. The effects of selective estrogen receptor modulators (SERMs) on breast tissue have received limited attention, although there have been several reports of tamoxifen decreasing mammographic tissue density in some women undergoing adjuvant or prophylactic breast cancer treatment. We report a case of a premenopausal woman treated with tamoxifen for 5 years whose mammographic density decreased while on tamoxifen and returned to her baseline density following termination of the drug.

Increased proinflammatory cytokine gene expression in the colonic mucosa of coeliac disease patients in the early period after gluten challenge.

Activation of T cells in the intestinal mucosa in response to gluten exposure is thought to play a key role in the pathogenesis of coeliac disease. Moreover, the response of the rectal mucosa to gluten challenge has been considered a useful predictor of gluten sensitivity in coeliac disease. In the present study, we assessed early changes in the expression of proinflammatory cytokine genes and the T cell receptor (TCR) Vbeta repertoire in the rectal mucosa of coeliac disease patients following experimental gluten challenge.

Biochemical and morphological differentiation of the human colonic epithelial cell line SW620 in the presence of dimethylsulfoxide.

In vitro models of intestinal cell differentiation provide an important adjunct for studying normal and abnormal intestinal epithelial cell differentiation. The studies reported herein describe morphologic and biochemical changes in the colonic epithelial cell line SW620 following dimethylsulfoxide (DMSO) incubation. Cells cultured in the presence of DMSO showed striking changes in morphology characterized by enlargement, elongation, and formation of process-like structures by light microscopy and a propensity to form microvillus-like structures by electron microscopy.

A tyrosine sulfated human glycoprotein with an unusual cell distribution.

We describe a human integral cell surface glycoprotein (Mr 142 kD), recognized by monoclonal antibody M2B3. This glycoprotein is absent from resting peripheral blood lymphocytes, but becomes expressed in significant levels with mitogen activation. The M2B3 glycoprotein is present on epithelial cells in the basal layer of epidermal and esophageal tissue as well as in several fresh tumors examined.

HIV-1 infection and expression in human colonic cells: infection and expression in CD4+ and CD4- cell lines.

Three human colonic epithelial cell lines, SW620, HT29, and T84, were characterized with respect to HIV-1 infection and gene expression. SW620 and HT29, but not T84, could be infected with HIV-1. CD4 messenger RNA and its protein product were identified in SW620 cells but not in HT29 or T84 cells.

Detection of individual Peyer's patch T cells that produce interleukin-5 and interferon-gamma.

A method was developed to detect individual interferon-gamma (IFN-gamma)- and interleukin-5 (IL-5)-producing cells among freshly isolated T cell populations and long term lines of CD4+ Peyer's patch T cells using frozen semi-thin sections of paraformaldehyde fixed-T cells and immunofluorescence techniques. Using this method, individual CD4+ Peyer's patch T cells could be shown to produce IFN-gamma, characteristic of the T helper 1 (Th1) T cell type, IL-5, characteristic of the T helper 2 (Th2) T cell type, as well as both IFN-gamma and IL-5. These data support the notion that Th1 and Th2 cells derive from a common T cell precursor.