Bovine Parainfluenza-3 Virus Detection Methods and Prevalence in Cattle: A Systematic Review and Meta-Analysis.

Bovine parainfluenza-3 virus (BPI3V) is an important respiratory pathogen in cattle, contributing to syndromes in the bovine respiratory disease complex (BRDC). Despite its significance, the understanding of its prevalence remains fragmented, especially within the larger framework of BRDC. This systematic review and meta-analysis aimed to determine the global prevalence of BPI3V in cattle using varied detection methods and to highlight associated risk factors. Of 2187 initially retrieved articles, 71 were selected for analysis, covering 32 countries. Depending on the detection method employed, the meta-analysis revealed significant variations in BPI3V prevalence. In the general cattle population, the highest prevalence was observed using the antibody detection method, with a proportion of 0.64. In contrast, in cattle with BRDC, a prevalence of 0.75 was observed. For the antigen detection method, a prevalence of 0.15 was observed, exclusively in cattle with BRDC. In nucleic acid detection, a prevalence of 0.05 or 0.10 was observed in the general and BRDC cattle populations, respectively. In virus isolation methods, a prevalence of 0.05 or 0.04 was observed in the general and BRDC cattle populations, respectively. These findings highlight the differences in the detection ability of different methods in identifying BPI3V. Other factors, such as country, study year, coinfections, farm size, the presence of respiratory signs, sex, and body weight, may also affect the prevalence. Most studies were anchored within broader BRDC investigations or aimed at detecting other diseases, indicating a potential under-representation of focused BPI3V research. BPI3V plays an important role in BRDC, with its prevalence varying significantly based on the detection methodology. To further understand its unique role within BRDC and pave the way for targeted interventions, there is an evident need for independent, dedicated research on BPI3V.

An overview of the detection of bovine respiratory disease complex pathogens using immunohistochemistry: emerging trends and opportunities.

The bovine respiratory disease complex (BRDC) is caused by a variety of pathogens, as well as contributing environmental and host-related risk factors. BRDC is the costliest disease for feedlot cattle globally. Immunohistochemistry (IHC) is a valuable tool for enhancing our understanding of BRDC given its specificity, sensitivity, cost-effectiveness, and capacity to provide information on antigen localization and immune response. Emerging trends in IHC include the use of multiplex IHC for the detection of coinfections, the use of digital imaging and automation, improved detection systems using enhanced fluorescent dyes, and the integration of IHC with spatial transcriptomics. Overall, identifying biomarkers for early detection, utilizing high-throughput IHC for large-scale studies, developing standardized protocols and reagents, and integrating IHC with other technologies are some of the opportunities to enhance the accuracy and applicability of IHC. We summarize here the various techniques and protocols used in IHC and highlight their current and potential role in BRDC research.

Comparative Analysis of the Prevalence of Bovine Viral Diarrhea Virus in Cattle Populations Based on Detection Methods: A Systematic Review and Meta-Analysis.

Infectious diseases of cattle, including bovine viral diarrhea (BVD), pose a significant health threat to the global livestock industry. This study aimed to investigate the prevalence and risk factors associated with bovine viral diarrhea virus (BVDV) infections in cattle populations through a systematic review and meta-analysis. PubMed, Web of Science, and Scopus were systematically searched for relevant articles reporting the prevalence of and associated risk factors in studies published between 1 January 2000 and 3 February 2023. From a total of 5111 studies screened, 318 studies were included in the final analysis. BVDV prevalence in cattle populations was estimated using various detection methods. The analysis detected heterogeneity in prevalence, attributed to detection techniques and associated risk factors. Antibody detection methods exhibited a higher prevalence of 0.43, reflecting the cumulative effect of detecting both active and past infections. Antigen detection methods showed a prevalence of 0.05, which was lower than antibody methods. A prevalence of 0.08 was observed using nucleic acid detection methods. The health status of the examined cattle significantly influenced the prevalence of BVDV. Cattle with bovine respiratory disease complex (BRDC) exhibited higher antibody (prevalence of 0.67) and antigen (prevalence 0.23) levels compared to cattle with reproductive problems (prevalence 0.13) or diarrhea (prevalence 0.01). Nucleic acid detection methods demonstrated consistent rates across different health conditions. Age of cattle influenced prevalence, with higher rates in adults compared to calves. Risk factors related to breeding and reproduction, such as natural or extensive breeding and a history of abortion, were associated with increased prevalence. Coinfections with pathogens like bovine herpesvirus-1 or Neospora caninum were linked to higher BVDV prevalence. Management practices, such as commingling, introducing new cattle, and direct contact with neighboring farms, also influenced prevalence. Herd attributes, including larger herd size, and the presence of persistently infected cattle, were associated with higher prevalence. These findings indicated the importance of detection methods and risk factors in BVDV epidemiological studies.

Prevalence and clinical significance of koala retrovirus in two South Australian koala (Phascolarctos cinereus) populations.

PURPOSE: Koala retrovirus (KoRV-A) is 100  % prevalent in northern Australian (Queensland and New South Wales) koala populations, where KoRV-B has been associated with Chlamydia pecorum disease and the development of lymphosarcoma. In southern populations (Victoria and South Australia), KoRV-A is less prevalent and KoRV-B has not been detected in Victoria, while the current prevalence in South Australian populations is unknown but is thought to be low. This study aimed to determine (i) the prevalence of KoRV in the two largest South Australian koala populations [Kangaroo Island (KI) and Mount Lofty Ranges (MLR)], (ii) KoRV subtype and (iii) if an association between KoRV and C. pecorum exists. METHODOLOGY: Wild koalas were sampled in KI ( n =170) between 2014 and 2017 and in MLR ( n =75) in 2016. Clinical examinations were performed, with blood collected for KoRV detection and typing by PCR. RESULTS: KoRV prevalence was 42.4  % [72/170, 95 % confidence interval (CI): 34.9-49.8  %] in KI and 65.3  % (49/75, 95 % CI: 54.6-76.1  %) in MLR. Only KoRV-A, and not KoRV-B, was detected in both populations. In MLR, there was no statistical association between KoRV and C. pecorum infection (P =0.740), or KoRV and C. pecorum disease status ( P=0.274), although KoRV-infected koalas were more likely to present with overt C. pecorum disease than subclinical infection (odds ratio: 3.15, 95 % CI: 0.91-5.39). CONCLUSION: KoRV-A is a prevalent pathogen in wild South Australian koala populations. Future studies should continue to investigate KoRV and C. pecorum associations, as the relationship is likely to be complex and to differ between the northern and southern populations.

Newer pharmacological approaches for antioxidant neuroprotection in traumatic brain injury.

Reactive oxygen species-induced oxidative damage remains an extensively validated secondary injury mechanism in traumatic brain injury (TBI) as demonstrated by the efficacy of various pharmacological antioxidants agents in decreasing post-traumatic free radical-induced lipid peroxidation (LP) and protein oxidative damage in preclinical TBI models. Based upon strong preclinical efficacy results, two antioxidant agents, the superoxide radical scavenger polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) and the 21-aminosteroid LP inhibitor tirilazad, which inhibits lipid peroxidation, (LP) were evaluated in large phase III trials in moderately- and severely-injured TBI patients. Both failed to improve 6 month survival and neurological recovery. However, in the case of tirilazad, a post hoc analysis revealed that the drug significantly improved survival of male TBI patients who exhibited traumatic subarachnoid hemorrhage (tSAH) that occurs in half of severe TBIs. In addition to reviewing the clinical trial results with PEG-SOD and tirilazad, newer antioxidant approaches which appear to improve neuroprotective efficacy and provide a longer therapeutic window in rodent TBI models will be presented. The first approach involves pharmacological enhancement of the multi-mechanistic Nrf2-antioxidant response element (ARE) pathway. The second involves scavenging of the neurotoxic LP-derived carbonyl compounds 4-hydroxynonenal (4-HNE) and acrolein which are highly damaging to neural protein and stimulate additional free radical generation. A third approach combines mechanistically complimentary antioxidants to interrupt post-TBI oxidative neurodegeneration at multiple points in the secondary injury cascade. These newer strategies appear to decrease variability in the neuroprotective effect which should improve the feasibility of achieving successful translation of antioxidant therapy to TBI patients.

Screening for depression in young Indigenous people: building on a unique community initiative.

Gurriny Yealamucka Health Service Aboriginal Corporation (GYHSAC) is an Indigenous community-controlled health organisation providing comprehensive primary care to the people of Yarrabah in far north Queensland, Australia. GYHSAC conducts an annual Young Person's Health Check (YPC) for people aged 15-25 years based on the Medical Benefits Schedule Item 715. However, the YPC is constantly evolving to meet the needs of the community, and in 2016, in response to concerns about psychological risk among Indigenous youth, GYHSAC teamed up with James Cook University to trial an adapted PHQ-9 depression screening tool (aPHQ-9) as part of the YPC. This study describes the 2016 YPC event, reports the prevalence of depressive symptoms, examines local issues related to the use of the screening tool and proposes recommendations for future health screening. Experienced health professionals conducted the aPHQ-9 assessment in a private area of the clinic. One-in-five young people were found to have moderate-severe symptoms or self-harm ideation in the previous 2 weeks; they were referred to the mental health service. The aPHQ-9 screening process was found to be straightforward and well accepted by staff and youth. Importantly, it provided valuable 'space' to facilitate communication on sensitive issues and was a conduit for speedy referral and follow up by trained staff. Based on our experience, we recommend dedicated depression screening in future routine community health checks for young people and adults.

Switchgrass (Panicum virgatum) Intercropping within Managed Loblolly Pine (Pinus taeda) Does Not Affect Wild Bee Communities.

Intensively-managed pine (Pinus spp.) have been shown to support diverse vertebrate communities, but their ability to support invertebrate communities, such as wild bees, has not been well-studied. Recently, researchers have examined intercropping switchgrass (Panicum virgatum), a native perennial, within intensively managed loblolly pine (P. taeda) plantations as a potential source for cellulosic biofuels. To better understand potential effects of intercropping on bee communities, we investigated visitation of bees within three replicates of four treatments of loblolly pine in Mississippi, U.S.A.: 3-4 year old pine plantations and 9-10 year old pine plantations with and without intercropped switchgrass. We used colored pan traps to capture bees during the growing seasons of 2013 and 2014. We captured 2507 bees comprised of 18 different genera during the two-year study, with Lasioglossum and Ceratina being the most common genera captured. Overall, bee abundances were dependent on plantation age and not presence of intercropping. Our data suggests that switchgrass does not negatively impact or promote bee communities within intensively-managed loblolly pine plantations.

A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.

Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose (13)C sodium acetate ((13)C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of (13)CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT(®) L100-55 on gelatin capsules and also on DRcaps(®). Test results demonstrated that DRcaps(®) coated with EUDRAGIT(®) L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.

Nrf2-ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice.

The importance of free radical-induced oxidative damage after traumatic brain injury (TBI) has been well documented. Despite multiple clinical trials with radical-scavenging antioxidants that are neuroprotective in TBI models, none is approved for acute TBI patients. As an alternative antioxidant target, Nrf2 is a transcription factor that activates expression of antioxidant and cytoprotective genes by binding to antioxidant response elements (AREs) within DNA. Previous research has shown that neuronal mitochondria are susceptible to oxidative damage post-TBI, and thus the current study investigates whether Nrf2-ARE activation protects mitochondrial function when activated post-TBI. It was hypothesized that administration of carnosic acid (CA) would reduce oxidative damage biomarkers in the brain tissue and also preserve cortical mitochondrial respiratory function post-TBI. A mouse controlled cortical impact (CCI) model was employed with a 1.0mm cortical deformation injury. Administration of CA at 15 min post-TBI reduced cortical lipid peroxidation, protein nitration, and cytoskeletal breakdown markers in a dose-dependent manner at 48 h post-injury. Moreover, CA preserved mitochondrial respiratory function compared to vehicle animals. This was accompanied by decreased oxidative damage to mitochondrial proteins, suggesting the mechanistic connection of the two effects. Lastly, delaying the initial administration of CA up to 8h post-TBI was still capable of reducing cytoskeletal breakdown, thereby demonstrating a clinically relevant therapeutic window for this approach. This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI.

Increase in DNA vaccine efficacy by virosome delivery and co-expression of a cytolytic protein.

The potential of DNA vaccines has not been realised due to suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and an effective immune response to the immunogen. Initially, we examined the delivery of a DNA vaccine encoding a model antigen, luciferase (LUC), to the respiratory tract of mice by encapsulation in a virosome. Virosomes that incorporated influenza virus haemagglutinin effectively delivered DNA to cells in the mouse respiratory tract and resulted in antigen expression and systemic and mucosal immune responses to the immunogen after an intranasal (IN) prime/intradermal (ID) boost regimen, whereas a multidose ID regimen only generated systemic immunity. We also examined systemic immune responses to LUC after ID vaccination with a DNA vaccine, which also encoded one of the several cytolytic or toxic proteins. Although the herpes simplex virus thymidine kinase, in the presence of the prodrug, ganciclovir, resulted in cell death, this failed to increase the humoral or cell-mediated immune responses. In contrast, the co-expression of LUC with the rotavirus non-structural protein 4 (NSP4) protein or a mutant form of mouse perforin, proteins which are directly cytolytic, resulted in increased LUC-specific humoral and cell-mediated immunity. On the other hand, co-expression of LUC with diphtheria toxin subunit A or overexpression of perforin or NSP4 resulted in a lower level of immunity. In summary, the efficacy of DNA vaccines can be improved by targeted IN delivery of DNA or by the induction of cell death in vaccine-targeted cells after ID delivery.

DNA vaccines encoding membrane-bound or secreted forms of heat shock protein 70 exhibit improved potency.

Traditional vaccine strategies are inefficient against challenge with complex pathogens including HIV; therefore, novel vaccine technologies are required. DNA vaccines are attractive as they are relatively cheap and easy to manufacture, but a major limitation has been their lack of immunogenicity in humans, which may be overcome with the incorporation of an adjuvant. HSP70 is a recognised damage-associated molecular pattern, which is a potential adjuvant. We investigated the immunogenicity of a DNA vaccine encoding HIV gag and HSP70; the latter was genetically modified to produce cytoplasmic, secreted or membrane-bound HSP70, the expression of which was controlled by an independent promoter. The DNA was administered to C57BL/6 mice to evaluate gag-specific T-cell responses. Our results demonstrated the ability of membrane-bound and secreted HSP70 to significantly enhance gag-specific T-cell responses and increase the breadth of T-cell responses to include subdominant epitopes. Membrane-bound or secreted HSP70 also significantly improved the multifunctionality of HIV-specific T cells and T-cell proliferation, which is important for maintaining T-cell integrity. Most importantly, the inclusion of membrane-bound HSP70, secreted HSP70 or a combination significantly increased protection in mice challenged with EcoHIV, a chimeric virus that replicates in mouse leukocytes in vivo.

Temporal and spatial dynamics of nrf2-antioxidant response elements mediated gene targets in cortex and hippocampus after controlled cortical impact traumatic brain injury in mice.

The pathophysiological importance of oxidative damage after traumatic brain injury (TBI) has been extensively demonstrated. The transcription factor nuclear factor erythoid related factor 2 (Nrf2) mediates antioxidant and cytoprotective genes by binding to antioxidant response elements (ARE) present in nuclear DNA. In this study, we characterized the time course of Nrf2-ARE-mediated expression in the cortex and hippocampus using a unilateral controlled cortical impact model of focal TBI. Ipsilateral hippocampal and cortical tissue was collected for Western-blot protein analysis (n=6/group) or quantitative reverse transcription-polymerase chain reaction for mRNA (n=3/group) at 3, 6, 12, 24, 48, and 72 h or 1 week post-injury. Multiple genes mediated by Nrf2-ARE were altered post-TBI. Specifically, Nrf2 mRNA increased significantly post-TBI at 48 and 72 h in the cortex and at 48 and 72 h and 1 week in the hippocampus with a coincident increase in glial fibrillary acidic protein mRNA, thereby implying this response is likely occurring in astrocytes. Presumably linked to Nrf2 activation, heme-oxygenase-1, nicotinamide adenine dinucleotide phosphate-quinone-oxidoreductase 1, glutathione reductase, and catalase mRNA overlap throughout the post-injury time course. This study demonstrates the first evidence of such changes during the first week after focal TBI and that increases in expression of some Nrf2-ARE-mediated cytoprotective genes are not observed until 24-48 h post-injury. Unfortunately, this does not precede, but rather coincides with, the occurrence of lipid peroxidative damage. This is the first known comparison between the time course of peroxidative damage and that of Nrf2-ARE activation during the first week post-TBI. These results underscore the necessity to discover pharmacological agents to accelerate and amplify Nrf2-ARE-mediated expression early post-TBI.

Induction of antigen-positive cell death by the expression of perforin, but not DTa, from a DNA vaccine enhances the immune response.

The failure of traditional protein-based vaccines to prevent infection by viruses such as HIV or hepatitis C highlights the need for novel vaccine strategies. DNA vaccines have shown promise in small animal models, and are effective at generating anti-viral T cell-mediated immune responses; however, they have proved to be poorly immunogenic in clinical trials. We propose that the induction of necrosis will enhance the immune response to vaccine antigens encoded by DNA vaccines, as necrotic cells are known to release a range of intracellular factors that lead to dendritic cell (DC) activation and enhanced cross-presentation of antigen. Here we provide evidence that induction of cell death in DNA vaccine-targeted cells provides an adjuvant effect following intradermal vaccination of mice; however, this enhancement of the immune response is dependent on both the mechanism and timing of cell death after antigen expression. We report that a DNA vaccine encoding the cytolytic protein, perforin, resulted in DC activation, enhanced broad and multifunctional CD8 T-cell responses to the HIV-1 antigen GAG and reduced viral load following challenge with a chimeric virus, EcoHIV, compared with the canonical GAG DNA vaccine. This effect was not observed for a DNA vaccine encoding an apoptosis-inducing toxin, DTa, or when the level of perforin expression was increased to induce cell death sooner after vaccination. Thus, inducing lytic cell death following a threshold level of expression of a viral antigen can improve the immunogenicity of DNA vaccines, whereas apoptotic cell death has an inhibitory effect on the immune response.

The virus inoculum volume influences outcome of influenza A infection in mice.

When establishing animal models of viral respiratory infection, the optimal dose and route of delivery are critical to ensure reproducible outcomes. The mouse model for influenza infection is widely used due to the small animal size and simplicity of viral inoculation. During establishment of a mouse model of influenza A infection we observed a marked shift in morbidity when identical influenza A inoculum doses were delivered in less than 35 µL. We show for the first time that mice challenged with a 25 µL inoculum volume readily recovered following infection with an infectious dose of influenza A virus that was fatal when inoculated in 35 or 50 µL volumes.

Administration of the Nrf2-ARE activators sulforaphane and carnosic acid attenuates 4-hydroxy-2-nonenal-induced mitochondrial dysfunction ex vivo.

The transcription factor NF-E2-related factor 2 (Nrf2) mediates transcription of antioxidant/cytoprotective genes by binding to the antioxidant-response element (ARE) within DNA. Upregulation of these genes constitutes a pleiotropic cytoprotective defense pathway, which has been shown to produce neuroprotection in numerous models by decreasing lipid peroxidation (LP) as measured by the neurotoxic LP by-product 4-hydroxynonenal (4-HNE). As neuronal mitochondria have previously been shown to be susceptible to insult-induced LP-mediated oxidative damage, we sought to mechanistically investigate whether Nrf2-ARE activation in vivo could protect mitochondria from subsequent 4-HNE exposure ex vivo. Young adult male CF-1 mice were administered one of two known Nrf2-ARE activators as single intraperitoneal doses-sulforaphane (SFP; 5.0mg/kg) or carnosic acid (CA; 1.0mg/kg)-or their respective vehicles 48 h before Ficoll isolation of rat cerebral cortical mitochondria. Purified mitochondria were then exposed ex vivo to 4-HNE for 15 min at 37 °C, which we showed to cause a concentration-related inhibition of mitochondrial respiration together with covalent binding of 4-HNE to mitochondrial proteins. We chose a 30 µM concentration of 4-HNE, which produced an approximately 50% inhibition of complex I- or complex II-driven respiration, to assess whether prior in vivo Nrf2-ARE-activating compounds would increase the resistance of the isolated cortical mitochondria to 4-HNE's mitotoxic effects. Administration of either compound significantly increased (p < 0.05) expression of heme oxygenase-1 mRNA in cortical tissue 48 h postadministration, verifying that both compounds were capable of inducing the Nrf2-ARE pathway. Moreover, the prior in vivo administration of SFP and CA significantly (p < 0.05) attenuated 4-HNE-induced inhibition of mitochondrial respiration for complex I, but only carnosic acid acted to protect complex II. Furthermore, both CA and SFP significantly (p < 0.05) reduced the amount of 4-HNE bound to mitochondrial proteins as determined by Western blot. These results demonstrate the capability of in vivo Nrf2-ARE induction to protect from 4-HNE toxicity to cortical mitochondria ex vivo. Ongoing studies will determine the therapeutic efficacy of Nrf2-ARE activators to attenuate traumatic brain injury-induced pathophysiology.

Phenelzine mitochondrial functional preservation and neuroprotection after traumatic brain injury related to scavenging of the lipid peroxidation-derived aldehyde 4-hydroxy-2-nonenal.

Phenelzine (PZ) is a scavenger of the lipid peroxidation (LP)-derived reactive aldehyde 4-hydroxynonenal (4-HNE) due to its hydrazine functional group, which can covalently react with 4-HNE. In this study, we first examined the ability of PZ to prevent the respiratory depressant effects of 4-HNE on normal isolated brain cortical mitochondria. Second, in rats subjected to controlled cortical impact traumatic brain injury (CCI-TBI), we evaluated PZ (10 mg/kg subcutaneously at 15 minutes after CCI-TBI) to attenuate 3-hour post-TBI mitochondrial respiratory dysfunction, and in separate animals, to improve cortical tissue sparing at 14 days. While 4-HNE exposure inhibited mitochondrial complex I and II respiration in a concentration-dependent manner, pretreatment with equimolar concentrations of PZ antagonized these effects. Western blot analysis demonstrated a PZ decrease in 4-HNE in mitochondrial proteins. Mitochondria isolated from peri-contusional brain tissue of CCI-TBI rats treated with vehicle at 15 minutes after injury showed a 37% decrease in the respiratory control ratio (RCR) relative to noninjured mitochondria. In PZ-treated rats, RCR suppression was prevented (P<0.05 versus vehicle). In another cohort, PZ administration increased spared cortical tissue from 86% to 97% (P<0.03). These results suggest that PZ's neuroprotective effect is due to mitochondrial protection by scavenging of LP-derived 4-HNE.

Current and emerging immunotherapeutic approaches to treat and prevent peanut allergy.

Peanut-allergen hypersensitivity reactions, which can result in anaphylactic episodes and death, affect approximately 1% of the general population. Currently, strict avoidance of allergenic food is the only available treatment for this food-induced allergic reaction; however, the innocuous presence of trace amounts of peanut protein contaminating food products makes avoidance extremely difficult, especially in children. Therefore, safe and inexpensive therapeutic strategies aimed at prevention and treatment of peanut allergies is urgently required. This review summarizes the current state of knowledge of adaptive immune recognition and responsiveness to peanut allergens and how this can be integrated and subverted into new therapeutic treatment regimens for these dangerous allergic responses. The potential for new strategic vaccination-based interventions to either moderate or prevent these types of responses from occurring is also discussed.

Relationship of nitric oxide synthase induction to peroxynitrite-mediated oxidative damage during the first week after experimental traumatic brain injury.

We have previously shown the pathophysiological importance of the reactive nitrogen species peroxynitrite (PN) formed from the reaction of nitric oxide (•NO) and superoxide (O(2)(•-)) radicals and its involvement in lipid peroxidation (LP) and protein nitration damage in brain tissue following traumatic brain injury (TBI). Nitric oxide is produced by at least three isoforms of the enzyme nitric oxide synthase (NOS) including: endothelial NOS (eNOS) in the CNS vasculature, neuronal NOS (nNOS), and inducible NOS (iNOS) in macrophages/microglia. In view of the requirement of •NO synthesis for PN formation, we sought to address the time course of NOS expression (mRNA by real time quantitative PCR and protein by western blot) after TBI in comparison with the time course of PN-mediated protein nitration (3-nitrotyrosine, 3-NT) in ipsilateral cortex (CTX) and hippocampus (HIPP) between 3 hours and 1 week post-injury using a controlled cortical impact (CCI) mouse model of TBI in young adult CF-1 mice. Protein nitration showed a progressive posttraumatic increase that became significant in CTX at 24 hours and then peaked at 72 hours in both CTX and HIPP. During the increase in PN-derived 3-NT, there was no increase in either CTX or HIPP eNOS mRNA levels, whereas eNOS protein levels were significantly (p<0.05) increased at 48 and 72 hours in both brain regions. There was a significant decrease in HIPP, but not CTX nNOS mRNA; however, nNOS protein did not change except for a significant increase in CTX at 1 week. There was significantly increased CTX and HIPP iNOS mRNA levels at 24, 48, and 72 hours (p<.05) post-injury. In contrast, no change was seen in CTX or HIPP iNOS protein at any timepoint. Taken together, eNOS protein expression and iNOS mRNA appear to bear a coincident temporal relationship to the time course of PN-mediated protein nitrative damage after CCI-TBI suggesting that both constitutive and inducible NOS isoforms contribute •NO for PN formation and 3-NT protein modification after TBI.

Selective polarization imager for contrast enhancements in remote scattering media.

Conventional intensity imaging through turbid media suffers from rapid loss of image contrast due to light scattering from particles or random variations of refractive index. This paper features the development of an active imaging, snapshot, system design and postprocessing algorithms that differentiate between radiation that scatters or reflects from remote, obscured objects and the radiation from the scattering media itself through a combination of polarization difference imaging, channel blurring, and Fourier spatial filtering. The produced sensor acquires and processes image data in real time, yielding improved image contrasts by factors of 10 or greater for dense water vapor obscurants.

Preclinical efficacy studies of influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine.

A universal influenza vaccine that does not require annual reformulation would have clear advantages over the currently approved seasonal vaccine. In this study, we combined the mucosal adjuvant alpha-galactosylceramide (αGalCer) and peptides designed across the highly conserved influenza precursor haemagglutinin (HA(0)) cleavage loop as a vaccine. Peptides designed across the HA(0) of influenza A/H3N2 viruses, delivered to mice via the intranasal route with αGalCer as an adjuvant, provided 100 % protection following H3N2 virus challenge. Similarly, intranasal inoculation of peptides across the HA(0) of influenza A/H5N1 with αGalCer completely protected mice against heterotypic challenge with H3N2 virus. Our data suggest that these peptide vaccines effectively inhibited subsequent influenza A/H3N2 virus replication. In contrast, only 20 % of mice vaccinated with αGalCer-adjuvanted peptides spanning the HA(0) of H5N1 survived homologous viral challenge, possibly because the HA(0) of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA(0) peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine.