Phloem loading in the sucrose-export-defective (SXD-1) mutant maize is limited by callose deposition at plasmodesmata in bundle sheath-vascular parenchyma interface

Using Lucifer Yellow we have demonstrated that the phloem-loading pathway from the mesophyll to the bundle sheath-vascular parenchyma interface in Zea mays source leaves follows a symplasmic route in small and intermediate vascular bundles in control as well as in the green sections of mutant sucrose-export-defective (SXD-1) plants. In the anthocyanin-rich mutant leaf sections, Lucifer Yellow transport was prohibited along the same path, at the bundle sheath-vascular parenchyma interface in particular. Plasmodesmata at the latter interface in SXD-1 anthocyanin-rich leaf sections appear to be structurally altered through callose deposition at the plasmodesmal orifices. We suggest that a transport bottleneck at the bundle sheath-vascular parenchyma interface is thus orchestrated and regulated through callose formation, preventing symplasmic transport across this important loading interface

Relative uptake of minoxidil into appendages and stratum corneum and permeation through human skin in vitro

We examined uptake of the model therapeutic agent, minoxidil, into appendages, stratum corneum (SC), and through human skin, under the influence of different vehicles. Quantitative estimation of therapeutic drug deposition into all three areas has not previously been reported. Finite doses of minoxidil (2%, w/v) in formulations containing varying amounts of ethanol, propylene glycol (PG), and water (60:20:20, 80:20:0, and 0:80:20 by volume, respectively) were used. Minoxidil in SC (by tape stripping), appendages (by cyanoacrylate casting), and receptor fluid was determined by liquid scintillation counting. At early times (30 min, 2 h), ethanol-containing formulations (60:20:20 and 80:20:0) caused significantly greater minoxidil retention in SC and appendages, compared to the formulation lacking ethanol (0:80:20). A significant increase in minoxidil receptor penetration occurred with the PG-rich 0:80:20 formulation after 12 h. We showed that deposition of minoxidil into appendages, SC, and skin penetration into receptor fluid were similar in magnitude. Transport by the appendageal route is likely to be a key determinant of hair growth promotion by minoxidil. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:712–718, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64562/1/21856_ftp.pd

Disease Introduction Is Associated With a Phase Transition in Bighorn Sheep Demographics

Ecological theory suggests that pathogens are capable of regulating or limiting host population dynamics, and this relationship has been empirically established in several settings. However, although studies of childhood diseases were integral to the development of disease ecology, few studies show population limitation by a disease affecting juveniles. Here, we present empirical evidence that disease in lambs constrains population growth in bighorn sheep (Ovis canadensis) based on 45 years of population‐level and 18 years of individual‐level monitoring across 12 populations. While populations generally increased (λ = 1.11) prior to disease introduction, most of these same populations experienced an abrupt change in trajectory at the time of disease invasion, usually followed by stagnant‐to‐declining growth rates (λ = 0.98) over the next 20 years. Disease‐induced juvenile mortality imposed strong constraints on population growth that were not observed prior to disease introduction, even as adult survival returned to pre‐invasion levels. Simulations suggested that models including persistent disease‐induced mortality in juveniles qualitatively matched observed population trajectories, whereas models that only incorporated all‐age disease events did not. We use these results to argue that pathogen persistence may pose a lasting, but under‐recognized, threat to host populations, particularly in cases where clinical disease manifests primarily in juveniles

Contact Networks and Mortality Patterns Suggest Pneumonia-Causing Pathogens may Persist in Wild Bighorn Sheep

Efficacy of disease control efforts is often contingent on whether the disease persists locally in the host population or is repeatedly introduced from an alternative host species. Local persistence is partially determined by the interaction between host contact structure and disease transmission rates: relatively isolated host groups facilitate pathogen persistence by slowing the rate at which highly transmissible pathogens access new susceptibles; alternatively, isolated host groups impede persistence for pathogens with low transmission rates by limiting the number of available hosts and forcing premature fade-out. Here, we use long-term data from the Hells Canyon region to investigate whether variable host contact patterns are associated with survival outcomes for 46 cohorts of bighorn sheep (Ovis canadensis) lambs subject to recurrent pneumonia outbreaks. We build social contact networks for each lamb cohort, and quantify variation in lamb mortality attributable to populations, years, and groups. We then refine estimates of chronic carriage rates in ewes, and disease-induced mortality rates in lambs, by finding parameters for the disease process that produce lamb morality rates similar to those observed when simulated on the observed host contact networks. Our results suggest that summer lamb hazards are spatially structured at the subpopulation level: 92.5 percent of the variation in lamb hazards during pneumonia outbreak years was attributable to sub-population-level groups, whereas 1.7 percent and 5.6 percent were attributable to year and population, respectively.  Additionally, the posterior distribution generated by our disease transmission model suggests that pneumonia-causing pathogens may persist locally in bighorn sheep populations, even during apparently healthy years

Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines

BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines

Elective Open Suprarenal Aneurysm Repair in England from 2000 to 2010 an Observational Study of Hospital Episode Statistics

Background: Open surgery is widely used as a benchmark for the results of fenestrated endovascular repair of complex abdominal aortic aneurysms (AAA). However, the existing evidence stems from single-centre experiences, and may not be reproducible in wider practice. National outcomes provide valuable information regarding the safety of suprarenal aneurysm repair. Methods: Demographic and clinical data were extracted from English Hospital Episodes Statistics for patients undergoing elective suprarenal aneurysm repair from 1 April 2000 to 31 March 2010. Thirty-day mortality and five-year survival were analysed by logistic regression and Cox proportional hazards modeling. Results: 793 patients underwent surgery with 14% overall 30-day mortality, which did not improve over the study period. Independent predictors of 30-day mortality included age, renal disease and previous myocardial infarction. 5-year survival was independently reduced by age, renal disease, liver disease, chronic pulmonary disease, and known metastatic solid tumour. There was significant regional variation in both 30-day mortality and 5-year survival after risk-adjustment. Regional differences in outcome were eliminated in a sensitivity analysis for perioperative outcome, conducted by restricting analysis to survivors of the first 30 days after surgery. Conclusions: Elective suprarenal aneurysm repair was associated with considerable mortality and significant regional variation across England. These data provide a benchmark to assess the efficacy of complex endovascular repair of supra-renal aneurysms, though cautious interpretation is required due to the lack of information regarding aneurysm morphology. More detailed study is required, ideally through the mandatory submission of data to a national registry of suprarenal aneurysm repair

Pneumonia in Bighorn Sheep: Testing the Super-Spreader Hypothesis

Following introduction of pneumonia, disease can persist in bighorn sheep (Ovis canadensis) populations for decades as annual or sporadic pneumonia epidemics in lambs.  Recurring years of depressed recruitment due to high rates of pneumonia-induced mortality in juveniles is a major obstacle to population recovery.  Management strategies for resolving this problem have so far been elusive. We are investigating the feasibility of removing individual “super-spreaders” to improve lamb survival.  Individual variation in infection and transmission is well documented in human diseases (e.g. “Typhoid Mary”).  We are testing the hypothesis that pneumonia epidemics in lambs are initiated by transmission of pathogens from a few “chronic-shedder” ewes. We have completed the first year of a 5-year project in the Hells Canyon region of Idaho, Oregon, and Washington, and in a captive population at South Dakota State University. Through repeated testing of free-ranging individuals in Hells Canyon, we have identified individual differences in shedding of Mycoplasma ovipneumoniae, a primary pathogen in the bighorn sheep respiratory disease complex.  We also found that when penned separately in captivity, lambs of ewes that consistently tested positive (chronic shedders) were infected and died of pneumonia, whereas lambs born to ewes from an infected population that tested negative (non-shedders), were not infected and survived.  Over the next 4 years we plan to 1) continue and expand testing of free-ranging and captive animals, 2) determine whether removal of chronic-shedder ewes improves lamb survival in free-ranging populations, 3) expand and replicate chronic-shedder commingling experiments in captivity, and 4) establish and monitor a new population founded with non-shedders from an infected population

Athletes Perceive Weighted Baseballs to Carry a Notable Injury Risk, yet Still Use Them Frequently: A Multicenter Survey Study

INTRODUCTION: Weighted baseball use in throwing programs is widespread; however, their use remains controversial. Prior research shows that weighted baseball programs can increase ball velocity but potentially increase throwing arm injuries. This study aims to ascertain perceptions of weighted baseballs among elite baseball players. METHODS: A created online survey questioned common practices, throwing regimens, injury risk factors, and weighted baseball program use. The questions were modeled to ascertain the perceptions of elite baseball players to understand their experience with weighted baseballs. Descriptive statistical analysis was conducted. RESULTS: Three hundred seventy-six baseball players with a mean age of 20 ± 2 years completed the survey; 64% of the players (239/376) were pitchers. 71% (267/376) reported the use of weighted baseballs. Of those, 75% (199/267) thought it made them a better player. Overall, 73% (275/377) thought weighted baseballs are a risk for injury. 17% (46/267) attributed their injury to using weighted baseballs. Overall, participants reported a mean 72% ± 30% likelihood of future weighted baseball use. CONCLUSION: Most of the participating elite adult baseball players reported prior weighted baseball use with a corresponding improvement in pitching performance despite a perceived increased injury risk. Nearly 20% of the players attributed pain or injury to weighted baseball use. Moreover, the players surveyed intend to continue using weighted baseballs because of the perceived performance benefit

Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress.

Fetal hypoxia is a common complication of pregnancy. It has been shown to programme cardiac and endothelial dysfunction in the offspring in adult life. However, the mechanisms via which this occurs remain elusive, precluding the identification of potential therapy. Using an integrative approach at the isolated organ, cellular and molecular levels, we tested the hypothesis that oxidative stress in the fetal heart and vasculature underlies the molecular basis via which prenatal hypoxia programmes cardiovascular dysfunction in later life. In a longitudinal study, the effects of maternal treatment of hypoxic (13% O(2)) pregnancy with an antioxidant on the cardiovascular system of the offspring at the end of gestation and at adulthood were studied. On day 6 of pregnancy, rats (n = 20 per group) were exposed to normoxia or hypoxia ± vitamin C. At gestational day 20, tissues were collected from 1 male fetus per litter per group (n = 10). The remaining 10 litters per group were allowed to deliver. At 4 months, tissues from 1 male adult offspring per litter per group were either perfusion fixed, frozen, or dissected for isolated organ preparations. In the fetus, hypoxic pregnancy promoted aortic thickening with enhanced nitrotyrosine staining and an increase in cardiac HSP70 expression. By adulthood, offspring of hypoxic pregnancy had markedly impaired NO-dependent relaxation in femoral resistance arteries, and increased myocardial contractility with sympathetic dominance. Maternal vitamin C prevented these effects in fetal and adult offspring of hypoxic pregnancy. The data offer insight to mechanism and thereby possible targets for intervention against developmental origins of cardiac and peripheral vascular dysfunction in offspring of risky pregnancy

Genetic stock identification of Atlantic salmon (Salmo salar) populations in the southern part of the European range

notes: PMCID: PMC2882343© 2010 Griffiths et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Anadromous migratory fish species such as Atlantic salmon (Salmo salar) have significant economic, cultural and ecological importance, but present a complex case for management and conservation due to the range of their migration. Atlantic salmon exist in rivers across the North Atlantic, returning to their river of birth with a high degree of accuracy; however, despite continuing efforts and improvements in in-river conservation, they are in steep decline across their range. Salmon from rivers across Europe migrate along similar routes, where they have, historically, been subject to commercial netting. This mixed stock exploitation has the potential to devastate weak and declining populations where they are exploited indiscriminately. Despite various tagging and marking studies, the effect of marine exploitation and the marine element of the salmon lifecycle in general, remain the "black-box" of salmon management. In a number of Pacific salmonid species and in several regions within the range of the Atlantic salmon, genetic stock identification and mixed stock analysis have been used successfully to quantify exploitation rates and identify the natal origins of fish outside their home waters - to date this has not been attempted for Atlantic salmon in the south of their European range.European Union INTERREG IIIB programme (Atlantic Salmon Arc Project [ASAP], Project No. 040)