Impact of CD40 ligand, B cells, and mast cells in peanut-induced anaphylactic responses

The effector immune mechanisms underlying peanut-induced anaphylaxis remain to be fully elucidated. We investigated the relative contribution of Igs, mast cells (MCs), and FcepsilonRI in the elicitation of anaphylaxis in a murine model. Assessment of peanut hypersensitivity reactions was performed clinically and biologically. Our data show that wild-type (WT; C57BL/6 strain) mice consistently developed severe anaphylaxis (median clinical score: 3.5/5), an approximately 8 degrees C drop in core body temperature, and significantly increased plasma levels of histamine and leukotrienes. CD40 ligand- and B cell-deficient mice presented evidence of allergic sensitization as demonstrated by production of Th2-associated cytokines by splenocytes and a late-phase inflammatory response that were both indistinguishable to those detected in WT mice. However, CD40 ligand- and B cell-deficient mice did not exhibit any evidence of anaphylaxis. Our data also show that MC-deficient (Kit(W)/Kit(W-v)) mice did not suffer, unlike their littermate controls, anaphylactic reactions despite the fact that serum levels of peanut-specific Igs were similarly elevated. Finally, FcepsilonRI-deficient mice experienced anaphylactic responses although to a significantly lesser degree than those observed in WT mice. Thus, these data demonstrate that the presence of peanut-specific Abs along with functional MCs comprise a necessary and sufficient condition for the elicitation of peanut-induced anaphylaxis. That the absence of FcepsilonRI prevented the development of anaphylaxis only partially insinuates the contribution of an IgE-independent pathway, and suggests that strategies to impair MC degranulation may be necessary to improve the efficacy of anti-IgE therapy.     

Adolescents' perceived weight associated with depression in young adulthood: a longitudinal study

Objective: The objective of this study is to examine whether adolescents’ measured BMI and self‐ or mother's perception of weight status at age 14 are associated with depression at age 21. Research Methods and Procedures: The study participants were a subsample of 2017 participants of the Mater–University of Queensland Study of Pregnancy and Its Outcomes, a population‐based birth cohort study, which commenced in 1981 in Brisbane, Australia, for whom measured BMI at ages 14 and 21 and information on self‐reported mental health problems were available at the age 21 follow‐up. A total of 1802 individuals had measured BMI and reported weight perception in a supplementary questionnaire at 14 years, and their self‐reported mental health problems were reported at 21 years. Mental health was measured using Center for Epidemiology Studies Depression Scale and Young Adults Self‐Reported depression/anxiety at 21 years of age. Results: We found that both young adult males and females who perceived themselves as overweight at age 14 had more mental health problems compared with those who perceived themselves as the right weight. When we combined adolescents’ weight perception with their measured BMI categories, weight perception but not measured overweight was associated with mental health problems for males and females at age 21. This association remained after adjusting for potential confounders, including adolescents’ behavioral problems, family meals, diet, physical activity, and television watching. Conclusions: This study suggests that the perception of being overweight during adolescence is a significant risk factor for depression in young adult men and women. The perception of being overweight during adolescence should be considered a possible target for a prevention intervention.     

The effect of INA [(R)-1-O-(1-pyrenylmethyl)glycerol] insertions on the structure and biological activity of a G-quadruplex from a critical KRAS G-rich sequence

Quadruplex-forming oligonucleotides containing INA [(R)-1-O-(1-pyrenylmethyl)glycerol] insertions have been designed and studied for their capacity to inhibit the expression of the KRAS oncogene in pancreatic adenocarcinoma cells. It is found that INA can influence the folding topology of the G-quadruplex. The oligonucleotides forming the most stable G-quadruplex (ODN-637) is found to exhibit the highest bioactivity.     

Phytoplankton vertical distributions and composition in Baltic Sea cyanobacterial blooms

We studied the vertical structure of the phytoplankton community in two toxic cyanobacterial blooms in the offshore Baltic Sea. In 1994, vertically separated potentially toxic, diazotrophic and mixotrophic species (belonging to Cyanophyceae, Dinophyceae and Prymnesiophyceae) dominated. In 1997, picocyanobacteria, mainly in colonies, made up 40–50% of the total phytoplankton carbon biomass in the top 20 m both day and night. Colony-forming species of picocyanobacteria seem to be occasionally important and hitherto underestimated in the Baltic Sea.We found species-specific depth distribution patterns. Nodularia spumigena and Anabaena spp. were observed mainly above 10 m depth, while Aphanizomenon sp. was mostly found deeper, especially at night. Dinophysis norvegica was only abundant near the seasonal pycnocline and showed very limited diurnal migration. Other flagellates, including small Cryptophyceae and 10 identified Chrysochromulina species, occurred down to 40 m depth. Their vertical migration may help to retrieve nutrients from below the summer pycnocline.We conclude that considerable differences in dominating functional groups may occur between years/bloom stages, and that the vertical distribution pattern of many species is recurring at similar environmental conditions, suggesting species-specific niche-separation.     

Feral horse impacts on threatened plants and animals in sub‐alpine and montane environments in Victoria,Australia

Feral herbivores are a major driver of biodiversity loss globally and can alter the structure, composition and functioning of ecosystems. The direct impacts of feral herbivores on plant communities are well studied, but the direct and indirect effect they have on wildlife is not well understood. In Victoria (south‐eastern Australia), a large feral Horse (Equus caballus) population coincides with highly sensitive and nationally endangered Alpine Sphagnum Bogs and Associated Fens communities, and several threatened animal species. We assessed the impact of feral horses on this ecological community and the Alpine Water Skink (Eulamprus kosciuskoi) and the Broad‐toothed Rat (Mastacomys fuscus) at 20 sites with varying levels of horse disturbance. We used scat counts to determine an index of feral horse abundance and quantified impacts associated with their presence in the landscape. Active searches were used for Alpine Water Skink and scat and runway surveys for Broad‐toothed Rat. We also measured the vegetation structure and the abundance of different vegetation types (life forms). Our results suggest that feral horses are associated with vegetation types and characteristics that negatively influence the presence or abundance of Alpine Water Skink and Broad‐toothed Rat. Sites with high horse activity had more low‐growing forbs, and the abundance of Alpine Water Skink was negatively related to this vegetation type. Grasses, sedges, rushes and shrubs were also less dense and lower in height in high horse activity sites, and Broad‐toothed Rat was less likely to be present in areas with these habitat attributes. We recommend that feral horses are controlled to protect these threatened vertebrate species and their Sphagnum bog habitat.     

Gene-by-Sex Interactions in Mitochondrial Functions and Cardio-Metabolic Traits

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Precipitation of complex antibody solutions: influence of contaminant composition and cell culture medium on the precipitation behavior

Preparative protein precipitation is known as a cost-efficient and easy-to-use alternative to chromatographic purification steps. This said, at the moment, there is no process for monoclonal antibodies (mAb) on the market, although especially polyethylene glycol-induced precipitation has shown great potential. One reason might be the highly complex behavior of each component of a crude feedstock during the precipitation process. For different investigated mAbs, significant variations in the host cell protein (HCP) reduction are observed. In contrast to the precipitation behavior of single components, the interactions and interplay in a complex feedstock are not fully understood yet. This work discusses the influence of contaminants on the precipitation behavior of two different mAbs, an IgG1, and an IgG2. By spiking the mAbs with mock solution, a complex feedstock could successfully be mimicked. Spiking contaminants influenced the yield and purity of the mAbs after the precipitation step, compared to the precipitation behavior of the single components. The mixture showed a decrease in the contaminant and mAb solubility. By re-buffering the mock solution prior to spiking, special salts, small molecules like amino acids, vitamins, or sugars could be depleted while larger ones like HCP or DNA were still present. Therefore, it was possible to distinguish the influence of small molecules and larger ones. Hence, mAb–macromolecular interaction could be identified as a possible reason for the observed higher precipitation propensity, while small molecules of the cell culture medium were identified as solubilisation factors during the precipitation process.

     

Essential waters: Young bull sharks in Fiji's largest riverine system

Coastal and estuarine systems provide critical shark habitats due to their relatively high productivity and shallow, protected waters. The young (neonates, young‐of‐the‐year, and juveniles) of many coastal shark species occupy a diverse range of habitats and areas where they experience environmental variability, including acute and seasonal shifts in local salinities and temperatures. Although the location and functioning of essential shark habitats has been a focus in recent shark research, there is a paucity of data from the South Pacific. In this study, we document the temporal and spatial distribution, age class composition, and environmental parameters of young bull sharks (Carcharhinus leucas) in the Rewa, Sigatoka, and Navua Rivers, Fiji's three largest riverine systems. One hundred and seventy‐two young bull sharks were captured in fisheries‐independent surveys from January 2016 to April 2018. The vast majority of the captures were neonates. Seasonality in patterns of occurrence of neonate individuals suggests a defined parturition period during summer. Environmental parameters between the Rewa and the Sigatoka River differed significantly, as did the recorded young bull sharks abundance. According to the surveys, young bull sharks occur in all three rivers with the Rewa River likely representing essential habitat for newly born bull sharks. These results enhance the understanding of bull shark ecology in Fiji and provide a scientific basis for the implementation of local conservation strategies that contribute to the protection of critical habitats.     

Characterising deviation from treat-to-target strategies for early rheumatoid arthritis: the first three years

IntroductionTreat-to-target (T2T) strategies using a protocol of pre-defined adjustments of disease-modifying anti-rheumatic drugs (DMARDs) according to disease activity improve outcomes for patients with rheumatoid arthritis (RA). However, successful implementation may be limited by deviations from the protocol. The aim of this study was to determine the prevalence of protocol deviation, explore the reasons and identify subsets of patients in whom treatment protocols are more difficult to follow.MethodsIn this retrospective cohort study, treatment-naïve patients with RA of less than one year’s duration, attending a dedicated early arthritis clinic between 2001 and 2013, were followed for three years from initiation of combination therapy with conventional DMARDs which was subsequently modified according to a T2T protocol. At each clinic visit, whether deviation from the protocol occurred, the type of deviation and the reasons for deviation were assessed. The relationship between protocol deviations and baseline variables was determined using linear regression analysis.ResultsIn total, 198 patients contributed 3,654 clinic visits. The prevalence of protocol deviations was 24.5% and deviation in at least at one clinic visit was experienced by 90.4% of patients. The median time to first deviation was 30 weeks. Continuing existing treatment rather than intensifying therapy was the most common type of deviation (59.9%). Patient and physician related factors were the most common reasons for deviation, each accounting for 24.7% of deviations, followed by toxicities (23.3%) and comorbidities (20.0%). The prevalence of protocol deviations was lower among patients who achieved remission after three years (13.1%; 162 deviations out of 1,228 visits) compared with those who were not in remission (30.9%; 523/1692) (P <0.0001). On multivariate analysis, only body mass index (P = 0.003) and helplessness score (P = 0.04) were independent predictors of protocol deviations although the predictive power of the model was not strong (R² = 0.17).ConclusionsDeviation from a T2T protocol occurred in one quarter of visits, indicating that applying the T2T approach is feasible in clinical practice. Failure to escalate dose when indicated was commonly encountered, and just under half of the observed deviations were related to either toxicities or comorbidities and were therefore justifiable on clinical grounds.