Effects of perinatal exposure to PCBs and dioxins on play behavior in Dutch children at school age.

Polychlorinated biphenyls (PCBs) and dioxins are known as neurotoxic compounds that may modulate sex steroid hormones. Steroid hormones play a mediating role in brain development and may influence behaviors that show sex differences, such as childhood play behavior. In this study we evaluated the effects of perinatal exposure to environmental levels of PCBs and dioxins on childhood play behavior and whether the effects showed sex differences. As part of the follow-up to the Dutch PCB/dioxin study at school age, we used the Pre-School Activity Inventory (PSAI) to assess play behavior in the Rotterdam cohort (n = 207). The PSAI assesses masculine or feminine play behavior scored on three subscales: masculine, feminine, and composite. Prenatal exposure to PCBs was defined as the sum of PCB 118, 138, 153, and 180 in maternal and cord plasma and breast milk. For breast milk we measured additional PCBs as well as 17 dioxins. Respondents returned 160 questionnaires (age 7.5 years +/- 0.4). Effects of prenatal exposure to PCBs, measured in maternal and cord plasma, on the masculine and composite scales were different for boys and girls (p <.05). In boys, higher prenatal PCB levels were related with less masculinized play, assessed by the masculine scale (p(maternal) =.042; p(cord) =.001) and composite scale (p(cord) =.011), whereas in girls higher PCB levels were associated with more masculinized play, assessed by the composite scale (p(PCBmilk) =.028). Higher prenatal dioxin levels were associated with more feminized play in boys as well as girls, assessed by the feminine scale (p =.048). These effects suggest prenatal steroid hormone imbalances caused by prenatal exposure to environmental levels of PCBs, dioxins, and other related organochlorine compounds

Structural characterization and immunogenicity in wild-type and immune tolerant mice of degraded recombinant human interferon Alpha2b

Purpose: This study was conducted to study the influence of protein structure on the immunogenicity in wild-type and immune tolerant mice of well-characterized degradation products of recombinant human interferon alpha2b (rhIFNα2b). Methods: RhIFNα2b was degraded by metal-catalyzed oxidation (M), cross-linking with glutaraldehyde (G), oxidation with hydrogen peroxide (H), and incubation in a boiling water bath (B). The products were characterized with UV absorption, circular dichroism and fluorescence spectroscopy, gel permeation chromatography, reverse-phase high-pressure liquid chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, and mass spectrometry. The immunogenicity of the products was evaluated in wild-type mice and in transgenic mice immune tolerant for hIFNα2. Serum antibodies were detected by enzyme-linked immunosorbent assay or surface plasmon resonance. Results: M-rhIFNα2b contained covalently aggregated rhIFNα2b with three methionines partly oxidized to methionine sulfoxides. G-rhIFNα2b contained covalent aggregates and did not show changes in secondary structure. H-rhIFNα2b was only chemically changed with four partly oxidized methionines. B-rhIFNα2b was largely unfolded and heavily aggregated. Nontreated (N) rhIFNα2b was immunogenic in the wild-type mice but not in the transgenic mice, showing that the latter were immune tolerant for rhIFNα2b. The anti-rhIFNα2b antibody levels in the wild-type mice depended on the degradation product: M-rhIFNα2b > H-rhIFNα2b ∼ N-rhIFNα2b ≫ B-rhIFNα2b; G-rhIFNα2b did not induce anti-rhIFNα2b antibodies. In the transgenic mice, only M-rhIFNα2b could break the immune tolerance. Conclusions: RhIFNα2b immunogenicity is related to its structural integrity. Moreover, the immunogenicity of aggregated rhIFNα2b depends on the structure and orientation of the constituent protein molecules and/or on the aggregate size

Evaluation of factors associated with bulk milk somatic cell count and total plate count in Indonesian smallholder dairy farms

Increasing milk quality in smallholder dairy farms will result in a greater quantity of milk being delivered to milk collection centers, an increased milk price for farmers and consequently an improved farmers’ livelihood. However, little research on milk quality has been performed on smallholder farms in Southeast Asia. The objective of this study was to identify risk factors associated with somatic cell count (SCC) and total plate count (TPC) in Indonesian smallholder dairy farms. One dairy cooperative in West Java, Indonesia was selected based on its willingness to participate. All 119 member farmers in the cooperative, clustered in six groups, were interviewed and a bulk milk sample from all farms was collected in April 2022. Risk factors associated with dairy farms’ SCC and TPC were investigated using multivariable population-averaged generalized estimating equations (GEE) models. The mean geometric SCC and TPC from these farms were 529,665 cells/mL of milk and 474,492 cfu/mL of milk, respectively. Five risk factors including manure removal frequency, receiving mastitis treatment training, washing the udder using soap, number of workers, and ownership of the pasture area were associated with SCC. Two risk factors, manure removal frequency and dairy income contribution, were associated with TPC. These findings can therefore be used as a starting point to improve udder health and milk quality in Indonesia and other countries where smallholder farmers play a significant role in milk production

The effects of pause software on the temporal characteristics of computer use.

The study investigated the natural work-pause pattern of computer users and the possible effects of imposing pause regimes on this pattern. Hereto, the precise timing of computer events was recorded across a large number of days. It was found that the distribution of the pause durations was extremely skewed and that pauses with twice the duration are twice less likely to occur. The effects of imposing pause regimes were studied by performing a simulation of commercially available pause software. It was found that depending on the duration of the introduced pause, the software added 25-57% of the pauses taken naturally. Analysis of the timing of the introduced pauses revealed that a large number of spontaneous pauses were taken close to the inserted pause. Considering the disappointing results of studies investigating the effects of introducing (active) pauses during computer work, this study has cast doubt on the usefulness of introducing short duration pauses

Measuring Generalization of Visuomotor Perturbations in Wrist Movements Using Mobile Phones

Recent studies in motor control have shown that visuomotor rotations for reaching have narrow generalization functions: what we learn during movements in one direction only affects subsequent movements into close directions. Here we wanted to measure the generalization functions for wrist movement. To do so we had 7 subjects performing an experiment holding a mobile phone in their dominant hand. The mobile phone's built in acceleration sensor provided a convenient way to measure wrist movements and to run the behavioral protocol. Subjects moved a cursor on the screen by tilting the phone. Movements on the screen toward the training target were rotated and we then measured how learning of the rotation in the training direction affected subsequent movements in other directions. We find that generalization is local and similar to generalization patterns of visuomotor rotation for reaching

A framework to assess the resilience of farming systems

Agricultural systems in Europe face accumulating economic, ecological and societal challenges, raising concerns about their resilience to shocks and stresses. These resilience issues need to be addressed with a focus on the regional context in which farming systems operate because farms, farmers’ organizations, service suppliers and supply chain actors are embedded in local environments and functions of agriculture. We define resilience of a farming system as its ability to ensure the provision of the system functions in the face of increasingly complex and accumulating economic, social, environmental and institutional shocks and stresses, through capacities of robustness, adaptability and transformability. We (i) develop a framework to assess the resilience of farming systems, and (ii) present a methodology to operationalize the framework with a view to Europe’s diverse farming systems. The framework is designed to assess resilience to specific challenges (specified resilience) as well as a farming system’s capacity to deal with the unknown, uncertainty and surprise (general resilience). The framework provides a heuristic to analyze system properties, challenges (shocks, long-term stresses), indicators to measure the performance of system functions, resilience capacities and resilience-enhancing attributes. Capacities and attributes refer to adaptive cycle processes of agricultural practices, farm demographics, governance and risk management. The novelty of the framework pertains to the focal scale of analysis, i.e. the farming system level, the consideration of accumulating challenges and various agricultural processes, and the consideration that farming systems provide multiple functions that can change over time. Furthermore, the distinction between three resilience capacities (robustness, adaptability, transformability) ensures that the framework goes beyond narrow definitions that limit resilience to robustness. The methodology deploys a mixed-methods approach: quantitative methods, such as statistics, econometrics and modelling, are used to identify underlying patterns, causal explanations and likely contributing factors; while qualitative methods, such as interviews, participatory approaches and stakeholder workshops, access experiential and contextual knowledge and provide more nuanced insights. More specifically, analysis along the framework explores multiple nested levels of farming systems (e.g. farm, farm household, supply chain, farming system) over a time horizon of 1-2 generations, thereby enabling reflection on potential temporal and scalar trade-offs across resilience attributes. The richness of the framework is illustrated for the arable farming system in Veenkoloniën, the Netherlands. The analysis reveals a relatively low capacity of this farming system to transform and farmers feeling distressed about transformation, while other members of their households have experienced many examples of transformation

Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II

Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin/lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. A Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wildtype. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin2 inserts into the membrane and we propose this is the first step in pore formation, mediated by the nisin N-terminus–lipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation