A cross-sectional study to collect risk factors associated with stillbirths in pig herds

The aim of this study was to identify risk factors for stillborn piglets at herd level in commercial pig herds. A written questionnaire, containing semi-open questions directly or indirectly related to stillborn piglets, was sent to 250 randomly selected pig herds (>150 sows) in northern Belgium. In total 111/250 questionnaires were returned (response rate of 44.4%) and 107 were valid for analysis. The average reported frequency of stillbirth was 7.5% (S.D. 2.8%). The relationship between risk factors and stillbirths was evaluated with a generalized linear effects model with the percentage of stillborn piglets as outcome variable. Type of breed used on the farm was significantly (P < 0.01) associated with the percentage of stillborn piglets. A high temperature in the farrowing unit (≥22 °C compared to <22 °C) was associated with significantly (P < 0.01) more stillbirths, whereas showering sows with warm water before parturition resulted in significantly less stillbirths (5.8%) than no showering (7.7%) (P < 0.01) and was not significantly different from showering with cold water (7.0%) (P = 0.26). When supervision of farrowing was performed occasionally, significantly more stillbirths (8.1%) were observed in comparison with no attending to farrowing (6.5%) (P < 0.01) or frequent supervision of farrowing (6.9%) (P < 0.01). Significant interactions were found between breed and showering sows prior parturition or supervision of sows at parturition, and between temperature in the farrowing unit at parturition and showering procedure of the sows. In conclusion, this study has clearly demonstrated that breed is a major factor involved in the frequency of stillbirth. Additionally, some management practices before or at parturition may reduce the number of stillborn piglets.     

How efficiently do corn‐ and soybean‐based cropping systems use water? A systems modeling analysis

Agricultural systems are being challenged to decrease water use and increase production while climate becomes more variable and the world's population grows. Low water use efficiency is traditionally characterized by high water use relative to low grain production and usually occurs under dry conditions. However, when a cropping system fails to take advantage of available water during wet conditions, this is also an inefficiency and is often detrimental to the environment. Here, we provide a systems‐level definition of water use efficiency (sWUE) that addresses both production and environmental quality goals through incorporating all major system water losses (evapotranspiration, drainage, and runoff). We extensively calibrated and tested the Agricultural Production Systems sIMulator (APSIM) using 6 years of continuous crop and soil measurements in corn‐ and soybean‐based cropping systems in central Iowa, USA. We then used the model to determine water use, loss, and grain production in each system and calculated sWUE in years that experienced drought, flood, or historically average precipitation. Systems water use efficiency was found to be greatest during years with average precipitation. Simulation analysis using 28 years of historical precipitation data, plus the same dataset with ± 15% variation in daily precipitation, showed that in this region, 430 mm of seasonal (planting to harvesting) rainfall resulted in the optimum sWUE for corn, and 317 mm for soybean. Above these precipitation levels, the corn and soybean yields did not increase further, but the water loss from the system via runoff and drainage increased substantially, leading to a high likelihood of soil, nutrient, and pesticide movement from the field to waterways. As the Midwestern United States is predicted to experience more frequent drought and flood, inefficiency of cropping systems water use will also increase. This work provides a framework to concurrently evaluate production and environmental performance of cropping systems.     

Have we overestimated the benefit of human(ized) antibodies?

The infusion of animal-derived antibodies has been known for some time to trigger the generation of antibodies directed at the foreign protein as well as adverse events including cytokine release syndrome. These immunological phenomena drove the development of humanized and fully human monoclonal antibodies. The ability to generate human(ized) antibodies has been both a blessing and a curse. While incremental gains in the clinical efficacy and safety for some agents have been realized, a positive effect has not been observed for all human(ized) antibodies. Many human(ized) antibodies trigger the development of anti-drug antibody responses and infusion reactions. The current belief that antibodies need to be human(ized) to have enhanced therapeutic utility may slow the development of novel animal-derived monoclonal antibody therapeutics for use in clinical indications. In the case of murine antibodies, greater than 20% induce tolerable/negligible immunogenicity, suggesting that in these cases humanization may not offer significant gains in therapeutic utility. Furthermore, humanization of some murine antibodies may reduce their clinical effectiveness. The available data suggest that the utility of human(ized) antibodies needs to be evaluated on a case-by-case basis, taking a cost-benefit approach, taking both biochemical characteristics and the targeted therapeutic indication into account.Key words: immunogenicity, human anti-mouse antibody, cytokine release syndrome     

Age and intraspecific diversity of resilient Acropora communities in Belize

Coral Reefs - The corals Acropora palmata and A. cervicornis are important Caribbean reef-builders that have faced significant mortality in recent decades. While many studies have focused on the...     

Tolerance induced by apoptotic antigen-coupled leukocytes is induced by PD-L1+ and IL-10-producing splenic macrophages and maintained by T regulatory cells

Ag-specific tolerance is a highly desired therapy for immune-mediated diseases. Intravenous infusion of protein/peptide Ags linked to syngeneic splenic leukocytes with ethylene carbodiimide (Ag-coupled splenocytes [Ag-SP]) has been demonstrated to be a highly efficient method for inducing peripheral, Ag-specific T cell tolerance for treatment of autoimmune disease. However, little is understood about the mechanisms underlying this therapy. In this study, we show that apoptotic Ag-SP accumulate in the splenic marginal zone, where their uptake by F4/80(+) macrophages induces production of IL-10, which upregulates the expression of the immunomodulatory costimulatory molecule PD-L1 that is essential for Ag-SP tolerance induction. Ag-SP infusion also induces T regulatory cells that are dispensable for tolerance induction but required for long-term tolerance maintenance. Collectively, these results indicate that Ag-SP tolerance recapitulates how tolerance is normally maintained in the hematopoietic compartment and highlight the interplay between the innate and adaptive immune systems in the induction of Ag-SP tolerance. To our knowledge, we show for the first time that tolerance results from the synergistic effects of two distinct mechanisms, PD-L1-dependent T cell-intrinsic unresponsiveness and the activation of T regulatory cells. These findings are particularly relevant as this tolerance protocol is currently being tested in a Phase I/IIa clinical trial in new-onset relapsing-remitting multiple sclerosis.     

An Mll-dependent Hox program drives hematopoietic progenitor expansion

Chromosomal translocations disrupting the Mixed lineage leukemia (Mll) gene result in leukemia, with aberrant expression of some native Mll target genes (reviewed in). The Mll gene encodes a Trithorax-group chromatin regulator that is essential for the development of hematopoietic stem cells (HSCs) during embryogenesis. Like Trithorax, MLL positively regulates clustered homeodomain or Hox genes, yet the role of Hox genes collectively in the development of the mammalian hematopoietic system has been difficult to ascertain because of redundancy among Hox paralogs. Here, we show that in the absence of MLL, early hematopoietic progenitors develop despite reduced expression of HoxA, HoxB, and HoxC genes. However, these progenitors exhibit a marked reduction in their ability to generate hematopoietic colonies, a subsequent process requiring cell division and differentiation. Reactivation of a subset of Hox genes or, remarkably, reexpression of a single Hox gene in Mll-deficient progenitors rescued hematopoietic-colony frequency and growth. In contrast, expression of other MLL target genes such as Pitx2 or expression of anti-apoptotic BCL-2 failed to rescue hematopoietic-colony frequency. Furthermore, our results highlight a shared function of Hox proteins at this point in the development of the hematopoietic system.     

The utility of Shewanella japonica for microbial fuel cells

Shewanella-containing microbial fuel cells (MFCs) typically use the fresh water wild-type strain Shewanella oneidensis MR-1 due to its metabolic diversity and facultative oxidant tolerance. However, S. oneidensis MR-1 is not capable of metabolizing polysaccharides for extracellular electron transfer. The applicability of Shewanella japonica (an agar-lytic Shewanella strain) for power applications was analyzed using a diverse array of carbon sources for current generation from MFCs, cellular physiological responses at an electrode surface, biofilm formation, and the presence of soluble extracellular mediators for electron transfer to carbon electrodes. Critically, air-exposed S. japonica utilizes biosynthesized extracellular mediators for electron transfer to carbon electrodes with sucrose as the sole carbon source.     

Spatial patterns of tree recruitment in a relict population of Pinus uncinata: forest expansion through stratified diffusion

Aim To infer future changes in the distribution of isolated relict tree populations at the limit of a species’ geographical range, a deep understanding of the regeneration niche and the spatial pattern of tree recruitment is needed. Location A relict Pinus uncinata population located at the south‐western limit of distribution of the species in the Iberian System of north‐eastern Spain. Methods Pinus uncinata individuals were mapped within a 50 × 40‐m plot, and their size, age and reproductive status were estimated. Data on seed dispersal were obtained from a seed‐release experiment. The regeneration niche of the species was assessed based on the associations of seedling density with substrate and understorey cover. The spatial pattern of seedlings was described using point‐pattern (Ripley's K) and surface‐pattern (correlograms, Moran's I) analyses. Statistical and inverse modelling were used to characterize seedling clustering. Results Pine seedlings appeared aggregated in 6‐m patches. Inverse modelling estimated a longer mean dispersal distance (27 m), which corresponded to the size of a large cluster along the north to north‐eastward direction paralleled by an eastward trend of increasing seedling age. The two spatial scales of recruitment were related to two dispersal processes. The small‐scale clustering of seedlings was due to local seed dispersal in open areas near the edge of Calluna vulgaris mats: the regeneration niche. The long‐range expansion might be caused by less frequent medium‐distance dispersal events due to the dominant north‐westerly winds. Main conclusions To understand future range shifts of marginal tree populations, data on seed dispersal, regeneration niche and spatial pattern of recruitment at local scales should be obtained. The monitoring of understorey communities should be a priority in order to predict correctly shifts in tree species range in response to global warming.     

Role of IFN-gamma in an experimental murine model of West Nile virus-induced seizures

Seizures are a major complication of viral encephalitis. However, the mechanisms of seizure-associated neuronal dysfunction remain poorly understood. We report that intranasal inoculation with West Nile virus (WNV) (Sarafend) causes limbic seizures in C57BL/6 mice, but not in interferon (IFN)-gamma-deficient (IFN-gamma-/-) mice. Both strains showed similar levels of virus in the brain, as well as similar concentrations of the cytokines, tumor necrosis factor and interleukin-6, both of which can alter neuronal excitability. Experiments in chimeric IFN-gamma-/- mice reconstituted with IFN-gamma-producing leukocytes showed that IFN-gamma is not required during central nervous system infection for limbic seizure development, suggesting a role for IFN-gamma in the developing brain. This was supported responses to pentylenetetrazole, kainic acid (KA), and N-methyl-d-aspartate (NMDA). Both strains of mice exhibited similar behavior after pentylenetetrazole challenge. However, while NMDA and KA treatment resulted in characteristic seizures in C57BL/6 mice, these responses were diminished (NMDA treatment) or absent (KA treatment) in IFN-gamma-/- mice. Furthermore, NMDA-receptor blockade with MK-801 in WNV-infected C57BL/6 mice abrogated seizures and prolonged survival. Our data show that IFN-gamma plays an important role in the development of the excitatory seizure pathways in the brain and that these cascades become pathogenic in encephalitic WNV infection.