Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange

Antibodies play a central role in immunity by forming an interface with the innate immune system and, typically, mediate proinflammatory activity. We describe a novel posttranslational modification that leads to anti-inflammatory activity of antibodies of immunoglobulin G, isotype 4 (IgG4). IgG4 antibodies are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light chain (half-molecule) with a heavy-light chain pair from another molecule, which results in bispecific antibodies. Mutagenesis studies revealed that the third constant domain is critical for this activity. The impact of IgG4 Fab arm exchange was confirmed in vivo in a rhesus monkey model with experimental autoimmune myasthenia gravis. IgG4 Fab arm exchange is suggested to be an important biological mechanism that provides the basis for the anti-inflammatory activity attributed to IgG4 antibodies.     

Complete photo-induced breakup of the H2 molecule as a probe of molecular electron correlation

Despite decades of progress in quantum mechanics, electron correlation effects are still only partially understood. Experiments in which both electrons are ejected from an oriented hydrogen molecule by absorption of a single photon have recently demonstrated a puzzling phenomenon: The ejection pattern of the electrons depends sensitively on the bond distance between the two nuclei as they vibrate in their ground state. Here, we report a complete numerical solution of the Schr?dinger equation for the double photoionization of H2. The results suggest that the distribution of photoelectrons emitted from aligned molecules reflects electron correlation effects that are purely molecular in origin.     

A NEW APPROACH TO HOLISTIC NITROGEN MANAGEMENT IN CHINA

● Progress on nitrogen management in agriculture is overviewed in China. ● 4R principles are key to high N use efficiency and low N losses in soil-crop systems. ● A new framework of food-chain-N-management is proposed. ● China’s success in N management provides models for other countries. Since the 1980s, the widespread use of N fertilizer has not only resulted in a strong increase in agricultural productivity but also caused a number of environmental problems, induced by excess reactive N emissions. A range of approaches to improve N management for increased agricultural production together with reduced environmental impacts has been proposed. The 4R principles (right product, right amount, right time and right place) for N fertilizer application have been essential for improving crop productivity and N use efficiency while reducing N losses. For example, site-specific N management (as part of 4R practice) reduced N fertilizer use by 32% and increased yield by 5% in China. However, it has not been enough to overcome the challenge of producing more food with reduced impact on the environment and health. This paper proposes a new framework of food-chain-nitrogen-management (FCNM). This involves good N management including the recycling of organic manures, optimized crop and animal production and improved human diets, with the aim of maximizing resource use efficiency and minimizing environmental emissions. FCNM could meet future challenges for food demand, resource sustainability and environmental safety, key issues for green agricultural transformation in China and other countries.     

Fractionation of wheat and wheat flour into starch and gluten: overview of the main processes and the factors involved

The starch and gluten components of wheat flour or whole wheat kernels can be separated by a number of industrial processes. This review provides a summary of these processes from both starting materials. The wheat constituents of importance in the fractionation processes are briefly introduced, and the different fractionation processes described with emphasis on the parameters affecting the separation, such as flour composition, mixing and washing water, processing aids (with an emphasis on enzymes) and kernel pre-treatment (pearling) in the case of flour fractionation and steeping conditions and processing aids in the case of whole wheat. Although fractionation of flour is the basis for the current industrial processes, starch yields are impaired by starch damage as a result of milling and loss of starch to milling streams. On the other hand fractionation of whole kernels often leads to impaired gluten production as a result of harsh process conditions which ‘devitalise’ the gluten.     

Maxillary Granulomatous Inflammation Caused by Halicephalobus gingivalis (Nematoda) in a Connemara Mare in Belgium

A 5-year-old anorexic and lethargic Connemara mare presented with severe facial swelling and dyspnea. No distinct central nervous symptoms were present. Radiographs of the skull showed diffuse radiolucency with loss of definition of the periodontal lamina dura and swelling of the decalcified nasal bones. Given the severe bone damage and its poor general condition, the pony was euthanized. Histological evaluation of the lesion revealed a granulomatous reaction with numerous sections of adult and juvenile nematodes, which were morphologically and molecularly identified as Halicephalobus gingivalis. The position of this facultative parasite within its free-living congeners is reviewed in this article, and the possible infection routes are discussed. This report presents the first record of equine halicephalobiasis in Belgium.     

Columnaris disease in fish: a review with emphasis on bacterium-host interactions

Flavobacterium columnare (F. columnare) is the causative agent of columnaris disease. This bacterium affects both cultured and wild freshwater fish including many susceptible commercially important fish species. F. columnare infections may result in skin lesions, fin erosion and gill necrosis, with a high degree of mortality, leading to severe economic losses. Especially in the last decade, various research groups have performed studies aimed at elucidating the pathogenesis of columnaris disease, leading to significant progress in defining the complex interactions between the organism and its host. Despite these efforts, the pathogenesis of columnaris disease hitherto largely remains unclear, compromising the further development of efficient curative and preventive measures to combat this disease. Besides elaborating on the agent and the disease it causes, this review aims to summarize these pathogenesis data emphasizing the areas meriting further investigation.     

Light and transmission electron microscopy of Vibrio campbellii infection in gnotobiotic Artemia franciscana and protection offered by a yeast mutant with elevated cell wall glucan

Luminescent vibrios are amongst the most important pathogens in aquaculture, affecting almost all types of cultured organisms. Vibrio campbellii is one of these most important pathogens. In this study, the effects of feeding mnn9 yeast cell wall mutant and wild type yeast strain were investigated in the digestive tract of brine shrimp nauplii, Artemia franciscana, after experimental infection with V. campbellii (LMG 21363). Gnotobiotic A. franciscana nauplii were fed daily with dead Aeromonas hydrophila LVS3, and with either wild type strain of baker's yeast, Saccharomyces cerevisiae, or mutant strain mnn9, of which the cell wall contains elevated chitin and glucan and lower mannose levels. After three days of feeding, some nauplii were challenged with V. campbellii. Mean survival (%), individual length (mm) and total length (mm) at one day and two days after challenge were significantly higher in the group fed mnn9 than in the group fed wild type yeast (81 ± 1.50 and 63 ± 0.49, 1.56 ± 0.07 and 1.13 ± 0.02, 38.21 ± 3.11 and 21.26 ± 0.81 respectively for one day and 50 ± 2.37 and 20 ± 1.41, 2.33 ± 0.01 and 1.24 ± 0.04, 34.97 ± 5.56 and 7.45 ± 1.63 for two days after challenge). Histological examination revealed that the luminal diameter and enterocyte height of both mid- and hindgut were larger in the mnn9-fed group. Colonization of the gut lumen by V. campbellii could be observed by transmission electron microscopy for the group of nauplii fed with wild type yeast. Furthermore, it was observed that V. campbellii caused damage to the gut epithelium including shortening and disappearance of the microvilli, destruction of the apical cell membrane and cell lysis in the nauplii fed wild type yeast. The gut epithelium remained intact in challenged nauplii fed mnn9 yeast. The morphological findings of the present study further substantiate previous studies reporting a protective effect of this yeast cell wall mutant.     

Antimicrobials in beekeeping

The bee diseases American and European foulbrood and nosemosis can be treated with anti-infectious agents. However, in the EU and the USA the use of these agents in beekeeping is strictly regulated due to the lack of tolerance (e.g. Maximum Residue Limit) for residues of antibiotics and chemotherapeutics in honey. This article reviews the literature dealing with antimicrobials of interest in apiculture, stability of these antimicrobials in honey, and disposition of the antimicrobials in honeybee hives.